WorldWideScience

Sample records for factors key regulators

  1. Ethylene, a key factor in the regulation of seed dormancy

    Directory of Open Access Journals (Sweden)

    Françoise eCORBINEAU

    2014-10-01

    Full Text Available Ethylene is an important component of the gaseous environment, and regulates numerous plant developmental processes including seed germination and seedling establishment. Dormancy, the inability to germinate in apparently favorable conditions, has been demonstrated to be regulated by the hormonal balance between abscisic acid (ABA and gibberellins (GAs. Ethylene plays a key role in dormancy release in numerous species, the effective concentrations allowing the germination of dormant seeds ranging between 0.1 and 200 μL L-1. Studies using inhibitors of ethylene biosynthesis or of ethylene action and analysis of mutant lines altered in genes involved in the ethylene signaling pathway (etr1, ein2, ain1, etr1, and erf1 demonstrate the involvement of ethylene in the regulation of germination and dormancy. Ethylene counteracts ABA effects through a regulation of ABA metabolism and signaling pathways. Moreover, ethylene insensitive mutants in Arabidopsis are more sensitive to ABA and the seeds are more dormant. Numerous data also show an interaction between ABA, GAs and ethylene metabolism and signaling pathways. It has been increasingly demonstrated that reactive oxygen species (ROS may play a significant role in the regulation of seed germination interacting with hormonal signaling pathways. In the present review the responsiveness of seeds to ethylene will be described, and the key role of ethylene in the regulation of seed dormancy via a cross-talk between hormones and other signals will be discussed.

  2. Key factors regulating the mass delivery of macromolecules to model cell membranes

    DEFF Research Database (Denmark)

    Campbell, Richard A.; Watkins, Erik B.; Jagalski, Vivien

    2014-01-01

    We show that both gravity and electrostatics are key factors regulating interactions between model cell membranes and self-assembled liquid crystalline aggregates of dendrimers and phospholipids. The system is a proxy for the trafficking of reservoirs of therapeutic drugs to cell membranes for slow...... of the aggregates to activate endocytosis pathways on specific cell types is discussed in the context of targeted drug delivery applications....

  3. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  4. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  5. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

  6. Key role of the kidney in the regulation of fibroblast growth factor 23

    DEFF Research Database (Denmark)

    Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob

    2015-01-01

    was significantly increased in BNX rats. The rapid rise in FGF23 after BNX was independent of parathyroid hormone or FGF receptor signaling. No evidence of early stimulation of FGF23 gene expression in the bone was found. Furthermore, acute severe hyperphosphatemia or hypercalcemia had no impact on intact FGF23......High circulating levels of fibroblast growth factor 23 (FGF23) have been demonstrated in kidney failure, but mechanisms of this are not well understood. Here we examined the impact of the kidney on the early regulation of intact FGF23 in acute uremia as induced by bilateral or unilateral...

  7. Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

    Directory of Open Access Journals (Sweden)

    Shiro Koizume

    2015-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

  8. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

    DEFF Research Database (Denmark)

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

    2013-01-01

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

  9. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    Science.gov (United States)

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  10. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin

    2014-04-04

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. Indeed, incompatible plant-pathogen interactions are well known to induce the hypersensitive response, a localized cell death. Mutational analyses have identified several key PCD components, and we recently identified the mips1 mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for the key enzyme catalyzing the limiting step of myoinositol synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD by screening for mutants that display transcriptomic profiles opposing that of the mips1 mutant. Our screen identified the oxt6 mutant, which has been described previously as being tolerant to oxidative stress. In the oxt6 mutant, a transfer DNA is inserted in the CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30) gene, which encodes a polyadenylation factor subunit homolog. We show that CPSF30 is required for lesion formation in mips1 via SA-dependent signaling, that the prodeath function of CPSF30 is not mediated by changes in the glutathione status, and that CPSF30 activity is required for Pseudomonas syringae resistance. We also show that the oxt6 mutation suppresses cell death in other lesion-mimic mutants, including lesion-simulating disease1, mitogen-activated protein kinase4, constitutive expressor of pathogenesis-related genes5, and catalase2, suggesting that CPSF30 and, thus, the control of messenger RNA 3′ end processing, through the regulation of SA production, is a key component of plant immune responses. © 2014 American Society of Plant Biologists. All rights reserved.

  11. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

    Science.gov (United States)

    Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

    2013-03-01

    Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

  12. Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet; Biensø, Rasmus Sjørup; Hassing, Helle Adser

    2015-01-01

    As the demand for hepatic glucose production increases during exercise, regulation of liver substrate choice and gluconeogenic activity becomes essential. The aim of the present study was to investigate the effect of a single exercise bout on gluconeogenic protein content and regulation of enzymes...... involved in substrate utilization in the liver. Mice were subjected to 1 h of treadmill exercise, and livers were removed immediately, 4 or 10 h after exercise. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) mRNA contents in the liver increased immediately after exercise, while...... phosphorylation decreased immediately after exercise may indicate that carbohydrates rather than fatty acids are utilized for oxidation in the liver during non-exhaustive exercise....

  13. Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases.

    Science.gov (United States)

    Zhang, Kuan; Zhu, Lingling; Fan, Ming

    2011-01-01

    Oxygen is vital to maintain the normal functions of almost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases, or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.076-7.6 mmHg) and in adult brain (11.4-53.2 mmHg), decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs) in vitro cultures at different oxygen concentration (15.2-152 mmHg) and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (22.8-76 mmHg) can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, Bone morphogenetic protein and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

  14. Oxygen, a key factor regulating cell behaviour during neurogenesis and cerebral diseases

    Directory of Open Access Journals (Sweden)

    Kuan eZhang

    2011-04-01

    Full Text Available Oxygen is vital to maintain the normal functions of alomost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.01%- 1% and in adult brain (1.5%-7%, decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs in vitro cultures at different oxygen concentration (2%-20% and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (3%-10% is known can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, BMP and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

  15. The Arabidopsis Transcription Factor AtTCP15 Regulates Endoreduplication by Modulating Expression of Key Cell-cycle Genes

    Institute of Scientific and Technical Information of China (English)

    Zi-Yu Li; Bin Li; Ai-Wu Dong

    2012-01-01

    Plant cells frequently undergo endoreduplication,a modified cell cycle in which genome is repeatedly replicated without cytokinesis.As the key step to achieve final size and function for cells,endoreduplication is prevalent during plant development.However,mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood.Here,we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes,as well as in rapidly dividing and vascular tissues.Expression of AtTCP15SRDX,AtTCP15 fused with a SRDX repressor domain,induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis.On the contrary,overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells.Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation.AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes,which play key roles in endoreduplication.Taken together,AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

  16. Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

    LENUS (Irish Health Repository)

    Ristola, Mervi

    2009-08-24

    Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

  17. Pou1f1, the key transcription factor related to somatic growth in tilapia (Orechromis niloticus), is regulated by two independent post-transcriptional regulation mechanisms.

    Science.gov (United States)

    Wang, Dongfang; Qin, Jingkai; Jia, Jirong; Yan, Peipei; Li, Wensheng

    2017-01-29

    This study aims to determine the post-transcriptional regulation mechanism of the transcription factor pou1f1 (pou class 1 homeobox 1), which is the key gene for pituitary development, somatic growth in vertebrates, and transcription of several hormone genes in teleost fish. MicroRNA miR-223-3p was identified as a bona fide target of pou1f; overexpression of miR-223-3p in primary pituitary cells led to the down-regulation of pou1f1 and downstream genes, and inhibition of miR-223-3p led to the up-regulation of pou1f1 in Nile tilapia dispersed primary pituitary cells. An adenylate-uridylate-rich element (AU-Rich element) was found in the 3'UTR of pou1f1 mRNA, and deletion of the AU-Rich element led to slower mRNA decay and therefore more protein output. A potential mutual relationship between miR-223-3p and the AU-rich element was also investigated, and the results demonstrated that with or without the AU-Rich element, miR-223-3p induced the up-regulation of a reporter system under serum starvation conditions, indicating that miR-223-3p and the AU-Rich element function independent of each other. This study is the first to investigate the post-transcriptional mechanism of pou1f1, which revealed that miR-223-3p down-regulated pou1f1 and downstream gene expressions, and the AU-Rich element led to rapid decay of pou1f1 mRNA. MicroRNA miR-223-3p and the AU-Rich element co-regulated the post-transcriptional expression of pou1f1 independently in Nile tilapia, demonstrating that pou1f1 is under the control of a dual post-transcription regulation mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

    Directory of Open Access Journals (Sweden)

    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

  19. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    Science.gov (United States)

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  20. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin; Garmier, Marie; De Bont, Linda; Soubigou-Taconnat, Ludivine; Mazubert, Christelle; Benhamed, Moussa; Raynaud, Cé cile; Bergounioux, Catherine; Delarue, Marianne

    2014-01-01

    striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD

  1. Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin

    Science.gov (United States)

    Thakur, Ram Krishna; Yadav, Vinod Kumar; Kumar, Akinchan; Singh, Ankita; Pal, Krishnendu; Hoeppner, Luke; Saha, Dhurjhoti; Purohit, Gunjan; Basundra, Richa; Kar, Anirban; Halder, Rashi; Kumar, Pankaj; Baral, Aradhita; Kumar, MJ Mahesh; Baldi, Alfonso; Vincenzi, Bruno; Lorenzon, Laura; Banerjee, Rajkumar; Kumar, Praveen; Shridhar, Viji; Mukhopadhyay, Debabrata; Chowdhury, Shantanu

    2014-01-01

    Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. PMID:25249619

  2. P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

    Science.gov (United States)

    Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

    2016-10-01

    Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. SUPPLY CHAIN MANAGEMENT – KEY FACTORS

    OpenAIRE

    Magdalena Daniela DINU

    2014-01-01

    This paper exposes Supply Chain Management by its key factors. Briefly, where the Supply Chain Management is treated as strategic part of a company then maintaining both control and influence throughout the entire supply chain are key factors and critical to success. On the other hand, finding the right partner to manage the non-strategic Supply Chains would be another key factor too. To define the most important key factors within Supply Chain Management means a deeply understanding of bot...

  4. The four key characteristics of interpersonal emotion regulation.

    Science.gov (United States)

    Niven, Karen

    2017-10-01

    Emotion researchers are increasingly interested in processes by which people influence others' feelings. Although one such process, interpersonal emotion regulation, has received particular attention in recent years, there remains confusion about exactly how to define this process. The present article aims to distinguish interpersonal emotion regulation from other, related processes by outlining its four key characteristics. Specifically, interpersonal emotion regulation is presented as a process of (i) regulation, that (ii) has an affective target, (iii) is deliberate, and (iv) has a social target. Considering these characteristics raises questions for future research concerning factors that may influence the process of interpersonal emotion regulation, why interpersonal emotion regulation sometimes fails, and whether interventions can improve people's use of interpersonal emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. SUPPLY CHAIN MANAGEMENT – KEY FACTORS

    Directory of Open Access Journals (Sweden)

    Magdalena Daniela DINU

    2014-06-01

    Full Text Available This paper exposes Supply Chain Management by its key factors. Briefly, where the Supply Chain Management is treated as strategic part of a company then maintaining both control and influence throughout the entire supply chain are key factors and critical to success. On the other hand, finding the right partner to manage the non-strategic Supply Chains would be another key factor too. To define the most important key factors within Supply Chain Management means a deeply understanding of both Supply Chain’ s components, procedures, workflow, processes and the importance of Supply Chain Management into maximizing company's value. SCORE model able to provide solid information about measuring performance and identifying priorities within Supply Chain Management will help us to understand the key factors by analyzing its elements: Plan, Source, Make, Deliver,Return, Enable. These elements covers all the challenging areas from first to third tier of Supply Chain Management.

  6. The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Gutiérrez Rodrigo A

    2008-09-01

    Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

  7. Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: modulation by the Nrf2/Trx axis.

    Science.gov (United States)

    Niso-Santano, Mireia; González-Polo, Rosa A; Bravo-San Pedro, José M; Gómez-Sánchez, Rubén; Lastres-Becker, Isabel; Ortiz-Ortiz, Miguel A; Soler, Germán; Morán, José M; Cuadrado, Antonio; Fuentes, José M

    2010-05-15

    Although oxidative stress is fundamental to the etiopathology of Parkinson disease, the signaling molecules involved in transduction after oxidant exposure to cell death are ill-defined, thus making it difficult to identify molecular targets of therapeutic relevance. We have addressed this question in human dopaminergic neuroblastoma SH-SY5Y cells exposed to the parkinsonian toxin paraquat (PQ). This toxin elicited a dose-dependent increase in reactive oxygen species and cell death that correlated with activation of ASK1 and the stress kinases p38 and JNK. The relevance of these kinases in channeling PQ neurotoxicity was demonstrated with the use of interference RNA for ASK1 and two well-established pharmaceutical inhibitors for JNK and p38. The toxic effect of PQ was substantially attenuated by preincubation with vitamin E, blocking ASK1 pathways and preventing oxidative stress and cell death. In a search for a physiological pathway that might counterbalance PQ-induced ASK1 activation, we analyzed the role of the transcription factor Nrf2, master regulator of redox homeostasis, and its target thioredoxin (Trx), which binds and inhibits ASK1. Trx levels were undetectable in Nrf2-deficient mouse embryo fibroblasts (MEFs), whereas they were constitutively high in Keap1-deficient MEFs as well as in SH-SY5Y cells treated with sulforaphane (SFN). Consistent with these data, Nrf2-deficient MEFs were more sensitive and Keap1-deficient MEFs and SH-SY5Y cells incubated with SFN were more resistant to PQ-induced cell death. This study identifies ASK1/JNK and ASK1/p38 as two critical pathways involved in the activation of cell death under oxidative stress conditions and identifies the Nrf2/Trx axis as a new target to block these pathways and protect from oxidant exposure such as that found in Parkinson and other neurodegenerative diseases. Copyright 2010 Elsevier Inc. All rights reserved.

  8. The regulation, the key for the development of renewable energies

    International Nuclear Information System (INIS)

    Saez de Miera, G.

    2007-01-01

    Regulation, rather than mere availability of resources-water, wind, sun-, is the key factor for an appropriate development of the renewable energies. A comparative analysis of the main regulatory support schemes feed-in-tariffs, green certificates and auctions is done in this paper, concluding that systems based on feed-in-tariff are more efficient and effective. Finally, we describe and analyze the regulatory arrangements in place to support wind energy in Spain, a well-known worldwide success, which is based on three basic foundations: predictability, stability and sufficiency. (Author)

  9. Mediator: A key regulator of plant development.

    Science.gov (United States)

    Buendía-Monreal, Manuel; Gillmor, C Stewart

    2016-11-01

    Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Key Success Factors in Medical Tourism Marketing

    OpenAIRE

    Yung-Sheng Yang

    2013-01-01

    The planners in tourism businesses and medical institutes, the evaluation criteria and dimensions for Medical Tourism Marketing are determined by experts through expert interviews. The weights and correlations among the dimensions and criteria are determined by Analytic Hierarchy Process (AHP) to construct an evaluating indicator model suitable for Medical Tourism Marketing. By organizing the overall weight of the key success factors in Medical Tourism Marketing, the top five indicators conta...

  11. SARS: Key factors in crisis management.

    Science.gov (United States)

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  12. KEY FACTORS IN MARKETING FOCUSED SERVICES BUSINESSES

    Directory of Open Access Journals (Sweden)

    Doris Yohanna Martínez Castrillón

    2016-07-01

    Full Text Available This article aims to identify the key success factors in the marketing area and describe them as managerial allies for companies that wish to position themselves in the market under a good sustainable performance , for it has been consulted theoretical references of Marketing as a management partner with collection and integration of data. Methodologically, it is located within the type of descriptive research field, with a design of transactional non-experimental, with an intentional non-probabilistic stratified sample of four reporting units. The findings established fifteen (15 points of influence called "key success factors (FCE in the area of marketing, and managerial allies of service companies in the security, surveillance and protection sector in industrial, commercial and residential sectors. Finally, it is intended that the actions of marketing service companies should focus to the welfare of both the organization, such as users, both in the environment, and economic, social and technological, characterized by ethics, sustainable development and transparency to respond appropriately.

  13. BENCHMARKING - PRACTICAL TOOLS IDENTIFY KEY SUCCESS FACTORS

    Directory of Open Access Journals (Sweden)

    Olga Ju. Malinina

    2016-01-01

    Full Text Available The article gives a practical example of the application of benchmarking techniques. The object of study selected fashion store Company «HLB & M Hennes & Mauritz», located in the shopping center «Gallery», Krasnodar. Hennes & Mauritz. The purpose of this article is to identify the best ways to develop a fashionable brand clothing store Hennes & Mauritz on the basis of benchmarking techniques. On the basis of conducted market research is a comparative analysis of the data from different perspectives. The result of the author’s study is a generalization of the ndings, the development of the key success factors that will allow to plan a successful trading activities in the future, based on the best experience of competitors.

  14. KEY PERFORMING FACTORS OF LEADING ROMANIAN COMPANIES

    Directory of Open Access Journals (Sweden)

    BURJA CAMELIA

    2014-08-01

    Full Text Available The analysis of financial economic ratios provides managers and external partners feedback on the results obtained from operational activities and the associated performance and risks. This paper studies the functional dependence of the companies’ success (on performance over internal financial management elements. The research was carried out for the most traded non-financial securities Bucharest listed companies and covers the period 2011- 2013. To carry out its purpose it analyzed the interdependence between the key financial ratios, studying the impact of liquidity ratios, solvency and efficiency on profitability. The study provides empirical evidences to identify factors that have ensured the performance of companies and their ranking in the segment of the most traded companies in Romania. Results suggest the view that the source of company success on the capital market lies in the positive signals sent to investors regarding profitability and the low risk of solvency. This study gives additional information for managerial decision-making in order to create more value and a better positioning of the companies in the market

  15. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  16. Key factors of teenagers' mobile advertising acceptance

    OpenAIRE

    Martí Parreño, José; Sanz Blas, Silvia; Ruiz Mafé, Carla; Aldás Manzano, Joaquín

    2013-01-01

    Purpose – The purpose of this paper is to analyse key drivers of teenagers’ attitude toward mobile advertising and its effects on teenagers’ mobile advertising acceptance. Design/methodology/approach – A proposed model of affective (irritation and entertainment) and cognitive (perceived usefulness) antecedents of attitude toward mobile advertising and its effects on mobile advertising acceptance is analysed. The sample consisted of 355 Spanish teenagers. The model was tested us...

  17. EG-VEGF: a key endocrine factor in placental development.

    Science.gov (United States)

    Brouillet, Sophie; Hoffmann, Pascale; Feige, Jean-Jacques; Alfaidy, Nadia

    2012-10-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Key Success Factors in Business Intelligence

    Directory of Open Access Journals (Sweden)

    Szymon Adamala

    2011-12-01

    Full Text Available Business Intelligence can bring critical capabilities to an organization, but the implementation of such capabilities is often plagued with problems. Why is it that certain projects fail, while others succeed? The aim of this article is to identify the factors that are present in successful Business Intelligence projects and to organize them into a framework of critical success factors. A survey was conducted during the spring of 2011 to collect primary data on Business Intelligence projects. Findings confirm that Business Intelligence projects are wrestling with both technological and non-technological problems, but the non-technological problems are found to be harder to solve as well as more time consuming than their counterparts. The study also shows that critical success factors for Business Intelligence projects are different from success factors for Information Systems projects in general. Business Intelligences projects have critical success factors that are unique to the subject matter. Major differences can be found primarily among non-technological factors, such as the presence of a specific business need and a clear vision to guide the project. Success depends on types of project funding, the business value provided by each iteration in the project and the alignment of the project to a strategic vision for Business Intelligence at large. Furthermore, the study provides a framework for critical success factors that, explains sixty-one percent of variability of success for projects. Areas which should be given special attention include making sure that the Business Intelligence solution is built with the end users in mind, that the Business Intelligence solution is closely tied to the company’s strategic vision and that the project is properly scoped and prioritized to concentrate on the best opportunities first.

  19. WRKY transcription factors: key components in abscisic acid signalling.

    Science.gov (United States)

    Rushton, Deena L; Tripathi, Prateek; Rabara, Roel C; Lin, Jun; Ringler, Patricia; Boken, Ashley K; Langum, Tanner J; Smidt, Lucas; Boomsma, Darius D; Emme, Nicholas J; Chen, Xianfeng; Finer, John J; Shen, Qingxi J; Rushton, Paul J

    2012-01-01

    WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination. For over 15 years, limited evidence has been available suggesting that WRKY TFs may play roles in regulating plant responses to the phytohormone abscisic acid (ABA), notably some WRKY TFs are ABA-inducible repressors of seed germination. However, the roles of WRKY TFs in other aspects of ABA signalling, and the mechanisms involved, have remained unclear. Recent significant progress in ABA research has now placed specific WRKY TFs firmly in ABA-responsive signalling pathways, where they act at multiple levels. In Arabidopsis, WRKY TFs appear to act downstream of at least two ABA receptors: the cytoplasmic PYR/PYL/RCAR-protein phosphatase 2C-ABA complex and the chloroplast envelope-located ABAR-ABA complex. In vivo and in vitro promoter-binding studies show that the target genes for WRKY TFs that are involved in ABA signalling include well-known ABA-responsive genes such as ABF2, ABF4, ABI4, ABI5, MYB2, DREB1a, DREB2a and RAB18. Additional well-characterized stress-inducible genes such as RD29A and COR47 are also found in signalling pathways downstream of WRKY TFs. These new insights also reveal that some WRKY TFs are positive regulators of ABA-mediated stomatal closure and hence drought responses. Conversely, many WRKY TFs are negative regulators of seed germination, and controlling seed germination appears a common function of a subset of WRKY TFs in flowering plants. Taken together, these new data demonstrate that WRKY TFs are key nodes in ABA-responsive signalling networks. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  20. Personality, a key factor in personalized medicine?

    NARCIS (Netherlands)

    Boersma, Gretha J.; Benthem, Lambertus; van Beek, Andre P.; van Dijk, Gertjan; Scheurink, Anton J. W.

    2011-01-01

    The incidence of health problems resulting from obesity is growing and obesity and its related diseases has become one of the main causes in death in industrialized societies. Environmental influences are crucial for the interactions between genetic, neurohormonal and metabolic factors that may be

  1. Helicopter training simulators: Key market factors

    Science.gov (United States)

    Mcintosh, John

    1992-01-01

    Simulators will gain an increasingly important role in training helicopter pilots only if the simulators are of sufficient fidelity to provide positive transfer of skills to the aircraft. This must be done within an economic model of return on investment. Although rotor pilot demand is still only a small percentage of overall pilot requirements, it will grow in significance. This presentation described the salient factors influencing the use of helicopter training simulators.

  2. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  3. Key factors in successful green roof training

    International Nuclear Information System (INIS)

    Seeger, H.; Ansel, W.

    2004-01-01

    The green roof market in Germany has increased significantly in the past 3 decades, reaching a market share of 11 to 14 per cent. Three factors were responsible for the success of the green roof movement in Germany, namely the early introduction of quality standards and guidelines; the scientific investigation of ecological and economic benefits and the development of innovative and reliable technologies. In addition, seminars and workshops targeted at relevant groups encouraged green roof construction. Training courses and seminars proved to be efficient communication tools with the advantage of direct feedback from the participants to address sophisticated green roof problems and to integrate current ecological and economic frameworks. The content of the courses were tailored to the specific needs of the participants. In addition, organizers had considerable knowledge of green roof technology and related disciplines. The green roof guidelines in Germany are based on a range of scientific studies from universities, technical colleges and regional research institutions. These studies explored the technical performance of different green roof constructions and the ecological benefits for people and the environment. The market development in Germany is backed by the development of a wide range of innovative technologies which offer solutions for nearly all green roof issues, such as landscaping of sloped, barrel shaped roofs with low load bearing capacities. The German company ZinCo offers the international market a range of well tested and proven green roof systems for intensive and extensive roofs. Their flexible modular products can be adapted to the needs of different roof constructions and to locally specific climatic conditions. 6 refs., 1 fig

  4. Liver physiological polyploidization: MicroRNA-122 a key regulator.

    Science.gov (United States)

    Celton-Morizur, Séverine; Desdouets, Chantal

    2017-03-01

    Polyploidy is defined as an increase in genome DNA content and is observed in all mammalian species. Polyploidy is a common characteristic of hepatocytes. Polyploidization occurs mainly during liver development, but also in adults with increasing age or due to cellular stress. During liver development, hepatocytes polyploidization occurs through cytokinesis failure leading to the genesis of binucleate hepatocytes. Recently, Hsu et al. demonstrated that miR-122 is a key regulator of hepatic binucleation. In fact, during liver development, miR-122 directly antagonizes procytokinesis targets and thus induces cytokinesis failure leading to the genesis of binucleate hepatocytes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Key factors influencing the implementation success of home telecare application.

    NARCIS (Netherlands)

    Postema, T.R.F.; Peeters, J.M.; Friele, R.D.

    2012-01-01

    Rationale: The introduction of home telecare in healthcare organizations has shown mixed results in practice. The aim of this study is to arrive at a set of key factors that can be used in further implementation of video communication. We argue that key factors are mainly found in the organizational

  6. Model of key success factors for Business Intelligence implementation

    Directory of Open Access Journals (Sweden)

    Peter Mesaros

    2016-07-01

    Full Text Available New progressive technologies recorded growth in every area. Information-communication technologies facilitate the exchange of information and it facilitates management of everyday activities in enterprises. Specific modules (such as Business Intelligence facilitate decision-making. Several studies have demonstrated the positive impact of Business Intelligence to decision-making. The first step is to put in place the enterprise. The implementation process is influenced by many factors. This article discusses the issue of key success factors affecting to successful implementation of Business Intelligence. The article describes the key success factors for successful implementation and use of Business Intelligence based on multiple studies. The main objective of this study is to verify the effects and dependence of selected factors and proposes a model of key success factors for successful implementation of Business Intelligence. Key success factors and the proposed model are studied in Slovak enterprises.

  7. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    Science.gov (United States)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  8. The concept of key success factors: Theory and method

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Ellegaard, Charlotte

    1992-01-01

    Executive summary: 1. The term key success factors can be used in four different ways: a) as a necessary ingre-dient in a management information system, b) as a unique characteristic of a company, c) as a heuristic tool for managers to sharpen their thinking, d) as a description of the major skills...... and resources required to be successful in a given market. We adopt the last view. 2. The actual key success factors on a market, and those key success factors perceived by decision-makers in companies operating in the market, will be different. A number of psychological mechanisms result in misperceptions...... or resource that a business can i in, which, on the market the business is operating on, explains a major part of the observable differences in perceived value and/or relative costs. 4. Key success factors differ from core skills and resources, which are prerequisites for being on a market, but do not explain...

  9. Fatty Acid–Regulated Transcription Factors in the Liver

    Science.gov (United States)

    Jump, Donald B.; Tripathy, Sasmita; Depner, Christopher M.

    2014-01-01

    Fatty acid regulation of hepatic gene transcription was first reported in the early 1990s. Several transcription factors have been identified as targets of fatty acid regulation. This regulation is achieved by direct fatty acid binding to the transcription factor or by indirect mechanisms where fatty acids regulate signaling pathways controlling the expression of transcription factors or the phosphorylation, ubiquitination, or proteolytic cleavage of the transcription factor. Although dietary fatty acids are well-established regulators of hepatic transcription factors, emerging evidence indicates that endogenously generated fatty acids are equally important in controlling transcription factors in the context of glucose and lipid homeostasis. Our first goal in this review is to provide an up-to-date examination of the molecular and metabolic bases of fatty acid regulation of key transcription factors controlling hepatic metabolism. Our second goal is to link these mechanisms to nonalcoholic fatty liver disease (NAFLD), a growing health concern in the obese population. PMID:23528177

  10. Analysis of Key Factors Driving Japan’s Military Normalization

    Science.gov (United States)

    2017-09-01

    no change to our policy of not giving in to terrorism.”40 Though the prime minister was democratically supported, Koizumi’s leadership style took...of the key driving factors of Japan’s normalization. The areas of prime ministerial leadership , regional security threats, alliance issues, and...analysis of the key driving factors of Japan’s normalization. The areas of prime ministerial leadership , regional security threats, alliance issues, and

  11. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  12. PPARα is a key regulator of hepatic FGF21

    International Nuclear Information System (INIS)

    Lundasen, Thomas; Hunt, Mary C.; Nilsson, Lisa-Mari; Sanyal, Sabyasachi; Angelin, Bo; Alexson, Stefan E.H.; Rudling, Mats

    2007-01-01

    The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARα). Fasting or treatment of mice with the PPARα agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARα deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARα levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARα for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARα response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARα in humans will be of great interest

  13. A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

    Science.gov (United States)

    Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya

    2017-01-01

    Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140

  14. DISTANCE AS KEY FACTOR IN MODELLING STUDENTS’ RECRUITMENT BY UNIVERSITIES

    Directory of Open Access Journals (Sweden)

    SIMONA MĂLĂESCU

    2015-10-01

    Full Text Available Distance as Key Factor in Modelling Students’ Recruitment by Universities. In a previous paper analysing the challenge of keeping up with the current methodologies in the analysis and modelling of students’ recruitment by universities in the case of some ECE countries which still don’t register or develop key data to take advantage from the state of the art knowledge on the domain, we have promised to approach the factor distance in a future work due to the extent of the topic. This paper fulfill that promise bringing a review of the literature especially dealing with modelling the geographical area of recruiting students of an university, where combining distance with the proximate key factors previously reviewed, complete the meta-analysis of existing literature we have started a year ago. Beyond the theoretical benefit from a practical perspective, the metaanalysis aimed at synthesizing elements of good practice that can be applied to the local university system.

  15. Functional Imaging of Autonomic Regulation: Methods and Key Findings

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    2016-01-01

    Full Text Available Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI. The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: 1 describe the fMRI neuroimaging methodology for assessment of autonomic neural control, 2 outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, 3 illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and 4 highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with

  16. Positioning and deciding : key factors for talent development in soccer

    NARCIS (Netherlands)

    Kannekens, R.; Elferink-Gemser, M. T.; Visscher, C.

    2011-01-01

    Talent identification and development implicate recognizing youth players who will be successful in the future and guiding them to the top. A major determinant of this success is tactical skills. To identify possible key factors that help in predicting success over time, this study assesses the

  17. Unity power factor switching regulator

    Science.gov (United States)

    Rippel, Wally E. (Inventor)

    1983-01-01

    A single or multiphase boost chopper regulator operating with unity power factor, for use such as to charge a battery is comprised of a power section for converting single or multiphase line energy into recharge energy including a rectifier (10), one inductor (L.sub.1) and one chopper (Q.sub.1) for each chopper phase for presenting a load (battery) with a current output, and duty cycle control means (16) for each chopper to control the average inductor current over each period of the chopper, and a sensing and control section including means (20) for sensing at least one load parameter, means (22) for producing a current command signal as a function of said parameter, means (26) for producing a feedback signal as a function of said current command signal and the average rectifier voltage output over each period of the chopper, means (28) for sensing current through said inductor, means (18) for comparing said feedback signal with said sensed current to produce, in response to a difference, a control signal applied to the duty cycle control means, whereby the average inductor current is proportionate to the average rectifier voltage output over each period of the chopper, and instantaneous line current is thereby maintained proportionate to the instantaneous line voltage, thus achieving a unity power factor. The boost chopper is comprised of a plurality of converters connected in parallel and operated in staggered phase. For optimal harmonic suppression, the duty cycles of the switching converters are evenly spaced, and by negative coupling between pairs 180.degree. out-of-phase, peak currents through the switches can be reduced while reducing the inductor size and mass.

  18. 76 FR 68314 - Special Local Regulations; Key West World Championship, Atlantic Ocean; Key West, FL

    Science.gov (United States)

    2011-11-04

    ... are available online by going to http://www.regulations.gov , inserting USCG-2011-0942 in the... emphasizes the importance of quantifying both costs and benefits, of reducing costs, of harmonizing rules... Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution...

  19. Rab proteins: The key regulators of intracellular vesicle transport

    International Nuclear Information System (INIS)

    Bhuin, Tanmay; Roy, Jagat Kumar

    2014-01-01

    Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future

  20. Rab proteins: The key regulators of intracellular vesicle transport

    Energy Technology Data Exchange (ETDEWEB)

    Bhuin, Tanmay [Cell and Developmental Biology Unit, Department of Zoology, The University of Burdwan, Golapbag 713104 (India); Roy, Jagat Kumar, E-mail: jkroy@bhu.ac.in [Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005 (India)

    2014-10-15

    Vesicular/membrane trafficking essentially regulates the compartmentalization and abundance of proteins within the cells and contributes in many signalling pathways. This membrane transport in eukaryotic cells is a complex process regulated by a large and diverse array of proteins. A large group of monomeric small GTPases; the Rabs are essential components of this membrane trafficking route. Most of the Rabs are ubiquitously expressed proteins and have been implicated in vesicle formation, vesicle motility/delivery along cytoskeleton elements and docking/fusion at target membranes through the recruitment of effectors. Functional impairments of Rabs affecting transport pathways manifest different diseases. Rab functions are accompanied by cyclical activation and inactivation of GTP-bound and GDP-bound forms between the cytosol and membranes which is regulated by upstream regulators. Rab proteins are characterized by their distinct sub-cellular localization and regulate a wide variety of endocytic, transcytic and exocytic transport pathways. Mutations of Rabs affect cell growth, motility and other biological processes. - Highlights: • Rab proteins regulate different signalling pathways. • Deregulation of Rabs is the fundamental causes of a variety of human diseases. • This paper gives potential directions in developing therapeutic targets. • This paper also gives ample directions for modulating pathways central to normal physiology. • These are the huge challenges for drug discovery and delivery in near future.

  1. ERP IMPLANTATION: KEY FACTORS OF SUCCESS AND IMPACT ON PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Dumitru Valentin

    2008-05-01

    Full Text Available The implantation of an ERP (abbreviation for "Enterprise Resource Planning" system is an enterprise project that implies the remodeling of the information system, mostly the rethinking of management procedures within the organization. The expansion and the complexity of these projects demand a theoretical framework and « optimal practices » in order to model and to evaluate the key factors of implementation success and to analyze its impact on the organization’s performance. The research problem of our communication can be divided into three research questions: - What conceptual framework for ERP implantation? - What are the key factors of success in ERP implantation? - What is the relationship between ERP implantation and enterprise performance?

  2. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    Science.gov (United States)

    2011-01-01

    networks that take inputs from numerous stimuli and that they are involved in mediating responses to numerous phytohormones including salicylic acid ... jasmonic acid , ABA and GA. These roles in multiple signalling pathways may in turn partly explain the pleiotropic effects commonly seen when TF genes are...Review article WRKY transcription factors: key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1

  3. Human-automation collaboration in manufacturing: identifying key implementation factors

    OpenAIRE

    Charalambous, George; Fletcher, Sarah; Webb, Philip

    2013-01-01

    Human-automation collaboration refers to the concept of human operators and intelligent automation working together interactively within the same workspace without conventional physical separation. This concept has commanded significant attention in manufacturing because of the potential applications, such as the installation of large sub-assemblies. However, the key human factors relevant to human-automation collaboration have not yet been fully investigated. To maximise effective implement...

  4. Exploring key factors in online shopping with a hybrid model.

    Science.gov (United States)

    Chen, Hsiao-Ming; Wu, Chia-Huei; Tsai, Sang-Bing; Yu, Jian; Wang, Jiangtao; Zheng, Yuxiang

    2016-01-01

    Nowadays, the web increasingly influences retail sales. An in-depth analysis of consumer decision-making in the context of e-business has become an important issue for internet vendors. However, factors affecting e-business are complicated and intertwined. To stimulate online sales, understanding key influential factors and causal relationships among the factors is important. To gain more insights into this issue, this paper introduces a hybrid method, which combines the Decision Making Trial and Evaluation Laboratory (DEMATEL) with the analytic network process, called DANP method, to find out the driving factors that influence the online business mostly. By DEMATEL approach the causal graph showed that "online service" dimension has the highest degree of direct impact on other dimensions; thus, the internet vendor is suggested to made strong efforts on service quality throughout the online shopping process. In addition, the study adopted DANP to measure the importance of key factors, among which "transaction security" proves to be the most important criterion. Hence, transaction security should be treated with top priority to boost the online businesses. From our study with DANP approach, the comprehensive information can be visually detected so that the decision makers can spotlight on the root causes to develop effectual actions.

  5. Market Makers' Recognition of Key Success Factors in Electronic Marketplaces

    Directory of Open Access Journals (Sweden)

    Rosemary Stockdale

    2003-05-01

    Full Text Available This study examines the recognition and use of critical success factors by market makers in electronic marketplaces. A content analysis of e-marketplace websites enabled an examination of how these factors have been incorporated into marketplace sites. Evidence of market makers’ awareness of the success factors was found in all the sites although there remain questions and issues to be addressed. Awareness of the need for critical mass and privacy were very evident, but the key factors of security, technological infrastructure and neutrality were identified as areas of concern. Evidence of an awareness of the importance of trust by market makers was found, but more effective signalling of trust to buyers and sellers within the marketplaces is required.

  6. The autoregulatory loop: A common mechanism of regulation of key ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... The genes involved in the sex determination cascade such as Sex-lethal (Sxl) in Drosophila melanogaster, transformer (tra) in many other dipterans, coleopterans and hymenopterans, Feminizer (fem) in Apis mellifera, and IGF-II mRNA-binding protein (Bmimp) in Bombyx mori are reported to be regulated ...

  7. Identifying key hospital service quality factors in online health communities.

    Science.gov (United States)

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

    2015-04-07

    The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

  8. The microbiome: A key regulator of stress and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kieran Rea

    2016-10-01

    In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.

  9. [Analysis on the key factors affecting the inheritance of the acupuncture learning].

    Science.gov (United States)

    Li, Su-yun; Zhang, Li-jian; Gang, Wei-juan; Xu, Wen-bin; Xu, Qing-yan

    2010-06-01

    On the basis of systematicly reviewing the developmental history of acupuncture and moxibustion and profoundly understanding its academic connotations, the authors of the present article make a summary and analysis on the key factors influencing the development of acupuncturology. These key factors are (1) the emergence of "microacupuncture needle regulating-Qi" and the establishement of their corresponding theory system, (2) a large number of practitioners who inherited the learnings of acupuncturology generations by generations, and abundant medical classical works which recorded the valuable academic thoughts and clinical experience of the predecesors, (3) the application of acupuncture charts and manikins, and (4) modernizing changes of acupuncture learnings after introduction of western medicine to China. Just under the influence of these key factors, the acupuncture medicine separates itself from the level of the simple experience medicine, and has formed a set of special theory system and developed into a mature subject.

  10. The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension.

    LENUS (Irish Health Repository)

    Martin, Ronny

    2011-04-01

    The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues.

  11. Syndecans – key regulators of cell signaling and biological functions

    DEFF Research Database (Denmark)

    Afratis, Nikolaos A.; Nikitovic, Dragana; Multhaupt, Hinke A.B.

    2017-01-01

    molecules during cancer initiation and progression. Particularly syndecans interact with other cell surface receptors, such as growth factor receptors and integrins, which lead to activation of downstream signaling pathways, which are critical for the cellular behavior. Moreover, this review describes...

  12. Key factors of successful JIT integration with IBS - An overview

    Science.gov (United States)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  13. Factors that regulate embryonic gustatory development

    Directory of Open Access Journals (Sweden)

    Krimm Robin F

    2007-09-01

    Full Text Available Abstract Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP. As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF, functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-β-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and

  14. Stensund wastewater aquaculture. Studies of key factors for its optimization

    Energy Technology Data Exchange (ETDEWEB)

    Guterstam, B.; Forsberg, L.E. [Stensund Ecological Center, Stensunds Fold Center, S-61991 Trosa (Sweden); Buczynska, A. [Faculty of Process and Environmental Engineering, Technical University of Lodz, 175 Wolczanska strasse, PL-90942 Lodz (Poland); Frelek, K. [Department of Analytical Chemistry, Medical University of Gdansk, Al. Gen. J. Hallera 107, PL-80416 Gdansk (Poland); Pilkaityte, R. [Natural Science Faculty, University of Klaipeda, LT-5813 Klaipeda (Lithuania); Reczek, L. [Department of Water Supply and Sewage Systems, Warsaw Agricultural University, 166 Nowoursynowska strasse, PL-02787 Warsaw (Poland); Rucevska, I. [Latvian Environmental Data Center, Straumes 2, Jurmala LV 2015 (Latvia)

    1998-10-21

    This paper is a summary of an in-depth study of key factors in the function of a 7-year-old aquaculture system designed for treatment and recycling of domestic wastewater at Stensund, Trosa, Sweden. The reported areas are: wastewater flows, reduction of biochemical oxygen demand (BOD), chemical oxygen demand (COD), phosphorus, nitrogen, and fecal bacteria. Plant production is recorded as harvested biomass, and energy results are given as generated heat and electricity consumption. Special studies were conducted on the reduction of copper by anaerobic treatment. Nitrification was studied with different filter media. Microalgal autofocculation of phosphorus was studied in relation to pH and water hardness for the green algal genus Scenedesmus. Limiting factors for the growth of Daphnia magna in the zooplankton step of the constructed aquatic food-web was studied in a specially designed reproduction test. The results are analyzed in order to optimize the function of the wastewater aquaculture

  15. Key factors of low carbon development strategy for sustainable transport

    Science.gov (United States)

    Thaveewatanaseth, K.; Limjirakan, S.

    2018-02-01

    Cities become more vulnerable to climate change impacts causing by urbanization, economic growth, increasing of energy consumption and carbon dioxide (CO2) emissions. People who live in the cities have already been affected from the impacts in terms of socioeconomic and environmental aspects. Sustainable transport plays the key role in CO2 mitigation and contributes positive impacts on sustainable development for the cities. Several studies in megacities both in developed and developing countries support that mass transit system is an important transportation mode in CO2 mitigation and sustainable transport development. This paper aims to study key factors of low carbon development strategy for sustainable transport. The Bangkok Mass Rapid Transit System (MRT) located in Bangkok was the study area. Data collection was using semi-structured in-depth interview protocol with thirty respondents consisting of six groups i.e. governmental agencies, the MRT operators, consulting companies, international organizations, non-profit organizations, and experts. The research findings highlighted the major factors and supplemental elements composing of institution and technical capacity, institutional framework, policy setting and process, and plan of implementation that would support more effective strategic process for low carbon development strategy (LCDS) for sustainable transport. The study would highly recommend on readiness of institution and technical capacities, stakeholder mapping, high-level decision- makers participation, and a clear direction of the governmental policies that are strongly needed in achieving the sustainable transport.

  16. Key Success Factors in E-Learning in Medical Education

    Directory of Open Access Journals (Sweden)

    Hassan Emami

    2009-08-01

    Full Text Available Background and purpose: As in many countries, Medical Education (ME is offered in three levels including Undergraduate ME, Graduate ME, and Continuing ME. Informtion tehnology development has provided a suitable chance for ME. E-learning in ME is growing more and more. The present study seeks to determine the key success factors (KSF in E-learning in medical fields.Methods: KSF has been scrutinized in the literature following of which, and due to similarity, a classification with seven groupings was established including institutional factor, technology, interested parties, information knowledge, methods and approaches educational resources, and environmental factors. Through a questionnaire, the data were gatered from the information technology (IT directors in all medical universities throughout the country. The data collected were subjected to factorial analysis. Data from heads of educational groups were obtained through focus group discussion. Cronbach reliability coefficient was calculated for questionnaire used. Factorial analysis was used to identify meaningful KSF. T-Test, and one-way variance analysis as well as Pearson’s correlation were used. The analysis was conducted with SPSS softwareResults: The results showed no significant differences between age, sex, career, and level of education, and KSF. The preparedness factors were analyzed through group discussions with the heads of the academic departments under the study. By factorial analyses, five factors were found including the departmental interest and potential (27.3%, task performance potential (25.1%, E-teaching development in basic and clinical sciences , and continuing education (20.1%, suitable cultural environment (16.8%, and infrastructures (10.8%. Fisher Exeact Test was used to compare the obtained ratios in 5% curve whose results showed that among the three factors including legal and technocal environment, specialized hardwareand software, and high speed internet

  17. Flg22-Triggered Immunity Negatively Regulates Key BR Biosynthetic Genes.

    Science.gov (United States)

    Jiménez-Góngora, Tamara; Kim, Seong-Ki; Lozano-Durán, Rosa; Zipfel, Cyril

    2015-01-01

    In plants, activation of growth and activation of immunity are opposing processes that define a trade-off. In the past few years, the growth-promoting hormones brassinosteroids (BR) have emerged as negative regulators of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), promoting growth at the expense of defense. The crosstalk between BR and PTI signaling was described as negative and unidirectional, since activation of PTI does not affect several analyzed steps in the BR signaling pathway. In this work, we describe that activation of PTI by the bacterial PAMP flg22 results in the reduced expression of BR biosynthetic genes. This effect does not require BR perception or signaling, and occurs within 15 min of flg22 treatment. Since the described PTI-induced repression of gene expression may result in a reduction in BR biosynthesis, the crosstalk between PTI and BR could actually be negative and bidirectional, a possibility that should be taken into account when considering the interaction between these two pathways.

  18. Oxidative stress: a key regulator of leiomyoma cell survival.

    Science.gov (United States)

    Fletcher, Nicole M; Abusamaan, Mohammed S; Memaj, Ira; Saed, Mohammed G; Al-Hendy, Ayman; Diamond, Michael P; Saed, Ghassan M

    2017-06-01

    To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. Prospective experimental study. University medical center. Cells established from myometrium and uterine fibroid from the same patients. Cells were exposed to normal (20% O 2 ) or hypoxic (2% O 2 ) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism. Nitrate/nitrite (iNOS activity indicator), iNOS, Bcl-2/Bax ratio, MPO, and caspase-3 activities and levels were determined by means of Greiss assay, real-time reverse-transcription polymerase chain reaction, and ELISA. Data were analyzed with the use of SPSS by means of one-way analysis of variance with Tukey post hoc analysis and independent t tests. MPO, iNOS, and nitrate/nitrite expression were higher in leiomyoma than in myometrial cells, and they were further enhanced by hypoxia in myometrial cells. Treatment with the use of DCA decreased MPO, iNOS, and nitrate/nitrite levels and negated the effect of hypoxia in both types of cells. Leiomyoma cells showed less apoptosis, as indicated by both caspase-3 activity and the Bcl-2/Bax ratio, than myometrial cells. Hypoxia further decreased apoptosis in myometrial cells with no further effect on leiomyoma cells. Treatment with DCA resulted in increased apoptosis in both types of cells, even in the presence of hypoxia. Shifting anaerobic to aerobic metabolism with the use of DCA resulted in an increase in apoptosis in leiomyoma cells and protected myometrial cells from the acquisition of the leiomyoma-like phenotype. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Phosphodiesterase 1 regulation is a key mechanism in vascular aging

    DEFF Research Database (Denmark)

    Niño, Paula K Bautista; Durik, Matej; Danser, A H Jan

    2015-01-01

    Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role...... in human age-related vascular disease. To test our hypothesis, we combined experiments in mice with genomic instability resulting from the defective nucleotide excision repair gene ERCC1 (Ercc1(d/-) mice), human VSMC cultures and population genome-wide association studies (GWAS). Aortic rings of Ercc1(d...... in lungs was higher in Ercc1(d/-) mice. No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1(d/-) mice compared with WT. Senescent human VSMC showed elevated PDE1A and PDE1C and PDE5 mRNA levels (11.6-, 9- and 2.3-fold respectively), which associated...

  20. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury.

    Science.gov (United States)

    El Agha, Elie; Bellusci, Saverio

    2014-01-01

    Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.

  1. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury

    Directory of Open Access Journals (Sweden)

    Elie El Agha

    2014-01-01

    Full Text Available Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.

  2. Key factors influencing lung cancer survival in northern Italy.

    Science.gov (United States)

    Mangone, Lucia; Minicozzi, Pamela; Vicentini, Massimo; Giacomin, Adriano; Caldarella, Adele; Cirilli, Claudia; Falcini, Fabio; Giorgi Rossi, Paolo; Sant, Milena

    2013-06-01

    Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003-2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna - where sophisticated diagnostic examinations were performed more often - had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60-61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02-1.48) than Modena (reference). Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  4. Predictive model identifies key network regulators of cardiomyocyte mechano-signaling.

    Directory of Open Access Journals (Sweden)

    Philip M Tan

    2017-11-01

    Full Text Available Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration. The model identifies calcium, actin, Ras, Raf1, PI3K, and JAK as key regulators of cardiac mechano-signaling and characterizes crosstalk logic imparting differential control of transcription by AT1R, integrins, and calcium channels. We find that while these regulators maintain mostly independent control over distinct groups of transcription factors, synergy between multiple pathways is necessary to activate all the transcription factors necessary for gene transcription and hypertrophy. We also identify a PKG-dependent mechanism by which valsartan/sacubitril, a combination drug recently approved for treating heart failure, inhibits stretch-induced hypertrophy, and predict further efficacious pairs of drug targets in the network through a network-wide combinatorial search.

  5. Power factor regulation for household usage

    Science.gov (United States)

    Daud, Nik Ghazali Nik; Hashim, Fakroul Ridzuan; Tarmizi, Muhammad Haziq Ahmad

    2018-02-01

    Power factor regulator technology has recently drawn attention to the consumer and to power generation company in order for consumers to use electricity efficiently. Controlling of power factor for efficient usage can reduce the production of power in fulfilment demands hence reducing the greenhouse effect. This paper presents the design method of power factor controller for household usage. There are several methods to improve the power factor. The power factor controller used by this method is by using capacitors. Total harmonic distortion also has become a major problem for the reliability of the electrical appliances and techniques to control it will be discussed.

  6. Key success factors in enterprises practicing social marketing

    Directory of Open Access Journals (Sweden)

    Lin, Mong-Mei

    2014-11-01

    Full Text Available Enterprises could create multi-service values of customer satisfaction, enterprise profit, and social benefit through Social Marketing. Constructing a positive Social Service Value Chain to achieve mind management in marketing would reinforce the core competitive advantages of an enterprise, enhance high-quality services, and lead the enterprise to sustainable management. With the Delphi Method, a questionnaire is applied to assess the key success factors in enterprises practicing Social Marketing. The superiors and the employees in Formosa Plastics Group were selected as the research participants for 200 questionnaires. A total of 133 valid copies are retrieved, with a retrieval rate of 67%. According to the overall weights of the key success factors in enterprises practicing Social Marketing, the following summary is concluded. 1. The evaluation criteria in Organizational Characteristics are ordered in the following way: Intrinsic Structure, Internal Environment, Cost Effectiveness, Organizational Advantage, Organizational Weakness, and Inspiration. 2. The evaluation criteria in the External Environment are ordered this way: Information Resources, Environmental Opportunities, and Environmental Threats. 3. The order of the evaluation criteria in Marketing Strategy is Appropriate Media, Targeted Objects, Market Selection, Market Response, and Behavioral Change. 4. The evaluation criteria in Process Orientation are ordered in the following way: Tracking Adjustment, Feedback Systems, Operation Performance, and Operation Processes.A través del márquetin social, las empresas podrían crear valores de multiservicio para la satisfacción del cliente, para incrementar los beneficios de la empresa y para beneficiar a la sociedad. La construcción de una Cadena de Valor de Servicio Social positiva para conseguir una gestión mental en el márquetin reforzaría las principales ventajas competitivas de una empresa, realzaría servicios de alta calidad y

  7. ORIENTATION: KEY TO THE OODA LOOP – THE CULTURE FACTOR

    Directory of Open Access Journals (Sweden)

    Donald A. MACCUISH

    2012-01-01

    Full Text Available The late Colonel John Boyd developed what he called the OODA-Loop as both a learning and decision making model to help us better understand how we make decisions and learn. His OODA-Loop model consists of non-sequential elements: Observe – Orient – Decide – Action. He contended if one could cycle through these phases quicker and more accurately than one’s adversary you could then get inside your adversary’s OODA-Loop and “win”. The key to the OODA-Loop he noted is Orientation. He only drew one diagram of his OODA-Loop. Only in the Orientation phase did he elaborate component elements. These elements are: Cultural Traditions, Genetic Heritage, Analysis/Synthesis, New Information, and Previous Experience. All of these elements he contended are interconnected. Thus, the interaction of all these factors effects how we orient ourselves to the situation at hand. In this article I will share my view of the “Culture Factor” in Orientation.

  8. Key Success Factors and Guidance for International Collaborative Design Projects

    Directory of Open Access Journals (Sweden)

    Robby Soetanto

    2015-11-01

    Full Text Available In the built environment (BE sector, the co-creation process of design demands understanding of requirements (as viewed by parties involved, mobilisation of tacit knowledge, negotiation, and complex exchange of information. The need to collaborate over distance has further exacerbated the complexity of the process, and, in itself, represents a significant challenge for BE professionals who are increasingly expected to undertake this process within globally distributed virtual teams. The research aims to identify key success factors and develop guidance for international collaborative design projects, via the implementation of collaborative design courses in UK and Canadian universities over three academic years. Questionnaire surveys, focus groups, observation of online meetings, personal reflections provided data for the analysis. The findings reveal the significance of the perceived risk of collaboration and a difference in preferred communication mode between architects and civil/structural engineers. These findings suggest the impact of training in the subject discipline, and that the opportunity for co-located working has helped the development of trust. The guidance is aimed at BE educators who wish to implement this activity in their courses.

  9. The Assistant Manager - a Key Factor of the Managerial Team

    Directory of Open Access Journals (Sweden)

    Lecturer Ph. D. Niculina Vargolici

    2009-05-01

    Full Text Available The new economic context, marked by the crisis and by radical transformations of the labor market, generates the need for more and more sophisticated skills for the assistant manager. That is because the efficiency of the secretarial activity implies both strategic skills and complex abilities, starting from knowledge about the specific activity of the company/institution where the person works as assistant manager, to connected areas such as: management, marketing, human resources, brand communication, company’s culture etc. Whether the manager changes his job together with the “boss”, or the boss is changed and he is bond to adapt to new conditions, a strong team spirit between the manager and his assistant is one of the most important elements that contribute to the productivity and efficiency of the both. The loyalty to the boss and to the company where he works, his adaptation capacity, his competence and his professionalism make the today’s assistant manager a key factor of the managerial team. The essence of the assistant manager job consists in making more efficient the managerial activities, namely, to make it respond to the expectations expressed or not of the manager, or even to anticipate them.

  10. Key factors that influence for seasonal production of Guinea grass

    Directory of Open Access Journals (Sweden)

    Leandro Coelho de Araujo

    Full Text Available ABSTRACT: Climate, soil and management are the main drives for growth and production of tropical pastures. Thus, a better understanding of the effects of these factors and their interactions under climate conditions is required to obtain effective management options. Here, we used data from two field trials to research on climate and management interactions on the production seasonality of Panicum maximum Jacq. Treatments included four sampling times (250, 500, 750, and 1000 °C accumulated during eight regrowth period, under irrigated and rainfed conditions and, cuts were made to simulate grazing intensity. All treatments were arranged in a completely randomized block design with four replications. At each sampling time, basal tillers were sampled to observe meristematic differentiation and were linked with the respective daylength. Soil moisture was determined, and the water availability index (WAI was calculated. The dry matter production (DMP was taken and relative productivity was calculated. Soil moisture was the key seasonal drive in spring-summer and the WAI could be used to adjust the maximum production for that season. The major drive for DMP in fall was the daylength, which was found at 11.81 h. For all seasons, DMP correlated better with the residues in early regrowth phase (r = 0.82 and p < 0.0001 and with degree-days at final regrowth phase (r = 0.73 p < 0.01. Applying these critical values to management guidelines should make Guinea grass DMP more efficient on tropical farms.

  11. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  12. Key Factors for Nuclear Being Economic after Fukushima

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Myung Sub; Park, Seo Yeon [KEPCO International Nuclear Graduate School, Ulju (Korea, Republic of)

    2012-05-15

    It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

  13. Key Factors for Nuclear Being Economic after Fukushima

    International Nuclear Information System (INIS)

    Roh, Myung Sub; Park, Seo Yeon

    2012-01-01

    It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

  14. Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review

    Energy Technology Data Exchange (ETDEWEB)

    Viglizzo, E.F., E-mail: evigliz@cpenet.com.ar [INTA, EEA Anguil, Grupo de Investigaciones en Gestión Ambiental (GIGA), Av. Spinetto 785, 6300 Santa Rosa, La Pampa (Argentina); INCITAP-CONICET, Ruta 35, km 335, 6300 Santa Rosa, La Pampa (Argentina); UNLPam, Facultad de Ciencias Exactas y Naturales, Av. Uruguay 151, 6300 Santa Rosa, La Pampa (Argentina); Jobbágy, E.G. [CONICET, Andes 950, 5700 San Luis, San Luis (Argentina); Grupo de Estudios Ambientales IMASL, Ejército de los, Andes 950, 5700 San Luis, San Luis (Argentina); Ricard, M.F. [INCITAP-CONICET, Ruta 35, km 335, 6300 Santa Rosa, La Pampa (Argentina); UNLPam, Facultad de Ciencias Exactas y Naturales, Av. Uruguay 151, 6300 Santa Rosa, La Pampa (Argentina); Paruelo, J.M. [Laboratorio de Análisis Regional y Teledetección, Departamento de Métodos Cuantitativos Sistemas de información, Facultad de Agronomía and IFEVA, Universidad de Buenos Aires and CONICET, Av. San Martín 4453, 1417 Buenos Aires (Argentina)

    2016-08-15

    Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed. - Highlights: • The partition of regulatory services in ecosystems poses a major policy challenge. • We examined how partitions occur at the hydrosphere

  15. Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review

    International Nuclear Information System (INIS)

    Viglizzo, E.F.; Jobbágy, E.G.; Ricard, M.F.; Paruelo, J.M.

    2016-01-01

    Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed. - Highlights: • The partition of regulatory services in ecosystems poses a major policy challenge. • We examined how partitions occur at the hydrosphere

  16. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Rao, L.V.M.; Rapaport, S.I.

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  17. Energy efficiency and CO2: is electricity the key factor?

    Energy Technology Data Exchange (ETDEWEB)

    Bamberger, Y.

    2007-07-01

    Europe must face soon to the depletion of fossil energy resources. Efficiency in end energy uses is a key to prepare this challenge. First, the report shows that significant energy efficiency capacities remain in the main economy sectors in France and Europe: buildings, industry, transportation. The key technologies, mainly electricity-driven, are briefly presented, together with the related main tracks for R and D: heat pumps, thermal insulation, induction and mechanical vapour compression for industry, plugged hybrid vehicle, LED sources for lighting. Their ability to decrease CO2 emissions is shown. Control equipment and users behaviour are pointed out, mainly with the key role of price energy with recent French experience : load shifting, peak shaving. Finally, the report shows that a firm policy, based on high performance equipments, could lead to a significant decrease of energy needs in France around 2030.

  18. Key Success Factors for Organizational Innovation in the Fashion Industry

    Directory of Open Access Journals (Sweden)

    Fabio De Felice

    2013-08-01

    on the Balanced Scorecard (BSC and the Analytic Network Process (ANP, called ‘MAB’ – Multi-criteria Assessment Balanced Scorecard. Firstly, key performance indicators (KPIs are evaluated in order to assess the performance level of a typical fashion industry. The development of an index system and methods is aimed to form a set of useful tools for policy-makers to facilitate the transformation of an industrial development mode and support the performance of the fashion industry.

  19. Safety and reliability in industrial organizations - The key factors

    International Nuclear Information System (INIS)

    Cooke, R.A.; Sarkis, H.D.

    1992-01-01

    A survey-based technique has been developed that measures and generates comparative data on important organizational, work group, and job-level variables that are directly related to on-the-job accidents. This paper describes the results of an analysis of data from more than 2,700 employees in the chemical, oil, construction, and wood products industries. These analyses indicate that several key variables are significantly related to accidents in the workplace

  20. The adenoid as a key factor in upper airway infections.

    Science.gov (United States)

    van Cauwenberge, P B; Bellussi, L; Maw, A R; Paradise, J L; Solow, B

    1995-06-01

    The adenoids (and the nasopharynx) play a key role in the normal functioning and in various pathologies of the upper respiratory tract. In this paper the role of adenoidal pathology and the beneficial effect of adenoidectomy in some upper respiratory tract and facial anomalies and diseases are discussed; otitis media with effusion, recurrent acute otitis media, sinusitis, snoring and sleep apnea and abnormal patterns in the midface growth and development.

  1. Self-regulated learning: A key learning effect of feedback in a ...

    African Journals Online (AJOL)

    Background. Problem-based learning (PBL) has been adopted across many health professions training institutions. Small-group student tutorials are a major component of PBL. Facilitator feedback during a tutorial is a key activity to promote self-regulated learning. Objective. To explore ways in which students use feedback ...

  2. 75 FR 72655 - Marine Sanitation Device Discharge Regulations for the Florida Keys National Marine Sanctuary

    Science.gov (United States)

    2010-11-26

    ... National Marine Sanctuary AGENCY: Office of National Marine Sanctuaries (ONMS), National Oceanic and... the regulations for the Florida Keys National Marine Sanctuary (FKNMS or sanctuary) by eliminating the exemption that allows discharges from within the boundary of the sanctuary of biodegradable effluent...

  3. Macrophages and fibroblasts : key regulators in wound healing, fibrosis and the foreign body reaction

    NARCIS (Netherlands)

    Ploeger, Diana

    2017-01-01

    Macrophages and fibroblasts are key regulators in wound healing, fibrosis and foreign body reaction (FBR). After injury macrophages migrate through the extracellular matrix (ECM) towards the wounded area, and adopt a M1 or M2 phenotype. M1 macrophages are associated with tissue injury and

  4. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    Science.gov (United States)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

    Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

  5. Determination of specificity influencing residues for key transcription factor families

    DEFF Research Database (Denmark)

    Patel, Ronak Y.; Garde, Christian; Stormo, Gary D.

    2015-01-01

    Transcription factors (TFs) are major modulators of transcription and subsequent cellular processes. The binding of TFs to specific regulatory elements is governed by their specificity. Considering the gap between known TFs sequence and specificity, specificity prediction frameworks are highly de...

  6. 153 Pedagogical Content Knowledge: A Key Factor in Teaching ...

    African Journals Online (AJOL)

    Nekky Umera

    expression in some media to project images in visual forms which are inherently embedded ... factor. As first described by Shulman (1986, 1987), PCK is a teachers' ..... ability and power of observation to represent foreshortening accurately in.

  7. Key Factors Influencing Customer Satisfaction in Korea's Mobile Service Sector

    OpenAIRE

    JAE YOUNG KIM; HYUNG SEOK LEE

    2013-01-01

    Advances in wireless technology have expanded the existing internet environment and accelerated the rapid development of mobile service. Many previous studies were conducted on users’ needs and satisfaction prior to the expansion of the mobile service. Thus, the impact of mobile service factors on user satisfaction has important implications for both academics and practitioners. This study investigates the factors affecting user satisfaction related to mobile service. First, this study extrac...

  8. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

    Science.gov (United States)

    Hirota, Simon A; Ng, Jeffrey; Lueng, Alan; Khajah, Maitham; Parhar, Ken; Li, Yan; Lam, Victor; Potentier, Mireille S; Ng, Kelvin; Bawa, Misha; McCafferty, Donna-Marie; Rioux, Kevin P; Ghosh, Subrata; Xavier, Ramnik J; Colgan, Sean P; Tschopp, Jurg; Muruve, Daniel; MacDonald, Justin A; Beck, Paul L

    2011-06-01

    Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  9. An Analysis of Key Factors in Developing a Smart City

    Directory of Open Access Journals (Sweden)

    Aidana Šiurytė

    2016-06-01

    Full Text Available The concept Smart City is used widely but it is perceived differently as well. Literature review reveals key elements of the Smart City – Information and Communication Technologies and Smart Citizens. Nevertheless, raising public awareness is not a priority of local municipalities which are trying to develop cities. Focus group discussion aims to analyse citizens’ insights in regards to the Smart City and their contribution to creation of it. Case study of Vilnius examines a position of mu-nicipality in developing city as smart. Study contains suggestions for the improvement of communication in the city. Methods employed: comparative literature analysis, focus group investigation, case study.

  10. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    and enhanced expressions of ethanol-tolerance genes associated with heat shock proteins, trehalose-glycolysis-pentose phosphate pathways and PDR gene family are accountable for the tolerant yeast to withstand the ethanol stress, maintain active metabolisms, and complete ethanol fermentation under the ethanol stress. Transcription factor Msn4p appeared to be a key regulator of gene interactions for ethanol-tolerance in the tolerant yeast Y-50316.

  11. Key factors driving corporate social responsibility of Vietnamese firms

    NARCIS (Netherlands)

    Kabir, Mohammed Rezaul; Thai Minh, H.

    2016-01-01

    We examine the impact of firm, corporate governance and managerial characteristics on the corporate social responsibility (CSR) activities of Vietnamese listed firms. Our results show that export-oriented firms engage in more CSR activities. As for corporate governance factors, we observe that

  12. Agricultural Cooperatives in the Netherlands: key success factors

    NARCIS (Netherlands)

    Bijman, J.

    2016-01-01

    The paper argues that the ongoing success of agricultural cooperatives in the Netherlands can be explained by the combination of five factors. First, the Netherlands has an enabling cooperative legislation. Second, cooperatives in the Netherlands have been able to maintain effective member control

  13. Migration towards fibre to the home: key cost factors

    Science.gov (United States)

    Zhou, L. W.; Mas Machuca, C.; Zhao, R.; Grunert, K.

    2010-12-01

    This paper presents a comprehensive cost model for migration towards FTTH, some case study results from different network area scenarios, as well as the identification of the most important cost factors to be considered by operators aiming at increasing the profitability of their networks.

  14. Key factors in children's competence to consent to clinical research

    NARCIS (Netherlands)

    Hein, Irma M.; Troost, Pieter W.; Lindeboom, Robert; Benninga, Marc A.; Zwaan, C. Michel; van Goudoever, Johannes B.; Lindauer, Ramón J. L.

    2015-01-01

    Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors

  15. Behaviour, the key factor for sports injury prevention.

    Science.gov (United States)

    Verhagen, Evert A L M; van Stralen, Maartje M; van Mechelen, Willem

    2010-11-01

    Safety in sports and physical activity is an important prerequisite for continuing participation in sports, as well as for maintenance of a healthy physically active lifestyle. For this reason, prevention, reduction and control of sports injuries are important goals for society as a whole. Recent advances in sports medicine discuss the need for research on real-life injury prevention. Such views call for a more behavioural approach when it comes to actual sports injury prevention. Nevertheless, the role of behaviour in sports injury prevention remains under-researched. In order to push the field of sports injury prevention forward, this article provides an overview of the relationship between behaviour and sports injury risk. Different types of behaviour relate to injury risk factors and injury mechanisms. Behaviour that influences risk factors and injury mechanisms is not confined only to the athlete. Various types of behaviour by, for example, the coach, referee, physical therapist or sports associations, also influence risk factors and injury mechanisms. In addition, multiple behaviours often act together. Some types of behaviour may directly affect injury risk and are by definition a risk factor. Other behaviours may only affect risk factors and injury mechanisms, and influence injury risk indirectly. Recent ideas on injury prevention that call for studies on real-life injury prevention still rely heavily on preventive measures that are established through efficacy research. A serious limitation in such an approach is that one expects that proven preventive measures will be adopted if the determinants and influences of sports safety behaviours are understood. Therefore, if one truly wants to prevent sports injuries in a real-life situation, a broader research focus is needed. In trying to do so, we need to look at lessons learned from other fields of injury prevention research.

  16. Key Success Factors of Innovation in Multinational Agrifood Prospector Companies

    OpenAIRE

    Fortuin, Frances T.J.M.; Batterink, Maarten H.; Omta, S.W.F. (Onno)

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) assesses a company’s drivers and barriers to innovation and benchmarks the critical success and failure factors of its innovation projects with data of agrifood prospector companies around the world. The present paper discusses its application in 12 multinational agrifood prospector companies in the Netherlands and France. It is concluded that WIAT by uncovering the tacit knowledge of the innovation project team creates opportunities for subs...

  17. Model of key success factors for Business Intelligence implementation

    OpenAIRE

    Peter Mesaros; Tomas Mandicak; Daniela Mackova; Stefan Carnicky; Martina Habinakova; Marcela Spisakova

    2016-01-01

    New progressive technologies recorded growth in every area. Information-communication technologies facilitate the exchange of information and it facilitates management of everyday activities in enterprises. Specific modules (such as Business Intelligence) facilitate decision-making. Several studies have demonstrated the positive impact of Business Intelligence to decision-making. The first step is to put in place the enterprise. The implementation process is influenced by many factors. This a...

  18. Empirical Investigation of Key Business Factors for Digital Game Performance

    OpenAIRE

    Aleem, Saiqa; Capretz, Luiz Fernando; Ahmed, Faheem

    2015-01-01

    Game development is an interdisciplinary concept that embraces software engineering, business, management, and artistic disciplines. This research facilitates a better understanding of the business dimension of digital games. The main objective of this research is to investigate empirically the effect of business factors on the performance of digital games in the market and to answer the research questions asked in this study. Game development organizations are facing high pressure and compet...

  19. Maturation of arteriovenous fistula: Analysis of key factors

    Directory of Open Access Journals (Sweden)

    Muhammad A. Siddiqui

    2017-12-01

    Full Text Available The growing proportion of individuals suffering from chronic kidney disease has considerable repercussions for both kidney specialists and primary care. Progressive and permanent renal failure is most frequently treated with hemodialysis. The efficiency of hemodialysis treatment relies on the functional status of vascular access. Determining the type of vascular access has prime significance for maximizing successful maturation of a fistula and avoiding surgical revision. Despite the frequency of arteriovenous fistula procedures, there are no consistent criteria applied before creation of arteriovenous fistulae. Increased prevalence and use of arteriovenous fistulae would result if there were reliable criteria to assess which arteriovenous fistulae are more likely to reach maturity without additional procedures. Published studies assessing the predictive markers of fistula maturation vary to a great extent with regard to definitions, design, study size, patient sample, and clinical factors. As a result, surgeons and specialists must decide which possible risk factors are most likely to occur, as well as which parameters to employ when evaluating the success rate of fistula development in patients awaiting the creation of permanent access. The purpose of this literature review is to discuss the role of patient factors and blood markers in the development of arteriovenous fistulae.

  20. Key factors in children's competence to consent to clinical research.

    Science.gov (United States)

    Hein, Irma M; Troost, Pieter W; Lindeboom, Robert; Benninga, Marc A; Zwaan, C Michel; van Goudoever, Johannes B; Lindauer, Ramón J L

    2015-10-24

    Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P competence judgments was 71.5 %. Only age and intelligence significantly and independently explained the variance in competence judgments, explaining 56.6 % and 12.7 % of the total variance respectively. SES, male gender, disease experience and ethnicity each explained less than 1 % of the variance in competence judgments. Contextual factors together explained an extra 2.8 % (P > 0.05). Age is the factor that

  1. A Key Factor of the DCF Model Coherency

    Directory of Open Access Journals (Sweden)

    Piotr Adamczyk

    2017-04-01

    Full Text Available Aim/purpose - The aim of this paper is to provide economically justified evidence that the business value calculated by income valuation methods is the same, regardless of the type of cash flow used in the valuation algorithm. Design/methodology/approach - The evidence was arrived at using free cash flow to equity (FCFE, debt (FCFD and firm (FCFF. The article draws attention to the FCFF method's particular popularity in income valuation, based on analysts' practice. It shows an overview of various approaches to determine the capital structure in the formula for WACC, both in practice and theory. Finally, it examines an empirical example with the authors' own derivations and postulates. Findings - The conclusion drawn from the conducted analysis is that the key to the reconciliation process, and thus DCF model coherency, is to apply the appropriate method of capital structure estimation during the calculation of the weighted average cost of capital (WACC. This capital structure will henceforth be referred to as 'income weights'. Research implications/limitations - It should be noted that the obtained compliance of valuation results does not imply that the income valuation becomes an objective way of determining business value. It still remains subjective. Originality/value/contribution - According to the presented approach, the DCF model's subjectivism is limited to the forecasts. The rest is the algorithm which, based on the principles of mathematics, should be used in the same way in every situation.

  2. Reliable LED Lighting Technologies: Key Factors and Procurement Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Lynn; Arquit Niederberger, Anne

    2015-10-08

    Abstract— Lighting systems have the ability to transform the economic and educational infrastructure of disadvantaged communities, and eradicating “light poverty” has become one of the primary goals of the International Year of Light 2015. Solid-state lighting (SSL) technology, based on light-emitting diode (LED) light sources, has emerged as the next generation of lighting technology, with a current global market penetration of roughly 5%. This paper will report on recent research on understanding SSL lighting system reliability (failure modes, environmental stressors, electrical power quality); discuss the implications of SSL technology reliability for providing lighting services; and suggest practical approaches to ensure SSL reliability to benefit humanity. Among the key findings from this work is that LED sources can be extremely reliable, withstanding a broad range of environmental stresses without failure. Nonetheless, SSL lighting systems can have a negative impact on electrical power reliability, as well as on the affordability of lighting services, without attention to the quality of the accompanying power infrastructure. It is therefore critical to ensure that the performance of the power supply electronics used in lighting systems is matched to the quality of the power source, when evaluating energy efficient lighting choices.

  3. Risk factors for vascular dementia: Hypotension as a key point

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2008-04-01

    Full Text Available Rita Moretti, Paola Torre, Rodolfo M Antonello, Davide Manganaro, Cristina Vilotti, Gilberto PizzolatoDepartment of Internal Medicine and Clinical Neurology University of Trieste, ItalyAbstract: Physiologically, the cerebral autoregulation system allows maintenance of constant cerebral blood flow over a wide range of blood pressure. In old people, there is a progressive reshape of cerebral autoregulation from a sigmoid curve to a straight line. This implies that any abrupt change in blood pressure will result in a rapid and significant change in cerebral blood flow. Hypertension has often been observed to be a risk factor for vascular dementia (VaD and sometimes for Alzheimer disease although not always. Indeed, high blood pressure may accelerate cerebral white matter lesions, but white matter lesions have been found to be facilitated by excessive fall in blood pressure, including orthostatic dysregulation and postprandial hypotension. Many recent studies observed among other data, that there was a correlation between systolic pressure reduction and cognitive decline in women, which was not accounted for by other factors. Baseline blood pressure level was not significantly related to cognitive decline with initial good cognition. Some researchers speculate that blood pressure reduction might be an early change of the dementing process. The most confounding factor is that low pressure by itself might be a predictor of death; nevertheless, the effect of low blood pressure on cognition is underestimated because of a survival bias. Another explanation is that clinically unrecognized vascular lesions in the brain or atherosclerosis are responsible for both cognitive decline and blood pressure reduction. We discuss the entire process, and try to define a possible mechanism that is able to explain the dynamic by which hypotension might be related to dementia.Keywords: vascular dementia, hypotension, low blood pressure, alzheimer disease

  4. Key factors for a high-quality VR experience

    Science.gov (United States)

    Champel, Mary-Luc; Doré, Renaud; Mollet, Nicolas

    2017-09-01

    For many years, Virtual Reality has been presented as a promising technology that could deliver a truly new experience to users. The media and entertainment industry is now investigating the possibility to offer a video-based VR 360 experience. Nevertheless, there is a substantial risk that VR 360 could have the same fate as 3DTV if it cannot offer more than just being the next fad. The present paper aims at presenting the various quality factors required for a high-quality VR experience. More specifically, this paper will focus on the main three VR quality pillars: visual, audio and immersion.

  5. Modeling lichen communities : ecological key factors in a changing environment

    OpenAIRE

    Lopes, Pedro António Pinho, 1976-

    2010-01-01

    Tese de doutoramento, Biologia (Ecologia), Universidade de Lisboa, Faculdade de Ciências, 2010 O fenómeno das alterações globais influencia o funcionamento de muitos dos sistemas planetários. Embora os factores ambientais associados a esse fenómeno funcionem numa escala global, os seus efeitos nos ecossistemas têm de ser estudados localmente. Este estudo é complexo não só pela necessidade de obter informação com uma elevada resolução espacial, mas também pela dificuldade de estarmos a trab...

  6. Decommissioning: Regulatory activities and identification of key organizational and human factors safety issues

    International Nuclear Information System (INIS)

    Durbin, N.E.; Melber, B.D.; Lekberg, A.

    2001-12-01

    In the late 1990's the Swedish government decided to shut down Unit 1 of the Barsebaeck nuclear power plant. This report documents some of the efforts made by the Swedish Nuclear Power Inspectorate (SKI) to address human factors and organizational issues in nuclear safety during decommissioning of a nuclear facility. This report gives a brief review of the background to the decommissioning of Barsebaeck 1 and points out key safety issues that can arise during decommissioning. The main regulatory activities that were undertaken were requirements that the plant provide special safety reports on decommissioning focusing on first, the operation of both units until closure of Unit 1 and second, the operation of Unit 2 when Unit 1 was closed. In addition, SKI identified areas that might be affected by decommissioning and called these areas out for special attention. With regard to these areas of special attention, SKI required that the plant provide monthly reports on changing and emerging issues as well as self-assessments of the areas to be addressed in the special safety reports. Ten key safety issues were identified and evaluated with regard to different stages of decommissioning and with regard to the actions taken by Barsebaeck. Some key conclusions from SKI's experience in regulating a decommissioning nuclear power plant conclude the report

  7. Key biogeochemical factors affecting soil carbon storage in Posidonia meadows

    KAUST Repository

    Serrano, Oscar

    2016-08-15

    Biotic and abiotic factors influence the accumulation of organic carbon (C-org) in seagrass ecosystems. We surveyed Posidonia sinuosa meadows growing in different water depths to assess the variability in the sources, stocks and accumulation rates of Corg. We show that over the last 500 years, P. sinuosa meadows closer to the upper limit of distribution (at 2-4 m depth) accumulated 3- to 4-fold higher C-org stocks (averaging 6.3 kg C-org m(-2) at 3- to 4-fold higher rates (12.8 gC(org) m(-2) yr(-1) ) compared to meadows closer to the deep limits of distribution (at 6-8 m depth; 1.8 kg C-org m(-2) and 3.6 g C-org m(-2) yr(-1) . In shallower meadows, C-org stocks were mostly derived from seagrass detritus (88% in average) compared to meadows closer to the deep limit of distribution (45% on average). In addition, soil accumulation rates and fine-grained sediment content (< 0.125 mm) in shallower meadows (2.0 mm yr(-1) and 9 %, respectively) were approximately 2-fold higher than in deeper meadows (1.2 mm yr(-1) and 5 %, respectively). The C-org stocks and accumulation rates accumulated over the last 500 years in bare sediments (0.6 kg C-org m(-2) and 1.2 g C-org m(-2) yr(-1)were 3- to 11-fold lower than in P. sinuosa meadows, while fine-grained sediment content (1 %) and seagrass detritus contribution to the Corg pool (20 %) were 8- and 3-fold lower than in Posidonia meadows, respectively. The patterns found support the hypothesis that Corg storage in seagrass soils is influenced by interactions of biological (e.g., meadow productivity, cover and density), chemical (e.g., recalcitrance of Corg stocks) and physical (e.g., hydrodynamic energy and soil accumulation rates) factors within the meadow. We conclude that there is a need to improve global estimates of seagrass carbon storage accounting for biogeochemical factors driving variability within habitats.

  8. UNIVERSITIES AND INCUBATORS: KEY FACTORS DRIVING ENTREPRENEURSHIP AND SOCIOECONOMIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Liane Mahlmann Kipper

    2014-12-01

    Full Text Available Economic diversification is an utterly important factor for regions that are directly or indirectly related to any productive mechanisms and seek to strengthen their foundations for the generation of jobs and income. Within this context, to invest in business preparation and maturation, especially in the ones related to the technological area, turns out to be an interesting mean of diversifying a regional economy that is facing the risk of stagnation. This study considers the importance of the role taken on by universities and their incubators in driving entrepreneurship and supporting the creation of new companies and the innovative capacity of a country through knowledge transfer amongst universities and companies, generating benefits and socioeconomic progress in a country. It also conducts a case study on a company of the information technology area, recently incubated and whose major objective consists in becoming part of this economic diversification basis.

  9. Enzymatic biodiesel synthesis. Key factors affecting efficiency of the process

    Energy Technology Data Exchange (ETDEWEB)

    Szczesna Antczak, Miroslawa; Kubiak, Aneta; Antczak, Tadeusz; Bielecki, Stanislaw [Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Technical University of Lodz, Stefanowskiego 4/10, 90-924 Lodz (Poland)

    2009-05-15

    Chemical processes of biodiesel production are energy-consuming and generate undesirable by-products such as soaps and polymeric pigments that retard separation of pure methyl or ethyl esters of fatty acids from glycerol and di- and monoacylglycerols. Enzymatic, lipase-catalyzed biodiesel synthesis has no such drawbacks. Comprehension of the latter process and an appreciable progress in production of robust preparations of lipases may soon result in the replacement of chemical catalysts with enzymes in biodiesel synthesis. Engineering of enzymatic biodiesel synthesis processes requires optimization of such factors as: molar ratio of substrates (triacylglycerols: alcohol), temperature, type of organic solvent (if any) and water activity. All of them are correlated with properties of lipase preparation. This paper reports on the interplay between the crucial parameters of the lipase-catalyzed reactions carried out in non-aqueous systems and the yield of biodiesel synthesis. (author)

  10. Elucidating key factors affecting radionuclide aging in soils

    Energy Technology Data Exchange (ETDEWEB)

    Roig, M. [Universitat Politecnica Catalunya, Institut de Tecniques Energetiques, Barcelona (Spain); Rigola, A.; Vidal, M.; Rauret, G. [Barcelona Univ., Dept. de Quimica Analitica (Spain)

    2004-07-01

    Mechanistic studies allow at present to describe the processes governing the short-term interaction of radiostrontium and radiocaesium in soils. The initial sorption step can be described through the estimation of the soil-soil solution distribution coefficient from soil parameters, as cationic exchange capacity, radiocaesium interception potential and concentration of competing ions in the soil solution. After the initial soil-radionuclide interaction, a fraction of radionuclide is no longer available for exchange with the solution, and it remains fixed in the solid fraction. At present, the initial fixed fraction of a radionuclide in a given soil cannot be predicted from soil properties. Besides, little is known about soil and environmental factors (e.g., temperature; hydric regime) provoking the increase in the fixed fraction with time, the so-called aging process. This process is considered to control the reduction of food contamination with time at contaminated scenarios. Therefore, it is crucial to be able to predict the radionuclide aging in the medium and long term for a better risk assessment, especially when a decision has to be made between relying on natural attenuation versus implementing intervention actions. Here we study radiostrontium and radiocaesium aging in a set of soils, covering a wide range of soil types of contrasting properties (e.g., loamy calcareous; podzol; chernozem, organic). Three factors are separately and simultaneously tested: time elapsed since contamination, temperature and hydric regime. Changes in the radionuclide fixed fraction are estimated with a leaching test based on the use of a mild extractant solution. In addition to this, secondary effects on the radiocaesium interception potential in various soils are also considered. (author)

  11. Some considerations on the key economic factors of ISER development

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki

    1987-01-01

    In Sweden and the U.S., experiments are being made for testing and verification of the basic PIUS principle and the stability of interfaces at high temperature and high pressure. Japan's Ministry of International Trade and Industry envisaged, in its 1986 future planning of nuclear power, a nuclear capacity of 87 GWe in 2010 and 137 GWe in 2030. Before contemplating an actual siting of ISER near or in an city, ISER experimental reactor must pass severe tests. Required tests for ISER, however, are simple and limited, because the probable frequency and characteristics of major abnormal situations can be well identified and defined in the course of conceptual design and detailed safety analyses. Economy of LWRs in general, and PIUS-ISER in particular, rests on many factors including the services for the front end, uranium supply-enrichment and the back end of its fuel cycle; spent fuel storage and low level waste management; and the safety and availability of the reactor. PIUS-ISER has several unique features that are not available in existing LWRs. These features are related with control rod, control room, reliance on natural circulation cooling, source term, containment, BOP and emergency AC power. Technological development work for ISER should cover interface design, steam generator, antiseismic design, and pool water cooling measures. (Nogami, K.)

  12. Jasmonate-responsive transcription factors regulating plant secondary metabolism.

    Science.gov (United States)

    Zhou, Meiliang; Memelink, Johan

    2016-01-01

    Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Sox9b is a key regulator of pancreaticobiliary ductal system development.

    Directory of Open Access Journals (Sweden)

    Marion Delous

    Full Text Available The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the

  14. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Dan-Dan Cao

    2016-05-01

    Full Text Available MicroRNAs (miRNAs are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.

  15. Fibroblast Growth Factor Signaling in Metabolic Regulation.

    Science.gov (United States)

    Nies, Vera J M; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T; Atkins, Annette R; Evans, Ronald M; Jonker, Johan W; Downes, Michael Robert

    2015-01-01

    The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  16. A single cis element maintains repression of the key developmental regulator Gata2.

    Directory of Open Access Journals (Sweden)

    Jonathan W Snow

    2010-09-01

    Full Text Available In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element -1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the -1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the -1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.

  17. Key factors influencing the implementation success of a home telecare application.

    NARCIS (Netherlands)

    Postema, T.R.F.; Peeters, J.M.; Freide, R.D.

    2012-01-01

    Rationale The introduction of home telecare in healthcare organizations has shown mixed results in practice. The aim of this study is to arrive at a set of key factors that can be used in further implementation of video communication. We argue that key factors are mainly found in the organizational

  18. The transcription factor NFATp plays a key role in susceptibility to TB in mice.

    Directory of Open Access Journals (Sweden)

    Laura E Via

    Full Text Available In T cells, the transcription factor nuclear factor of activated T cells p (NFATp is a key regulator of the cytokine genes tumor necrosis factor (TNF and interferon-γ (IFN-γ. Here, we show that NFATp-deficient (NFATp(-/- mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4(+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC. The rapid mortality and disease severity observed in MTb-infected NFATp(-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp(-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

  19. The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS.

    Directory of Open Access Journals (Sweden)

    Sujitha Duggimpudi

    Full Text Available Genetic translocation of EWSR1 to ETS transcription factor coding region is considered as primary cause for Ewing sarcoma. Previous studies focused on the biology of chimeric transcription factors formed due to this translocation. However, the physiological consequences of heterozygous EWSR1 loss in these tumors have largely remained elusive. Previously, we have identified various mRNAs bound to EWS using PAR-CLIP. In this study, we demonstrate CCDC6, a known cell cycle regulator protein, as a novel target regulated by EWS. siRNA mediated down regulation of EWS caused an elevated apoptosis in cells in a CCDC6-dependant manner. This effect was rescued upon re-expression of CCDC6. This study provides evidence for a novel functional link through which wild-type EWS operates in a target-dependant manner in Ewing sarcoma.

  20. Fibroblast growth factor signaling in metabolic regulation

    Directory of Open Access Journals (Sweden)

    Vera eNies

    2016-01-01

    Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

  1. Regulation of Memory Formation by the Transcription Factor XBP1

    Directory of Open Access Journals (Sweden)

    Gabriela Martínez

    2016-02-01

    Full Text Available Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer’s disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR, mediating adaptation to endoplasmic reticulum (ER stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long-term potentiation (LTP, whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF, a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress.

  2. SCOR based key success factors in cooking oil supply chain buyers perspective in Padang City

    Science.gov (United States)

    Zahara, Fatimah; Hadiguna, Rika Ampuh

    2017-11-01

    Supply chain of cooking oil is a network of companies from palm oil as raw material to retailers which work to create the value and deliver products into the end consumers. This paper is aimed to study key success factors based on consumer's perspective as the last stage in the supply chain. Consumers who are examined in this study are restaurants management or owners. Restaurant is the biggest consumption of cooking oil. The factors is studied based on Supply Chain Operation Reference (SCOR) version 10.0. Factors used are formulated based on the third-level metrics of SCOR Model. Factors are analyzed using factors analysis. This study found factors which become key success factors in managing supply chain of cooking oil encompass reliability, responsiveness and agility. Key success factors can be applied by governments as policy making and cooking oil companies as formulation of the distribution strategies.

  3. NLRC5: a key regulator of MHC class I-dependent immune responses.

    Science.gov (United States)

    Kobayashi, Koichi S; van den Elsen, Peter J

    2012-12-01

    The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

  4. MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators.

    Directory of Open Access Journals (Sweden)

    Siva K Panguluri

    Full Text Available Diabetes is a metabolic disorder that ultimately results in major pathophysiological complications in the cardiovascular system. Diabetics are predisposed to higher incidences of sudden cardiac deaths (SCD. Several studies have associated diabetes as a major underlying risk for heart diseases and its complications. The diabetic heart undergoes remodeling to cope up with the underlying changes, however ultimately fails. In the present study we investigated the changes associated with a key ion channel and transcriptional factors in a diabetic heart model. In the mouse db/db model, we identified key transcriptional regulators and mediators that play important roles in the regulation of ion channel expression. Voltage-gated potassium channel (Kv4.2 is modulated in diabetes and is down regulated. We hypothesized that Kv4.2 expression is altered by potassium channel interacting protein-2 (KChIP2 which is regulated upstream by NFkB and miR-301a. We utilized qRT-PCR analysis and identified the genes that are affected in diabetes in a regional specific manner in the heart. At protein level we identified and validated differential expression of Kv4.2 and KChIP2 along with NFkB in both ventricles of diabetic hearts. In addition, we identified up-regulation of miR-301a in diabetic ventricles. We utilized loss and gain of function approaches to identify and validate the role of miR-301a in regulating Kv4.2. Based on in vivo and in vitro studies we conclude that miR-301a may be a central regulator for the expression of Kv4.2 in diabetes. This miR-301 mediated regulation of Kv4.2 is independent of NFkB and Irx5 and modulates Kv4.2 by direct binding on Kv4.2 3'untranslated region (3'-UTR. Therefore targeting miR-301a may offer new potential for developing therapeutic approaches.

  5. Combinatorial regulation of tissue specification by GATA and FOG factors

    Science.gov (United States)

    Chlon, Timothy M.; Crispino, John D.

    2012-01-01

    The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

  6. Dopamine is a key regulator in the signalling pathway underlying predator-induced defences in Daphnia

    Science.gov (United States)

    Weiss, Linda C.; Leese, Florian; Laforsch, Christian; Tollrian, Ralph

    2015-01-01

    The waterflea Daphnia is a model to investigate the genetic basis of phenotypic plasticity resulting from one differentially expressed genome. Daphnia develops adaptive phenotypes (e.g. morphological defences) thwarting predators, based on chemical predator cue perception. To understand the genomic basis of phenotypic plasticity, the description of the precedent cellular and neuronal mechanisms is fundamental. However, key regulators remain unknown. All neuronal and endocrine stimulants were able to modulate but not induce defences, indicating a pathway of interlinked steps. A candidate able to link neuronal with endocrine responses is the multi-functional amine dopamine. We here tested its involvement in trait formation in Daphnia pulex and Daphnia longicephala using an induction assay composed of predator cues combined with dopaminergic and cholinergic stimulants. The mere application of both stimulants was sufficient to induce morphological defences. We determined dopamine localization in cells found in close association with the defensive trait. These cells serve as centres controlling divergent morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine is involved in proliferation and structural formation of morphological defences. Furthermore, dopamine pathways appear to be interconnected with endocrine pathways, and control juvenile hormone and ecdysone levels. In conclusion, dopamine is suggested as a key regulator of phenotypic plasticity. PMID:26423840

  7. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Directory of Open Access Journals (Sweden)

    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  8. Factoring RSA keys from certified smart cards : Coppersmith in the wild

    NARCIS (Netherlands)

    Bernstein, D.J.; Chang, Y.A.; Cheng, C.M.; Chou, L.P.; Heninger, N.; Lange, T.; Someren, van N.

    2013-01-01

    An attacker can efficiently factor at least 184 distinct 1024-bit RSA keys from Taiwan's national "Citizen Digital Certificate" database. The big story here is that these keys were generated by government-issued smart cards that were certified secure. The certificates had all the usual buzzwords:

  9. Application of the Value Optimization Model of Key Factors Based on DSEM

    Directory of Open Access Journals (Sweden)

    Chao Su

    2016-01-01

    Full Text Available The key factors of the damping solvent extraction method (DSEM for the analysis of the unbounded medium are the size of bounded domain, the artificial damping ratio, and the finite element mesh density. To control the simulation accuracy and computational efficiency of the soil-structure interaction, this study establishes a value optimization model of key factors that is composed of the design variables, the objective function, and the constraint function system. Then the optimum solutions of key factors are obtained by the optimization model. According to some comparisons of the results provided by the different initial conditions, the value optimization model of key factors is feasible to govern the simulation accuracy and computational efficiency and to analyze the practical unbounded medium-structure interaction.

  10. Using the key success factor concept in competitor intelligence and benchmarking

    DEFF Research Database (Denmark)

    Bisp, Søren; Sørensen, Elin; Grunert, Klaus G.

    1997-01-01

    A key success factor is regarded as a skill or a resource that a business can invest in, which explains a major part of the observable differences in perceived value of the offer and/or relative costs of bringing that offer to the marketplace. Key success factors are potentially useful in structu......A key success factor is regarded as a skill or a resource that a business can invest in, which explains a major part of the observable differences in perceived value of the offer and/or relative costs of bringing that offer to the marketplace. Key success factors are potentially useful...... in structuring the generation of market intelligence in competitor analysis and benchmarking. To this end, a method was developed, based on a reverse laddering procedure, which elicits decision-makers' subjec causal maps. When aggregated, these maps can be used to derive competitor analysis systems. The paper...

  11. Dnmt3a in the dorsal dentate gyrus is a key regulator of fear renewal.

    Science.gov (United States)

    Gong, Zhiting; Zhou, Qiang

    2018-03-23

    Renewal of extinguished fear memory in an altered context is widely believed to be a major limiting issue for exposure therapy in treating various psychiatric diseases. Effective prevention of fear renewal will significantly improve the efficacy of exposure therapy. DNA methyltransferase (DNMTs) mediated epigenetic processes play critical roles in long term memory, but little is known about their functions in fear memory extinction or renewal. Here we investigated whether DNMTs regulate fear renewal after extinction. We found that elevated Dnmt3a level in the dorsal dentate gyrus (dDG) of hippocampus was associated with the absence of fear renewal in an altered context after extinction training. Overexpression and knockdown of Dnmt3a in the dDG regulated the occurrence of fear renewal in a bi-directional manner. In addition, Dnmt3a overexpression was associated with elevated expression of c-Fos in the dDG during extinction training. Furthermore, we found that renewal of remote fear memory can be prevented, and the absence of renewal was concurrent with an elevated Dnmt3a level. Our results indicate that Dnmt3a in the dDG is a key regulator of fear renewal after extinction, and Dnmt3a may play a critical role in controlling fear memory return and thus has therapeutic values.

  12. GREEN KEY AS A MOTIVATING FACTOR FOR STAFF LOYALTY AND SATISFACTION

    OpenAIRE

    Mozgov, Maxim

    2017-01-01

    This thesis is connected to staff motivation: which kind of motivation tools motivate employees, and does the Green Key motivate employees to work in the organization which is holding this eco label. The main goal of the thesis was determine the influence of the Green Key on motivation and sustainable development. The objectives of the thesis were to find out which motivational factors are present in the current hotel for employees to perform their job better. Which motivational factors are t...

  13. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks.

    Science.gov (United States)

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-11-30

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost.

  14. Identification of the key factors for success in the hotel sector

    Directory of Open Access Journals (Sweden)

    Fernando Campa-Planas

    2018-02-01

    Design/methodology: A review of the literature has been carried out, which has provided references related to the hotel sector and different factors that impact it. The knowledge provided by the scientific community through the articles and texts consulted are reflected in this document and allow us to determine the existence of the key factors for success.  Contributions/results: Considering the importance of the hotel sector in the Spanish economy, this study identifies the key factors in the different hotel establishments. However, the materialization of these factors provides and shows us which financial aspects, management systems and other more global aspects, such as longevity or location, enable the company to be successful in the hotel sector.  Originality/value: Based on the literature reviewed, a list of key factors for success in the hotel sector was composed. This also revealed a lack of similar studies on this topic.

  15. Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

    Science.gov (United States)

    Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

    2016-09-09

    Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators

  16. EVALUATING KEY ENVIRONMENTAL RISK FACTORS FOR POLLUTION AT INTERNATIONAL PORTS IN TAIWAN

    Directory of Open Access Journals (Sweden)

    Kuan-Hao Chang

    2017-01-01

    Full Text Available The main purpose of this paper is to use the fuzzy analytic hierarchy process (FAHP approach to evaluate the key environmental risk factors for pollution at international ports in Taiwan. Relying on the literature and experts’ opinions, a hierarchical structure with three risk aspects and thirteen risk factors is first constructed, and a FAHP model then proposed. Based on data from the AHP experts’ questionnaires, we use the FAHP approach to determine key environmental risk factors. Finally, the results show that: (1 Air pollution is the most important aspect of environmental pollution at international ports in Taiwan. (2 In order of relative importance, the top five key environmental risk factors for pollution at international ports in Taiwan are the oil leaks from ships, volatile organic compounds (VOCs, exhaust emissions from ships at berth, harmful coatings on ships' hulls, and ships' failure to use low-pollution fuel. Furthermore, some discussions are provided for port authority in Taiwan.

  17. Regulative change targeting energy performance of buildings in Sweden. Key drivers and main implications

    Energy Technology Data Exchange (ETDEWEB)

    Fuglseth, Bente Beckstroem

    2009-02-15

    This report has explored changes in two regulations targeting energy performance of buildings in Sweden, energy requirements and certification of buildings. The objective has been to investigate the effect of the implementation of the EU directive on energy performance of buildings (EPBD) on these two regulations and to what degree the directive can explain the regulative changes. The analytical framework has also included domestic factors; the influence of the national government and the organizational field. The analysis revealed that whereas the EPBD has acted only as facilitator in connection with the changes in energy requirements, it has been the sole driver of some of the changes in Sweden's new certification system. Several of the changes during the period studied can however be traced to the national government and the organizational field. But the EPBD has also worked as a facilitator of the changes promoted by domestic actors. The directive has been used to legitimize radical changes that would have been difficult to implement in other ways. (Author). 40 refs., 2 tabs

  18. Examining the Key Factors Affecting e-Service Quality of Small Online Apparel Businesses in Malaysia

    OpenAIRE

    Che Nawi Noorshella; Al Mamun Abdullah; Ahmad Raston Nursalihah

    2015-01-01

    e-Service quality (eSQ) is increasingly recognized as an important aspect, as well as the key to determining the competitive advantage and factor in the long-term retention of firms operating online. This study, therefore, is aimed at identifying the key determinants of eSQ among the small online apparel businesses in Malaysia. This study used a cross-sectional design, and data were collected from 765 customers who pur...

  19. Specificity determinants for autoproteolysis of LexA, a key regulator of bacterial SOS mutagenesis.

    Science.gov (United States)

    Mo, Charlie Y; Birdwell, L Dillon; Kohli, Rahul M

    2014-05-20

    Bacteria utilize the tightly regulated stress response (SOS) pathway to respond to a variety of genotoxic agents, including antimicrobials. Activation of the SOS response is regulated by a key repressor-protease, LexA, which undergoes autoproteolysis in the setting of stress, resulting in derepression of SOS genes. Remarkably, genetic inactivation of LexA's self-cleavage activity significantly decreases acquired antibiotic resistance in infection models and renders bacteria hypersensitive to traditional antibiotics, suggesting that a mechanistic study of LexA could help inform its viability as a novel target for combating acquired drug resistance. Despite structural insights into LexA, a detailed knowledge of the enzyme's protease specificity is lacking. Here, we employ saturation and positional scanning mutagenesis on LexA's internal cleavage region to analyze >140 mutants and generate a comprehensive specificity profile of LexA from the human pathogen Pseudomonas aeruginosa (LexAPa). We find that the LexAPa active site possesses a unique mode of substrate recognition. Positions P1-P3 prefer small hydrophobic residues that suggest specific contacts with the active site, while positions P5 and P1' show a preference for flexible glycine residues that may facilitate the conformational change that permits autoproteolysis. We further show that stabilizing the β-turn within the cleavage region enhances LexA autoproteolytic activity. Finally, we identify permissive positions flanking the scissile bond (P4 and P2') that are tolerant to extensive mutagenesis. Our studies shed light on the active site architecture of the LexA autoprotease and provide insights that may inform the design of probes of the SOS pathway.

  20. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    Science.gov (United States)

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

  2. Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

    Science.gov (United States)

    Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

    2018-05-21

    The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  3. Key Economic Parameters for an Optimal Pharmacy Network in a Regulated Environment

    Directory of Open Access Journals (Sweden)

    Franjo MLINARIC

    2016-10-01

    Full Text Available Pharmacies are an integral part of the modern healthcare system which strives for a holistic and effi cient care. General practitioners and pharmacists are held in high esteem among local communities as they are the fi rst point of contact when people have health issues. However, a strong demand for health services in developed countries and its present fi nancing schemes undermined the sustainability of the whole health system (8.9% of GDP in 2013 and growing. According to WHO and EU recommendations, the whole healthcare system shall accept a holistic approach and focus on education, prevention and proper medicine consume. Part of this strategy is a seamless care concept, where medical doctors and pharmacists build a team around the well-being of a patient. Financing scheme incentives and KPI’s (key performance indicators will be focused on keeping people healthy, instead of paying for procedures. The future healthcare ecosystem obliges pharmacists to optimize network coverage and to extend health services. Nevertheless, their growth strategy needs to be gradual, considering the present level of network coverage, the low pace of private and public expenditures for medicine and services, and the fact that a new fi nancing model for pharmacies is still unknown. Thus, we expect the development of pharmacy network in regulated environment to be fi nanced predominantly from retained earnings in publicly owned pharmacies and by awarding pharmacy concessions.

  4. Studies of key success factors of product development success: A reinterpretation of results

    DEFF Research Database (Denmark)

    Plichta, Kirsten; Harmsen, Hanne

    In this paper the general validity of the research area of key factors of success in product development is discussed. To be more specific we argue that validity hinges on the causal relation between success and success factrors ­ a relation that unaccounted for in the empirical studies....... The theoretical tradition of the resource-based perspective provides ­ at least to some extent ­ an account of this causality. An important point in the paper is that the key factors of success in the empi studies are not factors causally related to success, but at the most a number of valuable resources and thus......, but in the studies problems concerning implementation are not discussed. When the lists factors of success are interprested as valuable resources and capabilities, we show that some implications on the implementability might be deduced from the resource-based perspective....

  5. Key lessons: Twelve factors critical to the success of WDM at the ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    English · Français ... Key lessons: Twelve factors critical to the success of WDM at the policy and at the operational levels ... from slums in central New Delhi to the city's desolate periphery face daily indignities and danger as they collect water o.

  6. Agri-Environmental Resource Management by Large-Scale Collective Action: Determining KEY Success Factors

    Science.gov (United States)

    Uetake, Tetsuya

    2015-01-01

    Purpose: Large-scale collective action is necessary when managing agricultural natural resources such as biodiversity and water quality. This paper determines the key factors to the success of such action. Design/Methodology/Approach: This paper analyses four large-scale collective actions used to manage agri-environmental resources in Canada and…

  7. Students' educational careers in Higher Education: a search into key factors regarding study outcome

    NARCIS (Netherlands)

    Dr. Cyrille A.C. Van Bragt

    2010-01-01

    Students' educational careers in Higher Education: a search into key factors regarding study outcome One of the political goals of the EU is to develop 'the most competitive knowledge-based economy in the world by 2010'. The Dutch knowledge economy faces an increased demand for highly-educated

  8. A qualitative study of the key factors in implementing telemedical monitoring of diabetic foot ulcer patients

    DEFF Research Database (Denmark)

    Rasmussen, B S B; Jensen, L K; Froekjaer, J

    2015-01-01

    of a telemedical intervention. We posed the following research question: What are the key organizational factors in the implementation of telemedicine in wound care? METHODS: In connection with a randomized controlled trial of telemedical intervention for patients with diabetic foot ulcers in the region...

  9. Key Motivational Factors in the Retention of Three Generations of Public High School Mathematics Teachers

    Science.gov (United States)

    Pospichal, Wendy

    2011-01-01

    Purpose: The purpose of this study was to describe and compare the similarities and differences between five key motivational factors: (a) new teacher induction, (b) noninduction mentor support in the early years of teaching, (c) salary and benefits, (d) working conditions, and (e) administrative support influential in retention of employment in…

  10. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    Science.gov (United States)

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  11. Six Key Factors for Changing Preservice Teachers' Attitudes/Beliefs about Diversity

    Science.gov (United States)

    Garmon, M. Arthur

    2005-01-01

    In this article the author postulates there are six key factors associated with changing preservice teachers' attitudes toward and beliefs about diversity-their dispositions, which include openness, self-awarenesss/self-reflectiveness, and commitment to social justice; and their experiences, which include intercultural, educational, and support…

  12. Transcriptional regulation by competing transcription factor modules.

    Directory of Open Access Journals (Sweden)

    Rutger Hermsen

    2006-12-01

    Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

  13. Exploring the factors influencing clinical students' self-regulated learning

    NARCIS (Netherlands)

    Berkhout, Joris J.; Helmich, Esther; Teunissen, Pim W.; van den Berg, Joost W.; van der Vleuten, Cees P. M.; Jaarsma, A. Debbie C.

    2015-01-01

    The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and regulatory bodies. Supporting the development of SRL skills has proven difficult because self-regulation is a complex interactive process and we know relatively little about the factors

  14. From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis

    Directory of Open Access Journals (Sweden)

    Zuzanna Rzepka

    2016-06-01

    Full Text Available Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI or 5,6-dihydroxyindole-2-carboxylic acid (DHICA. Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCβ cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones. Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells.

  15. Key Factors of Quality in the Sector of Tourism Services Providers: Case Study: Czech Republic

    Directory of Open Access Journals (Sweden)

    Ida Vajčnerová

    2014-01-01

    Full Text Available The paper summarizes main results of partial research aimed at detection of the key factors affecting quality in the sector of tourism services providers, namely tour operators and travel agencies. A primary questionnaire survey was conducted; the researched factors were distributed in the context of service quality dimensions (Grönroos model; the dimensions were tested in relation to sex, age and education of the respondents (ANOVA; Brown-Forsythe test. Assurance was identified as the most important dimension. The output of the study is determining the significance of individual quality factors from the perspective of a potential customer when selecting a service provider.

  16. Response regulator heterodimer formation controls a key stage in Streptomyces development.

    Directory of Open Access Journals (Sweden)

    Mahmoud M Al-Bassam

    2014-08-01

    Full Text Available The orphan, atypical response regulators BldM and WhiI each play critical roles in Streptomyces differentiation. BldM is required for the formation of aerial hyphae, and WhiI is required for the differentiation of these reproductive structures into mature spores. To gain insight into BldM function, we defined the genome-wide BldM regulon using ChIP-Seq and transcriptional profiling. BldM target genes clustered into two groups based on their whi gene dependency. Expression of Group I genes depended on bldM but was independent of all the whi genes, and biochemical experiments showed that Group I promoters were controlled by a BldM homodimer. In contrast, Group II genes were expressed later than Group I genes and their expression depended not only on bldM but also on whiI and whiG (encoding the sigma factor that activates whiI. Additional ChIP-Seq analysis showed that BldM Group II genes were also direct targets of WhiI and that in vivo binding of WhiI to these promoters depended on BldM and vice versa. We go on to demonstrate that BldM and WhiI form a functional heterodimer that controls Group II promoters, serving to integrate signals from two distinct developmental pathways. The BldM-WhiI system thus exemplifies the potential of response regulator heterodimer formation as a mechanism to expand the signaling capabilities of bacterial cells.

  17. Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

    International Nuclear Information System (INIS)

    Casula, Milena; Sini, MariaCristina; Palomba, Grazia; The Italian Melanoma Intergroup; Palmieri, Giuseppe; Muggiano, Antonio; Cossu, Antonio; Budroni, Mario; Caracò, Corrado; Ascierto, Paolo A; Pagani, Elena; Stanganelli, Ignazio; Canzanella, Sergio

    2009-01-01

    Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16 CDKN2A , BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16 CDKN2A genes. For melanoma susceptibility, investigations at germline level indicated that p16 CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16 CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16 CDKN2A silencing). Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

  18. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

    Science.gov (United States)

    Dinan, Timothy G.

    2016-01-01

    Abstract There is a growing realisation that the gut–brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age‐related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long‐term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics. PMID:27641441

  19. Regulation of Specialized Metabolism by WRKY Transcription Factors

    Science.gov (United States)

    Schluttenhofer, Craig; Yuan, Ling

    2015-01-01

    WRKY transcription factors (TFs) are well known for regulating plant abiotic and biotic stress tolerance. However, much less is known about how WRKY TFs affect plant-specialized metabolism. Analysis of WRKY TFs regulating the production of specialized metabolites emphasizes the values of the family outside of traditionally accepted roles in stress tolerance. WRKYs with conserved roles across plant species seem to be essential in regulating specialized metabolism. Overall, the WRKY family plays an essential role in regulating the biosynthesis of important pharmaceutical, aromatherapy, biofuel, and industrial components, warranting considerable attention in the forthcoming years. PMID:25501946

  20. Chemistry of fog: Factors regulating its composition

    Energy Technology Data Exchange (ETDEWEB)

    Sigg, L.; Stumm, W.; Zobrist, J.; Zuercher, F.

    1987-05-01

    Fog droplets acquire their composition, in principle, by similar mechanisms as cloudwater droplets. The solute concentrations of fogwater (H/sup +/, NH/sub 4/+, NO/sub 3//sup -/, SO/sub 4//sup 2-/, Cl/sup -/, organic acids, and trace metals) are 10-50 times higher than those of rainwater. Urban fogs reflect in their composition the effect of local emissions. Occasionally, very acidic fogs, often due to HCl contamination, with pH values as low as 2 were observed. Fogs can affect ecosystems by concentrating, moving, and depositing chemicals and atmospheric pollutants. Basically, the major composition of fogwater results from the interaction of SO/sub 2/, NO/sub x/, CO/sub 2/, HCl, and NH/sub 3/ with H/sub 2/O in an oxidative environment (O/sub 2/, O/sub 3/, OH/sup ./, H/sub 2/O/sub 2/, sunlight) and in the presence of some traces that may act as redox catalysts (metals such as Cu, Fe, Mn, organic material such as hydrocarbons, and dust and soot surfaces). - The composition of numerous (radiation type) ground-level fogs, and their variation with time from formation to dissipation, have been investigated in Duebendorf (near Zuerich) in order to evaluate the factors that influence the composition; specifically to explore the mechanisms of NO/sub 3//sup -/ and SO/sub 4//sup 2/ incorperation Surprisingly constant motor propertions of NH/sub 4//sup +/:SO/sub 4//sup 2-/:NO/sub 3//sup -/ were observed in the fog. The results do not permit to establish unambiguously to what extent the inclusion of SO/sub 4//sup 2-/ and NO/sub 3//sup -/ into the fogwater is due to the oxidation of absorbed and dissolved SO/sub 2/ and the scavenging of gaseous HNO/sub 3/ or by dissolution of ambient previously formed ammonium sulfate and ammonium nitrate aerosols.

  1. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray.

    Science.gov (United States)

    Xie, Wengui; Ji, Lixin; Zhao, Teng; Gao, Pengfei

    2015-05-09

    A number of genes have been identified to be related with primary osteoporosis while less is known about the comprehensive interactions between regulating genes and proteins. We aimed to identify the differentially expressed genes (DEGs) and regulatory effects of transcription factors (TFs) involved in primary osteoporosis. The gene expression profile GSE35958 was obtained from Gene Expression Omnibus database, including 5 primary osteoporosis and 4 normal bone tissues. The differentially expressed genes between primary osteoporosis and normal bone tissues were identified by the same package in R language. The TFs of these DEGs were predicted with the Essaghir A method. DAVID (The Database for Annotation, Visualization and Integrated Discovery) was applied to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DEGs. After analyzing regulatory effects, a regulatory network was built between TFs and the related DEGs. A total of 579 DEGs was screened, including 310 up-regulated genes and 269 down-regulated genes in primary osteoporosis samples. In GO terms, more up-regulated genes were enriched in transcription regulator activity, and secondly in transcription factor activity. A total 10 significant pathways were enriched in KEGG analysis, including colorectal cancer, Wnt signaling pathway, Focal adhesion, and MAPK signaling pathway. Moreover, total 7 TFs were enriched, of which CTNNB1, SP1, and TP53 regulated most up-regulated DEGs. The discovery of the enriched TFs might contribute to the understanding of the mechanism of primary osteoporosis. Further research on genes and TFs related to the WNT signaling pathway and MAPK pathway is urgent for clinical diagnosis and directing treatment of primary osteoporosis.

  2. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

    Directory of Open Access Journals (Sweden)

    Shuai Zhao

    Full Text Available In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

  3. Predicting Arrest in a Sample of Youth Perinatally Exposed to HIV: The Intersection of HIV and Key Contextual Factors.

    Science.gov (United States)

    Elkington, Katherine S; Peters, Zachary; Choi, C Jean; Bucek, Amelia; Leu, Cheng-Shiun; Abrams, Elaine J; Mellins, Claude A

    2017-11-22

    We examined the role of youth HIV status and other key factors on past-year arrest in perinatally HIV-exposed but uninfected (PHIV-) and perinatally HIV-infected (PHIV+) youth using data from a multi-site study of psychosocial behaviors in PHIV-exposed urban youth (N = 340; 61% PHIV+; 51% female; ages 9-16 at baseline). Youth and caregivers were administered 5 interviews, spanning approximately 7.5 years. Using longitudinal logistic mixed-effect models, we explored the association between past year arrest, internal [e.g., substance use disorder (SUD)] and external (e.g., neighborhood arrest rates) contextual factors, and social-regulation processes (e.g., in-school/work). Arrest rates increased from 2.6 to 19.7% across follow-ups; there were no differences in arrest over time by HIV status. In the final model, odds of arrest were greater for youth who were male, with SUD, ≥ 18 years old, with high levels of city stress, and neither in school nor employed. PHIV-exposed, urban youth have much higher rates of arrest than national samples. Lack of differences in arrest by HIV status suggests key contextual factors are more important in promoting arrest.

  4. Key Factors Affecting Construction Safety Performance in Developing Countries: Evidence from Cambodia

    Directory of Open Access Journals (Sweden)

    Serdar Durdyev

    2017-12-01

    Full Text Available Although proper safety management in construction is of utmost importance; anecdotal evidence suggests that safety is not adequately considered in many developing countries. This paper considers the key variables affecting construction safety performance in Cambodia. Using an empirical questionnaire survey targeting local construction professionals, respondents were invited to rate the level of importance of 30 variables identified from the seminal literature. The data set was subjected to factor analysis. Correlations between the variables show that five key factors underlie the challenges facing the local industry; management and organisation, resources, site management, cosmetic and workforce. It is found that the forefront construction professionals (top management and government authorities should take more responsibilities for further improvements in safety performance on project sites. Findings and recommendations of this study may be useful to construction professional who are seeking ways to improve safety records in developing countries.

  5. Three-factor anonymous authentication and key agreement scheme for Telecare Medicine Information Systems.

    Science.gov (United States)

    Arshad, Hamed; Nikooghadam, Morteza

    2014-12-01

    Nowadays, with comprehensive employment of the internet, healthcare delivery services is provided remotely by telecare medicine information systems (TMISs). A secure mechanism for authentication and key agreement is one of the most important security requirements for TMISs. Recently, Tan proposed a user anonymity preserving three-factor authentication scheme for TMIS. The present paper shows that Tan's scheme is vulnerable to replay attacks and Denial-of-Service attacks. In order to overcome these security flaws, a new and efficient three-factor anonymous authentication and key agreement scheme for TMIS is proposed. Security and performance analysis shows superiority of the proposed scheme in comparison with previously proposed schemes that are related to security of TMISs.

  6. APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death

    DEFF Research Database (Denmark)

    Fortin, A; Cregan, S P; MacLaurin, J G

    2001-01-01

    p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulati...

  7. Key factors of case management interventions for frequent users of healthcare services: a thematic analysis review.

    Science.gov (United States)

    Hudon, Catherine; Chouinard, Maud-Christine; Lambert, Mireille; Diadiou, Fatoumata; Bouliane, Danielle; Beaudin, Jérémie

    2017-10-22

    The aim of this paper was to identify the key factors of case management (CM) interventions among frequent users of healthcare services found in empirical studies of effectiveness. Thematic analysis review of CM studies. We built on a previously published review that aimed to report the effectiveness of CM interventions for frequent users of healthcare services, using the Medline, Scopus and CINAHL databases covering the January 2004-December 2015 period, then updated to July 2017, with the keywords 'CM' and 'frequent use'. We extracted factors of successful (n=7) and unsuccessful (n=6) CM interventions and conducted a mixed thematic analysis to synthesise findings. Chaudoir's implementation of health innovations framework was used to organise results into four broad levels of factors: (1) ,environmental/organisational level, (2) practitioner level, (3) patient level and (4) programme level. Access to, and close partnerships with, healthcare providers and community services resources were key factors of successful CM interventions that should target patients with the greatest needs and promote frequent contacts with the healthcare team. The selection and training of the case manager was also an important factor to foster patient engagement in CM. Coordination of care, self-management support and assistance with care navigation were key CM activities. The main issues reported by unsuccessful CM interventions were problems with case finding or lack of care integration. CM interventions for frequent users of healthcare services should ensure adequate case finding processes, rigorous selection and training of the case manager, sufficient intensity of the intervention, as well as good care integration among all partners. Other studies could further evaluate the influence of contextual factors on intervention impacts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted

  8. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    International Nuclear Information System (INIS)

    Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

    2011-01-01

    The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

  9. Key Factors Affecting the Price of Airbnb Listings: A Geographically Weighted Approach

    OpenAIRE

    Zhihua Zhang; Rachel J. C. Chen; Lee D. Han; Lu Yang

    2017-01-01

    Airbnb has been increasingly gaining popularity since 2008 due to its low prices and direct interactions with the local community. This paper employed a general linear model (GLM) and a geographically weighted regression (GWR) model to identify the key factors affecting Airbnb listing prices using data sets of 794 samples of Airbnb listings of business units in Metro Nashville, Tennessee. The results showed that the GWR model performs better than the GLM in terms of accuracy and affected vari...

  10. Nicotine affects rat Leydig cell function in vivo and vitro via down-regulating some key steroidogenic enzyme expressions.

    Science.gov (United States)

    Guo, Xiaoling; Wang, Huang; Wu, Xiaolong; Chen, Xianwu; Chen, Yong; Guo, Jingjing; Li, Xiaoheng; Lian, Qingquan; Ge, Ren-Shan

    2017-12-01

    Nicotine is consumed largely as a component of cigarettes and has a potential effect on pubertal development of Leydig cells in males. To investigate its effects, 49-day-old male Sprague Dawley rats received intraperitoneal injections of nicotine (0.5 or 1 mg/kg/day) for 2 weeks and immature Leydig cells were isolated from the testes of 35-day-old rats and treated with nicotine (0.05-50 μM). Serum hormones, Leydig cell number and related gene expression levels after in vivo treatment were determined and medium androgen levels were measured and cell cycle, apoptosis, mitochondrial membrane potential (△Ψm), and reactive oxygen species (ROS) of Leydig cells after in vitro treatment were measured. In vivo exposure to nicotine lowered serum luteinizing hormone, follicle stimulating hormone, and testosterone levels and reduced Leydig cell number and gene expression levels. Nicotine in vitro inhibited androgen production in Leydig cells by downregulating the expression levels of P450 cholesterol side cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, and steroidogenic factor 1 at different concentration ranges. In conclusion, nicotine disrupts Leydig cell steroidogenesis during puberty possibly via down-regulating some key steroidogenic enzyme expressions. Copyright © 2017. Published by Elsevier Ltd.

  11. Exploring the Key Risk Factors for Application of Cloud Computing in Auditing

    Directory of Open Access Journals (Sweden)

    Kuang-Hua Hu

    2016-08-01

    Full Text Available In the cloud computing information technology environment, cloud computing has some advantages such as lower cost, immediate access to hardware resources, lower IT barriers to innovation, higher scalability, etc., but for the financial audit information flow and processing in the cloud system, CPA (Certified Public Accountant firms need special considerations, for example: system problems, information security and other related issues. Auditing cloud computing applications is the future trend in the CPA firms, given this issue is an important factor for them and very few studies have been conducted to investigate this issue; hence this study seeks to explore the key risk factors for the cloud computing and audit considerations. The dimensions/perspectives of the application of cloud computing audit considerations are huge and cover many criteria/factors. These risk factors are becoming increasingly complex, and interdependent. If the dimensions could be established, the mutually influential relations of the dimensions and criteria determined, and the current execution performance established; a prioritized improvement strategy designed could be constructed to use as a reference for CPA firm management decision making; as well as provide CPA firms with a reference for build auditing cloud computing systems. Empirical results show that key risk factors to consider when using cloud computing in auditing are, in order of priority for improvement: Operations (D, Automating user provisioning (C, Technology Risk (B and Protection system (A.

  12. Factors affecting self-regulated learning in medical students: a qualitative study.

    Science.gov (United States)

    Jouhari, Zahra; Haghani, Fariba; Changiz, Tahereh

    2015-01-01

    Clinical courses are required of all medical students and means that they must develop the key skill of self-regulation during learning. The ability to self-regulate learning strategies is affected by different factors. This study determined the views of medical students on the factors affecting self-regulated learning (SRL). This study uses a qualitative approach and the content analysis method. Nineteen medical students in their fourth, fifth, and sixth years of study at Isfahan University of Medical Science participated in semi-structured, in-depth interviews. The students were selected using purposive sampling based on their overall grade point average (GPA). Five main themes were found to affect SRL. These themes included family with the two subthemes of family supervisory and supportive roles; peers with the two subthemes of facilitating and inhibiting roles; instructors with the two subthemes of personal and educational instructor's characteristics; educational environment with the two subthemes of facilitator and inhibitor roles; and student with the two subthemes of facilitating and inhibiting personal factors. The outcomes of student understanding of the factors affecting self-regulation indicate that facilitating factors should be used on an individual basis to reduce the effect of inhibiting factors to improve self-regulation in students.

  13. Study of dynamic amplification factor of DEMO blanket caused by a gap at the supporting key

    International Nuclear Information System (INIS)

    Frosi, Paolo; Mazzone, Giuseppe

    2015-01-01

    Highlights: • With the preliminary hypothesis established, the dynamic displacements are not so high and the state of stress (not reported) does not exhibit large region with plastic strain. • The dynamic displacements show a certain dependency from the mesh adopted, and the geometry chosen. • The energy (kinetic or strain) of the whole structure gives useful information about the key behavior during impact. • In order to better understand the overall phenomenon other details (non-linear material, better evaluation of damping, other disruption rise-times and so on. - Abstract: Among the design activities of the in vessel components for DEMO promoted by European Fusion Development Agreement (EFDA) organization, this work deals with the gap required at the supporting keys of the blanket. Due to its higher operating temperatures compared to the vacuum vessel (VV) ones, this gap will increase during operation. The electro magnetic (EM) loads due to fast disruptions occur on a short time and might accelerate the blanket significantly before it touches the supporting keys, causing an impact of the blanket itself onto the keys. Depending on their stiffness, the EM loads with their short time scale could excite the structure's natural frequencies, causing dynamic amplification. Both phenomena (impact and dynamic amplification) can cause stresses in the structure significantly higher than the static ones. This work develops a finite element model of DEMO blanket to study its non-linear transient dynamic behavior under impact loadings. A VV sector, the ribs between the inner and outer VV, the backward manifolds and the supporting keys of the blanket have been modeled. The analyses have been performed with Abaqus [1] and Ansys [2] FEM codes focused on the displacements of the keys in their housing on the blanket. The dynamic amplification factor has been evaluated as the ratio of dynamic to static displacements in meaningful points of the structure for a growing gap

  14. Study of dynamic amplification factor of DEMO blanket caused by a gap at the supporting key

    Energy Technology Data Exchange (ETDEWEB)

    Frosi, Paolo, E-mail: paolo.frosi@enea.it; Mazzone, Giuseppe

    2015-10-15

    Highlights: • With the preliminary hypothesis established, the dynamic displacements are not so high and the state of stress (not reported) does not exhibit large region with plastic strain. • The dynamic displacements show a certain dependency from the mesh adopted, and the geometry chosen. • The energy (kinetic or strain) of the whole structure gives useful information about the key behavior during impact. • In order to better understand the overall phenomenon other details (non-linear material, better evaluation of damping, other disruption rise-times and so on. - Abstract: Among the design activities of the in vessel components for DEMO promoted by European Fusion Development Agreement (EFDA) organization, this work deals with the gap required at the supporting keys of the blanket. Due to its higher operating temperatures compared to the vacuum vessel (VV) ones, this gap will increase during operation. The electro magnetic (EM) loads due to fast disruptions occur on a short time and might accelerate the blanket significantly before it touches the supporting keys, causing an impact of the blanket itself onto the keys. Depending on their stiffness, the EM loads with their short time scale could excite the structure's natural frequencies, causing dynamic amplification. Both phenomena (impact and dynamic amplification) can cause stresses in the structure significantly higher than the static ones. This work develops a finite element model of DEMO blanket to study its non-linear transient dynamic behavior under impact loadings. A VV sector, the ribs between the inner and outer VV, the backward manifolds and the supporting keys of the blanket have been modeled. The analyses have been performed with Abaqus [1] and Ansys [2] FEM codes focused on the displacements of the keys in their housing on the blanket. The dynamic amplification factor has been evaluated as the ratio of dynamic to static displacements in meaningful points of the structure for a growing

  15. A simple repeat polymorphism in the MITF-M promoter is a key regulator of white spotting in dogs.

    Directory of Open Access Journals (Sweden)

    Izabella Baranowska Körberg

    Full Text Available The white spotting locus (S in dogs is colocalized with the MITF (microphtalmia-associated transcription factor gene. The phenotypic effects of the four S alleles range from solid colour (S to extreme white spotting (s(w. We have investigated four candidate mutations associated with the s(w allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.

  16. Key factors in the successful implementation of enterprise resource planning system

    Directory of Open Access Journals (Sweden)

    Farajollah Rahnavard

    2014-04-01

    Full Text Available Enterprise Resource Planning Systems (ERP are considered as the newest and most effective tools of enterprise resource planning and include an interconnected information, management and engineering system that meets all the needs of an organization. ERP implementation is costly and time-consuming and makes fundamental change in the process, if not implemented correctly it will cause challenges in most parts of the organization and will certainly fail. Therefore, the identification of key success factors in implementing ERP helps organizations avoid the loss of the project. This research aims to identify key success factors for ERP by examining 185 managers, professionals, experts of the Information and Communication Technology Institute associated with the Ministry of Communications and Information Technology of Iran. A questionnaire was used to collect data. Findings from exploratory factor analysis indicate that five factors: 1 user friendliness, flexible and consistency 2 establishment of project management; 3 alignment with user needs; 4 Management of organizational changes, and 5 observing the principles of successful implementation of ERP affect the institute and the corresponding suggestions are proposed consistent with these findings.

  17. Effect of 3 Key Factors on Average End to End Delay and Jitter in MANET

    Directory of Open Access Journals (Sweden)

    Saqib Hakak

    2015-01-01

    Full Text Available A mobile ad-hoc network (MANET is a self-configuring infrastructure-less network of mobile devices connected by wireless links where each node or mobile device is independent to move in any desired direction and thus the links keep moving from one node to another. In such a network, the mobile nodes are equipped with CSMA/CA (carrier sense multiple access with collision avoidance transceivers and communicate with each other via radio. In MANETs, routing is considered one of the most difficult and challenging tasks. Because of this, most studies on MANETs have focused on comparing protocols under varying network conditions. But to the best of our knowledge no one has studied the effect of other factors on network performance indicators like throughput, jitter and so on, revealing how much influence a particular factor or group of factors has on each network performance indicator. Thus, in this study the effects of three key factors, i.e. routing protocol, packet size and DSSS rate, were evaluated on key network performance metrics, i.e. average delay and average jitter, as these parameters are crucial for network performance and directly affect the buffering requirements for all video devices and downstream networks.

  18. 77 FR 23425 - Revisions of Boundaries, Regulations and Zoning Scheme for Florida Keys National Marine Sanctuary...

    Science.gov (United States)

    2012-04-19

    .... Increase abundance and condition of selected key species including corals, queen conch, long spined sea..., Rooms 165 C and D, 2295 Victoria Ave., Fort Myers, FL 33901. Consultation Under National Historic...

  19. Examining the Key Factors Affecting e-Service Quality of Small Online Apparel Businesses in Malaysia

    Directory of Open Access Journals (Sweden)

    Che Nawi Noorshella

    2015-04-01

    Full Text Available e-Service quality (eSQ is increasingly recognized as an important aspect, as well as the key to determining the competitive advantage and factor in the long-term retention of firms operating online. This study, therefore, is aimed at identifying the key determinants of eSQ among the small online apparel businesses in Malaysia. This study used a cross-sectional design, and data were collected from 765 customers who purchased apparel online at the point-of-purchase. Findings of this study indicate that “product information quality,” “website design,” “security and privacy,” and “expected consumer service” are the key determinants of eSQ among small online apparel businesses in Malaysia. The implication for the owner-managers of the apparel businesses in Malaysia is that they must be aware of the significance of the key eSQ indicators while designing their businesses, to attract and retain customers.

  20. Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest.

    Science.gov (United States)

    Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

    2015-08-20

    Tropical rainforests cover over 50% of all known plant and animal species and provide a variety of key resources and ecosystem services to humans, largely mediated by metabolic activities of soil microbial communities. A deep analysis of soil microbial communities and their roles in ecological processes would improve our understanding on biogeochemical elemental cycles. However, soil microbial functional gene diversity in tropical rainforests and causative factors remain unclear. GeoChip, contained almost all of the key functional genes related to biogeochemical cycles, could be used as a specific and sensitive tool for studying microbial gene diversity and metabolic potential. In this study, soil microbial functional gene diversity in tropical rainforest was analyzed by using GeoChip technology. Gene categories detected in the tropical rainforest soils were related to different biogeochemical processes, such as carbon (C), nitrogen (N) and phosphorus (P) cycling. The relative abundance of genes related to C and P cycling detected mostly derived from the cultured bacteria. C degradation gene categories for substrates ranging from labile C to recalcitrant C were all detected, and gene abundances involved in many recalcitrant C degradation gene categories were significantly (P rainforest. Soil available N could be the key factor in shaping the soil microbial functional gene structure and metabolic potential.

  1. The Key Factors Analysis of Palisades Temperature in Deep Open-pit Mine

    Science.gov (United States)

    Wang, Yuan; Du, Cuifeng; Jin, Wenbo; Wang, Puyu

    2018-01-01

    In order to study the key factors of palisades temperature field in a deep open-pit mine in the natural environment, the influence of natural factors on the palisades temperature in a deep open-pit mine were analysed based on the principle of heat transfer. Four typical places with different ways of solar radiation were selected to carry out the field test. The results show that solar radiation, atmospheric temperature, and wind speed are three main factors affecting the temperature of palisades and that the direct sunlight plays a leading role. The time period of the sun shining directly on the shady slope of the palisades is short because of blocking effect, whose temperature changes in a smaller scale. At the same time, the sun slope of the palisades suffers from the solar radiation for a long time, whose temperature changes in a larger scale, and the variation is similar to the air temperature.

  2. The development of today's mineable oil sands projects, the key factors influencing economics

    International Nuclear Information System (INIS)

    Lynn, J.R.

    1991-01-01

    Many factors influence the perception of economic performance for developing projects. Some of these factors can be controlled by the developer, while some are outside the developer's sphere of influence. Technology selection, management systems, stakeholder involvement, environmental responsiveness and risk management are areas that may be influenced, however interest rates, product prices and currency exchange all have a measurable effect on project economics and are beyond a developer's control. Economic considerations for evaluating mineable oil sand development projects are outlined, focussing on the key factors unique to such developments in general and to the OSLO project in particular. The OSLO project is a proposed $5 billion energy development that entails constructing an open pit oil sands mine and a bitumen extraction facility north of Fort McMurray, Alberta, coupled with a bitumen upgrader in the Redwater area. 7 figs

  3. Two-Factor User Authentication with Key Agreement Scheme Based on Elliptic Curve Cryptosystem

    Directory of Open Access Journals (Sweden)

    Juan Qu

    2014-01-01

    Full Text Available A password authentication scheme using smart card is called two-factor authentication scheme. Two-factor authentication scheme is the most accepted and commonly used mechanism that provides the authorized users a secure and efficient method for accessing resources over insecure communication channel. Up to now, various two-factor user authentication schemes have been proposed. However, most of them are vulnerable to smart card loss attack, offline password guessing attack, impersonation attack, and so on. In this paper, we design a password remote user authentication with key agreement scheme using elliptic curve cryptosystem. Security analysis shows that the proposed scheme has high level of security. Moreover, the proposed scheme is more practical and secure in contrast to some related schemes.

  4. Polypyrimidine Tract Binding Protein Homologs from Arabidopsis Are Key Regulators of Alternative Splicing with Implications in Fundamental Developmental Processes[W

    Science.gov (United States)

    Rühl, Christina; Stauffer, Eva; Kahles, André; Wagner, Gabriele; Drechsel, Gabriele; Rätsch, Gunnar; Wachter, Andreas

    2012-01-01

    Alternative splicing (AS) generates transcript variants by variable exon/intron definition and massively expands transcriptome diversity. Changes in AS patterns have been found to be linked to manifold biological processes, yet fundamental aspects, such as the regulation of AS and its functional implications, largely remain to be addressed. In this work, widespread AS regulation by Arabidopsis thaliana Polypyrimidine tract binding protein homologs (PTBs) was revealed. In total, 452 AS events derived from 307 distinct genes were found to be responsive to the levels of the splicing factors PTB1 and PTB2, which predominantly triggered splicing of regulated introns, inclusion of cassette exons, and usage of upstream 5′ splice sites. By contrast, no major AS regulatory function of the distantly related PTB3 was found. Dependent on their position within the mRNA, PTB-regulated events can both modify the untranslated regions and give rise to alternative protein products. We find that PTB-mediated AS events are connected to diverse biological processes, and the functional implications of selected instances were further elucidated. Specifically, PTB misexpression changes AS of PHYTOCHROME INTERACTING FACTOR6, coinciding with altered rates of abscisic acid–dependent seed germination. Furthermore, AS patterns as well as the expression of key flowering regulators were massively changed in a PTB1/2 level-dependent manner. PMID:23192226

  5. Transcription factors involved in the regulation of natural killer cell development and function: an update

    Directory of Open Access Journals (Sweden)

    Martha Elia Luevano

    2012-10-01

    Full Text Available Natural Killer (NK cells belong to the innate immune system and are key effectors in the immune response against cancer and infection. Recent studies have contributed to the knowledge of events controlling NK cell fate. The use of knockout mice has enabled the discovery of key transcription factors (TFs essential for NK cell development and function. Yet, unwrapping the downstream targets of these TFs and their influence on NK cells remains a challenge. In this review we discuss the latest TFs described to be involved in the regulation of NK cell development and maturation.

  6. Key Factors for the Linkage Strategy between R and D and Commercialization for Gen-ΙV

    International Nuclear Information System (INIS)

    Lee, Kyoungmi; Hong, Jung Suk

    2013-01-01

    The Fukushima nuclear disaster has leaded to enhance the safety and the cost-effectiveness of technology for the future so that advanced countries such as United Sates and France have concerned about a next generation nuclear power plant, Gen-IV(Generation-IV Reactor). Considering various characteristics of nuclear R and D, it is necessary to have more elaborated strategies for the effective development of the next generation of nuclear technology. In this study, we suggest 5 key factors for the successful commercialization of Gen-IV by analyzing the distinct characteristics of nuclear R and D with Gen-IV and CSF(Critical Success Factor)s of several cases in these field and conducting the FGI(Focus Group Interview). Considering these results, we could find and suggest some important points for further strategy for Gen-IV. That is, following five key factors for the linkage improvement between R and D and commercialization of Gen-IV should be considered: the participation of nuclear power plant operators from the beginning, the establishment of consistent and comprehensive plan/roadmap/detailed strategy, the technology development based on global energy issues and international cooperation, the stable and clear funding plans for long-term projects, the cooperation of relative ministries. Gen-IV system is getting a positive response in that it accompanies long-term R and D plans in Korea. We think that the standard of Gen-IV would lead the next generation of nuclear industry if the proper strategy for the cooperation between the private sector and the regulation from the beginning. Moreover, we expect that this study will facilitate its development process from R and D to commercialization

  7. Key Factors for the Linkage Strategy between R and D and Commercialization for Gen-ΙV

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyoungmi; Hong, Jung Suk [Korean Institute of S and T Evaluation and Planning, Seoul (Korea, Republic of)

    2013-05-15

    The Fukushima nuclear disaster has leaded to enhance the safety and the cost-effectiveness of technology for the future so that advanced countries such as United Sates and France have concerned about a next generation nuclear power plant, Gen-IV(Generation-IV Reactor). Considering various characteristics of nuclear R and D, it is necessary to have more elaborated strategies for the effective development of the next generation of nuclear technology. In this study, we suggest 5 key factors for the successful commercialization of Gen-IV by analyzing the distinct characteristics of nuclear R and D with Gen-IV and CSF(Critical Success Factor)s of several cases in these field and conducting the FGI(Focus Group Interview). Considering these results, we could find and suggest some important points for further strategy for Gen-IV. That is, following five key factors for the linkage improvement between R and D and commercialization of Gen-IV should be considered: the participation of nuclear power plant operators from the beginning, the establishment of consistent and comprehensive plan/roadmap/detailed strategy, the technology development based on global energy issues and international cooperation, the stable and clear funding plans for long-term projects, the cooperation of relative ministries. Gen-IV system is getting a positive response in that it accompanies long-term R and D plans in Korea. We think that the standard of Gen-IV would lead the next generation of nuclear industry if the proper strategy for the cooperation between the private sector and the regulation from the beginning. Moreover, we expect that this study will facilitate its development process from R and D to commercialization.

  8. cAMP and EPAC are key players in the regulation of the signal transduction pathway involved in the α-hemolysin autophagic response.

    Directory of Open Access Journals (Sweden)

    María Belén Mestre

    Full Text Available Staphylococcus aureus is a microorganism that causes serious diseases in the human being. This microorganism is able to escape the phagolysosomal pathway, increasing intracellular bacterial survival and killing the eukaryotic host cell to spread the infection. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. We have shown that the pore-forming toxin α-hemolysin (Hla is the S. aureus-secreted factor responsible for the activation of the autophagic pathway and that this response occurs through a PI3K/Beclin1-independent form. In the present report we demonstrate that cAMP has a key role in the regulation of this autophagic response. Our results indicate that cAMP is able to inhibit the autophagy induced by Hla and that PKA, the classical cAMP effector, does not participate in this regulation. We present evidence that EPAC and Rap2b, through calpain activation, are the proteins involved in the regulation of Hla-induced autophagy. Similar results were obtained in cells infected with different S. aureus strains. Interestingly, in this report we show, for the first time to our knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing phagosome. We believe that our findings have important implications in understanding innate immune processes involved in intracellular pathogen invasion of the host cell.

  9. Expression of Peroxisome Proliferator-Activated Receptor-γ in Key Neuronal Subsets Regulating Glucose Metabolism and Energy Homeostasis

    OpenAIRE

    Sarruf, David A.; Yu, Fang; Nguyen, Hong T.; Williams, Diana L.; Printz, Richard L.; Niswender, Kevin D.; Schwartz, Michael W.

    2008-01-01

    In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-γ agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARγ is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARγ distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spa...

  10. Social Cognition and Executive Functions As Key Factors for Effective Pedagogy in Higher Education.

    Science.gov (United States)

    Correia, Rut; Navarrete, Gorka

    2017-01-01

    Higher education (HE) faces the challenge of responding to an increasing diversity. In this context, more attention is being paid to teachers and teaching skills positively related to students learning. Beyond the knowledges identified as key components of an effective teacher, teachers also need to be capable of unraveling what their students think and believe, and how they accommodate the new information. More importantly, teachers need to be able to adapt their own teaching to their audience's needs. In learners, social cognition (SC) has been related to a better receptivity to the different teacher-student interactions. Since these interactions are bidirectional, SC could also help to explain teachers' receptiveness to the information available in feedback situations. However, little is known about how SC is related to teacher development, and therefore teaching effectiveness, in HE. In addition, executive functions (EFs), closely related to SC, could play a key role in the ability to self-regulate their own teaching to better answering their students emerging needs. Although there is wide evidence regarding the association of EFs to performance in high demanding settings, as far as we know, there are no studies exploring the relationship between teachers' EFs and teaching effectiveness in HE. Establishing a positive association between teaching effectiveness and these socio-cognitive functions could be a promising first step in designing professional development programs that promote HE academics' ability to understand and care about students thoughts and emotions, to eventually adapt their teaching to their students needs for a better learning.

  11. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.

    Science.gov (United States)

    Park, YoHan; Park, YoungHo

    2016-12-14

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.

  12. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks

    Science.gov (United States)

    Park, YoHan; Park, YoungHo

    2016-01-01

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.’s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment. PMID:27983616

  13. Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulation.

    Science.gov (United States)

    Pragman, Alexa A; Schlievert, Patrick M

    2004-10-01

    Staphylococcus aureus is a pathogenic microorganism that is responsible for a wide variety of clinical infections. These infections can be relatively mild, but serious, life-threatening infections may result from the expression of staphylococcal virulence factors that are coordinated by virulence regulators. Much work has been done to characterize the actions of staphylococcal virulence regulators in broth culture. Recently, several laboratories showed that transcriptional analyses of virulence regulators in in vivo animal models or in human infection did not correlate with transcriptional analyses accomplished in vitro. In describing the differences between in vitro and in vivo transcription of staphylococcal virulence regulators, we hope to encourage investigators to study virulence regulators using infection models whenever possible.

  14. Effect of Loads and Other Key Factors on Oil-Transformer Ageing: Sustainability Benefits and Challenges

    Directory of Open Access Journals (Sweden)

    Radu Godina

    2015-10-01

    Full Text Available Transformers are one of the more expensive pieces of equipment found in a distribution network. The transformer’s role has not changed over the last decades. With simple construction and at the same time mechanically robust, they offer long term service that on average can reach half a century. Today, with the ongoing trend to supply a growing number of non-linear loads along with the notion of distributed generation (DG, a new challenge has arisen in terms of transformer sustainability, with one of the possible consequences being accelerated ageing. In this paper we carefully review the existing studies in the literature of the effect of loads and other key factors on oil-transformer ageing. The state-of-the-art is reviewed, each factor is analysed in detail, and in the end a smart transformer protection method is sought in order to monitor and protect it from upcoming challenges.

  15. CHILD-PARENT VIOLENCE: MAIN CHARACTERISTICS, RISK FACTORS AND KEYS TO INTERVENTION

    Directory of Open Access Journals (Sweden)

    M. Luisa Martínez

    2015-09-01

    Full Text Available Child-parent Violence (hereinafter CPV is an increasingly evident problem in the social, health, and judicial protection systems which, however, continue to show a number of major deficiencies with respect to the main characteristics of CPV, the people involved, the underlying factors, and efficacious interventions. Nevertheless, there is a consensus regarding its devastating consequences. The present bibliographical review is focused on analysing the problem of CPV with the aim of offering useful data for future research and intervention proposals. Specifically, this paper provides a definition of CPV and its types, some data on prevalence, the main characteristics of aggressive children and abused parents, and the most important individual, family, school and community risk factors highlighted in the current scientific literature. The keys areas of intervention with this group are also presented.

  16. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  17. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  18. Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

    Directory of Open Access Journals (Sweden)

    Anna Klimaszewska

    2011-11-01

    Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

  19. Cytokinins as key regulators in plant–microbe–insect interactions: connecting plant growth and defence

    NARCIS (Netherlands)

    Giron, D.; Frago, E.; Glevarec, G.; Pieterse, C.M.J.; Dicke, M.

    2013-01-01

    1. Plant hormones play important roles in regulating plant growth and defence by mediating developmental processes and signalling networks involved in plant responses to a wide range of parasitic and mutualistic biotic interactions. 2. Plants are known to rapidly respond to pathogen and herbivore

  20. PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

    Directory of Open Access Journals (Sweden)

    Dan Cheng

    Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

  1. Self-regulation – the key to progress in clinical reasoning? | Postma ...

    African Journals Online (AJOL)

    Both groups lauded the scaffolding that the case-based curriculum provided. Strategic thinking, goal orientation and self-regulation ability were identified in group 1. A lack of diligence, poor data-processing ability and a possible lack of interest were identified in group 2 students, who were unaware of learning opportunities.

  2. Identification of the key ecological factors influencing vegetation degradation in semi-arid agro-pastoral ecotone considering spatial scales

    Science.gov (United States)

    Peng, Yu; Wang, Qinghui; Fan, Min

    2017-11-01

    When assessing re-vegetation project performance and optimizing land management, identification of the key ecological factors inducing vegetation degradation has crucial implications. Rainfall, temperature, elevation, slope, aspect, land use type, and human disturbance are ecological factors affecting the status of vegetation index. However, at different spatial scales, the key factors may vary. Using Helin County, Inner-Mongolia, China as the study site and combining remote sensing image interpretation, field surveying, and mathematical methods, this study assesses key ecological factors affecting vegetation degradation under different spatial scales in a semi-arid agro-pastoral ecotone. It indicates that the key factors are different at various spatial scales. Elevation, rainfall, and temperature are identified as crucial for all spatial extents. Elevation, rainfall and human disturbance are key factors for small-scale quadrats of 300 m × 300 m and 600 m × 600 m, temperature and land use type are key factors for a medium-scale quadrat of 1 km × 1 km, and rainfall, temperature, and land use are key factors for large-scale quadrats of 2 km × 2 km and 5 km × 5 km. For this region, human disturbance is not the key factor for vegetation degradation across spatial scales. It is necessary to consider spatial scale for the identification of key factors determining vegetation characteristics. The eco-restoration programs at various spatial scales should identify key influencing factors according their scales so as to take effective measurements. The new understanding obtained in this study may help to explore the forces which driving vegetation degradation in the degraded regions in the world.

  3. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  4. Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man

    Science.gov (United States)

    Flanagan, Sarah E.; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M.; Edge, Julie A.; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A.L.; Edghill, Emma L.; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T.

    2014-01-01

    Summary Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development. PMID:24411943

  5. Key Factors to Determine the Borehole Spacing in a Deep Borehole Disposal for HLW

    International Nuclear Information System (INIS)

    Lee, Jongyoul; Choi, Heuijoo; Lee, Minsoo; Kim, Geonyoung; Kim, Kyeongsoo

    2015-01-01

    Deep fluids also resist vertical movement because they are density stratified and reducing conditions will sharply limit solubility of most dose critical radionuclides at the depth. Finally, high ionic strengths of deep fluids will prevent colloidal transport. Therefore, as an alternative disposal concept, i.e., deep borehole disposal technology is under consideration in number of countries in terms of its outstanding safety and cost effectiveness. In this paper, the general concept for deep borehole disposal of spent fuels or high level radioactive wastes which has been developed by some countries according to the rapid advance in the development of drilling technology, as an alternative method to the deep geological disposal method, was reviewed. After then an analysis on key factors for the distance between boreholes for the disposal of HLW was carried out. In this paper, the general concept for deep borehole disposal of spent fuels or HLW wastes, as an alternative method to the deep geological disposal method, were reviewed. After then an analysis on key factors for the determining the distance between boreholes for the disposal of HLW was carried out. These results can be used for the development of the HLW deep borehole disposal system

  6. Key Factors to Determine the Borehole Spacing in a Deep Borehole Disposal for HLW

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jongyoul; Choi, Heuijoo; Lee, Minsoo; Kim, Geonyoung; Kim, Kyeongsoo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    Deep fluids also resist vertical movement because they are density stratified and reducing conditions will sharply limit solubility of most dose critical radionuclides at the depth. Finally, high ionic strengths of deep fluids will prevent colloidal transport. Therefore, as an alternative disposal concept, i.e., deep borehole disposal technology is under consideration in number of countries in terms of its outstanding safety and cost effectiveness. In this paper, the general concept for deep borehole disposal of spent fuels or high level radioactive wastes which has been developed by some countries according to the rapid advance in the development of drilling technology, as an alternative method to the deep geological disposal method, was reviewed. After then an analysis on key factors for the distance between boreholes for the disposal of HLW was carried out. In this paper, the general concept for deep borehole disposal of spent fuels or HLW wastes, as an alternative method to the deep geological disposal method, were reviewed. After then an analysis on key factors for the determining the distance between boreholes for the disposal of HLW was carried out. These results can be used for the development of the HLW deep borehole disposal system.

  7. Key Success Factors of Renewable Energy Projects Implementation in Rural Areas of Indonesia

    Directory of Open Access Journals (Sweden)

    Wati Hermawati

    2017-12-01

    Full Text Available This paper is an exploratory study on renewable energy implementation in the rural areas of Indonesia. The study aim was to investigate the factors contributing to the sustainability of renewable energy projects in the rural areas. It mostly uses a qualitative approach. Primary data was mainly obtained from in-depth interviews conducted in site areas with the project owners, project managers, a key person in each local government, industry representatives, and the local community, including local leaders and users of renewable energy. Secondary data in the form of various official project reports was also used. The results indicated that the success of energy project implementation lay not only in good technology performance and long-term maintenance, but was also highly dependent on six key factors, namely: (1 project planning and development; (2 community participation; (3 active communication and beneficiaries; (4 availability of maintenance program, workshop and technician; (5 project management and institutionalization; (6 local government support and networks. The findings from this study provide useful insights to all stakeholders involved in the implementation of renewable energy technology for the rural areas in Indonesia.

  8. Key factors influencing the intention of telecare adoption: an institutional perspective.

    Science.gov (United States)

    Liu, Chung-Feng

    2011-05-01

    The objective of this study was to explore key factors of influence on the adoption of telecare by care institutions. This investigation was based on an extensive Technology-Organization-Environment framework comprising the four constructs of technology, organization, environment, and the project planning as well as corresponding variables. This study utilized a self-administered questionnaire for data collection, focusing on the managers of all 339 nursing homes in Taiwan for the census survey. A total of 70 valid questionnaires yielded a response rate of 20.65%. After analyzing the responses through the Partial Least Squares approach, government support, technological knowledge, supplier support, team skills, and compatibility were found to be the five key factors that positively impact intention to adopt telecare from an institutional perspective. The results of this study indicated that care institutions, for the most part, are willing to develop telecare and are already incorporating preliminary applications of telecare, such as distance learning and resident positioning. Solutions to potential issues related to implementing telecare in practice are also proposed in this study.

  9. Impact of Environmental Factors on the Regulation of Cyanotoxin Production

    Science.gov (United States)

    Boopathi, Thangavelu; Ki, Jang-Seu

    2014-01-01

    Cyanobacteria are capable of thriving in almost all environments. Recent changes in climatic conditions due to increased human activities favor the occurrence and severity of harmful cyanobacterial bloom all over the world. Knowledge of the regulation of cyanotoxins by the various environmental factors is essential for effective management of toxic cyanobacterial bloom. In recent years, progress in the field of molecular mechanisms involved in cyanotoxin production has paved the way for assessing the role of various factors on the cyanotoxin production. In this review, we present an overview of the influence of various environmental factors on the production of major group of cyanotoxins, including microcystins, nodularin, cylindrospermopsin, anatoxins and saxitoxins. PMID:24967641

  10. Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.

    Science.gov (United States)

    Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J

    2015-06-01

    In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (padvanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Key factors for the implementation of successful, stand-alone village electrification schemes in Peru

    Science.gov (United States)

    Sanchez-Campos, Teodoro

    The hypothesis of this work is that there are social, financial, technical, managerial institutional and political key factors that may either support or prevent the success of small stand alone energy systems in rural areas. This research work aims at contributing to the identification of such factors and study their relevance to the performance and sustainability of stand alone energy systems in rural areas; to meet its purpose, a wide range of literature was reviewed including rural electrification programmes and projects, research and development projects on access to electricity in rural areas, impact studies and others, and a field research survey was done the Andes and Upper Jungle regions in Peru. Nineteen possible critical factors were identified, thirteen with relevance at the local context (the community or village), and six with relevance at the national (or wider) context. From literature review it was found that the possible local critical factors were relevant only to four categories of factors instead of the six considered initially (i.e. social, financial, technological and managerial): the other two categories, political and institutional were found to be more relevant to the national context, therefore those were included in the group of possible critical factors of wider context. A series of questionnaires were designed to collect field data information, which was later used to analyse and establish the relation of each identified factor with the success of the systems studied. The survey research was implemented in 14 villages, 7 with small diesel sets and 7 with small hydropower schemes, all spread in the Andes and Upper Jungle of Peru, which were carefully selected to be representative of regions with isolated stand alone systems and with different socioeconomic background. Out of the 13 possible critical factors of local context, it was found that only 3 are really critical, the others are important but not critical; one of them (technical

  12. TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2016-01-01

    Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae.

  13. PCP-B class pollen coat proteins are key regulators of the hydration checkpoint in Arabidopsis thaliana pollen-stigma interactions.

    Science.gov (United States)

    Wang, Ludi; Clarke, Lisa A; Eason, Russell J; Parker, Christopher C; Qi, Baoxiu; Scott, Rod J; Doughty, James

    2017-01-01

    The establishment of pollen-pistil compatibility is strictly regulated by factors derived from both male and female reproductive structures. Highly diverse small cysteine-rich proteins (CRPs) have been found to play multiple roles in plant reproduction, including the earliest stages of the pollen-stigma interaction. Secreted CRPs found in the pollen coat of members of the Brassicaceae, the pollen coat proteins (PCPs), are emerging as important signalling molecules that regulate the pollen-stigma interaction. Using a combination of protein characterization, expression and phylogenetic analyses we identified a novel class of Arabidopsis thaliana pollen-borne CRPs, the PCP-Bs (for pollen coat protein B-class) that are related to embryo surrounding factor (ESF1) developmental regulators. Single and multiple PCP-B mutant lines were utilized in bioassays to assess effects on pollen hydration, adhesion and pollen tube growth. Our results revealed that pollen hydration is severely impaired when multiple PCP-Bs are lost from the pollen coat. The hydration defect also resulted in reduced pollen adhesion and delayed pollen tube growth in all mutants studied. These results demonstrate that AtPCP-Bs are key regulators of the hydration 'checkpoint' in establishment of pollen-stigma compatibility. In addition, we propose that interspecies diversity of PCP-Bs may contribute to reproductive barriers in the Brassicaceae. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  14. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  15. Key Factors Controlling the Applicability and Efficiency of Bioremediation of Chlorinated Ethenes In Situ

    Science.gov (United States)

    Zhang, M.; Yoshikawa, M.; Takeuchi, M.; Komai, T.

    2012-12-01

    Bioremediation has been considered as one of environmentally friendly and cost effective approaches for cleaning up the sites polluted by organic contaminants, such as chlorinated ethenes. Although bioremediation, in its widest sense, is not new, and many researches have been performed on bioremediation of different kinds of pollutants, an effective design and implication of in situ bioremediation still remains a challenging problem because of the complexity. Many factors may affect the applicability and efficiency of bioremediation of chlorinated ethenes in situ, which include the type and concentration of contaminants, biological, geological and hydro-geological conditions of the site, physical and chemical characteristics of groundwater and soils to be treated, as well as the constraints in engineering. In this presentation, an overview together with a detailed discussion on each factor will be provided. The influences of individual factors are discussed using the data obtained or cited from different sites and experiments, and thus under different environmental conditions. The results of this study illustrated that 1) the establishment of microbial consortium is of crucial importance for a complete degradation of chlorinated ethenes, 2) in situ control of favorable conditions for increasing microbial activities for bio-degradation through a designed pathway is the key to success, 3) the focus of a successful remediation system is to design an effective delivery process that is capable of producing adequate amendment mixing of contaminant-degrading bacteria, appropriate concentrations of electron acceptors, electron donors, and microbial nutrients in the subsurface treatment area.

  16. Key factors of project success in family small and medium-sized companies: the theoretical review

    Directory of Open Access Journals (Sweden)

    Sinisa Arsic

    2017-10-01

    Full Text Available The paper proposes a systematization of the key success factors of projects, through the theoretical review of family-owned companies operating in the EU market. It is the small and medium companies that in their own way contribute to the overall success of the national economy in terms of economic activity, increased employment, development activities and defining better business environment. The theoretical review observed numerous studies of family businesses, and the contribution of this work is in the systematization of the results of previous research – over three horizons, i.e., over the role of managers in the creation of successful projects (or owner if it is a family enterprise, institutional support for companies in Serbia and the EU, specific industries and the parent (regional markets where a family company operates. Project management, as a general representation of the concept of implementation of strategic and operational endeavors, contains many specifics in terms of critical success factors of projects depending on the environment in which they are implemented. The goal of the paper is reflected in the identification and presentation of critical success factors of projects implemented in family companies. The paper concludes with a discussion of the research results in relation to the existing, similar research studies, as well as with the announcement of future research, which will examine the conclusions drawn on a real sample.

  17. Identification of key factors affecting the water pollutant concentration in the sluice-controlled river reaches of the Shaying River in China via statistical analysis methods.

    Science.gov (United States)

    Dou, Ming; Zhang, Yan; Zuo, Qiting; Mi, Qingbin

    2015-08-01

    The construction of sluices creates a strong disturbance in water environmental factors within a river. The change in water pollutant concentrations of sluice-controlled river reaches (SCRRs) is more complex than that of natural river segments. To determine the key factors affecting water pollutant concentration changes in SCRRs, river reaches near the Huaidian Sluice in the Shaying River of China were selected as a case study, and water quality monitoring experiments based on different regulating modes were implemented in 2009 and 2010. To identify the key factors affecting the change rates for the chemical oxygen demand of permanganate (CODMn) and ammonia nitrogen (NH3-N) concentrations in the SCRRs of the Huaidian Sluice, partial correlation analysis, principal component analysis and principal factor analysis were used. The results indicate four factors, i.e., the inflow quantity from upper reaches, opening size of sluice gates, water pollutant concentration from upper reaches, and turbidity before the sluice, which are the common key factors for the CODMn and NH3-N concentration change rates. Moreover, the dissolved oxygen before a sluice is a key factor for the permanganate concentration from CODMn change rate, and the water depth before a sluice is a key factor for the NH3-N concentration change rate. Multiple linear regressions between the water pollutant concentration change rate and key factors were established via multiple linear regression analyses, and the quantitative relationship between the CODMn and NH3-N concentration change rates and key affecting factors was analyzed. Finally, the mechanism of action for the key factors affecting the water pollutant concentration changes was analyzed. The results reveal that the inflow quantity from upper reaches, opening size of sluice gates, permanganate concentration from CODMn from upper reaches and dissolved oxygen before the sluice have a negative influence and the turbidity before the sluice has a positive

  18. Ppd-1 is a key regulator of inflorescence architecture and paired spikelet development in wheat.

    Science.gov (United States)

    Boden, Scott A; Cavanagh, Colin; Cullis, Brian R; Ramm, Kerrie; Greenwood, Julian; Jean Finnegan, E; Trevaskis, Ben; Swain, Steve M

    2015-01-26

    The domestication of cereal crops such as wheat, maize, rice and barley has included the modification of inflorescence architecture to improve grain yield and ease harvesting(1). Yield increases have often been achieved through modifying the number and arrangement of spikelets, which are specialized reproductive branches that form part of the inflorescence. Multiple genes that control spikelet development have been identified in maize, rice and barley(2-5). However, little is known about the genetic underpinnings of this process in wheat. Here, we describe a modified spikelet arrangement in wheat, termed paired spikelets. Combining comprehensive QTL and mutant analyses, we show that Photoperiod-1 (Ppd-1), a pseudo-response regulator gene that controls photoperiod-dependent floral induction, has a major inhibitory effect on paired spikelet formation by regulating the expression of FLOWERING LOCUS T (FT)(6,7). These findings show that modulated expression of the two important flowering genes, Ppd-1 and FT, can be used to form a wheat inflorescence with a more elaborate arrangement and increased number of grain producing spikelets.

  19. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.

    Science.gov (United States)

    Neumann, I D

    2008-06-01

    In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

  20. Tetraspanin CD9: A Key Regulator of Cell Adhesion in the Immune System

    Directory of Open Access Journals (Sweden)

    Raquel Reyes

    2018-04-01

    Full Text Available The tetraspanin CD9 is expressed by all the major subsets of leukocytes (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, granulocytes, monocytes and macrophages, and immature and mature dendritic cells and also at a high level by endothelial cells. As a typical member of the tetraspanin superfamily, a prominent feature of CD9 is its propensity to engage in a multitude of interactions with other tetraspanins as well as with different transmembrane and intracellular proteins within the context of defined membranal domains termed tetraspanin-enriched microdomains (TEMs. Through these associations, CD9 influences many cellular activities in the different subtypes of leukocytes and in endothelial cells, including intracellular signaling, proliferation, activation, survival, migration, invasion, adhesion, and diapedesis. Several excellent reviews have already covered the topic of how tetraspanins, including CD9, regulate these cellular processes in the different cells of the immune system. In this mini-review, however, we will focus particularly on describing and discussing the regulatory effects exerted by CD9 on different adhesion molecules that play pivotal roles in the physiology of leukocytes and endothelial cells, with a particular emphasis in the regulation of adhesion molecules of the integrin and immunoglobulin superfamilies.

  1. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

    Directory of Open Access Journals (Sweden)

    Mee-Sup Yoon

    2017-10-01

    Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

  2. Tracing a key player in the regulation of plant architecture: the columnar growth habit of apple trees (Malus × domestica).

    Science.gov (United States)

    Petersen, Romina; Krost, Clemens

    2013-07-01

    Plant architecture is regulated by a complex interplay of some key players (often transcription factors), phytohormones and other signaling molecules such as microRNAs. The columnar growth habit of apple trees is a unique form of plant architecture characterized by thick and upright stems showing a compaction of internodes and carrying short fruit spurs instead of lateral branches. The molecular basis for columnar growth is a single dominant allele of the gene Columnar, whose identity, function and gene product are unknown. As a result of marker analyses, this gene has recently been fine-mapped to chromosome 10 at 18.51-19.09 Mb [according to the annotation of the apple genome by Velasco (2010)], a region containing a cluster of quantitative trait loci associated with plant architecture, but no homologs to the well-known key regulators of plant architecture. Columnar apple trees have a higher auxin/cytokinin ratio and lower levels of gibberellins and abscisic acid than normal apple trees. Transcriptome analyses corroborate these results and additionally show differences in cell membrane and cell wall function. It can be expected that within the next year or two, an integration of these different research methodologies will reveal the identity of the Columnar gene. Besides enabling breeders to efficiently create new apple (and maybe related pear, peach, cherry, etc.) cultivars which combine desirable characteristics of commercial cultivars with the advantageous columnar growth habit using gene technology, this will also provide new insights into an elevated level of plant growth regulation.

  3. A Secure Three-Factor User Authentication and Key Agreement Protocol for TMIS With User Anonymity.

    Science.gov (United States)

    Amin, Ruhul; Biswas, G P

    2015-08-01

    Telecare medical information system (TMIS) makes an efficient and convenient connection between patient(s)/user(s) and doctor(s) over the insecure internet. Therefore, data security, privacy and user authentication are enormously important for accessing important medical data over insecure communication. Recently, many user authentication protocols for TMIS have been proposed in the literature and it has been observed that most of the protocols cannot achieve complete security requirements. In this paper, we have scrutinized two (Mishra et al., Xu et al.) remote user authentication protocols using smart card and explained that both the protocols are suffering against several security weaknesses. We have then presented three-factor user authentication and key agreement protocol usable for TMIS, which fix the security pitfalls of the above mentioned schemes. The informal cryptanalysis makes certain that the proposed protocol provides well security protection on the relevant security attacks. Furthermore, the simulator AVISPA tool confirms that the protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The security functionalities and performance comparison analysis confirm that our protocol not only provide strong protection on security attacks, but it also achieves better complexities along with efficient login and password change phase as well as session key verification property.

  4. Adjuvants are key factors for the development of future vaccines: Lessons from the Finlay Adjuvant platform

    Directory of Open Access Journals (Sweden)

    Oliver ePérez

    2013-12-01

    Full Text Available The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs, AFPL (proteoliposome and AFCo (cochleate, were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

  5. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  6. Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

    Science.gov (United States)

    Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

    2009-08-01

    Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

  7. Resources changes: a key factor in a new uranium production economic cycle

    International Nuclear Information System (INIS)

    Capus, G.; Caumartin, P.

    1996-01-01

    Since the end of 1994, a change has been underway in the uranium market. As usual in such cases, surprise and disbelief first dominated, but the market actors have been adjusting quickly to what now appears to be a return to primary production as the predominant factor in uranium supply. It is a matter of fact that the fundamentals will determine the course of the uranium market, as with other cyclical commodity markets. Comparing 1995 with 1975, a time of rocketing prices and production, and forecasting another cycle with similar characteristics to the last one is tempting, but illusory. However, examining the relative conditions prevailing at these times provides keys that may be helpful in understanding future developments. (author)

  8. Competences and knowledge: Key-factors in the smart city of the future

    Directory of Open Access Journals (Sweden)

    Saverio Salerno

    2014-12-01

    Full Text Available The effective and modern management of competence development, which represents a distinguishing key-factor in future Smart Cities, cannot be limited to the Learning Management exclusively, but rather be inclusive of aspects pertaining to Human Capital and Performance Management in a holistic vision that encompasses not only the sphere of operations but also the tactical and strategic levels. In particular, organizations need solutions that especially integrate Learning Management, Performance Management, and Human Resource Management (HRM. We propose an approach considering the competences as key-factors in the management and valorization of Human Capital and making use of a socio-constructivist learning model, based on the explicit (ontological modeling of domain competences as well as a learner and didactic oriented approach. Unlike most of the current solutions, far from the proposed vision and concentrated on specific functionalities and not on the processes as a whole, the solution offered by MOMA, spin-off of the Research Group of the University of Salerno led by Prof. Salerno, is here presented as a demonstrative case of the proposed methodology and approach. A distinctive feature of our proposal, supported by the MOMA solution is the adoption of semantic technologies that for instance allows for the discovery of unpredictable paths linking them in the Knowledge Graph. Finally, we discuss how this framework can be applied in the context of the Smart Cities of the future, taking advantage of the features, enabled especially by semantics, of researching, creating, combining, delivering and using in a creative manner the resources of superior quality offered by Smart Cities.

  9. Exploring the factors influencing clinical students' self-regulated learning.

    Science.gov (United States)

    Berkhout, Joris J; Helmich, Esther; Teunissen, Pim W; van den Berg, Joost W; van der Vleuten, Cees P M; Jaarsma, A Debbie C

    2015-06-01

    The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and regulatory bodies. Supporting the development of SRL skills has proven difficult because self-regulation is a complex interactive process and we know relatively little about the factors influencing this process in real practice settings. The aim of our study was therefore to identify factors that support or hamper medical students' SRL in a clinical context. We conducted a constructivist grounded theory study using semi-structured interviews with 17 medical students from two universities enrolled in clerkships. Participants were purposively sampled to ensure variety in age, gender, experience and current clerkship. The Day Reconstruction Method was used to help participants remember their activities of the previous day. The interviews were transcribed verbatim and analysed iteratively using constant comparison and open, axial and interpretive coding. Self-regulated learning by students in the clinical environment was influenced by the specific goals perceived by students, the autonomy they experienced, the learning opportunities they were given or created themselves, and the anticipated outcomes of an activity. All of these factors were affected by personal, contextual and social attributes. Self-regulated learning of medical students in the clinical environment is different for every individual. The factors influencing this process are affected by personal, social and contextual attributes. Some of these are similar to those known from previous research in classroom settings, but others are unique to the clinical environment and include the facilities available, the role of patients, and social relationships pertaining to peers and other hospital staff. To better support students' SRL, we believe it is important to increase students' metacognitive awareness and to offer students more tailored learning opportunities. © 2015 John Wiley & Sons Ltd.

  10. MicroRNAs: not ‘fine-tuners’ but key regulators of neuronal development and function

    Directory of Open Access Journals (Sweden)

    Gregory eDavis

    2015-11-01

    Full Text Available microRNAs (miRNAs are a class of short non-coding RNAs that operate as prominent post-transcriptional regulators of eukaryotic gene expression. miRNAs are abundantly expressed in the brain of most animals and exert diverse roles. The anatomical and functional complexity of brain requires the precise coordination of multi-layered gene regulatory networks. The flexibility, speed and reversibility of miRNA function provide precise temporal and spatial gene regulatory capabilities that are crucial for the correct functioning of the brain. Studies have shown that the underlying molecular mechanisms controlled by miRNAs in the nervous systems of invertebrate and vertebrate models are remarkably conserved in humans. We endeavour to provide insight into the roles of miRNAs in the nervous systems of these model organisms and discuss how such information may be used to inform regarding diseases of the human brain.

  11. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

    DEFF Research Database (Denmark)

    Withers, Sarah B.; Forman, Ruth; Meza-Perez, Selene

    2017-01-01

    Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils...... in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability...... of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source...

  12. EXO70C2 is a key regulatory factor for optimal tip growth of pollen

    KAUST Repository

    Synek, Lukas

    2017-03-30

    The exocyst, an eukaryotic tethering complex, co-regulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, C1, C2, F1, H3, H5, and H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollen-specific depletion of the closest paralog, EXO70C1, using ami-RNA in the exo70C2 mutant background resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP-tagged and expressed under their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. Expression of EXO70C2-GFP complemented aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes.

  13. Structural imbalances as a key factor of unemployment in the Russian labor market

    Directory of Open Access Journals (Sweden)

    I V Trotsuk

    2015-12-01

    Full Text Available In recent years, the problems of the Russian labor market, especially the scale and characteristics of youth unemployment, get very emotional and negative coverage in the scientific and journalistic discourses. The authors seek to show without any emotional evaluations what are the objective macroeconomic causes of the current situation with unemployment, especially youth unemployment. First, the authors identify the main challenges the labor market faces today in terms of the interaction of its key actors (workers, owners of the means of production, educational institutions and various intermediaries, including the state regulating the features of labor recruitment. Second, the article shows the main trends of the last decade that change the structure of employment of the economically active population. Third, the authors name the basic structural imbalances in the Russian labor market, primarily structural and professional imbalance between the demand for labor, the demand for vocational training and offer of educational services, which is quite evident, albeit in different ways, in all spheres of the economy. Fourth, the article describes the specific features of the youth labor market as both affected and contributing to the structural imbalances. Finally, the authors propose a methodology of macroeconomic forecasting that may reduce the problems the Russian society faces in the field of employment.

  14. PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

    Directory of Open Access Journals (Sweden)

    Asoka Banno

    2018-01-01

    Full Text Available Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

  15. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    International Nuclear Information System (INIS)

    Sudo, Tatsuhiko; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-01-01

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38α is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38α, we utilized newly established mouse fibroblast cell lines originated from a p38α null mouse, namely, a parental cell line without p38α gene locus, knockout of p38α (KOP), Zeosin-resistant (ZKOP), revertant of p38α (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38α. The loss of MAPKAPK2 expression accompanied by the defect of p38α is confirmed in an embryonic extract prepared from p38α null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have established cell lines that can be used in

  16. The regulation of the chloroplast proton motive force plays a key role for photosynthesis in fluctuating light.

    Science.gov (United States)

    Armbruster, Ute; Correa Galvis, Viviana; Kunz, Hans-Henning; Strand, Deserah D

    2017-06-01

    Plants use sunlight as their primary energy source. During photosynthesis, absorbed light energy generates reducing power by driving electron transfer reactions. These are coupled to the transfer of protons into the thylakoid lumen, generating a proton motive force (pmf) required for ATP synthesis. Sudden alterations in light availability have to be met by regulatory mechanisms to avoid the over-accumulation of reactive intermediates and maximize energy efficiency. Here, the acidification of the lumen, as an intermediate product of photosynthesis, plays an important role by regulating photosynthesis in response to excitation energy levels. Recent findings reveal pmf regulation and the modulation of its composition as key determinants for efficient photosynthesis, plant growth, and survival in fluctuating light environments. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

    DEFF Research Database (Denmark)

    Menzel, Tobias; Nähse-Kumpf, Viola; Kousholt, Arne Nedergaard

    2011-01-01

    To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2......, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main...

  18. Public/private partners. Key factors in creating a strategic alliance for community health.

    Science.gov (United States)

    Nelson, J C; Rashid, H; Galvin, V G; Essien, J D; Levine, L M

    1999-04-01

    The rapidly evolving American health system creates economic and societal incentives for public and private health organizations to collaborate. Despite the apparent benefits of collaboration, there is a paucity of information available to help local agencies develop partnerships. This study, itself a collaboration between a school of public health (SPH) and a Georgia health district, was undertaken to identify critical factors necessary to successfully initiate and sustain a public/private community health collaboration. Professional staff at the SPH conducted 26 standardized interviews involving participants from Cobb and Douglas counties Boards of Health; Promina Northwest (now known as Wellstar), a not-for-profit health system; and community stakeholders. Content analysis of each interview question was performed and comparisons were made both within each group and across groups. Trends were identified in the following key areas: vision of health care for Cobb and Douglas counties, forces driving collaboration, strengths of each organization, critical negotiating issues, and potential community gain resulting from the partnership. A shared vision between potential collaborators facilitates communication regarding strategies to achieve common goals. A previous history of working together in limited capacities allowed the partners to develop trust and respect for one another prior to entering negotiations. These factors, when taken in conjunction with each organization's strong leadership and knowledge of the community, build a strong foundation for a successful partnership.

  19. Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

    Science.gov (United States)

    Li, Dong; Zhou, Changsong

    2011-01-01

    Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

  20. Organization of anti-phase synchronization pattern in neural networks: what are the key factors?

    Directory of Open Access Journals (Sweden)

    Dong eLi

    2011-12-01

    Full Text Available Anti-phase oscillation has been widely observed in cortical neuralnetwork. Elucidating the mechanism underlying the organization ofanti-phase pattern is of significance for better understanding morecomplicated pattern formations in brain networks. In dynamicalsystems theory, the organization of anti-phase oscillation patternhas usually been considered to relate to time-delay in coupling.This is consistent to conduction delays in real neural networks inthe brain due to finite propagation velocity of action potentials.However, other structural factors in cortical neural network, suchas modular organization (connection density and the coupling types(excitatory or inhibitory, could also play an important role. Inthis work, we investigate the anti-phase oscillation patternorganized on a two-module network of either neuronal cell model orneural mass model, and analyze the impact of the conduction delaytimes, the connection densities, and coupling types. Our resultsshow that delay times and coupling types can play key roles in thisorganization. The connection densities may have an influence on thestability if an anti-phase pattern exists due to the other factors.Furthermore, we show that anti-phase synchronization of slowoscillations can be achieved with small delay times if there isinteraction between slow and fast oscillations. These results aresignificant for further understanding more realistic spatiotemporaldynamics of cortico-cortical communications.

  1. A key inactivation factor of HeLa cell viability by a plasma flow

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takehiko; Yokoyama, Mayo [Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Johkura, Kohei, E-mail: sato@ifs.tohoku.ac.jp [Department of Histology and Embryology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621 (Japan)

    2011-09-21

    Recently, a plasma flow has been applied to medical treatment using effects of various kinds of stimuli such as chemical species, charged particles, heat, light, shock wave and electric fields. Among them, the chemical species are known to cause an inactivation of cell viability. However, the mechanisms and key factors of this event are not yet clear. In this study, we focused on the effect of H{sub 2}O{sub 2} in plasma-treated culture medium because it is generated in the culture medium and it is also chemically stable compared with free radicals generated by the plasma flow. To elucidate the significance of H{sub 2}O{sub 2}, we assessed the differences in the effects of plasma-treated medium and H{sub 2}O{sub 2}-added medium against inactivation of HeLa cell viability. These two media showed comparable effects on HeLa cells in terms of the survival ratios, morphological features of damage processes, permeations of H{sub 2}O{sub 2} into the cells, response to H{sub 2}O{sub 2} decomposition by catalase and comprehensive gene expression. The results supported that among chemical species generated in a plasma-treated culture medium, H{sub 2}O{sub 2} is one of the main factors responsible for inactivation of HeLa cell viability. (fast track communication)

  2. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development.

    Science.gov (United States)

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W; Bischof, Johannes; Hens, Korneel; van Nimwegen, Erik; Basler, Konrad; Deplancke, Bart

    2015-04-01

    Transcription factors (TFs) are key regulators of cell fate. The estimated 755 genes that encode DNA binding domain-containing proteins comprise ∼ 5% of all Drosophila genes. However, the majority has remained uncharacterized so far due to the lack of proper genetic tools. We generated 594 site-directed transgenic Drosophila lines that contain integrations of individual UAS-TF constructs to facilitate spatiotemporally controlled misexpression in vivo. All transgenes were expressed in the developing wing, and two-thirds induced specific phenotypic defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with both methods indicating a great potential for misexpression to characterize novel functions in wing growth, patterning, and development. Thus, our UAS-TF library provides an important addition to the genetic toolbox of Drosophila research, enabling the identification of several novel wing development-related TFs. In parallel, we established the chromatin landscape of wing imaginal discs by ChIP-seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering revealed six distinct chromatin states, with two clusters showing enrichment for both active and repressive marks. TFs that carry such "bivalent" chromatin are highly enriched for causing misexpression phenotypes in the wing, and analysis of existing expression data shows that these TFs tend to be differentially expressed across the wing disc. Thus, bivalently marked chromatin can be used as a marker for spatially regulated TFs that are functionally relevant in a developing tissue. © 2015 Schertel et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Gut TFH and IgA: key players for regulation of bacterial communities and immune homeostasis.

    Science.gov (United States)

    Kato, Lucia M; Kawamoto, Shimpei; Maruya, Mikako; Fagarasan, Sidonia

    2014-01-01

    The main function of the immune system is to protect the host against pathogens. However, unlike the systemic immune system, the gut immune system does not eliminate, but instead nourishes complex bacterial communities and establishes advanced symbiotic relationships. Immunoglobulin A (IgA) is the most abundant antibody isotype in mammals, produced mainly in the gut. The primary function of IgA is to maintain homeostasis at mucosal surfaces, and studies in mice have demonstrated that IgA diversification has an essential role in the regulation of gut microbiota. Dynamic diversification and constant adaptation of IgA responses to local microbiota require expression of activation-induced cytidine deaminase by B cells and control from T follicular helper and Foxp3(+) T cells in germinal centers (GCs). We discuss the finely tuned regulatory mechanisms for IgA synthesis in GCs of Peyer's patches and emphasize the roles of CD4(+) T cells for IgA selection and the maintenance of appropriate gut microbial communities required for immune homeostasis.

  4. A proactive public information policy: a key element for regulator independence and credibility

    International Nuclear Information System (INIS)

    Kindelan, J.M.

    2001-01-01

    The future of the nuclear industry will depend to a large extent on the perception that the members of the public have of it. However, our mission as regulatory bodies is not to change the pro-or anti- nuclear feelings of the public, but to set in them the confidence that the use currently made of nuclear energy is carried out with the greatest guarantees of safety. We should continue to avoid their feeling of fear without reasons or their perception of uncertainty regarding processes that are duly controlled and supervised. I am convinced that whatever progress we make in increasing transparency will lead to an increase in the public credibility of the organisations that we represent. The reason underlying our need for this credibility, this reputation for autonomy and efficiency, for good performance, is that without it we will not have sufficient authority in the eyes of the regulated sector or other private political and economic interests, and will not, therefore, be in a position to provide a sensation of confidence to the members of the public, whose tranquillity and interests are our obligation. (author)

  5. STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function

    Directory of Open Access Journals (Sweden)

    Kiviluoto Santeri

    2011-04-01

    Full Text Available Abstract Stromal interaction molecules (STIM were identified as the endoplasmic-reticulum (ER Ca2+ sensor controlling store-operated Ca2+ entry (SOCE and Ca2+-release-activated Ca2+ (CRAC channels in non-excitable cells. STIM proteins target Orai1-3, tetrameric Ca2+-permeable channels in the plasma membrane. Structure-function analysis revealed the molecular determinants and the key steps in the activation process of Orai by STIM. Recently, STIM1 was found to be expressed at high levels in skeletal muscle controlling muscle function and properties. Novel STIM targets besides Orai channels are emerging. Here, we will focus on the role of STIM1 in skeletal-muscle structure, development and function. The molecular mechanism underpinning skeletal-muscle physiology points toward an essential role for STIM1-controlled SOCE to drive Ca2+/calcineurin/nuclear factor of activated T cells (NFAT-dependent morphogenetic remodeling programs and to support adequate sarcoplasmic-reticulum (SR Ca2+-store filling. Also in our hands, STIM1 is transiently up-regulated during the initial phase of in vitro myogenesis of C2C12 cells. The molecular targets of STIM1 in these cells likely involve Orai channels and canonical transient receptor potential (TRPC channels TRPC1 and TRPC3. The fast kinetics of SOCE activation in skeletal muscle seem to depend on the triad-junction formation, favoring a pre-localization and/or pre-formation of STIM1-protein complexes with the plasma-membrane Ca2+-influx channels. Moreover, Orai1-mediated Ca2+ influx seems to be essential for controlling the resting Ca2+ concentration and for proper SR Ca2+ filling. Hence, Ca2+ influx through STIM1-dependent activation of SOCE from the T-tubule system may recycle extracellular Ca2+ losses during muscle stimulation, thereby maintaining proper filling of the SR Ca2+ stores and muscle function. Importantly, mouse models for dystrophic pathologies, like Duchenne muscular dystrophy, point towards an

  6. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    OpenAIRE

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all th...

  7. Key factors affecting the deployment of electricity generation technologies in energy technology scenarios

    International Nuclear Information System (INIS)

    Ruoss, F.; Turton, H.; Hirschberg, S.

    2009-12-01

    This report presents the findings of a survey of key factors affecting the deployment of electricity generation technologies in selected energy scenarios. The assumptions and results of scenarios, and the different models used in their construction, are compared. Particular attention is given to technology assumptions, such as investment cost or capacity factors, and their impact on technology deployment. We conclude that the deployment of available technologies, i.e. their market shares, can only be explained from a holistic perspective, and that there are strong interactions between driving forces and competing technology options within a certain scenario. Already the design of a scenario analysis has important impacts on the deployment of technologies: the choice of the set of available technologies, the modeling approach and the definition of the storylines determine the outcome. Furthermore, the quantification of these storylines into input parameters and cost assumptions drives technology deployment, even though differences across the scenarios in cost assumptions are not observed to account for many of the observed differences in electricity technology deployment. The deployment can only be understood after a consideration of the interplay of technology options and the scale of technology deployment, which is determined by economic growth, end-use efficiency, and electrification. Some input parameters are of particular importance for certain technologies: CO 2 prices, fuel prices and the availability of carbon capture and storage appear to be crucial for the deployment of fossil-fueled power plants; maximum construction rates and safety concerns determine the market share of nuclear power; the availability of suitable sites represents the most important factor for electricity generation from hydro and wind power plants; and technology breakthroughs are needed for solar photovoltaics to become cost-competitive. Finally, this analysis concludes with a review

  8. Key factors affecting the deployment of electricity generation technologies in energy technology scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Ruoss, F.; Turton, H.; Hirschberg, S.

    2009-12-15

    This report presents the findings of a survey of key factors affecting the deployment of electricity generation technologies in selected energy scenarios. The assumptions and results of scenarios, and the different models used in their construction, are compared. Particular attention is given to technology assumptions, such as investment cost or capacity factors, and their impact on technology deployment. We conclude that the deployment of available technologies, i.e. their market shares, can only be explained from a holistic perspective, and that there are strong interactions between driving forces and competing technology options within a certain scenario. Already the design of a scenario analysis has important impacts on the deployment of technologies: the choice of the set of available technologies, the modeling approach and the definition of the storylines determine the outcome. Furthermore, the quantification of these storylines into input parameters and cost assumptions drives technology deployment, even though differences across the scenarios in cost assumptions are not observed to account for many of the observed differences in electricity technology deployment. The deployment can only be understood after a consideration of the interplay of technology options and the scale of technology deployment, which is determined by economic growth, end-use efficiency, and electrification. Some input parameters are of particular importance for certain technologies: CO{sub 2} prices, fuel prices and the availability of carbon capture and storage appear to be crucial for the deployment of fossil-fueled power plants; maximum construction rates and safety concerns determine the market share of nuclear power; the availability of suitable sites represents the most important factor for electricity generation from hydro and wind power plants; and technology breakthroughs are needed for solar photovoltaics to become cost-competitive. Finally, this analysis concludes with a

  9. Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance

    Directory of Open Access Journals (Sweden)

    Paola Giussani

    2014-03-01

    Full Text Available Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (αNeu5Ac(2-8αNeu5Ac(2-3βGal(1-4βGlc(1-1Cer or N-glycolyl GM3 (αNeu5Ac (2-3βGal(1-4βGlc(1-1Cer and de-N-acetyl GM3 (NeuNH(2βGal(1-4βGlc(1-1Cer endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy.

  10. Reversible oxidative modification: a key mechanism of Na+-K+ pump regulation.

    Science.gov (United States)

    Figtree, Gemma A; Liu, Chia-Chi; Bibert, Stephanie; Hamilton, Elisha J; Garcia, Alvaro; White, Caroline N; Chia, Karin K M; Cornelius, Flemming; Geering, Kaethi; Rasmussen, Helge H

    2009-07-17

    Angiotensin II (Ang II) inhibits the cardiac sarcolemmal Na(+)-K(+) pump via protein kinase (PK)C-dependent activation of NADPH oxidase. We examined whether this is mediated by oxidative modification of the pump subunits. We detected glutathionylation of beta(1), but not alpha(1), subunits in rabbit ventricular myocytes at baseline. beta(1) Subunit glutathionylation was increased by peroxynitrite (ONOO(-)), paraquat, or activation of NADPH oxidase by Ang II. Increased glutathionylation was associated with decreased alpha(1)/beta(1) subunit coimmunoprecipitation. Glutathionylation was reversed after addition of superoxide dismutase. Glutaredoxin 1, which catalyzes deglutathionylation, coimmunoprecipitated with beta(1) subunit and, when included in patch pipette solutions, abolished paraquat-induced inhibition of myocyte Na(+)-K(+) pump current (I(p)). Cysteine (Cys46) of the beta(1) subunit was the likely candidate for glutathionylation. We expressed Na(+)-K(+) pump alpha(1) subunits with wild-type or Cys46-mutated beta(1) subunits in Xenopus oocytes. ONOO(-) induced glutathionylation of beta(1) subunit and a decrease in Na(+)-K(+) pump turnover number. This was eliminated by mutation of Cys46. ONOO(-) also induced glutathionylation of the Na(+)-K(+) ATPase beta(1) subunit from pig kidney. This was associated with a approximately 2-fold decrease in the rate-limiting E(2)-->E(1) conformational change of the pump, as determined by RH421 fluorescence. We propose that kinase-dependent regulation of the Na(+)-K(+) pump occurs via glutathionylation of its beta(1) subunit at Cys46. These findings have implications for pathophysiological conditions characterized by neurohormonal dysregulation, myocardial oxidative stress and raised myocyte Na(+) levels.

  11. MicroRNA-34a: A Key Regulator in the Hallmarks of Renal Cell Carcinoma

    Science.gov (United States)

    Hussein, Mohammad H.; Al-Qahtani, Saeed Awad M.; Shaalan, Aly A. M.

    2017-01-01

    Renal cell carcinoma (RCC) incidence has increased over the past two decades. Recent studies reported microRNAs as promising biomarkers for early cancer detection, accurate prognosis, and molecular targets for future treatment. This study aimed to evaluate the expression levels of miR-34a and 11 of its bioinformatically selected target genes and proteins to test their potential dysregulation in RCC. Quantitative real-time PCR for miR-34a and its targets; MET oncogene; gene-regulating apoptosis (TP53INP2 and DFFA); cell proliferation (E2F3); and cell differentiation (SOX2 and TGFB3) as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1, and Ki67 protein expression have been performed in 85 FFPE RCC tumor specimens. Clinicopathological parameter correlation and in silico network analysis have also implicated. We found RCC tissues displayed significantly higher miR-34a expression level than their corresponding noncancerous tissues, particularly in chromophobic subtype. MET and E2F3 were significantly upregulated, while TP53INP2 and SOX2 were downregulated. ROC analysis showed high diagnostic performance of miR-34a (AUC = 0.854), MET (AUC = 0.765), and E2F3 (AUC = 0.761). The advanced pathological grade was associated with strong TGFB1, VEGFA, and Ki67 protein expression and absent Tp53 staining. These findings indicate miR-34a along with its putative target genes could play a role in RCC tumorigenesis and progression. PMID:29104726

  12. MicroRNA-34a: A Key Regulator in the Hallmarks of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Eman A. Toraih

    2017-01-01

    Full Text Available Renal cell carcinoma (RCC incidence has increased over the past two decades. Recent studies reported microRNAs as promising biomarkers for early cancer detection, accurate prognosis, and molecular targets for future treatment. This study aimed to evaluate the expression levels of miR-34a and 11 of its bioinformatically selected target genes and proteins to test their potential dysregulation in RCC. Quantitative real-time PCR for miR-34a and its targets; MET oncogene; gene-regulating apoptosis (TP53INP2 and DFFA; cell proliferation (E2F3; and cell differentiation (SOX2 and TGFB3 as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1, and Ki67 protein expression have been performed in 85 FFPE RCC tumor specimens. Clinicopathological parameter correlation and in silico network analysis have also implicated. We found RCC tissues displayed significantly higher miR-34a expression level than their corresponding noncancerous tissues, particularly in chromophobic subtype. MET and E2F3 were significantly upregulated, while TP53INP2 and SOX2 were downregulated. ROC analysis showed high diagnostic performance of miR-34a (AUC = 0.854, MET (AUC = 0.765, and E2F3 (AUC = 0.761. The advanced pathological grade was associated with strong TGFB1, VEGFA, and Ki67 protein expression and absent Tp53 staining. These findings indicate miR-34a along with its putative target genes could play a role in RCC tumorigenesis and progression.

  13. The vision of immigrant students about key factors and skills for access to college

    Directory of Open Access Journals (Sweden)

    Elena Cano García

    2015-05-01

    Full Text Available One of the most important challenges in education is working against absenteeism and school dropout. Especially relevant is the case of immigrant students who are a vulnerable group, fact that causes a high difference in results between immigrants and native students, so that only a very small percentage reaches college.For this reason, the study “Competencies and keys for an educational success from the perspective of college students’ children of immigrants” (2009 ARAF1 00010 has sought to identify the key factors and skills that college students from immigrant families in Catalonia (Spain feel have been useful for their educational success, educational success seen as the enrolment in programs beyond compulsory education.The study methodology has been predominantly qualitative using three different sources of data collection: life stories, audiovisual narratives and questionnaires. Specifically for this article we refer to the results analyzed through the life stories of 13 college students from immigrant backgrounds who had done all or part of their primary school in the Spanish education system, considering for their selecting the age of arrival, their nationality and the variety of universities and degrees where they were enrolled.The results of the study support the findings of previous researches (Aja et al.; Huguet & Navarro, 2006; Ferrer, 2009; OECD, 2010; Instituto de Evaluación, 2010. Student participants have referred to the importance of family expectations and support, especially when it has been given in conjunction with the school. They especially emphasized the role of mothers as a basic figure to encourage perseverance and dedication to studies. Moreover, in the educational environment it has been particularly appreciated the role the high school teachers who in many cases were the key on having great expectations for them and communicating these explicitly. Finally, regarding the competences, which have been the focus

  14. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    NARCIS (Netherlands)

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the

  15. Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43

    NARCIS (Netherlands)

    Boogerd, Kees-Jan; Wong, L. Y. Elaine; Christoffels, Vincent M.; Klarenbeek, Meinke; Ruijter, Jan M.; Moorman, Antoon F. M.; Barnett, Phil

    2008-01-01

    AIMS: T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering

  16. The Populus ARBORKNOX1 homeodomain transcription factor regulates woody growth through binding to evolutionarily conserved target genes of diverse function

    Science.gov (United States)

    Lijun Liu; Matthew S. Zinkgraf; H. Earl Petzold; Eric P. Beers; Vladimir Filkov; Andrew Groover

    2014-01-01

    The class I KNOX homeodomain transcription factor ARBORKNOX1 (ARK1) is a key regulator of vascular cambium maintenance and cell differentiation in Populus. Currently, basic information is lacking concerning the distribution, functional characteristics, and evolution of ARK1 binding in the Populus genome.

  17. Plutonium in the environment: key factors related to impact assessment in case of an accidental atmospheric release

    Energy Technology Data Exchange (ETDEWEB)

    Guetat, P. [CEA Valduc, 21 - Is-sur-Tille (France); Moulin, V.; Reiller, P. [CEA Saclay, 91 (FR)] (and others)

    2009-07-01

    This paper deals with plutonium and key factors related to impact assessment. It is based on recent work performed by CEA which summarize the main features of plutonium behaviour from sources inside installations to the environment and man, and to report current knowledge on the different parameters used in models for environmental and radiological impact assessment. These key factors are illustrated through a case study based on an accidental atmospheric release of Pu in a nuclear facility. (orig.)

  18. Study of the key factors affecting the triple grid lifetime of the LIPS-300 ion thruster

    Science.gov (United States)

    Mingming, SUN; Liang, WANG; Juntai, YANG; Xiaodong, WEN; Yongjie, HUANG; Meng, WANG

    2018-04-01

    In order to ascertain the key factors affecting the lifetime of the triple grids in the LIPS-300 ion thruster, the thermal deformation, upstream ion density and component lifetime of the grids are simulated with finite element analysis, fluid simulation and charged-particle tracing simulation methods on the basis of a 1500 h short lifetime test. The key factor affecting the lifetime of the triple grids in the LIPS-300 ion thruster is obtained and analyzed through the test results. The results show that ion sputtering erosion of the grids in 5 kW operation mode is greater than in the case of 3 kW. In 5 kW mode, the decelerator grid shows the most serious corrosion, the accelerator grid shows moderate corrosion, and the screen grid shows the least amount of corrosion. With the serious corrosion of the grids in 5 kW operation mode, the intercept current of the acceleration and deceleration grids increases substantially. Meanwhile, the cold gap between the accelerator grid and the screen grid decreases from 1 mm to 0.7 mm, while the cold gap between the accelerator grid and the decelerator grid increases from 1 mm to 1.25 mm after 1500 h of thruster operation. At equilibrium temperature with 5 kW power, the finite element method (FEM) simulation results show that the hot gap between the screen grid and the accelerator grid reduces to 0.2 mm. Accordingly, the hot gap between the accelerator grid and the decelerator grid increases to 1.5 mm. According to the fluid method, the plasma density simulated in most regions of the discharge chamber is 1 × 1018‑8 × 1018 m‑3. The upstream plasma density of the screen grid is in the range 6 × 1017‑6 × 1018 m‑3 and displays a parabolic characteristic. The charged particle tracing simulation method results show that the ion beam current without the thermal deformation of triple grids has optimal perveance status. The ion sputtering rates of the accelerator grid hole and the decelerator hole are 5.5 × 10‑14 kg s‑1 and

  19. Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

    Science.gov (United States)

    Luna-Zurita, Luis; Stirnimann, Christian U; Glatt, Sebastian; Kaynak, Bogac L; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K; Pollard, Katherine S; Müller, Christoph W; Bruneau, Benoit G

    2016-02-25

    Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Culture conditions for equine bone marrow mesenchymal stem cells and expression of key transcription factors during their differentiation into osteoblasts

    Science.gov (United States)

    2013-01-01

    Background The use of equine bone marrow mesenchymal stem cells (BMSC) is a novel method to improve fracture healing in horses. However, additional research is needed to identify optimal culture conditions and to determine the mechanisms involved in regulating BMSC differentiation into osteoblasts. The objectives of the experiments were to determine: 1) if autologous or commercial serum is better for proliferation and differentiation of equine BMSC into osteoblasts, and 2) the expression of key transcription factors during the differentiation of equine BMSC into osteoblasts. Equine BMSC were isolated from the sterna of 3 horses, treated with purchased fetal bovine serum (FBS) or autologous horse serum (HS), and cell proliferation determined. To induce osteoblast differentiation, cells were incubated with L-ascorbic acid-2-phosphate and glycerol-2-phosphate in the presence or absence of human bone morphogenetic protein2 (BMP2), dexamethasone (DEX), or combination of the two. Alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was determined by ELISA. Total RNA was isolated from differentiating BMSC between d 0 to 18 to determine expression of runt-related transcription factor2 (Runx2), osterix (Osx), and T-box3 (Tbx3). Data were analyzed by ANOVA. Results Relative to control, FBS and HS increased cell number (133 ± 5 and 116 ± 5%, respectively; P  0.8). Runt-related transcription factor2 expression increased 3-fold (P equine BMSC into osteoblasts. In addition, expression of Runx2 and osterix increased and expression of Tbx3 is reduced during differentiation. PMID:24169030

  1. Expression of factors and key components associated with the PI3K signaling pathway in colon cancer.

    Science.gov (United States)

    Chen, Hua; Gao, Junyi; Du, Zhenhua; Zhang, Xuequn; Yang, Fei; Gao, Wei

    2018-04-01

    The pathophysiology of colorectal cancer (CRC) has not been fully elucidated. The dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway frequently contributes to the tumorigenesis and progression of human cancer. The aim of the present study was to explore the expression and clinical significance of a number of associated factors and key components of the PI3K signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (p110α), phosphorylated protein kinase B (p-Akt) Ser473, p-mammalian target of rapamycin (mTOR) Ser2448, cyclin D1, cyclin dependent kinase (CDK)4, RELA proto-oncogene, nuclear factor-κβ subunit (p65), Ras and extracellular signal-regulated kinase (ERK)1/2 in human CRC. The expression of target proteins was detected using immunohistochemistry (IHC) in 65 CRC cases and 15 colonic adenoma cases. The association between the expression of target proteins and clinical pathological parameters was analyzed using a χ 2 test. IHC results revealed that the expression of all target proteins was significantly increased in CRC tissues compared with in colonic adenoma tissues (P0.05). Cyclin D1, CDK4 and Ras were revealed to be expressed significantly higher in poorly differentiated CRC compared with moderately differentiated CRC (Pcancer tissues with lymph node metastasis compared with cancer tissues without lymph node metastasis (P<0.05). These results suggest that the target proteins may all participate in the tumorigenesis of CRC. Furthermore, cyclin D1, CDK4, Ras, p65 and ERK1/2 may be important in the progression of CRC. The results of the present study may provide novel predictive factors and therapeutic targets for CRC.

  2. Proteolysis of proBDNF is a key regulator in the formation of memory.

    Directory of Open Access Journals (Sweden)

    Philip Barnes

    2008-09-01

    Full Text Available It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.

  3. MGMT expression: insights into its regulation. 1. Epigenetic factors

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2013-03-01

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT is the DNA repair enzyme responsible for removing of alkylation adducts from the O6-guanine in DNA. Despite MGMT prevents mutations and cell death, this enzyme can provide resistance of cancer cells to alkylating agents of chemotherapy. The high intra- and inter-individual variations in the human MGMT expression level have been observed indicating to a complicated regulation of this gene. This review is focused on the study of epigenetic factors which could be potentially involved in regulation of the human MGMT gene expression. These include chromatin remodeling via histone modifications and DNA methylation of promoter region and gene body, as well as RNA-based mechanisms, alternative splicing, protein post- translational modifications, and other.

  4. Coagulation factor VII is regulated by androgen receptor in breast cancer.

    Science.gov (United States)

    Naderi, Ali

    2015-02-01

    Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. OsbZIP58, a basic leucine zipper transcription factor, regulates starch biosynthesis in rice endosperm.

    Science.gov (United States)

    Wang, Jie-Chen; Xu, Heng; Zhu, Ying; Liu, Qiao-Quan; Cai, Xiu-Ling

    2013-08-01

    Starch composition and the amount in endosperm, both of which contribute dramatically to seed yield, cooking quality, and taste in cereals, are determined by a series of complex biochemical reactions. However, the mechanism regulating starch biosynthesis in cereal seeds is not well understood. This study showed that OsbZIP58, a bZIP transcription factor, is a key transcriptional regulator controlling starch synthesis in rice endosperm. OsbZIP58 was expressed mainly in endosperm during active starch synthesis. osbzip58 null mutants displayed abnormal seed morphology with altered starch accumulation in the white belly region and decreased amounts of total starch and amylose. Moreover, osbzip58 had a higher proportion of short chains and a lower proportion of intermediate chains of amylopectin. Furthermore, OsbZIP58 was shown to bind directly to the promoters of six starch-synthesizing genes, OsAGPL3, Wx, OsSSIIa, SBE1, OsBEIIb, and ISA2, and to regulate their expression. These findings indicate that OsbZIP58 functions as a key regulator of starch synthesis in rice seeds and provide new insights into seed quality control.

  6. Original article Key factors for successful solving of mathematical word problems in fifth-grade learners

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    Marija Kavkler

    2014-05-01

    Full Text Available BACKGROUND Difficulties in solving mathematical word problems (MWP are one of the most common reasons for weak mathematics performance, and poor mathematical literacy has important implications for an individual’s further education, employment opportunities, mental health and quality of life in today’s modern technological society. The purpose of the study was to examine whether Slovenian good and poor MWP solvers differ in arithmetic knowledge and skills, non-verbal reasoning, pupils’ self-evaluations of MWP abilities, teachers’ assessment of their mathematical knowledge and what strategies fifth- grade learners use in solving MWP. PARTICIPANTS AND PROCEDURE The larger sample included 233 pupils from 14 fifth-grade classes (mean age 10 years 3 months and 14 teachers. On the basis of the teachers’ opinions and the results of MWP solving two sub-samples of 24 students were formed, good and poor MWP solvers. Several tests were used to determine MWP solving ability, automation of arithmetic facts and procedures as well as Raven’s SPM. Questionnaires for pupils were used to assess pupils’ estimations of MWP tasks’ difficulty, their own ability to solve them and the strategies used. To assess pupils’ knowledge a questionnaire for teachers was used. RESULTS Slovenian 5 th graders in the larger sample generally used very few empirically proven effective cognitive and metacognitive strategies to solve MWP. Pupils with lower achievement in solving MWP, compared to pupils with higher achievement demonstrated significantly less automated arithmetic facts and procedures of the algorithm, less flexible use of arithmetic skills, as well as qualitatively different MWP solving, which is also related to their lower non-verbal reasoning. Teachers’ assessments and pupils’ self-assessments matched the achieved test results. CONCLUSIONS The results exposed important key factors for successful solving of mathematical word problems with

  7. Dome effect of black carbon and its key influencing factors: a one-dimensional modelling study

    Science.gov (United States)

    Wang, Zilin; Huang, Xin; Ding, Aijun

    2018-02-01

    Black carbon (BC) has been identified to play a critical role in aerosol-planetary boundary layer (PBL) interaction and further deterioration of near-surface air pollution in megacities, which has been referred to as the dome effect. However, the impacts of key factors that influence this effect, such as the vertical distribution and aging processes of BC, as well as the underlying land surface, have not been quantitatively explored yet. Here, based on available in situ measurements of meteorology and atmospheric aerosols together with the meteorology-chemistry online coupled model WRF-Chem, we conduct a set of parallel simulations to quantify the roles of these factors in influencing the BC dome effect and surface haze pollution. Furthermore, we discuss the main implications of the results to air pollution mitigation in China. We found that the impact of BC on the PBL is very sensitive to the altitude of aerosol layer. The upper-level BC, especially that near the capping inversion, is more essential in suppressing the PBL height and weakening the turbulent mixing. The dome effect of BC tends to be significantly intensified as BC mixed with scattering aerosols during winter haze events, resulting in a decrease in PBL height by more than 15 %. In addition, the dome effect is more substantial (up to 15 %) in rural areas than that in the urban areas with the same BC loading, indicating an unexpected regional impact of such an effect to air quality in countryside. This study indicates that China's regional air pollution would greatly benefit from BC emission reductions, especially those from elevated sources from chimneys and also domestic combustion in rural areas, through weakening the aerosol-boundary layer interactions that are triggered by BC.

  8. Regulation of cardiac microRNAs by serum response factor

    Directory of Open Access Journals (Sweden)

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  9. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  10. Using sensitivity analysis to identify key factors for the propagation of a plant epidemic.

    Science.gov (United States)

    Rimbaud, Loup; Bruchou, Claude; Dallot, Sylvie; Pleydell, David R J; Jacquot, Emmanuel; Soubeyrand, Samuel; Thébaud, Gaël

    2018-01-01

    Identifying the key factors underlying the spread of a disease is an essential but challenging prerequisite to design management strategies. To tackle this issue, we propose an approach based on sensitivity analyses of a spatiotemporal stochastic model simulating the spread of a plant epidemic. This work is motivated by the spread of sharka, caused by plum pox virus , in a real landscape. We first carried out a broad-range sensitivity analysis, ignoring any prior information on six epidemiological parameters, to assess their intrinsic influence on model behaviour. A second analysis benefited from the available knowledge on sharka epidemiology and was thus restricted to more realistic values. The broad-range analysis revealed that the mean duration of the latent period is the most influential parameter of the model, whereas the sharka-specific analysis uncovered the strong impact of the connectivity of the first infected orchard. In addition to demonstrating the interest of sensitivity analyses for a stochastic model, this study highlights the impact of variation ranges of target parameters on the outcome of a sensitivity analysis. With regard to sharka management, our results suggest that sharka surveillance may benefit from paying closer attention to highly connected patches whose infection could trigger serious epidemics.

  11. Post-Mergers and Acquisitions: The Motives, Success Factors and Key Success Indicators

    Directory of Open Access Journals (Sweden)

    Hatem El Zuhairy

    2015-07-01

    Full Text Available There is a wide body of evidence showing a significant increase in the adoption of mergers and acquisitions (M&A worldwide. Moreover, research confirms that the integration and implementation stage (post-M&A has a major impact on the success or failure of a merger or acquisition. Therefore it has become increasingly important to explore the post-M&A phase further in order to support the management teams of organizations pursuing a merger or acquisition in meeting all their desired objectives. This paper proposes a framework to help in the successful execution of M&A. The framework contains three main elements: the motives, success factors and key success indicators (KSI. A qualitative research approach using the multiple case study methodology was conducted to test the framework. Ten case studies were selected from the industrial sector in Egypt and used to validate the research. The final version of the M&A framework was provided after applying the research results. Considering the practical implications of the M&A framework, a tool was proposed for its application in light of the balanced scorecard (BSC methodology. The proposed M&A scorecard tool should be used in the strategic planning and execution of M&A. Both the proposed M&A framework and the M&A scorecard tool should be used to guide the implementation of M&A in order to increase the success rate enjoyed by organizations.

  12. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

    Directory of Open Access Journals (Sweden)

    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  13. What to copy: the key factor of observational learning in striped jack (Pseudocaranx dentex) juveniles.

    Science.gov (United States)

    Takahashi, K; Masuda, R; Yamashita, Y

    2014-03-01

    Animals in social environments can enhance their learning efficiency by observing the behaviour of others. Our previous study showed that learning efficiency of schooling fish increased through the observation of the behaviour of trained demonstrator conspecifics. The present study aimed to verify the key factor of observational learning by investigating what information is important for social transmission of feeding information. A striped jack (Pseudocaranx dentex) observer was provided with one of the five observation treatments: (a) pellets observation, where pellets were dropped near the aeration in an adjacent tank; (b) responding conspecific observation, where a trained conspecific demonstrator responded to the aeration without food in the adjacent tank; (c) foraging conspecific observation, where a conspecific demonstrator foraged near the aeration in the adjacent tank; (d) nearby pellets observation, where pellets were dropped in a transparent column near the aeration in the observer tank; and (e) foraging heterospecific observation, where a filefish (Stephanolepis cirrhifer) demonstrator foraged near the aeration in the adjacent tank. The response to the aeration in these observers was compared with that of controls who did not observe any behaviour. Only individuals who observed foraging conspecifics showed a response to the aeration after observing. These results suggest that observer fish acquire feeding information not through recognition of prey items or through imitation of the demonstrator, but through the vicarious reinforcement of a conspecific for foraging.

  14. Key Factors Affecting the Price of Airbnb Listings: A Geographically Weighted Approach

    Directory of Open Access Journals (Sweden)

    Zhihua Zhang

    2017-09-01

    Full Text Available Airbnb has been increasingly gaining popularity since 2008 due to its low prices and direct interactions with the local community. This paper employed a general linear model (GLM and a geographically weighted regression (GWR model to identify the key factors affecting Airbnb listing prices using data sets of 794 samples of Airbnb listings of business units in Metro Nashville, Tennessee. The results showed that the GWR model performs better than the GLM in terms of accuracy and affected variable selections. Statistically significant differences varied across regions in Metro Nashville. The coefficients illustrate a decreasing trend while there is an increase in the distance from the listed units to the convention center, which indicates that Airbnb listing prices are more sensitive to the distance from the convention center in the central area than in other areas. These findings can also provide implications for stakeholders such as Airbnb hosts to gain a better understanding of the market situation and formulate a suitable pricing strategy.

  15. Effects of key factors on solar aided methane steam reforming in porous medium thermochemical reactor

    International Nuclear Information System (INIS)

    Wang, Fuqiang; Tan, Jianyu; Ma, Lanxin; Leng, Yu

    2015-01-01

    Highlights: • Effects of key factors on chemical reaction for solar methane reforming are studied. • MCRT and FVM method coupled with UDFs is used to establish numerical model. • Heat and mass transfer model coupled with thermochemical reaction is established. • LTNE model coupled with P1 approximation is used for porous matrix solar reactor. • A formula between H 2 production and conductivity of porous matrix is put forward. - Abstract: With the aid of solar energy, methane reforming process can save up to 20% of the total methane consumption. Monte Carlo Ray Tracing (MCRT) method and Finite Volume Method (FVM) combined method are developed to establish the heat and mass transfer model coupled with thermochemical reaction kinetics for porous medium solar thermochemical reactor. In order to provide more temperature information, local thermal non-equilibrium (LTNE) model coupled with P1 approximation is established to investigate the thermal performance of porous medium solar thermochemical reaction. Effects of radiative heat loss and thermal conductivity of porous matrix on temperature distribution and thermochemical reaction for solar driven steam methane reforming process are numerically studied. Besides, the relationship between hydrogen production and thermal conductivity of porous matrix are analyzed. The results illustrate that hydrogen production shows a 3 order polynomial relation with thermal conductivity of porous matrix

  16. On key factors influencing ductile fractures of dual phase (DP) steels

    International Nuclear Information System (INIS)

    Sun, X.; Choi, K.S.; Soulami, A.; Liu, W.N.; Khaleel, M.A.

    2009-01-01

    In this paper, we examine the key factors influencing ductile failure of various grades of dual phase (DP) steels using the microstructure-based modeling approach. Various microstructure-based finite element models are generated based on the actual microstructures of DP steels with different martensite volume fractions. These models are, then, used to investigate the influence of ductility of the constituent ferrite phase and also the influence of voids introduced in the ferrite phase on the overall ductility of DP steels. It is found that with volume fraction of martensite in the microstructure less than 15%, the overall ductility of the DP steels strongly depends on the ductility of the ferrite matrix, hence pre-existing micro-voids in the microstructure significantly reduce the overall ductility of the steel. When the volume fraction of martensite is above 15%, the pre-existing voids in the ferrite matrix does not significantly reduce the overall ductility of the DP steels, and the overall ductility is more influenced by the mechanical property disparity between the two phases. The applicability of the phase inhomogeneity driven ductile failure of DP steels is then discussed based on the obtained computational results for various grades of DP steels, and the experimentally obtained scanning electron microscopy (SEM) pictures of the corresponding grades of DP steels near fracture surface are used as evidence for result validations.

  17. Hydrogen peroxide sensing, signaling and regulation of transcription factors

    Directory of Open Access Journals (Sweden)

    H. Susana Marinho

    2014-01-01

    Full Text Available The regulatory mechanisms by which hydrogen peroxide (H2O2 modulates the activity of transcription factors in bacteria (OxyR and PerR, lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4 and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1 are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1 synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for

  18. Antibiotic distribution channels in Thailand: results of key-informant interviews, reviews of drug regulations and database searches.

    Science.gov (United States)

    Sommanustweechai, Angkana; Chanvatik, Sunicha; Sermsinsiri, Varavoot; Sivilaikul, Somsajee; Patcharanarumol, Walaiporn; Yeung, Shunmay; Tangcharoensathien, Viroj

    2018-02-01

    To analyse how antibiotics are imported, manufactured, distributed and regulated in Thailand. We gathered information, on antibiotic distribution in Thailand, in in-depth interviews - with 43 key informants from farms, health facilities, pharmaceutical and animal feed industries, private pharmacies and regulators- and in database and literature searches. In 2016-2017, licensed antibiotic distribution in Thailand involves over 700 importers and about 24 000 distributors - e.g. retail pharmacies and wholesalers. Thailand imports antibiotics and active pharmaceutical ingredients. There is no system for monitoring the distribution of active ingredients, some of which are used directly on farms, without being processed. Most antibiotics can be bought from pharmacies, for home or farm use, without a prescription. Although the 1987 Drug Act classified most antibiotics as "dangerous drugs", it only classified a few of them as prescription-only medicines and placed no restrictions on the quantities of antibiotics that could be sold to any individual. Pharmacists working in pharmacies are covered by some of the Act's regulations, but the quality of their dispensing and prescribing appears to be largely reliant on their competences. In Thailand, most antibiotics are easily and widely available from retail pharmacies, without a prescription. If the inappropriate use of active pharmaceutical ingredients and antibiotics is to be reduced, we need to reclassify and restrict access to certain antibiotics and to develop systems to audit the dispensing of antibiotics in the retail sector and track the movements of active ingredients.

  19. Identifying a key physical factor sensitive to the performance of Madden-Julian oscillation simulation in climate models

    Science.gov (United States)

    Kim, Go-Un; Seo, Kyong-Hwan

    2018-01-01

    A key physical factor in regulating the performance of Madden-Julian oscillation (MJO) simulation is examined by using 26 climate model simulations from the World Meteorological Organization's Working Group for Numerical Experimentation/Global Energy and Water Cycle Experiment Atmospheric System Study (WGNE and MJO-Task Force/GASS) global model comparison project. For this, intraseasonal moisture budget equation is analyzed and a simple, efficient physical quantity is developed. The result shows that MJO skill is most sensitive to vertically integrated intraseasonal zonal wind convergence (ZC). In particular, a specific threshold value of the strength of the ZC can be used as distinguishing between good and poor models. An additional finding is that good models exhibit the correct simultaneous convection and large-scale circulation phase relationship. In poor models, however, the peak circulation response appears 3 days after peak rainfall, suggesting unfavorable coupling between convection and circulation. For an improving simulation of the MJO in climate models, we propose that this delay of circulation in response to convection needs to be corrected in the cumulus parameterization scheme.

  20. The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.

    Science.gov (United States)

    Khan, Sumbul Jawed; Abidi, Syeda Nayab Fatima; Skinner, Andrea; Tian, Yuan; Smith-Bolton, Rachel K

    2017-07-01

    Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

  1. Key Success Factors in the Brazilian Coffee Agrichain: Present and Future Challenges

    Directory of Open Access Journals (Sweden)

    Luciana Florêncio de Almeida

    2017-01-01

    Full Text Available Coffee production has grown 100% in volume over the past 30 years, accounting for 144 million coffee bags produced in 2015. Brazil responded to 42% of this production, along with Vietnam (19%, Colombia (9%, Indonesia (8%, and Ethiopia (4% (OIC, 2016. Following this pace, the consumption expanded not only in such traditional markets as the United States (4.2 kg/year, Germany (6.9 kg/year, and France (5.7 kg/year but also in tea-driven markets, such as Japan, Korea, Russia, and China (CECAFE, 2013. In 2015, Brazil harvested 43.2 million 60-kg bags of green coffee, 32 million of which were of Arabica coffee and 11.2 million of a Conilon species (CONAB, 2016. The planted area in Brazil is 2.3 million hectares, and there are about 287,000 producers, predominantly mini- and small farmers. Having continental dimensions, the country presents a variety of climates, reliefs, altitudes, and latitudes that allow the production of a wide range of types and qualities of coffee (MAPA, 2016. This research aimed to clarify present and future challenges for the Brazilian coffee agrichain, considering the growing demand and also competitiveness between the coffee countries’ producers. To capture the vivid perception of the actors in the coffee chain, a qualitative approach was employed. The research was conducted in three phases. In the first phase, 10 coffee specialists were interviewed to identify the coffee sector’s main milestones for Brazil over the next 30 years. The findings culminated in eight key success factors for coffee-farming management. Finally, in the second phase, the results of phase two were submitted for analysis by 39 coffee farmers through three discussion panels held in the major producing regions: Sul de Minas (corresponding to 25% of the national production, Cerrado Mineiro (with 10%, and Matas de Minas (with 16% (MAPA, 2016. The third phase comprised the data analysis, aggregating the patterns by regions and by critical factors. The

  2. Environmental impact and risk assessments and key factors contributing to the overall uncertainties.

    Science.gov (United States)

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Regulation of basophil and mast cell development by transcription factors

    Directory of Open Access Journals (Sweden)

    Haruka Sasaki

    2016-04-01

    Full Text Available Basophils and mast cells play important roles in host defense against parasitic infections and allergic responses. Several progenitor populations, either shared or specific, for basophils and/or mast cells have been identified, thus elucidating the developmental pathways of these cells. Multiple transcription factors essential for their development and the relationships between them have been also revealed. For example, IRF8 induces GATA2 expression to promote the generation of both basophils and mast cells. The STAT5-GATA2 axis induces C/EBPα and MITF expression, facilitating the differentiation into basophils and mast cells, respectively. In addition, C/EBPα and MITF mutually suppress each other's expression. This review provides an overview of recent advances in our understanding of how transcription factors regulate the development of basophils and mast cells.

  4. Thioredoxin reductase is a key factor in the oxidative stress response of Lactobacillus plantarum WCFS1

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    Teusink Bas

    2007-08-01

    Full Text Available Abstract Background Thioredoxin (TRX is a powerful disulfide oxido-reductase that catalyzes a wide spectrum of redox reactions in the cell. The aim of this study is to elucidate the role of the TRX system in the oxidative stress response in Lactobacillus plantarum WCFS1. Results We have identified the trxB1-encoded thioredoxin reductase (TR as a key enzyme in the oxidative stress response of Lactobacillus plantarum WCFS1. Overexpression of the trxB1 gene resulted in a 3-fold higher TR activity in comparison to the wild-type strain. Subsequently, higher TR activity was associated with an increased resistance towards oxidative stress. We further determined the global transcriptional response to hydrogen peroxide stress in the trxB1-overexpression and wild-type strains grown in continuous cultures. Hydrogen peroxide stress and overproduction of TR collectively resulted in the up-regulation of 267 genes. Additionally, gene expression profiling showed significant differential expression of 27 genes in the trxB1-overexpression strain. Over expression of trxB1 was found to activate genes associated with DNA repair and stress mechanisms as well as genes associated with the activity of biosynthetic pathways for purine and sulfur-containing amino acids. A total of 16 genes showed a response to both TR overproduction and hydrogen peroxide stress. These genes are involved in the purine metabolism, energy metabolism (gapB as well as in stress-response (groEL, npr2, and manganese transport (mntH2. Conclusion Based on our findings we propose that overproduction of the trxB1-encoded TR in L. plantarum improves tolerance towards oxidative stress. This response coincides with simultaneous induction of a group of 16 transcripts of genes. Within this group of genes, most are associated with oxidative stress response. The obtained crossover between datasets may explain the phenotype of the trxB1-overexpression strain, which appears to be prepared for encountering

  5. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels.

    Science.gov (United States)

    Zhang, Ren

    2012-08-10

    The metabolic syndrome, a common disorder including glucose intolerance and dyslipidemia, poses a major public health issue. Patients with high blood lipids, such as triglycerides, are at high risk in developing atherosclerotic cardiovascular diseases. To identify genes involved in metabolism, we performed RNA-seq experiments on the liver and fat in mice treated with a high-fat diet or fasting, and identified Gm6484 (named Lipasin) as a novel nutritionally regulated gene. Human LIPASIN is liver specific, while the mouse one is enriched in the liver and fat, including both brown and white adipose tissues. Obesity increases liver Lipasin, whereas fasting reduces its expression in fat. ANGPTL3 (Angiopoietin-like 3) and ANGPTL4 are critical regulators of blood lipids. LIPASIN shares homology with ANGPTL3's N-terminal domain that is needed for lipid regulation, and with ANGPTL4's N-terminal segment that mediates lipoprotein lipase (LPL) binding. Lipasin overexpression by adenoviruses in mice increases serum triglyceride levels, and a recombinant Lipasin inhibits LPL activity. Therefore, a potential mechanism for Lipasin-mediated triglyceride elevation is through reduced triglyceride clearance by LPL inhibition. Lipasin is thus a novel nutritionally-regulated liver-enriched factor that plays a role in lipid metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms

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    Simona-Adriana Manea

    2015-08-01

    Full Text Available NADPH oxidases (Nox represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS. Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases.

  7. Finding of key factors in creating small business system’s success : The case study in Thai restaurants in Sweden

    OpenAIRE

    Maleekaew, Chiraluck; Sudthamnong, Sirinun

    2007-01-01

    Research Questions: Which factors are the actual impacts for the success of Thai restaurant in Sweden? Aims of Research: To investigate the key factors that may cause the success within a restaurant. The success of the restaurant in this research is a restaurant that has positive financial result, revenue more than cost. Positive financial result shows that they manage the quality of the restaurant effectively. Methodology: This thesis studies and analyzes the variables and factors in process...

  8. Environmental impact and risk assessments and key factors contributing to the overall uncertainties

    International Nuclear Information System (INIS)

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems. - Highlights: • Source term uncertainties: ignoring radionuclide speciation radioactive particles, the inventory can be underestimated. • Ecosystem transfer uncertainties: Ignoring time dependent interactions, transfer rates and pathways can be wrongly assessed. • Exposure uncertainties: ignoring stressor interactions and effects, effects cannot be judged. • Response uncertainties: ignoring sensitive stages transgenerational effects impact and risks can be underestimated.

  9. The Canadian Natural Health Products (NHP regulations: industry perceptions and compliance factors

    Directory of Open Access Journals (Sweden)

    Boon Heather

    2006-05-01

    Full Text Available Abstract Background The use of natural health products, such as vitamins, minerals, and herbs, by Canadians has been increasing with time. As a result of consumer concern about the quality of these products, the Canadian Department of Health created the Natural Health Products (NHP Regulations. The new Canadian regulations raise questions about whether and how the NHP industry will be able to comply and what impact they will have on market structure. The objectives of this study were to explore who in the interview sample is complying with Canada's new NHP Regulations (i.e., submitted product licensing applications on time; and explore the factors that affect regulatory compliance. Methods Twenty key informant interviews were conducted with employees of the NHP industry. The structured interviews focused on the level of satisfaction with the Regulations and perceptions of compliance and non-compliance. Interviews were tape recorded and then transcribed verbatim. Data were independently coded, using qualitative content analysis. Team meetings were held after every three to four interviews to discuss emerging themes. Results The major finding of this study is that most (17 out of 20 companies interviewed were beginning to comply with the new regulatory regime. The factors that contribute to likelihood of regulatory compliance were: perceptions and knowledge of the regulations and business size. Conclusion The Canadian case can be instructive for other countries seeking to implement regulatory standards for natural health products. An unintended consequence of the Canadian NHP regulations may be the exit of smaller firms, leading to industry consolidation.

  10. The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats.

    Directory of Open Access Journals (Sweden)

    Yinghua Shi

    Full Text Available To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC and total bile acids (TBA levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1 The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group (P<0.05. (2 Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05. TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05. (3 mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05, as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05. The activities of these enzymes also paralleled the observed changes in mRNA levels. (4 There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1 the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2 the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

  11. Distributed Factorization Computation on Multiple Volunteered Mobile Resource to Break RSA Key

    Science.gov (United States)

    Jaya, I.; Hardi, S. M.; Tarigan, J. T.; Zamzami, E. M.; Sihombing, P.

    2017-01-01

    Similar to common asymmeric encryption, RSA can be cracked by usmg a series mathematical calculation. The private key used to decrypt the massage can be computed using the public key. However, finding the private key may require a massive amount of calculation. In this paper, we propose a method to perform a distributed computing to calculate RSA’s private key. The proposed method uses multiple volunteered mobile devices to contribute during the calculation process. Our objective is to demonstrate how the use of volunteered computing on mobile devices may be a feasible option to reduce the time required to break a weak RSA encryption and observe the behavior and running time of the application on mobile devices.

  12. Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone

    Directory of Open Access Journals (Sweden)

    Xingming Shi

    2007-01-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR-γ belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP, fat (e.g., leptin, muscle (e.g., myostatin, or bone (e.g., GILZ can in turn modulate PPAR expression and/or function. Of the two PPAR-γ isoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation.

  13. Regulation of bitter taste responses by tumor necrosis factor.

    Science.gov (United States)

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Prairie Pothole Region wetlands and subsurface drainage systems: Key factors for determining drainage setback distances

    Science.gov (United States)

    Tangen, Brian; Wiltermuth, Mark T.

    2018-01-01

    Use of agricultural subsurface drainage systems in the Prairie Pothole Region of North America continues to increase, prompting concerns over potential negative effects to the Region's vital wetlands. The U.S. Fish and Wildlife Service protects a large number of wetlands through conservation easements that often utilize standard lateral setback distances to provide buffers between wetlands and drainage systems. Because of a lack of information pertaining to the efficacy of these setback distances for protecting wetlands, information is required to support the decision making for placement of subsurface drainage systems adjacent to wetlands. We used qualitative graphical analyses and data comparisons to identify characteristics of subsurface drainage systems and wetland catchments that could be considered when assessing setback distances. We also compared setback distances with catchment slope lengths to determine if they typically exclude drainage systems from the catchment. We demonstrated that depth of a subsurface drainage system is a key factor for determining drainage setback distances. Drainage systems located closer to the surface (shallow) typically could be associated with shorter lateral setback distances compared with deeper systems. Subsurface drainage systems would be allowed within a wetland's catchment for 44–59% of catchments associated with wetland conservation easements in North Dakota. More specifically, results suggest that drainage setback distances generally would exclude drainage systems from catchments of the smaller wetlands that typically have shorter slopes in the adjacent upland contributing area. For larger wetlands, however, considerable areas of the catchment would be vulnerable to drainage that may affect wetland hydrology. U.S. Fish and Wildlife Service easements are associated with > 2,000 km2 of wetlands in North Dakota, demonstrating great potential to protect these systems from drainage depending on policies for installing

  15. Myocardin-related transcription factor regulates Nox4 protein expression

    DEFF Research Database (Denmark)

    Rozycki, Matthew; Bialik, Janne Folke; Speight, Pam

    2016-01-01

    translocation of MRTF. Because the Nox4 promoter harbors a serum response factor/MRTF cis-element (CC(A/T)6GG box), we asked if MRTF (and thus cytoskeleton organization) could regulate Nox4 expression. We show that Nox4 protein is robustly induced in kidney tubular cells exclusively by combined application...... TGFβ/contact disruption-provoked Nox4 protein and mRNA expression, Nox4 promoter activation, and reactive oxygen species production. Mutation of the CC(A/T)6GG box eliminates the synergistic activation of the Nox4 promoter. Jasplakinolide-induced actin polymerization synergizes with TGFβ to facilitate...... MRTF-dependent Nox4 mRNA expression/promoter activation. Moreover, MRTF inhibition prevents Nox4 expression during TGFβ-induced fibroblast-myofibroblast transition as well. Although necessary, MRTF is insufficient; Nox4 expression also requires TGFβ-activated Smad3 and TAZ/YAP, two contact...

  16. Oxygen, a key factor regulating cell behaviour during neurogenesis and cerebral diseases

    OpenAIRE

    Kuan eZhang; Lingling eZhu; Ming eFan

    2011-01-01

    Oxygen is vital to maintain the normal functions of alomost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases or in the ...

  17. Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.

    Science.gov (United States)

    Aprelikova, Olga; Chandramouli, Gadisetti V R; Wood, Matthew; Vasselli, James R; Riss, Joseph; Maranchie, Jodi K; Linehan, W Marston; Barrett, J Carl

    2004-06-01

    Hypoxia and induction of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) is a hallmark of many tumors. Under normal oxygen tension HIF-alpha subunits are rapidly degraded through prolyl hydroxylase dependent interaction with the von Hippel-Lindau (VHL) tumor suppressor protein, a component of E3 ubuiquitin ligase complex. Using microarray analysis of VHL mutated and re-introduced cells, we found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with known HIF target genes, while the other two family members (PHD1 and 2) did not respond to VHL. We further tested the regulation of these genes by HIF-1 and HIF-2 and found that siRNA targeted degradation of HIF-1alpha and HIF-2alpha results in decreased hypoxia-induced PHD3 expression. Ectopic overexpression of HIF-2alpha in two different cell lines provided a much better induction of PHD3 gene than HIF-1alpha. In contrast, we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF-2alpha. However, induction of PHD2 by hypoxia has HIF-1-independent and -dependent components. Short-term hypoxia (4 h) results in induction of PHD2 independent of HIF-1, while PHD2 accumulation by prolonged hypoxia (16 h) was decreased by siRNA-mediated degradation of HIF-1alpha subunit. These data further advance our understanding of the differential role of HIF factors and putative feedback loop in HIF regulation. Copyright 2004 Wiley-Liss, Inc.

  18. Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.

    Science.gov (United States)

    Laperrousaz, Elise; Moullé, Valentine S; Denis, Raphaël G; Kassis, Nadim; Berland, Chloé; Colsch, Benoit; Fioramonti, Xavier; Philippe, Erwann; Lacombe, Amélie; Vanacker, Charlotte; Butin, Noémie; Bruce, Kimberley D; Wang, Hong; Wang, Yongping; Gao, Yuanqing; Garcia-Caceres, Cristina; Prévot, Vincent; Tschöp, Matthias H; Eckel, Robert H; Le Stunff, Hervé; Luquet, Serge; Magnan, Christophe; Cruciani-Guglielmacci, Céline

    2017-07-01

    Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.

  19. Regulation of stem cell factor expression in inflammation and asthma

    Directory of Open Access Journals (Sweden)

    Carla A Da Silva

    2005-03-01

    Full Text Available Stem cell factor (SCF is a major mast cell growth factor, which could be involved in the local increase of mast cell number in the asthmatic airways. In vivo, SCF expression increases in asthmatic patients and this is reversed after treatment with glucocorticoids. In vitro in human lung fibroblasts in culture, IL-1beta, a pro-inflammatory cytokine, confirms this increased SCF mRNA and protein expression implying the MAP kinases p38 and ERK1/2 very early post-treatment, and glucocorticoids confirm this decrease. Surprisingly, glucocorticoids potentiate the IL-1beta-enhanced SCF expression at short term treatment, implying increased SCF mRNA stability and SCF gene transcription rate. This potentiation involves p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1 also confirm this increase and decrease of SCF expression by IL-1beta and glucocorticoids, and the potentiation by glucocorticoids of the IL-1beta-induced SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation, and the effect of IL-1beta or glucocorticoids alone. DNA binding of GR and NF-kappaB are also demonstrated for these effects. In conclusion, this review concerns new mechanisms of regulation of SCF expression in inflammation that could lead to potential therapeutic strategy allowing to control mast cell number in the asthmatic airways.

  20. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jacqueline G. Miller

    2016-03-01

    Full Text Available Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.

  1. On the Security of a Two-Factor Authentication and Key Agreement Scheme for Telecare Medicine Information Systems.

    Science.gov (United States)

    Arshad, Hamed; Teymoori, Vahid; Nikooghadam, Morteza; Abbassi, Hassan

    2015-08-01

    Telecare medicine information systems (TMISs) aim to deliver appropriate healthcare services in an efficient and secure manner to patients. A secure mechanism for authentication and key agreement is required to provide proper security in these systems. Recently, Bin Muhaya demonstrated some security weaknesses of Zhu's authentication and key agreement scheme and proposed a security enhanced authentication and key agreement scheme for TMISs. However, we show that Bin Muhaya's scheme is vulnerable to off-line password guessing attacks and does not provide perfect forward secrecy. Furthermore, in order to overcome the mentioned weaknesses, we propose a new two-factor anonymous authentication and key agreement scheme using the elliptic curve cryptosystem. Security and performance analyses demonstrate that the proposed scheme not only overcomes the weaknesses of Bin Muhaya's scheme, but also is about 2.73 times faster than Bin Muhaya's scheme.

  2. Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts.In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real-time PCR, western blotting and functional assays.We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases.

  3. Identify and rank key factors influencing the adoption of cloud computing for a healthy Electronics

    Directory of Open Access Journals (Sweden)

    Javad Shukuhy

    2015-02-01

    Full Text Available Cloud computing as a new technology with Internet infrastructure and new approaches can be significant benefits in providing medical services electronically. Aplying this technology in E-Health requires consideration of various factors. The main objective of this study is to identify and rank the factors influencing the adoption of e-health cloud. Based on the Technology-Organization-Environment (TOE framework and Human-Organization-Technology fit (HOT-fit model, 16 sub-factors were identified in four major factors. With survey of 60 experts, academics and experts in health information technology and with the help of fuzzy analytic hierarchy process had ranked these sub-factors and factors. In the literature, considering newness this study, no internal or external study, have not alluded these number of criteria. The results show that when deciding to adopt cloud computing in E-Health, respectively, must be considered technological, human, organizational and environmental factors.

  4. Drug packaging. A key factor to be taken into account when choosing a treatment.

    Science.gov (United States)

    2011-10-01

    A drug's packaging contributes to its harm-benefit balance. Highlighting the key practical information and identifying potential sources of error or mix-ups is part and parcel of the correct use of medicines. Select labelling that clearly and prominently displays the important information, including the international nonproprietary name (INN).

  5. Wnt-inducible protein (WISP-1 is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Melanie Königshoff

    2006-12-01

    Full Text Available Fibrotic lung disease is characterized by distorted lung architecture and severe loss of respiratory function secondary to alveolar epithelial cell (AEC hyperplasia, enhanced extracellular matrix (ECM deposition and fibroblast proliferation. Repetitive epithelial injuries with impaired alveolar wound healing and altered AEC gene expression represent a trigger mechanism for development of fibrosis. To reveal gene regulatory networks in lung fibrosis, we compared gene expression profiles of freshly isolated AEC obtained from mice 14 days after saline or bleomycin (BM instillation using whole genome microarray analysis. Several genes of the Wnt signaling pathway, in particular WISP-1, a member of the CCN family, were highly regulated. WISP-1 protein expression was demonstrated in proliferating AEC in BM-treated lungs by immunofluorescence. When analyzing all six CCN family members, WISP-1 was upregulated the most 14 days after BM challenge, as analyzed by qRT-PCR. To elucidate WISP-1 function, cultured primary mouse AEC were stimulated with WISP-1 and demonstrated a 230% increase in proliferation, analyzed by 3H-thymidine incorporation. This was mediated through enhanced phosphorylation, but not expression of protein kinase B (PKB/Akt, as detected by immunoblot. Finally, increased expression of WISP-1 was detected in lung homogenates and isolated AEC from IPF patients, using qRT-PCR. Immunohistochemical analysis of WISP-1 and Ki67 verified the existence of hyperplastic and proliferative AEC expressing WISP-1 in vivo. Our study thus identifies WISP-1 as a novel regulator of AEC injury and repair, and suggests that WISP-1 is a key mediator in pulmonary fibrosis.

  6. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility

    Directory of Open Access Journals (Sweden)

    Violeta Calle-Guisado

    2017-01-01

    Full Text Available AMP-activated kinase (AMPK, a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work′s aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS in the presence or absence of the AMPK inhibitor compound C (CC. AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

  7. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility

    Science.gov (United States)

    Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

    2017-01-01

    AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%–80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied. PMID:27678462

  8. Identifying key factors for mobilising under-utilised low carbon land resources : A case study on Kalimantan

    NARCIS (Netherlands)

    Goh, Chun Sheng; Junginger, Martin; Potter, Lesley; Faaij, André; Wicke, Birka

    2018-01-01

    Mobilising under-utilised low carbon (ULC) land for future agricultural expansion helps minimising further carbon stock loss. This study examined the regency cases in Kalimantan, a carbon loss hotspot, to understand the key factors for mobilising ULC land via narrative interviews with a range of

  9. Management competences become key factor for success. Competition market energy; Managementkompetenzen werden Schluesselfaktor fuer Erfolg. Wettbewerbsmarkt Energie

    Energy Technology Data Exchange (ETDEWEB)

    Bausch, A. [Allgemeine Betriebswirtschaftlehre/Internationales Management, Friedrich-Schiller-Univ. Jena (Germany); Strategisches Management und Controlling, Jacobs Univ. Bremen (Germany); Fritz, T. [Jacobs University Bremen (Germany); Werthschulte, S.; Schumacher, T.; Holst, A.; Schiegg, T. [Accenture GmbH (Germany)

    2007-07-09

    In view of deregulation, enhanced competition and a multitude of options for action, clear strategic positioning and a strong operative management have become key factors of success. The authors of the study 'Value Creator III' investigated the approaches that made current industrial leaders successful and the challenges to be met in the future. (orig.)

  10. Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges

    NARCIS (Netherlands)

    Burgos, Daniel; Koper, Rob

    2005-01-01

    Burgos, D., Koper, R. (2005) Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges. In E-Journal of Educational Research, Assessment and Evaluation, vol. 11, issue 2 [www.uv.es/RELIEVE]. Available at

  11. Regulation of the yeast metabolic cycle by transcription factors with periodic activities

    Directory of Open Access Journals (Sweden)

    Pellegrini Matteo

    2011-10-01

    Full Text Available Abstract Background When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can also be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Knowing the transcription factors involved in the yeast metabolic cycle is helpful for determining the cascade of regulatory events that cause these patterns. Results Transcription factor activities were estimated by linear regression using time series and genome-wide transcription factor binding data. Time-translation matrices were estimated using least squares and were used to model the interactions between the most significant transcription factors. The top transcription factors have functions involving respiration, cell cycle events, amino acid metabolism and glycolysis. Key regulators of transitions between phases of the yeast metabolic cycle appear to be Hap1, Hap4, Gcn4, Msn4, Swi6 and Adr1. Conclusions Analysis of the phases at which transcription factor activities peak supports previous findings suggesting that the various cellular functions occur during specific phases of the yeast metabolic cycle.

  12. A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

    Science.gov (United States)

    Hoseinzade, Zohre; Mokhtari, Ahmad Reza

    2017-10-01

    Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

  13. [PRODUCT OF THE BMI1--A KEY COMPONENT OF POLYCOMB--POSITIVELY REGULATES ADIPOCYTE DIFFERENTIATION OF MOUSE MESENCHYMAL STEM CELLS].

    Science.gov (United States)

    Petrov, N S; Vereschagina, N A; Sushilova, E N; Kropotov, A V; Miheeva, N F; Popov, B V

    2016-01-01

    Bmil is a key component of Polycomb (PcG), which in mammals controls the basic functions of mammalian somatic stem cells (SSC) such as self-renewal and differentiation. Bmi1 supports SSC via transcriptional suppression of genes associated with cell cycle and differentiation. The most studied target genes of Bmi1 are the genes of Ink4 locus, CdkI p16(Ink4a) and p1(Arf), suppression of which due to activating mutations of the BMI1 results in formation of cancer stem cells (CSC) and carcinomas in various tissues. In contrast, inactivation of BMI1 results in cell cycle arrest and cell senescence. Although clinical phenomena of hypo- and hyperactivation of BMI1 are well known, its targets and mechanisms of regulation of tissue specific SSC are still obscure. The goal of this study was to evaluate the regulatory role of BMI1 in adipocyte differentiation (AD) of mouse mesenchymal stem cells (MSC). Induction of AD in mouse MSC of the C3H10T1/2 cell line was associated with an increase in the expression levels of BMI1, the genes of pRb family (RB, p130) and demethylase UTX, but not methyltransferase EZH2, whose products regulate the methylation levels of H3K27. It was observed earlier that H3K27me3 may play the role of the epigenetic switch by promoting AD of human MSC via activating expression of the PPARγ2, the master gene of AD (Hemming et al., 2014). Here we show that inactivation of BMI1 using specific siRNA slows and decreases the levels of AD, but does not abolish it. This is associated with a complete inhibition of the expression of adipogenic marker genes--PPARγ2, ADIPOQ and a decrease in the expression of RB, p130, but not UTX. The results obtained give evidence that the epigenetic mechanism regulating AD differentiation in mouse and human MSC is different.

  14. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

    International Nuclear Information System (INIS)

    Caiazzo, Massimiliano; Colucci-D'Amato, Luca; Esposito, Maria T.; Parisi, Silvia; Stifani, Stefano; Ramirez, Francesco; Porzio, Umberto di

    2010-01-01

    Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

  15. Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

    Energy Technology Data Exchange (ETDEWEB)

    Caiazzo, Massimiliano, E-mail: caiazzo@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Istituto di diagnosi e cura ' Hermitage Capodimonte,' 80131 Naples (Italy); Colucci-D' Amato, Luca, E-mail: luca.colucci@unina2.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy); Dipartimento di Scienze della Vita, Seconda Universita di Napoli, 81100 Caserta (Italy); Esposito, Maria T., E-mail: maria_teresa.esposito@kcl.ac.uk [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Parisi, Silvia, E-mail: parisi@ceinge.unina.it [CEINGE Biotecnologie Avanzate, 80145 Naples (Italy); Stifani, Stefano, E-mail: stefano.stifani@mcgill.ca [Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4 (Canada); Ramirez, Francesco, E-mail: francesco.ramirez@mssm.edu [Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029 (United States); Porzio, Umberto di, E-mail: diporzio@igb.cnr.it [Institute of Genetics and Biophysics ' A. Buzzati-Traverso,' CNR, 80131 Naples (Italy)

    2010-08-15

    Previous gene targeting studies in mice have implicated the nuclear protein Krueppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates.

  16. Key Factors Affecting Construction Safety Performance in Developing Countries: Evidence from Cambodia

    OpenAIRE

    Durdyev, Serdar; Mohamed, Sherif; Lay, Meng Leang; Ismail, Syuhaida

    2017-01-01

    Although proper safety management in construction is of utmost importance; anecdotal evidence suggests that safety is not adequately considered in many developing countries. This paper considers the key variables affecting construction safety performance in Cambodia. Using an empirical questionnaire survey targeting local construction professionals, respondents were invited to rate the level of importance of 30 variables identified from the seminal literature. The data set was subjected to f...

  17. Starting a hospital-based home health agency: Part II--Key success factors.

    Science.gov (United States)

    Montgomery, P

    1993-09-01

    In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control.

  18. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    Science.gov (United States)

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  19. From Loose Groups to Effective Teams: The Nine Key Factors of the Team Landscape.

    Science.gov (United States)

    Sheard, A. G.; Kakabadse, A. P.

    2002-01-01

    A loose group of individuals working on a task differs from an effective team on nine factors: clearly defined goals, priorities, roles and responsibilities, self-awareness, leadership, group dynamics, communications, content, and infrastructure. Ways to eliminate barriers and speed formation of effective teams could be based on those factors.…

  20. Regulation of Brain-Derived Neurotrophic Factor and Growth Factor Signaling Pathways by Tyrosine Phosphatase Shp2 in the Retina: A Brief Review

    Directory of Open Access Journals (Sweden)

    Mojdeh Abbasi

    2018-03-01

    Full Text Available SH2 domain-containing tyrosine phosphatase-2 (PTPN11 or Shp2 is a ubiquitously expressed protein that plays a key regulatory role in cell proliferation, differentiation and growth factor (GF signaling. This enzyme is well expressed in various retinal neurons and has emerged as an important player in regulating survival signaling networks in the neuronal tissues. The non-receptor phosphatase can translocate to lipid rafts in the membrane and has been implicated to regulate several signaling modules including PI3K/Akt, JAK-STAT and Mitogen Activated Protein Kinase (MAPK pathways in a wide range of biochemical processes in healthy and diseased states. This review focuses on the roles of Shp2 phosphatase in regulating brain-derived neurotrophic factor (BDNF neurotrophin signaling pathways and discusses its cross-talk with various GF and downstream signaling pathways in the retina.

  1. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  2. Factors affecting the regulation of pacing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mauger AR

    2014-09-01

    Full Text Available Alexis R Mauger Endurance Research Group, School of Sport and Exercise Sciences, Faculty of Science, University of Kent, Chatham, UK Abstract: During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed "exercise-induced pain". Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing. Keywords: pain, exercise-induced pain, discomfort, exercise performance, self-paced

  3. The forkhead transcription factor FoxY regulates Nanos.

    Science.gov (United States)

    Song, Jia L; Wessel, Gary M

    2012-10-01

    FoxY is a member of the forkhead transcription factor family that appeared enriched in the presumptive germ line of sea urchins (Ransick et al. Dev Biol 2002;246:132). Here, we test the hypothesis that FoxY is involved in germ line determination in this animal. We found two splice forms of FoxY that share the same DNA-binding domain, but vary in the carboxy-terminal trans-activation/repression domain. Both forms of the FoxY protein are present in the egg and in the early embryo, and their mRNAs accumulate to their highest levels in the small micromeres and adjacent non-skeletogenic mesoderm. Knockdown of FoxY resulted in a dramatic decrease in Nanos mRNA and protein levels as well as a loss of coelomic pouches in 2-week-old larvae. Our results indicate that FoxY positively regulates Nanos at the transcriptional level and is essential for reproductive potential in this organism. Copyright © 2012 Wiley Periodicals, Inc.

  4. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  5. BPR implementation process: an analysis of key success and failure factors

    Directory of Open Access Journals (Sweden)

    Mohamad Reza Khoshlafz

    2016-08-01

    Full Text Available This paper investigates the effects of different factors influencing on the successful implementation of the business process re-engineering (BPR in Iran. The study selects 386 experts randomly and using some statistical tests examines the effects of four groups of factors including strategic, organizational, methodologic and technological & educational issues on the success of the BPR implementation in Iran. The study designs a questionnaire in Likert scale and distributes it among some experts where Cronbach alpha was calculated as 0.71. The implementation of Pearson correlation ratio has confirmed that technological and educational factors marinated the highest effects (r = 0.523, Sig. = 0.000 followed by strategic (r = 0.505, Sig. = 0.000, organizational (r = 0.352, Sig. = 0.000 and methodologic issues (r = 0.267, Sig. = 0.000. In addition, the implementation of Stepwise regression has confirmed that technological & educational, strategic and methodologic factors influence on BPR in Iran.

  6. PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.

    Science.gov (United States)

    Tepper, Ronald G; Ashraf, Jasmine; Kaletsky, Rachel; Kleemann, Gunnar; Murphy, Coleen T; Bussemaker, Harmen J

    2013-08-01

    Reduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (class I) and downregulating other (class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genome-wide mRNA expression responsiveness to DAF-16 with genome-wide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (class II) genes by binding to the DAF-16-associated element (DAE). DAF-16 directly regulates class I genes only, through the DAF-16-binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components

    Czech Academy of Sciences Publication Activity Database

    Steringer, J. P.; Lange, S.; Čujová, Sabína; Šachl, Radek; Poojari, C.; Lolicato, F.; Beutel, O.; Müller, H.-M.; Unger, S.; Coskun, U.; Honigmann, A.; Vattulainen, I.; Hof, Martin; Freund, Ch.; Nickel, W.

    2017-01-01

    Roč. 6, č. 2017 (2017), č. článku e28985. ISSN 2050-084X R&D Projects: GA ČR(CZ) GC14-03141J Institutional support: RVO:61388955 Keywords : Unconventional protein secretion * Fibroblast Growth Factor 2 * Protein translocation across membranes Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 7.725, year: 2016

  8. Visual control as a key factor in a production process of a company from automotive branch

    Directory of Open Access Journals (Sweden)

    Stanisław Borkowski

    2013-04-01

    Full Text Available This article presents a theoretical basis for one type of control in enterprises – visual control. It presents the meaning of visual control in the Toyota Production System and BOST researches as a tool of measure, among other things, the importance of visual control in production companies. The level of importance of visual control usage as one of the production process elements in the analysed company was indicated. The usage of visual control is a main factor in a production process of the analyzed company, the factor which provides continuous help to employees to check whether the process differs from the standard. The characteristic progression of production process elements was indicated and the SW factor (the use of visual control took the third place, PE factor (interruption of production when it detects a problem of quality turned out to be the most important one, while the least important was the EU factor (granting power of attorney down. The main tools for this evaluation: an innovative BOST survey - Toyota's management principles in questions, in particular, the Pareto-Lorenz diagram, radar graph and series of importance as graphical interpretation tools, were used to present the importance of each factor in relation to individual assessments.

  9. Human resource development – A key factor for the sustainable development of Albania

    Directory of Open Access Journals (Sweden)

    Perlat Lame

    2004-01-01

    Full Text Available This article deals with the current situation of labor resources in Albania and its trends from the viewpoint of their contributions to the overall country progress. A real partnership between business and public institutions, the efforts to formalize the economy, to promote discipline and better application of international standards are considered key issues for the future country developments. The effective management of human resources and coordination could not be reached without profound structural and economic reforms, without free entrepreneurship initiative encouragement, and without mutual confidence between the employers and the employees.

  10. Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

    Science.gov (United States)

    Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

    2017-06-01

    In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells. Copyright © 2017 Endocrine Society

  11. Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

    Directory of Open Access Journals (Sweden)

    Adam Z. Blatt

    2017-11-01

    Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

  12. The key factors affecting students' individual interest in school science lessons

    Science.gov (United States)

    Cheung, Derek

    2018-01-01

    Individual interest in school science lessons can be defined as a relatively stable and enduring personal emotion comprising affective and behavioural reactions to events in the regular science lessons at school. Little research has compared the importance of different factors affecting students' individual interest in school science lessons. The present study aimed to address this gap, using a mixed methods design. Qualitative interview data were collected from 60 Hong Kong junior secondary school students, who were asked to describe the nature of their interest in science lessons and the factors to which they attribute this. Teacher interviews, parent interviews, and classroom observations were conducted to triangulate student interview data. Five factors affecting students' individual interest in school science lessons were identified: situational influences in science lessons, individual interest in science, science self-concept, grade level, and gender. Quantitative data were then collected from 591 students using a questionnaire. Structural equation modelling was applied to test a hypothesised model, which provided an acceptable fit to the student data. The strongest factor affecting students' individual interest in school science lessons was science self-concept, followed by individual interest in science and situational influences in science lessons. Grade level and gender were found to be nonsignificant factors. These findings suggest that teachers should pay special attention to the association between academic self-concept and interest if they want to motivate students to learn science at school.

  13. Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills and school factors (low-level classroom task-goal orientation, which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school's tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students' belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change.

  14. Akirin1 (Mighty), a novel promyogenic factor regulates muscle regeneration and cell chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Salerno, Monica Senna; Dyer, Kelly; Bracegirdle, Jeremy; Platt, Leanne; Thomas, Mark; Siriett, Victoria [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand); Kambadur, Ravi [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand); School of Biological Sciences, Nanyang Technological University, Singapore (Singapore); Sharma, Mridula, E-mail: bchmridu@nus.edu.sg [Functional Muscle Genomics, AgResearch, Hamilton (New Zealand)

    2009-07-15

    Akirin1 (Mighty) is a downstream target gene of myostatin and has been shown to be a promyogenic factor. Although expressed in many tissues, akirin1 is negatively regulated by myostatin specifically in skeletal muscle tissue. In this manuscript we have characterized the possible function of akirin1 in postnatal muscle growth. Molecular and immunohistological analyses indicated that while low levels of akirin1 are associated with quiescent satellite cells (SC), higher levels of akirin1 are detected in activated proliferating SC indicating that akirin1 could be associated with satellite cell activation. In addition to SC, macrophages also express akirin1, and increased expression of akirin1 resulted in more efficient chemotaxis of both macrophages and myoblasts. Akirin1 appears to regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. Expression analysis during muscle regeneration also indicated that akirin1 expression is detected very early (day 2) in regenerating muscle, and expression gradually peaks to coincide the nascent myotube formation stage of muscle regeneration. Based on these results we propose that akirin1 could be acting as a transducer of early signals of muscle regeneration. Thus, we speculate that myostatin regulates key steps of muscle regeneration including chemotaxis of inflammatory cells, SC activation and migration through akirin1.

  15. Akirin1 (Mighty), a novel promyogenic factor regulates muscle regeneration and cell chemotaxis

    International Nuclear Information System (INIS)

    Salerno, Monica Senna; Dyer, Kelly; Bracegirdle, Jeremy; Platt, Leanne; Thomas, Mark; Siriett, Victoria; Kambadur, Ravi; Sharma, Mridula

    2009-01-01

    Akirin1 (Mighty) is a downstream target gene of myostatin and has been shown to be a promyogenic factor. Although expressed in many tissues, akirin1 is negatively regulated by myostatin specifically in skeletal muscle tissue. In this manuscript we have characterized the possible function of akirin1 in postnatal muscle growth. Molecular and immunohistological analyses indicated that while low levels of akirin1 are associated with quiescent satellite cells (SC), higher levels of akirin1 are detected in activated proliferating SC indicating that akirin1 could be associated with satellite cell activation. In addition to SC, macrophages also express akirin1, and increased expression of akirin1 resulted in more efficient chemotaxis of both macrophages and myoblasts. Akirin1 appears to regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. Expression analysis during muscle regeneration also indicated that akirin1 expression is detected very early (day 2) in regenerating muscle, and expression gradually peaks to coincide the nascent myotube formation stage of muscle regeneration. Based on these results we propose that akirin1 could be acting as a transducer of early signals of muscle regeneration. Thus, we speculate that myostatin regulates key steps of muscle regeneration including chemotaxis of inflammatory cells, SC activation and migration through akirin1.

  16. Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression.

    Science.gov (United States)

    Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A

    2014-05-02

    To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.

  17. In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

    Science.gov (United States)

    Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

    2018-01-01

    Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

  18. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis.

    Science.gov (United States)

    Sarruf, David A; Yu, Fang; Nguyen, Hong T; Williams, Diana L; Printz, Richard L; Niswender, Kevin D; Schwartz, Michael W

    2009-02-01

    In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-gamma agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARgamma is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARgamma distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spanning the hypothalamus, the ventral tegmental area, and the nucleus tractus solitarius. In several brain areas, nuclear PPARgamma immunoreactivity was detected in cells that costained for neuronal nuclei, a neuronal marker. In the hypothalamus, PPARgamma immunoreactivity was observed in a majority of neurons in the arcuate (including both agouti related protein and alpha-MSH containing cells) and ventromedial hypothalamic nuclei and was also present in the hypothalamic paraventricular nucleus, the lateral hypothalamic area, and tyrosine hydroxylase-containing neurons in the ventral tegmental area but was not expressed in the nucleus tractus solitarius. To validate and extend these histochemical findings, we generated mice with neuron-specific PPARgamma deletion using nestin cre-LoxP technology. Compared with littermate controls, neuron-specific PPARgamma knockout mice exhibited dramatic reductions of both hypothalamic PPARgamma mRNA levels and PPARgamma immunoreactivity but showed no differences in food intake or body weight over a 4-wk study period. We conclude that: 1) PPARgamma mRNA and protein are expressed in the hypothalamus, 2) neurons are the predominant source of PPARgamma in the central nervous system, although it is likely expressed by nonneuronal cell types as well, and 3) arcuate nucleus neurons that control energy homeostasis and glucose metabolism are among those in which PPARgamma is expressed.

  19. Identification of trans-acting factors regulating SamDC expression in Oryza sativa

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in [Department of Crop Soil and Environmental Sciences, University of Arkansas, Fayetteville, AR 72701 (United States); Division of Plant Biology, Bose Institute, Kolkata (India); Roychoudhury, Aryadeep [Post Graduate Department of Biotechnology, St. Xavier' s College (Autonomous), 30, Mother Teresa Sarani, Kolkata - 700016, West Bengal (India); Sengupta, Dibyendu N. [Division of Plant Biology, Bose Institute, Kolkata (India)

    2014-03-07

    Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.

  20. Clusters Regarding Key Factors Affecting Changes in Accounting, Finance, Administration and Management Control

    Directory of Open Access Journals (Sweden)

    Rodica Gabriela Blidisel

    2010-01-01

    Full Text Available During the last decade, important changes have occurred in public governance, which has evolved in this time from hierarchical bureaucracy to participatory governance, where the role of citizens in public decision-making process is more direct. There were performed reforms in finance, management administration and finances of public sector. Starting from the factors that influenced during the history the accounting, finances, administration and management control, we want to test the factors that affect the changes of these elements in Romanian environment.

  1. Analysis of key hardware factors and countermeasure for restricting 49-2 swimming pool reactor lifetime

    International Nuclear Information System (INIS)

    Zhang Yadong; Guo Yue; Yang Xiao; Wang Yiwei; Wang Zhanwen

    2013-01-01

    Safe operation is the most important factor to determine the lifetime of aged 49-2 swimming pool reactor. In this paper, the hardware factors of lifetime were analyzed, such as the pool concrete aging, corrosion of aluminum container and primary coolant system, and graphite swelling etc., and then the corresponding measures such as surveillance, prevention and maintenance were purposed. The results show that 49-2 swimming pool reactor can continue to operate safely due to that container is safe under 8 degree earthquake, the reactor is safe on flood level of once per millennium, adding dam break, and the ageing condition of primary coolant system and container is acceptable. (authors)

  2. A pea chloroplast translation elongation factor that is regulated by abiotic factors

    International Nuclear Information System (INIS)

    Singh, B.N.; Mishra, R.N.; Agarwal, Pradeep K.; Goswami, Mamta; Nair, Suresh; Sopory, S.K.; Reddy, M.K.

    2004-01-01

    We report the cloning and characterization of both the cDNA (tufA) and genomic clones encoding for a chloroplast translation elongation factor (EF-Tu) from pea. The analysis of the deduced amino acids of the cDNA clone reveals the presence of putative transit peptide sequence and four GTP binding domains and two EF-Tu signature motifs in the mature polypeptide region. Using in vivo immunostaining followed by confocal microscopy pea EF-Tu was localized to chloroplast. The steady state transcript level of pea tufA was high in leaves and not detectable in roots. The expression of this gene is stimulated by light. The differential expression of this gene in response to various abiotic stresses showed that it is down-regulated in response to salinity and ABA and up-regulated in response to low temperature and salicylic acid treatment. These results indicate that regulation of pea tufA may have an important role in plant adaptation to environmental stresses

  3. Key Success Factors of Innovation in Multinational Agri-food Prospector Companies

    NARCIS (Netherlands)

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F.

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) compares the self assessment of the drivers and barriers to innovation at the company level and the critical success and failure factors of innovation at the project level with data of agrifood prospector firms around the world. In total 46 innovation

  4. Key factors affecting the predation risk on insects on leaves in temperate floodplain forest

    Czech Academy of Sciences Publication Activity Database

    Drozdová, M.; Šipoš, Jan; Drozd, P.

    2013-01-01

    Roč. 110, č. 3 (2013), s. 469-476 ISSN 1210-5759 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional support: RVO:67179843 Keywords : Diptera * Calliphoridae * Calliphora vicina * insect predators * living prey * temporal and spatial differences * clumped dispersal of attacks Subject RIV: EH - Ecology, Behaviour Impact factor: 1.076, year: 2013

  5. Key Factors in Smoking Cessation Intervention among 15-16-Year-Olds

    Science.gov (United States)

    Heikkinen, Anna Maria; Broms, Ulla; Pitkaniemi, Janne; Koskenvuo, Markku; Meurman, Jukka

    2009-01-01

    The authors aimed to investigate factors associated with smoking cessation among adolescents after tobacco intervention. They examined smokers (n = 127) from one birth cohort (n = 545) in the city of Kotka in Finland. These smokers were randomized in 3 intervention groups the dentist (n = 44) and the school nurse (n = 42 groups), and a control…

  6. The Key Factors Affecting Students' Individual Interest in School Science Lessons

    Science.gov (United States)

    Cheung, Derek

    2018-01-01

    Individual interest in school science lessons can be defined as a relatively stable and enduring personal emotion comprising affective and behavioural reactions to events in the regular science lessons at school. Little research has compared the importance of different factors affecting students' individual interest in school science lessons. The…

  7. Key-socio economic factors influencing sustainable land management investments in the West Usambara Highlands, Tanzania

    NARCIS (Netherlands)

    Nyanga, A.W.; Kessler, C.A.; Tenge, A.J.M.

    2016-01-01

    Low investments in sustainable land management (SLM) limit agricultural production in the East African Highlands, leading to increased soil erosion, low productivity of land and food insecurity. Recent studies in the region show that different socio-economic factors influence SLM investments by

  8. Developmental regulation of human truncated nerve growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  9. Developmental regulation of human truncated nerve growth factor receptor

    International Nuclear Information System (INIS)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  10. The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

    International Nuclear Information System (INIS)

    Kwon, Oh Hyung; Lee, Chong-Kil; Lee, Young Ik; Paik, Sang-Gi; Lee, Hyun-Jun

    2005-01-01

    Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1 -/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation

  11. Circadian transcription factor BMAL1 regulates innate immunity against select RNA viruses.

    Science.gov (United States)

    Majumdar, Tanmay; Dhar, Jayeeta; Patel, Sonal; Kondratov, Roman; Barik, Sailen

    2017-02-01

    BMAL1 (brain and muscle ARNT-like protein 1, also known as MOP3 or ARNT3) belongs to the family of the basic helix-loop-helix (bHLH)-PAS domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. Here, we report that BMAL1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the Paramyxoviridae family, namely RSV and PIV3. Embryonic fibroblasts from Bmal1 -/- mice produced nearly 10-fold more progeny virus than their wild type controls. These results were supported by animal studies whereby pulmonary infection of RSV produced a more severe disease and morbidity in Bmal1 -/- mice. These results show that BMAL1 can regulate cellular innate immunity against specific RNA viruses.

  12. Examining key factors and influential actors involved in the decision to relocate into assisted living: A sample funding proposal

    OpenAIRE

    Wilson, Ashleigh Leah Davidson

    2013-01-01

    This capstone project presents a conceptually grounded, methodologically appropriate and logistically feasible Canadian Institutes of Health Research (CIHR) funding proposal. By examining key factors and influential actors involved in the decision to relocate into an assisted living facility (ALF), the proposed study will provide insight into and a rich description of the decision making process as it unfolds. Presented in the format of a CIHR pilot study grant, the proposal details a qualita...

  13. Exploring the factors influencing clinical students' self-regulated learning

    NARCIS (Netherlands)

    Berkhout, Joris J.; Helmich, Esther; Teunissen, Pim W.; van den Berg, Joost W.; van der Vleuten, Cees P. M.; Jaarsma, A. Debbie C.

    OBJECTIVES: The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and regulatory bodies. Supporting the development of SRL skills has proven difficult because self-regulation is a complex interactive process and we know relatively little about

  14. Exploring the factors influencing clinical students' self-regulated learning

    NARCIS (Netherlands)

    Berkhout, J.J.; Helmich, E.; Teunissen, P.W.; Berg, J.W. Ten; Vleuten, C.P.M. van der; Jaarsma, A.D.

    2015-01-01

    OBJECTIVES: The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and regulatory bodies. Supporting the development of SRL skills has proven difficult because self-regulation is a complex interactive process and we know relatively little about

  15. Reducing behavioural risk factors for cancer: An affect regulation perspective.

    Science.gov (United States)

    O'Leary, Daniel; Suri, Gaurav; Gross, James J

    2018-01-01

    Nearly half of all cancer deaths are attributable to preventable causes, primarily unhealthy behaviours such as tobacco use, alcohol use and overeating. In this review, we argue that people engage in these behaviours, at least in part, as a means of regulating their affective states. To better understand why people engage in these behaviours and how researchers might design interventions to promote the selection of healthier methods for regulating affect, we propose a conceptual model of affect regulation. We synthesise research from both the stress and coping tradition as well as the emotion and emotion regulation tradition, two literatures that are not typically integrated. In so doing, we indicate where researchers have made headway in understanding these behaviours as affect regulation and note how our model could be used to structure future work in a way that would be particularly advantageous to cancer control efforts.

  16. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands

    Science.gov (United States)

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A.; van der Linden, Giel T. J.; Schaminée, Joop H. J.; Siepel, Henk; Kleijn, David

    2014-01-01

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

  17. Key factors contributing to accident severity rate in construction industry in Iran: a regression modelling approach.

    Science.gov (United States)

    Soltanzadeh, Ahmad; Mohammadfam, Iraj; Moghimbeigi, Abbas; Ghiasvand, Reza

    2016-03-01

    Construction industry involves the highest risk of occupational accidents and bodily injuries, which range from mild to very severe. The aim of this cross-sectional study was to identify the factors associated with accident severity rate (ASR) in the largest Iranian construction companies based on data about 500 occupational accidents recorded from 2009 to 2013. We also gathered data on safety and health risk management and training systems. Data were analysed using Pearson's chi-squared coefficient and multiple regression analysis. Median ASR (and the interquartile range) was 107.50 (57.24- 381.25). Fourteen of the 24 studied factors stood out as most affecting construction accident severity (p<0.05). These findings can be applied in the design and implementation of a comprehensive safety and health risk management system to reduce ASR.

  18. EXO70C2 is a key regulatory factor for optimal tip growth of pollen

    Czech Academy of Sciences Publication Activity Database

    Synek, Lukáš; Vukašinović, Nemanja; Kulich, I.; Hála, Michal; Aldorfová, Klára; Fendrych, Matyáš; Žárský, Viktor

    2017-01-01

    Roč. 174, č. 1 (2017), s. 223-240 ISSN 0032-0889 R&D Projects: GA ČR GA15-24711S Grant - others:GA MŠk(CZ) LO1417 Institutional support: RVO:61389030 Keywords : ARABIDOPSIS EXOCYST COMPLEX * CELL-WALL * VESICLE TRAFFICKING Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 6.456, year: 2016

  19. Key Success Factors of Innovation in Multinational Agri-food Prospector Companies

    OpenAIRE

    Fortuin, F.T.J.M.; Batterink, M.H.; Omta, S.W.F.

    2007-01-01

    The Wageningen Innovation Assessment Tool (WIAT) compares the self assessment of the drivers and barriers to innovation at the company level and the critical success and failure factors of innovation at the project level with data of agrifood prospector firms around the world. In total 46 innovation projects, 11 successfully concluded and 6 failed projects, as well as 29 running projects in 12 multinational agrifood prospector companies in the Netherlands and France, two innovation consortia ...

  20. Key factors influencing the incidence of hemolysis: A critical appraisal of current evidence.

    Science.gov (United States)

    McCaughey, Euan James; Vecellio, Elia; Lake, Rebecca; Li, Ling; Burnett, Leslie; Chesher, Douglas; Braye, Stephen; Mackay, Mark; Gay, Stephanie; Badrick, Tony; Westbrook, Johanna; Georgiou, Andrew

    2017-01-01

    Hemolysis is a leading cause of pre-analytical laboratory errors. The identification of contributing factors is an important step towards the development of effective practices to reduce and prevent hemolysis. We performed a review of PUBMED, Embase, Medline and CINAHL to identify articles published between January 2000 and August 2016 that identified factors influencing in vitro hemolysis rates. The 40 studies included in this review provide excellent evidence that hemolysis rates are higher in Emergency Departments (EDs), for non-antecubital draws, for specimens drawn using an intravenous catheter compared to venipuncture and for samples transported by pneumatic tube compared to by hand. There is also good evidence that hemolysis rates are higher when specimens are not collected by professional phlebotomists, larger volume specimen tubes are used, specimen tubes are filled less than halfway and tourniquet time is greater than one minute. The results of this review suggest that hospitals and clinical laboratories should consider deploying phlebotomists in EDs, drawing all blood through a venipuncture, using the antecubital region as the optimum blood collection site and transporting specimens by laboratory assistant/other personnel, or if this in not practical, ensuring that pneumatic transport systems are validated, maintained and monitored. Studies also recommend making hemolysis a hospital-wide issue and ensuring high-quality staff training and adherence to standard operating procedures to reduce hemolysis rates. Awareness of the factors that influence hemolysis rates, and adoption of strategies to mitigate these risk factors, is an important step towards creating quality practices to reduce hemolysis rates and improve the quality of patient care.

  1. Key factors determining success of primary eye care through vision centres in rural India: Patients′ perspectives

    Directory of Open Access Journals (Sweden)

    Vilas Kovai

    2012-01-01

    Full Text Available Aim : This paper intends to discuss the patients′ perspective on the determinants of primary eye care services from vision centers (VC in rural India. Materials and Methods : A retrospective study design and interview method was used on 127 randomly selected patients who accessed the 4 VCs in 2007. Factor analyses and linear regression models were used to predict the associations with patient satisfaction. Results : The three factors derived from factor analyses were: (1-vision technician (VT, (2-location of VC, and (3-access to VC; explaining 60% of the variance in total patients′ satisfaction with VC. The first model (R2 : 0.61; F 1,124=144.36, P <0.001, indicated that respondents who had ′difficulty to travel to the place of VC′ and those who can afford to pay had less satisfaction with VT services. The second model (R2 =0.18; F 1,124=29.5, P <0.001 explained that respondents′ difficulty to identify the building of VC had decreased patients′ satisfaction and the third model (R2 =0.36; F 1,124=45.6, P <0.001 indicated that those who had to travel<5 km to the VC and had 0.38 units of increased satisfaction level with the services of VC. Conclusion : A good VT can enhance patient satisfaction. However, patient expectations are not only confined to the provider but also other factors such as ability to pay and convenient transportation that helps patients reach the location of the VC with ease.

  2. A structured elicitation method to identify key direct risk factors for the management of natural resources

    Directory of Open Access Journals (Sweden)

    Michael Smith

    2015-11-01

    Full Text Available The high level of uncertainty inherent in natural resource management requires planners to apply comprehensive risk analyses, often in situations where there are few resources. In this paper, we demonstrate a broadly applicable, novel and structured elicitation approach to identify important direct risk factors. This new approach combines expert calibration and fuzzy based mathematics to capture and aggregate subjective expert estimates of the likelihood that a set of direct risk factors will cause management failure. A specific case study is used to demonstrate the approach; however, the described methods are widely applicable in risk analysis. For the case study, the management target was to retain all species that characterise a set of natural biological elements. The analysis was bounded by the spatial distribution of the biological elements under consideration and a 20-year time frame. Fourteen biological elements were expected to be at risk. Eleven important direct risk factors were identified that related to surrounding land use practices, climate change, problem species (e.g., feral predators, fire and hydrological change. In terms of their overall influence, the two most important risk factors were salinisation and a lack of water which together pose a considerable threat to the survival of nine biological elements. The described approach successfully overcame two concerns arising from previous risk analysis work: (1 the lack of an intuitive, yet comprehensive scoring method enabling the detection and clarification of expert agreement and associated levels of uncertainty; and (2 the ease with which results can be interpreted and communicated while preserving a rich level of detail essential for informed decision making.

  3. Turbidity in oil-in-water-emulsions - Key factors and visual perception.

    Science.gov (United States)

    Linke, C; Drusch, S

    2016-11-01

    The aim of the present study is to systematically describe the factors affecting turbidity in beverage emulsions and to get a better understanding of visual perception of turbidity. The sensory evaluation of the human visual perception of turbidity showed that humans are most sensitive to turbidity differences between two samples in the range between 1000 and 1500 NTU (ratio) (nephelometric turbidity units). At very high turbidity values >2000 TU in NTU (ratio) were needed to distinguish between samples that they were perceived significantly different. Particle size was the most important factor affecting turbidity. It was shown that a maximum turbidity occurs at a mean volume - surface diameter of 0.2μm for the oil droplet size. Additional parameters were the refractive index, the composition of the aqueous phase and the presence of excess emulsifier. In a concentration typical for a beverage emulsion a change in the refractive index of the oil phase may allow the alteration of turbidity by up to 30%. With the knowledge on visual perception of turbidity and the determining factors, turbidity can be tailored in product development according to the customer requirements and in quality control to define acceptable variations in optical appearance. Copyright © 2016. Published by Elsevier Ltd.

  4. Patterns of justice involvement among adults with schizophrenia and bipolar disorder: key risk factors.

    Science.gov (United States)

    Robertson, Allison G; Swanson, Jeffrey W; Frisman, Linda K; Lin, Hsiuju; Swartz, Marvin S

    2014-07-01

    Adults with serious mental illness have a relatively high risk of criminal justice involvement. Some risk factors for justice involvement are known, but the specific interaction of these risk factors has not been examined. This study explored the interaction of gender, substance use disorder, and psychiatric diagnosis among patients with schizophrenia or bipolar disorder to identify subgroups at higher risk of justice involvement. Administrative service records of 25,133 adults with schizophrenia or bipolar disorder who were clients of Connecticut's public behavioral health system during 2005-2007 were merged with state records of criminal convictions, incarceration, and other measures of justice involvement. The main effects and the effects of interactions of gender, substance use disorder, and psychiatric diagnosis on risk of justice involvement ("offending") were estimated by using multivariable logistic regression. Men with bipolar disorder and co-occurring substance use disorder had the highest absolute risk of offending in every category of justice involvement. For both men and women, bipolar disorder was associated with an increased risk of offending versus schizophrenia, but the increase was significantly greater for women. Substance use disorder also increased risk of offending more among women than men, especially among those with schizophrenia. Men and women with bipolar disorder and substance use disorders have much higher risk of justice involvement than those with schizophrenia, especially those without a substance use disorder. Research is needed to validate these effects in other populations and specify risk factors for justice involvement among adults with mental illness.

  5. Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model

    Directory of Open Access Journals (Sweden)

    Shanmugam M Jeyakumar

    2015-01-01

    Full Text Available During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life. Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain.

  6. Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs.

    Science.gov (United States)

    Gil, Olga; Díaz, Ivan; Vilaplana, Cristina; Tapia, Gustavo; Díaz, Jorge; Fort, María; Cáceres, Neus; Pinto, Sergio; Caylà, Joan; Corner, Leigh; Domingo, Mariano; Cardona, Pere-Joan

    2010-04-06

    A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans.

  7. Human and organisational factors as key levers of performance in D and D project management - 59323

    International Nuclear Information System (INIS)

    Flament, Thierry; Willmann, Bertrand; Laval, Gregoire de; Lemarch, Jean-Louis; Cordoba, Alain

    2012-01-01

    Document available in abstract form only. Full text of publication follows: In a number pf D and D projects, the type of installations to be dismantled and the variety of their equipments (glove-boxes, tanks..) and the products present on site (plutonium, uranium) in the form of powder are making many operations manual ones. Key phases in HR and organisation management: - The first D and D experience, the learning curve ramp-up - To begin any project, you usually try to benefit from benchmark of similar projects to be able to build up the first scenario, by using the best practices. The first experimental team consisted of operators who already had experienced dismantling at least once in the course of their career. This first dismantling operation is preferably to be conducted on an installation relatively poorly contaminated. This was to implement the correct techniques thus reducing the consequences of a possible unforeseen event. The capitalisation on the return on experience The success of this first dismantling site operation allowed us to implement a process of experience feedback to build the scenarios and the operating procedures of the following sites. In particular, targeted safety-security stop points are positioned for validation on the operations by people responsible for safety and security

  8. Logic programming reveals alteration of key transcription factors in multiple myeloma.

    Science.gov (United States)

    Miannay, Bertrand; Minvielle, Stéphane; Roux, Olivier; Drouin, Pierre; Avet-Loiseau, Hervé; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Attal, Michel; Facon, Thierry; Munshi, Nikhil C; Moreau, Philippe; Campion, Loïc; Magrangeas, Florence; Guziolowski, Carito

    2017-08-23

    Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.

  9. Key Factors for Determining Risk of Groundwater Impacts Due to Leakage from Geologic Carbon Sequestration Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, Susan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Keating, Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mansoor, Kayyum [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dai, Zhenue [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sun, Yunwei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Trainor-Guitton, Whitney [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brown, Chris [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bacon, Diana [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-01-06

    The National Risk Assessment Partnership (NRAP) is developing a science-based toolset for the analysis of potential impacts to groundwater chemistry from CO2 injection (www.netldoe.gov/nrap). The toolset adopts a stochastic approach in which predictions address uncertainties in shallow underwater and leakage scenarios. It is derived from detailed physics and chemistry simulation results that are used to train more computationally efficient models,l referred to here as reduced-order models (ROMs), for each component system. In particular, these tools can be used to help regulators and operators understand the expected sizes and longevity of plumes in pH, TDS, and dissolved metals that could result from a leakage of brine and/or CO2 from a storage reservoir into aquifers. This information can inform, for example, decisions on monitoring strategies that are both effective and efficient. We have used this approach to develop predictive reduced-order models for two common types of reservoirs, but the approach could be used to develop a model for a specific aquifer or other common types of aquifers. In this paper we describe potential impacts to groundwater quality due to CO2 and brine leakage, discuss an approach to calculate thresholds under which "no impact" to groundwater occurs, describe the time scale for impact on groundwater, and discuss the probability of detecting a groundwater plume should leakage occur.

  10. Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

    LENUS (Irish Health Repository)

    Ryan, S

    2012-02-01

    Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis at all stages of atheroma formation. Increased levels of various circulating markers of inflammation including tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6), IL-8 and C-reactive protein (CRP) have been reported as associated with future cardiovascular risk. There is increasing evidence of elevated inflammatory markers in OSAS with a significant fall after effective treatment with continuous positive airway pressure. This evidence is particularly strong for TNFalpha, whereas studies on IL6 and CRP have yielded conflicting results possibly due to the confounding effects of obesity. Cell culture and animal studies have significantly contributed to our understanding of the underlying mechanisms of the association between OSAS and inflammation. Intermittent hypoxia, the hallmark of OSAS, results in activation of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein (AP)-1. These promote activation of various inflammatory cells, particularly lymphocytes and monocytes, with the downstream consequence of expression of pro-inflammatory mediators that may lead to endothelial dysfunction. This review provides a critical analysis of the current evidence for an association between OSAS, inflammation and cardiovascular disease, discusses basic mechanisms that may be responsible for this association and proposes future research possibilities.

  11. Hydrology and human behavior: two key factors of diarrhea incidence in montane tropical humid areas

    Science.gov (United States)

    Boithias, Laurie; Choisy, Marc; Souliyaseng, Noy; Jourdren, Marine; Quet, Fabrice; Buisson, Yves; Thammahacksa, Chanthamousone; Silvera, Norbert; Latsachack, Keooudone; Sengtaheuanghoung, Oloth; Pierret, Alain; Rochelle-Newall, Emma; Becerra, Sylvia; Ribolzi, Olivier

    2017-04-01

    The global burden of diarrhea is a leading cause of morbidity and mortality worldwide. In montane areas of South-East Asia such as northern Laos, recent changes in land use have induced increased runoff, soil erosion and in-stream suspended sediment loads, and potential pathogen dissemination. In this study we hypothesized that climate factors combined with human behavior control diarrhea incidence, either because higher rainfall, leading to higher stream discharges, suspended sediment loads and Fecal Indicator Bacteria (FIB) counts, are associated with higher numbers of reported diarrhea cases during the rainy season, or because water shortage leads to the use of less safe water sources during the dry season. For this mixed methods approach, we conducted a retrospective time series analysis of meteorological variables (rainfall, air temperature), hydrological variables (discharge, suspended sediments, FIB counts, water temperature) at the outlet of 2 catchments in Northern Lao PDR, and the number of diarrheal disease cases reported in 6 health centers located in the Luang Prabang Province. We also examined the socio-behavioral factors potentially affecting vulnerability to the effect of the climate factors, such as drinking water sources and hygiene habits. We found the FIB Escherichia coli to be present all year long (100-1,000 MPN 100 mL-1) indicating that fecal contamination is ubiquitous and constant. We found that populations switch their water supply from wells to surface water during drought periods, the latter of which appear to be at higher risk of bacterial contamination than municipal water fountains. We thus found that water shortage in the Luang Prabang area triggers diarrhea peaks during the dry and hot season and that rainfall and aquifer refill ends the epidemic during the wet season. We thus found that anthropogenic drivers, such as hygiene practices, were at least as important as environmental drivers in determining the seasonal pattern of a

  12. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  13. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    International Nuclear Information System (INIS)

    Brinkmann, Markus; Eichbaum, Kathrin; Kammann, Ulrike; Hudjetz, Sebastian; Cofalla, Catrina; Buchinger, Sebastian; Reifferscheid, Georg; Schüttrumpf, Holger; Preuss, Thomas

    2014-01-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios

  14. Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification

    DEFF Research Database (Denmark)

    Nicoll, Rachel; Zhao, Ying; Wiklund, Urban

    2017-01-01

    for CAC scoring. RESULTS: Among all patients, male sex (OR = 4.85, pdyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension...... and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p... males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes....

  15. Key factors influencing rates of heterotrophic sulfate reduction in active seafloor hydrothermal massive sulfide deposits

    Directory of Open Access Journals (Sweden)

    Kiana Laieikawai Frank

    2015-12-01

    Full Text Available Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep gradients in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42-, DOC on sulfate reduction rates and metabolic energy yields in material recovered from a hydrothermal flange from the Grotto edifice in the Main Endeavor Field, Juan de Fuca Ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli, and maximum sulfate reduction rates were observed at 50 °C and pH 6, suggesting that the in situ community of sulfate-reducing organisms in Grotto flanges may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate reduction within the complex gradients inherent to seafloor hydrothermal deposits.

  16. Hiring and Retention: Key Factors in Increasing Gender Diversity in the Geosciences

    Science.gov (United States)

    Holmes, M.; O'Connell, S.; Frey, C.

    2004-12-01

    Graduation and hiring data of geoscientists over the last ten years indicate that the largest leak in the academic pipeline for women geoscientists is at hiring into tenure-track positions. Anecdotal explanations for this leak generally cite a lack of females in the applicant pool, but women in tenure-track positions anecdotally cite a lack of family-friendly practices by academic departments. Both ideas are currently being tested via surveys of geoscience departments. Is there a way to attract more women to the field to increase the applicant pool? Results of focus groups of geoscientists indicate that both men and women are attracted into the field of geosciences by the same types of events: over one-third became a geoscientist by randomly walking into an undergraduate class and finding themselves captivated by the topic and/or a dynamic instructor. The subject matter itself attracts another one-fourth, and family members encourage another one-fifth of geoscientists to initially enter the field. Slightly more women cite the first attractor of undergraduate class, but the principal draw for our future workforce, male and female, is good instruction of freshman courses. Retention of women in academia is another key issue. The proportion that considers leaving after working towards one or more degrees is highly skewed by gender: one-half of female and only one-third of male geoscientists considered leaving the field at some time in their career. The reasons for considering leaving also differ by gender. Males cite financial issues, including an uncertain job market. Females cite two principal reasons for considering leaving: family issues and difficulties with a graduate advisor. Strategies currently exist for "family issues", including stop-the-clock (of tenure for family needs), assignment shift, on-campus daycare facilities, and unflinching administrative support for such practices. Graduate advising is a learnable skill, and more attention needs to be paid to

  17. Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells*

    Science.gov (United States)

    Parolini, Isabella; Federici, Cristina; Raggi, Carla; Lugini, Luana; Palleschi, Simonetta; De Milito, Angelo; Coscia, Carolina; Iessi, Elisabetta; Logozzi, Mariantonia; Molinari, Agnese; Colone, Marisa; Tatti, Massimo; Sargiacomo, Massimo; Fais, Stefano

    2009-01-01

    Exosomes secreted by normal and cancer cells carry and deliver a variety of molecules. To date, mechanisms referring to tumor exosome trafficking, including release and cell-cell transmission, have not been described. To gain insight into this, exosomes purified from metastatic melanoma cell medium were labeled with a lipid fluorescent probe, R18, and analyzed by spectrofluorometry and confocal microscopy. A low pH condition is a hallmark of tumor malignancy, potentially influencing exosome release and uptake by cancer cells. Using different pH conditions as a modifier of exosome traffic, we showed (i) an increased exosome release and uptake at low pH when compared with a buffered condition and (ii) exosome uptake by melanoma cells occurred by fusion. Membrane biophysical analysis, such as fluidity and lipid composition, indicated a high rigidity and sphingomyelin/ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) content in exosomes released at low pH. This was likely responsible for the increased fusion efficiency. Consistent with these results, pretreatment with proton pump inhibitors led to an inhibition of exosome uptake by melanoma cells. Fusion efficiency of tumor exosomes resulted in being higher in cells of metastatic origin than in those derived from primary tumors or normal cells. Furthermore, we found that caveolin-1, a protein involved in melanoma progression, is highly delivered through exosomes released in an acidic condition. The results of our study provide the evidence that exosomes may be used as a delivery system for paracrine diffusion of tumor malignancy, in turn supporting the importance of both exosomes and tumor pH as key targets for future anti-cancer strategies. PMID:19801663

  18. Microenvironmental pH is a key factor for exosome traffic in tumor cells.

    Science.gov (United States)

    Parolini, Isabella; Federici, Cristina; Raggi, Carla; Lugini, Luana; Palleschi, Simonetta; De Milito, Angelo; Coscia, Carolina; Iessi, Elisabetta; Logozzi, Mariantonia; Molinari, Agnese; Colone, Marisa; Tatti, Massimo; Sargiacomo, Massimo; Fais, Stefano

    2009-12-04

    Exosomes secreted by normal and cancer cells carry and deliver a variety of molecules. To date, mechanisms referring to tumor exosome trafficking, including release and cell-cell transmission, have not been described. To gain insight into this, exosomes purified from metastatic melanoma cell medium were labeled with a lipid fluorescent probe, R18, and analyzed by spectrofluorometry and confocal microscopy. A low pH condition is a hallmark of tumor malignancy, potentially influencing exosome release and uptake by cancer cells. Using different pH conditions as a modifier of exosome traffic, we showed (i) an increased exosome release and uptake at low pH when compared with a buffered condition and (ii) exosome uptake by melanoma cells occurred by fusion. Membrane biophysical analysis, such as fluidity and lipid composition, indicated a high rigidity and sphingomyelin/ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) content in exosomes released at low pH. This was likely responsible for the increased fusion efficiency. Consistent with these results, pretreatment with proton pump inhibitors led to an inhibition of exosome uptake by melanoma cells. Fusion efficiency of tumor exosomes resulted in being higher in cells of metastatic origin than in those derived from primary tumors or normal cells. Furthermore, we found that caveolin-1, a protein involved in melanoma progression, is highly delivered through exosomes released in an acidic condition. The results of our study provide the evidence that exosomes may be used as a delivery system for paracrine diffusion of tumor malignancy, in turn supporting the importance of both exosomes and tumor pH as key targets for future anti-cancer strategies.

  19. Social learning as a key factor in sustainability transitions: The case of Okayama City

    Science.gov (United States)

    Didham, Robert J.; Ofei-Manu, Paul; Nagareo, Masaaki

    2017-12-01

    The Okayama Education for Sustainable Development (ESD) Project is an ongoing initiative in Okayama City, Japan, established in 2005 by the Regional Centre of Expertise (RCE) Okayama and the Okayama Municipal Government with the aim "to create a community where people learn, think and act together towards realising a sustainable society". With a diverse participant base of over 240 organisations - including community learning centres ( kominkans), schools, universities and non-governmental organisations (NGOs) - this initiative has administered numerous programmes. It has engaged a large and diverse group of citizens from Okayama City in exploring sustainability issues through collective discussion, envisioning and practice with the aim of living more sustainable lives. The decade-long experience of the Okayama ESD Project has gained international attention, and the "Okayama Model" is considered an inspiring example of community-based ESD due to the positive changes it has supported. In this article, the Okayama ESD Project is presented as a case study on effective social learning for sustainability. In particular, the practical efforts made are examined to provide insights into how various elements of a social learning process were strengthened and linked to create active learning cycles among community members. In addition, the conditions for creating an effective learning community are investigated, while the practical actions taken are examined in relation to creating an effective social learning process. Finally, this article presents the important role which social learning has played in Okayama City's transition to sustainability and identifies the key efforts made to address and link each of these elements of social learning into a dynamic cycle.

  20. Key factors impacting on diagnosis and treatment for vulvar cancer for Indigenous women: findings from Australia.

    Science.gov (United States)

    McGrath, Pam; Rawson, Nicole

    2013-10-01

    To date, there has been limited research on the topic of vulvar cancer. This paper provides findings from a qualitative study conducted with Indigenous women in East Arnhem Land, Northern Territory, Australia on the psychosocial impact of diagnosis and treatment for vulvar cancer. The insights from the study outlined in this paper not only make a contribution to deepening our understanding of the experience of vulvar cancer for Indigenous women, but provide practical recommendations to ensure effective and early engagement for diagnosis and treatment. A qualitative research method was employed through in-depth, open-ended interviews. The participants of the study were a purposive sample of Indigenous women with the condition, health professionals, and Aboriginal health workers. There were a total of 40 participants; with twelve (n = 12) Indigenous women affected with the condition, fourteen (n = 14) Aboriginal Health Workers, ten (n = 10) nurses, three (n = 3) doctors, and one (n = 1) community member. This paper addresses three key issues highlighted by the participants which include the fact that the private nature of the disease makes the condition 'women's business', that there is a sense of shame associated with the condition, and that there is fear and worry generated by the seriousness of the condition. The private nature of the disease and the sense of shame associated with the condition impact upon the diagnosis and treatment for many Indigenous women. In addition, the limitation of resources for health service delivery for East Arnhem Land exacerbates the problems faced by these communities. This paper puts forward suggestions to facilitate early diagnosis and treatment for women affected with the condition.

  1. Large research infrastrucures and networking. Two key factors for maintaining nuclear expertise in Europe

    International Nuclear Information System (INIS)

    Cognet, G.; Iracane, D.

    2004-01-01

    Large research infrastructures are of key importance to improve the efficiency and the safety of nuclear energy production. To support present and coming power reactors and fuel cycle facilities and to develop future systems, it is necessary to optimise these infrastructures and their use by taking into account the networking of existing facilities, the access by the European researchers to conduct their own research projects and the creation of new installations when facing ageing issues. Large infrastructures include material testing reactor, hot laboratories for material and fuel under irradiation studies, fuel cycle researches and facilities dedicated to severe accident studies. For example, the CEA severe accident study platform has been recently used by a Bulgarian team to conduct its own research project with a grant provided by the European Commission. Furthermore, because present European material testing reactors are ageing, renewing the irradiation capability is an important and structuring stake for the fission research in Europe in order to continue safe and optimised operations of existing reactors, to support Generation 4 RTD and to keep alive competences. Considering that, CEA has decided to launch the project Jules Horowitz aiming at building a new research reactor. The access to the CEA facilities, including the Jules Horowitz reactor, combined with equivalent possibilities of access to other European facilities through a specific platform would help to develop a long-term vision, to create a coherent and dynamic strategy, to contribute to the stimulation of a large cooperation on nuclear fission, to enable a common approach of safety issues, to gather competencies, to promote the attractiveness of nuclear research to young scientists and to maintain European nuclear expertise at the highest level. This paper intends to provide a view of the existing and needed infrastructures, discuss the ways of access and finally open the discussion on the

  2. The HIV/AIDS Epidemic in the Dominican Republic: Key Contributing Factors.

    Science.gov (United States)

    Rojas, Patria; Malow, Robert; Ruffin, Beverly; Rothe, Eugenio M; Rosenberg, Rhonda

    2011-01-01

    This article reviews HIV/AIDS epidemiological data and recent research conducted in the Dominican Republic, with a focus on explaining the variability in estimated seroincidence and prevalence within the country. HIV seroprevalence estimates range from 1.0% (in the general population) to 11.0% among men who have sex with men (MSM). Some have indicated that the highest HIV seroprevalence occurs in Haitian enclaves called bateyes (US Agency for International Development [USAID], 2008), which are migrant worker shantytowns primarily serving the sugar industry in the Dominican Republic. Others report higher or comparable rates to the bateyes in areas related to the tourism and sex industries. As in other Caribbean and Latin American countries, reported HIV transmission in the Dominican Republic is predominantly due to unprotected heterosexual sex and the infection rate has been increasing disproportionally among women. The Dominican Republic represents two thirds of the Hispaniola island; the western one third is occupied by Haiti, the nation with the highest HIV prevalence in the western hemisphere. Although data is limited, it shows important differences in seroprevalence and incidence between these two countries, but commonalities such as poverty, gender inequalities, and stigma appear to be pivotal factors driving the epidemic. This article will discuss these and other factors that may contribute to the HIV epidemic in the Dominican Republic, as well as highlight the gaps in the literature and provide recommendations to guide further work in this area, particularly in the role of governance in sustainable HIV prevention.

  3. Education of staff--a key factor for a safe environment in day care.

    Science.gov (United States)

    Sellström, E; Bremberg, S

    2000-05-01

    In order to create a safe environment in day-care settings, an understanding of factors within the organization of day care, factors which influence safety, is essential. Day-care directors in 83 daycare centres completed a mail-in survey that contained questions about professional experience, the day-care centre's organization of child safety measures and a battery of questions designed to evaluate the directors' perceptions and beliefs about child safety. The day-care directors also carried out a safety inspection at their centre. The results were analysed using the multivariate logistic regression technique. The existence of a continuing plan for continued staff education in child safety was shown to be the strongest predictor of few safety hazards in day-care centres. The day-care directors' perceptions and beliefs about injury prevention were of less importance. This study indicates that in order to promote safety in day-care settings, an on-going plan for continued staff education in child safety should be a matter of routine. The introduction of such a plan should be the concern of the individual day-care directors, policy-makers and managers at the local and national level, and health professionals working in this field.

  4. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Energy Technology Data Exchange (ETDEWEB)

    Rummel, L.; MartInez-AbraIn, A.; Mayol, J.; Ruiz-Olmo, J.; Mañas, F.; Jimenez, J.; Gomez, J.A.; Oro, D.

    2016-07-01

    Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations) are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild) and translocation effort (propagule size and program duration). After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years. (Author)

  5. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Directory of Open Access Journals (Sweden)

    Rummel, L.

    2016-06-01

    Full Text Available Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild and translocation effort (propagule size and program duration. After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years.

  6. Organisation as a key factor in Localised Agri-Food Systems (LAFS

    Directory of Open Access Journals (Sweden)

    Corrado Giacomini

    2015-05-01

    Full Text Available Most studies of Localised Agri-Food Systems (LAFS focus on the localised concentration of members and firms, and pay less attention to organisational factors, particularly those of an exogenous nature. This paper focuses on the role of organisation in a LAFS, assessing the efficacy of EU organisational measures aimed at strengthening the concentration of supply from the recent CAP reform 2014-2020. The paper has three sections. Part One describes the evolution of the concept of LAFS. Part Two examines the leading role played by institutions in organising relationships between firms in a LAFS. The example provided is that of the measures affecting the organisation of supply introduced by the recent CAP reform, 2014-2020. It makes particular reference to the Distretto del pomodoro da industria – Nord Italia (‘Industrial Tomato District – Northern Italy’. Part Three describes how organisational factors can lead to the creation of a LAFS, while the criterion of proximity is necessary but not sufficient.

  7. Developing Talented Soccer Players: An Analysis of Socio-Spatial Factors as Possible Key Constraints

    Directory of Open Access Journals (Sweden)

    Serra-Olivares Jaime

    2016-12-01

    Full Text Available Most studies on the identification and development of soccer talent have been one-dimensional in nature. Although some multi-dimensional analyses have been conducted, few research studies have assessed in any depth the socio-spatial factors influencing talent development. The aim of this particular study was to analyse variations in the international representation of clubs (n = 821 and countries (n = 59 in the development of players who took part in the 2014 FIFA Soccer World Cup. Clubs and countries were ranked and divided into quartiles according to the number of players developed between the ages of 15 and 21 (clubs and countries that developed players for at least three years between these ages and the number of official league matches played by these players up to the age of 23. Significant variations were observed between clubs in terms of the number of developed players who took part in the World Cup and the number of official league matches played by these players up to the age of 23 (p < .05, and also between countries (p < .05. The findings reveal the need to carry out more in-depth studies into the type of training and competition engaged in by elite players in the period of development between the ages of 15 and 21. It may be the case that these factors are potentially decisive socio-spatial constraints in the development of soccer talent.

  8. Key factors to understanding the conflictive situation in North-East India

    Directory of Open Access Journals (Sweden)

    Jordi Urgell García

    2010-04-01

    Full Text Available This article aims to help expand our understanding of the armed conflicts and social tensions that exist in the Northeast of India, by examining the different levels at which conflict takes place, as well as by analysing some of the causes and factors involved in these contexts. To this end, the article is structured into three parts. In the first, the authors describe briefly the antecedents of the different conflicts and tensions, in order to establish a map of same and to contextualise them historically and socially. In the second part, five issues are analysed: armed conflicts as multifactorial realities that require examination in both regional and individual terms; the issue of demography as the constitutive factor of many discourses and accounts of the causes of disputes in the region; the Indian government’s responses to the conflicts; the role played by international regional actors and, finally, the dimension of gender in the conflicts. The third and final part includes some closing reflections, by way of a conclusion.

  9. POSITIONING KNOWLEDGE MANAGEMENT AS KEY SUCCESS FACTOR IN THE GROWTH OF COOPERATIVES IN MALAYSIA

    Directory of Open Access Journals (Sweden)

    Yeop Hussin Bidin

    2007-01-01

    Full Text Available Economic and business challenges in the new millennium have shaped the manner cooperative movement in Malaysia charts its future outlook. After almost 82 years, a national policy was launched by the Government on January 2004 to assist in the comprehensive development of the cooperative movement. The National CooperativePolicy (NCP will ensure that the huge resources of the cooperatives can be harnessed to generate and contribute to the economic growth of the country. However, in the light of many issues such as weak structure and the absence of good corporate governance in some cooperatives, the present Cooperative Act 1993 is being reviewed and several new provisions would be added to increase supervision, monitoring and enforcement against existing cooperatives in alaysia. It is quite imperative that by regulating the operation of cooperatives will require also the managing of intellectual and human capital assets that exist in the movement. Through establishing a framework and terms of reference such that fundamental elements of knowledge management can be instilled areprerequisites to developing innovativeness in this growing economic sector. The sharing of knowledge among the cooperatives will eventually produce better and more educated human resources that are able to experience greater control over the works and the administration of their quality working life. Structural analysis of the cooperative movement indicates the significant influence of knowledge management in sustaining its future growth given the timely introduction of the NCP. Thus, measures taken to underline this influence will also be addressed to represent the cooperative movement's readiness to face economic and business challenges in Malaysia.

  10. Syntactic computation in the human brain: the degree of merger as a key factor.

    Directory of Open Access Journals (Sweden)

    Shinri Ohta

    Full Text Available Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t, although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that "the Degree of Merger" (DoM in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and "DoM+number of Search (searching syntactic features" were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG, respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R. lateral premotor cortex and R. F3op/F3t

  11. Key biogeochemical factors affecting soil carbon storage in Posidonia meadows

    KAUST Repository

    Serrano, Oscar; Ricart, Aurora M.; Lavery, Paul S.; Mateo, Miguel Angel; Arias-Ortiz, Ariane; Masque, Pere; Rozaimi, Mohammad; Steven, Andy; Duarte, Carlos M.

    2016-01-01

    Biotic and abiotic factors influence the accumulation of organic carbon (C-org) in seagrass ecosystems. We surveyed Posidonia sinuosa meadows growing in different water depths to assess the variability in the sources, stocks and accumulation rates of Corg. We show that over the last 500 years, P. sinuosa meadows closer to the upper limit of distribution (at 2-4 m depth) accumulated 3- to 4-fold higher C-org stocks (averaging 6.3 kg C-org m(-2) at 3- to 4-fold higher rates (12.8 gC(org) m(-2) yr(-1) ) compared to meadows closer to the deep limits of distribution (at 6-8 m depth; 1.8 kg C-org m(-2) and 3.6 g C-org m(-2) yr(-1) . In shallower meadows, C-org stocks were mostly derived from seagrass detritus (88% in average) compared to meadows closer to the deep limit of distribution (45% on average). In addition, soil accumulation rates and fine-grained sediment content (< 0.125 mm) in shallower meadows (2.0 mm yr(-1) and 9 %, respectively) were approximately 2-fold higher than in deeper meadows (1.2 mm yr(-1) and 5 %, respectively). The C-org stocks and accumulation rates accumulated over the last 500 years in bare sediments (0.6 kg C-org m(-2) and 1.2 g C-org m(-2) yr(-1)were 3- to 11-fold lower than in P. sinuosa meadows, while fine-grained sediment content (1 %) and seagrass detritus contribution to the Corg pool (20 %) were 8- and 3-fold lower than in Posidonia meadows, respectively. The patterns found support the hypothesis that Corg storage in seagrass soils is influenced by interactions of biological (e.g., meadow productivity, cover and density), chemical (e.g., recalcitrance of Corg stocks) and physical (e.g., hydrodynamic energy and soil accumulation rates) factors within the meadow. We conclude that there is a need to improve global estimates of seagrass carbon storage accounting for biogeochemical factors driving variability within habitats.

  12. Key Factors That Influence The Performance Properties Of ARP/MCU Saltstone Mixes

    International Nuclear Information System (INIS)

    Harbour, J.; Edwards, T.; Williams, V.

    2009-01-01

    At the Saltstone Production Facility (SPF), decontaminated salt solution (DSS) is combined with premix (a cementitious mixture of portland cement (PC), blast furnace slag (BFS) and Class F fly ash (FA)) in a Readco mixer to produce fresh (uncured) Saltstone. After transfer to the Saltstone Disposal Facility (SDF) the hydration reactions initiated during the contact of the premix and salt solution continue during the curing period to produce the hardened waste form product. The amount of heat generated from hydration and the resultant temperature increase in the vaults depend on the composition of the decontaminated salt solution being dispositioned as well as the grout formulation (mix design). This report details the results from Task 3 of the Saltstone Variability Study for FY09 which was performed to identify, and quantify when possible, those factors that drive the performance properties of the projected ARP/MCU Batches. A baseline ARP/MCU mix (at 0.60 water to cementitious materials (w/cm) ratio) was established and consisted of the normal premix composition and a salt solution that was an average of the projected compositions of the last three ARP/MCU batches developed by T. A. Le. This task introduced significant variation in (1) wt % slag, w/cm ratio, and wt % portland cement about the baseline mix and (2) the temperature of curing in order to better assess the dependence of the performance properties on these factors. Two separate campaigns, designated Phase 10 and Phase 11, were carried out under Task 3. Experimental designs and statistical analyses were used to search for correlation among properties and to develop linear models to predict property values based on factors such as w/cm ratio, slag concentration, and portland cement concentration. It turns out that the projected salt compositions contained relatively high amounts of aluminate (0.22 M) even though no aluminate was introduced due to caustic aluminate removal from High Level Waste. Previous

  13. Quality services as a key factor of competitiveness of transport companies

    Directory of Open Access Journals (Sweden)

    Bogetić Srđan

    2014-01-01

    Full Text Available This paper deals with the question of the service quality as an important factor of transport companies in the process of improving competitiveness. Due to global competition and great opportunities that are offered to customers, transporting enterprises need to change their current relationship with the end consumer in order to improve the quality of offered services. Traffic enterprises have realized that improvement of the business processes comes with the use of modern ICT solutions and applications that will ensure that protection of the environment has been taken into account and the quality of service improved as well. Domestic traffic enterprises are not yet ready to accept the change of the way of conducting their business, which furtherly affects the quality of services, and they are still not prepared for the arrival of competition in the transport market.

  14. Lake variability: Key factors controlling mercury concentrations in New York State fish

    International Nuclear Information System (INIS)

    Simonin, Howard A.; Loukmas, Jefferey J.; Skinner, Lawrence C.; Roy, Karen M.

    2008-01-01

    A 4 year study surveyed 131 lakes across New York State beginning in 2003 to improve our understanding of mercury and gather information from previously untested waters. Our study focused on largemouth and smallmouth bass, walleye and yellow perch, common piscivorous fish shown to accumulate high mercury concentrations and species important to local fisheries. Fish from Adirondack and Catskill Forest Preserve lakes generally had higher mercury concentrations than those from lakes in other areas of the state. Variability between nearby individual lakes was observed, and could be due to differences in water chemistry, lake productivity or the abundance of wetlands in the watershed. We found the following factors impact mercury bioaccumulation: fish length, lake pH, specific conductivity, chlorophyll a, mercury concentration in the water, presence of an outlet dam and amount of contiguous wetlands. - Lake water chemistry variables, dams, and wetlands play major roles in determining fish mercury concentrations

  15. Study on the Key Factor Parameters to Increase Productivity in Construction and Manufacturing Industries.

    Science.gov (United States)

    Almazyed, K.; Alaswad, A.; Olabi, A. G.

    2016-02-01

    Proper management of human and non-human resources in construction and manufacturing projects can give-in considerable savings in time and cost. Construction and Manufacturing industry faces issues in connection with problems related with productivity and the problems are usually connected with performance of employees. The performance of employees is affected by many factors. In this paper a survey was made on respondents who are employed various projects of Saudi Arabia. The researcher developed a theoretical framework from the existing research which was used as a Model to collect and analyze the field data to test the hypothesis. In this research activity three predictors (commitment, job satisfaction and job performance) for determining the change in productivity. The results highlight that commitment and job performance (respectively) are the two predictors which are explaining 37% of variation in the productivity of the companies. The results also show that Job Satisfaction has no role in the prediction of productivity.

  16. Motivation and engagement in computer-based learning tasks: investigating key contributing factors

    Directory of Open Access Journals (Sweden)

    Michela Ott, Mauro Tavella

    2010-04-01

    Full Text Available This paper, drawing on a research project concerning the educational use of digital mind games with primary school students, aims at giving a contribution to the understanding of which are the main factors influencing student motivation during computer-based learning activities. It puts forward some ideas and experience based reflections, starting by considering digital games that are widely recognized as the most promising ICT tools to enhance student motivation. The project results suggest that student genuine engagement in learning activities is mainly related to the actual possession of the skills and of the cognitive capacities needed to perform the task. In this perspective, cognitive overload should be regarded as one of the main reasons contributing to hinder student motivation and, consequently, should be avoided. Other elements such as game attractiveness and experimental setting constraints resulted to have a lower effect on student motivation.

  17. Merkel Cell Carcinoma: An Update of Key Imaging Techniques, Prognostic Factors, Treatment, and Follow-up.

    Science.gov (United States)

    Llombart, B; Kindem, S; Chust, M

    2017-03-01

    Merkel cell carcinoma, though rare, is one of the most aggressive tumors a dermatologist faces. More than a third of patients with this diagnosis die from the disease. Numerous researchers have attempted to identify clinical and pathologic predictors to guide prognosis, but their studies have produced inconsistent results. Because the incidence of Merkel cell carcinoma is low and it appears in patients of advanced age, prospective studies have not been done and no clear treatment algorithm has been developed. This review aims to provide an exhaustive, up-to-date account of Merkel cell carcinoma for the dermatologist. We describe prognostic factors and the imaging techniques that are most appropriate for evaluating disease spread. We also discuss current debates on treating Merkel cell carcinoma. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Kyosuke Yamanishi

    Full Text Available Major depressive disorder (MDD is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of

  19. Sexual Education of Young University Students: Some Key Factors and Challenges

    Directory of Open Access Journals (Sweden)

    María Luisa Preinfalk-Fernández

    2015-09-01

    Full Text Available In general terms, higher education institutions not only face the challenge of teaching some discipline to their students, but also of strengthening their life skills. Since university students are majorly young, the desire to provide them with comprehensive training is particularly relevant, since it is at this stage of life when they model their behavior for adulthood. In this training challenge, sex education plays a decisive role. This research paper aims to show that factors such as information gaps, unsafe sexual practices, myths, prejudices and stereotypes persist in the university student population and do not allow them to live sexuality safely and pleasurable. Moreover, these factors show Costa Rica’s need for higher education institutions to strengthen their actions in sex education. A brief tour is made from various angles through the sexual experiences of the university student population, namely: their perceptions about the training requirements they face, their main concerns, their unsafe sexual practices, their inability to negotiate sexual and reproductive health care, their knowledge and preventive practices in terms of sexual and reproductive health, the existence of forms of violence within university life, among others. The findings set out are part of a larger research, based on contributions from the theory of gender and social constructionism. Such data derives from the application of a questionnaire to a sample stratified by unequal conglomerates composed of 766 regular students of undergraduate courses, enrolled in the first cycle of 2011, at Universidad Nacional de Costa Rica. The margin of error is 1.5% and the confidence level, 95%. The data was tabulated using the software CSPRO and analyzed with software R. After obtaining the results of the instrument’s application, a focus group was created with the participation of professionals who teach sexuality courses in this university, and two other groups with

  20. Smoking in pregnancy a key factor for sudden infant death among Māori.

    Science.gov (United States)

    MacFarlane, M; Mitchell, E A; Thompson, J M D; Lawton, B; Zuccollo, J; Elder, D; Taylor, B; McDonald, G; Stewart, A W; Percival, T; Baker, N; Schlaud, M; Fleming, P

    2018-06-05

    To examine the Sudden Unexpected Death in Infancy (SUDI) disparity between Māori and non-Māori in New Zealand. A nationwide prospective case-control study ran from March 2012-February 2015. Exposure to established SUDI risk factors was analysed to investigate the disparity experienced by Māori. Infant ethnicity was based on mother's ethnicity. Māori ethnicity was prioritised. Non-Māori includes Pacific, Asian, NZ European and Other. There were 137 cases and 649 controls. The Māori SUDI rate was 1.41/1,000 live births compared to 0.53/1,000 for non-Māori. Parents/caregivers of 133 cases (97%) and 258 controls (40%) were interviewed. Smoking in pregnancy was associated with an equally-increased SUDI risk for Māori (adjusted OR=8.11, 95%CI=2.64, 24.93) and non-Māori (aOR=5.09, 95% CI=1.79, 14.47), as was bed-sharing (aOR=3.66, 95% CI=1.49, 9.00 versus aOR=11.20, 95% CI=3.46, 36.29). Bed-sharing prevalence was similar, however more Māori controls smoked during pregnancy (46.7%) than non-Māori (22.8%). The main contributor relating to increased SUDI risk for Māori/non-Māori infants is the combination of smoking in pregnancy and bed-sharing. The association between known SUDI risk factors, including bed-sharing and/or smoking in pregnancy and SUDI risk, is the same regardless of ethnicity. Māori infants are exposed more frequently to both behaviours because of the higher Māori smoking rate. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Hydrophobic environment is a key factor for the stability of thermophilic proteins.

    Science.gov (United States)

    Gromiha, M Michael; Pathak, Manish C; Saraboji, Kadhirvel; Ortlund, Eric A; Gaucher, Eric A

    2013-04-01

    The stability of thermophilic proteins has been viewed from different perspectives and there is yet no unified principle to understand this stability. It would be valuable to reveal the most important interactions for designing thermostable proteins for such applications as industrial protein engineering. In this work, we have systematically analyzed the importance of various interactions by computing different parameters such as surrounding hydrophobicity, inter-residue interactions, ion-pairs and hydrogen bonds. The importance of each interaction has been determined by its predicted relative contribution in thermophiles versus the same contribution in mesophilic homologues based on a dataset of 373 protein families. We predict that hydrophobic environment is the major factor for the stability of thermophilic proteins and found that 80% of thermophilic proteins analyzed showed higher hydrophobicity than their mesophilic counterparts. Ion pairs, hydrogen bonds, and interaction energy are also important and favored in 68%, 50%, and 62% of thermophilic proteins, respectively. Interestingly, thermophilic proteins with decreased hydrophobic environments display a greater number of hydrogen bonds and/or ion pairs. The systematic elimination of mesophilic proteins based on surrounding hydrophobicity, interaction energy, and ion pairs/hydrogen bonds, led to correctly identifying 95% of the thermophilic proteins in our analyses. Our analysis was also applied to another, more refined set of 102 thermophilic-mesophilic pairs, which again identified hydrophobicity as a dominant property in 71% of the thermophilic proteins. Further, the notion of surrounding hydrophobicity, which characterizes the hydrophobic behavior of residues in a protein environment, has been applied to the three-dimensional structures of elongation factor-Tu proteins and we found that the thermophilic proteins are enriched with a hydrophobic environment. The results obtained in this work highlight the

  2. Overall analysis of the cost key factors for the nuclear energy

    International Nuclear Information System (INIS)

    Caero, M.

    1996-01-01

    In 1995, 25,8 % of the world electricity consumption was of nuclear origin, while in the EU this figure is increased up to 50,6 %. In order to maintain and even to increase its share in the electricity generation, Nuclear Energy needs to achieve a good economic performance as a base load source when compared with its competitors, basically coal and gas fired plants. Fossil-fired generation costs have declined over the past ten years, mainly due to lower fossil fuel prices. This factor together with the recently observed tendency of higher discount rates to be applied are challenging the attractiveness of the nuclear energy. Nuclear energy is a capital intensive option. Taken into account extensive standardization programs has been established aiming at cost reductions as well as to increase efficiency of nuclear energy utilization, among their main purposes. Externalities play an important role, as they are already internalized in nuclear generation costs. This is not true for many existing coal-fired plants. Even a great uncertainly exists on greenhouse gas effects. Also decisions on greenhouse gas control and their impact on carbonaceous fuel generation costs cannot be clearly predicted, even in the immediate future. Macroeconomic factors like employment, competitiveness, energy conservation, energy availability, energy demand control, etc are positively influenced by the use of nuclear energy. A sustainable economic development cannot be achieved only relying on fossil fuel generation. As a wrap up sustainable development demands nuclear energy in order to cover the future objectives of energy availability, environmental control and energy cost control. (author)

  3. A Key Role for NF-κB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions

    Directory of Open Access Journals (Sweden)

    Alexander Visekruna

    2012-01-01

    Full Text Available The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five family members have been identified in mammals: RelA (p65, c-Rel, RelB, and the precursor proteins NF-κB1 (p105 and NF-κB2 (p100, that are processed into p50 and p52, respectively. While RelA-containing dimers are present in most cell types, c-Rel complexes are predominately found in cells of hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune function such as Il2 and Foxp3 are directly regulated by c-Rel. Additionally, c-Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is crucial for T-cell differentiation and effector functions. Accordingly, c-Rel expression in T cells and antigen-presenting cells (APCs controls a delicate balance between tolerance and immunity. This review gives a selective overview on recent progress in understanding of diverse roles of c-Rel in regulating adaptive immunity.

  4. Frizzled 2 is a key component in the regulation of TOR signaling-mediated egg production in the mosquito Aedes aegypti.

    Science.gov (United States)

    Weng, Shih-Che; Shiao, Shin-Hong

    2015-06-01

    The Wnt signaling pathway was first discovered as a key event in embryonic development and cell polarity in Drosophila. Recently, several reports have shown that Wnt stimulates translation and cell growth by activating the mTOR pathway in mammals. Previous studies have demonstrated that the Target of Rapamycin (TOR) pathway plays an important role in mosquito vitellogenesis. However, the interactions between these two pathways are poorly understood in the mosquito. In this study, we hypothesized that factors from the TOR and Wnt signaling pathways interacted synergistically in mosquito vitellogenesis. Our results showed that silencing Aedes aegypti Frizzled 2 (AaFz2), a transmembrane receptor of the Wnt signaling pathway, decreased the fecundity of mosquitoes. We showed that AaFz2 was highly expressed at the transcriptional and translational levels in the female mosquito 6 h after a blood meal, indicating amino acid-stimulated expression of AaFz2. Notably, the phosphorylation of S6K, a downstream target of the TOR pathway, and the expression of vitellogenin were inhibited in the absence of AaFz2. A direct link was found in this study between Wnt and TOR signaling in the regulation of mosquito reproduction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Cytokinin response factors regulate PIN-FORMED auxin transporters

    Czech Academy of Sciences Publication Activity Database

    Šimášková, M.; O'Brien, J.A.; Khan, M.; Van Noorden, G.; Ötvös, K.; Vieten, A.; De Clercq, E.; Van Haperen, J.M.A.; Cuesta, C.; Hoyerová, Klára; Vanneste, S.; Marhavý, P.; Wabnik, K.; Van Breusegem, F.; Nowack, M.; Murphy, A.; Friml, J.; Weijers, D.; Beeckman, T.; Benková, E.

    2015-01-01

    Roč. 6, NOV (2015), s. 8717 ISSN 2041-1723 Institutional support: RVO:61389030 Keywords : ARABIDOPSIS -THALIANA * ROOT-MERISTEM * TRANSCRIPTION FACTORS Subject RIV: ED - Physiology Impact factor: 11.329, year: 2015

  6. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  7. Solution scanning as a key policy tool: identifying management interventions to help maintain and enhance regulating ecosystem services

    Directory of Open Access Journals (Sweden)

    William J. Sutherland

    2014-06-01

    Full Text Available The major task of policy makers and practitioners when confronted with a resource management problem is to decide on the potential solution(s to adopt from a range of available options. However, this process is unlikely to be successful and cost effective without access to an independently verified and comprehensive available list of options. There is currently burgeoning interest in ecosystem services and quantitative assessments of their importance and value. Recognition of the value of ecosystem services to human well-being represents an increasingly important argument for protecting and restoring the natural environment, alongside the moral and ethical justifications for conservation. As well as understanding the benefits of ecosystem services, it is also important to synthesize the practical interventions that are capable of maintaining and/or enhancing these services. Apart from pest regulation, pollination, and global climate regulation, this type of exercise has attracted relatively little attention. Through a systematic consultation exercise, we identify a candidate list of 296 possible interventions across the main regulating services of air quality regulation, climate regulation, water flow regulation, erosion regulation, water purification and waste treatment, disease regulation, pest regulation, pollination and natural hazard regulation. The range of interventions differs greatly between habitats and services depending upon the ease of manipulation and the level of research intensity. Some interventions have the potential to deliver benefits across a range of regulating services, especially those that reduce soil loss and maintain forest cover. Synthesis and applications: Solution scanning is important for questioning existing knowledge and identifying the range of options available to researchers and practitioners, as well as serving as the necessary basis for assessing cost effectiveness and guiding implementation strategies. We

  8. Key factors in the use of DDES for the flow around a simplified car

    International Nuclear Information System (INIS)

    Ashton, N.; Revell, A.

    2015-01-01

    Highlights: • Systematic sensitivity study to investigate accuracy of DDES with varying grid, numerics and underlying RANS model. • Demonstrated the potential for a loss of accuracy when using DDES with insufficient mesh refinement or too dissipative numerical scheme. • Highlighted that common user-controlled parameters can yield differences on the same scale as using different approaches. • Indentified ‘grey-area’ behaviour of DDES at point of separation which leads to erroneous prediction of flow. • Demonstrated that this can be overcome via the injection of synthetic fluctuations upstream of the onset of separation. - Abstract: The Ahmed car body represents a generic vehicle exhibiting key aspects of the 3D flow arising due to standard automobile designs. It is recognised to be a challenging test case for the turbulence modelling community; combining strong separation with a pair of counter-rotating vortices, which interact to produce a downstream recirculation region. In recent years this case has been extensively studied using a range of methods, with varying success. In general, conclusions have been made on the basis of the standard form of each model, while in the present work we focus on variants of the common Delayed Detached-Eddy Simulation (DDES) approach, in order to demonstrate its sensitivity to commonly varied aspects of its usage. We demonstrate that variations in the usage of a single approach can easily be of the order of those observed when using different approaches. Previous studies, reconfirmed here, indicate that the majority of standard single point closure turbulence models are unable to provide a satisfactory prediction of the recirculating flow region aft of the body. This holds regardless of mesh resolution, model selection or numerical scheme. These models under-predict levels of turbulence over the slanted back, leading to over-prediction of the size of the separation region. DDES can offer an improved prediction

  9. Protein Adsorption Patterns and Analysis on IV Nanoemulsions—The Key Factor Determining the Organ Distribution

    Directory of Open Access Journals (Sweden)

    Mirko Jansch

    2012-12-01

    Full Text Available Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern, typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface. The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics.

  10. Protein Adsorption Patterns and Analysis on IV Nanoemulsions-The Key Factor Determining the Organ Distribution.

    Science.gov (United States)

    Keck, Cornelia M; Jansch, Mirko; Müller, Rainer H

    2012-12-21

    Intravenous nanoemulsions have been on the market for parenteral nutrition since the 1950s; meanwhile, they have also been used successfully for IV drug delivery. To be well tolerable, the emulsions should avoid uptake by the MPS cells of the body; for drug delivery, they should be target-specific. The organ distribution is determined by the proteins adsorbing them after injection from the blood (protein adsorption pattern), typically analyzed by two-dimensional polyacrylamide gel electrophoresis, 2-D PAGE. The article reviews the 2-D PAGE method, the analytical problems to be faced and the knowledge available on how the composition of emulsions affects the protein adsorption patterns, e.g., the composition of the oil phase, stabilizer layer and drug incorporation into the interface or oil core. Data were re-evaluated and compared, and the implications for the in vivo distribution are discussed. Major results are that the interfacial composition of the stabilizer layer is the main determining factor and that this composition can be modulated by simple processes. Drug incorporation affects the pattern depending on the localization of the drug (oil core versus interface). The data situation regarding in vivo effects is very limited; mainly, it has to be referred to in the in vivo data of polymeric nanoparticles. As a conclusion, determination of the protein adsorption patterns can accelerate IV nanoemulsion formulation development regarding optimized organ distribution and related pharmacokinetics.

  11. Sonic hedgehog from both nerves and epithelium is a key trophic factor for taste bud maintenance.

    Science.gov (United States)

    Castillo-Azofeifa, David; Losacco, Justin T; Salcedo, Ernesto; Golden, Erin J; Finger, Thomas E; Barlow, Linda A

    2017-09-01

    The integrity of taste buds is intimately dependent on an intact gustatory innervation, yet the molecular nature of this dependency is unknown. Here, we show that differentiation of new taste bud cells, but not progenitor proliferation, is interrupted in mice treated with a hedgehog (Hh) pathway inhibitor (HPI), and that gustatory nerves are a source of sonic hedgehog (Shh) for taste bud renewal. Additionally, epithelial taste precursor cells express Shh transiently, and provide a local supply of Hh ligand that supports taste cell renewal. Taste buds are minimally affected when Shh is lost from either tissue source. However, when both the epithelial and neural supply of Shh are removed, taste buds largely disappear. We conclude Shh supplied by taste nerves and local taste epithelium act in concert to support continued taste bud differentiation. However, although neurally derived Shh is in part responsible for the dependence of taste cell renewal on gustatory innervation, neurotrophic support of taste buds likely involves a complex set of factors. © 2017. Published by The Company of Biologists Ltd.

  12. Preparedness for physiotherapy in private practice: Novices identify key factors in an interpretive description study.

    Science.gov (United States)

    Atkinson, Robyn; McElroy, Theresa

    2016-04-01

    Physiotherapists in Australia deliver services to a diverse range of clients, across many settings, however little research exists examining graduate preparedness for practice, even in the populous field of private practice. To explore novice physiotherapist perspectives on preparedness for work in private practice. The qualitative approach of interpretive description was used to guide in-depth interviews with 8 novice physiotherapists from 3 universities working in 5 private practices in Melbourne. All interviews were digitally recorded, transcribed verbatim and analyzed thematically. Four main themes influencing graduate preparedness for work in private practice were identified: 1) non-curricular experiences (e.g. sports training) 2) elective curricular: practicum experiences; 3) curricular: attainment of skills specific to private practice; and 4) the private practice setting: supportive colleagues. This combination of non-curricular, curricular, and practice setting factors offered the necessary scaffolding for the graduates to report feeling prepared for work in private practice. Non-curricular activities, radiological instruction, clinical placements, building supportive colleague relations and professional development in private practice are recommended as potential means of building preparedness in novice therapists. Findings have implications for physiotherapy students, educators and private practice clinics looking to recruit new graduates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    Science.gov (United States)

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  14. Health, Islam and Alternative Capitalism. Three possible Key Factors in Developing Somaliland

    Directory of Open Access Journals (Sweden)

    Daria Zizzola

    2012-02-01

    Full Text Available The main aim of this paper is to investigate the socio, political and economic dynamics that have occurred in Somaliland in the last decades. Even though this country is still unrecognized by the international community, Somaliland’s economy has undertaken an enduring growth, above all in the private entrepreneurial sector. The author argues that religion has had an important role in the Somali cultural and social identification. According to this assumption, the article analyzes the Islamic factor by showing how it has led to the creation of many alternative connections supported by mutual trust and religious solidarity among involved communities. These connections are somehow fulfilling the absence of political legitimacy while progressively substituting conventional routes of intra-national negotiation, like diplomacy. To confirm this tendency, specific arguments are drawn from Somaliland’s health sector. The health care system is considered a preferential index to evaluate the level of national development. Above all, the private non-profit sector gives some evidence of the Somali capacity of running competitive private businesses while multiplying simultaneously their resources and suppliers with a consequent increase in autonomy and efficiency. This successful compromise bears the fruits of Somali engagement and can be identified by their inexhaustible adaptability to adverse conditions and their ability to avoid, not deny, the rational rules imposed by external actors and their ostensible, insurmountable interests.

  15. Trench angle: a key design factor for a deep trench superjunction MOSFET

    International Nuclear Information System (INIS)

    Kang, Hyemin; Lee, Jaegil; Lee, Kwangwon; Choi, Youngchul

    2015-01-01

    Why is the development of a deep trench superjunction (SJ) MOSFET above 600 V and under 8.0 mohm · cm 2 difficult? A deep trench SJ MOSFET is expected to have a low turn-on resistance because the post thermal process after the epitaxial process, which is normally used in a multi-step epitaxy structure, is unnecessary. When designing a deep trench SJ MOSFET, the trench angle is the most important factor because this determines the breakdown voltage (BV) and BV variations. In this paper, we investigated how the trench angle affects the BV and BV window as a condition of the possible thermal process. By employing a physical concept, ΔCharge, we explained why the maximum BV is decreased and the BV window is increased as the trench angle decreases. Also, we systematically scrutinized the transition of the vertical electric field by varying the trench angle. Furthermore, in a real case, the principle of the trench angle which contributes to the deviation of the charge imbalance and specific resistance of SJ is described. Finally, we discuss the challenge of SJ MOSFET development in the industry. (paper)

  16. A Robust and Anonymous Two Factor Authentication and Key Agreement Protocol for Telecare Medicine Information Systems.

    Science.gov (United States)

    Xiong, Hu; Tao, Junyi; Chen, Yanan

    2016-11-01

    Nowadays people can get many services including health-care services from distributed information systems remotely via public network. By considering that these systems are built on public network, they are vulnerable to many malicious attacks. Hence it is necessary to introduce an effective mechanism to protect both users and severs. Recently many two-factor authentication schemes have been proposed to achieve this goal. In 2016, Li et al. demonstrated that Lee et al.'s scheme was not satisfactory to be deployed in practice because of its security weaknesses and then proposed a security enhanced scheme to overcome these drawbacks. In this paper, we analyze Li et al.'s scheme is still not satisfactory to be applied in telecare medicine information systems (TMIS) because it fails to withstand off-line dictionary attack and known session-specific temporary information attack. Moreover, their scheme cannot provide card revocation services for lost smart card. In order to solve these security problems, we propose an improved scheme. Then we analyze our scheme by using BAN-logic model and compare the improved scheme with related schemes to prove that our scheme is advantageous to be applied in practice.

  17. Key factors in work engagement and job motivation of teaching faculty at a university medical centre.

    Science.gov (United States)

    van den Berg, B A M; Bakker, Arnold B; Ten Cate, Th J

    2013-11-01

    This study reports about teacher motivation and work engagement in a Dutch University Medical Centre (UMC). We examined factors affecting the motivation for teaching in a UMC, the engagement of UMC Utrecht teaching faculty in their work, and their engagement in teaching compared with engagement in patient care and research. Based on a pilot study within various departments at the UMCU, a survey on teaching motivation and work engagement was developed and sent to over 600 UMCU teachers. About 50 % responded. Work engagement was measured by the Utrecht Work Engagement Scale, included in this survey. From a list of 22 pre-defined items, 5 were marked as most motivating: teaching about my own speciality, noticeable appreciation for teaching by my direct superior, teaching small groups, feedback on my teaching performance, and freedom to determine what I teach. Feedback on my teaching performance showed the strongest predictive value for teaching engagement. Engagement scores were relatively favourable, but engagement with patient care was higher than with research and teaching. Task combinations appear to decrease teaching engagement. Our results match with self-determination theory and the job demands-resources model, and challenge the policy to combine teaching with research and patient care.

  18. THE QUALITY OF THE TOURIST DESTINATIONS A KEY FACTOR FOR INCREASING THEIR ATTRACTIVENESS

    Directory of Open Access Journals (Sweden)

    Daliborka Blazeska

    2015-12-01

    Full Text Available Taking into consideration that the tourism is extremely important for any country including Republic of Macedonia, it is necessary to pay attention to the quality of the tourist destinations and increasing of their attractiveness. So winners in the field of tourism will be those countries that have attractive tourist destination that will attract a lot of visitors. In this paper is defined the relationship between the factors of attractiveness of the destination and the achieving of competitiveness. In order to become competitive in the global market, the tourist destination has to be innovative and to continually search for new competitive advantages. Those kind of competitive advantages enable stable and long-term sustainable development of the tourist destination. In this paper special emphasis is put to the monitoring of the quality of the tourist destination with constant inquiries of the tourists (domestic and foreign regarding the most important segments of the quality of the tourist product which they are using, in order to perceive the satisfaction or the eventual dissatisfaction in order to be taken concrete strategies for the following period. The obtained results clearly confirm the dissatisfaction with the road infrastructure and signalization, the price of the services and the conditions for the stay, as well as the additional attractions that were expected to get.

  19. Security analysis and improvements of two-factor mutual authentication with key agreement in wireless sensor networks.

    Science.gov (United States)

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-04-09

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes.

  20. Behavioural laterality as a factor in emotional regulation.

    Science.gov (United States)

    Rempala, Daniel M

    2014-01-01

    Individuals who perform a variety of tasks using one side of their bodies (i.e., high-dominance people) are thought to differ from individuals who perform a variety of tasks with both sides of their body (i.e., low-dominance people) in several neurological and cognitive characteristics. We examined whether behavioural laterality predicted the efficacy of different emotional regulation strategies. Specifically, we thought that behavioural laterality would influence verbal strategies (associated with left hemisphere activation) when regulating anxiety (associated with right hemisphere activation). In three studies participants presented in front of small audiences. Behavioural laterality (as measured by a modified handedness inventory) positively correlated with presentation anxiety, such that "low-dominance" participants reported less anxiety than "high-dominance" participants, but only when using cognitive reappraisal (a verbal strategy), not attention deployment or response modulation (behavioural strategies). These results provide preliminary evidence that individual differences in behavioural laterality mediate the efficacy of certain emotional regulation strategies.

  1. CHANGES IN HIGHER EDUCATION: A COMPARISON OF KEY FACTORS CONCERNING UNIVERSITIES IN AUSTRIA AND SWITZERLAND

    Directory of Open Access Journals (Sweden)

    Robert Rybnicek

    2016-10-01

    Full Text Available Society has changed sustainably and universities have thus faced new requirements. As a result of competition and globalization, education and knowledge management had to be adapted. Universities were forced to establish a modern management system primarily known from the private sector and governments had to reconsider their legal and economic relationship to universities. In recent years, many countries have implemented new rules for their universities. Two of these countries were Austria and Switzerland. But even when they pursued the same goals, they have chosen quite different approaches and as a matter of fact achieved very differing results. The objective of this study was twofold. Firstly, we analyzed the challenges and contradictions when implementing a modern university model. Secondly, we investigated specific characteristics of the university systems of Austria and Switzerland to identify factors that may have impacted the performance and success of the universities. Referring to our first objective, a literature review has revealed severe contradictions between modern university management and the traditional understanding of it. While the traditional scheme has focused mainly on research, teaching is becoming more relevant in the new demand orientated university. Also, the freedom of science and teaching is limited by the strong orientation on goals that have been agreed upon with the government. Further contradictions can be identified in autonomy, budgeting, leadership, hierarchy, and employee participation. To examine the second research aim, we reviewed national and international databases and reports. Our results emphasize the importance of monetary aspects, the student-teacher-ratio, autonomy, and the relevance of the universities’ reputation and acceptance within society and politics. Our findings can help to understand the different approaches which have been chosen to cope with global changes in higher education. They

  2. HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder.

    Science.gov (United States)

    Trazzi, Stefania; Fuchs, Claudia; Viggiano, Rocchina; De Franceschi, Marianna; Valli, Emanuele; Jedynak, Paulina; Hansen, Finn K; Perini, Giovanni; Rimondini, Roberto; Kurz, Thomas; Bartesaghi, Renata; Ciani, Elisabetta

    2016-09-15

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in the brain. Mutations of the CDKL5 gene lead to CDKL5 disorder, a neurodevelopmental pathology that shares several features with Rett Syndrome and is characterized by severe intellectual disability. The phosphorylation targets of CDKL5 are largely unknown, which hampers the discovery of therapeutic strategies for improving the neurological phenotype due to CDKL5 mutations. Here, we show that the histone deacetylase 4 (HDAC4) is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes HDAC4 cytoplasmic retention. Nuclear HDAC4 binds to chromatin as well as to MEF2A transcription factor, leading to histone deacetylation and altered neuronal gene expression. By using a Cdkl5 knockout (Cdkl5 -/Y) mouse model, we found that hypophosphorylated HDAC4 translocates to the nucleus of neural precursor cells, thereby reducing histone 3 acetylation. This effect was reverted by re-expression of CDKL5 or by inhibition of HDAC4 activity through the HDAC4 inhibitor LMK235. In Cdkl5 -/Y mice treated with LMK235, defective survival and maturation of neuronal precursor cells and hippocampus-dependent memory were fully normalized. These results demonstrate a critical role of HDAC4 in the neurodevelopmental alterations due to CDKL5 mutations and suggest the possibility of HDAC4-targeted pharmacological interventions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Understanding key factors affecting electronic medical record implementation: a sociotechnical approach.

    Science.gov (United States)

    Cucciniello, Maria; Lapsley, Irvine; Nasi, Greta; Pagliari, Claudia

    2015-07-17

    Recent health care policies have supported the adoption of Information and Communication Technologies (ICT) but examples of failed ICT projects in this sector have highlighted the need for a greater understanding of the processes used to implement such innovations in complex organizations. This study examined the interaction of sociological and technological factors in the implementation of an Electronic Medical Record (EMR) system by a major national hospital. It aimed to obtain insights for managers planning such projects in the future and to examine the usefulness of Actor Network Theory (ANT) as a research tool in this context. Case study using documentary analysis, interviews and observations. Qualitative thematic analysis drawing on ANT. Qualitative analyses revealed a complex network of interactions between organizational stakeholders and technology that helped to shape the system and influence its acceptance and adoption. The EMR clearly emerged as a central 'actor' within this network. The results illustrate how important it is to plan innovative and complex information systems with reference to (i) the expressed needs and involvement of different actors, starting from the initial introductory phase; (ii) promoting commitment to the system and adopting a participative approach; (iii) defining and resourcing new roles within the organization capable of supporting and sustaining the change and (iv) assessing system impacts in order to mobilize the network around a common goal. The paper highlights the organizational, cultural, technological, and financial considerations that should be taken into account when planning strategies for the implementation of EMR systems in hospital settings. It also demonstrates how ANT may be usefully deployed in evaluating such projects.

  4. Reduced lung cancer mortality in dairy farmers: is endotoxin exposure the key factor?

    Science.gov (United States)

    Mastrangelo, G; Marzia, V; Marcer, G

    1996-11-01

    From two areas in the Province of Padova, we selected 2,283 male farmers who worked either in cattle raising or in crop/orchard cultivation. There were 422 cohort deaths from 1970 to 1992. Using the regional population as a reference, the standardized mortality ratio (SMR) was calculated, with 95% confidence intervals (CI) based on the Poisson distribution. Cancer mortality was significantly reduced among the 1,561 dairy farmers (SMR = 0.65; CI = 0.53-0.81); there was a significant decrease in lung cancer (SMR = 0.49; CI = 0.31-0.74), whereas a significant increase from brain tumors was found (SMR = 2.83; CI = 1.04-6.17). Neither overall cancer mortality nor the lung cancer SMR deviated significantly from unity for the 722 crop/orchard farmers. Among dairy farmers, moreover, lung cancer SMRs showed a significant downward trend across the quartiles of increasing length of work, 0.96 in the first quartile, and 0.48, 0.40, and 0.25 in the second, third, and fourth quartiles, respectively. Moreover, lung cancer risk decreased with increasing farm land area, with SMRs in the quartiles of 0.89, 0.37, 0.41 and 0.19. This decrease cannot be attributed to either a selection (healthy worker effect) or a confounding (lower percentage of smokers) bias. Nor was it due to an artifact introduced by differences in age distribution among the quartiles. Dairy farmers are known to be exposed to higher airborne endotoxin concentrations; reasonably, this cumulative exposure increases further with years of work and area of farm. Endotoxins may have protected the dairy farmers against lung cancer through the tumor necrosis factor produced by alveolar macrophages.

  5. A review of international biobanks and networks: success factors and key benchmarks.

    Science.gov (United States)

    Vaught, Jim; Kelly, Andrea; Hewitt, Robert

    2009-09-01

    Biobanks and biobanking networks are involved in varying degrees in the collection, processing, storage, and dissemination of biological specimens. This review outlines the approaches that 16 of the largest biobanks and biobanking networks in Europe, North America, Australia, and Asia have taken to collecting and distributing human research specimens and managing scientific initiatives while covering operating costs. Many are small operations that exist as either a single or a few freezers in a research laboratory, hospital clinical laboratory, or pathology suite. Larger academic and commercial biobanks operate to support large clinical and epidemiological studies. Operational and business models depend on the medical and research missions of their institutions and home countries. Some national biobanks operate with a centralized physical biobank that accepts samples from multiple locations. Others operate under a "federated" model where each institution maintains its own collections but agrees to list them on a central shared database. Some collections are "project-driven" meaning that specimens are collected and distributed to answer specific research questions. "General" collections are those that exist to establish a reference collection, that is, not to meet particular research goals but to be available to respond to multiple requests for an assortment of research uses. These individual and networked biobanking systems operate under a variety of business models, usually incorporating some form of partial cost recovery, while requiring at least partial public or government funding. Each has a well-defined biospecimen-access policy in place that specifies requirements that must be met-such as ethical clearance and the expertise to perform the proposed experiments-to obtain samples for research. The success of all of these biobanking models depends on a variety of factors including well-defined goals, a solid business plan, and specimen collections that are

  6. Nrf2 transcription factor gene regulates basal transcription of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... induction in the Nrf2(-/-) mouse brain. In contrast, there ... mouse brain by any of the chemicals used . Key words: .... The blots were then probed with the human SOD2 .... Nrf2, null and wild mice as part of my PhD work. I wish.

  7. Environmental contaminants and microRNA regulation: Transcription factors as regulators of toxicant-altered microRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Sollome, James; Martin, Elizabeth [Department of Environmental Science & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Sethupathy, Praveen [Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC (United States); Fry, Rebecca C., E-mail: rfry@unc.edu [Department of Environmental Science & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC (United States)

    2016-12-01

    MicroRNAs (miRNAs) regulate gene expression by binding mRNA and inhibiting translation and/or inducing degradation of the associated transcripts. Expression levels of miRNAs have been shown to be altered in response to environmental toxicants, thus impacting cellular function and influencing disease risk. Transcription factors (TFs) are known to be altered in response to environmental toxicants and play a critical role in the regulation of miRNA expression. To date, environmentally-responsive TFs that are important for regulating miRNAs remain understudied. In a state-of-the-art analysis, we utilized an in silico bioinformatic approach to characterize potential transcriptional regulators of environmentally-responsive miRNAs. Using the miRStart database, genomic sequences of promoter regions for all available human miRNAs (n = 847) were identified and promoter regions were defined as − 1000/+500 base pairs from the transcription start site. Subsequently, the promoter region sequences of environmentally-responsive miRNAs (n = 128) were analyzed using enrichment analysis to determine overrepresented TF binding sites (TFBS). While most (56/73) TFs differed across environmental contaminants, a set of 17 TFs was enriched for promoter binding among miRNAs responsive to numerous environmental contaminants. Of these, one TF was common to miRNAs altered by the majority of environmental contaminants, namely SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 3 (SMARCA3). These identified TFs represent candidate common transcriptional regulators of miRNAs perturbed by environmental toxicants. - Highlights: • Transcription factors that regulate environmentally-modulated miRNA expression are understudied • Transcription factor binding sites (TFBS) located within DNA promoter regions of miRNAs were identified. • Specific transcription factors may serve as master regulators of environmentally-mediated microRNA expression.

  8. Environmental contaminants and microRNA regulation: Transcription factors as regulators of toxicant-altered microRNA expression

    International Nuclear Information System (INIS)

    Sollome, James; Martin, Elizabeth; Sethupathy, Praveen; Fry, Rebecca C.

    2016-01-01

    MicroRNAs (miRNAs) regulate gene expression by binding mRNA and inhibiting translation and/or inducing degradation of the associated transcripts. Expression levels of miRNAs have been shown to be altered in response to environmental toxicants, thus impacting cellular function and influencing disease risk. Transcription factors (TFs) are known to be altered in response to environmental toxicants and play a critical role in the regulation of miRNA expression. To date, environmentally-responsive TFs that are important for regulating miRNAs remain understudied. In a state-of-the-art analysis, we utilized an in silico bioinformatic approach to characterize potential transcriptional regulators of environmentally-responsive miRNAs. Using the miRStart database, genomic sequences of promoter regions for all available human miRNAs (n = 847) were identified and promoter regions were defined as − 1000/+500 base pairs from the transcription start site. Subsequently, the promoter region sequences of environmentally-responsive miRNAs (n = 128) were analyzed using enrichment analysis to determine overrepresented TF binding sites (TFBS). While most (56/73) TFs differed across environmental contaminants, a set of 17 TFs was enriched for promoter binding among miRNAs responsive to numerous environmental contaminants. Of these, one TF was common to miRNAs altered by the majority of environmental contaminants, namely SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 3 (SMARCA3). These identified TFs represent candidate common transcriptional regulators of miRNAs perturbed by environmental toxicants. - Highlights: • Transcription factors that regulate environmentally-modulated miRNA expression are understudied • Transcription factor binding sites (TFBS) located within DNA promoter regions of miRNAs were identified. • Specific transcription factors may serve as master regulators of environmentally-mediated microRNA expression

  9. Soil parameters are key factors to predict metal bioavailability to snails based on chemical extractant data

    International Nuclear Information System (INIS)

    Pauget, B.; Gimbert, F.; Scheifler, R.; Coeurdassier, M.; Vaufleury, A. de

    2012-01-01

    Although soil characteristics modulate metal mobility and bioavailability to organisms, they are often ignored in the risk assessment of metal transfer. This paper aims to determine the ability of chemical methods to assess and predict cadmium (Cd), lead (Pb) and zinc (Zn) environmental bioavailability to the land snail Cantareus aspersus. Snails were exposed in the laboratory for 28 days to 17 soils from around a former smelter. The soils were selected for their range of pH, organic matter, clay content, and Cd, Pb and Zn concentrations. The influence of soil properties on environmental availability (estimated using HF-HClO 4 , EDTA, CaCl 2 , NH 4 NO 3 , NaNO 3 , free ion activity and total dissolved metal concentration in soil solution) and on environmental bioavailability (modelled using accumulation kinetics) was identified. Among the seven chemical methods, only the EDTA and the total soil concentration can be used to assess Cd and Pb environmental bioavailability to snails (r² adj = 0.67 and 0.77, respectively). For Zn, none of the chemical methods were suitable. Taking into account the influence of the soil characteristics (pH and CEC) allows a better prediction of Cd and Pb environmental bioavailability (r² adj = 0.82 and 0.83, respectively). Even though alone none of the chemical methods tested could assess Zn environmental bioavailability to snails, the addition of pH, iron and aluminium oxides allowed the variation of assimilation fluxes to be predicted. A conceptual and practical method to use soil characteristics for risk assessment is proposed based on these results. We conclude that as yet there is no universal chemical method to predict metal environmental bioavailability to snails, and that the soil factors having the greatest impact depend on the metal considered. - Highlights: ► New approach to identify chemical methods able to predict metal bioavailability to snails. ► Bioavailability of cadmium, lead and zinc to snails was determined by

  10. Soil parameters are key factors to predict metal bioavailability to snails based on chemical extractant data

    Energy Technology Data Exchange (ETDEWEB)

    Pauget, B.; Gimbert, F., E-mail: frederic.gimbert@univ-fcomte.fr; Scheifler, R.; Coeurdassier, M.; Vaufleury, A. de

    2012-08-01

    Although soil characteristics modulate metal mobility and bioavailability to organisms, they are often ignored in the risk assessment of metal transfer. This paper aims to determine the ability of chemical methods to assess and predict cadmium (Cd), lead (Pb) and zinc (Zn) environmental bioavailability to the land snail Cantareus aspersus. Snails were exposed in the laboratory for 28 days to 17 soils from around a former smelter. The soils were selected for their range of pH, organic matter, clay content, and Cd, Pb and Zn concentrations. The influence of soil properties on environmental availability (estimated using HF-HClO{sub 4}, EDTA, CaCl{sub 2}, NH{sub 4}NO{sub 3}, NaNO{sub 3}, free ion activity and total dissolved metal concentration in soil solution) and on environmental bioavailability (modelled using accumulation kinetics) was identified. Among the seven chemical methods, only the EDTA and the total soil concentration can be used to assess Cd and Pb environmental bioavailability to snails (r Superscript-Two {sub adj} = 0.67 and 0.77, respectively). For Zn, none of the chemical methods were suitable. Taking into account the influence of the soil characteristics (pH and CEC) allows a better prediction of Cd and Pb environmental bioavailability (r Superscript-Two {sub adj} = 0.82 and 0.83, respectively). Even though alone none of the chemical methods tested could assess Zn environmental bioavailability to snails, the addition of pH, iron and aluminium oxides allowed the variation of assimilation fluxes to be predicted. A conceptual and practical method to use soil characteristics for risk assessment is proposed based on these results. We conclude that as yet there is no universal chemical method to predict metal environmental bioavailability to snails, and that the soil factors having the greatest impact depend on the metal considered. - Highlights: Black-Right-Pointing-Pointer New approach to identify chemical methods able to predict metal bioavailability

  11. The KNOXI Transcription Factor SHOOT MERISTEMLESS Regulates Floral Fate in Arabidopsis.

    Science.gov (United States)

    Roth, Ohad; Alvarez, John; Levy, Matan; Bowman, John L; Ori, Naomi; Shani, Eilon

    2018-05-09

    Plants have evolved a unique and conserved developmental program that enables the conversion of leaves into floral organs. Elegant genetic and molecular work has identified key regulators of flower meristem identity. However, further understanding of flower meristem specification has been hampered by redundancy and by pleiotropic effects. The KNOXI transcription factor SHOOT MERISTEMLESS (STM) is a well-characterized regulator of shoot apical meristem maintenance. Arabidopsis thaliana stm loss-of-function mutants arrest shortly after germination, and therefore the knowledge on later roles of STM in later processes, including flower development, is limited. Here, we uncover a role for STM in the specification of flower meristem identity. Silencing STM in the APETALA1 (AP1) expression domain in the ap1-4 mutant background resulted in a leafy-flower phenotype, and an intermediate stm-2 allele enhanced the flower meristem identity phenotype of ap1-4. Transcriptional profiling of STM perturbation suggested that STM activity affects multiple floral fate genes, among them the F-Box protein-encoding gene UNUSUAL FLORAL ORGANS (UFO). In agreement with this notion, stm-2 enhanced the ufo-2 floral fate phenotype, and ectopic UFO expression rescued the leafy flowers in genetic backgrounds with compromised AP1 and STM activities. This work suggests a genetic mechanism that underlies the activity of STM in the specification of flower meristem identity. © 2018 American Society of Plant Biologists. All rights reserved.

  12. Computer-aided study of key factors determining high mechanical properties of nanostructured surface layers in metal-ceramic composites

    Science.gov (United States)

    Konovalenko, Igor S.; Shilko, Evgeny V.; Ovcharenko, Vladimir E.; Psakhie, Sergey G.

    2017-12-01

    The paper presents the movable cellular automaton method. It is based on numerical models of surface layers of the metal-ceramic composite NiCr-TiC modified under electron beam irradiation in inert gas plasmas. The models take into account different geometric, concentration and mechanical parameters of ceramic and metallic components. The authors study the contributions of key structural factors in mechanical properties of surface layers and determine the ranges of their variations by providing the optimum balance of strength, strain hardening and fracture toughness.

  13. Toward a cognitive-affective model of goal-setting in rehabilitation: is self-regulation theory a key step?

    Science.gov (United States)

    Siegert, Richard J; McPherson, Kathryn M; Taylor, William J

    2004-10-21

    The aim of this article is to argue that self-regulation theory might offer a useful model for clinical practice, theory-building and empirical research on goal-setting in rehabilitation. Relevant literature on goal-setting and motivation in rehabilitation is considered and some problematic issues for current practice and future research are highlighted. Carver and Scheier's self-regulation theory and its application to rehabilitation research is examined. It is argued that self-regulation theory offers a robust theoretical framework for goal-setting and one in which the salient concepts of motivation and emotion are prominent. Self-regulation theory offers a potentially useful heuristic framework for rehabilitation research.

  14. Genome Binding and Gene Regulation by Stem Cell Transcription Factors

    NARCIS (Netherlands)

    J.H. Brandsma (Johan)

    2016-01-01

    markdownabstractNearly all cells of an individual organism contain the same genome. However, each cell type transcribes a different set of genes due to the presence of different sets of cell type-specific transcription factors. Such transcription factors bind to regulatory regions such as promoters

  15. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  16. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  17. [Hunger and satiety factors in the regulation of pleasure associated with feeding behavior].

    Science.gov (United States)

    Fetissov, Sergueï O

    2016-01-01

    Feeding is an instinctive behavior accompanied by rewarding feeling of pleasure during obtaining and ingesting food, corresponding to the preparatory and consummatory phases of motivated behavior, respectively. Perception of this emotional state together with alternating feelings of hunger and satiety drives the feeding behavior. Because alterations of feeding behavior including either overeating or anorexia may lead to obesity and cachexia, respectively, understanding the neurochemical mechanisms of regulation of feeding pleasure may help to develop new therapies of these diseases. The dopamine (DA) system of the mesolimbic projections plays a key role in behavioral reward in general and is also involved in regulating feeding-associated pleasure in the forebrain including the nucleus accumbens (NAc) and the lateral hypothalamic area (LHA). It suggests that this DA system can be selectively activated by factors specific to different types of motivated behavior including hunger- and satiety- related hormones. Indeed, central administrations of either orexigenic ghrelin or anorexigenic α-melanocyte-stimulating hormone (α-MSH) increase DA release in the NAc. However, DA has also been shown to inhibit food intake when injected into the LHA, historically known as a « hunger center », indicating DA functional involvement in regulation of both appetite and feeding pleasure. Although both NAc and LHA contain neurons expressing melanocortin receptors, only the LHA receives the α-MSH containing nerve terminals from the α-MSH producing neurons of the hypothalamic arcuate nucleus, the main relay of the peripheral hunger and satiety signals to the brain. A recent study showed that α-MSH in the LHA enhances satiety and inhibits feeding pleasure while potently stimulating DA release in this area during both preparatory and consummatory phases of feeding. It suggests that altered signaling by α-MSH to the DA system in the LHA may be involved in the pathophysiology of

  18. Arabidopsis MADS-Box Transcription Factor AGL21 Acts as Environmental Surveillance of Seed Germination by Regulating ABI5 Expression.

    Science.gov (United States)

    Yu, Lin-Hui; Wu, Jie; Zhang, Zi-Sheng; Miao, Zi-Qing; Zhao, Ping-Xia; Wang, Zhen; Xiang, Cheng-Bin

    2017-06-05

    Seed germination is a crucial checkpoint for plant survival under unfavorable environmental conditions. Abscisic acid (ABA) signaling plays a vital role in integrating environmental information to regulate seed germination. It has been well known that MCM1/AGAMOUS/DEFICIENS/SRF (MADS)-box transcription factors are key regulators of seed and flower development in Arabidopsis. However, little is known about their functions in seed germination. Here we report that MADS-box transcription factor AGL21 is a negative regulator of seed germination and post-germination growth by controlling the expression of ABA-INSENSITIVE 5 (ABI5) in Arabidopsis. The AGL21-overexpressing plants were hypersensitive to ABA, salt, and osmotic stresses during seed germination and early post-germination growth, whereas agl21 mutants were less sensitive. We found that AGL21 positively regulated ABI5 expression in seeds. Consistently, genetic analyses showed that AGL21 is epistatic to ABI5 in controlling seed germination. Chromatin immunoprecipitation assays further demonstrated that AGL21 could directly bind to the ABI5 promoter in plant cells. Moreover, we found that AGL21 responded to multiple environmental stresses and plant hormones during seed germination. Taken together, our results suggest that AGL21 acts as a surveillance integrator that incorporates environmental cues and endogenous hormonal signals into ABA signaling to regulate seed germination and early post-germination growth. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  19. Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.

    Directory of Open Access Journals (Sweden)

    Barbara Gawronska-Kozak

    Full Text Available Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process.

  20. [Discussion on developing a data management plan and its key factors in clinical study based on electronic data capture system].

    Science.gov (United States)

    Li, Qing-na; Huang, Xiu-ling; Gao, Rui; Lu, Fang

    2012-08-01

    Data management has significant impact on the quality control of clinical studies. Every clinical study should have a data management plan to provide overall work instructions and ensure that all of these tasks are completed according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the data management plan (DMP) is an auditable document requested by regulatory inspectors and must be written in a manner that is realistic and of high quality. The significance of DMP, the minimum standards and the best practices provided by GCDMP, the main contents of DMP based on electronic data capture (EDC) and some key factors of DMP influencing the quality of clinical study were elaborated in this paper. Specifically, DMP generally consists of 15 parts, namely, the approval page, the protocol summary, role and training, timelines, database design, creation, maintenance and security, data entry, data validation, quality control and quality assurance, the management of external data, serious adverse event data reconciliation, coding, database lock, data management reports, the communication plan and the abbreviated terms. Among them, the following three parts are regarded as the key factors: designing a standardized database of the clinical study, entering data in time and cleansing data efficiently. In the last part of this article, the authors also analyzed the problems in clinical research of traditional Chinese medicine using the EDC system and put forward some suggestions for improvement.

  1. Identifying key factors and strategies for reducing industrial CO2 emissions from a non-Kyoto protocol member's (Taiwan) perspective

    International Nuclear Information System (INIS)

    Lin, Sue J.; Lu, I.J.; Lewis, Charles

    2006-01-01

    In this study we use Divisia index approach to identify key factors affecting CO 2 emission changes of industrial sectors in Taiwan. The changes of CO 2 emission are decomposed into emission coefficient, energy intensity, industrial structure and economic growth. Furthermore, comparisons with USA, Japan, Germany, the Netherlands and South Korea are made to have a better understanding of emission tendency in these countries and to help formulate our CO 2 reduction strategies for responding to the international calls for CO 2 cuts. The results show that economic growth and high energy intensity were two key factors for the rapid increase of industrial CO 2 emission in Taiwan, while adjustment of industrial structure was the main component for the decrease. Although economic development is important, Taiwan must keep pace with the international trends for CO 2 reduction. Among the most important strategies are continuous efforts to improve energy intensity, fuel mix toward lower carbon, setting targets for industrial CO 2 cuts, and advancing green technology through technology transfer. Also, the clean development mechanism (CDM) is expected to play an important role in the future

  2. Factors influencing subject selection in upper secondary education (Key Stage 4 for males and females in England

    Directory of Open Access Journals (Sweden)

    Joanne Vaughan

    2015-08-01

    Full Text Available Background Research to date has investigated the potential factors that influence students’ decisions in opting to study certain subjects during their upper secondary education. Trends in subject selection at this level (Key Stage 4 have been maintained over time and have consistently displayed comparable differences for males and females. It is recognised that males typically opt for subjects such as physical education and science, while females are traditionally noted as favouring the arts and humanities. These educational decisions may impact on future occupational directions. In light of recent initiatives, such as the English Baccalaureate, it is of interest to explore whether such measures have had an influence on this noted gender gap. Participants and procedure The present study investigates the potential predictors of subject selection, while controlling for gender, offering a specific focus on the education system in England. Attention is given to students’ perceived academic ability and attitude toward school, and how such factors may guide subject choice. Participants (N = 276 were students currently in the process of selecting optional modules for Key Stage 4 study. Results The findings demonstrate that female students are less likely than their male counterparts to opt for physical education (PE and business studies/information and communication technology (ICT as preferred modules, in comparison to ‘creative and performance’ subjects (reference category. Higher levels of reported masculinity were also shown to relate to the up-take of PE at Key Stage 4. Conclusions The implications of these findings are discussed in relation to existing research and practical contributions to the educational arena.

  3. The spatial expression and regulation of transcription factors IDEF1 and IDEF2

    Science.gov (United States)

    Kobayashi, Takanori; Ogo, Yuko; Aung, May Sann; Nozoye, Tomoko; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Yamakawa, Takashi; Nishizawa, Naoko K.

    2010-01-01

    Background and Aims Under conditions of low iron availability, rice plants induce genes involved in iron uptake and utilization. The iron deficiency-responsive cis-acting element binding factors 1 and 2 (IDEF1 and IDEF2) regulate transcriptional response to iron deficiency in rice roots. Clarification of the functions of IDEF1 and IDEF2 could uncover the gene regulation mechanism. Methods Spatial patterns of IDEF1 and IDEF2 expression were analysed by histochemical staining of IDEF1 and IDEF2 promoter-GUS transgenic rice lines. Expression patterns of the target genes of IDEF1 and IDEF2 were analysed using transformants with induced or repressed expression of IDEF1 or IDEF2 grown in iron-rich or in iron-deficient solutions for 1 d. Key Results IDEF1 and IDEF2 were highly expressed in the basal parts of the lateral roots and vascular bundles. IDEF1 and IDEF2 expression was dominant in leaf mesophyll and vascular cells, respectively. These expression patterns were similar under both iron-deficient and iron-sufficient conditions. IDEF1 was strongly expressed in pollen, ovaries, the aleurone layer and embryo. IDEF2 was expressed in pollen, ovaries and the dorsal vascular region of the endosperm. During seed germination, IDEF1 and IDEF2 were expressed in the endosperm and embryo. Expression of IDEF1 target genes was regulated in iron-rich roots similar to early iron-deficiency stages. In addition, the expression patterns of IDEF2 target genes were similar between iron-rich conditions and early or subsequent iron deficiency. Conclusions IDEF1 and IDEF2 are constitutively expressed during both vegetative and reproductive stages. The spatial expression patterns of IDEF1 and IDEF2 overlap with their target genes in restricted cell types, but not in all cells. The spatial expression patterns and gene regulation of IDEF1 and IDEF2 in roots are generally conserved under conditions of iron sufficiency and deficiency, suggesting complicated interactions with unknown factors for

  4. Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors.

    Science.gov (United States)

    Moriel-Carretero, María; Ovejero, Sara; Gérus-Durand, Marie; Vryzas, Dimos; Constantinou, Angelos

    2017-12-04

    Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the maintenance of chromosomal stability during DNA replication. FA proteins regulate replication dynamics, coordinate replication-coupled repair of interstrand DNA cross-links, and mitigate conflicts between replication and transcription. Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic cells. Furthermore, we find that DNA replication stress induces the release of SF3B1 from nuclear speckles in a manner that depends on FANCI and on the activity of the checkpoint kinase ATR. In chromatin, both FANCD2 and FANCI associate with SF3B1, prevent accumulation of postcatalytic intron lariats, and contribute to the timely eviction of splicing factors. We propose that FANCD2 and FANCI contribute to the organization of functional domains in chromatin, ensuring the coordination of DNA replication and cotranscriptional processes. © 2017 Moriel-Carretero et al.

  5. Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

    Science.gov (United States)

    Dufton, Neil P; Peghaire, Claire R; Osuna-Almagro, Lourdes; Raimondi, Claudio; Kalna, Viktoria; Chuahan, Abhishek; Webb, Gwilym; Yang, Youwen; Birdsey, Graeme M; Lalor, Patricia; Mason, Justin C; Adams, David H; Randi, Anna M

    2017-10-12

    The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg cEC-Het ) and inducible homozygous deficient mice (Erg iEC-KO ), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL 4 )-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

  6. The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

    Science.gov (United States)

    Tanimoto, Ryuta; Palladino, Chiara; Xu, Shi-Qiong; Buraschi, Simone; Neill, Thomas; Gomella, Leonard G; Peiper, Stephen C; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2017-12-01

    Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis. Copyright © 2017. Published by Elsevier B.V.

  7. Factors Influencing Self-Regulation in E-Learning 2.0: Confirmatory Factor Model

    Science.gov (United States)

    Zhao, Hong

    2016-01-01

    The importance of self-regulation in e-learning has been well noted in research. Relevant studies have shown a consistent positive correlation between learners' self-regulation and their success rate in e-learning. Increasing attention has been paid to developing learners' self-regulated abilities in e-learning. For students, what and how to learn…

  8. The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

    KAUST Repository

    Abulfaraj, Aala A.; Mariappan, Kiruthiga; Bigeard, Jean; Manickam, Prabhu; Blilou, Ikram; Guo, Xiujie; Al-Babili, Salim; Pflieger, Delphine; Hirt, Heribert; Rayapuram, Naganand

    2018-01-01

    Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

  9. The Arabidopsis homolog of human G3BP1 is a key regulator of stomatal and apoplastic immunity

    KAUST Repository

    Abulfaraj, Aala Abdulaziz Hussien

    2018-05-31

    Mammalian Ras-GTPase–activating protein SH3-domain–binding proteins (G3BPs) are a highly conserved family of RNA-binding proteins that link kinase receptor-mediated signaling to RNA metabolism. Mammalian G3BP1 is a multifunctional protein that functions in viral immunity. Here, we show that the Arabidopsis thaliana homolog of human G3BP1 negatively regulates plant immunity. Arabidopsis g3bp1 mutants showed enhanced resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato. Pathogen resistance was mediated in Atg3bp1 mutants by altered stomatal and apoplastic immunity. Atg3bp1 mutants restricted pathogen entry into stomates showing insensitivity to bacterial coronatine–mediated stomatal reopening. AtG3BP1 was identified as a negative regulator of defense responses, which correlated with moderate up-regulation of salicylic acid biosynthesis and signaling without growth penalty.

  10. Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E.

    Science.gov (United States)

    Mascher, Gerald; Mertaoja, Anna; Korkeala, Hannu; Lindström, Miia

    2017-10-01

    Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA-binding domain of Spo0A directly bound to a putative Spo0A-binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C. botulinum type E. Unlike other C. botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C. botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Deciphering the function and regulation of SbCAD2: A key lignin gene to improve sorghum biomass degradability

    Science.gov (United States)

    Genetic modification of lignin biosynthesis in the cell wall of biofuel feedstocks is likely one of the most effective ways to improve the conversion efficiency of cellulosic biomass to biofuel for the bioenergy industry. As a key enzyme that catalyzes the last step of monolignol synthesis, cinnamy...

  12. Defense of single-factor models of population regulation

    International Nuclear Information System (INIS)

    Tamarin, R.H.

    1978-01-01

    I reject a multifactorial approach to the study of the regulation of animal populations for two reasons. First, a mechanism suggested by Chitty, that has natural selection at its base, has not been adequately tested. Second, the multifactorial model suggested by Lidicker is untestable because of its vagueness. As a middle ground, I suggest a model that has natural selection as its mechanism, but is multifacturial because it allows many parameters to be the selective agents. I particularly emphasize prediction and selective dispersal. Methods to test this model are suggested

  13. HIF-1 α as a Key Factor in Bile Duct Ligation-Induced Liver Fibrosis in Rats.

    Science.gov (United States)

    Moczydlowska, Joanna; Miltyk, Wojciech; Hermanowicz, Adam; Lebensztejn, Dariusz M; Palka, Jerzy A; Debek, Wojciech

    2017-02-01

    Although several studies suggested hypoxia as an important microenvironmental factor contributing to inflammation and fibrosis in chronic liver diseases, the mechanism of this process is not fully understood. We considered hypoxia inducible factor (HIF-1α) as a key transcription factor in liver fibrosis. The aim of the study was to evaluate the mechanisms of signaling pathway during bile duct ligation (BDL)-induced liver fibrosis in rats. BDL animal model of liver fibrosis was used in the study. Male Wistar rats were divided randomly into two experimental groups: sham group (n = 15), BDL group (n = 30). Hydroxyproline (Hyp) content as a marker of collagen accumulation in liver of rats subjected to BDL was evaluated according to the method described by Gerling B et al. Expression of signaling proteins [integrin β 1 receptor, HIF-1α, nuclear factor kappa B (NF-κB), and transforming growth factor (TGF-β)] was evaluated applying Western-immunoblot analysis. In all experiments, the mean values for six assays ± standard deviations (SD) were calculated. The results were submitted to the statistical analysis using the Student's "t" test, accepting p bile ducts was found to increase Hyp content in rat liver, accompanied by increase of HIF-1α expression during 10 weeks after BDL. The Hyp level was time dependent. There was not such a difference in control group (p livers were increased 1 week after surgery and remained increased until the end of the experiment. The mechanism of development of liver fibrosis involves activation of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9), upregulation of HIF-1α transcriptional activity and its related factors, NF-κB and TGF-β. It suggests that they may represent targets for the treatment of the disease.

  14. Psychosocial and behavioural factors in the regulation of weight: Self-regulation, self-efficacy and locus control.

    Science.gov (United States)

    Menéndez-González, Lara; Orts-Cortés, María Isabel

    To identify the relationship and behaviour of the variables of self-control, self-efficacy and locus control in weight regulation of obese, overweight and normal weight adults. Transversal study undertaken in the Health Centre of El Coto (Gijón) from 1st April to 30th July 2015. Subjects between 18-65 years of age with a body mass index recording within the last two years. serious medical illness, eating disorders or pregnant women. Behavioural variables: self-regulation of body weight (Inventory of self-control of body weight), perceived self-efficacy in weight regulation (Inventory of perceived self-efficacy in weight regulation) and locus control in weight regulation (Inventory of locus control in weight regulation). Anthropometric variables: weight (kg) and height (m), body mass index. One hundred and six participants were included: 32 were obese, 28 overweight and 46 normal weight. Significant differences were found between the 3 study groups for total scale of self-efficacy (F=61.77; pcontrol (F=13.92; p=.019), other weighty influences of locus control (F=9.21; pcontrol (F=3.50; p=.011). The relationship between body mass index and behavioural variables of self-efficacy, self-regulation and locus control, suggests the need for healthcare professionals to include psychological factors of behaviour in any preventive action and intervention directed at weight control. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  15. A quantitative model of regulator's preference factor (RPF) in electricity-environment coordinated regulation system

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Yulong; Fu, Shijun [Economy and Business Administration School of Chongqing University, Chongqing 400030 (China)

    2010-12-15

    This paper explores quantification of regulator's preference factor (RPF) in electricity-environment coordinated regulation system. Based on social welfare economics, we articulately depict RPF's qualitative concept and its economic meaning. Then, applying abstract functions (i.e., abstract social welfare function, abstract utility function, and abstract production function), we deduce the partial-social-welfare elasticity, and build the mathematics model of maximizing social welfare. We nest this elasticity into the model's Kuhn-Tucker conditions, and obtain RPF's definition formula. By solving the Kuhn-Tucker conditions, we get RPF's quantitative formula, which solves the problem of hard to quantify regulator's preference in electricity-environment coordinated regulation system. The result shows that RPF only has relationship to subsystems' production function, and is independent of social welfare function and subsystems' utility function. Finally, we provide an empirical research based on the western region of China from year 1995 to 2004. It reveals that regulator has relative stability preference to mitigating pollutants. And validity test confirms that the empirical result is fit well to the practice. The RPF is truly a more general and valid instrument to measure regulator's preference in its regulated field. (author)

  16. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  17. Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

    Science.gov (United States)

    Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

    2006-05-01

    Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

  18. Regulation of follicular development by peptidic intraovarian factors

    OpenAIRE

    Lanuza, Guillermo

    1999-01-01

    El objetivo de esta tesis es el estudio de factores regulatorios, de producción y acción local, que controlan el desarrollo del folículo ovárico en mamíferos. En particular, se estudió el papel fisiológico de factores relacionados con el factor de crecimiento transformante-β (TGF-β).El modelo utilizado consistió en células de la granulosa inmaduras de rata cultivadas en condiciones definidas. Se determinó que las células de la granulosa producen TGF-β bioactivo, encontrándose su secreción baj...

  19. Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

    DEFF Research Database (Denmark)

    Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

    2015-01-01

    The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...

  20. Regulation of archicortical arealization by the transcription factor Zbtb20

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga; Tonchev, Anton B; Stoykova, Anastassia

    2012-01-01

    The molecular mechanisms of regionalization of the medial pallium (MP), the anlage of the hippocampus, and transitional (cingulate and retrosplenial) cortices are largely unknown. Previous analyses have outlined an important role of the transcription factor (TF) Zbtb20 for hippocampal CA1 field...

  1. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Czech Academy of Sciences Publication Activity Database

    Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

    2012-01-01

    Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

  2. Incorporating Human Factors into design change processes - a regulator's perspective

    International Nuclear Information System (INIS)

    Staples, L.; McRobbie, H.

    2003-01-01

    Nuclear power plants in Canada must receive written approval from the Canadian Nuclear Safety Commission (CNSC) when making certain changes that are defined in their licenses. The CNSC expects the design change process to include a method for ensuring that the human-machine interface and workplace design support the safe and reliable performance of required tasks. When reviewing design changes for approval, the CNSC looks for evidence of analysis work, use of appropriate human factors design guide-lines, and verification and validation testing of the design. In addition to reviewing significant design changes, evaluations are conducted to ensure design change processes adequately address human performance. Findings from reviews and evaluations highlight the need to integrate human factors into the design change process, provide human factors training and support to engineering staff, establish processes to ensure coordination between the various groups with a vested interest in human factors, and develop more rigorous methods to validate changes to maintenance, field operations and testing interfaces. (author)

  3. Membrane-bound transcription factors: regulated release by RIP or RUP.

    Science.gov (United States)

    Hoppe, T; Rape, M; Jentsch, S

    2001-06-01

    Regulated nuclear transport of transcription factors from cytoplasmic pools is a major route by which eukaryotes control gene expression. Exquisite examples are transcription factors that are kept in a dormant state in the cytosol by membrane anchors; such proteins are released from membranes by proteolytic cleavage, which enables these transcription factors to enter the nucleus. Cleavage can be mediated either by regulated intramembrane proteolysis (RIP) catalysed by specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent processing (RUP). In both cases processing can be controlled by cues that originate at or in the vicinity of the membrane.

  4. The RNA chaperone, Hfq, controls two luxR-type regulators and plays a key role in pathogenesis and production of antibiotics in Serratia sp. ATCC 39006.

    Science.gov (United States)

    Wilf, Nabil M; Williamson, Neil R; Ramsay, Joshua P; Poulter, Simon; Bandyra, Kasia J; Salmond, George P C

    2011-10-01

    Serratia sp. ATCC 39006 (S39006) is a Gram-negative bacterium that is virulent in plant (potato) and animal (Caenorhabditis elegans) models. It produces two secondary metabolite antibiotics, a prodigiosin and a carbapenem, and the exoenzymes, pectate lyase and cellulase. A complex regulatory network that includes quorum sensing (QS) controls production of prodigiosin. While many aspects of the regulation of the metabolites and exoenzymes are well understood, the potential role in this network of the RNA chaperone Hfq and dependent small regulatory RNAs has not been characterized. Hfq is an RNA chaperone involved in post-transcriptional regulation that plays a key role in stress response and virulence in diverse bacterial species. To explore whether Hfq-dependent processes might contribute to the regulation of antibiotic production we constructed an S39006 Δhfq mutant. Production of prodigiosin and carbapenem was abolished in this mutant strain, while production of the QS signalling molecule, butanoyl homoserine lactone (BHL), was unaffected. Using transcriptional fusions, we found that Hfq regulates the QS response regulators, SmaR and CarR. Additionally, exoenzyme production and swimming motility were decreased in a Δhfq mutant, and virulence was attenuated in potato and C. elegans models. These results suggest that an Hfq-dependent pathway is involved in the regulation of virulence and secondary metabolite production in S39006. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  5. Key factors influencing adoption of an innovation in primary health care: a qualitative study based on implementation theory

    Directory of Open Access Journals (Sweden)

    Carlfjord Siw

    2010-08-01

    Full Text Available Abstract Background Bridging the knowledge-to-practice gap in health care is an important issue that has gained interest in recent years. Implementing new methods, guidelines or tools into routine care, however, is a slow and unpredictable process, and the factors that play a role in the change process are not yet fully understood. There is a number of theories concerned with factors predicting successful implementation in various settings, however, this issue is insufficiently studied in primary health care (PHC. The objective of this article was to apply implementation theory to identify key factors influencing the adoption of an innovation being introduced in PHC in Sweden. Methods A qualitative study was carried out with staff at six PHC units in Sweden where a computer-based test for lifestyle intervention had been implemented. Two different implementation strategies, implicit or explicit, were used. Sixteen focus group interviews and two individual interviews were performed. In the analysis a theoretical framework based on studies of implementation in health service organizations, was applied to identify key factors influencing adoption. Results The theoretical framework proved to be relevant for studies in PHC. Adoption was positively influenced by positive expectations at the unit, perceptions of the innovation being compatible with existing routines and perceived advantages. An explicit implementation strategy and positive opinions on change and innovation were also associated with adoption. Organizational changes and staff shortages coinciding with implementation seemed to be obstacles for the adoption process. Conclusion When implementation theory obtained from studies in other areas was applied in PHC it proved to be relevant for this particular setting. Based on our results, factors to be taken into account in the planning of the implementation of a new tool in PHC should include assessment of staff expectations, assessment of the

  6. Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Rui-Yun Peng

    2016-01-01

    With key roles in essential brain functions ranging from the long-term potentiation (LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor (NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca2+,postsynaptic density 95 (PSD-95),calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ),protein kinase A (PKA),mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

  7. Studying work practices: a key factor in understanding accidents on the level triggered by a balance disturbance.

    Science.gov (United States)

    Derosier, C; Leclercq, S; Rabardel, P; Langa, P

    2008-12-01

    Accidents on the level (AOL) rank second amongst the most numerous and serious occupational accidents with days lost in France and are a major health and safety problem in every sector of activity. The case study described in this paper was conducted at a metallurgical company with 300 employees. The aims of this work were dual: 1) to extend the general knowledge required for preventing these accidents; 2) to propose prevention measures to this company. Existing data on company occupational accidents were gathered and analysed to identify a work situation that appeared likely to cause AOL. This work situation was analysed in detail. Several risk factors were identified within this work situation, by way of interviews with 12 operators. These risk factors concerned various dimensions of the work situation, particularly its physical dimension (e.g. templates structure) and organisational dimension (e.g. parts availability). Interviews were conducted, focusing on risk factors perceived by operators and involving allo-confrontations based on accounts of four AOL occurring in this situation. Allo-confrontations were interviews confronting operators with a risk occupational situation that was accidental for one of their colleagues, the latter being absent from the interview. Results highlighted the fact that the work practices implemented are key factors in understanding these accidents. This study underlines the role of work practices in AOL causality and prevention. It also provides explanations associated with various work situation dimensions involving adoption of more or less safe work practices. AOL are serious and frequent in occupational situations. Injury claims analysis and interviews in an industrial company emphasise the specific characteristics of an occupational situation and of prevention actions forming the basis of an intervention. The need for a better understanding of factors affecting work practice is highlighted in relation to research.

  8. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  9. Key factors influencing the stability of silane solution during long-term surface treatment on carbon steel

    International Nuclear Information System (INIS)

    Xian, Xiaochao; Chen, Minglu; Li, Lixin; Lin, Zhen; Xiang, Jun; Zhao, Shuo

    2013-01-01

    Highlights: •The corrosion-resistance time of silane films decreases with increasing cycle numbers. •The morphology of silane films prepared from aged solution is inhomogeneous. •Introduction of contamination ions is one reason for the poor property of aged solution. •Consumption of silane is the other reason for the poor property of aged solution. •Fe 3+ accumulated is the key factor influencing the property of silane solution. -- Abstract: The mixtures of bis-[trimethoxysilylpropyl]amine and vinyltriacetoxysilane were used for surface treatment of carbon steel, aiming to investigate the factors influencing the stability of silane solution during long-term experiment from two aspects. One is the concentrations of contamination ions, and the other is mass of silane consumed per cycle which is calculated according to concentration of Si measured by silicon molybdenum blue photometry. The results indicate that the accumulation of contamination ions, especially Fe 3+ , is the main factor leading to the condensation between the Si–OH groups in silane solution, which is responsible for the downward stability of silane solution

  10. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation

    KAUST Repository

    Guttery, David S.

    2014-07-09

    Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. © 2014 The Authors.

  11. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation

    KAUST Repository

    Guttery, David  S.; Poulin, Benoit; Ramaprasad, Abhinay; Wall, Richard  J.; Ferguson, David  J.P.; Brady, Declan; Patzewitz, Eva-Maria; Whipple, Sarah; Straschil, Ursula; Wright, Megan  H.; Mohamed, Alyaa  M.A.H.; Radhakrishnan, Anand; Arold, Stefan T.; Tate, Edward  W.; Holder, Anthony  A.; Wickstead, Bill; Pain, Arnab; Tewari, Rita

    2014-01-01

    Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. © 2014 The Authors.

  12. Security Analysis and Improvements of Two-Factor Mutual Authentication with Key Agreement in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Jiye Kim