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Sample records for ddr teilprojekt a1

  1. Forschungsdatenmanagement in DFG-Sonderforschungsbereichen: Teilprojekte Informationsinfrastruktur (INF-Projekte

    Directory of Open Access Journals (Sweden)

    Claudia Engelhardt

    2013-10-01

    Full Text Available Seit 2007 gibt es im Rahmen von DFG-Sonderforschungsbereichen die Möglichkeit, ein „Teilprojekt Informationsinfrastruktur” (kurz: INF-Projekt zu beantragen. Dieses dient dem Forschungsdatenmanagement innerhalb des Sonderforschungsbereiches, was sowohl die Konzeption des Datenmanagements als auch die Bereitstellung der erforderlichen Infrastruktur beinhalten kann. Das Konzept der INF-Projekte sieht dabei die Kooperation der Fachwissenschaft mit den Informationsinfrastruktureinrichtungen am Standort vor, beispielsweise mit der Bibliothek oder dem Rechenzentrum. In dieser Hinsicht können die INF-Projekte auch als ein spezifischer Anwendungsfall des Embedded Librarianship betrachtet werden. In dieser Arbeit werden die Ergebnisse einer Befragung und eines Workshops mit Vertretern der INF-Projekte vorgestellt, die interessante Einblicke in die Arbeit derselben gewähren. In 2007, ”Information Infrastructure” (INF projects were introduced within the context of the German Research Foundations Collaborative Research Centres. Their purpose is to facilitate research data management within the Collaborative Research Centres, which can include the approach to data management as well as the establishment of the necessary infrastructure. The concept of the INF projects is designed to encourage cooperation between researchers and their local infrastructure institutions, such as the library or the computing centre. In this regard, the INF projects can be viewed as examples of embedded librarianship. This article presents the results of a survey among and a workshop with members of the INF projects, providing interesting insights into their work.

  2. Use of Commercial FPGA-Based Evaluation Boards for Single-Event Testing of DDR2 and DDR3 SDRAMs

    Science.gov (United States)

    Ladbury, R. L.; Berg, M. D.; Wilcox, E. P.; LaBel, K. A.; Kim, H. S.; Phan, A. M.; Seidleck, C. M.

    2013-01-01

    We investigate the use of commercial FPGA based evaluation boards for radiation testing DDR2 and DDR3 SDRAMs. We evaluate the resulting data quality and the tradeoffs involved in the use of these boards.

  3. Connecting Community Security and DDR: Experiences from Burundi

    NARCIS (Netherlands)

    Willems, R.C.; Kleingeld, J.; van Leeuwen, M.

    2010-01-01

    The report is based on 10 weeks of field research in Burundi between April and June 2010, and looks at the linkages between community security and DDR. It opens with a discussion of local experiences with DDR programmes, analyzing the impact of its different components, and analyzing the local

  4. Image acquisition in general radiography: The utilisation of DDR

    International Nuclear Information System (INIS)

    Hayre, C.M.; Eyden, A.; Blackman, S.; Carlton, K.

    2017-01-01

    Objective: This article explores image acquisition with DDR. General radiographic technology continues to advance therefore it remains paramount to continually reflect on DDR hardware and software amongst radiographers in an imaging modality that constitutes approximately 90% of all radiological examinations. Method: This article reports findings from a wider ethnographic study of two general radiography environments in the United Kingdom (UK). Participant observation and semi-structured interviews were the methods used to uncover original data. Results: Two key themes are discussed. Firstly, ‘the extent of DDR knowledge’ amongst radiographers is examined. The findings uncover that not all radiographers have an adequate knowledge base with DDR technology. Secondly, ‘pitfalls and near misses with DDR’ is discussed. This theme highlights the potential danger of radiographers ‘over-repeating’ X-ray examinations, coincided with the occurrence of radiological incidents whereby a patient is exposed to ionising radiation with no added benefit. Conclusion: This paper concludes by challenging the current ‘skill base’ to operate DDR equipment. In addition, new pitfalls and near misses are highlighted, which may help forestall radiation incidents in the future. Dose and image optimisation remain central tenets to the role of the radiographer. Advances in knowledge: Few studies have challenged image acquisition with DDR. This study adds to existing knowledge by uncovering original phenomena that may initiate discussions within the radiography community and continually enhance healthcare delivery. - Highlights: • Radiographers may not have appropriate knowledge of DDR technology. • Suggests DDR may facilitate a ‘hit and miss’ approach to image acquisition. • Identifies radiographic errors with DDR, leading to radiological incidents.

  5. Monopoly of Force: The Nexus of DDR and SSR

    Science.gov (United States)

    2011-01-01

    Washington, DC, May 4, 2010. 52 Vanessa Farr, Albrecht Schnabel, and Henri Myrttinen, eds., Sexed Pistols: Gendered Impacts of Small Arms and...discussion of various lessons learned see Edward Bell and Charlotte Watson, DDR: Sup- porting Security and Development: The EU’s Added Value, London...45 Specker, The R-Phase of DDR Processes, 4. 46 This distinction has been made by many authors. See, for example, Ball and van de Goor, 2–3; Mark

  6. Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice

    International Nuclear Information System (INIS)

    Kawai, Ikuma; Hisaki, Tomoka; Sugiura, Koji; Naito, Kunihiko; Kano, Kiyoshi

    2012-01-01

    Highlights: ► Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase. ► DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. ► We produced in vitro and in vivo model to better understand the role of DDR2. ► DDR2 might play an inhibitory role in the proliferation of chondrocyte. -- Abstract: Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines. To investigate DDR2’s molecular role in endochondral cellular proliferation in vivo, we also produced transgenic mice in which the expression of truncated, kinase dead (KD) DDR2 protein is induced, and evaluated the DDR2 function in cellular proliferation in chondrocytes. Although the miDdr2-transfected ATDC5 cell lines retained normal differentiation ability, DDR2 reduction finally promoted cellular proliferation in proportion to the decreasing ratio of Ddr2 expression, and it also promoted earlier differentiation to cartilage cells by insulin induction. The layer of hypertrophic chondrocytes in KD Ddr2 transgenic mice was not significantly thicker than that of normal littermates, but the layer of proliferative chondrocytes in KD-Ddr2 transgenic mice was significantly thicker than that of normal littermates. Taken together, our data demonstrated that DDR2 might play a local and essential role in the

  7. Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Ikuma; Hisaki, Tomoka; Sugiura, Koji; Naito, Kunihiko [Laboratory of Applied Genetics, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo 113-8657 (Japan); Kano, Kiyoshi, E-mail: kanokiyo@yamaguchi-u.ac.jp [Laboratory of Developmental Biology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan. (Japan); Biomedical Science Center for Translational Research (BSCTR), The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi 753-8515 (Japan)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase. Black-Right-Pointing-Pointer DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. Black-Right-Pointing-Pointer We produced in vitro and in vivo model to better understand the role of DDR2. Black-Right-Pointing-Pointer DDR2 might play an inhibitory role in the proliferation of chondrocyte. -- Abstract: Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines. To investigate DDR2's molecular role in endochondral cellular proliferation in vivo, we also produced transgenic mice in which the expression of truncated, kinase dead (KD) DDR2 protein is induced, and evaluated the DDR2 function in cellular proliferation in chondrocytes. Although the miDdr2-transfected ATDC5 cell lines retained normal differentiation ability, DDR2 reduction finally promoted cellular proliferation in proportion to the decreasing ratio of Ddr2 expression, and it also promoted earlier differentiation to cartilage cells by insulin induction. The layer of hypertrophic chondrocytes in KD Ddr2 transgenic mice was not significantly thicker than that of normal littermates, but the layer of proliferative chondrocytes in KD-Ddr2 transgenic mice was significantly thicker than that of normal littermates

  8. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    Directory of Open Access Journals (Sweden)

    Maria E. Gonzalez

    2017-01-01

    Full Text Available Increased collagen deposition by breast cancer (BC-associated mesenchymal stem/multipotent stromal cells (MSC promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2 is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  9. From DDR to Security Promotion: Connecting national programs to community initiatives

    NARCIS (Netherlands)

    Verkoren, W.; Willems, R.C.; Kleingeld, J.; Rouw, H.

    2010-01-01

    Disarmament, demobilization and reintegration (DDR) is a set of activities that forms part of strategies for peacebuilding after civil war. DDR has become the standard way of addressing security threats in immediate post-conflict situations. However, DDR is designed to promote national security,

  10. Coordinated subprojects of the Austrian forest damage monitoring system; Koordinierte Teilprojekte des Oesterr. Waldschaden-Beobachtungssystem

    Energy Technology Data Exchange (ETDEWEB)

    Pollanschuetz, J

    1993-12-31

    Any actions to preserve nature as the base of our survival needs to rely on knowledge about the condition of ecosystems and their `evolutionary` trends. A monitoring system ensuring timely detection of a critical `evolution` of forests as sensitive bio-indicators is an absolute must when addressing the global threat to our living environment. The Austrian forest damage monitoring system addresses this task. It involves subprojects and interdisciplinary studies integrated within this biomonitoring system to enhance our knowledge about and detection capabilities for forest diseases and injuries. (orig.) [Deutsch] Massnahmen zur Bewahrung der Natur als Lebensgrundlage setzen das Wissen ueber den Zustand der Oekosysteme und Kenntnisse ueber deren Entwicklung voraus. Ein Ueberwachungssystem das rechtzeitig kritische Entwicklung am sensiblen Bioindikator Wald erkennen laesst, ist angesichts der Anzeichen einer globalen Bedrohung der belebten Umwelt eine zwingende Selbstverstaendlichkeit. Mit dem Waldschaden-Beobachtungssystem wird diesen Aufgabenstellungen Rechnung getragen. Durch die in diesem Biomonitoring-System integrierten Teilprojekte und interdisziplinaeren Untersuchungen wird auch ein wesentlicher Beitrag zur Erkennung von Ursachen fuer Waldschaeden und Waldkrankheiten geleistet. (orig.)

  11. The Struggle after Combat. The role of NGOs in DDR processes: Afganistan Case Study

    NARCIS (Netherlands)

    Frerks, G.E.; Gompelman, G.; Laar, van de S.; Klem, B.

    2008-01-01

    It has come to be well-recognised that effective DDR (Disarmant, Demobilisation and Reinregration of ex-combatants) is crucial for building durable peace and preventing a relapse into conflict. It has also become clear that DDR is difficult and that it is intertwined with other war to peace

  12. A pilot of a video game (DDR) to promote physical activity and decrease sedentary screen time.

    Science.gov (United States)

    Maloney, Ann E; Bethea, T Carter; Kelsey, Kristine S; Marks, Julie T; Paez, Sadye; Rosenberg, Angela M; Catellier, Diane J; Hamer, Robert M; Sikich, Linmarie

    2008-09-01

    We examined the feasibility of Dance Dance Revolution (DDR), a dance video game, in participants' homes, to increase physical activity (PA) and to decrease sedentary screen time (SST). Sixty children (7.5 +/- 0.5 years) were randomized in a 2:1 ratio to DDR or to wait-list control (10-week delay). DDR use was logged, PA was measured objectively by accelerometry. SST was self-reported at weeks 0 and 10. At week 28, after both groups had access to DDR, accelerometry and SST were repeated. Mean use of DDR was 89 +/- 82 (range 0-660 min) min per week (mpw). The DDR group showed increased vigorous PA and a reduction in light PA; the control group showed no increase in moderate and/or vigorous PA (MVPA) although they also had a reduction in light PA. Differences between the groups were not observed. The DDR group also reported a decrease in SST of -1.2 +/- 3.7 h per week (hpw) (P increase of +3.0 +/- 7.7 hpw (nonsignificant). The difference in SST between the groups was significant, with less SST in the DDR group. Between weeks 10 and 28, numeric reductions in SST were reported in both groups. In the DDR group, SST at week 28 (8.8 +/- 6.0 hpw) was lower than baseline (10.5 +/- 5.5 hpw; P increases in vigorous PA. Further study is needed to better characterize children and contexts in which DDR may promote a healthy lifestyle.

  13. Novel cross-talk between IGF-IR and DDR1 regulates IGF-IR trafficking, signaling and biological responses

    Science.gov (United States)

    Sacco, Antonella; Morcavallo, Alaide; Vella, Veronica; Voci, Concetta; Spatuzza, Michela; Xu, Shi-Qiong; Iozzo, Renato V.; Vigneri, Riccardo; Morrione, Andrea; Belfiore, Antonino

    2015-01-01

    The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression. Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. Significantly, DDR1 was critical for IGF-IR endocytosis and trafficking into early endosomes, IGF-IR protein expression and IGF-I intracellular signaling and biological effects, including cell proliferation, migration and colony formation. These biological responses were inhibited by DDR1 silencing and enhanced by DDR1 overexpression. Experiments in mouse fibroblasts co-transfected with the human IGF-IR and DDR1 gave similar results and indicated that, in the absence of IGF-IR, collagen-dependent phosphorylation of DDR1 is impaired. These results demonstrate a critical role of DDR1 in the regulation of IGF-IR action, and identify DDR1 as a novel important target for breast cancers that overexpress IGF-IR. PMID:25840417

  14. DDR and the Internal Organization of Non-State Armed Groups

    Directory of Open Access Journals (Sweden)

    Brian McQuinn

    2016-03-01

    Full Text Available This paper argues that demobilization, disarmament and reintegration (DDR trajectories of non-state armed groups are shaped by a group’s internal organization. Extensive research by political scientists has demonstrated a correlation between internal features of armed groups and their behaviour (e.g. extent of violence used against local communities. I extend this analysis to DDR outcomes by illustrating how two features of an armed group’s internal organization – command profile and financing architecture – influence post-conflict DDR trajectories. To substantiate the theory, four case studies from Colombia, Nepal and Libya are reviewed. The article concludes with the limitations and opportunities of this approach, including the potential of predicting DDR challenges.

  15. 3D PLUS HI-REL DDR2 Termination Regulator Module- A Building Block Function for High Reliability SDRAM DDR2 System Architecture

    Science.gov (United States)

    Perrot, Nicolas; Dubus, Patrick; Garcia-Sanchez, Esther

    2015-09-01

    Memory system architectures using DDR2 technology need to be compliant with JEDEC JESD8-15A standard [1]. Therefore a bus termination regulator able to sink and source current while regulating VTT voltage is used for this purpose. Such module has been developed by 3D PLUS and is the first space qualified DDR Termination Regulator (DDR2-TR) available on the market. It is based on an innovative Bang-Bang regulation principle, chosen for its speed performance and to guarantee an output voltage that remains within the predefined limits regardless of any output current transients. The output filter type is selected to make the module rugged to any overload condition without complex protection circuits. The module has been specifically designed for low input voltage, low noise and high reliability systems where space is a key consideration. The module uses the 3D PLUS SIP (System-In-Package) technology embedding 3 stacked PCBs. No external filters or decoupling capacitors are needed.

  16. DDR: Efficient computational method to predict drug–target interactions using graph mining and machine learning approaches

    KAUST Repository

    Olayan, Rawan S.; Ashoor, Haitham; Bajic, Vladimir B.

    2017-01-01

    but not all DTIs between them are not known. Using independent sources of evidence, we verify as correct 22 out of the top 25 DDR novel predictions. This suggests that DDR can be used as an efficient method to identify correct DTIs.

  17. DDR: Efficient computational method to predict drug–target interactions using graph mining and machine learning approaches

    KAUST Repository

    Olayan, Rawan S.

    2017-11-23

    Motivation Finding computationally drug-target interactions (DTIs) is a convenient strategy to identify new DTIs at low cost with reasonable accuracy. However, the current DTI prediction methods suffer the high false positive prediction rate. Results We developed DDR, a novel method that improves the DTI prediction accuracy. DDR is based on the use of a heterogeneous graph that contains known DTIs with multiple similarities between drugs and multiple similarities between target proteins. DDR applies non-linear similarity fusion method to combine different similarities. Before fusion, DDR performs a pre-processing step where a subset of similarities is selected in a heuristic process to obtain an optimized combination of similarities. Then, DDR applies a random forest model using different graph-based features extracted from the DTI heterogeneous graph. Using five repeats of 10-fold cross-validation, three testing setups, and the weighted average of area under the precision-recall curve (AUPR) scores, we show that DDR significantly reduces the AUPR score error relative to the next best start-of-the-art method for predicting DTIs by 34% when the drugs are new, by 23% when targets are new, and by 34% when the drugs and the targets are known but not all DTIs between them are not known. Using independent sources of evidence, we verify as correct 22 out of the top 25 DDR novel predictions. This suggests that DDR can be used as an efficient method to identify correct DTIs.

  18. Schriftstellerinnen der DDR und feministisches Bewußtsein im Staatssozialismus

    Directory of Open Access Journals (Sweden)

    Eva Kaufmann

    2001-11-01

    Full Text Available Seit den 1960er Jahren produzierten Schriftstellerinnen in der DDR wie Christa Wolf, Irmtraud Morgner, Sarah Kirsch, Brigitte Reimann, Charlotte Worgitzky, Lia Pirskawetz, und Maya Wiens eine vielfältige Literatur zu frauenrelevanten Themen. Den Obertitel „The Promised Land“ (das gelobte Land hat Lorna Martens Irmtraud Morgner entlehnt, der Autorin, die sie neben Christa Wolf als wichtigste Zeugin für „feminist writing“ in der DDR betrachtet. In Morgners Roman Leben und Abenteuer der Trobadora Beatriz steht der Begriff „gelobtes Land“ bezogen auf die DDR in einem ironischen Zusammenhang. Mit simplem Jaja oder Neinnein ist diesem „Ort des Wunderbaren“ (Morgner nicht beizukommen. Vergleichbares signalisiert auch das Fragezeichen, das Martens hinter den Begriff „Promised Land“ setzt. Der anspielungsreiche Verweis auf das Land erscheint auch insofern nützlich, als die Eigenart feministischen Schreibens genauer zu fassen ist, wenn über das Land selbst, namentlich seine Frauenpolitik, Auskünfte gegeben werden. Lorna Martens möchte herausfinden, wie Schriftstellerinnen in der DDR feministisches Bewusstsein artikuliert haben, d.h. feministisches Bewusstsein unter den vom Staatssozialismus geschaffenen Bedingungen.

  19. Komet 650. Project: Emission spectroscopy and acoustic pyrometry for control of modern steam generators. Final report; Komet 650. Teilprojekt: Emissionsspektroskopie und Schallpyrometrie zur Regelung moderner Dampferzeuger. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Moreno Rueda, R.; Frega Novales, L.; Ruiz, G.; Schulze-Kraasch, F.

    2002-01-31

    Two different techniques, i.e. acoustic pyrometry and emissionspectrometric tomography, were developed and combined into an online control system for optimization of gas and particle temperature and gas velocity both in flames and combustion chambers, in consideration of emissions and fuels, for a further improvement of the steam generator efficiency. [German] Das Ziel dieses Teilprojektes im BMBF-Verbundprogramm 'KOMET 650' war es, zwei unterschiedliche Messtechniken, die Schallpyrometrie und die emissionsspektroskopische Tomographie weiter zu entwickeln und zu einem onlinefaehigen Regelsystem zusammen zu fuehren. Letzteres soll sowohl die Einzelflammen als auch den gesamten Feuerraum bezueglich Gas-, Partikeltemperatur und Gasgeschwindigkeit unter Beachtung der Emissionen und unterschiedlicher Verbrennungseinsatzstoffe optimieren, und damit eine Verbesserung des Dampferzeugerwirkungsgrades zu bewirken. (orig.)

  20. The Candida albicans Ddr48 protein is essential for filamentation, stress response, and confers partial antifungal drug resistance.

    Science.gov (United States)

    Dib, Leila; Hayek, Peter; Sadek, Helen; Beyrouthy, Berna; Khalaf, Roy A

    2008-06-01

    Candida albicans is a dimorphic pathogenic fungus that causes mucosal and systemic infections. C. albicans pathogenicity is attributed to its ability to exist in different morphologic states and to respond to stress by up regulating several key genes. DDR48 is a stress-associated gene involved in DNA repair and in response to antifungal drug exposure. One allele of DDR48 was knocked out by homologous recombination that inserted a marker cassette in its position. Furthermore, reintroducing DDR48 on a plasmid created a revertant strain. Strains were grown on filamentation inducing and noninducing media, subjected to an oxidative stress challenge, injected into mice to assess virulence, and assayed for antifungal susceptibility by the E-test method. DDR48 was found to be haploid insufficient and possibly essential, since only a heterozygote, but not a homozygous, null mutant was generated. The mutant was filamentation defective on all hyphal media tested including serum and corn meal agar. Discrepancies in drug resistance profiles also were present: compared with the parental strain, DDR48/ddr48 heterozygote strain was susceptible in a dose-dependent manner to itraconazole and fluconazole and susceptible to ketoconazole. The mutant also appeared to be hypersensitive to a potentially lethal hydrogen peroxide challenge. However, no reduction in virulence of the mutant was observed. The present findings provide evidence that DDR48 is essential for filamentation, stress response, and possibly viability of C. albicans, making it a prime target for antifungal drug design.

  1. Large-signal characterization of DDR silicon IMPATTs operating in millimeter-wave and terahertz regime

    International Nuclear Information System (INIS)

    Acharyya, Aritra; Banerjee, J. P.; Chakraborty, Jit; Das, Kausik; Datta, Subir; De, Pritam; Banerjee, Suranjana

    2013-01-01

    The authors have carried out the large-signal characterization of silicon-based double-drift region (DDR) impact avalanche transit time (IMPATT) devices designed to operate up to 0.5 THz using a large-signal simulation method developed by the authors based on non-sinusoidal voltage excitation. The effect of band-to-band tunneling as well as parasitic series resistance on the large-signal properties of DDR Si IMPATTs have also been studied at different mm-wave and THz frequencies. Large-signal simulation results show that DDR Si IMPATT is capable of delivering peak RF power of 633.69 mW with 7.95% conversion efficiency at 94 GHz for 50% voltage modulation, whereas peak RF power output and efficiency fall to 81.08 mW and 2.01% respectively at 0.5 THz for same voltage modulation. The simulation results are compared with the experimental results and are found to be in close agreement. (semiconductor devices)

  2. Microarray data reveal relationship between Jag1 and Ddr1 in mouse liver.

    Directory of Open Access Journals (Sweden)

    Lara A Underkoffler

    Full Text Available Alagille syndrome is an autosomal dominant disorder involving bile duct paucity and cholestasis in addition to cardiac, skeletal, ophthalmologic, renal and vascular manifestations. Mutations in JAG1, encoding a ligand in the Notch signaling pathway, are found in 95% of patients meeting clinical criteria for Alagille syndrome. In order to define the role of Jag1 in the bile duct developmental abnormalities seen in ALGS, we previously created a Jag1 conditional knockout mouse model. Mice heterozygous for the Jag1 conditional and null alleles demonstrate abnormalities in postnatal bile duct growth and remodeling, with portal expansion and increased numbers of malformed bile ducts. In this study we report the results of microarray analysis and identify genes and pathways differentially expressed in the Jag1 conditional/null livers as compared with littermate controls. In the initial microarray analysis, we found that many of the genes up-regulated in the Jag1 conditional/null mutant livers were related to extracellular matrix (ECM interactions, cell adhesion and cell migration. One of the most highly up-regulated genes was Ddr1, encoding a receptor tyrosine kinase (RTK belonging to a large RTK family. We have found extensive co-localization of Jag1 and Ddr1 in bile ducts and blood vessels in postnatal liver. In addition, co-immunoprecipitation data provide evidence for a novel protein interaction between Jag1 and Ddr1. Further studies will be required to define the nature of this interaction and its functional consequences, which may have significant implications for bile duct remodeling and repair of liver injury.

  3. Channel Analysis for a 6.4 Gb s-1 DDR5 Data Buffer Receiver Front-End

    Science.gov (United States)

    Lehmann, Stefanie; Gerfers, Friedel

    2017-09-01

    In this contribution, the channel characteristic of the next generation DDR5-SDRAM architecture and possible approaches to overcome channel impairments are analysed. Because modern enterprise server applications and networks demand higher memory bandwidth, throughput and capacity, the DDR5-SDRAM specification is currently under development as a follow-up of DDR4-SDRAM technology. In this specification, the data rate is doubled to DDR5-6400 per IO as compared to the former DDR4-3200 architecture, resulting in a total per DIMM data rate of up to 409.6 Gb s-1. The single-ended multi-point-to-point CPU channel architecture in DDRX technology remains the same for DDR5 systems. At the specified target data rate, insertion loss, reflections, cross-talk as well as power supply noise become more severe and have to be considered. Using the data buffer receiver front-end of a load-reduced memory module, sophisticated equalisation techniques can be applied to ensure target BER at the increased data rate. In this work, the worst case CPU back-plane channel is analysed to derive requirements for receiver-side equalisation from the channel response characteristics. First, channel impairments such as inter-symbol-interference, reflections from the multi-point channel structure, and crosstalk from neighboring lines are analysed in detail. Based on these results, different correction methods for DDR5 data buffer front-ends are discussed. An architecture with 1-tap FFE in combination with a multi-tap DFE is proposed. Simulation of the architecture using a random input data stream is used to reveal the required DFE tap filter depth to effectively eliminate the dominant ISI and reflection based error components.

  4. Technical basis for the ITER detailed design report, cost review and safety analysis (DDR)

    International Nuclear Information System (INIS)

    1997-01-01

    The ITER Detailed Design Report (DDR), Cost Review and Safety Analysis is the 3rd major milestone representing the progress made in the ITER Engineering Design Activities. With the approval of the Interim Design Report (IDR), it has been possible to freeze the main concepts and system approaches for ITER and to develop the design in more detail for the individual components and sub-systems. This report, although designed to be fully understandable as a separate document, focusses particularly on the main changes since the IDR

  5. Technical basis for the ITER detailed design report, cost review and safety analysis (DDR)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    The ITER Detailed Design Report (DDR), Cost Review and Safety Analysis is the 3rd major milestone representing the progress made in the ITER Engineering Design Activities. With the approval of the Interim Design Report (IDR), it has been possible to freeze the main concepts and system approaches for ITER and to develop the design in more detail for the individual components and sub-systems. This report, although designed to be fully understandable as a separate document, focusses particularly on the main changes since the IDR. Refs, figs, tabs

  6. Experimental study on heavy-ion single event effect on nanometer DDR SRAM

    International Nuclear Information System (INIS)

    Luo Yinhong; Zhang Fengqi; Guo Hongxia; Zhou Hui; Wang Yanping; Zhang Keying

    2013-01-01

    Single event effect experimental study on 90 nm and 65 nm DDR SRAM were carried out, single event upset (SEU) cross section was discussed as a function of several parameters such as feature size, test pattern, incidence angle, supply voltage. Key influence factors and effect rule were analyzed. Feasibility of the current test method was discussed. Results indicate that, SEU cross section reduces as technologies scale down; the influence of test pattern and power supply on SEU cross section is small; tilt angle increases SEU cross section due to multiple upset increasement. The applicability of cosine tilt test method is correlative to ion species and linear energy transfer (LET) values. (authors)

  7. UV/Fenton photo-oxidation of Drimarene Dark Red (DDR) containing textile-dye wastewater

    Science.gov (United States)

    Hudaya, T.; Anthonios, J.; Septianto, E.

    2016-11-01

    Textile dye wastewater contains organic pollutants which are non-biodegradable, characterized by low BOD/COD ratio of typically Advanced Oxidation Processes (AOPs). One of the AOPs method which is the UV/H2O2/Fe2+ (or UV/Fenton) offers not only relatively low cost but also quite effective (in terms of color removal and reaction time) treatment. This particular research aimed to optimize the conditions of UV/Fenton photo-oxidation process for Drimarene Dark Red containing textile- dye wastewater. The two main operating conditions to be optimized were the initial concentration of H2O2 ranged between 0.022-0.078 %-w and the mol ratio of Fe2+: H2O2 was varied from 1: 13 up to 1: 45, using the Central Composite Design experimental matrix. The photo-oxidation was carried out at the optimum pH of 3 from some previous experiments. The best processing conditions of the photo-oxidation of Drimarene Dark Red (DDR) were found at the initial concentration of H2O2 at 0.050%-w and the mole ratio Fe2+: H2O2 of 1: 22. Under these conditions, the measured 2nd order pseudo-rate constantwas 0.021 M-1.min-1. The DDR color removal of 90% was surprisingly achievable within only 10 minutes reaction time.

  8. SU-F-SPS-08: Measuring the Interaction Of DDR Cell Receptors and Extracellular Matrix Collagen in Prostate Cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, J; Sarkar, A; Hoffmann, P [Wayne State University, Detroit, MI (United States); Suhail, A; Fridman, R [Wayne State University School of Medicine, Detroit, MI (United States)

    2016-06-15

    Purpose: Discoidin domain receptors (DDR) have recently been recognized as important players in cancer progression. DDRs are cell receptors that interact with collagen, an extracellular matrix (ECM) protein. However the detailed mechanism of their interaction is unclear. Here we attempted to examine their interaction in terms of structural (surface topography), mechanical (rupture force), and kinetic (binding probability) information on the single molecular scale with the use of atomic force microscopy (AFM). Methods: The Quantitative Nano-mechanical property Mapping (QNM) mode of AFM allowed to assess the cells in liquid growth media at their optimal physiological while being viable. Human benign prostate hyperplasia (BPH-1) cell line was genetically regulated to suppress DDR expression (DDR- cells) and was compared with naturally DDR expressing cells (DDR+). Results: Binding force measurements (n = 1000) were obtained before and after the two groups were treated with fibronectin (FN), an integrin-inhibiting antibody to block the binding of integrin. The quantification indicates that cells containing DDR bind with collagen at a most probable force of 80.3–83.0 ±7.6 pN. The probability of them binding is 0.167 when other interactions (mainly due to integrin-collagen binding) are minimized. Conclusion: Together with further force measurements at different pulling speeds will determine dissociation rate, binding distance and activation barrier. These parameters in benign cells provides some groundwork in understanding DDR’s behavior in various cell microenvironments such as in malignant tumor cells. Funding supported by Richard Barber Interdisciplinary Research Program of Wayne State University.

  9. SU-F-SPS-08: Measuring the Interaction Of DDR Cell Receptors and Extracellular Matrix Collagen in Prostate Cells

    International Nuclear Information System (INIS)

    Dong, J; Sarkar, A; Hoffmann, P; Suhail, A; Fridman, R

    2016-01-01

    Purpose: Discoidin domain receptors (DDR) have recently been recognized as important players in cancer progression. DDRs are cell receptors that interact with collagen, an extracellular matrix (ECM) protein. However the detailed mechanism of their interaction is unclear. Here we attempted to examine their interaction in terms of structural (surface topography), mechanical (rupture force), and kinetic (binding probability) information on the single molecular scale with the use of atomic force microscopy (AFM). Methods: The Quantitative Nano-mechanical property Mapping (QNM) mode of AFM allowed to assess the cells in liquid growth media at their optimal physiological while being viable. Human benign prostate hyperplasia (BPH-1) cell line was genetically regulated to suppress DDR expression (DDR- cells) and was compared with naturally DDR expressing cells (DDR+). Results: Binding force measurements (n = 1000) were obtained before and after the two groups were treated with fibronectin (FN), an integrin-inhibiting antibody to block the binding of integrin. The quantification indicates that cells containing DDR bind with collagen at a most probable force of 80.3–83.0 ±7.6 pN. The probability of them binding is 0.167 when other interactions (mainly due to integrin-collagen binding) are minimized. Conclusion: Together with further force measurements at different pulling speeds will determine dissociation rate, binding distance and activation barrier. These parameters in benign cells provides some groundwork in understanding DDR’s behavior in various cell microenvironments such as in malignant tumor cells. Funding supported by Richard Barber Interdisciplinary Research Program of Wayne State University

  10. Age-related modifications of type I collagen impair DDR1-induced apoptosis in non-invasive breast carcinoma cells.

    Science.gov (United States)

    Charles, Saby; Hassan, Rammal; Kevin, Magnien; Emilie, Buache; Sylvie, Brassart-Pasco; Laurence, Van-Gulick; Pierre, Jeannesson; Erik, Maquoi; Hamid, Morjani

    2018-05-07

    Type I collagen and DDR1 axis has been described to decrease cell proliferation and to initiate apoptosis in non-invasive breast carcinoma in three-dimensional cell culture matrices. Moreover, MT1-MMP down-regulates these effects. Here, we address the effect of type I collagen aging and MT1-MMP expression on cell proliferation suppression and induced-apoptosis in non-invasive MCF-7 and ZR-75-1 breast carcinoma. We provide evidence for a decrease in cell growth and an increase in apoptosis in the presence of adult collagen when compared to old collagen. This effect involves a differential activation of DDR1, as evidenced by a higher DDR1 phosphorylation level in adult collagen. In adult collagen, inhibition of DDR1 expression and kinase function induced an increase in cell growth to a level similar to that observed in old collagen. The impact of aging on the sensitivity of collagen to MT1-MMP has been reported recently. We used the MT1-MMP expression strategy to verify whether, by degrading adult type I collagen, it could lead to the same phenotype observed in old collagen 3D matrix. MT1-MMP overexpression abrogated the proliferation suppression and induced-apoptosis effects only in the presence of adult collagen. This suggests that differential collagen degradation by MT1-MMP induced a structural disorganization of adult collagen and inhibits DDR1 activation. This could in turn impair DDR1-induced cell growth suppression and apoptosis. Taken together, our data suggest that modifications of collagen structural organization, due to aging, contribute to the loss of the growth suppression and induced apoptosis effect of collagen in luminal breast carcinoma. MT1-MMP-dependent degradation and aging of collagen have no additive effects on these processes.

  11. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Thomale, Jürgen [Institute of Cell Biology, University Duisburg-Essen, 45122 Essen (Germany); Schupp, Nicole [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany)

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  12. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-01-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  13. Climate change and the Lower Weser region. Final report; Klimaaenderung und Unterweserregion (KLIMU) 'Fallstudie Weseraestuar'. Teilprojekt: Oekologischer Komplex. T. B: Klimasensitivitaet der Unterweser und ihrer Vorlaender. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Osterkamp, S.; Schirmer, M.

    2000-12-01

    The climate sensitivity of the aquatic, amphibic and terrestrial compartments of the lower Weser region was analyzed. This region, located between Bremen and Bremerhaven in northern Germany, is part of a bigger natural reserve ('Unterwesermarsch'). Vegetation and land use were mapped at the biotype level, and forecasts of changes to be expected were attempted on the basis of a regionalised climate scenario. Climate-induced changes in the topology of the headlands and in the morphology of the lower Weser river could not be taken into account. [German] In der vorliegenden Arbeit (Teil B: 'Klimasensitivitaet der Unterweser und ihrer Vorlaender') des Teilprojektes Oekologischer Komplex wird die Klimasensitivitaet der aquatischen, amphibischen und terrestrischen Lebensraeume der Unterweserregion analysiert. (Die Ergebnisse der Untersuchungen der Klimasensitivitaet der Marschen sind im Abschlussbericht des Teilprojektes Oekologischer Komplex, Teil A, Kraft and Schirmer 2000 beschrieben). Das Untersuchungsgebiet, im Norden Deutschlands zwischen Bremen und Bremerhaven gelegen, stellt den inneren Teil des Naturraumes Unterwesermarsch dar. Die Vegetation und die Nutzung des Gebietes wurde flaechendeckend auf der Ebene von Biotoptypenkartierungen erfasst. Prognosen der Flaechenbilanzen und der kuenftigen Veraenderung der Biotoptypen und der Fauna des Vorlandes und der Unterweser wurden auf der Grundlage eines regionalisierten Klimaszenarios vorgenommen. Klimabedingte Veraenderungen der Topografie der Vorlandbereiche und der Morphologie der Unterweser konnten innerhalb der vorliegenden Studie nicht beruecksichtigt werden. (orig.)

  14. Weibliche Arbeitserfahrungen in der DDR Women’s Work experiences in the GDR

    Directory of Open Access Journals (Sweden)

    Albrecht Wiesener

    2001-11-01

    Full Text Available Annegret Schüle kommt in ihrer Untersuchung zu dem Ergebnis, dass die DDR-Diktatur das Leben von Frauen mehr veränderte als das der Männer. Ihre auf Interviews basierende Untersuchung fokussiert den (Berufs-Alltag von Frauen in der Leipziger Baumwollspinnerei. Anhand der drei Kategorien „Generation“, „Frauenarbeit“ und „Vergemeinschaftung im Betrieb“ diskutiert sie die geführten Interviews , die Förderung weiblicher Erwerbstätiger einerseits und das Negativimage des Textilbetriebs andererseits. Die Autorin legt eine überzeugende Studie zur Erfahrungsgeschichte weiblicher Industriearbeit vor und zeigt am konkreten Beispiel, wie die DDR-Gesellschaft in einer von Frauen getragenen familiarisierten Betriebskultur nicht aufgebrochen, sondern in einer eigentümlichen Verbindung von Geborgenheit und Unterordnung reproduziert wurde.Schüle argues that the Eastern German dictatorship had a greater impact on the lives of women than on those of their male counterparts. Her research, based on interviews with female workers in a in a cotton-spinning factory in Leipzig, portrays women’s everyday-life and work, and offers a convincing study of the experience of female industrial workers. Using the three categories “cohort,” “women’s work,” and a discourse of “factory-as-community,” Schüle discusses her interviews with respect to the promotion of female textile workers on the one hand and the negative stereotypes associated with working in the textile industry on the other hand. Using concrete examples, Schüle demonstrates how a factory organised by women did not undermine the patriarchal frame in which it was embedded but how existing power differentials were reproduced as part of a discourse of family, security, and subordination.

  15. L'interconnexion entre la sécurité des communautés et les programmes de DDR: Un étude de terrain au Burundi

    NARCIS (Netherlands)

    Willems, R.C.; Kleingeld, J.; van Leeuwen, M

    2010-01-01

    The report is based on 10 weeks of field research in Burundi between April and June 2010, and looks at the linkages between community security and DDR. It opens with a discussion of local experiences with DDR programmes, analyzing the impact of its different components, and analyzing the local

  16. Genetic analysis identifies DDR2 as a novel gene affecting bone mineral density and osteoporotic fractures in Chinese population.

    Directory of Open Access Journals (Sweden)

    Yan Guo

    Full Text Available DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10-4, β: -0.018 for allele C, rs7553831 (P = 1.30×10-4, β: -0.018 for allele T, and rs6697469 (P = 1.59×10-3, β: -0.015 for allele C, separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10-4, β: -0.016 where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42 in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn't observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group.

  17. Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients

    International Nuclear Information System (INIS)

    Miao, Liyun; Zhang, Deping; Liu, Hongbing; Song, Yong; Wang, Yongsheng; Zhu, Suhua; Shi, Minke; Li, Yan; Ding, Jingjing; Yang, Jun; Ye, Qing; Cai, Hourong

    2014-01-01

    Although many of the recently approved genomically targeted therapies have improved outcomes for patients in non–small-cell lung cancer (NSCLC) with lung adenocarcinoma, little is known about the genomic alterations that drive lung squamous cell cancer (SCC) and development of effective targeted therapies in lung SCC is a promising area to be further investigated. Discoidin domain receptor 2 (DDR2), is a novel receptor tyrosine kinases that respond to several collagens and involved in tissue repair, primary and metastatic cancer progression. Expression of DDR2 mRNA was analyzed in 54 lung SCC tissues by qRT-PCR. Over-expression approaches were used to investigate the biological functions of DDR2 and its’ mutations in lung SCC cells. Conventional Sanger sequencing was used to investigate the mutations of DDR2 gene in 86 samples. The effect of DDR2 and its’ mutations on proliferation was evaluated by MTT and colony formation assays; cell migration and invasion was evaluated by trasnwell assays. Lung SCC cells stably transfected with pEGFP-DDR2 WT, pEGFP-DDR2-S131C or empty vector were injection into nude mice to study the effect of DDR2 and its’ mutation on tumorigenesis in vivo. Protein and mRNA expression levels of E-cadherin and MMP2 were determined by qRT-PCR and western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). In this study, we found that DDR2 mRNA levels were significantly decreased in 54 lung SCC tissues compared with normal lung tissues. Moreover, there were 3 novel DDR2 mutations (G531V, S131C, T681I) in 4 patients and provide the mutation rate of 4.6% in the 86 patients with lung SCC. The mutation of S131C in DDR2 could promote lung SCC cells proliferation, migration and invasion via inducing MMP-2, but reducing E-cadherin expression. These data indicated that the novel DDR2 mutation may contribute to the development and progression of lung SCC and this effect may be associated

  18. Waste Management Plan for the Drilling Within the Chromium Plume West of 100-D/DR Reactors

    International Nuclear Information System (INIS)

    R.E. Peterson

    1997-01-01

    This waste management plan provides guidance for managing drilling spoils generated during the installation of groundwater wells in the 100-D/DR Area, which is part of the 100-HR-3 Operable Unit. The wells are being installed to meet two objectives: (1) better define the nature and extent of a previously identified chromium plume in the area, and (2) act as groundwater extraction wells if the contamination warrants

  19. Diamond Based DDR IMPATTs: Prospects and Potentiality as Millimeter-Wave Source at 94 GHz Atmospheric Window

    Directory of Open Access Journals (Sweden)

    A. Acharyya

    2013-06-01

    Full Text Available Large-signal simulation is carried out in this paper to investigate the prospects and potentiality of Double-Drift Region (DDR Impact Avalanche Transit Time (IMPATT device based on semiconducting type-IIb diamond as millimeter-wave source operating at 94 GHz atmospheric window frequency. Large-signal simulation method developed by the authors and presented in this paper is based on non-sinusoidal voltage excitation. The simulation is carried out to obtain the large-signal characteristics such as RF power output, DC to RF conversion efficiency etc. of DDR diamond IMPATT device designed to operate at 94 GHz. The results show that the device is capable of delivering a peak RF power output of 7.01 W with 10.18% DC to RF conversion efficiency for a bias current density of 6.0×10^8 A m^-2 and voltage modulation of 60% at 94 GHz; whereas for the same voltage modulation 94 GHz DDR Si IMPATT can deliver only 693.82 mW RF power with 8.74 efficiency for the bias current density of 3.4×10^8 A m^-2.

  20. PEM-fuel cells for mobile application. Sub task: development of electrocatalysts. Final report; PEM-Brennstoffzelle fuer mobile Anwendung. Teilprojekt: Katalysatorenentwicklung. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Starz, K A

    1999-01-01

    PEM fuel cells are gaining increasing importance for use in automotive application. The goal of the research program reported here was to develop the basic technology and components for PEMFC stacks for use in transport applications. The sub-task of Degussa was to develop improved electrocatalysts for PEMFC single cells and stacks. The technical objectives of the research project were met. Electrocatalysts, characterized by a high Pt-dispersion, high surface area and excellent activity, were developed. With this material, considerable progress was made to reduce the total platinum loading of PEMFC cells and stacks to about 0,5 mgPt/cm{sup 2}. With this value, the goal of the program (<0,8 mg/cm{sup 2}) was significantly surpassed. Additionally, higher power densities of >0.4 W/cm{sup 2} were achieved at Degussa for hydrogen/air and reformate/air operation of the PEMFC. A CO-tolerant anode electrocatalyst, exhibiting a CO-tolerance of up to 100 ppm CO, enables the operation of PEMFC stacks with on-board generated methanol reformate. The performance of the new electrocatalyst materials was verified by DaimlerChrysler in a PEMFC demonstration stack at the end of the program. (orig.) [Deutsch] PEM-Brennstoffzellen gewinnen fuer die mobile Anwendung immer mehr an Bedeutung. Im Rahmen des hier beschriebenen Leitprojektes sollten die Basistechnologien fuer den Einsatz der PEM-Brennstoffzelle im mobilen Bereich (Elektrotraktion) entwickelt werden. Das Teilprojekt der Degussa befasst sich mit der Entwicklung von verbesserten Elektrokatalysatoren fuer PEM-Brennstoffzellenstacks. Die technischen Arbeitsziele des Vorhabens wurden erreicht. So konnten Elektrokatalysatoren bereitgestellt werden, die sich durch eine hohe Pt-Dispersion, eine grosse Pt-Oberflaeche sowie eine sehr gute Aktivitaet auszeichnen. Mit diesen Elektrokatalysatoren gelang es, die Platinbeladung der PEM-Elektroden (Anode und Kathode) erheblich abzusenken. Mit einer Gesamtplatinbeladung von 0,5 mg/cm{sup 2

  1. SAFIRA. Subproject B 3.1: reductive dechlorination of chloroaromatics by means of electrochemical methods and membrane-supported catalysts for in-situ treatment of contaminated groundwater. Final report; SAFIRA. Teilprojekt B 3.1: Reduktive Dechlorierung von Chloraromaten mit elektrochemischen Methoden und Membran-gestuetzten Katalysatoren zur in-situ-Behandlung von kontaminierten Grundwaessern. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Kopinke, F.D.; Mackenzie, K.; Koehler, R.; Battke, J.

    2002-12-31

    The objective of the sub-project was the development and experimental testing of a mainly passive, in situ technology for the abiotic dehalogenation of halogenated organic hydrocarbons (HOCs) within the aquifer. The technology to be developed should be applicable not only for aliphatic HOCs but also for dehalogenation of aromatic halogenated pollutants. During the first two years of the project, the main focus of our research was the development and testing of novel membrane-supported catalysts. The catalytically active component Pd was embedded in highly disperse form into non-porous silicone membranes in order to protect it from ionic catalyst poisons and erosion. At the laboratory scale, the novel catalysts proved their suitability for dehalogenation of various classes of HOCs within the water phase. The membrane-supported catalysts were developed in co-operation with a working group from the GKSS Geesthacht and their novelty was protected in a patent disclosure (DE 19952 732A1). Especially for their use under field conditions, membrane-supported Pd catalysts were produced as hollow fibres where the reaction partner hydrogen was fed from the interior of the fibres. Unfortunately, the high activity of these catalysts was not sustainable under Bitterfeld groundwater conditions - sulphur poisoning occurred due to non-ionic catalyst poisons situated in the aquifer and H{sub 2}S produced by sulphate-reducing bacteria. In order to enhance the catalyst stability and therefore their applicability in a scaled-up technology, our studies were then focused on the suppression of microbial activity and on catalyst regeneration. (orig.) [German] Das Ziel des Teilprojektes war die Entwicklung und experimentelle Pruefung eines weitgehend passiven, in-situ-tauglichen Verfahrens zur abiotischen Dehalogenierung von HKW im Aquifer, das auch auf halogenierte aromatische Verbindungen anwendbar ist. In den ersten zwei Jahren des Projektes stand die Entwicklung und Testung von Membran

  2. Description of work for the drilling within the chromium plume west of 100-D/DR Reactors

    International Nuclear Information System (INIS)

    Peterson, R.E.; Walker, L.D.

    1997-07-01

    This document describes the work scope associated with installing four new monitoring wells in the 100-D/DR Area (100-HR-3 Operable Unit). The strategy relies on estimates for flow paths that might have existed during operation of the 100-D Reactor and on experience gained during the recent installation of well 199-D4-1. A Data Quality Objectives (DQO) workshop was held to evaluate data collection needs during well installation. The workshop included input from key project team members and the lead regulatory agency. Decisions concerning data resulting from the DQO process have been incorporated into this document

  3. Schriftstellerinnen der DDR und feministisches Bewußtsein im Staatssozialismus GDR Women Authors and Feminist Consciousness During State Socialism

    Directory of Open Access Journals (Sweden)

    Eva Kaufmann

    2001-11-01

    Full Text Available Seit den 1960er Jahren produzierten Schriftstellerinnen in der DDR wie Christa Wolf, Irmtraud Morgner, Sarah Kirsch, Brigitte Reimann, Charlotte Worgitzky, Lia Pirskawetz, und Maya Wiens eine vielfältige Literatur zu frauenrelevanten Themen. Den Obertitel „The Promised Land“ (das gelobte Land hat Lorna Martens Irmtraud Morgner entlehnt, der Autorin, die sie neben Christa Wolf als wichtigste Zeugin für „feminist writing“ in der DDR betrachtet. In Morgners Roman Leben und Abenteuer der Trobadora Beatriz steht der Begriff „gelobtes Land“ bezogen auf die DDR in einem ironischen Zusammenhang. Mit simplem Jaja oder Neinnein ist diesem „Ort des Wunderbaren“ (Morgner nicht beizukommen. Vergleichbares signalisiert auch das Fragezeichen, das Martens hinter den Begriff „Promised Land“ setzt. Der anspielungsreiche Verweis auf das Land erscheint auch insofern nützlich, als die Eigenart feministischen Schreibens genauer zu fassen ist, wenn über das Land selbst, namentlich seine Frauenpolitik, Auskünfte gegeben werden. Lorna Martens möchte herausfinden, wie Schriftstellerinnen in der DDR feministisches Bewusstsein artikuliert haben, d.h. feministisches Bewusstsein unter den vom Staatssozialismus geschaffenen Bedingungen.From the 1960s on, women writers in the German Democratic Republic (GDR, including Christa Wolf, Irmtraud Morgner, Sarah Kirsch, Brigitte Reimann, Charlotte Worgitzky, Lia Pirskawetz, and Maya Wiens, produced a large body of writing on women’s issues. Martens wants to investigate how these women authors in the GDR have articulated their feminist consciousness under the conditions of state socialism. Martens’ use of the title The Promised Land is an allusion to a book by Irmtraud Morgner, an author whom, along with Christa Wolf, Martens considers one of the most important witnesses of feminist writing in the GDR. In Morgner’s book The Life and Adventures of Troubadour Beatriz the term “promised land” is being

  4. Implementing DDR in Settings of Ongoing Conflict: The Organization and Fragmentation of Armed Groups in the Democratic Republic of Congo (DRC

    Directory of Open Access Journals (Sweden)

    Joanne Richards

    2016-09-01

    Full Text Available Although it is common for armed groups to splinter (or “fragment” during contexts of multi-party civil war, current guidance on Disarmament, Demobilization, and Reintegration (DDR does not address the challenges that arise when recalcitrant fighters, unwilling to report to DDR, break ranks and form new armed groups. This Practice Note addresses this issue, drawing lessons from the multi-party context of the DRC and from the experiences of former members of three armed groups: the Rally for Congolese Democracy-Goma (RCD-Goma, the National Congress for the Defense of the People (CNDP, and the DRC national army (FARDC. While the findings indicate that the fragmentation of armed groups may encourage desertion and subsequent participation in DDR, they also show that active armed groups may monitor DDR programs and track those who demobilize. Remobilization may follow, either as active armed groups target ex-combatants for forced re-recruitment or as ex-combatants remobilize in armed groups of their own choice. Given these dynamics, practitioners in settings of partial peace may find it useful to consider non-traditional methods of DDR such as the use of mobile patrols and mobile disarmament units. The temporary relocation of ex-combatants to safe areas free from armed groups, or to protected transitional assistance camps, may also help to minimize remobilization during the reintegration phase.

  5. Whole Genome Analyses of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements

    Science.gov (United States)

    Egan, Jan B.; Barrett, Michael T.; Champion, Mia D.; Middha, Sumit; Lenkiewicz, Elizabeth; Evers, Lisa; Francis, Princy; Schmidt, Jessica; Shi, Chang-Xin; Van Wier, Scott; Badar, Sandra; Ahmann, Gregory; Kortuem, K. Martin; Boczek, Nicole J.; Fonseca, Rafael; Craig, David W.; Carpten, John D.; Borad, Mitesh J.; Stewart, A. Keith

    2014-01-01

    Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2. PMID:24505276

  6. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan B Egan

    Full Text Available Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  7. A novel Dance Dance Revolution (DDR) system for in-home training of stepping ability: basic parameters of system use by older adults.

    NARCIS (Netherlands)

    Smith, S.T.; Sherrington, C.; Studenski, S.A.; Schoene, D.; Lord, S.R.

    2011-01-01

    OBJECTIVE: This series of studies was conducted to develop and establish characteristics of exercise videogame play in older adults. The videogame was a modified version of the popular Dance Dance Revolution (DDR; Konomi). METHODS: Participants aged >/=70 were asked to make simple step movements in

  8. Well Completion Report for the Fiscal Year 1999 Drilling Within the Chromium Plume West of the 100-D/DR Reactors

    International Nuclear Information System (INIS)

    Ford, B. H.

    1999-01-01

    This report describes the fiscal year (FY) 1999 field activities associated with installing 12 groundwater monitoring wells in the vicinity of the 100-D Area chromium plume west of the 100-D/DR Reactors (100-HR-3 Operable Unit [OU]). The wells were installed to further investigate the extent of the hexavalent chromium hot spot west of the 100-D/DR Reactors and to support future remedial action decisions associated with the 100-HR-3 OU. These wells were designed for multi-purpose use (i.e., monitoring, extraction, and injection). In addition, one of the wells was installed to support the initial deployment of the In Situ Redox Manipulation (ISRM) technology to remediate the chromium plume

  9. Novel DDR Processing of Corn Stover Achieves High Monomeric Sugar Concentrations from Enzymatic Hydrolysis (230 g/L) and High Ethanol Concentration (10% v/v) During Fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiaowen; Jennings, Ed; Shekiro, Joe; Kuhn, Erik M.; O' Brien, Marykate; Wang, Wei; Schell, Daniel J.; Himmel, Mike; Elander, Richard T.; Tucker, Melvin P.

    2015-04-03

    Distilling and purifying ethanol, butanol, and other products from second and later generation lignocellulosic biorefineries adds significant capital and operating cost for biofuels production. The energy costs associated with distillation affects plant gate and life cycle analysis costs. Lower titers in fermentation due to lower sugar concentrations from pretreatment increase both energy and production costs. In addition, higher titers decrease the volumes required for enzymatic hydrolysis and fermentation vessels. Therefore, increasing biofuels titers has been a research focus in renewable biofuels production for several decades. In this work, we achieved over 200 g/L of monomeric sugars after high solids enzymatic hydrolysis using the novel deacetylation and disc refining (DDR) process on corn stover. The high sugar concentrations and low chemical inhibitor concentrations from the DDR process allowed ethanol titers as high as 82 g/L in 22 hours, which translates into approximately 10 vol% ethanol. To our knowledge, this is the first time that 10 vol% ethanol in fermentation derived from corn stover without any sugar concentration or purification steps has been reported. Techno-economic analysis shows the higher titer ethanol achieved from the DDR process could significantly reduce the minimum ethanol selling price from cellulosic biomass.

  10. Estimation of Most Favorable Optical Window Position Subject to Achieve Finest Optical Control of Lateral DDR IMPATT Diode Designed to Operate at W-Band

    Directory of Open Access Journals (Sweden)

    A. Acharyya

    2014-06-01

    Full Text Available The optimum position of the optical window (OW of illuminated lateral double-drift region (DDR impact avalanche transit time (IMPATT device has been determined subject to achieve the finest optical control of both DC and RF properties of the device. The OW is a tiny hole that has to be created on the oxide layer through which the light energy of appropriate wavelength can be coupled to the space charge region of the device. A non-sinusoidal voltage is assumed to be applied across the diode and the corresponding terminal current response is obtained from a two-dimensional (2-D large-signal (L-S simulation technique developed by the authors for illuminated lateral DDR IMPATT diode. Both the DC and L-S properties of the illuminated device based on Si, designed to operate at W-band frequencies (75 – 110 GHz are obtained from the said L-S simulation. Simulation is carried out for different incident optical power levels of different wavelengths (600 – 1000 nm by varying the position of the fixed sized OW on the oxide layer along the direction of electrical conduction of the device. Results show that, the most favorable optical tuning can be achieved when the OW is entirely created over the p-type depletion layer, i.e. when the photocurrent is purely electron dominated. Also the 700 nm wavelength is found to be most suitable wavelength for obtaining the maximum optical modulation of both DC and RF properties of the device.

  11. Nonlinear dynamics in chemical processes. Project A: Locally distributed periodic processes. Sub-project A3I: Catalitic afterburning. Nonlinear periodic front travelling processes. Final report; Nichtlineare Dynamik bei chemischen Prozessen. Projekt A: Oertlich verteilte periodische Prozesse. Teilprojekt A3I: Katalytische Nachverbrennung im Zirkulationsreaktor. Nichtlineare periodische Frontwanderungsprozesse. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Richter, M.; Reinhardt, H.J.; Roschka, E.

    1998-01-31

    The catalytic conversion of a HC/CHC mixture in a travelling reaction front was investigated in order to apply the circulation reactor principle to the catalytic afterburning of CHC-burdened off-gas. The sub-project `circulating reaction zones` comprised a model-supported analysis and synthesis for establishing process control concepts using the methods of nonlinear dynamics. The experiment showed that the circulation reactor adjusts to different states of operation autonomously. The region of stable oscillation shifts as a result of (reversible) deactivation of the catalyst. With suitable process control measures, the position-dependent maximum temperature of the circulating reaction front can be kept within the catalyst-specific limiting values for total oxidation resp. catalyst damage. On the basis fo the investigations, a technically mature concept for use of the circulation reactor for decomposition of hard-to-crack pollutants was obtained provided that a suitable catalyst is available. The main field of application is the catalytic afterburning of varying pollutant volumes in low-volume off-gas streams in order to make use of the autonomous adaptation of the reactor to a new operating state in case of changing reaction conditions. [Deutsch] Im Rahmen dieses Teilprojektes wurde die katalytische Zersetzung eines Kohlenwasserstoff-Chlorkohlenwasserstoff-Gemischs in wandernder Reaktionsfront untersucht, um das Prinzip des Zirkulationsreaktors auf die katalytische Nachverbrennung von CKW-haltigen Abgasen anzuwenden. Im Teilprojekt `Zirkulierende Reaktionszonen` erfolgte die modellgestuetzte Analyse und Synthese zur Ableitung von Prozessfuehrungskonzepten mit den Methoden der nichtlinearen Dynamik. Bei den Versuchen konnte ein autonomes Einschwingen des Zirkulationsreaktors auf verschiedene Betriebszustaende experimentell nachgewiesen werden. Der Bereich stabiler Oszillation verschiebt sich infolge (reversibler) Desaktivierung des Katalysators. Mit geeigneten

  12. Wie te laat komt! : het denken en handelen van de leden van het Politbüro en de regering van de DDR met betrekking tot het binnen- en buitenlands beleid gedurende de jaren 1985-1989

    NARCIS (Netherlands)

    Vogel, Pieter Johannes

    2011-01-01

    Met toepassing van de sociaal-constructivistische theorie van Wendt en de neo-institutionele theorie van Sabatier e.a. onderzocht Peter Vogel de situatie binnen het Politbüro en de regering in de nadagen (1985- 1989) van de DDR. Hij keek daarbij in hoeverre en in welke mate mentale constructies,

  13. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

    Science.gov (United States)

    Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

    2016-01-01

    Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (psleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells.

    Science.gov (United States)

    Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah; Pines, Alex; Bahjat, Mahnoush; Haazen, Lizette C J M; Olsen, Jesper V; Vrieling, Harry; Meerman, John H N; Mullenders, Leon H F; van de Water, Bob; Danen, Erik H J

    2013-01-22

    In pluripotent stem cells, DNA damage triggers loss of pluripotency and apoptosis as a safeguard to exclude damaged DNA from the lineage. An intricate DNA damage response (DDR) signaling network ensures that the response is proportional to the severity of the damage. We combined an RNA interference screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA damage repair, cell cycle and survival, and differentiation. Experimental probing of these networks identified a mode of DNA damage-induced Wnt signaling that limited apoptosis. Silencing or deleting the p53 gene demonstrated that genotoxic stress elicited Wnt signaling in a p53-independent manner. Instead, this response occurred through reduced abundance of Csnk1a1 (CK1α), a kinase that inhibits β-catenin. Together, our findings reveal a balance between p53-mediated elimination of stem cells (through loss of pluripotency and apoptosis) and Wnt signaling that attenuates this response to tune the outcome of the DDR.

  15. Balance del proceso de Desmovilización, Desarme y Reinserción (DDR de los bloques Cacique Nutibara y Héroes de Granada en la ciudad de Medellín Overview of the Process of Demobilization, Disarmament and Re-integration (DDR in the Cacique Nutibara and Héroes de Granada Blocks in the City of Medellín

    Directory of Open Access Journals (Sweden)

    Manuel Alberto Alonso Espinal

    2008-07-01

    Full Text Available El artículo realiza una descripción general y un balance del proceso de Desmovilización, Desarme y Reinserción (DDR de los bloques Cacique Nutibara y Héroes de Granada en la ciudad de Medellín. El primero, desmovilizado el 9 de diciembre de 2003, con 868 excombatientes y 467 armas entregadas; el segundo, el 1 de agosto de 2005, con 2.033 excombatientes y 1.120 armas entregadas. El artículo describe y analiza el proceso local, con base en las variables propuestas por Gleichman y su grupo de trabajo en el año de 2004, y lo contrapone con el nacional, a la vez que construye una serie hipótesis que se deben tener presentes a la hora de caracterizar la naturaleza del paramilitarismo en la ciudad. El resultado es un programa con fortalezas y logros, pero también con vacíos y limitaciones.This article carries out a general description and an overview of the processes of De-mobilization, Disarmament and Re-insertion (DDR in the Cacique Nutibara y Héroes de Granada blocks in the city of Medellín. The first of these areas, was demobilized December 9, 2003, with 868 ex-combatants and 467 weapons delivered; the second, August 1, 2005, with 2,033 ex-combatants and 1,120 weapons delivered. The article describes and analyzes the local processes, based on the variables proposed by Gleichman and his working group in the year 2004, it and contrasts them with the national one, at the same time building a series of hypotheses that should be kept in mind at the moment of characterizing the nature of para-militarism in the city. The result is a program with strengths and achievements, but also with empty spaces and limitations.

  16. Climate change and the Lower Weser region: Direct and indirect consequences of a climate change for the ecological situation in the Weser, the forelands and in the diked marshes. Final report; Klimaaenderung und Unterweserregion (KLIMU) 'Fallstudie Weseraestuar'. Direkte und indirekte Auswirkungen eines Klimawandels auf die oekologischen Verhaeltnisse in Weser, Vorland und Binnendeichsmarschen. Teilprojekt Oekologischer Komplex. T. A: Binnenland. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Kraft, D.; Schirmer, M.

    2001-03-01

    barrier or the reinforcement of the dikes) or in restrictions for the utilisation within storm surge relief polders. The possible future evolution of agriculture, as scetched in 'future scenarios', would - in case of intensification- be in contrast to the climate induced landscape evolution and act as a conflict promoter, whereas an extensification would be in line with landscape development and act reducing conflicts. (orig.) [German] Im Teilprojekt 'Oekologischer Komplex' des Verbundvorhabens 'Klimaaenderung und Unterweserregion' (KLIMU), ehemals 'Fallstudie Weseraestuar', werden die oekologischen Folgen eines Klimawandels fuer die Unterweser, die tidebeeinflussten Vorlaender und die eingedeichten Marschen abgeschaetzt. Fuer die Beschreibung des oekologischen Zustandes des Untersuchungsgebietes werden flaechendeckend die Biotoptypen nach DRACHENFELS aufgenommen und in einem GIS (ARC View/ARC Info) abgebildet, ergaenzt u.a. um Reliefdaten, Schutzstatus, landwirtschaftliche Nutzung und Bodenparameter. Wirkt auf diesen landschaftsoekologischen Status quo ein definiertes Zukunftsklima (Klimaszenario) mit +55 cm Meeresspiegel, +30 cm Tidehub, erhoehtem Jahresniederschlag (im Sommer -6%.) und um 2,7 C erhoehter Jahresmitteltemperatur ein, so ergeben sich die folgenden Auswirkungen (ohne Beruecksichtigung morphologischer Anpassung im Vorland), dargestellt im Abschlussbericht Teil A fuer die eingedeichte Marsch, und im Teil B fuer die Unterweser und die Vorlaender: die Flachwasserzonen in der Unterweser nehmen um 29%, die Wattflaechen um 55% und die Tideroehrichte um 250% zu; das unbedeichte Gruenland verliert seine landwirtschaftliche Nutzbarkeit und geht um 30% zurueck. CO{sub 2}- und Temperaturzunahme lassen die Biomasse des Roehrichts um bis zu 25% ansteigen, die Einwanderung von Neophyten und Neozoen wird beschleunigt. Insgesamt ergeben sich im Vorland naturnaehere Verhaeltnisse. Auch in der eingedeichten Marsch foerdert die erhoehte

  17. Decommissioning of NPP A-1

    International Nuclear Information System (INIS)

    Anon

    2009-01-01

    In this presentation the Operation history of A1 NPP, Project 'Decommissioning of A1 NPP' - I stage, Project 'Decommissioning of A1 NPP ' - II stage and Next stages of Project 'Decommissioning of A1 NPP ' are discussed.

  18. 1946 Whitewater-Animas DDR Aerial Photo Index

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — Aerial photographs are retrievable on a frame by frame basis. The aerial photo inventory contains imagery from various sources that are now archived at the Earth...

  19. An introduction to A1-homotopy theory

    International Nuclear Information System (INIS)

    Morel, F.

    2003-01-01

    This contribution covers simplicial sheaves, Quillen's homotopical algebra, unstable A 1 homotopy theory, connectivity and A 1 -localisation, stable A 1 homotopy theory of S 1 -spectra and P 1 -spectra

  20. A1C Test and Diabetes

    Science.gov (United States)

    ... Diagnosis The A1C Test & Diabetes The A1C Test & Diabetes On this page: What is the A1C test? ... the A1C test used to diagnose type 2 diabetes and prediabetes? Health care professionals can use the ...

  1. Hemoglobin A1c (HbA1c) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/hemoglobina1chba1ctest.html Hemoglobin A1c (HbA1c) Test To use the sharing features on this page, please enable JavaScript. What is a hemoglobin A1c (HbA1c) test? A hemoglobin A1c (HbA1c) test measures ...

  2. Blood Test: Hemoglobin A1C

    Science.gov (United States)

    ... Why Are Hemoglobin A1c Tests Done? When a child has diabetes, hemoglobin A1c levels are followed to see how well medicines are working. If a child with diabetes has a high hemoglobin A1c level, it may ...

  3. Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells

    DEFF Research Database (Denmark)

    Carreras Puigvert, Jordi; von Stechow, Louise; Siddappa, Ramakrishnaiah

    2013-01-01

    screen targeting all kinases, phosphatases, and transcription factors with global transcriptomics and phosphoproteomics to map the DDR in mouse embryonic stem cells treated with the DNA cross-linker cisplatin. Networks derived from canonical pathways shared in all three data sets were implicated in DNA...

  4. Led Astray by Hemoglobin A1c

    Directory of Open Access Journals (Sweden)

    Jean Chen MD

    2016-01-01

    Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

  5. NPP A-1 decommissioning - Phase I

    International Nuclear Information System (INIS)

    Krstenik, A.; Blazek, J.

    2000-01-01

    Nuclear power plant A-1 with output 150 MW e , with metallic natural uranium fuelled, CO 2 cooled and heavy water moderated reactor had been prematurely finally shut down in 1977. It is necessary to mention that neither operator nor regulatory and other authorities have been prepared for the solution of such situation. During next two consecutive years after shutdown main effort of operator focused on technical and administrative activities which are described in the previous paper together with approach, condition and constraints for NPP A-1 decommissioning as well as the work and research carried out up to the development and approval of the Project for NPP A-1 decommissioning - I. phase. Subject of this paper is description of: (1) An approach to NPP A -1 decommissioning; (2) An approach to development of the project for NPP A-1 decommissioning; (3) Project - tasks, scope, objectives; (4) Mode of the Project realisation; (5) Progress achieved up to the 1999 year. (authors)

  6. 32 CFR 352a.1 - Purpose.

    Science.gov (United States)

    2010-07-01

    ... DEFENSE FINANCE AND ACCOUNTING SERVICE (DFAS) § 352a.1 Purpose. Pursuant to the authority vested in the... Finance and Accounting Service (DFAS) as an Agency of the Department of Defense with responsibilities...

  7. Groundwater Energy Designer - Review of basic data and modification; Grundlagendatenueberpruefung und Anpassungen des Groundwater Energy Designer (Teilprojekt Programmoptimierung) - Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Poppei, J.; Mayer, G.; Schwarz, R.

    2009-12-15

    This report for the Swiss Federal Office of Energy (SFOE) reports on the extension and improvement of the Groundwater Energy Designer programme. A survey of selected existing small and medium sized ground-water heat pump systems formed the basis of the review. In this first phase of the project, a concept for measurement technologies to be used and the software changes necessary are discussed. The changes to the existing programme library to enable operation under Windows Vista, Windows 7 and Mac OSX are discussed. Also user dialogues were revised. New features and changes are presented and discussed, as are the functionality and user interface of the new version.

  8. 8 CFR 1274a.1 - Employer requirements.

    Science.gov (United States)

    2010-01-01

    ... 1274a.1 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE... proceedings. The procedures for hearings before an administrative law judge relating to civil penalties sought... administrative law judge and, to the extent relevant, to cases before an immigration judge or the Board of...

  9. Beyond HbA1c.

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-12-01

    It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience. The diaTribe Foundation convened a meeting on the topic of glycemic outcomes beyond HbA1c on 21 July 2017, in Bethesda (MD, USA), focusing on potential uses of continuous glucose monitoring (CGM). Understanding patterns of glycemia in people with diabetes has long been a focus of approaches to improving treatment, and over the past few years this has become an available modality for clinical practice. Glucose levels are not the only biologic parameters affecting HbA1c levels; HbA1c changes with anemia or, more subtly, with changes in rates of erythrocyte turnover not reflected in hemoglobin levels outside the normal range. Renal disease often is associated with lower HbA1c than would be predicted based on an individual's glycemic levels. Furthermore, HbA1c levels tend to increase with age and are higher in some ethnic groups; for example, people of African ethnicity have higher HbA1c levels than people of Northern European descent. Indeed, we have argued that even as a measure of mean glycemia HbA1c is inherently imprecise. Overall, for some 20% of people with diabetes, HbA1c levels are substantially higher, or substantially lower, than those that would be predicted from mean blood glucose levels. If one recognizes that HbA1c is, at best, a partial measure of mean glycemic exposure, one must surely accept that HbA1c does not reflect variability within a day, from day to day, and from period to period. Many glucose-lowering medicines, particularly the sulfonylureas and insulin, cause hypoglycemia, with consequent negative effects on quality of life and patient-reported outcomes, as well as association with weight gain and adverse macrovascular outcome; hypoglycemia will, of course, not be captured by HbA1c measurement. Based on these

  10. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

    Science.gov (United States)

    Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

    2010-01-01

    Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-κB ligand in the presence or absence of the A1R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A1R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A1R antagonist DPCPX inhibits osteoclast formation (IC50=1 nM), with altered morphology and reduced ability to resorb bone. A1R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A1R and further suggest that A1R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause.—Kara, F. M., Chitu, V., Sloane, J., Axelrod, M., Fredholm, B. B., Stanley, R., Cronstein, B. N. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PMID:20181934

  11. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

    OpenAIRE

    Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

    2010-01-01

    Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the pre...

  12. Decommissioning of NPP A1 - HWGCR type

    International Nuclear Information System (INIS)

    Burclova, J.

    1998-01-01

    Prototype nuclear power plant A-1 located at Jaslovske Bohunice, was a HWGCR with channel type reactor KS 150 (refuelling during operation) and capacity of 143 MWe. Single unit has been constructed with reactor hall building containing reactor vessel, heavy water system and equipment for spent fuel handling. Another compartment of main building contents coolant system piping, six steam generators and six turbo compressors, the turbine hall was equipped by three turbines. Unit also shares liquid radwaste treatment and storage buildings and ventilation systems including chimney. It started operation in 1972 and was shutdown in 1977 after primary coolant system integrity accident. In 1979 a final decision was made to decommission this plant. The absence of waste treatment technologies and repository and not sufficient storage capacity affected the planning and realization of decommissioning for NPP A-1. The decommissioning policy for the first stage is for lack of regulations based on 'case by case' strategy. For these reasons and for not existence of Decommissioning Found until 1995 the preferred decommissioning option is based on differed decommissioning with safe enclosure of confinement. Transfer of undamaged spent fuel cooled in organic coolant to Russia was finished in 1990. It was necessary to develop new technology for the damaged fuel preparation for transport. The barriers check-up and dismantling of secondary circuit and cooling towers was performed during 1989/90. The complex plan for the first phase of A-1 decommissioning - the status with treated operational radwaste, removed contamination and restored treated waste and spent fuel (in case of interruption of transfer to Russia) was developed in 1993-1994. Under this project bituminization of all liquid operational radwaste (concentrates) was performed during 1995/96, vitrification of inorganic spent fuel coolant started at 1996, decontamination of spent fuel pool coolant occurs (under AEA Technology

  13. Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis

    International Nuclear Information System (INIS)

    Boy, Christian; Meyer, Philipp T.; Kircheis, Gerald; Haussinger, Dieter; Holschbach, Marcus H.; Coenen, Heinz H.; Herzog, Hans; Elmenhorst, David; Kaiser, Hans J.; Zilles, Karl; Bauer, Andreas

    2008-01-01

    The cerebral mechanisms underlying hepatic encephalopathy (HE) are poorly understood. Adenosine, a neuromodulator that pre- and postsynaptically modulates neuronal excitability and release of classical neurotransmitters via A 1 adenosine receptors (A 1 AR), is likely to be involved. The present study investigates changes of cerebral A 1 AR binding in cirrhotic patients by means of positron emission tomography (PET) and [ 18 F]CPFPX, a novel selective A 1 AR antagonist. PET was performed in cirrhotic patients (n = 10) and healthy volunteers (n = 10). Quantification of in vivo receptor density was done by Logan's non-invasive graphical analysis (pons as reference region). The outcome parameter was the apparent binding potential (aBP, proportional to B max /K D ). Cortical and subcortical regions showed lower A 1 AR binding in cirrhotic patients than in controls. The aBP changes reached statistical significance vs healthy controls (p 1 AR binding may further aggravate neurotransmitter imbalance at the synaptic cleft in cirrhosis and hepatic encephalopathy. Different pathomechanisms may account for these alterations including decrease of A 1 AR density or affinity, as well as blockade of the A 1 AR by endogenous adenosine or exogenous xanthines. (orig.)

  14. Hyperparathyroidism complicating CYP 24A1 mutations.

    Science.gov (United States)

    Loyer, Camille; Leroy, Clara; Molin, Arnaud; Odou, Marie-Françoise; Huglo, Damien; Lion, Georges; Ernst, Olivier; Hoffmann, Maxime; Porchet, Nicole; Carnaille, Bruno; Pattou, François; Kottler, Marie-Laure; Vantyghem, Marie-Christine

    2016-10-01

    CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH) 2 D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD 3 /24-25-(OH)2D 3 >100 (Nhyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded. Copyright © 2016. Published by Elsevier Masson SAS.

  15. Experimental lysimetric device NPP A-1

    International Nuclear Information System (INIS)

    Matusek, I.; Plsko, J.

    2002-01-01

    In the frame of decommissioning of the NPP A-1 in the locality Jaslovske Bohunice the problem of remedial measures in scope of radioactive contaminated soils is also studied. These soils have originated in the area of the NPP A-1 by different mechanisms as the result of leakages from technology and in the present time they represent the secondary source of contamination of underground waters. Contaminated soils represent the particularity, because we can characterize them as voluminous radioactive contaminated residues with low-level or very low-level activity. EKOSUR Company in the frame of active underground water protection suggested more remedial measures. Two basic tasks are solved in the field of the contaminated soils: rehabilitation of contaminated soils or temporary immobilisation of radionuclides in the contaminated volumes, deposition of rehabilitated soils in the storage of landfill type. In the frame of engineering solution of the landfill storage the question of technology of own deposition of contaminated soils into storage area is important from the safety viewpoint. Therefore the Experimental lysimetric device was built for half-operational test of suggested technologies. This device contains 6 pieces of lysimeters with 6 active volumes of approximately 1 cubic meter. The aim of suggested and in the present time realised experiments is the practical modelling of influence of filtering of waters into storage of contaminated soils in configurational and qualitative different conditions of deposition of soils (for example exploitation of sorption materials). Also the structure of un-rehabilitated soils by the influence of natural downfalls activity is modelled in one lysimeter. In this issue the authors deal with the construction of lysimetric device, proposed experiments as like as gained results of observations. (authors)

  16. Ultraviolet A1 phototherapy: One center's experience

    Directory of Open Access Journals (Sweden)

    Sasi Kiran Attili

    2017-01-01

    Full Text Available Background: Ultraviolet A1(UVA1 phototherapy is increasingly being used in the treatment of morphea, atopic dermatitis, lupus and some other recalcitrant dermatoses. We present a retrospective review of our experience with this modality. Aim: To evaluate the treatment response rates for various dermatoses and adverse effects of UVA1 phototherapy. Methods: We reviewed phototherapy notes along with electronic and/or paper case records for all patients treated with UVA1 phototherapy from October 1996 to December 2008. Results: A total of 269 patients (outcomes available for 247 had 361 treatment courses (treatment data available for 317 courses over this period. We found phototherapy to be beneficial in 28 (53% of 53 patients with atopic dermatitis and 19 (51% of 37 patients with morphea. A beneficial outcome was recorded in all six (100% cases of urticaria and six (85.7% of seven patients treated for a polymorphic light eruption. Benefit was also recorded in systemic lupus erythematosus (8 (44.4% of 18, lichen sclerosus (6 (42.9% of 14, mastocytosis (2 (33.3% of 6, necrobiosis lipoidica (4 (30.8% of 13, granuloma annulare (2 (25% of 8, scleroderma (2 (22.2% of 9 and keloids (1 (7.7% of 13. Overall, treatment was well tolerated with no patients having to stop treatment due to adverse effects. Limitations: This is a retrospective study with no control group. Subjective/recall bias is quite possible as a number of patients were followed up over the phone. Conclusions: Our data suggest that ultraviolet A1 can be considered for the treatment of selected dermatoses. However, long-term malignancy risk is as yet unknown.

  17. Combining MOD10A1 and MYD10A1 Images For Snow Cover Area Monitoring

    Science.gov (United States)

    Tekeli, A. E.

    2008-12-01

    MOD10A1 and MYD10A1 daily snow cover maps at 500 m resolution are available from MODIS sensors on Terra and Aqua satellites. Aqua obtains the image of same region approximately three hours after Terra over Turkey region. MODIS is an optic sensor and cloud cover degrades the usability of derived snow cover maps. Moreover, spectral similarity between clouds and snow complicates their separability in visible imagery. Fortunately, dynamic behavior of clouds enables their discrimination from snow stationary on the surface. Combined use of MOD10A1 and MYD10A1 images mostly reduces the cloud cover present in one image alone and provides better representation of surface snow cover. Comparison of merged images with in situ data indicated higher hit ratios. The individual comparison of MOD10A1 and MYD10A1 images with ground data each yielded 31% hit ratio whereas, the merged images provided 38%. One-day shifts in comparisons increased hit ratios to 52 % and 46% whereas and two-day shifts gave 77 % and 79 % for MOD10A1 and MYD10A1 respectively. Merged maps yielded 54% and 83% for one and two day shifts. The improvement provided by the merging technique is found to be 7% for the present day, 7 % for one- day and 5% for two-day shifts for the whole season. Monthly decomposition resulted 25% improvement as the maximum. The snow cover product obtained by merging Terra and Aqua satellites provided higher hit ratios, as expected.

  18. Is the A1 a resonance

    International Nuclear Information System (INIS)

    Morgan, D.

    1975-06-01

    Data on diffractive and charge exchange 3π production in the Jsup(P) = 1 + state are shown to favour a resonance interpretation, although with a somewhat higher mass than the conventional A 1 bump. Data are fitted using a two-component model for the production amplitude. The first component comprises the Deck (Born) contribution and its re-scattering corrections; the second represents the so-called 'direct-production' term. The conventional isobar approximation to unitarity is demanded; this forbids the intrusion of additional phases in the Born term, such as arise from projecting a Reggeized Deck amplitude. As a consequence, the phase of the 1 + S 3π production amplitude is predicted to execute a standard resonant variation with Msup(3π). This carries a striking implication for the interfering 'background' waves, 1 + P, 2 - P, 0 - S, relative to which the 1 + S amplitude fails to register any appreciable phase variation in phenomenological analyses. There is no obvious objection to ascribing resonance status to these three channels, of which only one, the 0 - , demands a new (π ') resonance. A running theme, which recurs whenever the results of phenomenological 3-body phase shift analyses are appealed to, is that dynamical features are best viewed in terms of effective matrix elements rather than partial cross-sections. (author)

  19. Treadmill desks: A 1-year prospective trial.

    Science.gov (United States)

    Koepp, Gabriel A; Manohar, Chinmay U; McCrady-Spitzer, Shelly K; Ben-Ner, Avner; Hamann, Darla J; Runge, Carlisle F; Levine, James A

    2013-04-01

    Sedentariness is associated with weight gain and obesity. A treadmill desk is the combination of a standing desk and a treadmill that allow employees to work while walking at low speed. The hypothesis was that a 1-year intervention with treadmill desks is associated with an increase in employee daily physical activity (summation of all activity per minute) and a decrease in daily sedentary time (zero activity). Employees (n = 36; 25 women, 11 men) with sedentary jobs (87 ± 27 kg, BMI 29 ± 7 kg/m(2) , n = 10 Lean BMI 30 kg/m(2) ) volunteered to have their traditional desk replaced with a treadmill desk to promote physical activity for 1 year. Daily physical activity (using accelerometers), work performance, body composition, and blood variables were measured at Baseline and 6 and 12 months after the treadmill desk intervention. Subjects who used the treadmill desk increased daily physical activity from baseline 3,353 ± 1,802 activity units (AU)/day to, at 6 months, 4,460 ± 2,376 AU/day (P office workers without affecting work performance. Copyright © 2012 The Obesity Society.

  20. Architecture for a 1-GHz Digital RADAR

    Science.gov (United States)

    Mallik, Udayan

    2011-01-01

    An architecture for a Direct RF-digitization Type Digital Mode RADAR was developed at GSFC in 2008. Two variations of a basic architecture were developed for use on RADAR imaging missions using aircraft and spacecraft. Both systems can operate with a pulse repetition rate up to 10 MHz with 8 received RF samples per pulse repetition interval, or at up to 19 kHz with 4K received RF samples per pulse repetition interval. The first design describes a computer architecture for a Continuous Mode RADAR transceiver with a real-time signal processing and display architecture. The architecture can operate at a high pulse repetition rate without interruption for an infinite amount of time. The second design describes a smaller and less costly burst mode RADAR that can transceive high pulse repetition rate RF signals without interruption for up to 37 seconds. The burst-mode RADAR was designed to operate on an off-line signal processing paradigm. The temporal distribution of RF samples acquired and reported to the RADAR processor remains uniform and free of distortion in both proposed architectures. The majority of the RADAR's electronics is implemented in digital CMOS (complementary metal oxide semiconductor), and analog circuits are restricted to signal amplification operations and analog to digital conversion. An implementation of the proposed systems will create a 1-GHz, Direct RF-digitization Type, L-Band Digital RADAR--the highest band achievable for Nyquist Rate, Direct RF-digitization Systems that do not implement an electronic IF downsample stage (after the receiver signal amplification stage), using commercially available off-the-shelf integrated circuits.

  1. Alles Banane? Fiktionale Erinnerung an DDR und Wende in den ersten zwanzig Jahren nach dem Mauerfall

    NARCIS (Netherlands)

    Maczka, Iwona Maria

    2010-01-01

    How are the GDR and the fall of the Berlin Wall remembered? The dissertation “Alles Banane?” deals with this question. It assumes that identity, individual as well as collective, is a social, cultural and political construction based on the memory of the past. This construction is not only

  2. Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.

    Science.gov (United States)

    Harris, Dennis R; Tanaka, Masashi; Saveliev, Sergei V; Jolivet, Edmond; Earl, Ashlee M; Cox, Michael M; Battista, John R

    2004-10-01

    The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3' ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein.

  3. Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.

    Directory of Open Access Journals (Sweden)

    Dennis R Harris

    2004-10-01

    Full Text Available The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3' ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein.

  4. United Nations-Led Disarmament, Demobilization and Reintegration (DDR) in the Eastern Democratic Republic of Congo

    Science.gov (United States)

    2011-12-01

    absorb rebel units into the national army failed to deconstruct previous personal and ideological allegiances to the former rebel movement and thus...victors our outside interveners, such as India in Sri Lanka, the U.S. in Somalia and Haiti, and UN interventions in Albania and Haiti.30 Nevertheless...Reconstructing Masculinities : The Disarmament, Demobilization, and Reintegration of Former Combatants in Colombia.” Human Rights Quarterly, Vol.31

  5. Cytokine-induced 'bystander' senescence in DDR and immuno-surveillance

    Czech Academy of Sciences Publication Activity Database

    Hodný, Zdeněk; Hubáčková, Soňa; Bartek, Jiří

    2013-01-01

    Roč. 4, č. 10 (2013), s. 1552-1553 ISSN 1949-2553 Institutional support: RVO:68378050 Keywords : cell senescence * cytokines * immuno-surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.627, year: 2013

  6. Ein Werther der DDR : Plenzdorfs Neue Leiden des jungen W. im gespaltenen Deutschland

    OpenAIRE

    Jäger, Georg

    2009-01-01

    Die neuen Leiden des jungen W. wurden »bewußt auf Auslegbarkeit geschrieben« und irritierten die Kritiker durch »die ungeheure Breite der Assoziationsmöglichkeiten«. Durch die vier »strukturtragenden Schichten« oder Informationsebenen des Textes kommt es zu interferierenden Perspektiven: 1. die voranstehenden Dokumente (Zeitungsnotiz, drei Todesanzeigen), 2. »die szenisch-dialogisch objektivierte Erinnerungsperspektive der Eltern und Arbeitskollegen«, 3. die Kommentare Edgars »von jenseits de...

  7. MESSENGER E/V/H/SW EPPS CALIBRATED FIPS DDR V2.0

    Data.gov (United States)

    National Aeronautics and Space Administration — Abstract ======== This data set consists of the MESSENGER Energetic Particle and Plasma Spectrometer (EPPS) calibrated observations, also known as DDRs. The system...

  8. DDR-Landeskundliches im Deutschunterricht (East German Culture in the German Lesson).

    Science.gov (United States)

    Wazel, Gerhard

    1988-01-01

    Demonstrates with concrete examples from the texts of a German class for advanced learners how aspects of East German culture can be realized in vocabulary, in lectures, and in the development of listening comprehension and speaking skills. Texts are appended. (DJD)

  9. Evaluation of LLTR Series II tests A-1A and A-1B test results

    International Nuclear Information System (INIS)

    Shoopak, B.F.; Amos, J.C.; Norvell, T.J.

    1980-03-01

    The standard methodology, with minor modifications provides conservative yet realistic predictions of leaksite and other sodium system pressures in the LLTR Series II vessel and piping. The good agreement between predicted and measured pressures indicates that the TRANSWRAP/RELAP modeling developed from the Series I tests is applicable to larger scale units prototypical of the Clinch River steam generator design. Calculated sodium system pressures are sensitive to several modeling parameters including rupture disc modeling, acoustic velocity in the test vessel, and flow rate from the rupture tube. The acoustic velocity which produced best agreement with leaksite pressures was calculated based on the shroud diameter and shroud wall thickness. The corresponding rupture tube discharge coefficient was that of the standard design methodology developed from Series I testing. As found in Series I testing, the Series II data suggests that the leading edge of the flow in the relief line is two phase for a single, doubled-ended guillotine tube rupture. The steam generator shroud acts as if it is relatively transparent to the transmission of radial pressures to the vessel wall. Slightly lower sodium system maximum pressures measured during Test A-1b compared to Test A-1a are attributed to premature failure (failure at a lower pressure) of the rupture disc in contact with the sodium for test A-1b. The delay in failure of the second disc in Test A-1b, which was successfully modeled with TRANSWRAP, is attributed to the limited energy in the nitrogen injection

  10. Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia.

    Science.gov (United States)

    Teh, L K; Hashim, H; Zakaria, Z A; Salleh, M Z

    2012-08-01

    Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*, UUGT1A1*27 and UUGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UUGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction.

  11. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens

    2003-01-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...... effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement...

  12. Apolipoprotein A-1 (apoA-1) deposition in, and release from, the enterocyte brush border

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H; Rasmussen, Karina

    2012-01-01

    Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the pr......Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved...... transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen....

  13. 26 CFR 1.1311(a)-1 - Introduction.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Introduction. 1.1311(a)-1 Section 1.1311(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Readjustment of Tax Between Years and Special Limitations § 1.1311(a)-1 Introduction. (a...

  14. Cerebral adenosine A1 receptors are upregulated in rodent encephalitis

    NARCIS (Netherlands)

    Paul, Souman; Khanapur, Shivashankar; Boersma, Wytske; Sijbesma, Jurgen W.; Ishiwata, Kiichi; Elsinga, Philip H.; Meerlo, Peter; Doorduin, Janine; Dierckx, Rudi A.; van Waarde, Aren

    2014-01-01

    Adenosine A(1) receptors (A(1) Rs) are implied in the modulation of neuroinflammation. Activation of cerebral A(1) Rs acts as a brake on the microglial response after traumatic brain injury and has neuroprotective properties in animal models of Parkinson's disease and multiple sclerosis.

  15. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    NARCIS (Netherlands)

    Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; van den Dobbelsteen, Germie; van Ulsen, Peter; van der Ley, Peter; Kilian, Mogens; van de Winkel, Jan G. J.

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still

  16. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    DEFF Research Database (Denmark)

    Vidarsson, G; Overbeeke, N; Stemerding, AM

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...

  17. 26 CFR 1.501(a)-1 - Exemption from taxation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a) In...

  18. 26 CFR 31.3401(a)-1 - Wages.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Wages. 31.3401(a)-1 Section 31.3401(a)-1... Income Tax at Source § 31.3401(a)-1 Wages. (a) In general. (1) The term “wages” means all remuneration..., pensions, and retired pay are wages within the meaning of the statute if paid as compensation for services...

  19. Hemoglobin A1C: Past, present and future

    International Nuclear Information System (INIS)

    Aldasouqi, Saleh A.; Gossain, Ved V.

    2008-01-01

    Hemoglobin A1C (HbA1C) has been used for decades to monitor the controlof glycemia in diabetes. Although HbA1Cis currently undergoing a reassessmentand major developments have been underway in recent years, HbA1C is notrecommended at present for diabetes screening or diagnosis. The object ofthis review is to summarize the recent developments and to review a potentialdiagnostic role for HbA1C .Implementation of changes in HbA1C results andunits of measurements have been suggested for the purpose of teststandardization. These include lower reference ranges (by about 1.5-2 points)and measurement units expressed in percentage (%), as mg/dL (mmol/L) ormmol/mol (or a combination of these units). In diabetes screening anddiagnosis, the current diagnostic guidelines use measurement of plasmaglucose either fasting or after glucose load. These diagnostic methods haveshortcomings warranting a potential diagnostic role for HbA1C. While recentdevelopments in HbA1C methodologies are acknowledged, it is not yet knownwhich changes will be implemented and how soon. Given the recent literaturesupporting HbA1C diagnostic abilities and given the shortcomings of thecurrent guidelines, globally. Very recently, the first of suchrecommendations has been proposed by an expert panel as announced by the USEndocrine Society. (author)

  20. Drugs affecting HbA1c levels

    Directory of Open Access Journals (Sweden)

    Ranjit Unnikrishnan

    2012-01-01

    Full Text Available Glycated hemoglobin (HbA1c is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.

  1. 26 CFR 49.4262(a)-1 - Taxable transportation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Taxable transportation. 49.4262(a)-1 Section 49...) MISCELLANEOUS EXCISE TAXES FACILITIES AND SERVICES EXCISE TAXES Transportation of Persons § 49.4262(a)-1 Taxable transportation. (a) In general. Unless excluded under section 4262(b) (see § 49.4262(b)-1), taxable...

  2. Haemoglobin A1c : Historical overview and current concepts

    NARCIS (Netherlands)

    Lenters-Westra, Erna; Schindhelm, Roger K.; Bilo, Henk J.; Slingerland, Robbert J.

    Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a "gold

  3. Childhood presentation of COL4A1 mutations

    NARCIS (Netherlands)

    Shah, S.; Ellard, S.; Kneen, R.; Lim, M.; Osborne, N.; Rankin, J.; Stoodley, N.; van der Knaap, M.S.; Whitney, A.; Jardine, P.

    2012-01-01

    Aim To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. Method We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family

  4. Childhood presentation of COL4A1 mutations

    NARCIS (Netherlands)

    Shah, Siddharth; Ellard, Sian; Kneen, Rachel; Lim, Ming; Osborne, Nigel; Rankin, Julia; Stoodley, Neil; van der Knaap, Marjo; Whitney, Andrea; Jardine, Philip

    2012-01-01

    To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were

  5. An example of auto-anti-A1 agglutinins.

    Science.gov (United States)

    Wright, J; Lim, F C; Freedman, J

    1980-10-01

    The serum of an elderly man, group A, Le(a+b-), contained an IgM antibody that agglutinated his own cells and the cells of random group A1 donors. Over a period of 5 months, the titre of these auto-anti-A1 agglutinins was 4 at 22 degrees C.

  6. A1c Gear: Laboratory quality HbA1c measurement at the point of care.

    Science.gov (United States)

    Ejilemele, Adetoun; Unabia, Jamie; Ju, Hyunsu; Petersen, John R

    2015-05-20

    HbA1c is an important part of assessing the diabetic control and since the use of point-of-care devices for monitoring HbA1c is increasing, it is important to determine how these devices compare to the central laboratory. One hundred and twenty patient samples were analyzed on the Bio-Rad Variant™II and one POC analyzer (Sakae A1c Gear). Three patient sample pools containing ~5%, ~7%, and ~10% HbA1c levels were run over 20 days. Three reagent lots and three instruments were evaluated for the A1c Gear. The 120 patient samples showed strong correlation (R(2)>0.989) when compared to the Variant™II with means=8.06% and 7.81%, for Variant IIand A1c Gear, respectively. Changing reagent lots or instruments had no impact for the A1c Gear. The ~5%, ~7%, and ~10% pools within-run and between-run imprecision was between 0.87-1.33% and 1.03-1.32%, and 1.41-2.35% and 1.24-1.89% with total imprecision of 1.67-2.35% and 1.61-2.31% for the A1c Gear and Variant II, respectively. The A1c Gear showed a small negative bias (0.25% HbA1c) across HbA1c measurement ranges of Gear meets the criteria of total CV Gear can give results as precise as the laboratory at the POC. Copyright © 2015. Published by Elsevier B.V.

  7. [About the HbA1c in the elderly].

    Science.gov (United States)

    Farcet, Anaïs; Delalande, Géraldine; Oliver, Charles; Retornaz, Frédérique

    2016-03-01

    HbA1c product of non enzymatic glycation of HbA increases in relation with the mean blood glucose level during the former 2-3 months. HbA1c levels are correlated with the development of diabetic complications and HbA1c assessment is now the gold standard for evaluation of diabetes control. HbA1c level should not be higher than 7% to avoid these complications. However, in aged peoples, the objectives of diabetes control vary according to their health status. It must be good with HbA1c lower than 7-7.5% in healthy subjects and more relax in subjects with symptoms of frailty and risks of non perceived and self corrected hypoglycemia. Under these conditions, HbA1c values lower than 8 to 9% are advised. Nevertheless, hypoglycemia episodes may occur in patients with high HbA1c and capillary glucose follow-up is necessary for detection of such complications.

  8. Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

    Science.gov (United States)

    Rawłuszko-Wieczorek, Agnieszka Anna; Horst, Nikodem; Horbacka, Karolina; Bandura, Artur Szymon; Świderska, Monika; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2015-08-01

    Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Metamorphosis of NPP A1, V1, V2

    International Nuclear Information System (INIS)

    Dobak, D.; Moncekova, M.

    2005-01-01

    In this book the history of construction, commissioning and exploitation of NPP A1, NPP V1 and NPP V2 in Jaslovske Bohunice is presented on documentary photos. Vicinity around of these NPPs is presented, too

  10. 7 CFR 15a.1 - Purpose and effective date.

    Science.gov (United States)

    2010-01-01

    ... FROM FEDERAL FINANCIAL ASSISTANCE Introduction § 15a.1 Purpose and effective date. The purpose of this... education program or activity receiving Federal financial assistance, whether or not such program or...

  11. AMP is an adenosine A1 receptor agonist.

    Science.gov (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

    2012-02-17

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  12. Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

    Science.gov (United States)

    Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

    2018-05-25

    Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Impact of FDA-Approved Drugs on the Prostaglandin Transporter OATP2A1/SLCO2A1.

    Science.gov (United States)

    Kamo, Shunsuke; Nakanishi, Takeo; Aotani, Rika; Nakamura, Yoshinobu; Gose, Tomoka; Tamai, Ikumi

    2017-09-01

    To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored the impact of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty-one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with that on PGE 2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related to prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil, and losartan potassium, exhibited more than 90% PGE 2 uptake inhibition. Inhibitory affinity of suramin to OATP2A1 was the highest (IC 50,2A1 of 0.17 μM), and its IC 50 values to MRP4-mediated PGE 2 transport (IC 50,MRP4 ) and PGE 2 synthesis in human U-937 cells treated with phorbol 12-myristate 13-acetate (IC 50,Syn ) were 73.6 and 336.7 times higher than IC 50,2A1 , respectively. Moreover, structure-activity relationship study in 29 nonsteroidal anti-inflammatory drugs contained in the library displayed inhibitory activities of anthranilic acid derivatives, but enhancing effects of propionic acid derivatives. These results demonstrate that suramin is a potent selective inhibitor of OATP2A1, providing a comprehensive information about drugs in clinical use that interact with OATP2A1. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. PEM fuel cells for mobile applications. Project part: Membrane development. Final report; PEM-Brennstoffzellen fuer mobile Anwendungen. Teilprojekt: Membranentwicklung. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Frank, G

    1999-01-20

    Polymer-Electrolyte-Membrane Fuel Cells (PEMFC) are attractive candidates for next century propulsion systems in passenger cars. The technical feasibility has been demonstrated by several car manufacturers. Today, PEMFC lack economical viability. One of the reasons is the cost of currently used materials, e.g. membranes. This project target towards the development of low cost, non-fluorinated membranes, which fulfil all technical requirements in PEMFC systems. In the frame of this project we were able to successfully develop new membranes based on polyaromatic polymers, which can be produced on a technical scale. These membranes enabled high power densities, exceeding 700 mW/cm{sup 2} at 80 C and their longevity has been demonstrated successfully up to 5,000 hours. Therefore, these membranes have sufficient electrochemical stability for the application in fuel cells. The prices in mass production for these new membranes can get significantly below prices of fluorinated membranes. (orig.) [Deutsch] Polymer-Elektrolyt-Membran-Brennstoffzellen (PEMFC) gelten als aussichtsreiche Kandidaten fuer alternative Fahrzeugantriebe fuer das naechste Jahrzehnt. Die technische Machbarkeit ist bereits mehrfach demonstriert worden. Allerdings sind die Kosten der PEMFC-Systeme noch zu hoch u.a. durch zu hohe Kosten der eingesetzten Materialien, so auch der Membranen. Ziel des Projektes war daher die Entwicklung kostenguenstiger, nichtfluorierter Membranen, die die technischen Anforderungen fuer die Anwendung in der PEM-Brennstoffzelle erfuellen. Im Projekt konnten erfolgreich Membranen auf Basis polyaromatischer Polymere entwickelt werden, die sich auch im technischen Massstab herstellen lassen. Die Membranen ermoeglichen hohe Leistungsdichten groesser 700 mW/cm{sup 2} bei Betriebstemperaturen von 80 C. Die Lebensdauer der Membranen wurde erfolgreich ueber 5.000 Stunden nachgewiesen. Die elektrochemische Stabilitaet der untersuchten Materialien ist damit gegeben. Die Preise dieser Membranen koennen in Massenfertigung deutlich unter den heutigen Preisen verfuegbarer fluorierter Membranen liegen. (orig.)

  15. ARTS - adaptive runtime system for massively parallel systems. Final report; ARTS - optimale Ausfuehrungsunterstuetzung fuer komplexe Anwendungen auf massiv parallelen Systemen. Teilprojekt: Parallele Stroemungsmechanik. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Gentzsch, W.; Ferstl, F.; Paap, H.G.; Riedel, E.

    1998-03-20

    In the ARTS project, system software has been developed to support smog and fluid dynamic applications on massively parallel systems. The aim is to implement and test specific software structures within an adaptive run-time system to separate the parallel core algorithms of the applications from the platform independent runtime aspects. Only slight modifications is existing Fortran and C code are necessary to integrate the application code into the new object oriented parallel integrated ARTS framework. The OO-design offers easy control, re-use and adaptation of the system services, resulting in a dramatic decrease in development time of the application and in ease of maintainability of the application software in the future. (orig.) [Deutsch] Im Projekt ARTS wird Basissoftware zur Unterstuetzung von Anwendungen aus den Bereichen Smoganalyse und Stroemungsmechanik auf massiv parallelen Systemen entwickelt und optimiert. Im Vordergrund steht die Erprobung geeigneter Strukturen, um systemnahe Funktionalitaeten in einer Laufzeitumgebung anzusiedeln und dadurch die parallelen Kernalgorithmen der Anwendungsprogramme von den plattformunabhaengigen Laufzeitaspekten zu trennen. Es handelt sich dabei um herkoemmlich strukturierten Fortran-Code, der unter minimalen Aenderungen auch weiterhin nutzbar sein muss, sowie um objektbasiert entworfenen C-Code, der die volle Funktionalitaet der ARTS-Plattform ausnutzen kann. Ein objektorientiertes Design erlaubt eine einfache Kontrolle, Wiederverwendung und Adaption der vom System vorgegebenen Basisdienste. Daraus resultiert ein deutlich reduzierter Entwicklungs- und Laufzeitaufwand fuer die Anwendung. ARTS schafft eine integrierende Plattform, die moderne Technologien aus dem Bereich objektorientierter Laufzeitsysteme mit praxisrelevanten Anforderungen aus dem Bereich des wissenschaftlichen Hoechstleistungsrechnens kombiniert. (orig.)

  16. Trimester-specific reference intervals for haemoglobin A(1c) (HbA(1c)) in pregnancy.

    LENUS (Irish Health Repository)

    O'Connor, Catherine

    2011-11-26

    Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol\\/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol\\/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol\\/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol\\/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol\\/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

  17. Implementation of the II. Stage decommissioning of A1 NPP

    International Nuclear Information System (INIS)

    Ficher, T.

    2015-01-01

    Presentation is focused on the implementation of the II. stage decommissioning of A1 NPP. Introductory part focuses on brief characteristics of the power plant with a history of operation, basic technical parameters and actions that were made after operation. The next section describes the basic schedule for decommissioning, structure of management and implementation of the II. stage decommissioning of the A1 NPP and objectives of the individual stages. The last and largest part of the presentation is devoted to detailed description of the II. stage decommissioning of the A1 NPP, its individual tasks and verbal and visual description of the activities that were performed. Presented is decommissioning of the technology and construction of external objects NPP A1 including storage tanks for liquid RAW, next are presented activities carried out in the Main Production Unit - decommissioning of non-operating technologies in various places/rooms, management of waste arising from these activities, treatment of case of A1 long-term spent fuel storage and long-term spent fuel storage. The subsequent section is devoted to the management and handling of contaminated soil, concrete and construction waste, including management of VLLW. (authors)

  18. Current Status of HbA1c Biosensors

    Science.gov (United States)

    Lin, Hua; Yi, Jun

    2017-01-01

    Glycated hemoglobin (HbA1c) is formed via non-enzymatic glycosylation reactions at the α–amino group of βVal1 residues in the tetrameric Hb, and it can reflect the ambient glycemic level over the past two to three months. A variety of HbA1c detection methods, including chromatography, immunoassay, enzymatic measurement, electrochemical sensor and capillary electrophoresis have been developed and used in research laboratories and in clinics as well. In this review, we summarize the current status of HbA1c biosensors based on the recognition of the sugar moiety on the protein and also their applications in the whole blood sample measurements. PMID:28777351

  19. AMP Is an Adenosine A1 Receptor Agonist*

    Science.gov (United States)

    Rittiner, Joseph E.; Korboukh, Ilia; Hull-Ryde, Emily A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

    2012-01-01

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5′-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5′-monophosphonate, ACP) directly activated the adenosine A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A1R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A1R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A1R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine. PMID:22215671

  20. [Microsurgical anatomy importance of A1-anterior communicating artery complex].

    Science.gov (United States)

    Monroy-Sosa, Alejandro; Pérez-Cruz, Julio César; Reyes-Soto, Gervith; Delgado-Hernández, Carlos; Macías-Duvignau, Mario Alberto; Delgado-Reyes, Luis

    2013-01-01

    The anterior cerebral artery originates from the bifurcation of the internal carotid artery lateral to the optic chiasm, then joins with its contralateral counterpart via the anterior communicating artery. A1-anterior communicating artery complex is the most frequent anatomical variants and is the major site of aneurysms between 30 to 37%. Know the anatomy microsurgical, variants anatomical and importance of complex precommunicating segment-artery anterior communicating in surgery neurological of the pathology vascular, mainly aneurysms, in Mexican population. The study was performed in 30 brains injected. Microanatomy was studied (length and diameter) of A1-anterior communicating artery complex and its variants. 60 segments A1, the average length of left side was 11.35 mm and 11.84 mm was right. The average diameter of left was 1.67 mm and the right was 1.64 mm. The average number of perforators on the left side was 7.9 and the right side was 7.5. Anterior communicating artery was found in 29 brains of the optic chiasm, its course depended on the length of the A1 segment. The average length of the segment was 2.84 mm, the average diameter was 1.41 mm and the average number of perforators was 3.27. A1-anterior communicating artery complex variants were found in 18 (60%) and the presence of two blister-like aneurysms. It is necessary to understand the A1-anterior communicating artery complex microanatomy of its variants to have a three-dimensional vision during aneurysm surgery.

  1. Neutron density optimal control of A-1 reactor analoque model

    International Nuclear Information System (INIS)

    Grof, V.

    1975-01-01

    Two applications are described of the optimal control of a reactor analog model. Both cases consider the control of neutron density. Control loops containing the on-line controlled process, the reactor of the first Czechoslovak nuclear power plant A-1, are simulated on an analog computer. Two versions of the optimal control algorithm are derived using modern control theory (Pontryagin's maximum principle, the calculus of variations, and Kalman's estimation theory), the minimum time performance index, and the quadratic performance index. The results of the optimal control analysis are compared with the A-1 reactor conventional control. (author)

  2. The Correlation of Hemoglobin A1c to Blood Glucose

    OpenAIRE

    Sikaris, Ken

    2009-01-01

    The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this ...

  3. How does CKD affect HbA1c?

    Science.gov (United States)

    Bloomgarden, Zachary; Handelsman, Yehuda

    2018-04-01

    HOW DOES CHRONIC KIDNEY DISEASE AFFECT HBA1C?: A number of factors determine HbA1c other than the level of glucose exposure alone. In an subset analysis of the Atherosclerosis Risk in Communities study of 941 diabetic people with varying degrees of chronic kidney disease (CKD), as well as 724 who did not have CKD, and mean age in the eighth decade, Jung et al. ask whether HbA1c is reliable as an indicator of glycemia in people with kidney disease (CKD) to the same degree as in those not having kidney disease, and, if not, whether measures of glycated serum proteins may be more useful. The only available measure of glycemia for comparison was a single fasting glucose level, and the authors acknowledge that this gives an incomplete measure, particularly in people with relatively mild diabetes, whose mean HbA1c was 6.4%, with most having levels of 7.5% or lower. In patients of this sort, postprandial glucose levels may better explain variations in mean HbA1c. Recognizing that the dataset may be limited, Jung et al. nevertheless give an intriguingly negative answer to the first question, of the reliability of HbA1c with kidney disease. Using Deming regression analysis, Jung et al. showed that the correlation between HbA1c and fasting glucose weakens as renal function worsens, and, moreover, that this appears particularly to be the case in people with anemia (hemoglobin men and women, respectively), confirming earlier observations. Among those diabetic people with neither anemia nor CKD, the correlation coefficient between HbA1c and fasting glucose was r = 0.70, compared with r = 0.35 among those with both anemia and very severe CKD (estimated glomerular filtration rate [eGFR] perform SMBG to more adequately interpret HbA1c results. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  4. Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function.

    Directory of Open Access Journals (Sweden)

    Katrin Sebastian

    Full Text Available Organic anion transporting polypeptides (OATP/SLCO have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20 and genes implicated in developmental processes (e.g. TGM2. A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration.

  5. Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

    Science.gov (United States)

    Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

    2007-01-01

    Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

  6. Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

    African Journals Online (AJOL)

    α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

  7. Crystal structure, characterization and magnetic properties of a 1D ...

    Indian Academy of Sciences (India)

    Crystal structure, characterization and magnetic properties of a 1D copper(II) polymer incorporating a Schiff base with carboxylate side arm. SHYAMAPADA SHIT MADHUSUDAN NANDY CORRADO RIZZOLI CÉDRIC DESPLANCHES SAMIRAN MITRA. Regular Article Volume 128 Issue 6 June 2016 pp 913-920 ...

  8. Impact of corpulence parameters and haemoglobin A1c on ...

    African Journals Online (AJOL)

    We assessed the utility of body mass index (BMI), waist circumference (WC), and glycosylated haemoglobin (HbA1c) levels in metabolic control for type 2 diabetic patients. ... The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women.

  9. IEA SHC Task 42/ECES Annex 29 WG A1

    DEFF Research Database (Denmark)

    Ristić, Alenka; Furbo, Simon; Moser, Christoph

    2016-01-01

    An overview on the recent results on the engineering and characterization of sorption materials, PCMs and TCMs investigated in the working group WG A1 “Engineering and processing of TES materials” of IEA SHC Task 42 / ECES Annex 29 (Task 4229) entitled “Compact Thermal Energy Storage” is presented....

  10. Design of a 1 Tb/s superchannel coherent receiver

    NARCIS (Netherlands)

    Millar, D.S.; Maher, R.; Lavery, D.; Koike-Akino, T.; Pajovic, M.; Alvarado, A.; Paskov, M.; Kojima, K.; Parsons, K.; Thomsen, B.C.; Savory, S.J.; Bayvel, P.

    2016-01-01

    We describe the design of a trained and pilot-aided digital coherent receiver, capable of detecting a 1 Tb/s superchannel with a single optical front-end. Algorithms for receiver training are described, which calculate the equalizer coefficients, subchannel SNRs, and centroids of the transmitted

  11. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    Purpose: To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. Methods: The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. Results: In four families with

  12. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2010-01-01

    To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. In four families with mild osteogenesis

  13. Regulatory analysis for USI A-1, Water Hammer

    International Nuclear Information System (INIS)

    Serkiz, A.W.

    1984-03-01

    This is the staff's regulatory analysis dealing with the resolution of the Unresolved Safety Issue A-1, Water Hammer. This report contains the value-impact analysis for this issue, public comments received, and staff response, or action taken, in response to those comments. The staff's technical findings regarding water hammer in nuclear power plants are contained in NUREG-0927

  14. 26 CFR 1.167(a)-1 - Depreciation in general.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Depreciation in general. 1.167(a)-1 Section 1... Depreciation in general. (a) Reasonable allowance. Section 167(a) provides that a reasonable allowance for the... the taxpayer for the production of income shall be allowed as a depreciation deduction. The allowance...

  15. 26 CFR 31.3231(a)-1 - Who are employers.

    Science.gov (United States)

    2010-04-01

    ... insubstantial. (d) The term “employer” does not include any street, interurban, or suburban electric railway... Railroad Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(a)-1... connection with— (a) The transportation of passengers or property by railroad, or (b) The receipt, delivery...

  16. Low energy dynamics of self-dual A1 strings

    International Nuclear Information System (INIS)

    Gustavsson, Andreas

    2003-01-01

    We examine the interrelation between the (2,0) supersymmetric six-dimensional effective action for the A 1 theory, and the corresponding low-energy theory for the collective coordinates associated to selfdual BPS strings. We argue that this low energy theory is a two-dimensional N=4 supersymmetric sigma model

  17. Double Regge model for non diffractive A1 production

    International Nuclear Information System (INIS)

    Anjos, J.C.; Endler, A.; Santoro, A.; Simao, F.R.A.

    1977-07-01

    A Reggeized double-nucleon-exchange model is shown to be able to to reproduce qualitatively the non-diffractive A 1 production recently observed in the reaction K - p → Σ - π + π - π + at 4.15 GeV/c

  18. 26 CFR 1.926(a)-1 - Distributions to shareholders.

    Science.gov (United States)

    2010-04-01

    ... either of the administrative pricing methods of section 925(a)(1) or (2), (D) Out of earnings and profits... pricing method of section 925(a)(3), (E) Out of earnings and profits attributable to section 923(a)(2) non... income and other exempt foreign trade income determined under either of the administrative pricing...

  19. Decommissioning of the NPP A-1 heavy water management system

    International Nuclear Information System (INIS)

    Medved, J.; Rezbarik, J.; Vargovcik, L.; Vykukel, I.

    2015-01-01

    The paper deals with experience and techniques in the application of decontamination technology and remotely controlled robotic devices for the decontamination and dismantling of the heavy water management system during undergoing decommissioning process of the A-1 NPP as well as treatment of arising liquid waste All of these activities are characterized by high level of radioactivity and contamination. (authors)

  20. Relationships between hemoglobin A1c and spot glucose ...

    African Journals Online (AJOL)

    Background: Glycosylated hemoglobin, HbA1c is the most acceptable measure of chronic glycemia. It is not widely available and/or affordable in Nigeria. The mean of the monthly fasting plasma glucose (MFPG) of the preceding 3 months is often used as surrogate for assessing chronic glycemia. Objective: To determine the ...

  1. Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus.

    Science.gov (United States)

    McGrath, H

    2017-10-01

    Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these

  2. Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

    Science.gov (United States)

    2017-01-01

    Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of

  3. Annex A1: cornerstone of the five-yearly review

    CERN Multimedia

    Staff Association

    2016-01-01

    As a reminder; the purpose of the five-yearly review is to review the financial and social conditions of all CERN personnel whether employed (MPE) or associated (MPA)! In December 2015, the CERN Council approved the package proposed by the Management. Early this year, and as final act of the 2015 five-yearly review, the CERN Council may decide, if necessary and appropriate, to review the procedures defined in Annex A1 and applicable to future five-yearly reviews. At the meeting of TREF (TRipartite Employment Forum)  in early March 2016 discussions will take place between all stakeholders (representatives of Member States, Management and the Staff Association) and Council will take a decision in June 2016, on the basis of the Management's recommendations. What does Annex A1 say and where can I find it? Annex A1 (Article S V 1.02) is a part of the Staff Rules and Regulations. This annex defines: The five-yearly review of the financial and social conditions of the staff, fellows and MPA; The a...

  4. Das Sandmännchen, das aus der Kälte kam – DDR-Filmproduktionen im Kulturaustausch mit Schweden

    Directory of Open Access Journals (Sweden)

    Tilo Herrmann

    2006-01-01

    Full Text Available This essay uses the example of GDR film export to Sweden to examine specific objectives, internal planning, and results of GDR cultural policy in Sweden. It also investigates the Swedish receptions and the appraisals and patterns of argumentation to be found. The study is based on articles in Swedish daily press and technical journals and on internal documents of the East-German bureaucracy. The analysis is divided into several case studies which are restricted to the late 1960s and early 1970s, the heyday of GDR cultural activities in Sweden. After a glance at the situation in commercial film business, the focus shifts to a series of special film showings at the Swedish Film Institute's film club (SFI:s filmklubb.

  5. Employing Design and Development Research (DDR): Approaches in the Design and Development of Online Arabic Vocabulary Learning Games Prototype

    Science.gov (United States)

    Sahrir, Muhammad Sabri; Alias, Nor Aziah; Ismail, Zawawi; Osman, Nurulhuda

    2012-01-01

    The design and development research, first proposed by Brown and Collins in the 1990s, is currently among the well-known methods in educational research to test theory and validate its practicality. The method is also known as developmental research, design research, design-based research, formative research and design-cased and possesses…

  6. Der Leser macht das Kunstwerk? Brechts Gedicht “Der Rauch” und die Rezeptionsästhetik in der DDR

    Directory of Open Access Journals (Sweden)

    Rosani Ketzer Umbach

    2009-01-01

    Full Text Available The importance of the June 17th 1953 for the literature in the former German Democratic Republic (GDR shouldn’t be underestimated. Most of the active authors at that time took position in relation to the violent repression of the worker movement. So did it also the German writer and stage-manager Bertolt Brecht (1898-1956. How the poem “Der Rauch” (The smoke, written by him at the time of construction of regime and as reaction to the events of the June 17th, can still nowadays tell to the reader, is the topic of this work. It will be based on the literature theory in the GDR, which in the seventies was occupied with the reception theory.

  7. JNK inhibition sensitizes tumor cells to radiation-induced premature senescence via Bcl-2/ROS/DDR signaling pathway

    International Nuclear Information System (INIS)

    Lee, Jae Seon; Lee, Je Jung

    2009-01-01

    Premature senescence is considered as a cellular defense mechanism to prevent tumorigenesis. Although recent evidences demonstrate that c-Jun N-terminal kinase (JNK) is involved in the senescence process, the target and exact mechanism of JNK signaling in the regulation of cell proliferation has yet to be defined. In this study, we investigated the role of JNK in premature senescence and demonstrated JNK inhibition sensitized tumor cells to radiation-induced premature senescence

  8. DDR-Justiz und NS-Verbrechen Band 8 : Sammlung ostdeutscher Strafurteile wegen nationalsozialistischer Tötungsverbrechen

    NARCIS (Netherlands)

    Rüter, Christiaan F.

    2006-01-01

    Volume 8 contains the trial cases finalized between mid-May and the end of August 1949. Most of the cases in this volume involve denunciations, NS-crimes in detainment centers and final phase crimes. Also, there are some dealing with judicial crimes, mass extermination and war crimes, as well as

  9. Early rehabilitation of occupationally exposed persons in the Staatliches Amt fuer Atomsicherheit und Strahlenschutz der DDR. 2

    International Nuclear Information System (INIS)

    Arndt, D.; Lenz, U.; Rothe, E.; Schuettmann, W.

    1977-02-01

    Within the frame of a 3-year pilot study relating to the problem of early rehabilitation of occupationally exposed persons, 178 patients with 189 cases of illness were attended dermatologically and/or internally. Due to the high rate of improvement (67.7 %) the radiation fitness of the patients could be recovered or preserved in several cases, this being of great national economic benefit because of the high level of qualification to be found in this category of persons. The described prophylactic method of early rehabilitation is strongly recommended to the responsible medical officers as a means of optimizing their supervision activity. (author)

  10. What to Buy? The Role of Director of Defense Research and Engineering (DDR&E) Lessons from the 1970s

    Science.gov (United States)

    2011-01-01

    M. Thorndike , “Antisubmarine Warfare in World War II,” OEG Report No. 51 (Washington, DC: Operations Evaluation Group, 1946). The authors were not...Sternhell, Charles M. and Alan M. Thorndike . “Antisubmarine Warfare in World War II.” OEG Report No. 51. Washington, DC: Operations Evaluation Group

  11. Dietary Lecithin Decreases Skeletal Muscle COL1A1 and COL3A1 Gene Expression in Finisher Gilts

    Directory of Open Access Journals (Sweden)

    Henny Akit

    2016-06-01

    Full Text Available The purpose of this study was to investigate the effect of dietary lecithin on skeletal muscle gene expression of collagen precursors and enzymes involved in collagen synthesis and degradation. Finisher gilts with an average start weight of 55.9 ± 2.22 kg were fed diets containing either 0, 4, 20 or 80 g/kg soybean lecithin prior to harvest for six weeks and the rectus abdominis muscle gene expression profile was analyzed by quantitative real-time PCR. Lecithin treatment down-regulated Type I (α1 procollagen (COL1A1 and Type III (α1 procollagen (COL3A1 mRNA expression ( p < 0.05, respectively, indicating a decrease in the precursors for collagen synthesis. The α-subunit of prolyl 4-hydroxylase (P4H mRNA expression also tended to be down-regulated ( p = 0.056, indicating a decrease in collagen synthesis. Decreased matrix metalloproteinase-1 (MMP-1 mRNA expression may reflect a positive regulatory response to the reduced collagen synthesis in muscle from the pigs fed lecithin ( p = 0.035. Lecithin had no effect on tissue inhibitor metalloproteinase-1 (TIMP-1, matrix metalloproteinase-13 (MMP-13 and lysyl oxidase mRNA expression. In conclusion, lecithin down-regulated COL1A1 and COL3A1 as well as tended to down-regulate α-subunit P4H expression. However, determination of muscle collagen content and solubility are required to support the gene functions.

  12. CYP1A1 Genetic Polymorphisms in Ecuador, South America

    Directory of Open Access Journals (Sweden)

    César Paz-y-Miño

    2005-01-01

    Full Text Available A total of 108 individuals from the Ecuadorian population from rural and urban places were analyzed for two CYP1A1 gene polymorphisms. The frequency of the val allele at codon 462 was 0.50, while the frequency of the Msp I restriction site, m2 allele at the T6235C position was 0.70. These polymorphisms in Ecuador have higher frequencies if we compare with others around the world, with the exception of some South American population in Brazil and Chile.

  13. Value-impact analysis for USI A-1, water hammer

    International Nuclear Information System (INIS)

    Serkiz, A.W.

    1983-05-01

    The Unresolved Safety Issue (USI) A-1 deals with safety concerns related to water hammer occurrence in nucler power plants. The staff's concerns were prompted by the increasing frequency of water hammer occurrence in the mid-1970's as new plants were coming on line, and in particular, by the feedwater line rupture at Indian Point No. 2 in 1973 (attributed to water hammer induced by steam-void collapse). Principal concerns were: the potential for inadequate dynamic load design, disablement of safety systems, and the release of radioactivity. The staff's views were set forth in NUREG-0582 and water hammer was designated a USI in 1979

  14. Radiation supervision - NPPs A-1, V-1, V-2

    International Nuclear Information System (INIS)

    2000-01-01

    In this leaflet the radiation supervision of the nuclear power plants A-1, V-1, V-2 is presented. Off-site radiation supervision laboratory is a part of monitoring scheme of the NPPs. More than 1150 samples are taken from the environment annually. The tele-dosimetric system was constructed to improve the quality of the Bohunice NPPs operation impacts supervision. It has been running in a continuous operation from 1992 and providing supervision of the nuclear power plant off-site area within 25 kilometres. The tele-dosimetric system is described

  15. Wasp venom proteins: phospholipase A1 and B.

    Science.gov (United States)

    King, T P; Kochoumian, L; Joslyn, A

    1984-04-01

    Three major venom proteins from different species of wasps have been isolated and characterized. They are hyaluronidase, phospholipase, and antigen 5 of as yet unknown biochemical function. These three proteins are allergens in wasp venom-sensitive persons. The species of wasps studied, of the genus Polistes, were annularis, carolina, exclamans, fuscatus, and instabilis. Antigen 5 and phospholipase from wasp venoms were shown to be antigenically distinct from homologous proteins of yellowjacket venoms. The venom phospholipase from wasp, as well as that from yellowjacket (Vespula germanica), appears to have dual enzymatic specificities of the A1 and B types. That is, hydrolysis takes place at the 1-acyl residue of phosphatidylcholine and at the 1- or 2-acyl residue of lysophosphatidylcholine.

  16. Loss analysis of a 1 MW class HTS synchronous motor

    International Nuclear Information System (INIS)

    Baik, S K; Kwon, Y K; Kim, H M; Lee, J D; Kim, Y C; Park, H J; Kwon, W S; Park, G S

    2009-01-01

    The HTS (High-Temperature Superconducting) synchronous motor has advantages over the conventional synchronous motor such as smaller size and higher efficiency. Higher efficiency is due to smaller loss than the conventional motor, so it is important to do loss analysis in order to develop a machine with higher efficiency. This paper deals with machine losses those are dissipated in each part of a HTS synchronous motor. These losses are analyzed theoretically and compared with loss data obtained from experimental results of a 1 MW class HTS synchronous motor. Each machine loss is measured based on IEEE 115 standard and the results are analyzed and considered based on the manufacturing of the test machine.

  17. A 1.375-approximation algorithm for sorting by transpositions.

    Science.gov (United States)

    Elias, Isaac; Hartman, Tzvika

    2006-01-01

    Sorting permutations by transpositions is an important problem in genome rearrangements. A transposition is a rearrangement operation in which a segment is cut out of the permutation and pasted in a different location. The complexity of this problem is still open and it has been a 10-year-old open problem to improve the best known 1.5-approximation algorithm. In this paper, we provide a 1.375-approximation algorithm for sorting by transpositions. The algorithm is based on a new upper bound on the diameter of 3-permutations. In addition, we present some new results regarding the transposition diameter: we improve the lower bound for the transposition diameter of the symmetric group and determine the exact transposition diameter of simple permutations.

  18. Welding of the A1 reactor pressure vessel

    International Nuclear Information System (INIS)

    Becka, J.

    1975-01-01

    As concerns welding, the A-1 reactor pressure vessel represents a geometrically complex unit containing 1492 welded joints. The length of welded sections varies between 10 and 620 mm. At an operating temperature of 120 degC and a pressure of 650 N/cm 2 the welded joints in the reactor core are exposed to an integral dose of 3x10 18 n/cm 2 . The chemical composition is shown for pressure vessel steel as specified by CSN 413090.9 modified by Ni, Ti and Al additions, and for the welding electrodes used. The requirements are also shown for the mechanical properties of the base and the weld metals. The technique and conditions of welding are described. No defects were found in ultrasonic testing of welded joints. (J.B.)

  19. Xylitol inhibits J774A.1 macrophage adhesion in vitro

    Directory of Open Access Journals (Sweden)

    Aline Siqueira Ferreira

    2011-12-01

    Full Text Available The aim of this work was to evaluate the effect of xylitol on J774A.1 macrophage adhesion. Adhesion consisted of a three-hour interval, at room temperature, followed by washing and cell incubation at 37ºC/5% CO2/ 48h. Xylitol was used to treat the cells either before (for 24h or after the cell incubation (for 48h at 5% as final concentration in both the situations. It was found that xylitol was effective in preventing the adhesion in both the conditions in spite of the former being 100-fold greater and significant (p < 0.001. The results pointed to an important xylitol action on macrophage adhesion, which should be further investigated as an inflammatory control.

  20. Urethral polyp in a 1-month-old child

    Energy Technology Data Exchange (ETDEWEB)

    Beluffi, Giampiero [Department of Radiodiagnosis, IRCCS Policlinico S. Matteo, Section of Paediatric Radiology, Piazzale Golgi, 2, I-27100, Pavia PV (Italy); Berton, Francesca; Gola, Giada [University of Pavia, IRCCS Policlinico S. Matteo, Institute of Radiology, Pavia (Italy); Chiari, Giorgio; Romano, Piero; Cassani, Ferdinando [IRCCS Policlinico S. Matteo, Division of Paediatric Surgery, Pavia (Italy)

    2005-07-01

    Urethral polyps are a rare finding in children, particularly in the very young. They are suspected by the presence of various clinical signs such as obstruction, voiding dysfunction and haematuria. There is an association with other urinary tract congenital anomalies. They are usually benign fibro-epithelial lesions with no tendency to recur and are treated by surgical ablation, fulguration or laser therapy. We report a 1-month-old boy with an antenatally diagnosed left ectopic pelvic kidney, postnatal urinary tract infection and no clinical signs of obstruction. Voiding cystourethrography to exclude vesico-ureteric reflux showed a trabeculated bladder and a mobile filling defect in the posterior urethra. Owing to its large size, cystotomy was necessary to remove the polyp successfully. (orig.)

  1. Urethral polyp in a 1-month-old child

    International Nuclear Information System (INIS)

    Beluffi, Giampiero; Berton, Francesca; Gola, Giada; Chiari, Giorgio; Romano, Piero; Cassani, Ferdinando

    2005-01-01

    Urethral polyps are a rare finding in children, particularly in the very young. They are suspected by the presence of various clinical signs such as obstruction, voiding dysfunction and haematuria. There is an association with other urinary tract congenital anomalies. They are usually benign fibro-epithelial lesions with no tendency to recur and are treated by surgical ablation, fulguration or laser therapy. We report a 1-month-old boy with an antenatally diagnosed left ectopic pelvic kidney, postnatal urinary tract infection and no clinical signs of obstruction. Voiding cystourethrography to exclude vesico-ureteric reflux showed a trabeculated bladder and a mobile filling defect in the posterior urethra. Owing to its large size, cystotomy was necessary to remove the polyp successfully. (orig.)

  2. In vitro gibberellin A1 binding in Zea mays L

    International Nuclear Information System (INIS)

    Keith, B.; Rappaport, L.

    1987-01-01

    The first and second leaf sheaths of Zea mays L. cv Golden Jubilee were extracted and the extract centrifuged at 100,000g to yield a supernatant or cytosol fraction. Binding of [ 3 H]gibberellin A 1 (GA 1 ) to a soluble macromolecular component present in the cytosol was demonstrated at 4 0 C by Sephadex G-200 chromatography. The binding component was of high molecular weight (HMW) and greater than 500 kilodaltons. The HMW component was shown to be a protein and the 3 H-activity bound to this protein was largely [ 3 H]GA 1 and not a metabolite. Binding was pH sensitive but only a small percentage (20%) appeared to be exchangeable on addition of unlabeled GA 1 . Both biologically active and inactive GAs and non-GAs were able to inhibit GA 1 binding. [ 3 H]GA 1 binding to an intermediate molecular weight (IMW) fraction (40-100 kilodaltons) was also detected, provided cytosol was first desalted using Sephadex G-200 chromatography. Gel filtration studies suggest that the HMW binding component is an aggregate derived from the IMW fraction. The HMW binding fraction can be separated into two components using anion exchange chromatography

  3. Bootstrapping the (A1, A2) Argyres-Douglas theory

    Science.gov (United States)

    Cornagliotto, Martina; Lemos, Madalena; Liendo, Pedro

    2018-03-01

    We apply bootstrap techniques in order to constrain the CFT data of the ( A 1 , A 2) Argyres-Douglas theory, which is arguably the simplest of the Argyres-Douglas models. We study the four-point function of its single Coulomb branch chiral ring generator and put numerical bounds on the low-lying spectrum of the theory. Of particular interest is an infinite family of semi-short multiplets labeled by the spin ℓ. Although the conformal dimensions of these multiplets are protected, their three-point functions are not. Using the numerical bootstrap we impose rigorous upper and lower bounds on their values for spins up to ℓ = 20. Through a recently obtained inversion formula, we also estimate them for sufficiently large ℓ, and the comparison of both approaches shows consistent results. We also give a rigorous numerical range for the OPE coefficient of the next operator in the chiral ring, and estimates for the dimension of the first R-symmetry neutral non-protected multiplet for small spin.

  4. Molecular Dynamics Simulation of Cholera Toxin A-1 Polypeptide

    Directory of Open Access Journals (Sweden)

    Badshah Syed Lal

    2016-01-01

    Full Text Available A molecular dynamics (MD simulation study of the enzymatic portion of cholera toxin; cholera toxin A-1 polypeptide (CTA1 was performed at 283, 310 and 323 K. From total energy analysis it was observed that this toxin is stable thermodynamically and these outcomes were likewise confirmed by root mean square deviations (RMSD investigations. The Cα root mean square fluctuation (RMSF examinations revealed that there are a number of residues inside CTA1, which can be used as target for designing and synthesizing inhibitory drugs, in order to inactivate cholera toxin inside the human body. The fluctuations in the radius of gyration and hydrogen bonding in CTA1 proved that protein unfolding and refolding were normal routine phenomena in its structure at all temperatures. Solvent accessible surface area study identified the hydrophilic nature of the CTA1, and due to this property it can be a potential biological weapon. The structural identification (STRIDE algorithm for proteins was successfully used to determine the partially disordered secondary structure of CTA1. On account of this partially disordered secondary structure, it can easily deceive the proteolytic enzymes of the endoplasmic reticulum of host cells.

  5. Feasibility study of a 1-MW pulsed spallation source

    International Nuclear Information System (INIS)

    Cho, Y.; Chae, Y.C.; Crosbie, E.

    1995-01-01

    A feasibility study of a 1-MW pulsed spallation source based on a rapidly cycling proton synchrotron (RCS) has been completed. The facility consists of a 400-MeV HP - linac, a 30-Hz RCS that accelerates the 400-MeV beam to 2 GeV, and two neutron-generating target stations. The design time-averaged current of the accelerator system is 0.5 mA, or 1.04x1014 protons per pulse. The linac system consists of an H - ion source, a 2-MeV RFQ, a 70-MeV DTL and a 330-MeV CCL. Transverse phase space painting to achieve a Kapchinskij-Vladimirskij (K-V) distribution of the injected particles in the RCS is accomplished by charge exchange injection and programming of the closed orbit during injection. The synchrotron lattice uses FODO cells of ∼90 degrees phase advance. Dispersion-free straight sections are obtained by using a missing magnet scheme. Synchrotron magnets are powered by a dual-frequency resonant circuit that excites the magnets at a 20-Hz rate and de-excites them at a 60-Hz rate, resulting in an effective rate of 30 Hz, and reducing the required peak rf voltage by 1/3. A key feature, of the design of this accelerator system is that beam losses are from injection to extraction, reducing activation to levels consistent with hands-on maintenance. Details of the study are presented

  6. Detection of alkaptonuria in a 1-week-old infant.

    Science.gov (United States)

    Thalagahage, Krishan Nilantha Hewa; Jayaweera, Jayaweera Arachchige Asela Sampath; Kumbukgolla, Wikum Widuranga; Senavirathne, Indika

    2015-05-08

    Alkaptonuria is a rare disorder that results from an inherited deficiency of aromatic amino acid metabolism. Only 21% of the children under the age of 1 year having the disease are identified in clinics. We report a case of a 1-week-old child of a first-degree consanguineous couple with a symptom of frequent nappy staining. Analysis of urine showed a homogentisic acid concentration exceeding 200 mg/dL. The physical examination revealed that the child was healthy. The parents' watchfulness and the close attention paid to the child were the keys to the early detection of this rare disease. After identifying the disease, adequate follow-up of the patient is important to reduce further complications. Anti-inflammatory therapy and increasing the muscle strength by exercises such as swimming would be useful to restrict joint pains and immobilisation. A low protein diet also could be recommended; that fact is yet to be proven by clinical trials. 2015 BMJ Publishing Group Ltd.

  7. Optimizing the Construction of the A1 Collaboration Neutron Detector

    Science.gov (United States)

    Chinn, Edward; A1 Collaboration

    2016-09-01

    We report on the design and construction of a frame designed to optimize both the time efficiency and construction quality of the large scintillator elements These elements will be assembled to form a neutron detector for use by the A1 Collaboration at the Institute for Nuclear Physics in Mainz, Germany. The design had to provide adequate support for the 20 kg scintillator bars while gluing light guides and photomultiplier tubes to both sides of the bars using optical cement. The optical cement requires approximately 24 hours to dry and 100 bars have to be glued with this apparatus. To address each of these issues, several different prototypes were designed and reviewed. The selected apparatus minimized size to meet space constraints, with reduced material cost and provided the most time-efficient way to build the neutron detector. Once the schematic design was selected, we produced technical drawings in AutoDesk Inventor. Assembled the structure and completed gluing of the first batch of scintillators, in order to verify the performance. This apparatus was successful at producing high quality scintillators which were evaluated using cosmic rays. National Science Foundation Grant No. IIA-1358175.

  8. Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01

    DEFF Research Database (Denmark)

    Lüttkopf, D; Müller, U; Skov, P S

    2002-01-01

    of the recombinant variants: Cor a 1.0401>Cor a 1.0402 and 03>Cor a 1.0404 (the proline variant). Similar results for Cor a 1.0402 and 03 suggest a minor influence in IgE binding of cysteine in position 4, whereas proline in position 99 appears to be responsible for the decrease in IgE reactivity in Cor a 1...

  9. Monitoring of primary circuit and reactor of NPP A-1

    International Nuclear Information System (INIS)

    Prazska, M.; Majersky, M.; Rezbarik, J.; Sekely, S.; Vozarik, P.; Walthery, R.; Stuller, P.

    2005-01-01

    Nuclear Power Plant A-1 in Jaslovske Bohunice was commissioned in 1972. Heavy water moderated, carbon dioxide cooled channel type reactor was shut down after two accidents in 1977. During more serious second accident, the reduced coolant flow caused local overheating of the fuel and consequent damage/melting of the fuel channel. Both accidents had led to the damage of several fuel assemblies with extensive local damage of fuel claddings. As a consequence, the main cooling circuit was significantly contaminated by fission products and long-life alpha nuclides. The detailed monitoring of dose rates, smearable contamination and sampling of contamination was performed. Extended monitoring in reacto vessel, primary circuit pipes, turbo-compressors, steam generators, main valves, gas tanks and also heavy water system with collectors, coolers, distilling and purification station, pumps and valves was done. Appropriate devices and procedures for the monitoring and examination of the installations were prepared and applied. Obtained results will serve for the future planning of the decontamination and decommissioning works. The 3-D model of the reactor that had been developed as part of this Project proved invaluable for orientation, visualisation, planning and analysis of results. Dose rates were measured in the technological channels from the reactor hall floor to the bottom of the hot gas chamber in decrements of 1 m and 0.5 m. The highest absolute values of dose rates were found in channels located in the middle of the reactor (up to 1900 mGy/h in the active zone region). It is estimated that the total contaminated area of primary circuit equipment (pipework, steam generators and turbo-compressors) is some 48 000 m 2 . It follows that the total gamma contamination is of the order of 10 14 to 10 15 Bq and total alpha contamination 10 11 to 10 13 Bq. The total amount of deposits in the gas circuit is about 14.3 tons. (authors)

  10. Sistema E.V.A. 1.0

    Directory of Open Access Journals (Sweden)

    Díaz Córdova, D. M.

    2003-01-01

    Full Text Available Dentro del campo del crecimiento y desarrollo, el cálculo antropométrico, es una de las herramientas más utilizadas para encontrar indicadores válidos del estado general del crecimiento biológico de una población en su interacción con los diversos factores sociales. Frente al evidente proceso de pauperización por el que viene transcurriendo el país, la evaluación del estado nutricional de la población infantil, tanto en sus aspectos poblacionales como individuales, se hace necesaria y cotidiana. Presentamos aquí un software de escritorio que permite el cálculo y la graficación de las principales variables antropométricas. El E.V.A. 1.0 (Evaluación y Visualización Antropométrica brinda también la posibilidad de almacenar los datos, de incorporar tablas de comparación (por default el sistema trae las tablas de la SAP y del NCHS, y de exportar la información al programa EPINFO y a la mayoría de las aplicaciones estándar de escritorio (planillas de cálculo, procesadores de texto, etc.. La aplicación posee también una modalidad de sugerencias de diagnóstico, con referencias bibliográficas, que puede ser de ayuda, tanto para el profesional de A.P.S. como para el investigador.

  11. Experimental study of a 1 MW, 170 GHz gyrotron oscillator

    Science.gov (United States)

    Kimura, Takuji

    A detailed experimental study is presented of a 1 MW, 170 GHz gyrotron oscillator whose design is consistent with the ECH requirements of the International Thermonuclear Experimental Reactor (ITER) for bulk heating and current drive. This work is the first to demonstrate that megawatt power level at 170 GHz can be achieved in a gyrotron with high efficiency for plasma heating applications. Maximum output power of 1.5 MW is obtained at 170.1 GHz in 85 kV, 50A operation for an efficiency of 35%. Although the experiment at MIT is conducted with short pulses (3 μs), the gyrotron is designed to be suitable for development by industry for continuous wave operation. The peak ohmic loss on the cavity wall for 1 MW of output power is calculated to be 2.3 kW/cm2, which can be handled using present cooling technology. Mode competition problems in a highly over-moded cavity are studied to maximize the efficiency. Various aspects of electron gun design are examined to obtain high quality electron beams with very low velocity spread. A triode magnetron injection gun is designed using the EGUN simulation code. A total perpendicular velocity spread of less than 8% is realized by designing a low- sensitivity, non-adiabatic gun. The RF power is generated in a short tapered cavity with an iris step. The operating mode is the TE28,8,1 mode. A mode converter is designed to convert the RF output to a Gaussian beam. Power and efficiency are measured in the design TE28,8,1 mode at 170.1 GHz as well as the TE27,8,1 mode at 166.6 GHz and TE29,8,1 mode at 173.5 GHz. Efficiencies between 34%-36% are consistently obtained over a wide range of operating parameters. These efficiencies agree with the highest values predicted by the multimode simulations. The startup scenario is investigated and observed to agree with the linear theory. The measured beam velocity ratio is consistent with EGUN simulation. Interception of reflected beam by the mod-anode is measured as a function of velocity ratio

  12. Data of evolutionary structure change: 1AY4A-1YAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AY4A-1YAAA 1AY4 1YAA A A ---MLGNLKPQAPDKILALMGEFRADPRQGKIDLGVGVY...LPVQTYRYFDAETRGVDFEGMKADLAAAKKGDMVLLHGCCHNPTGANLTLDQWAEIASILEKTGALPLIDLAYQGFGD-GLEEDAAGTRLIASRIP---EVLIAASCS...ID>1YAA A 1YAAA A 1YAAA QGFATGDLDKD

  13. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    , Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided...... by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition....

  14. Isolation and characterization of cyp19a1a and cyp19a1b promoters in the protogynous hermaphrodite orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Zhang, Weimin; Lu, Huijie; Jiang, Haiyan; Li, Mu; Zhang, Shen; Liu, Qiongyou; Zhang, Lihong

    2012-02-01

    Aromatase (CYP19A1) catalyzes the conversion of androgens to estrogens. In teleosts, duplicated copies of cyp19a1 genes, namely cyp19a1a and cyp19a1b, were identified, however, the transcriptional regulation of these two genes remains poorly understood. In the present study, the 5'-flanking regions of the orange-spotted grouper cyp19a1a (gcyp19a1a) and cyp19a1b (gcyp19a1b) genes were isolated and characterized. The proximal promoter regions of both genes were relatively conserved when compared to those of the other teleosts. Notably, a conserved FOXO transcriptional factor binding site was firstly reported in the proximal promoter of gcyp19a1a, and deletion of the region (-112 to -60) containing this site significantly decreased the promoter activities. The deletion of the region (-246 to -112) containing the two conserved FTZ-F1 sites also dramatically decreased the transcriptional activities of gcyp19a1a promoter, and both two FTZ-F1 sites were shown to be stimulatory cis-acting elements. A FTZ-F1 homologue isolated from ricefield eel (eFTZ-F1) up-regulated gcyp19a1a promoter activities possibly via the FTZ-F1 sites, however, a previously identified orange-spotted grouper FTZ-F1 homologue (gFTZ-F1) did not activate the transcription of gcyp19a1a promoter unexpectedly. As to gcyp19a1b promoter, all the deletion constructs did not show good promoter activities in either TM4 or U251-MG cells. Estradiol (100nM) up-regulated gcyp19a1b promoter activities by about 13- and 36-fold in TM4 and U251-MG cells, respectively, via the conserved ERE motif, but did not stimulate gcyp19a1a promoter activities. These results are helpful to further elucidate the regulatory mechanisms of cyp19a1a and cyp19a1b expression in the orange-spotted grouper as well as other teleosts. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP.

    Science.gov (United States)

    Franz-Oberdorf, Katrin; Langer, Andreas; Strasser, Ralf; Isono, Erika; Ranftl, Quirin L; Wunschel, Christian; Schwab, Wilfried

    2017-10-01

    The strawberry fruit allergens Fra a 1.01E, Fra a 1.02 and Fra a 1.03 belong to the group of pathogenesis-related 10 (PR-10) proteins and are homologs of the major birch pollen Bet v 1 and apple allergen Mal d 1. Bet v 1 related proteins are the most extensively studied allergens but their physiological function in planta remains elusive. Since Mal d 1-Associated Protein has been previously identified as interaction partner of Mal d 1 we studied the binding of the orthologous Fra a 1-Associated Protein (FaAP) to Fra a 1.01E/1.02/1.03. As the C-terminal sequence of FaAP showed strong auto-activation activity in yeast 2-hybrid analysis a novel time resolved DNA-switching system was successfully applied. Fra a 1.01E, Fra a 1.02, and Fra a 1.03 bind to FaAP with K D of 4.5 ± 1.1, 15 ± 3, and 11 ± 2 nM, respectively. Fra a 1.01E forms a dimer, whereas Fra a 1.02 and Fra a 1.03 bind as monomer. The results imply that PR-10 proteins might be integrated into a protein-interaction network and FaAP binding appears to be essential for the physiological function of the Fra a 1 proteins. © 2017 Wiley Periodicals, Inc.

  16. Characterization of simvastatin acid uptake by organic anion transporting polypeptide 3A1 (OATP3A1) and influence of drug-drug interaction.

    Science.gov (United States)

    Atilano-Roque, Amandla; Joy, Melanie S

    2017-12-01

    Human organic anion transporting polypeptide 3A1 (OATP3A1) is predominately expressed in the heart. The ability of OATP3A1 to transport statins into cardiomyocytes is unknown, although other OATPs are known to mediate the uptake of statin drugs in liver. The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. Treatment with simvastatin acid reduced indoxyl sulfate-mediated reactive oxygen species and modulated OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. We observed a pH-dependent effect on OATP3A1 uptake, with more efficient simvastatin acid uptake at pH5.5 in HEK293 cells transfected with the OATP3A1 gene. The Michaelis-Menten constant (K m ) for simvastatin acid uptake by OATP3A1 was 0.017±0.002μM and the V max was 0.995±0.027fmol/min/10 5 cells. Uptake of simvastatin acid was significantly increased by known (benzylpenicillin and estrone-3-sulfate) and potential (indoxyl sulfate and cyclosporine) substrates of OATP3A1. In conclusion, the presence of OATP3A1 in cardiomyocytes suggests that this transporter may modulate the exposure of cardiac tissue to simvastatin acid due to its enrichment in cardiomyocytes. Increases in uptake of simvastatin acid by OATP3A1 when combined with OATP substrates suggest the potential for drug-drug interactions that could influence clinical outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, BW; Batten, MR; Kilian, Mogens

    2002-01-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were const...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....

  18. Immunoglobulins in nasal secretions of healthy humans: structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

    DEFF Research Database (Denmark)

    Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro....... Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11...... healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and...

  19. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Science.gov (United States)

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  20. A study assessing the association of glycated hemoglobin A1C (HbA1C associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    Directory of Open Access Journals (Sweden)

    Peng Chen

    Full Text Available Glycated hemoglobin A1C (HbA1C level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  1. Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry.

    Science.gov (United States)

    Clements, Mark A; Foster, Nicole C; Maahs, David M; Schatz, Desmond A; Olson, Beth A; Tsalikian, Eva; Lee, Joyce M; Burt-Solorzano, Christine M; Tamborlane, William V; Chen, Vincent; Miller, Kellee M; Beck, Roy W

    2016-08-01

    Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes. Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p HbA1c trajectory. Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

    Science.gov (United States)

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-03-01

    Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes

    DEFF Research Database (Denmark)

    Skriver, Mette Vinther; Sandbæk, Annelli; Kristensen, Jette Kolding

    2015-01-01

    OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individua...

  4. Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth.

    Science.gov (United States)

    Christiansen, Helena E; Lang, Michael R; Pace, James M; Parichy, David M

    2009-12-29

    Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development. We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically. Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype.

  5. Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease caused by Western diet containing benzo[a]pyrene in mice.

    Science.gov (United States)

    Uno, Shigeyuki; Nebert, Daniel W; Makishima, Makoto

    2018-03-01

    The Western diet contributes to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Benzo[a]pyrene (BaP), a prototypical environmental pollutant produced by combustion processes, is present in charcoal-grilled meat. Cytochrome P450 1A1 (CYP1A1) metabolizes BaP, resulting in either detoxication or metabolic activation in a context-dependent manner. To elucidate a role of CYP1A1-BaP in NAFLD pathogenesis, we compared the effects of a Western diet, with or without oral BaP treatment, on the development of NAFLD in Cyp1a1(-/-) mice versus wild-type mice. A Western diet plus BaP induced lipid-droplet accumulation in liver of Cyp1a1(-/-) mice, but not wild-type mice. The hepatic steatosis observed in Cyp1a1(-/-) mice was associated with increased cholesterol, triglyceride and bile acid levels. Cyp1a1(-/-) mice fed Western diet plus BaP had changes in expression of genes involved in bile acid and lipid metabolism, and showed no increase in Cyp1a2 expression but did exhibit enhanced Cyp1b1 mRNA expression, as well as hepatic inflammation. Enhanced BaP metabolic activation, oxidative stress and inflammation may exacerbate metabolic dysfunction in liver of Cyp1a1(-/-) mice. Thus, Western diet plus BaP induces NAFLD and hepatic inflammation in Cyp1a1(-/-) mice in comparison to wild-type mice, indicating a protective role of CYP1A1 against NAFLD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.

    Science.gov (United States)

    Gose, Tomoka; Nakanishi, Takeo; Kamo, Shunsuke; Shimada, Hiroaki; Otake, Katsumasa; Tamai, Ikumi

    2016-01-01

    Eicosapentaenoic acid (EPA)-derived prostaglandin E3 (PGE3) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE3. PGE3 uptake was assessed in HEK293 cells transfected with OATP2A1/SLCO2A1, OATP1B1/SLCO1B1, OATP2B1/SLCO2B1, OAT1/SLC22A6, OCT1/SLC22A1 or OCT2/SLC22A2 genes, compared with HEK293 cells transfected with plasmid vector alone (Mock). PGE3 uptake by OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by HEK/1B1, while no significantly higher uptake of PGE3 than Mock cells was detected by other transporters. Saturation kinetics in PGE3 uptake by HEK/2A1 estimated the Km as 7.202 ± 0.595 μM, which was 22 times higher than that of PGE2 (Km=0.331 ± 0.131 μM). Furthermore, tissue disposition of PGE3 was examined in wild-type (WT) and Slco2a1-deficient (Slco2a1(-/-)) mice after oral administration of EPA ethyl ester (EPA-E) when they underwent intraperitoneal injection of endotoxin (e.g., lipopolysaccharide). PGE3 concentration was significantly higher in the lung, and tended to increase in the colon, stomach, and kidney of Slco2a1(-/-), compared to WT mice. Ratio of PGE2 metabolite 15-keto PGE2 over PGE2 concentration was significantly lower in the lung and colon of Slco2a1(-/-) than that of WT mice, suggesting that PGE3 metabolism is downregulated in Slco2a1(-/-) mice. In conclusion, PGE3 was found to be a substrate of OATP2A1, and local disposition of PGE3 could be regulated by OATP2A1 at least in the lung. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The Long and Winding Road to Optimal HbA1c Measurement

    Science.gov (United States)

    Little, Randie R.; Rohlfing, Curt

    2016-01-01

    The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the “long and winding road” to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results. PMID:23318564

  8. Depleted aldehyde dehydrogenase 1A1 (ALDH1A1) reverses cisplatin resistance of human lung adenocarcinoma cell A549/DDP.

    Science.gov (United States)

    Wei, Yunyan; Wu, Shuangshuang; Xu, Wei; Liang, Yan; Li, Yue; Zhao, Weihong; Wu, Jianqing

    2017-01-01

    Cisplatin is the standard first-line chemotherapeutic agent for the treatment of non-small cell lung cancer (NSCLC). However, resistance to chemotherapy has been a major obstacle in the management of NSCLC. Aldehyde dehydrogenase 1A1 (ALDH1A1) overexpression has been observed in a variety of cancers, including lung cancer. The purpose of this study was to investigate the effect of ALDH1A1 expression on cisplatin resistance and explore the mechanism responsible. Reverse transcriptase-PCR was applied to measure the messenger RNA expression of ALDH1A1, while Western blot assay was employed to evaluate the protein expression of ALDH1A1, B-cell lymphoma 2, Bcl-2-like protein 4, phospho-protein kinase B (p-AKT) and AKT. A short hairpin RNA was used to knockdown ALDH1A1 expression. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the effect of ALDH1A1 decrease on cell viability. The cell apoptotic rate was tested using flow cytometry assay. ALDH1A1 is overexpressed in cisplatin resistant cell line A549/DDP, compared with A549. ALDH1A1 depletion significantly decreased A549/DDP proliferation, increased apoptosis, and reduced cisplatin resistance. In addition, the phosphoinositide 3-kinase (PI3K) / AKT pathway is activated in A549/DDP, and ALDH1A1 knockdown reduced the phosphorylation level of AKT. Moreover, the combination of ALDH1A1-short hairpin RNA and PI3K/AKT pathway inhibitor LY294002 markedly inhibited cell viability, enhanced apoptotic cell death, and increased cisplatin sensitivity. These results suggest that ALDH1A1 depletion could reverse cisplatin resistance in human lung cancer cell line A549/DDP, and may act as a potential target for the treatment of lung cancers resistant to cisplatin. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  9. Whole Blood Donation Affects the Interpretation of Hemoglobin A(1c)

    NARCIS (Netherlands)

    Dijkstra, Angelique; Lenters-Westra, Erna; de Kort, Wim; Bokhorst, Arlinke G.; Bilo, Henk J. G.; Slingerland, Robbert J.; Vos, Michel J.

    2017-01-01

    Introduction Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A(1c) (HbA(1c)) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA(1c) in both

  10. Whole Blood Donation Affects the Interpretation of Hemoglobin A1c

    NARCIS (Netherlands)

    Dijkstra, Angelique; Lenters-Westra, Erna; de Kort, Wim; Bokhorst, Arlinke G.; Bilo, Henk J. G.; Slingerland, Robbert J.; Vos, Michel J.

    2017-01-01

    Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A1c (HbA1c) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA1c in both non-diabetic blood donors

  11. HbA1c measurements from dried blood spots : validation and patient satisfaction

    NARCIS (Netherlands)

    Fokkema, Margaretha; Bakker, Andries J; de Boer, Fokje; Kooistra, Jeltsje; de Vries, Sifra; Wolthuis, Albert

    2009-01-01

    Background: This study evaluates HbA1c measurements from dried blood spots collected on filter paper and compares HbA1c from filter paper (capillary blood) with HbA1c measured in venous blood. Methods: Patient satisfaction was evaluated using a questionnaire. The performance with the filter paper

  12. Changing from glucose to HbA1c for diabetes diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Aneta Aleksandra; Petersen, Per Hyltoft; Green, Anders

    2014-01-01

    BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias ...

  13. Data of evolutionary structure change: 1AJ8A-1IOMA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AJ8A-1IOMA 1AJ8 1IOM A A LAKGLEDVYIDQTNICYIDGKEGKLYYRGYSVEELAELS...>GLY CA 362 ASP CA 303 LYS CA 256 1IOM... A 1IOMA EKLARLVAEKHGHS ARG CA 187 1IOM A 1IOM... 2.1075398921966553 2 1IOM

  14. 26 CFR 1.924(a)-1T - Temporary regulations; definition of foreign trading gross receipts.

    Science.gov (United States)

    2010-04-01

    ... trading gross receipts. 1.924(a)-1T Section 1.924(a)-1T Internal Revenue INTERNAL REVENUE SERVICE... United States § 1.924(a)-1T Temporary regulations; definition of foreign trading gross receipts. (a) In general. The term “foreign trading gross receipts” means any of the five amounts described in paragraphs...

  15. 26 CFR 301.6031(a)-1 - Return of partnership income.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Return of partnership income. 301.6031(a)-1....6031(a)-1 Return of partnership income. For provisions relating to the requirement of returns of partnership income, see § 1.6031(a)-1 of this chapter. [T.D. 8841, 64 FR 61502, Nov. 12, 1999] ...

  16. Higher Pretransplantation Hemoglobin A1c Is Associated With Greater Risk of Posttransplant Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Jung-Im Shin

    2017-11-01

    Discussion: Higher pretransplantation HbA1c above 5.4% is independently associated with greater risk of PTDM among kidney transplant recipients. A continuous relationship between pretransplantation HbA1c and risk of PTDM suggests that increased risk starts at HbA1c levels well below current thresholds for prediabetes.

  17. 40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Global Warming Potentials A Table A-1 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt. A, Table A-1 Table A-1 to Subpart A of Part 98—Global Warming...

  18. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certain prima facie investment companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment...

  19. 17 CFR 240.15a-1 - Securities activities of OTC derivatives dealers.

    Science.gov (United States)

    2010-04-01

    ... options, forwards, futures, swap agreements, or collars involving currencies, interest or other rates... derivatives dealers. 240.15a-1 Section 240.15a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Exemption of Certain Otc Derivatives Dealers § 240.15a-1...

  20. The structure of an E. coli tRNAfMet A1-U72 variant shows an unusual conformation of the A1-U72 base pair.

    Science.gov (United States)

    Monestier, Auriane; Aleksandrov, Alexey; Coureux, Pierre-Damien; Panvert, Michel; Mechulam, Yves; Schmitt, Emmanuelle

    2017-05-01

    Translation initiation in eukaryotes and archaea involves a methionylated initiator tRNA delivered to the ribosome in a ternary complex with e/aIF2 and GTP. Eukaryotic and archaeal initiator tRNAs contain a highly conserved A 1 -U 72 base pair at the top of the acceptor stem. The importance of this base pair to discriminate initiator tRNAs from elongator tRNAs has been established previously using genetics and biochemistry. However, no structural data illustrating how the A 1 -U 72 base pair participates in the accurate selection of the initiator tRNAs by the translation initiation systems are available. Here, we describe the crystal structure of a mutant E. coli initiator tRNA f Met A 1 -U 72 , aminoacylated with methionine, in which the C 1 :A 72 mismatch at the end of the tRNA acceptor stem has been changed to an A 1 -U 72 base pair. Sequence alignments show that the mutant E. coli tRNA is a good mimic of archaeal initiator tRNAs. The crystal structure, determined at 2.8 Å resolution, shows that the A 1 -U 72 pair adopts an unusual arrangement. A 1 is in a syn conformation and forms a single H-bond interaction with U 72 This interaction requires protonation of the N1 atom of A 1 Moreover, the 5' phosphoryl group folds back into the major groove of the acceptor stem and interacts with the N7 atom of G 2 A possible role of this unusual geometry of the A 1 -U 72 pair in the recognition of the initiator tRNA by its partners during eukaryotic and archaeal translation initiation is discussed. © 2017 Monestier et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  1. Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hong-Quan Duong

    2017-07-01

    Full Text Available Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2, a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1 and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1. NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU in pancreatic cancer cells.

  2. Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells

    DEFF Research Database (Denmark)

    Liu, Yawei; Marin, Andrea; Ejlerskov, Patrick

    2017-01-01

    Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice...... lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs. Passive transfer-EAE via IFNβ......-competent Tenc cells to mice lacking IFNβ and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes(Cre):Ifnar(fl/fl)) result in defective FoxA1(+)Tregs generation and aggravated neuroinflammation. IFNβ activates neuronal PI3K/Akt signalling and Akt binds to transcription factor FoxA1...

  3. Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers.

    Science.gov (United States)

    Fesseha, Betiel K; Abularrage, Christopher J; Hines, Kathryn F; Sherman, Ronald; Frost, Priscilla; Langan, Susan; Canner, Joseph; Likes, Kendall C; Hosseini, Sayed M; Jack, Gwendolyne; Hicks, Caitlin W; Yalamanchi, Swaytha; Mathioudakis, Nestoras

    2018-04-16

    This study evaluated the association between hemoglobin A 1c (A1C) and wound outcomes in patients with diabetic foot ulcers (DFUs). We conducted a retrospective analysis of an ongoing prospective, clinic-based study of patients with DFUs treated at an academic institution during a 4.7-year period. Data from 270 participants and 584 wounds were included in the analysis. Cox proportional hazards regression was used to assess the incidence of wound healing at any follow-up time in relation to categories of baseline A1C and the incidence of long-term (≥90 days) wound healing in relation to tertiles of nadir A1C change and mean A1C change from baseline, adjusted for potential confounders. Baseline A1C was not associated with wound healing in univariate or fully adjusted models. Compared with a nadir A1C change from baseline of -0.29 to 0.0 (tertile 2), a nadir A1C change of 0.09 to 2.4 (tertile 3) was positively associated with long-term wound healing in the subset of participants with baseline A1C healing was seen with the mean A1C change from baseline in this group. Neither nadir A1C change nor mean A1C change were associated with long-term wound healing in participants with baseline A1C ≥7.5%. There does not appear to be a clinically meaningful association between baseline or prospective A1C and wound healing in patients with DFUs. The paradoxical finding of accelerated wound healing and increase in A1C in participants with better baseline glycemic control requires confirmation in further studies. © 2018 by the American Diabetes Association.

  4. Use of Fructosyl Peptide Oxidase for HbA1c Assay

    Science.gov (United States)

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-01-01

    ARKRAY, Inc developed the world’s first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay “CinQ HbA1c” with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent. PMID:25633966

  5. Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

    International Nuclear Information System (INIS)

    Lemaire, Benjamin; Kubota, Akira; O'Meara, Conor M.; Lamb, David C.; Tanguay, Robert L.; Goldstone, Jared V.; Stegeman, John J.

    2016-01-01

    Cytochrome P450 (CYP) enzymes for which there is no functional information are considered “orphan” CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including the liver, heart, gonads, spleen and brain, as well as the eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to “deorphanization”, that is, identifying CYP20A1 functions and its roles in health and disease. - Highlights: • The “orphan” CYP20A1 was cloned from zebrafish and its sequence analyzed. • Knockdown of CYP20A1 reduced an optomotor response and elicited bursts of activity. • Effects of

  6. Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, Benjamin; Kubota, Akira; O' Meara, Conor M. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Lamb, David C. [Institute of Life Science, Medical School, Swansea University, Swansea (United Kingdom); Tanguay, Robert L. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Goldstone, Jared V. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Stegeman, John J., E-mail: jstegeman@whoi.edu [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States)

    2016-04-01

    Cytochrome P450 (CYP) enzymes for which there is no functional information are considered “orphan” CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including the liver, heart, gonads, spleen and brain, as well as the eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to “deorphanization”, that is, identifying CYP20A1 functions and its roles in health and disease. - Highlights: • The “orphan” CYP20A1 was cloned from zebrafish and its sequence analyzed. • Knockdown of CYP20A1 reduced an optomotor response and elicited bursts of activity. • Effects of

  7. Apolipoprotein A-1 (apoA-1) deposition in, and release from, the enterocyte brush border: a possible role in transintestinal cholesterol efflux (TICE)?

    Science.gov (United States)

    Danielsen, E Michael; Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte; Frenzel, Franz

    2012-03-01

    Transintestinal cholesterol efflux (TICE) has been proposed to represent a non-hepatobiliary route of cholesterol secretion directly "from blood to gut" and to play a physiologically significant role in excretion of neutral sterols, but so far little is known about the proteins involved in the process. We have previously observed that apolipoprotein A-1 (apoA-1) synthesized by enterocytes of the small intestine is mainly secreted apically into the gut lumen during fasting where its assembly into chylomicrons and basolateral discharge is at a minimal level. In the present work we showed, both by immunomicroscopy and subcellular fractionation, that a fraction of the apically secreted apoA-1 in porcine small intestine was not released from the cell surface but instead deposited in the brush border. Cholesterol was detected in immunoisolated microvillar apoA-1, and it was partially associated with detergent resistant membranes (DRMs), indicative of localization in lipid raft microdomains. The apolipoprotein was not readily released from microvillar vesicles by high salt or by incubation with phosphatidylcholine-specific phospholipase C or trypsin, indicating a relatively firm attachment to the membrane bilayer. However, whole bile or taurocholate efficiently released apoA-1 at low concentrations that did not solubilize the transmembrane microvillar protein aminopeptidase N. Based on these findings and the well known role played by apoA-1 in extrahepatic cellular cholesterol removal and reverse cholesterol transport (RCT), we propose that brush border-deposited apoA-1 in the small intestine acts in TICE by mediating cholesterol efflux into the gut lumen. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability.

    Science.gov (United States)

    Walker, G S; Chen, J Y; Hopkinson, H; Sainsbury, C A R; Jones, G C

    2018-06-01

    Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA 1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA 1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA 1c variability in Type 1 diabetes. People with Type 1 diabetes who had attended DAFNE were identified for inclusion from the Scottish Care Information-Diabetes dataset. HbA 1c median and variability, expressed as coefficient of variation (CV) before and after DAFNE was calculated. Some 1061 individuals participated in DAFNE education and 687 met the inclusion criteria. A significant median reduction in HbA 1c [-3.5 mmol/mol (-0.3%)] was seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen at 60 months of follow-up. HbA 1c variability as measured by CV was significantly lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR 0.05-0.10); P = 0.002. The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA 1c variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile. © 2018 Diabetes UK.

  9. Successful ABO-Incompatible Renal Transplantation:  Blood Group A1B Donor Into A2B Recipient With Anti-A1 Isoagglutinins.

    Science.gov (United States)

    Fadeyi, Emmanuel A; Stratta, Robert J; Farney, Alan C; Pomper, Gregory J

    2016-08-01

    Transplantation of the blood group A2B in a recipient was successfully performed in the setting of receiving a deceased donor kidney from an "incompatible" A1B donor. The donor and recipient were both typed for ABO blood group, including ABO genotyping. The donor and recipient were tested for ABO, non-ABO, and human leukocyte antigen (HLA) antibodies. The donor and recipient were typed for HLA antigens, including T- and B-flow cytometry crossmatch tests. The recipient's RBCs were negative with A1 lectin, and immunoglobulin G anti-A1 was demonstrated in the recipient's plasma. The donor-recipient pair was a four-antigen HLA mismatch, but final T- and B-flow cytometry crossmatch tests were compatible. The transplant procedure was uneventful; the patient experienced immediate graft function with no episodes of rejection or readmissions more than 2 years later. It may be safe to transplant across the A1/A2 blood group AB mismatch barrier in the setting of low titer anti-A1 isoagglutinins without the need for pretransplant desensitization even if the antibody produced reacts with anti-human globulin. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. The changing relationship between HbA1c and FPG according to different FPG ranges.

    Science.gov (United States)

    Guan, X; Zheng, L; Sun, G; Guo, X; Li, Y; Song, H; Tian, F; Sun, Y

    2016-05-01

    Since the American Diabetes Association included hemoglobin A1c (HbA1c) in the diagnostic criteria for diabetes in 2010, the clinical use of HbA1c has remained controversial. We explored the use of HbA1c for diagnosing diabetes and intermediate hyperglycemia in comparison with fasting plasma glucose (FPG). We screened 3710 adult subjects (mean age = 55.24 years) comprising 1704 males and 2006 females. We drew an receiver operating characteristic (ROC) curve to evaluate the ability of HbA1c to diagnose diabetes and intermediate hyperglycemia according to FPG. We used Kappa coefficient and Pearson's correlation coefficient to evaluate the relationship between HbA1c and FPG in different FPG ranges. The areas under ROC curve to diagnose diabetes and intermediate hyperglycemia were 0.859 (95 % CI 0.827-0.892) and 0.633 (95 % CI 0.615-0.651). The kappa coefficients between FPG and HbA1c for diagnosis of diabetes and intermediate hyperglycemia were 0.601 (P HbA1c was 0.640 (P HbA1c and FPG changed according to the different FPG ranges. When FPG was higher, the relationship was stronger. HbA1c and FPG were highly consistent in diagnosing diabetes, but they were not in predicting intermediate hyperglycemia.

  11. Phylogenetic relationships among Perissodactyla: secretoglobin 1A1 gene duplication and triplication in the Equidae family.

    Science.gov (United States)

    Côté, Olivier; Viel, Laurent; Bienzle, Dorothee

    2013-12-01

    Secretoglobin family 1A member 1 (SCGB 1A1) is a small anti-inflammatory and immunomodulatory protein that is abundantly secreted in airway surface fluids. We recently reported the existence of three distinct SCGB1A1 genes in the domestic horse genome as opposed to the single gene copy consensus present in other mammals. The origin of SCGB1A1 gene triplication and the evolutionary relationship of the three genes amongst Equidae family members are unknown. For this study, SCGB1A1 genomic data were collected from various Equus individuals including E. caballus, E. przewalskii, E. asinus, E. grevyi, and E. quagga. Three SCGB1A1 genes in E. przewalskii, two SCGB1A1 genes in E. asinus, and a single SCGB1A1 gene in E. grevyi and E. quagga were identified. Sequence analysis revealed that the non-synonymous nucleotide substitutions between the different equid genes coded for 17 amino acid changes. Most of these changes localized to the SCGB 1A1 central cavity that binds hydrophobic ligands, suggesting that this area of SCGB 1A1 evolved to accommodate diverse molecular interactions. Three-dimensional modeling of the proteins revealed that the size of the SCGB 1A1 central cavity is larger than that of SCGB 1A1A. Altogether, these findings suggest that evolution of the SCGB1A1 gene may parallel the separation of caballine and non-caballine species amongst Equidae, and may indicate an expansion of function for SCGB1A1 gene products. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status.

    Science.gov (United States)

    Rodriguez-Segade, Santiago; Garcia, Javier Rodriguez; García-López, José M; Gude, Francisco; Casanueva, Felipe F; Rs-Alonso, Santiago; Camiña, Félix

    2016-12-01

    Several hematological alterations are associated with altered hemoglobin A 1c (Hb A 1c ). However, there have been no reports of their influence on the rates of exceeding standard Hb A 1c thresholds by patients for whom Hb A 1c determination is requested in clinical practice. The initial data set included the first profiles (complete blood counts, Hb A 1c , fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A 1c . Fasting glucose, MCH, and age emerged as predictors of Hb A 1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A 1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A 1c , a 1 pg increase in MCH reduced the odds of Hb A 1c -defined dysglycemia, diabetes and poor glycemia control by 10%-14%. For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A 1c -based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A 1c levels in clinical practice. © 2016 American Association for Clinical Chemistry.

  13. CYP1A1, CYP1A2, SULT1A1 AND SULT1E1 ALLELIC POLYMORPHISM IN CASE OF GENITAL ENDOMETRIOSIS

    Directory of Open Access Journals (Sweden)

    Konstantin Sergeevich Kublinskiy

    2016-02-01

    Up-to-date molecular and genetic analyses reveal that women predisposed to genital endometriosis possess Allele G and Genotypes AG and GG of the polymorphic option A-4889G of the CYP1A1 gene and Allele A and Genotypes CA and AA of the polymorphic option C-734A of the CYP1A2 gene. The polymorphism of the promoter regions of the SULT1A1 (G-638A and SULT1E1 (C-174T genes is not associated with genital endometriosis in women.

  14. Gambaran Populasi Golongan Darah Subgroup A (A1, A2 di PMI Kulon Progo

    Directory of Open Access Journals (Sweden)

    Hieronymus Rayi Prasetya

    2017-08-01

    Full Text Available Subgroup A1 and A2 are the most important in the blood group A. Subgroup A1 has the A antigen more than A2 subgroup, the A2 subgroup can cause misidentification of blood group due to poor A antigen and genetic variation possessed. Misidentification of the blood group will increase the risk of transfusion reactions. This research aims to describe the A1 and A2 subgroup population in Kulon Progo district. This study was conducted with a cross sectional sampling technique. The sample in this study were taken from donors of blood group A in Kulon Progo Red Cross. Identification of A1 and A2 subgroup is done by using lectin (Dolichos biflorus extract. The result of the examination of 53 samples showed that 96,2% was A1 subgroup and 3,8% was A2 subgroup. Key words : Subgroup A1, Subgroup A2, Population, Kulon Progo

  15. Serological Analysis of Immunogenic Properties of Recombinant Meningococcus IgA1 Protease-Based Proteins.

    Science.gov (United States)

    Kotelnikova, O V; Zinchenko, A A; Vikhrov, A A; Alliluev, A P; Serova, O V; Gordeeva, E A; Zhigis, L S; Zueva, V S; Razgulyaeva, O A; Melikhova, T D; Nokel, E A; Drozhzhina, E Yu; Rumsh, L D

    2016-07-01

    Using the genome sequence of IgA1 protease of N. meningitidis of serogroup B, four recombinant proteins of different structure and molecular weight were constructed. These proteins were equal in inducing the formation of specific antibodies to IgA1 protease and had protective properties against meningococci. In the sera of immunized mice, anti-IgA1 protease antibodies were detected by whole-cell ELISA, which indicated the presence of IgA1 protease on the surface of these bacteria. We hypothesized that the protective properties of IgA1 protease-based antigens and IgA1 protease analogs could be realized not only via impairment of bacterium adhesion to the mucosa, but also via suppression of this pathogen in the organism. The presented findings seem promising for using these proteins as the basis for anti-meningococcus vaccine.

  16. Mehrsprachigkeit in der nachhaltigen Universität. Projektbericht

    OpenAIRE

    Gogolin, Ingrid; Androutsopoulos, Jannis; Bührig, Kristin; Giannoutsou, Margarita; Lengyel, Drorit; Maggu, Juliette; Mösko, Mike; Mueller, Jessica Terese; Oeter, Stefan; Schmitt, Claudia; Schroedler, Tobias; Schulz, Holger; Siemund, Peter

    2017-01-01

    Die ... Kapitel dieses Berichts widmen sich den vier Teilprojekten der Pilotstudie. In Kapitel 2 wird zunächst das Teilprojekt 1 „Die Sprachen der Wissenschaft: Eine Pilotstudie zur forschenden Reflexion über Mehrsprachigkeit am Beispiel Nachhaltigkeitsforschung“ vorgestellt, das der Dimension der Wissenschaftsreflexion im Nachhaltigkeitskonzept der Universität entspricht. [...] Kapitel 3 stellt das Teilprojekt 2 dar: „Mehrsprachigkeit in der Medizin - Eine Pilotstudie zu Bedarfen, Ressourcen...

  17. Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Withey Laura

    2007-07-01

    Full Text Available Abstract Background Cytochrome P450 (CYP enzymes have the potential to affect colorectal cancer (CRC risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones. Methods To investigate if common variants of CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1 and CYP19A1 influence CRC risk we genotyped 2,575 CRC cases and 2,707 controls for 20 single nucleotide polymorphisms (SNPs that have not previously been shown to have functional consequence within these genes. Results There was a suggestion of increased risk, albeit insignificant after correction for multiple testing, of CRC for individuals homozygous for CYP1B1 rs162558 and heterozygous for CYP1A2 rs2069522 (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03–1.80 and OR = 1.34, 95% CI: 1.00–1.79 respectively. Conclusion This study provides some support for polymorphic variation in CYP1A2 and CYP1B1 playing a role in CRC susceptibility.

  18. Proresolving protein Annexin A1: The role in type 2 diabetes mellitus and obesity.

    Science.gov (United States)

    Pietrani, Nathalia T; Ferreira, Cláudia N; Rodrigues, Kathryna F; Perucci, Luiza O; Carneiro, Fernanda S; Bosco, Adriana A; Oliveira, Marina C; Pereira, Solange S; Teixeira, Antônio L; Alvarez-Leite, Jacqueline I; Ferreira, Adaliene V; Sousa, Lirlândia P; Gomes, Karina B

    2018-04-17

    Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls. DM patients showed similar AnxA1 serum levels when compared to controls. However, when the individuals were stratified according to BMI, AnxA1 levels were higher in individuals with obesity than lean or overweight, and in overweight compared to lean individuals. Moreover, AnxA1 was correlated positively with IL-6 levels. AnxA1 levels were also positively correlated with BMI, waist circumference and waist-to-hip ratio. Furthermore, higher levels of cleaved AnxA1 were observed in adipose tissue from individuals with obesity, independently of DM status. Enhanced levels of AnxA1 in serum of individuals with obesity suggest an attempt to counter-regulate the systemic inflammation process in this disease. However, the higher levels of cleaved AnxA1 in the adipose tissue of individuals with obesity could compromise its anti-inflammatory and proresolving actions, locally. Considering our data, AnxA1 cleavage in the adipose tissue, despite increased serum levels of this protein, and consequently the failure in inflammation resolution, suggests an important pathophysiological mechanism involved in inflammatory status observed in obesity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?

    Science.gov (United States)

    Jones, Angus G.; Lonergan, Mike; Henley, William E.; Pearson, Ewan R.; Hattersley, Andrew T.; Shields, Beverley M.

    2016-01-01

    Aims Baseline HbA1c is a major predictor of response to glucose lowering therapy and therefore a potential confounder in studies aiming to identify other predictors. However, baseline adjustment may introduce error if the association between baseline HbA1c and response is substantially due to measurement error and regression to the mean. We aimed to determine whether studies of predictors of response should adjust for baseline HbA1c. Methods We assessed the relationship between baseline HbA1c and glycaemic response in 257 participants treated with GLP-1R agonists and assessed whether it reflected measurement error and regression to the mean using duplicate ‘pre-baseline’ HbA1c measurements not included in the response variable. In this cohort and an additional 2659 participants treated with sulfonylureas we assessed the relationship between covariates associated with baseline HbA1c and treatment response with and without baseline adjustment, and with a bias correction using pre-baseline HbA1c to adjust for the effects of error in baseline HbA1c. Results Baseline HbA1c was a major predictor of response (R2 = 0.19,β = -0.44,pHbA1c were associated with response, however these associations were weak or absent after adjustment for baseline HbA1c. Bias correction did not substantially alter associations. Conclusions Adjustment for the baseline HbA1c measurement is a simple and effective way to reduce bias in studies of predictors of response to glucose lowering therapy. PMID:27050911

  20. Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

    Directory of Open Access Journals (Sweden)

    Jung Il Son

    2013-10-01

    Full Text Available BackgroundRecently, a hemoglobin A1c (HbA1c level of 6.5% has been determined to be a criterion for diabetes mellitus (DM, and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels.MethodsAnemic subjects (n=112 and age- and sex-matched controls (n=217 who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup.ResultsClinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580. However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05.ConclusionThese results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

  1. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  2. HbA1c, fasting plasma glucose and the prediction of diabetes

    DEFF Research Database (Denmark)

    Soulimane, Soraya; Simon, Dominique; Shaw, Jonathan

    2012-01-01

    With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases.......With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases....

  3. Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

    OpenAIRE

    Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

    2014-01-01

    Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

  4. Analysis of HbA1c on an automated multicapillary zone electrophoresis system.

    Science.gov (United States)

    Rollborn, Niclas; Åkerfeldt, Torbjörn; Nordin, Gunnar; Xu, Xiao Yan; Mandic-Havelka, Aleksandra; Hansson, Lars-Olof; Larsson, Anders

    2017-02-01

    Hemoglobin A1c (HbA1c) is a frequently requested laboratory test and there is thus a need for high throughput instruments for this assay. We evaluated a new automated multicapillary zone electrophoresis instrument (Capillarys 3 Tera, Sebia, Lisses, France) for analysis of HbA1c in venous samples. Routine requested HbA1c samples were analyzed immunologically on a Roche c6000 instrument (n = 142) and then with the Capillarys 3 Tera instrument. The Capillarys 3 Tera instrument performed approximately 70 HbA1c tests/hour. There was a strong linear correlation between Capillarys 3 Tera and Roche Tina-Quant HbA1c Gen 3 assay (y = 1.003x - 0.3246 R 2  = .996). The total CV for the 12 capillaries varied between 0.8 and 2.2% and there was a good agreement between duplicate samples (R 2  = .997). In conclusion, the Capillarys 3 Tera instrument has a high assay capacity for HbA1c. It has a good precision and agreement with the Roche Tina-Quant HbA1c method and is well suited for high volume testing of HbA1c.

  5. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    OpenAIRE

    Chandrashekar, Vani

    2016-01-01

    Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman's rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to st...

  6. Recent Progress in Electrochemical HbA1c Sensors: A Review

    Directory of Open Access Journals (Sweden)

    Baozhen Wang

    2015-03-01

    Full Text Available This article reviews recent progress made in the development of electrochemical glycated hemoglobin (HbA1c sensors for the diagnosis and management of diabetes mellitus. Electrochemical HbA1c sensors are divided into two categories based on the detection protocol of the sensors. The first type of sensor directly detects HbA1c by binding HbA1c on the surface of an electrode through bio-affinity of antibody and boronic acids, followed by an appropriate mode of signal transduction. In the second type of sensor, HbA1c is indirectly determined by detecting a digestion product of HbA1c, fructosyl valine (FV. Thus, the former sensors rely on the selective binding of HbA1c to the surface of the electrodes followed by electrochemical signaling in amperometric, voltammetric, impedometric, or potentiometric mode. Redox active markers, such as ferrocene derivatives and ferricyanide/ferrocyanide ions, are often used for electrochemical signaling. For the latter sensors, HbA1c must be digested in advance by proteolytic enzymes to produce the FV fragment. FV is electrochemically detected through catalytic oxidation by fructosyl amine oxidase or by selective binding to imprinted polymers. The performance characteristics of HbA1c sensors are discussed in relation to their use in the diagnosis and control of diabetic mellitus.

  7. Analytical performances of a new enzymatic assay for hemoglobin A1c.

    Science.gov (United States)

    Jaisson, Stéphane; Desmons, Aurore; Renard, Benoît; Chevelle, Benjamin; Leroy, Nathalie; Gillery, Philippe

    2014-07-01

    HbA1c is considered the gold standard for the follow-up of diabetic patients and a new diagnostic tool for diabetes mellitus, which implies the availability of reliable assay methods. We have evaluated a new assay developed by Abbott Laboratories, based on the enzymatic quantification of HbA1c by a fructosyl dipeptide oxidase using Architect analyzers. Precision, linearity, correlation with a HPLC method, accuracy and potential impact interferences on HbA1c measurement have been evaluated. Intra-day and between-day CVs were lower than 1.2% and linearity was excellent from 19 mmol/mol (3.9%) to 163 mmol/mol (17.1%). The results were well correlated with those obtained by the HPLC (Variant II device, kit NU - BioRad): HbA1c [Architect, mmol/mol]=0.986×HbA1c [Variant II, mmol/mol]+0.713 (r=0.998, n=109). This method provided consistent results with IFCC titrated quality control samples. Classical interferences in HbA1c assays (i.e. labile HbA1c, carbamylated hemoglobin, triglycerides or bilirubin) did not have an impact on HbA1c quantification by this method. This new enzymatic assay proved to be a robust and reliable method for HbA1c measurement suitable for routine practice in clinical chemistry laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. FoxA1 as a lineage-specific oncogene in luminal type breast cancer

    International Nuclear Information System (INIS)

    Yamaguchi, Noritaka; Ito, Emi; Azuma, Sakura; Honma, Reiko; Yanagisawa, Yuka; Nishikawa, Akira; Kawamura, Mika; Imai, Jun-ichi

    2008-01-01

    The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells

  9. The Analysis of A1 Level Speaking Exam in Terms of Syntax: The Effect of General Competence on Syntax in A1 Level Speaking

    Science.gov (United States)

    Misir, Hülya

    2017-01-01

    This study aims at discovering the relevance of general competence of Turkish and Arab learners who have an A1 level of English proficiency in preparatory school of University of Turkish Aeronautical Association (UTAA) to their speaking skill in terms of syntax by analyzing the recordings of speaking exams in the first semester. One can ask why…

  10. Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome.

    Science.gov (United States)

    Zhang, Dandan; Li, Zhenli; Xu, Xiaohong; Zhou, Dan; Tang, Shunli; Yin, Xiaoyang; Xu, Fangying; Li, Hui; Zhou, Yuan; Zhu, Tao; Deng, Hong; Zhang, Shuai; Huang, Qiong; Wang, Jing; Yin, Wei; Zhu, Yimin; Lai, Maode

    2017-10-26

    Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

    Science.gov (United States)

    Manchala, Nageswar Reddy; Dungdung, Ranjeet; Pilankatta, Rajendra

    2017-10-01

    Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. © 2017 John Wiley & Sons Ltd.

  12. MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dong [Department of Dermatology, General Hospital of People' s Liberation Army, Beijing 100853 (China); The 309th Hospital of China People' s Liberation Army, Beijing 100091 (China); Wang, Junyun; Ding, Nan [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yongjun; Yang, Yaran [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Fang, Xiangdong, E-mail: fangxd@big.ac.cn [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hua, E-mail: luckhua301@163.com [Department of Dermatology, General Hospital of People' s Liberation Army, Beijing 100853 (China)

    2016-05-13

    MAGE-A1 belongs to the chromosome X-clustered genes of cancer-testis antigen family and is normally expressed in the human germ line but is also overexpressed in various tumors. Previous studies of MAGE-A1 in melanoma mainly focused on methylation changes or its role in immunotherapy, however, its biological functions in melanoma have remained unknown. In order to determine the role of MAGE-A1 in melanoma growth and metastasis, we manipulated melanoma cell lines with overexpression and knockdown of MAGE-A1. Integration of cell proliferation assays, transwell migration and invasion assays, and RNA-Seq analysis revealed that up-regulation of MAGE-A1 dramatically promoted proliferation, migration, and invasion of human melanoma cell lines in vitro, while down-regulation of MAGE-A1 inhibited those characteristics associated with tumor cells. Furthermore, transcriptome sequencing revealed that MAGE-A1 exerts its tumor promoting activity by activating p-C-JUN directly or through ERK-MAPK signaling pathways. Based on our findings, we propose that MAGE-A1 may be a potential therapeutic target for melanoma patients. - Highlights: • MAGE-A1 promotes proliferation and clone formation in melanoma cell lines. • MAGE-A1 enhances tumor cell migration and invasion in melanoma cell lines. • Network including C-JUN, IL8, and ARHGAP29 play critical role in malignant melanoma. • Oncogenic MAGE-A1 increases p-C-JUN levels, possibly via ERK-MAPK signaling pathway.

  13. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    Science.gov (United States)

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

  14. Crystalline silica is a negative modifier of pulmonary cytochrome P-4501A1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Battelli, L.A.; Ghanem, M.M.; Kashon, M.L.; Barger, M.; Ma, J.Y.C.; Simoskevitz, R.L.; Miles, P.R.; Hubbs, A.F. [NIOSH, Morgantown, WV (United States). Health Effects Laboratory Division

    2008-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion that are commonly inhaled by workers in the dusty trades. Many PAHs are metabolized by cytochrome P-4501A1 (CYP1A1), which may facilitate excretion but may activate pulmonary carcinogens. PAHs also stimulate their own metabolism by inducing CYP1A1. Recent studies suggest that respirable coal dust exposure inhibits induction of pulmonary CYP1A1 using the model PAH {beta}-naphthoflavone. The effect of the occupational particulate respirable crystalline silica was investigated on PAH-dependent pulmonary CYP1A1 induction. Male Sprague-Dawley rats were exposed to intratracheal silica or vehicle and then intraperitoneal {beta}-naphthoflavone, a CYP1A1 inducer, and/or phenobarbital, an inducer of hepatic CYP2B1, or vehicle. {beta}-Naphthoflavone induced pulmonary CYP1A1, but silica attenuated this {beta}-naphthoflavone-induced CYP1A1 activity and also suppressed the activity of CYP2B1, the major constituitive CYP in rat lung. The magnitude of CYP activity suppression was similar regardless of silica exposure dose within a range of 5 to 20 mg/rat. Phenobarbital and beta-naphthoflavone had no effect on pulmonary CYP2B1 activity. Both enzymatic immunohistochemistry and immunofluorescent staining for CYP1A1 indicated that sites of CYP1A1 induction were nonciliated airway epithelial cells, endothelial cells, and the alveolar septum. Our findings suggest that in PAH-exposed rat lung, silica is a negative modifier of CYP1A1 induction and CYP2B1 activity.

  15. Epigenetic Regulation of Vitamin D 24-Hydroxylase/CYP24A1 in Human Prostate Cancer

    Science.gov (United States)

    Luo, Wei; Karpf, Adam R.; Deeb, Kristin K.; Muindi, Josephia R.; Morrison, Carl D.; Johnson, Candace S.; Trump, Donald L.

    2010-01-01

    Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the CYP24A1 gene which is downregulated in human prostate cancer by unknown mechanisms. We found that CYP24A1 expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) activates CYP24A1 expression in prostate cancer cells. In vitro methylation of the CYP24A1 promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of CYP24A1 in prostate cancer cells. ChIP-qPCR reveals that specific histone modifications are associated with the CYP24A1 promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the CYP24A1 promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of VDR to the CYP24A1 promoter. RT-PCR analysis of paired human prostate samples reveals that CYP24A1 expression is down-regulated in prostate malignant lesions compared to adjacent histologically benign lesions. Bisulfite pyrosequencing shows that CYP24A1 gene is hypermethylated in malignant lesions compared to matched benign lesions. Our findings indicate that repression of CYP24A1 gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. PMID:20587525

  16. 17 CFR 270.19a-1 - Written statement to accompany dividend payments by management companies.

    Science.gov (United States)

    2010-04-01

    ... that an open-end company may treat as a separate source its net profits from such sales during its... specify the sources from which the remainder was paid. Every company which in any fiscal year elects to... dividend payments by management companies. 270.19a-1 Section 270.19a-1 Commodity and Securities Exchanges...

  17. 17 CFR 240.36a1-2 - Exemption from SIPA for OTC derivatives dealers.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from SIPA for OTC derivatives dealers. 240.36a1-2 Section 240.36a1-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations...

  18. The role of SLC2A1 in early onset and childhood absence epilepsies

    DEFF Research Database (Denmark)

    Muhle, Hiltrud; Helbig, Ingo; Frøslev, Tobias Guldberg

    2013-01-01

    Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset...

  19. Novel structural features of xylanase A1 from Paenibacillus sp. JDR-2

    Science.gov (United States)

    Franz J. St John; James F. Preston; Edwin Pozharski

    2012-01-01

    The Gram-positive bacterium Paenibacillus sp. JDR-2 (PbJDR2) has been shown to have novel properties in the utilization of the abundant but chemically complex hemicellulosic sugar glucuronoxylan. Xylanase A1 of PbJDR2 (PbXynA1) has been implicated in an efficient process in which extracellular...

  20. High maternal HbA1c is associated with overweight in neonates

    DEFF Research Database (Denmark)

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E

    2011-01-01

    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (= 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA) infa...

  1. Distinct HbA1c trajectories in a type 2 diabetes cohort

    NARCIS (Netherlands)

    Walraven, I.; Mast, M.R.; Hoekstra, T.; Jansen, A.P.D.; van der Heijden, A.A.W.A.; Rauh, S.P.; Rutters, F.; van 't Riet, E.; Elders, P.J.M.; Moll, A.C.; Polak, B.C.P.; Dekker, J.M.; Nijpels, G.

    2015-01-01

    Aims: The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. Study design and setting: Data from a

  2. REDUCTION OF ADENOSINE-A1-RECEPTORS IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMER HIPPOCAMPUS

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of

  3. Association of CYP1A1 gene polymorphism with chronic kidney disease: a case control study.

    Science.gov (United States)

    Siddarth, Manushi; Datta, Sudip K; Ahmed, Rafat S; Banerjee, Basu D; Kalra, Om P; Tripathi, Ashok K

    2013-07-01

    CYP1A1 is an important xenobiotic metabolizing enzyme, present in liver and kidney. Expression of CYP1A1 enzyme increases manifold when kidney cells are exposed to nephrotoxins/chemicals leading to oxidative stress-induced cell damage. To study the association of CYP1A1 gene polymorphism in patients of chronic kidney disease with unknown etiology (CKDU), we recruited 334 CKDU patients and 334 age and sex matched healthy controls. CYP1A1*2A and *2C polymorphisms were studied by PCR-RFLP and allele specific-PCR respectively. Subjects carrying at least one mutant allele of CYP1A1*2A (TC, CC) and *2C (AG, GG) were shown to be associated with 1.4-2-fold increased risk of CKDU. Also, genotypic combinations of hetero-/homozygous mutants of CYP1A1*2A (TC, CC) with hetero-/homozygous mutant genotypes of CYP1A1*2C (AG, GG) i.e. TC/AG (pCKDU with an odd ratio ranging 1.8-3.3 times approximately. This study demonstrates association of CYP1A1 polymorphisms with CKDU. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. 26 CFR 48.4216(a)-1 - Charges to be included in sale price.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Charges to be included in sale price. 48.4216(a)-1 Section 48.4216(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... sales promotion programs, or otherwise. With respect to the rules relating to exclusion (in the case of...

  5. Investigation and Analysis of Hemoglobin A1c Measurement Systems' Performance for 135 Laboratories in China

    Directory of Open Access Journals (Sweden)

    Hai-Jian Zhao

    2017-01-01

    Conclusions: This study indicated that, although participating laboratories were laboratories with better performance in China, the performances were still unsatisfactory. Actions should be taken to improve HbA1c measurement performance before we can include HbA1c assays in diabetes diagnosis in China.

  6. 17 CFR 240.11a-1 - Regulation of floor trading.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Regulation of floor trading... Securities Exchange Act of 1934 Adoption of Floor Trading Regulation (rule 11a-1) § 240.11a-1 Regulation of floor trading. (a) No member of a national securities exchange, while on the floor of such exchange...

  7. 17 CFR 275.204A-1 - Investment adviser codes of ethics.

    Science.gov (United States)

    2010-04-01

    ... ethics. 275.204A-1 Section 275.204A-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... codes of ethics. (a) Adoption of code of ethics. If you are an investment adviser registered or required... enforce a written code of ethics that, at a minimum, includes: (1) A standard (or standards) of business...

  8. Comparison of Technology Use between Biology and Physics Teachers in a 1:1 Laptop Environment

    Science.gov (United States)

    Crook, Simon J.; Sharma, Manjula D.; Wilson, Rachel

    2015-01-01

    Using a mixed-methods approach the authors compared the associated practices of senior physics teachers (n = 7) and students (n = 53) in a 1:1 laptop environment with those of senior biology teachers (n = 10) and students (n = 125) also in a 1:1 laptop environment, in seven high schools in Sydney, NSW, Australia. They found that the physics…

  9. A novel CYP1A1 gene polymorphism and the risk of head and neck ...

    African Journals Online (AJOL)

    Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. In this study, we assessed the role of CYP1A1 genotype in 388 head and neck cancer patients in Pakistani population via a case-control study. Polymerase chain reaction ...

  10. 26 CFR 1.6031(a)-1 - Return of partnership income.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Return of partnership income. 1.6031(a)-1...) INCOME TAX (CONTINUED) INCOME TAXES Information Returns § 1.6031(a)-1 Return of partnership income. (a) Domestic partnerships—(1) Return required. Except as provided in paragraphs (a)(3) and (c) of this section...

  11. Data of evolutionary structure change: 1A1SA-2ATCA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1A1SA-2ATCA 1A1S 2ATC A A VVSLAGRDLLCLQDYTAEEIWTILETAKMFKIWQKIGKP...entryChain> 2ATC A 2ATCA TEFSGNVP...entryChain> 2ATC A 2ATCA MVGDLKYG...ntryChain> 2ATC A 2ATCA ALAKFDGNR...VID> 3 2ATC A 2ATCA

  12. In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update

    Directory of Open Access Journals (Sweden)

    English E

    2014-07-01

    Full Text Available Emma English,1 Elise T Milosevich,1 W Garry John2 1School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom; 2Department of Clinical Biochemistry, Norfolk and Norwich University Hospital, Norwich, United Kingdom Abstract: It is fascinating to consider the analytical improvements that have occurred since glycated hemoglobin was first used in routine clinical laboratories for diabetes monitoring around 1977; at that time methods displayed poor precision, there were no calibrators or material with assayed values for quality control purposes. This review outlines the major improvements in hemoglobin A1c (HbA1c measurement that have occurred since its introduction, and reflects on the increased importance of this hemoglobin fraction in the monitoring of glycemic control. The use of HbA1c as a diagnostic tool is discussed in addition to its use in monitoring the patient with diabetes; the biochemistry of HbA1c formation is described, and how these changes to the hemoglobin molecule have been used to develop methods to measure this fraction. Standardization of HbA1c is described in detail; the development of the IFCC Reference Measurement Procedure for HbA1c has enabled global standardization to be achieved which has allowed global targets to be set for glycemic control and diagnosis. The importance of factors that may interfere in the measurement of HbA1c are highlighted. Keywords: glycated hemoglobin, HbA1c, IFCC

  13. Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography

    NARCIS (Netherlands)

    Bots, Michael; Stroobants, An K.; Delzenne, Barend; Soeters, Maarten R.; de Vries, Johan E.; Weykamp, Cas W.; Norg, Roelf J. C.; Veldthuis, Martijn; van Zwieten, Rob

    2015-01-01

    Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. Glycated forms of novel Hb variants were recognised in the blood of two patients with

  14. Col4a1 mutations cause progressive retinal neovascular defects and retinopathy.

    Science.gov (United States)

    Alavi, Marcel V; Mao, Mao; Pawlikowski, Bradley T; Kvezereli, Manana; Duncan, Jacque L; Libby, Richard T; John, Simon W M; Gould, Douglas B

    2016-01-27

    Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant-negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Müller cells and increased expression of pro-angiogenic factors in retinas from Col4a1(+/Δex41)mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk of retinal hemorrhages and that retinal examinations may be useful for identifying patients with COL4A1 and COL4A2 mutations who are also at elevated risk of hemorrhagic strokes.

  15. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Vani Chandrashekar

    2016-01-01

    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  16. 26 CFR 1.381(a)-1 - General rule relating to carryovers in certain corporate acquisitions.

    Science.gov (United States)

    2010-04-01

    ... corporate acquisitions. 1.381(a)-1 Section 1.381(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT...)-1 General rule relating to carryovers in certain corporate acquisitions. (a) Allowance of carryovers... requirements of section 354(b)(1)(A) and (B) are satisfied; and (v) A mere change in identity, form, or place...

  17. Production of the Allergenic Protein Alt a 1 by Alternaria Isolates from Working Environments

    Directory of Open Access Journals (Sweden)

    Justyna Skóra

    2015-02-01

    Full Text Available The aim of the study was to evaluate the ability of Alternaria isolates from workplaces to produce Alt a 1 allergenic protein, and to analyze whether technical materials (cellulose, compost, leather present within the working environment stimulate or inhibit Alt a 1 production (ELISA test. Studies included identification of the isolated molds by nucleotide sequences analyzing of the ITS1/ITS2 regions, actin, calmodulin and Alt a 1 genes. It has been shown that Alternaria molds are significant part of microbiocenosis in the archive, museum, library, composting plant and tannery (14%–16% frequency in the air. The presence of the gene encoding the Alt a 1 protein has been detected for the strains: Alternaria alternata, A. lini, A. limoniasperae A. nobilis and A. tenuissima. Environmental strains produced Alt a 1 at higher concentrations (1.103–6.528 ng/mL than a ATCC strain (0.551–0.975 ng/mL. It has been shown that the homogenization of the mycelium and the use of ultrafiltration allow a considerable increase of Alt a 1 concentration. Variations in the production of Alt a 1 protein, depend on the strain and extraction methods. These studies revealed no impact of the technical material from the workplaces on the production of Alt a 1 protein.

  18. 26 CFR 25.2523(a)-1 - Gift to spouse; in general.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Gift to spouse; in general. 25.2523(a)-1...) ESTATE AND GIFT TAXES GIFT TAX; GIFTS MADE AFTER DECEMBER 31, 1954 Deductions § 25.2523(a)-1 Gift to spouse; in general. (a) In general. In determining the amount of taxable gifts for the calendar quarter...

  19. The role of SCL2A1 in Early Onset and Childhood Absence Epilepsies

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    brother and the paternal grandmother. Conclusion: Our study confirmed the role of SLC2A1 mutation carriers in EOAE and demonstrated that SLC2A1 do not seem to play a major role in CAE and JAE. Since ketogenic diet is a well known treatment option in GLUT-1-deficiency, pediatricians as well as neurologists...

  20. Dynamic Regulation of FoxA1 by Steroid Receptors | Center for Cancer Research

    Science.gov (United States)

    The estrogen receptor (ER) is a key regulator in breast cancer initiation and progression. A widely discussed model proposes that forkhead box protein A1 (FoxA1) acts as a pioneer factor in cancer by binding and penetrating closed chromatin to allow access by transcription factors (TFs), including ER.

  1. 26 CFR 1.468A-1T - Nuclear decommissioning costs; general rules (temporary).

    Science.gov (United States)

    2010-04-01

    ... accrual method of accounting that do not elect the application of section 468A are not allowed a deduction... (temporary). 1.468A-1T Section 1.468A-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...-1T Nuclear decommissioning costs; general rules (temporary). (a) Introduction. Section 468A provides...

  2. Telemetry Standards, RCC Standard 106-17, Annex A.1, Pulse Amplitude Modulation Standards

    Science.gov (United States)

    2017-07-01

    Standard 106-17 Annex A.1, July 2017 A.1-iii Acronyms dB decibel FM frequency modulation IF intermediate frequency PAM pulse amplitude...premodulation filter when employed. b. One-fifth of the intermediate frequency (IF) bandwidth (3 dB points) selected from the IF bandwidths listed in

  3. Correlates of Cytochrome P450 1A1 Expression in Bottlenose Dolphin (Tursiops truncatus) Integument Biopsies

    NARCIS (Netherlands)

    Wilson, J.Y.; Wells, R.; Anguilar, A.; Borrell, A.; Tornero, V.; Reijnders, P.J.H.; Moore, M.

    2007-01-01

    Integument biopsy is a nondestructive method for sampling free-ranging cetaceans, which allows for the determination of both contaminant concentrations and biomarker responses. Cytochrome P450 1A1 (CYP1A1) expression is induced by polycyclic aromatic hydrocarbons and planar halogenated aromatic

  4. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    DEFF Research Database (Denmark)

    Carvill, Gemma L; McMahon, Jacinta M; Schneider, Amy

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutatio...

  5. Evaluation of P availability from Fe and A1 labelled (32P) phosphates

    International Nuclear Information System (INIS)

    Bittencourt, V.S.

    1975-07-01

    Synthetically Fe and A1 labelled phosphates ( 32 P) show a certain amount of available P to the plants when applied to Sao Paulo State soils. This availability decreases from considered amorphous A1-phosphate (A1-P sub(am)) to A1 phosphate with a certain cristalinity grade (A1-P sub(cr)) and than from this to Fe-P sub(am) followed by Fe-P sub(cr), and it is influenced by both the soil characteristics and mainly by the iron constituents of the samples. In this way, one can not expect that the 0,05 N 2 H SO 4 and the CHANG and JACKSON (1957a) solutions can define properly the available P of these soils. The addition of lime to the soils do not drive to a better P absorption by the plants and its effects are dubious

  6. Study on the DNA-protein crosslinks induced by chromium (VI) in SPC-A1

    Science.gov (United States)

    Liu, Yanqun; Ding, Jianjun; Lu, Xiongbing; You, Hao

    2018-01-01

    Objective: This study was designed to investigate the effect of chromium (VI) on DNA-protein crosslinks (DPC) of SPC-A1 cells. Methods: We exposed SPC-A1 cells were cultured in 1640 medium and treated with the SPC-A1 cells in vitro to different concentrations of Hexavalent chromium Cr(VI) for 2h, the KC1-SDS precipitation assay were used to measure the DNA-protein cross-linking effect. Results: All the different concentrations of Cr(VI) could cause the increase of DPC coefficient in SPC-A1 cells. But this effect was not significant (P>0.05) at low concentrations; while in high concentration Cr(VI) induced SPC-A1 cells could produce DNA-protein cross-linking effect significantly (P<0.05). Conclusions: chromium (VI) could induce DNA-protein crosslink.

  7. Trajectories of HbA1c Levels in Children and Youth with Type 1 Diabetes

    Science.gov (United States)

    Pinhas-Hamiel, Orit; Hamiel, Uri; Boyko, Valentina; Graph-Barel, Chana; Reichman, Brian; Lerner-Geva, Liat

    2014-01-01

    Purpose To illustrate the distribution of Hemoglobin A1c (HbA1c) levels according to age and gender among children, adolescents and youth with type 1 diabetes (T1DM). Methods Consecutive HbA1c measurements of 349 patients, aged 2 to 30 years with T1DM were obtained from 1995 through 2010. Measurement from patients diagnosed with celiac disease (n = 20), eating disorders (n = 41) and hemoglobinopathy (n = 1) were excluded. The study sample comprised 4815 measurements of HbA1c from 287 patients. Regression percentiles of HbA1c were calculated as a function of age and gender by the quantile regression method using the SAS procedure QUANTREG. Results Crude percentiles of HbA1c as a function of age and gender, and the modeled curves produced using quantile regression showed good concordance. The curves show a decline in HbA1c levels from age 2 to 4 years at each percentile. Thereafter, there is a gradual increase during the prepubertal years with a peak at ages 12 to 14 years. HbA1c levels subsequently decline to the lowest values in the third decade. Curves of females and males followed closely, with females having HbA1c levels about 0.1% (1.1 mmol/mol) higher in the 25th 50th and 75th percentiles. Conclusion We constructed age-specific distribution curves for HbA1c levels for patients with T1DM. These percentiles may be used to demonstrate the individual patient's measurements longitudinally compared with age-matched patients. PMID:25275650

  8. Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose?

    Directory of Open Access Journals (Sweden)

    So-Young Kim

    2014-01-01

    Full Text Available Background Published studies report inappropriately low hemoglobin A1C (HbA1c values that underestimate glycemia in HIV patients. Methods We reviewed the charts of all HIV patients with diabetes mellitus (DM at our clinic. Fifty-nine patients had HbA1c data, of whom 26 patients also had fructosamine data. We compared the most recent HbA1c to finger-stick (FS glucose averaged over three months, and fructosamine to FS averaged over six weeks. Predicted average glucose (pAG was calculated as reported by Nathan et al: pAG (mg/dL = 28.7 × A1C% – 46.7. Data were analyzed using the Statistical Analysis System (SAS and Kruskal–Wallis test. Results HbA1c values underestimated (UE actual average glucose (aAG in 19% of these patients and overestimated (OE aAG in 27%. HbA1c estimated aAG within the established range in only 54% of the patients. There were no statistical differences in the types of HIV medication used in patients with UE, OE, or accurately estimated (AE glycemia. A Spearman correlation coefficient between HbA1c and aAG was r = 0.53 ( P < 0.0001. Correlation between fructosamine and aAG was r = 0.47 ( P = 0.016. Conclusions The correlations between HbA1c and aAG and between fructosamine and aAG were weaker than expected, and fructosamine was not more accurate than HbA1c.

  9. Subgenotype A1 of HBV--tracing human migrations in and out of Africa.

    Science.gov (United States)

    Kramvis, Anna; Paraskevis, Dimitrios

    2013-01-01

    HBV subgenotype A1 is the dominant genotype A strain in Africa, with molecular characteristics differentiating it from A2, which prevails elsewhere. Outside Africa, A1 is confined to areas with migration history from Africa, including India and Latin America. The aim of this study was to reconstruct A1 phylogeny on a spatial scale in order to determine whether A1 can be used to track human migrations. A phylogenetic comparison of A1 was established using neighbour-joining analysis of complete genomes, and the Bayesian method, implemented in BEAST, was performed on the S region of isolates from 22 countries. Migration events were estimated by ancestral state reconstruction using the criterion of parsimony. From the tree reconstruction, nucleotide divergence calculations and migration analysis, it was evident that Africa was the source of dispersal of A1 globally, and its dispersal to Asia and Latin America occurred at a similar time period. Strains from South Africa were the most divergent, clustering in both the African and Asian/American clades and a South African subclade was the origin of A1. The effect of the 9th to 19th century trade and slave routes on the dispersal of A1 was evident and certain unexpected findings, such as the co-clustering of Somalian and Latin American strains, and the dispersal of A1 from India to Haiti, correlated with historical evidence. Phylogeographic analyses of subgenotype A1 can be used to trace human migrations in and out of Africa and the plausible sites of origin and migration routes are presented.

  10. NR4A1 is an endogenous inhibitor of vocal fold fibrosis.

    Science.gov (United States)

    Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C

    2017-09-01

    NR4A1 was recently identified as an endogenous inhibitor of transforming growth factor (TGF)-β-induced fibrosis, and the role of this nuclear receptor has not been elucidated in tissue health or the response to injury in the vocal folds. Given the clinical implications of vocal fold fibrosis, we investigated NR4A1 expression during vocal fold wound healing in vivo and the regulatory roles of NR4A1 on vocal fold fibroblasts (VFFs) in vitro with the ultimate goal of developing targeted therapies for this challenging patient population. In vivo and in vitro. In vivo, the temporal pattern of NR4A1 mRNA expression was quantified following rat vocal fold injury. In vitro, the role of NR4A1 on TGF-β1-mediated transcription of genes underlying fibrosis as well as myofibroblast differentiation and collagen gel contraction was quantified in our human VFF line. Small interfering RNA was employed to alter NR4A1 expression to further elucidate this complex system. Nr4a1 mRNA increased 1 day after injury and peaked at 7 days. Knockdown of NR4A1 resulted in upregulation of COL1A1 and TGF-β1, with TGF-β1 stimulation (both P vocal fold health or disease. Upregulation of TGF-β following vocal fold injury was concurrent with increased NR4A1 expression. These data provide a foundation for the development of therapeutic strategies given persistent TGF-β signaling in vocal fold fibrosis. N/A Laryngoscope, 127:E317-E323, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Harman induces CYP1A1 enzyme through an aryl hydrocarbon receptor mechanism

    International Nuclear Information System (INIS)

    El Gendy, Mohamed A.M.; El-Kadi, Ayman O.S.

    2010-01-01

    Harman is a common compound in several foods, plants and beverages. Numerous studies have demonstrated its mutagenic, co-mutagenic and carcinogenic effects; however, the exact mechanism has not been fully identified. Aryl hydrocarbon receptor (AhR) is a transcription factor regulating the expression of the carcinogen-activating enzyme; cytochrome P450 1A1 (CYP1A1). In the present study, we examined the ability of harman to induce AhR-mediated signal transduction in human and rat hepatoma cells; HepG2 and H4IIE cells. Our results showed that harman significantly induced CYP1A1 mRNA in a time- and concentration-dependent manner. Similarly, harman significantly induced CYP1A1 at protein and activity levels in a concentration-dependent manner. Moreover, the AhR antagonist, resveratrol, inhibited the increase in CYP1A1 activity by harman. The RNA polymerase inhibitor, actinomycin D, completely abolished the CYP1A1 mRNA induction by harman, indicating a transcriptional activation. The role of AhR in CYP1A1 induction by harman was confirmed by using siRNA specific for human AhR. The ability of harman to induce CYP1A1 was strongly correlated with its ability to stimulate AhR-dependent luciferase activity and electrophoretic mobility shift assay. At post-transcriptional and post-translational levels, harman did not affect the stability of CYP1A1 at the mRNA and the protein levels, excluding other mechanisms participating in the obtained effects. We concluded that harman can directly induce CYP1A1 gene expression in an AhR-dependent manner and may represent a novel mechanism by which harman promotes mutagenicity, co-mutagenicity and carcinogenicity.

  12. Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population.

    Science.gov (United States)

    Alam, Jawed; Ghosh, Prachetash; Ganguly, Mou; Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2015-01-01

    The duodenal ulcer promoting gene (dupA) and dupA cluster in Helicobacter pylori have been described as a risk factor for duodenal ulcer development in some populations. Polymorphic gene dupA can be divided into two groups, intact dupA1 (long or short type based on the presence or absence of 615-bp extra sequences at the 5' region) having complete reading frame and other truncated dupA2 having frame-shift mutation. This study was aimed to elucidate the role of dupA of H. pylori and their clusters in the disease manifestation of Indian population. A total of 170 H. pylori strains were screened for the presence of dupA, dupA alleles and dupA cluster by PCR and sequencing. Pro-inflammatory cytokine (IL-8) with different dupA variant H. pylori stimulated gastric epithelial cells (AGS cells) was measured by ELISA. A total of 50 strains (29.4%) were positive for dupA among the tested 170 strains. The prevalence of dupA1 in duodenal ulcer (DU) and non-ulcer dyspepsia (NUD) populations was found to be 25.5% (25/98) and 11.1% (8/72), respectively and 16.4% (28/170) of the tested strains had dupA1, cagA and vacAs1m1 positive. The distribution of long and short type dupA1 has not been significantly associated with the disease outcome. The dupA cluster analysis showed that 10.2% (10/98) and 8.3% (6/72) strains were positive among DU and NUD, respectively. IL-8 production was significantly higher in dupA1(+) , cagA (+), vacA (+) (902.5 ± 79.01 pg/mL) than dupA2 (+) , cagA (+) , vacA (+) (536.0 ± 100.4 pg/mL, P = 0.008) and dupA (-), cagA (+), vacA (+) (549.7 ± 104.1 pg/mL, P = 0.009). Phylogenetic analysis of dupA indicated that the Indian H. pylori strains clustered with East Asian strains but distinct from Western strains. This is the first known genetic element of Indian H. pylori that is genetically closer to the East Asian strains but differed from the Western strains. The intact dupA1 was significantly associated with DU than NUD (P = 0

  13. Annexin A1 is elevated in patients with COPD and affects lung fibroblast function

    Directory of Open Access Journals (Sweden)

    Lai TW

    2018-02-01

    Full Text Available Tianwen Lai,1,* Yanyu Li,1,* Zongjiong Mai,2 Xiaoxia Wen,1 Yingying Lv,1 Zhanqing Xie,3 Quanchao Lv,1 Min Chen,1 Dong Wu,1 Bin Wu1 1Department of Respiratory and Critical Care Medicine, 2Department of Oncology, 3Department of Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Purpose: Fibrosis in peripheral airways is responsible for airflow limitation in chronic obstructive pulmonary disease (COPD. Annexin A1 modulates several key biological events during inflammation. However, little is known about its role in airway fibrosis in COPD. We investigated whether levels of Annexin A1 were upregulated in patients with COPD, and whether it promoted airway fibrosis.Methods: We quantified serum Annexin A1 levels in never-smokers (n=12, smokers without COPD (n=11, and smokers with COPD (n=22. Correlations between Annexin A1 expression and clinical indicators (eg, lung function were assessed. In vitro, human bronchial epithelial (HBE cells were exposed to cigarette smoke extract (CSE and Annexin A1 expression was assessed. Primary human lung fibroblasts were isolated from patients with COPD and effects of Annexin A1 on fibrotic deposition of lung fibroblasts were evaluated.Results: Serum Annexin A1 was significantly higher in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines stage III or IV than in those with GOLD stages I or II (12.8±0.8 ng/mL versus 9.8±0.7 ng/mL; p=0.016. Annexin A1 expression was negatively associated with airflow obstruction (forced expiratory volume in one second % predicted; r=−0.72, p<0.001. In vitro, Annexin A1 was significantly increased in CSE-exposed HBE cells in a time- and concentration-dependent manner. Annexin A1 promoted lung fibroblasts proliferation, migration, differentiation, and collagen deposition via the ERK1/2 and p38 mitogen-activated protein kinase pathways

  14. Is insulin the preferred treatment for HbA1c >9%?

    Science.gov (United States)

    Bloomgarden, Zachary

    2017-09-01

    The algorithms and guidelines of the American Association of Clinical Endocrinologists and the American Diabetes Association recommend that insulin administration be strongly considered for people with type 2 diabetes (T2D) with HbA1c levels exceeding 9.0% and 10%, respectively. Although the caveat is given in both sets of recommendations that this is particularly appropriate when patients are "symptomatic," referring to urinary frequency with increased thirst and appetite, weight loss, and ketosis, the clinical definition of such presentations may be ill-defined, and it is noteworthy that both documents consider insulin to offer particular benefit under such circumstances. However, with multiple options for glycemic treatment, it is of interest to reconsider this argument for insulin use. It should be recalled that in the UK Prospective Diabetes Study, diet alone was associated with a reduction in HbA1c from 9% to 7%. Drug-naïve people with T2D do often show surprisingly strong reductions in HbA1c with metformin-based dual-agent oral treatment approaches; a recent report showed that even with baseline HbA1c >11%, the combination of metformin with a sulfonylurea, pioglitazone, or sitagliptin was associated with reduction in HbA1c from 11.6% to 6.0%. A 32-week study of the combination of rosiglitazone with metformin in patients with mean baseline HbA1c 8.9% showed a mean HbA1c reduction of 2.3%, and an open-label cohort with baseline HbA1c 11.8% had a reduction in HbA1c to 7.8%. With metformin plus sitagliptin, a mean placebo-adjusted HbA1c reduction of 2.1% from a baseline of 8.8% was reported, with those patients with baseline HbA1c >9% having a 2.6% reduction in HbA1c, and an open-label cohort with baseline HbA1c 11.2% having a 2.9% reduction in HbA1c. Similar 2% HbA1c reductions from baseline levels of 9.1% were seen with metformin in initial combination with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin. Although such dual oral agent

  15. Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge.

    Science.gov (United States)

    Ridgely, Sherritta L; Zhang, Baoshan; McGuire, Travis C

    2003-01-17

    Lipopeptide containing an ELA-A1-restricted cytotoxic T lymphocyte (CTL) epitope from the envelope surface unit (SU) protein of the EIAV(WSU5) strain was used to immunize three horses having the ELA-A1 haplotype. Peptide-specific ELA-A1-restricted CTL were induced in all three horses, although these were present transiently in PBMC. These horses were further immunized with lipopeptide containing the corresponding CTL epitope from the EIAV(PV) strain. Then, the three immunized horses and three non-immunized horses were challenged by intravenous inoculation with 300 TCID(50) EIAV(PV). All horses developed cell free viremia, fever and thrombocytopenia. However, there was a statistically lower fever and thrombocytopenia severity score in the immunized group. Shorter duration of plasma viral load in two of the three immunized horses likely explains the less severe clinical disease in this group. Results indicate that lipopeptide immunization had a protective effect against development of clinical disease following virus challenge.

  16. HTGT-Turbotech II. Project: 1.222: transonic diffusers and resulting unsteady effects. Final report; HTGT-Turbotech II. Teilprojekt 1.222: Transsonische Diffusoren und resultierende instationaere Effekte. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Stetter, H.; Margot-Peters, X.; Kraus, P.

    1999-12-01

    The tip gap between rotor blades and the casing of a turbomachine is essential for a safe operation. Behind the last stage the resulting leakage jet may however cause a supersonic flow region at the outer diffuser casing which can induce - due to shock/boundary layer interactions - unsteady shock oscillations. Until now this process can't be described numerically. Therefore the scope of this project was to provide an extensive validated numerical code which can be used simultaneously to optimize the diffuser's flow properties and to minimize the blade loading due to shock oscillations. Fundamental questions such as shock oscillation amplitudes and influence area of the leakage jet had been answered by using the hydraulic analogy. To realize the flow properties steady and unsteady flow measurements had been carried out at an air test rig to deliver boundary conditions and validation data for the numerical code. Concerning the numerical work an existent steady Navier-Stokes-Code had been upgraded to unsteady calculations. Some turbulence models had been tested to proof its qualification for separated unsteady flows. However with the intended solution approach - no full threedimensional discretisation - it has been found impossible to converge the unsteady shock/boundary layer interaction calculations. Reasons are re-entry flow at the diffuser outlet and the measured, significant circumferential variation of flow properties. However important insights to the continuous work could be extracted from the preliminary negative results of the numerical studies: The circumferential variation of the flow properties can locally cause re-entry flow at the diffuser outlet. In addition the unsteady shock/boundary-interactions vary round the periphere, but they could be influenced by locally applied methods. Therefore a proofed numerical treatment supposes detailed solutions for the modelling of boundary conditions for re-entry flow and unsteady circumferentially varying flow, respectively. (orig.) [German] Fuer den sicheren Betrieb von Turbomaschinen ist ein Spalt zwischen der Rotorbeschaufelung und der Gehaeusewand unerlaesslich. Der dadurch entstehende Leckagestrom kann nach der letzten Stufe an der Diffusoraussenwand ein Ueberschallgebiet hervorrufen, das aufgrund von Stoss-Grenzschicht-Wechselwirkungen zu instationaeren Stosspulsationen fuehren kann. Dieser Vorgang kann numerisch noch nicht beschrieben werden. Ziel des Vorhabens war es deshalb, ein umfassend validiertes Simulationsprogramm bereitzustellen, mit dem der Diffusor hinsichtlich des Druckrueckgewinns optimal ausgelegt und gleichzeitig die Schaufelbelastung infolge der Stosspulsation minimiert werden kann. Grundlegende Fragestellungen - u.a. Bereich der Stosswanderung, Einflussbereich des Leckagestroms - wurden mit Hilfe der Flachwasseranalogie geklaert. Zur Erfassung der Stroemungsverhaeltnisse wurden an einem luftdurchstroemten Modellversuchsstand stationaere und instationaere Stroemungsmessungen durchgefuehrt, die die Randbedingungen fuer das zu entwickelnde Simulationsprogramm lieferten und zum anderen zu dessen Validierung dienen sollten. Im Rahmen der numerischen Arbeiten wurde ein vorhandener, stationaer rechnender Navier-Stokes-Code auf die Berechnung instationaerer Vorgaenge erweitert. Dazu wurden u.a. auch verschiedene Turbulenzmodelle getestet, um deren Eignung fuer abgeloeste, instationaere Stroemungen zu pruefen. Die instationaeren Berechnungen der Stoss-Grenzschicht-Wechselwirkungen konnten jedoch mit dem beabsichtigten Loesungsansatz - keine voll dreidimensionale Diskretisierung - nicht zur Konvergenz gebracht werden. Ursachen sind Rueckstroemgebiete in der Diffusionsaustrittsebene sowie die experimentell ermittelte, deutliche Variation der Stroemungsfeldgroessen ueber dem Umfang. Aus dem vorlaeufig negativen Ergebnis der numerischen Arbeiten wurden jedoch wichtige Erkenntnisse fuer weiterfuehrende Arbeiten gewonnen: Die ueber den Umfang nicht konstanten Stroemungsgroessen im Diffusoraustritt koennen lokal zu Rueckstroemungen fuehren. Auch das instationaere Stoss-Grenzschichtenverhalten ist ueber den Umfang nicht gleichartig, es kann jedoch durch lokale Massnahmen beeinflusst werden. Die sichere numerische Behandlung setzt daher Detailloesungen fuer die Formulierung der Ranbedingungen im Austritt voraus, zum einen bei Rueckstroemung, zum anderen bei ueber den Umfang verteilten, instationaeren Stroemungsgroessen. (orig.)

  17. Closing loops for material flows in surface treatment processes. Pt. 14: ecological and economic assessment and optimization. Final report and appendix; Stoffkreislaufschliessung bei abtragenden Verfahren in Prozessloesungen. Teilprojekt 14: Oekologische und oekonomische Beurteilung und Optimierung. Endbericht und Anhang

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, G.; Ackermann, R.; Scholz, C. [and others

    2001-09-01

    The industrial surface treatment of metallic and non-metallic materials is a relevant area in environmental protection. The surface-treatment industry causes polluted waste water and in addition sludges contaminated with heavy metals, which often have to be deposited as hazardous waste. Improvement of process techniques of the surface treatment is therefore an effective possibility decreasing the environmental impact. Target of this section of the research project was the ecological and economic evaluation of potential optimization possibilities for the involved enterprises and the co-operation during the optimization. For this research assignment it was determined to operate with a bottom-up methodology as in the systems analysis. The general instrument results thus as a derivative from the analysis of the methodologies with the special examples, which are processed as sample solutions. Within the framework of the work took place a use of methodical items from the LCI and the business administration. Additionally methods of process engineering and of systems analysis were applied. For the fulfillment of the target within this research assignment an objective evaluation and optimization instrument was developed and tested. With the help of this instrument it is possible to judge whether modifications on system actually reduce the ecological and economic impacts within the total system boundaries. For the support of the instrument several software-programs were used and developed. In addition, generalizable process models were elaborated and algorithms for determination and conversion to flow of material-minimizing technologies were derived and represented in generally. (orig.) [German] Die industrielle Oberflaechenbehandlung mit den zahlreichen Moeglichkeiten der Beschichtung und Abtragung von vorwiegend metallischen Werkstoffen ist ein relevanter Bereich im Umweltschutz. Es fallen neben belasteten Abwaessern auch schwermetallhaltige Schlaemme an, die oft als besonders ueberwachungsbeduerftige Abfaelle deponiert werden muessen. Verbesserungen der Prozesstechniken bei galvanotechnischen und metallchemischen Verfahren bieten deshalb eine wirksame Moeglichkeit, die Ursachen dieser Umweltbelastung zu verringern. Ziel dieses Teilvorhabens war es, potentielle Optimierungsmoeglichkeiten fuer die betrachteten Unternehmen oekologisch und oekonomisch zu beurteilen und bei der Optimierung mitzuwirken. Fuer dieses Teilvorhaben wurde festgelegt, im Sinne der systemanalytischen Bottom-up-Vorgehensweise zu arbeiten. Daraus ergibt sich fuer die methodische Vorgehensweise eine Ableitung des verallgemeinerungsfaehigen Instrumentes aus der Analyse der Vorgehensweisen bei den speziellen Beispielen, die als Musterloesungen bearbeitet werden. Mit der Vorgabe des methodischen Rahmens erfolgte eine Vorauswahl der methodischen Elemente aus der Oekobilanzmethode und der Betriebswirtschaftslehre. Zusaetzlich zu diesen beiden Methoden wurden zur inhaltlichen und strukturellen Gliederung verfahrenstechnische und systemanalytische Methoden angewandt. Innerhalb dieses Teilvorhabens wurde fuer die Zielerfuellung ein objektives Beurteilungs- und Optimierungsinstrument entwickelt und erprobt. Mit Hilfe dieses Instrumentes koennen Veraenderungen in einem System dahingehend beurteilt werden, ob sie in den Gesamtsystemgrenzen die oekologischen und oekonomischen Belastungen tatsaechlich reduzieren. Zur Unterstuetzung des Instrumentes wurden mehrere EDV-Programme genutzt und entwickelt. Des weiteren wurden verallgemeinerungsfaehige Prozessmodelle erarbeitet und Algorithmen zur Ermittlung und Durchsetzung von stoffflussminimierten Technologien abgeleitet und in allgemeingueltiger Weise dargestellt. (orig.)

  18. Librarian - phase 2. Subproject: the application of reflectometric interference spectroscopy (RIfS) in biological systems. Final report; Librarian - Phase 2. Teilprojekt: Anwendung des Verfahrens der Reflektometrischen Schichtdickenmessung zur Signaldetektion in biologischen Testsystemen und Festphasensynthesen. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Birk, G.; Hadamovsky, S.

    2000-07-01

    Label free methods that do not require fluorescence markers or radioactive isotopes are of interest for high throughput screening applications. Thus, a new assay type for the RIfS technology was developed. These phosphorylation assay experiments were tested for reproducibility and were validated, initially using a single channel machine. The use of surface active materials to reduce or eliminate non specific binding is recommended. The non specific binding of the individual reagents was an important factor for their integration in the RIfS method. The immobilisation of binding reagents was tested using various methods. Since the various combinations are essentially limitless, they could not be explored to their full extent within the confines of this project. The application of the assay into microtitre plate format was not fully completed within the time frame allotted, however, has since been completed by one of the project participants as part of a further cooperation. Theoretically, this method is also suited to the robotics and sample throughput integral to a HTS system A comprehensive evaluation of RIfS technology regarding its entry into high throughput screening, however can only be made with reservation, due to the limited experience with its use in 96 and 384 microtitre plates. (orig.)

  19. Investigations of time-dependent water pollution effects of overburden dumps - partial project 1. Final report; Untersuchungen gewaesserrelevanter Einfluesse von Bergbauhalden in Abhaengigkeit von der Standzeit - Teilprojekt 1. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Beuge, P.; Dunger, C.; Mibus, J.; Starke, R.

    1998-02-01

    Management of overburden dumps necessitates careful stocktaking and precise definitions of pollutant emissions so that, if necessary, conclusions can be drawn concerning sanitation concepts in consideration of emission limits and environmental balances. In view of the large number of overburden dumps in Saxony, Saxony-Anhalt and Thuringia caused the authors to restrict their investigations to ore mines and to select elements characteristic of the worked deposits and their potential environmental effects. The following problems were investigated: Are overburden dumps significant emitters of elements at all? Which elements are emitted in what concentrations, in what form and up to what distance from the dump? Are there really different patterns for gangue and impregnation types? How big is the real reaction space of the dump? Should the whole dump be assumed to be a reservoir of elements for emission or just parts of it? What are the factors that most strongly influence element mobilisation and/or retention? What measures should be recommended for emission reduction or prevention from the aspects of necessity, economic efficiency and long-term stability? (orig./SR) [Deutsch] Es ergibt sich fuer den Umgang mit Halden die Notwendigkeit einer gruendlichen Bilanzierung und schaerferen Definition von Schadstoffemission aus ihnen, um daraus Konsequenzen fuer eventuell erforderliche Sanierungskonzeptionen unter Beruecksichtigung von Grenzwerteinhaltung und Umweltbilanz abzuleiten. Der Umfang der einzelnen Fragestellungen und die Bedeutung der Halden in Sachsen, Sachsen-Anhalt und Thueringen sowie Anzahl und ihr Inhalt fuehrte zur Beschraenkung auf den Erzbergbau und auf die Kontrolle ausgewaehlter Elemente, die fuer den jeweils abgebauten Lagerstaetteninhalt charakteristisch und fuer die Wirkung auf die Umwelt von Bedeutung sind. Folgende konkrete Fragestellungen sollen verfolgt werden: - Sind Halden ueberhaupt nennenswerte Emittenten von Elementen? - Welche Elemente werden in welchen Konzentrationen bis zu welchen Entfernungen von der Halde in welcher Form emittiert? - Existieren die vermuteten Unterschiede und Muster zwischen Gangerz- und Impraegnationstyp? - Wie gross ist der Reaktionsraum einer Halde wirklich? Muss der gesamte Haldenkoerper als potentielles Elementereservoir fuer Emissionen zum Ansatz gebracht werden oder nur Anteile? - Kommt es zur selbstaendigen Ausbildung von haldeninternen geochemischen Barrieren? - Welche Fakto ren beeinflussen am staerksten die Mobilisation bzw. Retention von Elementen? - Welche Massnahmen erscheinen fuer eine Emissionserniedrigung oder -verhinderung am geeignetsten unter den Gesichtspunkten der Notwendigkeit, der Oekonomie und der Langzeitstabilitaet? (orig./SR)

  20. Investigations of water pollution effects of mining spoil heaps depending on the period of existence. Final report. Part project 2; Untersuchungen gewaesserrelevanter Einfluesse von Bergbauhalden in Abhaengigkeit von der Standzeit. Abschlussbericht. Teilprojekt 2

    Energy Technology Data Exchange (ETDEWEB)

    Puchelt, H.; Stueben, D.; Berner, Z.; Kappes, B.

    1996-12-01

    Apart form the main elements, the Wiesloch Ag-Pb-Zn mineralisation contains a series of higly toxic trace elements. The main ore minerals of galena, zinc blende and Menikow pyrites also contain Tl, Cd, As and Sb up to the precent range. The main and trace element contents of ores, flotation residues and slags were examined in detail. Their weathering properties were estimated, depending on the time of existence, from new secondary mineral formations. An element displacement from the spoil heaps reaching several decimetres in the ceiling was shown. Strong contamination can be proved by washing out and dispersion of As and Tl in agriculturally used areas and can be found in plants. Using elution experiments, the metal release of hevy metals and arsenic from ores, flotation wastes and slags was examined for the quantitative estimation of the material transfer. Also, the excellent suitability of synthetic Fe-Mn hydroxides for the decontamination of water containing arsenic and heavy metals was shown. (orig.) [Deutsch] Die Wieslocher Ag-Pb-Zn-Vererzung enthaelt neben den Hauptelementen eine Reihe von hochtoxischen Spurenelementen. Die Haupterzminerale Bleiglanz, Zinkblende und Melnikowitpyrit enthalten zusaetzlich Tl, Cd, As sowie Sb bis in den Prozentbereich. Im Detail wurde der Haupt- und Spurenelementgehalt von Erzen, Flotationsrueckstaenden und Schlacken untersucht. Ihre Verwitterungseigenschaften wurden in Abhaengigkeit der Standzeit anhand von sekundaeren Mineralneubildungen abgeschaetzt. Eine mehrere dm-weit reichende Elementverlagerung aus Halden in das Liegende (Loessdecke) konnte nachgewiesen werden. Starke Kontaminationen sind durch Auswaschung und Dispersion von As und Tl in landwirtschaftlich genutzen Flaechen nachzuweisen und in Pflanzen wiederfindbar. Zur quantitativen Abschaetzung des Stofftransfers wurde anhand von Elutionsversuchen die Metallfreisetzung von Schwermetallen und Arsen aus Erz, Flotationsabgaengen und Schlacken untersucht. Ausserdem konnte die ausgezeichnete Eignung von kuenstlichen Fe-Mn-Hydroxiden fuer die Dekontamination von Arsen- und Schwermetall haltigen Waesser gezeigt werden. (orig.)

  1. HTGT-Turbotech II. Subproject 1.221: aerodynamic excitation of transonic turbine stages. Final report; HTGT-Turbotech II. Teilprojekt 1.221: Aerodynamische Anregung von transsonisch durchstroemten Turbinenstufen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Stetter, H.; Urban, B.; Bauer, H.

    1999-12-01

    For experimental investigations on shock-induced flutter in a linear transonic turbine cascade an elastic suspension system has been developed so that only aerodynamic coupling occurs in the system. The test facility uses super-heated steam as working fluid and enables Mach and Reynolds numbers to vary independently. The investigated cascade consists of seven prismatic blades. The profiles are taken from the tip section of a transonic low pressure steam turbine blade. Each blade is suspended by an elastic spring system which allows the respective blade to vibrate in a mode similar to the real blade's first bending mode. The examination mainly deals with the oscillatory behavior of the blades with respect to a variation in the isentropic outlet Mach number. In addition, the complex shock-boundary-layer interactions on the blades' suction sides are described. Flow computations are run by a finite volume Navier-Stokes solver that accounts for moving boundaries. A volume grid generator is integrated into the flow solver producing combined O- and H-type grids. Turbulence is modeled by a k-{epsilon} turbulence model using wall functions because of performance reasons. Some acceleration techniques for unsteady flow computations are investigated. Shock oscillations which occur on a DCA profile are simulated. For the simulation of the experimental setup the blade motions are prescribed. (orig.) [German] Fuer ein Spitzenschnittprofil einer ND-Endstufenschaufel sowie eine Gasturbinenschaufel wurden lineare Gitter bestehend aus jeweils sieben elastisch aufgehaengten Schaufeln entwickelt. Die Konstruktion der Aufhaengung gewaehrleistet, dass die Schaufeln lediglich durch aerodynamische Effekte zu freien Schwingungen angeregt werden koennen und in ihrem Schwingungsverhalten der ersten Biegeschwingung ihrer Originalschaufeln entsprechen. Ein gestimmtes und ungestimmtes ebenes Gitter wurde in einem Dampfversuchsstand mit Heissdampf durchstroemt, wobei das Flatterverhalten der Schaufeln von Dehnungsmessstreifen auf den Schaufeltraegern und die auftretenden Stossoszillationen mit Hilfe einer Hoch-Geschwindigkeits-Schlierenoptik, einer Laserschranke, applizierten Foliensensoren und instationaeren Drucksensoren erfasst wurde. Im transsonischen Bereich tritt beim ND-Spitzenschnittprofil ein hohes Anregungspotential durch Stossbewegungen auf. Beim Gasturbinengitter sind die Schwingungsamplituden auf Grund einer hohen Daempfung der elastischen Schaufelhalter geringer. Ein Rechenprogramm zur Simulation der transsonischen, reibungsbehafteten Stroemung durch axiale Turbomaschinen wurde auf die Behandlung bewegter Profile angepasst und fuer instationaere Stroemungssimulationen beschleunigt. Ein k-{epsilon}-Turbulenzmodell mit Wandfunktionen wurde implementiert und ein elliptisches 3D-Gittergenerierungsverfahren in den Stroemungsloeser integriert. An einem Doppelkreisbogenprofil wurden Stossoszillationen nachgerechnet. Die experimentell ermittelten Messdaten dienen als Validierungsgrundlage fuer die numerische Simulation der instationaeren Stroemung durch Schaufelreihen mit schwingenden Profilen. (orig.)

  2. Sub-project 'Simulation in mineral waste of secondary phase formation due to contact with drainage water'. Final report; Teilprojekt 'Simulation der Sekundaermineralbildung in mineralischen Reststoffen in Kontakt mit Sickerwasser'. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, U.; Kersten, M.

    2003-08-01

    3 mio. metric tons of bottom ash are produced by municipal solid waste incineration annually in Germany, which have to be recycled under tough environmental- and construction-based criteria. Before recycled, the ashes have to be reacted in open-air dumps for at least three months. A field-based survey under the framework of this project was conducted to study the ash ageing. This survey demonstrated that in practice these criteria are only partially reached in the topmost surficial layers of the 3-months ash humps due to hindrance of access by water and CO{sub 2}. According to a hypothesis worked out in earlier projects, the heavy metals remobilized from bottom ash are scavenged by secondary minerals formed during ageing, and kept therefore on a very low concentration niveau in the drainage water. In this project it was tried to simulate this long-term reaction sequence by addition of such sorbents to the short-term S4 leaching test already with fresh bottom ash. The main result is that the low metal concentration niveau was reached already within a few weeks of ash storage because the secondary mineral sorbents are apparently formed quite rapidly in sufficient amounts if both water and CO{sub 2} are allowed to drain the material. It is therefore not necessary to modify the S4 test for assessment according to the criteria ''Quellstaerke nach BBodSchV'', in case ash ageing is performed in an appropriate manner. Nonetheless, laboratory experiments showed that in open ash disposal systems but at enhanced gradient formation, considerable heavy metal fluxes may occur due to high remobilization rates, even at the overall low equilibrium concentrations. (orig.) [German] Bei der Siedlungsabfallverbrennung fallen jaehrlich ca. 3 Mio. Tonnen Rostasche an, die unter Einhaltung umwelt- und bautechnischer Kriterien wiederverwertet werden muessen. Vor der eigentlichen Verwertung ist eine dreimonatige Alterung der Aschen vorgeschrieben. Im Rahmen dieses Vorhabens wurde anhand von Feldversuchen unter praxisnahen Bedingungen gezeigt, dass die wasserwirtschaftliche Qualitaet bzw. Quellstaerke nach BbodSchV von Rostaschen durch die derzeit praktizierte Alterung nur partiell in den oberflaechennahen Haldenpartien verbessert wird. Weiterhin wurde auf Grundlage einer aus frueheren Vorhaben abgeleiteten Hypothese, dass die aus MVA-Schlacken freigesetzten Schwermetallgehalte ueber ein Sorptionsgleichgewicht mit Sekundaermineralen auf einem sehr niedrigen Niveau gehalten werden, untersucht, ob durch Zugabe entsprechender Sorbenten zum S4-Test nicht eine Simulation der sich langfristigen einstellenden Schwermetallkonzentrationen im Sickerwasser im Sinne einer Quellstaerkenprognose nach BBodSchV durchgefuehrt werden kann. Wesentliches Ergebnis ist, dass die relativ niedrigen Gleichgewichtskonzentrationen im S4-Test nicht signifikant durch Zugabe dieser Sorbenten veraendert werden, da ausreichende Mengen an Sekundaermineralen wahrscheinlich bereits binnen wenigen Wochen Lagerung in der Schlacke gebildet werden, wenn der Zutritt von CO{sub 2} und Wasser frei erfolgen kann. Allerdings zeigen die Laborversuche auch, dass trotz der relativ niedrigen Gleichgewichtskonzentrationen in offenen Systemen infolge der schnellen Freisetzungskinetik binnen kurzer Zeiten relevante Schwermetallfrachten veriagert werden koennen. (orig.)

  3. Decontamination of PAH polluted soils by fungi. Subproject: PAH degradation balance and testing of the extended laboratory process. Final report; Dekontamination von PAK belasteten Boeden durch Pilze. Teilprojekt: Bilanzierung des PAK-Abbaus und Erprobung des erweiterten Laborverfahrens. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Martens, R.; Zadrazil, F.; Wolter, M.; Bahadir, M.

    1997-09-01

    The aim of the research project was first to select a fungus with a high potential for mineralization of polycyclic aromatic hydrocarbons (PAH) and a good ability to colonize different soils. The application of this fungus for a degradation of PAH in soil had to be tested. In a screening of 57 white rot fungi the fungus Pleurotus sp. Florida fulfilled these requirements best. In pure culture it was able to metabolize and mineralize highly condensed 4-6 ring PAH to a great extent. For instance, up to 50% of {sup 14}C-pyrene or 39% of {sup 14}C-benzo(a)pyrene was mineralized to {sup 14}CO{sub 2} within 15 weeks. If different carriers for {sup 14}C-pyrene were used the mineralization correlated with the bioavailability, which was characterized by the desorption of the compound from the carriers with water. The mineralization of {sup 14}C-pyrene, {sup 14}C-benz(a)anthracene; {sup 14}C-benzo(a)-pyrene and {sup 14}C-dibenz(a, h)anthracene in native soils showed that a colonization with Pl. sp Florida inhibited the degradation of the less recalcitrant {sup 14}C-pyrene by the indigenous soil microflora. However, the mineralization of the carcinogenic, very recalcitrant and high condensed {sup 14}C-PAH was considerably supported by the fungus. Therefore this capabilities of the fungus could not be proven in a joint medium-scale soil experiment (0.8 m{sup 3} soil) which had been conducted within a parmership with scientists in Jena and an industriell firm. Because of safety aspects only the low condensed less recalcitrant PAH could be applied in this experiment. (orig./MG) [Deutsch] Ziel der Untersuchungen war es, zunaechst aus einer groesseren Zahl von Weissfaeulepilzen Pilze zu selektieren, die ein hohes Abbaupotential fuer PAK besitzen. Fuer die effektive Bildung der fuer den Xenobiotika-Abbau wahrscheinlich verantwortlichen lignolytischen Enzyme sollten die Pilze auf Stroh mit einer Kontamination von {sup 14}C-Pyren angezogen werden. An Hand der Freisetzung von {sup 14}CO{sub 2}, war eine Klassifizierung der Pilze hinsichtlich ihres Abbaupotentials vorzunehmen. Unter Beruecksichtigung der Faehigkeit besonders potenter Arten zum dauerhaften Einwachsen in verschiedene Boeden und ihrer Kultivierbarkeit sollte ein Pilz ausgewaehlt werden. Mit diesem Pilz sollten dann weitere Abbaustudien in Reinkultur mit markierten und unmarkierten, hochkondensierten PAK durchgefuehrt werden. Dabei waren Fragen der Bioverfuegbarkeit der PAK zu beruecksichtigen. Anschliessend war die Uebertragung der Reinkulturergebnisse auf verschiedene Boeden zu untersuchen. (orig./MG)

  4. [Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

    Science.gov (United States)

    Huang, Ying; Su, Jian; Huang, Xiaosui; Lu, Danxia; Xie, Zhi; Yang, Suqing; Guo, Weibang; Lv, Zhiyi; Wu, Hongsui; Zhang, Xuchao

    2017-12-20

    Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

  5. Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1.

    Directory of Open Access Journals (Sweden)

    Anna Pakula

    Full Text Available OBJECTIVES: Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD. METHODS: Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy. RESULTS: cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients. CONCLUSIONS: In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease.

  6. Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC) study.

    Science.gov (United States)

    Liang, Jun; Zhou, Na; Teng, Fei; Zou, Caiyan; Xue, Ying; Yang, Manqing; Song, Huaidong; Qi, Lu

    2012-01-01

    The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women. After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05). HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.

  7. Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC study.

    Directory of Open Access Journals (Sweden)

    Jun Liang

    Full Text Available OBJECTIVE: The American Diabetes Association (ADA recently published new clinical guidelines in which hemoglobin A1c (HbA1c was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT. RESEARCH DESIGN AND METHODS: The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV and HbA1c were measured in 5,098 men and women. RESULTS: After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend 0.05. CONCLUSIONS: HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.

  8. Identification of a novel signaling pathway and its relevance for GluA1 recycling.

    Directory of Open Access Journals (Sweden)

    Guiscard Seebohm

    Full Text Available We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3 increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve and the generation of PI(3,5P(2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5P(2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory.

  9. Hemoglobin A1c can be helpful in predicting progression to diabetes after Whipple procedure.

    Science.gov (United States)

    Hamilton, Lisa; Jeyarajah, D Rohan

    2007-01-01

    Normoglycemic patients undergoing pancreaticoduodenectomy (Whipple procedure) often inquire whether they will be diabetic postoperatively. There is limited information on this issue. We therefore looked at a more subtle measurement of long-term glycemic control, hemoglobin A1c (HgbA1c), as a prognostic tool in predicting progression to diabetes post Whipple. A retrospective review over a 6-year period of all patients undergoing Whipple procedures at a single institution was conducted. In all, 27 patients had no prior history of diabetes, complete follow-up, and measured preoperative HgbA1c values. Postoperative diabetes was defined as the need for oral hypoglycemic agents or insulin. These charts were analyzed for progression to diabetes after Whipple. Of the 27 patients, 10 were considered to have postoperative diabetes. The average preoperative HgbA1c value for these patients was 6.3+/-0.66. This was statistically different from the 17 patients without postoperative diabetes (average HgbA1c 5.2+/-0.39, pWhipple operation if the preoperative HgbA1c value is in the normal range. The apparent utility of HgbA1c in predicting postoperative diabetes in this small study suggests that this laboratory test may be very helpful in counseling patients for Whipple operation.

  10. SULT1A1 copy number variation: ethnic distribution analysis in an Indian population.

    Science.gov (United States)

    Almal, Suhani; Padh, Harish

    2017-11-01

    Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes involved in metabolism of numerous xenobiotics, drugs and endogenous compounds. Interindividual variation in sulfonation capacity is important for determining an individual's response to xenobiotics. SNPs in SULTs, mainly SULT1A1 have been associated with cancer risk and also with response to therapeutic agents. Copy number variation (CNVs) in SULT1A1 is found to be correlated with altered enzyme activity. This short report primarily focuses on CNV in SULT1A1 and its distribution among different ethnic populations around the globe. Frequency distribution of SULT1A1 copy number (CN) in 157 healthy Indian individuals was assessed using florescent-based quantitative PCR assay. A range of 1 to >4 copies, with a frequency of SULT1A1 CN =2 (64.9%) the highest, was observed in our (Indian) population. Upon comparative analysis of frequency distribution of SULT1A1 CN among diverse population groups, a statistically significant difference was observed between Indians (our data) and African-American (AA) (p = 0.0001) and South African (Tswana) (p populations. Distribution of CNV in the Indian population was found to be similar to that in European-derived populations of American and Japanese. CNV of SULT1A1 varies significantly among world populations and may be one of the determinants of health and diseases.

  11. Carbon Monoxide Releasing Molecule-A1 (CORM-A1) Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

    Science.gov (United States)

    Almeida, Ana S; Soares, Nuno L; Vieira, Melissa; Gramsbergen, Jan Bert; Vieira, Helena L A

    2016-01-01

    Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO) is an endogenous product of heme degradation by heme oxygenase (HO) activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC). Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA) supplemented with CO-releasing molecule A1 (CORM-A1). CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells) and a decrease in cell death (lower propidium iodide (PI) uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells). CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS) generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors in CO

  12. The transcription factor Lc-Maf participates in Col27a1 regulation during chondrocyte maturation

    Energy Technology Data Exchange (ETDEWEB)

    Mayo, Jaime L.; Holden, Devin N. [Department of Microbiology and Molecular Biology, Brigham Young University, 591 WIDB, Provo, UT 84602 (United States); Barrow, Jeffery R. [Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602 (United States); Bridgewater, Laura C., E-mail: laura_bridgewater@byu.edu [Department of Microbiology and Molecular Biology, Brigham Young University, 591 WIDB, Provo, UT 84602 (United States)

    2009-08-01

    The transcription factor Lc-Maf, which is a splice variant of c-Maf, is expressed in cartilage undergoing endochondral ossification and participates in the regulation of type II collagen through a cartilage-specific Col2a1 enhancer element. Type XXVII and type XI collagens are also expressed in cartilage during endochondral ossification, and so enhancer/reporter assays were used to determine whether Lc-Maf could regulate cartilage-specific enhancers from the Col27a1 and Col11a2 genes. The Col27a1 enhancer was upregulated over 4-fold by Lc-Maf, while the Col11a2 enhancer was downregulated slightly. To confirm the results of these reporter assays, rat chondrosarcoma (RCS) cells were transiently transfected with an Lc-Maf expression plasmid, and quantitative RT-PCR was performed to measure the expression of endogenous Col27a1 and Col11a2 genes. Endogenous Col27a1 was upregulated 6-fold by Lc-Maf overexpression, while endogenous Col11a2 was unchanged. Finally, in situ hybridization and immunohistochemistry were performed in the radius and ulna of embryonic day 17 mouse forelimbs undergoing endochondral ossification. Results demonstrated that Lc-Maf and Col27a1 mRNAs are coexpressed in proliferating and prehypertrophic regions, as would be predicted if Lc-Maf regulates Col27a1 expression. Type XXVII collagen protein was also most abundant in prehypertrophic and proliferating chondrocytes. Others have shown that mice that are null for Lc-Maf and c-Maf have expanded hypertrophic regions with reduced ossification and delayed vascularization. Separate studies have indicated that Col27a1 may serve as a scaffold for ossification and vascularization. The work presented here suggests that Lc-Maf may affect the process of endochondral ossification by participating in the regulation of Col27a1 expression.

  13. Predictors of HbA1c levels in patients initiating metformin.

    Science.gov (United States)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

    2016-12-01

    The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. We conducted a cohort study including type 2 diabetes patients who received their first metformin prescription between 2007 and 2013 in the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was HbA1c level at follow-up adjusted for baseline HbA1c; the secondary outcome was failing to achieve the target HbA1c level of 53 mmol/mol. Associations were analyzed by linear and logistic regression. Multiple imputation was used for missing data. Additional analyses stratified by dose and adherence level were conducted. The cohort included 6050 patients initiating metformin. Baseline HbA1c at target consistently predicted better HbA1c outcomes. Longer diabetes duration and lower total cholesterol level at baseline were predictors for higher HbA1c levels at 6 months. At 18 months, cholesterol level was not a predictor. Longer diabetes duration was also associated with not achieving the target HbA1c at follow-up. The association for longer diabetes duration was especially seen in patients starting on low dose treatment. No consistent associations were found for comorbidity and comedication. Diabetes duration was a relevant predictor of HbA1c levels after 6 and 18 months of follow-up in patients initiating metformin treatment. Given the study design, no causal inference can be made. Our study suggests that prompt treatment intensification may be needed in patients who have a longer diabetes duration at treatment initiation.

  14. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

    Science.gov (United States)

    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  15. Diagnostic accuracy of HbA1c in diabetes between Eastern and Western.

    Science.gov (United States)

    Yan, Shuang; Liu, Siying; Zhao, Yashuang; Zhang, Wencui; Sun, Xiaohui; Li, Jianing; Jiang, Fuli; Ju, Jiaming; Lang, Ning; Zhang, Yingqi; Zhou, Weiyu; Li, Qiang

    2013-07-01

    In 2010, the American Diabetes Association recommended the use of HbA1c as a diagnostic criterion for diabetes. However, HbA1c is not an accepted diagnostic tool for diabetes in Eastern Asia, because genetic differences compromise the standardization of the diagnostic cut-off point. This study evaluated differences in the use of HbA1c for diagnosing diabetes in Eastern and Western populations and investigated whether HbA1c cut-off point of ≥ 6.5% is diagnostic of diabetes in patients from Eastern Asia. Literature was obtained from MEDLINE, EMBASE and Cochrane databases. The pooled sensitivity and specificity of each HbA1c cut-off point were extracted and compared between Western and Eastern populations. Differences in the cut-off point for diagnosing diabetes in each region were compared by examining differences in the area under summary receiver operating characteristic (SROC) curves. Twelve publications from Eastern countries (n = 59,735) and 13 from Western countries (n = 22,954) were included in the analysis. Areas under SROC curves in the Eastern and Western groups were 0.9331 and 0.9120, respectively (P = 0.98). The cut-off point of the highest Youden index was 6.0%. At the HbA1c cut-off point of 6.5%, the pooled sensitivity and specificity were 58.7% and 98.4% for Eastern countries and 65.5% and 98.1% for Western countries, respectively. HbA1c exhibits the same diagnostic value for diabetes in Eastern and Western populations. In both populations, HbA1c levels > 6.0% identify the population at high risk of diabetes, and HbA1c > 6.5% is diagnostic of clinically established diabetes. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  16. Impact of HbA1c Testing at Point of Care on Diabetes Management

    Science.gov (United States)

    Schnell, Oliver; Crocker, J. Benjamin; Weng, Jianping

    2016-01-01

    Diabetes is a highly prevalent disease also implicated in the development of several other serious complications like cardiovascular or renal disease. HbA1c testing is a vital step for effective diabetes management, however, given the low compliance to testing frequency and, commonly, a subsequent delay in the corresponding treatment modification, HbA1c at the point of care (POC) offers an opportunity for improvement of diabetes care. In this review, based on data from 1999 to 2016, we summarize the evidence supporting a further implementation of HbA1c testing at POC, discuss its limitations and propose recommendations for further development. PMID:27898388

  17. Immunopositivity for histone macroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Francesca Rappa

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously.We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN and the phosphatase and tensin homolog (PTEN liver specific knock-out (KO mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry.Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p<0.01 in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2, when compared to steatosis (<2% of hepatocytes positive for either isoform. The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2.These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC.

  18. Endogenous activation of adenosine A(1) receptors accelerates ischemic suppression of spontaneous electrocortical activity

    DEFF Research Database (Denmark)

    Ilie, Andrei; Ciocan, Dragos; Zagrean, Ana-Maria

    2006-01-01

    Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior to major alterations in ionic homeostasis. It was found in vitro during ischemia that the rapidly formed adenosine, resulting from the intracellular breakdown of ATP, may inhibit synaptic transmission via the A(1......) receptor subtype. The link between endogenous A(1) receptor activation during ischemia and the suppression of spontaneous electrocortical activity has not yet been established in the intact brain. The aim of this study was to investigate in vivo the effects of A(1) receptor antagonism by 8-cyclopentyl-1...

  19. O2(a1Δ) vibrational kinetics in oxygen-iodine laser

    Science.gov (United States)

    Torbin, A. P.; Pershin, A. A.; Heaven, M. C.; Azyazov, V. N.; Mebel, A. M.

    2018-04-01

    Kinetics of vibrationally-excited singlet oxygen O2(a1Δ,ν) in gas mixture O3/N2/CO2 was studied using a pulse laser technique. Molecules O2(a1Δ,ν) were produced by laser photolysis of ozone at 266 nm. The O3 molecules number density was followed using time-resolved absorption spectroscopy. It was found that an upper bound for the rate constant of chemical reaction O2(a1Δ,ν)+ O3 is about 10-15 cm3/s. The rate constants of O2(a1Δ,ν= 1, 2 and 3) quenching by CO2 are presented.

  20. 17 CFR 240.17a-1 - Recordkeeping rule for national securities exchanges, national securities associations...

    Science.gov (United States)

    2010-04-01

    ... national securities exchanges, national securities associations, registered clearing agencies and the... Certain Stabilizing Activities § 240.17a-1 Recordkeeping rule for national securities exchanges, national...) Every national securities exchange, national securities association, registered clearing agency and the...

  1. Experimental verification of the new RISOe-A1 airfoil family for wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Dahl, K S; Fuglsang, P; Antoniou, I [Risoe National Lab., Roskilde (Denmark)

    1999-03-01

    This paper concerns the experimental verification of a new airfoil family for wind turbines. The family consist of airfoils in the relative thickness range from 15% to 30%. Three airfoils, Risoe-A1-18, Risoe-A1-21, and Risoe-A1-24 were tested in a wind tunnel. The verification consisted of both static and dynamic measurements. Here, the static results are presented for a Reynolds number of 1.6x10{sup 6} for the following airfoil configurations: smooth surface (all three airfoils) and Risoe-A1-24 mounted with leading edge roughness, vortex generators, and Gurney-flaps, respectively. All three airfoils have constant lift curve slope and almost constant drag coefficient until the maximum lift coefficient of about 1.4 is reached. The experimental results are compared with corresponding computational from the general purpose flow solver, EllipSys2D, showing good agreement. (au)

  2. Genetics Home Reference: COL4A1-related brain small-vessel disease

    Science.gov (United States)

    ... hemorrhage Johns Hopkins Medicine Department of Neurology and Neurosurgery: Intracerebral Hemorrhage Johns Hopkins Medicine Department of Neurology and Neurosurgery: Stroke MalaCards: col4a1-related brain small-vessel disease ...

  3. Association of fibrinogen with HbA1C in diabetic foot ulcer

    Science.gov (United States)

    Pase, M. A.; Gatot, D.; Lindarto, D.

    2018-03-01

    Fibrinogen is one of the inflammatory markers of vascular changes and endothelial dysfunction in diabetic patients. The aim of this study to associate serum fibrinogen levels with HbA1C in diabetic foot ulcer (DFU). This study was cross-sectional and retrospective in DFU patients from January to July 2017 in Haji Adam Malik Central General Hospital. The patients enrolled in the study were T2DM with DFU as a complication. The grading of DFU was evaluated according to the Wagner’s Classification. Serum fibrinogen level, HbA1C and ankle-brachial index (ABI) were carried out directly in the patients. Fibrinogen serum levels were found significantly with HbA1C (P=0.001, r=0.387) and ABI (P=0.008, r=-0.454). Fibrinogen serum levels in DFU patients were positively correlated with HbA1C and significantly higher in patients with poor glycemic control.

  4. Hemoglobine A1c. Ontwikkeling van een bepalingsmethode en enige klinische toepassingen

    NARCIS (Netherlands)

    Miedema, Kornelis

    1981-01-01

    In dit proefschrift wordt een kolomchromatografische bepalingsmethode van het HbA1c beschreven. Het belang van deze bepaling voor de controle van patiënten met diabetes mellites wordt in een aantal klinische studies nagegaan. ... Zie: Samenvatting

  5. Maternal obesity alters feto-placental Cytochrome P4501A1 activity

    Science.gov (United States)

    DuBois, Barent N.; O’Tierney, Perrie; Pearson, Jacob; Friedman, Jacob E.; Thornburg, Kent; Cherala, Ganesh

    2012-01-01

    Cytochrome P4501A1 (CYP1A1), an important drug metabolizing enzyme, is expressed in human placenta throughout gestation as well as in fetal liver. Obesity, a chronic inflammatory condition, is known to alter CYP enzyme expression in non-placental tissues. In the present study, we test the hypothesis that maternal obesity alters the distribution of CYP1A1 activity in feto-placental unit. Placentas were collected from non-obese (BMI30) women at term. Livers were collected from gestation day 130 fetuses of non-human primates fed either control diet or high-fat diet (HFD). Cytosol and microsomes were collected using differential centrifugation, and incubated with 7-Ethoxyresorufin. The CYP1A1 specific activity (pmoles of resorufin formed/min/mg of protein) was measured at excitation/emission wavelength of 530/590nm. Placentas of obese women had significantly reduced microsomal CYP1A1 activity compared to non-obese women (0.046 vs. 0.082; p<0.05); however no such effect was observed on cytosolic activity. Similarly, fetal liver from HFD fed mothers had significantly reduced microsomal CYP1A1 activity (0.44±0.04 vs. 0.20±0.10; p<0.05), with no significant difference in cytosolic CYP1A1 activity (control, 1.23±0.20; HFD, 0.80±0.40). Interestingly, multiple linear regression analyses of placental efficiency indicates cytosolic CYP1A1 activity is a main effect (5.67±2.32 (β±SEM); p=0.022) along with BMI (−0.57±0.26; p=0.037), fetal gender (1.07±0.26; p<0.001), and maternal age (0.07±0.03; p=0.011). In summary, while maternal obesity affects microsomal CYP1A1 activity alone, cytosolic activity along with maternal BMI is an important determinant of placental efficiency. Together, these data suggest that maternal lifestyle could have a significant impact on CYP1A1 activity, and hints at a possible role for CYP1A1 in feto-placental growth and thereby well-being of fetus. PMID:23046808

  6. Barriers to A1C testing among a managed care population.

    Science.gov (United States)

    Delaronde, Steven

    2005-01-01

    The purpose of this study is to explore reasons adults with diabetes do not receive at least 2 A1C tests per year as recommended by the American Diabetes Association (ADA). ConnectiCare, a regional managed care company based in Farmington, Connecticut, identified adult members with diabetes who did not have a medical claim for an A1C laboratory test from their physician. A questionnaire was sent to 740 randomly selected members asking them to report the number of A1C tests they received in the past 12 months and reasons for not receiving the number of tests recommended by the ADA. After sending an automated telephone reminder to nonrespondents, a 26% (n = 192) response rate was achieved. Thirty-three percent of respondents (n = 63) reported having diabetes and receiving fewer than 2 A1C tests in the past year. Respondents were equally divided between men and women, with a mean age of 58 years. The primary reasons given for not obtaining at least 2 A1C tests as recommended by the ADA were that respondents were unaware that the test is recommended (49%), not informed of the need for the test by their physician (38%), never heard of the A1C test (33%), and not seen regularly by their physician (19%). Diabetes self-management education remains an important means of encouraging adherence to important ADA recommendations such as regular A1C testing. Barriers to A1C testing can be addressed in multiple settings, including individual and group education, disease management programs, and physician education.

  7. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

    2015-01-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

  8. Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance.

    Science.gov (United States)

    Pappas, Colleen; Andel, Ross; Infurna, Frank J; Seetharaman, Shyam

    2017-02-01

    As the ageing population grows, it is important to identify strategies to moderate cognitive ageing. We examined glycated haemoglobin (HbA1c) and diabetes in relation to level and change in episodic memory in older adults with and without diabetes. Data from 4419 older adults with (n=950) and without (n=3469) diabetes participating in a nationally representative longitudinal panel study (the Health and Retirement Study) were examined. Average baseline age was 72.66 years and 58% were women. HbA1c was measured in 2006 and episodic memory was measured using immediate and delayed list recall over 4 biennial waves between 2006 and 2012. Growth curve models were used to assess trajectories of episodic memory change. In growth curve models adjusted for age, sex, education, race, depressive symptoms and waist circumference, higher HbA1c levels and having diabetes were associated with poorer baseline episodic memory (p=0.036 and HbA1c on episodic memory decline was smaller than the effect of age. The results were stronger for women than men and were not modified by age or race. When the main analyses were estimated for those with and without diabetes separately, HbA1c was significantly linked to change in episodic memory only among those with diabetes. Higher HbA1c and diabetes were both associated with declines in episodic memory, with this relationship further exacerbated by having diabetes and elevated HbA1c. HbA1c appeared more important for episodic memory performance among women than men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Should haemoglobin A1C be used for diagnosis of diabetes mellitus

    African Journals Online (AJOL)

    2016-03-28

    Mar 28, 2016 ... duration of contact of the red blood cells with glucose in the blood. Thus, decreased erythropoiesis ... individuals with a normal red blood cell lifespan, the level of. HbA1c is related to the circulating plasma .... Pani LN, Korenda L, Meigs JB, Driver C, Chamany S, Fox CS, et al. Effect of aging on A1C levels in ...

  10. Red cell distribution width is associated with hemoglobin A1C elevation, but not glucose elevation.

    Science.gov (United States)

    Bao, Xue; Wan, Min; Gu, Yeqing; Song, Yanqi; Zhang, Qing; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Shi, HongBin; Su, Qian; Fang, Liyun; Yang, Huijun; Yu, Fei; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Wang, Guolin; Yu, Ming; Niu, Kaijun

    2017-10-01

    To investigate the association between red cell distribution width (RDW) and elevation of glucose/glycated hemoglobin (HbA1c). An analysis was conducted using data from a prospective cohort study of adults. People without prediabetes or diabetes (n=7,795) were followed for a mean of 2.90years (range: 1-7years, 95% confidence interval: 2.86-2.94years). Glucose elevation is defined as fasting glucose levels exceeding 5.6mmol/l, or 2-hour glucose values in the oral glucose tolerance test exceeding 7.8mmol/l. HbA1c elevation is defined as a HbA1c value exceeding a normal limit of 39mmol/mol (5.7%). Adjusted Cox proportional hazards regression models were used to assess the association between RDW quartiles and elevation of HbA1c/glucose. The multiple-adjusted hazard ratios (95% confidence interval) of HbA1c elevation for increased quartiles of RDW were 1.00 (reference), 1.08 (0.89, 1.30), 1.28 (1.07, 1.54), and 1.54 (1.29, 1.85) (P for trend<0.0001). However, no significant association was observed between RDW and blood glucose (fasting and postprandial). Elevated RDW is independently related to future HbA1c elevation, but not to glucose elevation. This suggests that RDW may associate with HbA1c through a non-glycemic way, which should be taken into consideration when using HbA1c as a diagnostic criterion of prediabetes or diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Comparison of Hemoglobin A1c assay performance on two different commercial systems

    Directory of Open Access Journals (Sweden)

    Jozo Ćorić

    2015-04-01

    Full Text Available Introduction: Glycated hemoglobin (HbA1c is formed by non-enzymatic binding of glucose to the free amino group of the N-terminal end of the ß-chain of hemoglobin A. HbA1c is representative of the mean blood glucose level over three months. The aim of the study was to evaluate the Hemoglobin A1c immunoturbidimetric assay performance on two different commercial systems.Methods: We evaluated the precision and trueness for determination of HbA1c in whole blood. Concentrations of total hemoglobin and HbA1c were evaluated on Dimension Xpand (Siemens and Cobas 501 (Roche analyzers. HbA1c was measured in a latex agglutination inhibition test. Commercial controls Liquichek Diabetes Control Level 1 and Liquichek Diabetes Control Level 2 (Bio Rad at two levels were used for quality control. Analytical validation of HbA1c included: within-run imprecision, between-day imprecision, inaccuracy and comparison determination on the human samples on 2 systems: Dimension Xpand and Cobas 501 analyzers. Results: Within-run imprecision on the commercially controls for Level 1 is 4.5% and Level 2 is 3.2% between-day imprecision on commercially controls is 6.1% Level 1 and 5.1% Level 2 for respectively inac- curacy on commercially controls for Level 1 is 1.8% and Level 2 is 4.8%. Method comparison on human samples shows the correlation coefficient of 0.99.Conclusion: The presented results of the analytical evaluation methods for the determination of HbA1c showed an acceptable accuracy and precision.

  12. A novel research model for evaluating sunscreen protection in the UV-A1.

    Science.gov (United States)

    Figueiredo, Sônia Aparecida; de Moraes, Dayane Cristina; Vilela, Fernanda Maria Pinto; de Faria, Amanda Natalina; Dos Santos, Marcelo Henrique; Fonseca, Maria José Vieira

    2018-01-01

    The use of a broad spectrum sunscreen is considered one of the main and most popular measures for preventing the damaging effects of ultraviolet radiation (UVR) on the skin. In this study we have developed a novel in vitro method to assess sunscreens efficacy to protect calcineurin enzyme activity, a skin cell marker. The photoprotective efficacy of sunscreen products was assessed by measuring the UV-A1 radiation-induced depletion of calcineurin (Cn) enzyme activity in primary neonatal human dermal fibroblast (HDFn) cell lysates. After exposure to 24J/cm 2 UV-A1 radiation, the sunscreens containing larger amounts of UV-A1 filters (brand B), the astaxanthin (UV-A1 absorber) and the Tinosorb® M (UV-A1 absorber) were capable of preventing loss of Cn activity when compared to the sunscreens formulations of brand A (low concentration of UV-A1 filters), with the Garcinia brasiliensis extract (UV-B absorber) and with the unprotected cell lysate and exposed to irradiation (Irradiated Control - IC). The Cn activity assay is a reproducible, accurate and selective technique for evaluating the effectiveness of sunscreens against the effects of UV-A1 radiation. The developed method showed that calcineurin activity have the potential to act as a biological indicator of UV-A1 radiation-induced damages in skin and the assay might be used to assess the efficacy of sunscreens agents and plant extracts prior to in vivo tests. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

    Science.gov (United States)

    Calanna, S; Scicali, R; Di Pino, A; Knop, F K; Piro, S; Rabuazzo, A M; Purrello, F

    2014-06-01

    We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. HbA1c Identifies Subjects With Prediabetes and Subclinical Left Ventricular Diastolic Dysfunction.

    Science.gov (United States)

    Di Pino, Antonino; Mangiafico, Sarah; Urbano, Francesca; Scicali, Roberto; Scandura, Salvatore; D'Agate, Veronica; Piro, Salvatore; Tamburino, Corrado; Purrello, Francesco; Rabuazzo, Agata Maria

    2017-10-01

    Prediabetes is associated with subclinical cardiac changes associated with heart failure development. We investigated diastolic function and its association with markers of glycation and inflammation related to cardiovascular disease in patients with prediabetes. We focused on individuals with prediabetes identified only by glycated hemoglobin A1c [HbA1c; 5.7% to 6.4% and normal fasting glucose (NFG) and normal glucose tolerance (NGT) after an oral glucose tolerance test (OGTT)]. Cross-sectional study. Departments of Clinical and Experimental Medicine and Cardiology, University of Catania, Catania, Italy. HbA1c, OGTT, Doppler echocardiography, soluble receptor for advanced glycation end products (sRAGEs), and endogenous secretory RAGE (esRAGE) were evaluated. We recruited 167 subjects with NFG/NGT who were stratified according to HbA1c level: controls (HbA1c prediabetes (HbA1c 5.7% to 6.4%). Patients with HbA1c prediabetes (n = 106) showed a lower peak mitral inflow in early diastole (E wave) to late diastolic atrial filling velocity (A wave) ratio (E/A ratio) than controls (n = 61) (1.10 ± 0.24 vs 1.18 ± 0.23; P prediabetes exhibited subclinical cardiac alterations associated with sRAGE, esRAGE, and HbA1c. These subjects would not have been classified as having prediabetes on the basis of fasting glycemia or post-OGTT values. Copyright © 2017 Endocrine Society

  15. Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry.

    Directory of Open Access Journals (Sweden)

    Athena Starlard-Davenport

    Full Text Available CYP19A1 facilitates the bioconversion of estrogens from androgens. CYP19A1 intron single nucleotide polymorphisms (SNPs may alter mRNA splicing, resulting in altered CYP19A1 activity, and potentially influencing disease susceptibility. Genetic studies of CYP19A1 SNPs have been well documented in populations of European ancestry; however, studies in populations of African ancestry are limited. In the present study, ten 'candidate' intronic SNPs in CYP19A1 from 125 African Americans (AA and 277 European Americans (EA were genotyped and their frequencies compared. Allele frequencies were also compared with HapMap and ASW 1000 Genomes populations. We observed significant differences in the minor allele frequencies between AA and EA in six of the ten SNPs including rs10459592 (p<0.0001, rs12908960 (p<0.0001, rs1902584 (p = 0.016, rs2470144 (p<0.0001, rs1961177 (p<0.0001, and rs6493497 (p = 0.003. While there were no significant differences in allele frequencies between EA and CEU in the HapMap population, a 1.2- to 19-fold difference in allele frequency for rs10459592 (p = 0.004, rs12908960 (p = 0.0006, rs1902584 (p<0.0001, rs2470144 (p = 0.0006, rs1961177 (p<0.0001, and rs6493497 (p = 0.0092 was observed between AA and the Yoruba (YRI population. Linkage disequilibrium (LD blocks and haplotype clusters that is unique to the EA population but not AA was also observed. In summary, we demonstrate that differences in the allele frequencies of CYP19A1 intron SNPs are not consistent between populations of African and European ancestry. Thus, investigations into whether CYP19A1 intron SNPs contribute to variations in cancer incidence, outcomes and pharmacological response seen in populations of different ancestry may prove beneficial.

  16. Persistent Notochord in a Fetus with COL2A1 Mutation

    Directory of Open Access Journals (Sweden)

    Elisabeth Codsi

    2015-01-01

    Full Text Available Multiple anomalies including micromelia, poor mineralization of the vertebrae, and a persistent notochord were identified on second trimester ultrasound in a fetus with a COL2A1 mutation. To our knowledge, this represents the first case of a persistent notochord associated with a COL2A1 mutation in humans. In this case report, we describe ultrasound and postmortem findings and review the pathogenesis associated with a persistent notochord.

  17. Reliability analysis of the automatic control of the A-1 power plant coolant temperature

    International Nuclear Information System (INIS)

    Kuklik, B.; Semerad, V.; Chylek, Z.

    Reliability analysis of the automatic control of the A-1 reactor coolant temperature is performed taking into account the effect of both the dependent failures and the routine maintenance of control system components. In a separate supplement, reliability analysis is reported of coincidence systems of the A-1 power plant reactor. Both safe and unsafe failures are taken into consideration as well as the effect of maintenance of the respective branch elements

  18. Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

    Science.gov (United States)

    Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

    2014-01-01

    Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716

  19. Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1c

    DEFF Research Database (Denmark)

    Borg, R.; Vistisen, D.; Witte, D.R.

    2010-01-01

    Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods.......Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods....

  20. From civilians to soldiers and from soldiers to civilians: a micro-approach to disarmament, demobilization, and reintegration (DDR) in Sudan

    NARCIS (Netherlands)

    Baas, S.

    2011-01-01

    This dissertation investigates the processes of mobilization and demobilization of fighters during civil war. Why do civilians, at some point during a conflict, decide to participate in the violence of the war? What are the consequences of becoming part of a guerilla movement? And, once a civil war

  1. Die DDR zwischen Einheit und Abgrenzung : Höhepunkte aus der deutschen Geschichte als Paradigmen politischen Wandels : Luther, Friedrich II. und Bismarck

    NARCIS (Netherlands)

    Brinks, Jan Herman

    1991-01-01

    Im Jahre 1945 befand sich die Geschichte Deutschlands, darin besteht Konsens unter Historikern aller Richtungen, an einem ihrer tiefgreifendsten Wendepunkte. Die Ereignissein Hiroshima und in Potsdam im Sommer jenes Jahres, so urteilt Werner Conze, markieren einschneidenste Zäsuren der europdischen,

  2. „Überholen ohne einzuholen“ Die Entwicklung von Technologien für übermorgen in Kernenergie und Mikroelektronik der DDR

    Science.gov (United States)

    Barkleit, Gerhard

    Dem nuklearen Patt zwischen Ostblock und westlichem Staatenbündnis ist es nach weitgehend übereinstimmender Auffassung von Politik und Wissenschaft zu danken, dass der "Kalte Krieg" in der zweiten Hälfte des 20. Jahrhunderts nicht zum weltumfassenden Flächenbrand eskalierte. An der raschen Herstellung dieses Patts waren zwei Dresdner Physiker maßgeblich beteiligt, deren einer im Manhattan-Projekt in den USA gearbeitet hatte und später in England der Spionage für die Sowjetunion und des Verrats des Know-how der Atombombe überführt wurde.

  3. «Tu, solo, con la storia alle spalle». Durs Grünbein e la DDR: un bilancio critico

    Directory of Open Access Journals (Sweden)

    Daniele Vecchiato

    2011-10-01

    Full Text Available This paper analyses some of the most significant (post-GDR poems by Grünbein and traces the development of aesthetic and poetological issues that are central to the poet’s oeuvre. It provides an articulated overview of Grünbein’s poetics by examining funda­mental themes like the love/hate attitude towards his hometown Dresden, the comple­mentary concepts of history and memory, and the materialism of the body as an antidote to utopias.

  4. Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR and Inflammation: Focus on the Gastrointestinal (GI Tract

    Directory of Open Access Journals (Sweden)

    Evagelia Spanou

    2017-05-01

    Full Text Available The fundamental role of human Toll-like receptors (TLRs and NOD-like receptors (NLRs, the two most studied pathogen recognition receptors (PRRs, is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

  5. Le mythe du jeune désœuvré: analyse des interventions DDR en Côte d’Ivoire

    NARCIS (Netherlands)

    Chelpi-den Hamer, M.

    2009-01-01

    Les processus de prévention et de résolution des conflits sont en grande partie basés sur l’idée qu’un changement positif peut être induit par des interventions ciblées et planifiées. Il faut pourtant éviter de surestimer l’impact de telles interventions. Cet article explore comment de jeunes civils

  6. Association of Intact dupA (dupA1) rather than dupA1 cluster with duodenal ulcer in Indian population

    OpenAIRE

    Alam, Jawed; Ghosh, Prachetash; Ganguly, Mou; Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2015-01-01

    Background The duodenal ulcer promoting gene (dupA) and dupA cluster in Helicobacter pylori have been described as a risk factor for duodenal ulcer development in some populations. Polymorphic gene dupA can be divided into two groups, intact dupA1 (long or short type based on the presence or absence of 615-bp extra sequences at the 5? region) having complete reading frame and other truncated dupA2 having frame-shift mutation. This study was aimed to elucidate the role of dupA of H. pylori and...

  7. FoxA1 binding to the MMTV LTR modulates chromatin structure and transcription

    International Nuclear Information System (INIS)

    Holmqvist, Per-Henrik; Belikov, Sergey; Zaret, Kenneth S.; Wrange, Oerjan

    2005-01-01

    Novel binding sites for the forkhead transcription factor family member Forkhead box A (FoxA), previously referred to as Hepatocyte Nuclear Factor 3 (HNF3), were found within the mouse mammary tumor virus long terminal repeat (MMTV LTR). The effect of FoxA1 on MMTV LTR chromatin structure, and expression was evaluated in Xenopus laevis oocytes. Mutagenesis of either of the two main FoxA binding sites showed that the distal site, -232/-221, conferred FoxA1-dependent partial inhibition of glucocorticoid receptor (GR) driven MMTV transcription. The proximal FoxA binding segment consisted of two individual FoxA sites at -57/-46 and -45/-34, respectively, that mediated an increased basal MMTV transcription. FoxA1 binding altered the chromatin structure of both the inactive- and the hormone-activated MMTV LTR. Hydroxyl radical foot printing revealed FoxA1-mediated changes in the nucleosome arrangement. Micrococcal nuclease digestion showed the hormone-dependent sub-nucleosome complex, containing ∼120 bp of DNA, to be expanded by FoxA1 binding to the proximal segment into a larger complex containing ∼200 bp. The potential function of the FoxA1-mediated expression of the MMTV provirus for maintenance of expression in different tissues is discussed

  8. Endophilin-A1 BAR domain interaction with arachidonyl CoA.

    Science.gov (United States)

    Petoukhov, Maxim V; Weissenhorn, Winfried; Svergun, Dmitri I

    2014-01-01

    Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.

  9. Retinoids repress Ah receptor CYP1A1 induction pathway through the SMRT corepressor

    International Nuclear Information System (INIS)

    Fallone, Frederique; Villard, Pierre-Henri; Seree, Eric; Rimet, Odile; Nguyen, Quock Binh; Bourgarel-Rey, Veronique; Fouchier, Francis; Barra, Yves; Durand, Alain; Lacarelle, Bruno

    2004-01-01

    CYP1A1 isoform is mainly regulated by the transcription factor AhR and to a lesser extent by the nuclear receptor RAR. The effect of a coexposure with 3MC, a AhR ligand, and RA, a RAR ligand, which are, respectively, strong and weak CYP1A1 inducers, is poorly known. We showed in Caco-2 cells that addition of RA significantly decreased 3MC-induced CYP1A1 expression by -55% for mRNA level and -30% for promoter and enzymatic activities. We further showed that RA decreased AhR protein level. Moreover, a physical interaction between AhR and the RAR-corepressor SMRT has been described in vitro. Using the corepressor inhibitor TSA, transfected-cells with SMRT cDNA, and coimmunoprecipitation experiments, we demonstrated that RA addition repressed AhR function through a marked AhR/SMRT physical interaction. This interaction explains the decrease of 3MC-induced CYP1A1 expression. This new mechanism involving the repression of AhR-induced CYP1A1 expression by retinoids allows better knowledge of the CYP1A1 regulation

  10. Stability study for magnetic reagent assaying Hb and HbA1c

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Wen-Pin [Actherm Inc., Hsinchu 200, Taiwan (China); Chieh, J.J.; Yang, C.C. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Yang, S.Y. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); MagQu Co., Ltd., Sindian Dist., New Taipei City 231, Taiwan (China); Chen, Po-Yu; Huang, Yu-Hao [Actherm Inc., Hsinchu 200, Taiwan (China); Hong, Y.W. [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China); Horng, H.E., E-mail: phyfv001@ntnu.edu.tw [Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei 116, Taiwan (China)

    2013-01-15

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe{sub 3}O{sub 4} magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 Degree-Sign C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: Black-Right-Pointing-Pointer The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. Black-Right-Pointing-Pointer The magnetic nanoparticles with antibodies are highly stable in solutions. Black-Right-Pointing-Pointer No significant mutual interference between Hb and HbA1c in assays is observed. Black-Right-Pointing-Pointer High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  11. Stability study for magnetic reagent assaying Hb and HbA1c

    International Nuclear Information System (INIS)

    Hsieh, Wen-Pin; Chieh, J.J.; Yang, C.C.; Yang, S.Y.; Chen, Po-Yu; Huang, Yu-Hao; Hong, Y.W.; Horng, H.E.

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe 3 O 4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2–8 °C. This means that the reagents synthesized in this work are promising for practical applications. - Highlights: ► The properties of assaying Hb and HbA1c using immunomagnetic reduction are studied. ► The magnetic nanoparticles with antibodies are highly stable in solutions. ► No significant mutual interference between Hb and HbA1c in assays is observed. ► High-sensitivity assays on Hb and HbA1c using immunomagnetic reduction are achieved.

  12. Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

    Directory of Open Access Journals (Sweden)

    Yanrui Yang

    2018-05-01

    Full Text Available Endophilin A1 is a member of the N-BAR domain-containing endophilin A protein family that is involved in membrane dynamics and trafficking. At the presynaptic terminal, endophilin As participate in synaptic vesicle recycling and autophagosome formation. By gene knockout studies, here we report that postsynaptic endophilin A1 functions in synaptic plasticity. Ablation of endophilin A1 in the hippocampal CA1 region of mature mouse brain impairs long-term spatial and contextual fear memory. Its loss in CA1 neurons postsynaptic of the Schaffer collateral pathway causes impairment in their AMPA-type glutamate receptor-mediated synaptic transmission and long-term potentiation. In KO neurons, defects in the structural and functional plasticity of dendritic spines can be rescued by overexpression of endophilin A1 but not A2 or A3. Further, endophilin A1 promotes actin polymerization in dendritic spines during synaptic potentiation. These findings reveal a physiological role of endophilin A1 distinct from that of other endophilin As at the postsynaptic site.

  13. Association of plasma PCB levels and HbA1c concentration in Iran.

    Science.gov (United States)

    Eftekhari, Sahar; Aminian, Omid; Moinfar, Zeinab; Schettgen, Thomas; Kaifie, Andrea; Felten, Michael; Kraus, Thomas; Esser, André

    2018-01-01

    The rapid increase in prevalence of diabetes mellitus over the last decades warrants more attention to the effects of environmental and occupational exposures on glucose metabolism. Our study aimed to assess the association between the plasma levels of various congeners of polychlorinated biphenyls (PCBs) and the serum concentration of glycated haemoglobin (HbA1c). Our study population consisted of 140 Iranian adults from seven different occupational groups and a group of non-occupationally exposed female participants. The plasma concentration of PCBs were determined at the laboratory of occupational toxicology at RWTH Aachen University, Germany. We considered an HbA1c concentration of 5.7% and more as indicating a disturbed glucose metabolism. Logistic regression was used to assess the association between quartiles of concentrations of PCB congeners and serum HbA1c. Participants with an increased HbA1c value had higher plasma levels of PCB 138, 153, 180 and the PCB sum, although this association was statistically not significant. There was no significant difference between the levels of PCB 138, 153, 180, the sum of these congeners, and PCB 118 in their quartiles when comparing with HbA1c concentrations. For our cohort, we could not demonstrate a significant association between PCB and HbA1c concentrations indicating a disturbance of glucose metabolism.

  14. Che a 1: recombinant expression, purification and correspondence to the natural form.

    Science.gov (United States)

    Barderas, Rodrigo; Villalba, Mayte; Rodríguez, Rosalía

    2004-12-01

    Pollinosis to chenopods is one of the main causes of allergy in desertic regions and it is increasing in the South of Europe and Western USA. Che a 1 is a major allergen for chenopod-allergic subjects and belongs to the Ole-e-1-like family of proteins. Pichia pastoris yeast has been used as expression system to produce the recombinant form of Che a 1 (rChe a 1). The allergen was isolated using a gel permeation column and reverse-phase/high-performance liquid chromatography. Molecular characterization was performed using Edman degradation, mass spectrometry and concanavalin A staining. Sera from patients allergic to chenopod pollen, as well as polyclonal and monoclonal antibodies raised against Ole e 1, were used in immunoblotting, ELISA and inhibition assays for immunological characterization of rChe a 1. The allergen was purified to homogeneity with a final yield of 15 mg/l of cell culture and showed a glycosylated character. N-terminal amino acid sequence of rChe a 1 and molecular mass were according to those of the protein isolated from chenopod pollen. The recombinant allergen maintained the IgG and IgE epitopes of the natural allergen deduced from the immunological assays. Structural and in vitro immunological properties of rChe a 1 produced in P. pastoris were equivalent to those of the natural form of the allergen and, thus, it could be used in testing patients allergic to chenopods. 2004 S. Karger AG, Basel.

  15. O2(a1Δ) Quenching In The O/O2/O3 System

    Science.gov (United States)

    Azyazov, V. N.; Mikheyev, P. A.; Postell, D.; Heaven, M. C.

    2010-10-01

    The development of discharge singlet oxygen generators (DSOG's) that can operate at high pressures is required for the power scaling of the discharge oxygen iodine laser. In order to achieve efficient high-pressure DSOG operation it is important to understand the mechanisms by which singlet oxygen (O2(a1Δ)) is quenched in these devices. It has been proposed that three-body deactivation processes of the type O2(a1Δ)+O+M→2O2+M provide significant energy loss channels. To further explore these reactions the physical and reactive quenching of O2(a1Δ) in O(3P)/O2/O3/CO2/He/Ar mixtures has been investigated. Oxygen atoms and singlet oxygen molecules were produced by the 248 nm laser photolysis of ozone. The kinetics of O2(a1Δ) quenching were followed by observing the 1268 nm fluorescence of the O2a1Δ-X3∑ transition. Fast quenching of O2(a1Δ) in the presence of oxygen atoms and molecules was observed. The mechanism of the process has been examined using kinetic models, which indicate that quenching by vibrationally excited ozone is the dominant reaction.

  16. O2(a1Δ) Quenching In The O/O2/O3 System

    International Nuclear Information System (INIS)

    Azyazov, V. N.; Mikheyev, P. A.; Postell, D.; Heaven, M. C.

    2010-01-01

    The development of discharge singlet oxygen generators (DSOG's) that can operate at high pressures is required for the power scaling of the discharge oxygen iodine laser. In order to achieve efficient high-pressure DSOG operation it is important to understand the mechanisms by which singlet oxygen (O 2 (a 1 Δ)) is quenched in these devices. It has been proposed that three-body deactivation processes of the type O 2 (a 1 Δ)+O+M→2O 2 +M provide significant energy loss channels. To further explore these reactions the physical and reactive quenching of O 2 (a 1 Δ) in O( 3 P)/O 2 /O 3 /CO 2 /He/Ar mixtures has been investigated. Oxygen atoms and singlet oxygen molecules were produced by the 248 nm laser photolysis of ozone. The kinetics of O 2 (a 1 Δ) quenching were followed by observing the 1268 nm fluorescence of the O 2 a 1 Δ-X 3 Σ transition. Fast quenching of O 2 (a 1 Δ) in the presence of oxygen atoms and molecules was observed. The mechanism of the process has been examined using kinetic models, which indicate that quenching by vibrationally excited ozone is the dominant reaction.

  17. COL11A1 in FAP polyps and in sporadic colorectal tumors

    International Nuclear Information System (INIS)

    Fischer, Heléne; Salahshor, Sima; Stenling, Roger; Björk, Jan; Lindmark, Gudrun; Iselius, Lennart; Rubio, Carlos; Lindblom, Annika

    2001-01-01

    We previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer

  18. Evaluation of the DCA Vantage analyzer for HbA 1c assay.

    Science.gov (United States)

    Szymezak, Jean; Leroy, Nathalie; Lavalard, Emmanuelle; Gillery, Philippe

    2008-01-01

    Measurement of HbA 1c is key in monitoring diabetic patients in both laboratories and clinical units, where HbA 1c results are used as part of patient education. We have evaluated the DCA Vantage, a new device for immunological assay of HbA 1c. HbA 1c results obtained were evaluated in terms of precision, linearity, specificity and practicability, and were compared with results obtained by a Variant II HPLC method. The method exhibited intra- and inter-assay coefficients of variation lower than 2.6% and 4.0%, respectively, and good correlation with the comparison HPLC method (r2=0.9776). No interference was noted in the presence of labile HbA 1c or carbamylated hemoglobin. The new device exhibited improved practicability characteristics and allowed better sample identification, better management of quality control routines and greater connectivity possibilities compared to the previous DCA 2000 analyzer. This new analyzer exhibited analytical and practical characteristics very suitable for HbA 1c assay for laboratory or point-of-care use according to good laboratory practice.

  19. Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish.

    Science.gov (United States)

    Pott, Alexander; Bock, Sarah; Berger, Ina M; Frese, Karen; Dahme, Tillman; Keßler, Mirjam; Rinné, Susanne; Decher, Niels; Just, Steffen; Rottbauer, Wolfgang

    2018-05-08

    The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na + /K + -ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na + /K + -ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na + /K + -ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na + /K + -ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na + /K + -ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization. Copyright © 2018. Published by Elsevier Ltd.

  20. Mechanistic Scrutiny Identifies a Kinetic Role for Cytochrome b5 Regulation of Human Cytochrome P450c17 (CYP17A1, P450 17A1.

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    Alexandr N Simonov

    Full Text Available Cytochrome P450c17 (P450 17A1, CYP17A1 is a critical enzyme in the synthesis of androgens and is now a target enzyme for the treatment of prostate cancer. Cytochrome P450c17 can exhibit either one or two physiological enzymatic activities differentially regulated by cytochrome b5. How this is achieved remains unknown. Here, comprehensive in silico, in vivo and in vitro analyses were undertaken. Fluorescence Resonance Energy Transfer analysis showed close interactions within living cells between cytochrome P450c17 and cytochrome b5. In silico modeling identified the sites of interaction and confirmed that E48 and E49 residues in cytochrome b5 are essential for activity. Quartz crystal microbalance studies identified specific protein-protein interactions in a lipid membrane. Voltammetric analysis revealed that the wild type cytochrome b5, but not a mutated, E48G/E49G cyt b5, altered the kinetics of electron transfer between the electrode and the P450c17. We conclude that cytochrome b5 can influence the electronic conductivity of cytochrome P450c17 via allosteric, protein-protein interactions.

  1. BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes.

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    Ollitrault, David; Legendre, Florence; Drougard, Carole; Briand, Mélanie; Benateau, Hervé; Goux, Didier; Chajra, Hanane; Poulain, Laurent; Hartmann, Daniel; Vivien, Denis; Shridhar, Vijayalakshmi; Baldi, Alfonso; Mallein-Gerin, Frédéric; Boumediene, Karim; Demoor, Magali; Galera, Philippe

    2015-02-01

    Osteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets.

  2. Hemorheological alterations in adults with prediabetes identified by hemoglobin A1c levels.

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    Marini, M A; Fiorentino, T V; Andreozzi, F; Mannino, G C; Succurro, E; Sciacqua, A; Perticone, F; Sesti, G

    2017-07-01

    A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (β = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical

  3. HbA1c for diagnosis and prognosis of gestational diabetes mellitus.

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    Kwon, Soon Sung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Han; Lim, Jong-Baeck

    2015-10-01

    HbA1c is a widely used marker in diagnosing type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational diabetes mellitus (GDM) is not established. Here, we evaluated the clinical usefulness of HbA1c in diagnosing GDM and predicting the risk of future type 2 DM development among GDM patients. This retrospective, cross-sectional study included 321 subjects who underwent 100-g oral glucose tolerance tests (OGTT) during pregnancy. HbA1c and other variables were analyzed to evaluate their diagnostic performance for GDM. To evaluate the clinical usefulness of HbA1c in predicting future type 2 DM development, we classified GDM subjects who had more than 3 months of follow-up data into two subgroups: those who developed postpartum type 2 DM (PDM) and those who did not. HbA1c was significantly higher in the GDM group than in the normal control group. With the 100-g OGTT as reference, HbA1c showed 91.3% sensitivity and 62% specificity at a cut-off value of 5.05% (32 mmol/mol) for GDM diagnosis. At a cut-off value of 5.25% (34 mmol/mol), sensitivity was 73.6% and specificity was 77.2%. HbA1c levels during pregnancy were higher in those with PDM than in those without PDM (5.91 [41 mmol/mol] vs. 5.44% [36 mmol/mol], p<0.001). The prognostic value of HbA1c for PDM was evaluated by ROC curve analysis, with sensitivity of 78.6% and specificity of 72.5% at a cut-off value of 5.55% (37 mmol/mol). HbA1c showed high sensitivity with relatively low specificity for diagnosis of GDM in pregnant women and was a potential predictor of PDM. HbA1c may be able to be used as a simple and less invasive alternative screening test for OGTT in GDM patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

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    Jeon, Ja Young; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Kim, Nan Hee; Kim, Jae Hyeon; Kim, Chul Sik; Song, Kee-Ho; Won, Jong Chul; Lim, Soo; Choi, Sung Hee; Jang, Myoung-jin; Kim, Yuna; Oh, Kyungwon

    2013-01-01

    Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%. Results When we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5%) and 19.3% (men, 23.8%; women, 14.9%), respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4%) and 38.3% (men, 41%; women, 35.7%), respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate. Conclusion We concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes. PMID:24199164

  5. Prevalence of Diabetes and Prediabetes according to Fasting Plasma Glucose and HbA1c

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    Ja Young Jeon

    2013-10-01

    Full Text Available BackgroundDue to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG level only or the combination of FPG and HbA1c tests.MethodsData from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time <8 hours, missing values from fasting glucose or HbA1c level, previous diagnosis of diabetes made by physicians, or current use of antidiabetic medications. Diabetes was defined as FPG ≥126 mg/dL, previous diagnosis of diabetes made by a medical doctor, current use of antidiabetic medications, and/or HbA1c ≥6.5%. Prediabetes was defined as FPG of 100 to 125 mg/dL and/or HbA1c of 5.7% to 6.4%.ResultsWhen we used FPG only, the prevalence of diabetes and prediabetes were 10.5% (men, 12.6%; women, 8.5% and 19.3% (men, 23.8%; women, 14.9%, respectively. When HbA1c was included as a diagnostic test, the prevalence of diabetes and prediabetes increased to 12.4% (men, 14.5%; women, 10.4% and 38.3% (men, 41%; women, 35.7%, respectively. Participants with HbA1c ≥6.5% and fasting glucose level <126 mg/dL were older and had lower estimated glomerular filtration rate.ConclusionWe concluded that using fasting glucose level only may result in an underestimation of diabetes and prediabetes. HbA1c is an acceptable complementary diagnostic test for diabetes in Korean patients. However, national standardization is needed to order to use HbA1c as a diagnostic method of diabetes and prediabetes.

  6. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.

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    Paula Breitenbach Renz

    Full Text Available Gestational diabetes mellitus (GDM is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT. This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT.This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated.Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33% were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%. This cut-off point presented 100% specificity but very low sensitivity (7%. Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8% showed adequate specificity in diagnosing GDM (94.9% but low sensitivity (26.4%. Unlike, HbA1c values of 31 mmol/mol (5.0% presented adequate sensitivity (89.7% but low specificity (32.6% to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%, the positive and negative likelihood ratios were 5.14 (95%CI 2.49-10.63 and 0.78 (0.68-0.88, respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone.Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

  7. Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent.

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    Schmechel, Donald E; Edwards, Christopher L

    2012-12-01

    Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a

  8. HbA1c as a predictor of diabetes after gestational diabetes mellitus.

    Science.gov (United States)

    Claesson, Rickard; Ignell, Claes; Shaat, Nael; Berntorp, Kerstin

    2017-02-01

    We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Role of HbA1c in predicting risk for congenital malformations.

    Science.gov (United States)

    Hammouda, Sahar Ali Ibrahim; Hakeem, Rubina

    2015-12-01

    Association between conventionally identified hyperglycemias and rates of congenital abnormalities is known; however there is less information about role of HbA1c in determining gestational hyperglycemias and associated risks. This study tried to explore the association between HbA1c in women without known diabetes at first antenatal visit and risk of congenital malformations (CM) among Saudi women living at Al-Madinah Al-Monawarah. Eleven hundred and eighty (1180), healthy, first-trimester pregnant Saudi females without known diabetes, were selected from various antenatal care clinics of Al-Madinah Al-Monawarah city. General clinical and biochemical data was collected for this study by researchers at first visit and the time of delivery. Nearly one fifth (19.6%) of mothers had above normal HbA1c (>5.7) at first visit. Rates of CM had significant positive association with level of HbA1c. Rate of CM among those who had HbA1c in diabetes range, pre-diabetes range or normal range was 27.8%, 9.8% and 3.0%, respectively. The difference was significant between normal and pre-diabetes at the level P=0.000 and between pre-diabetes and diabetes at level P=0.038. In this study HbA1c is found to be a valuable predictor of risk of congenital malformations. This observation calls for further studies and establishment of policies for care of pregnant mothers having higher than normal HbA1c at first visit. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  10. Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan.

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    Yue Chen

    Full Text Available A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%, together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15% but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a while 12 (38% were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan.

  11. Stronger relationship of serum apolipoprotein A-1 and B with diabetic retinopathy than traditional lipids

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    B S Ankit

    2017-01-01

    Full Text Available Aim: Diabetic retinopathy (DR is the most common preventable cause of blindness where early detection and treatment can be sight-saving. Search for biomarkers of the disease has been relentless. We aimed to determine whether lipoproteins apolipoproteins A1 and B1 (Apo-A1 and Apo-B1 have stronger associations with DR in contrast to conventionally measured low-density lipoprotein (LDL and high-density lipoprotein cholesterol levels. Materials and Methods: We performed a cross-sectional study and studied 117 patients. Serum lipid profile was assessed by autoanalyzer. Serum Apo-A1 and Apo-B were measured using immunoturbidimetric kit on an autoanalyzer. Apo-B/A1 ratio was calculated. Retinopathy was graded from the digital retinal photographs, taken with nonmydriatic auto fundus camera and classified according to International Clinical DR Disease Severity Scale. Results: Mean Apo-A1 for mild, moderate, severe retinopathy, and proliferative DR (PDR shows a significant negative correlation (P = 0.001 with severity of retinopathy. Mean Apo-B for mild, moderate, severe, PDR displayed a significant positive correlation with severity of retinopathy (P = 0.001. Mean Apo-B/A1 for mild, moderate, severe, PDR showed highly significant positive correlation with severity of retinopathy (P < 0.001. In contrast, mean LDL for mild, moderate, severe, PDR showed insignificant association with severity of DR (P = 0.081. Conclusion: Apo-A1 and Apo-B have a stronger association with the development of DR than traditional lipids and can thus facilitate early detection and treatment of the disease.

  12. Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

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    Andreia Matos

    2016-01-01

    Full Text Available There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903 and COMT (rs4680 polymorphisms in 130 cervical cancer cases (c-cancer and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p=0.002. The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p=0.002. Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p<0.001. For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p=0.006 and TT&HL genotypes had a protection effect (OR = 0.24, p<0.001. The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer (p<0.001 and p=0.037, resp.. C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.

  13. Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

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    Flower Roderick J

    2011-10-01

    Full Text Available Abstract Background The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1 is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. Results Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i the degree of inflammation at day 7; and ii indexes of fibrosis (assessed by deposition of hydroxyproline in the lung at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-β1, IFN-γ and TNF-α generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21 or therapeutically (from day 14 onward, ameliorated both signs of inflammation and fibrosis. Conclusion Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.

  14. Inflammatory conditions induce IRES-dependent translation of cyp24a1.

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    Daniela Rübsamen

    Full Text Available Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR-kinase, alternative modes of translation, such as internal ribosome entry site (IRES-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM. Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.

  15. Fast Dissemination of New HIV-1 CRF02/A1 Recombinants in Pakistan

    Science.gov (United States)

    Chen, Yue; Hora, Bhavna; DeMarco, Todd; Shah, Sharaf Ali; Ahmed, Manzoor; Sanchez, Ana M.; Su, Chang; Carter, Meredith; Stone, Mars; Hasan, Rumina; Hasan, Zahra; Busch, Michael P.; Denny, Thomas N.; Gao, Feng

    2016-01-01

    A number of HIV-1 subtypes are identified in Pakistan by characterization of partial viral gene sequences. Little is known whether new recombinants are generated and how they disseminate since whole genome sequences for these viruses have not been characterized. Near full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes or next generation sequencing from 34 HIV-1-infected individuals in Pakistan. Phylogenetic tree analysis showed that the newly characterized sequences were 16 subtype As, one subtype C, and 17 A/G recombinants. Further analysis showed that all 16 subtype A1 sequences (47%), together with the vast majority of sequences from Pakistan from other studies, formed a tight subcluster (A1a) within the subtype A1 clade, suggesting that they were derived from a single introduction. More in-depth analysis of 17 A/G NFLG sequences showed that five shared similar recombination breakpoints as in CRF02 (15%) but were phylogenetically distinct from the prototype CRF02 by forming a tight subcluster (CRF02a) while 12 (38%) were new recombinants between CRF02a and A1a or a divergent A1b viruses. Unique recombination patterns among the majority of the newly characterized recombinants indicated ongoing recombination. Interestingly, recombination breakpoints in these CRF02/A1 recombinants were similar to those in prototype CRF02 viruses, indicating that recombination at these sites more likely generate variable recombinant viruses. The dominance and fast dissemination of new CRF02a/A1 recombinants over prototype CRF02 suggest that these recombinant have more adapted and may become major epidemic strains in Pakistan. PMID:27973597

  16. Neue biosensorische Prinzipien für die Hämoglobin-A1c Bestimmung

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    Stöllner, Daniela

    2002-06-01

    Hämoglobin-A1c (HbA1c) ist ein Hämoglobin (Hb)-Subtypus, der durch nicht-enzymatische Glykierung des N-terminalen Valinrestes der Hämoglobin-beta-Kette entsteht. Das gemessene Verhältnis von HbA1c zum Gesamt-Hämoglobin (5-20 % bei Diabetikern) repräsentiert den Mittelwert der Blutglucosekonzentration über einen zweimonatigen Zeitraum und stellt zur Beurteilung der diabetischen Stoffwechsellage eine Ergänzung zur Akutkontrolle der Glukosekonzentration dar. Ziel der vorliegenden Arbeit war es, einen amperometrischen Biosensor für die Bestimmung des medizinisch relevanten Parameters HbA1c zu entwickeln. Durch Selektion geeigneter Bioerkennungselemente und deren Immobilisierung unter Erhalt der Bindungsfunktion für die Zielmoleküle Hämoglobin bzw. HbA1c wurden spezifische, hochaffine und regenerationsstabile Sensoroberflächen geschaffen. Für die Entwicklung des HbA1c-Biosensors wurden zwei Konzepte - Enzymsensor und Immunosensor - miteinander verglichen. Die enzymatische Umsetzung von HbA1c erfolgte mit der Fructosylamin Oxidase (FAO) aus Pichia pastoris N 1-1 unter Freisetzung von H2O2, welches sowohl optisch über eine Indikatorreaktion als auch elektrochemisch nach Einschluss der FAO in PVA-SbQ und Fixierung des Immobilisats vor einer H2O2-Elektrode nachgewiesen wurde. Die Kalibration des Enzymsensors mit der HbA1c-Modellsubstanz Fructosyl-Valin ergab Nachweisgrenzen, die ausserhalb des physiologisch relevanten HbA1c-Konzentrationsbereich lagen. Aus der Umsetzung von glykierten Peptiden mit einer nicht HbA1c analogen Aminosäurensequenz, z.B. Fructosyl-Valin-Glycin wurde zudem eine geringe HbA1c-Spezifität abgeleitet. Für den Immunosensor wurden zwei heterogene Immunoassay-Formate unter Verwendung von hochaffinen und spezifischen Antikörpern in Kombination mit Glucose Oxidase (GOD) als Markerenzym zum Nachweis von HbA1c untersucht. Beim indirekt-kompetitiven Immunoassay wurde anstelle des kompletten HbA1c-Moleküls das glykierte Pentapeptid

  17. HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

    Science.gov (United States)

    Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

    2017-01-01

    Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

  18. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

    Science.gov (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

    2013-12-01

    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

  19. Effects of α-Thalassemia on HbA1c Measurement.

    Science.gov (United States)

    Xu, Anping; Ji, Ling; Chen, Weidong; Xia, Yong; Zhou, Yu

    2016-11-01

    α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA 1c measurement. A total of 189 samples from nondiabetic patients were analyzed. HbA 1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA 2 were also performed. All samples were confirmed by genotyping for thalassemia. In patients with two or three functional α-genes, HbA 1c values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA 1c levels were significantly different from those of controls (P 0.05). In this study, HbA 1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. © 2016 Wiley Periodicals, Inc.

  20. Molecular characterization of subgenotype A1 (subgroup Aa) of hepatitis B virus.

    Science.gov (United States)

    Kramvis, Anna; Kew, Michael C

    2007-07-01

    Subgenotypes of hepatitis B virus (HBV) were first recognized after a unique segment of genotype A was identified when sequencing the preS2/S region of southern African HBV isolates. Originally named subgroup A', subsequently called subgroup Aa (for Africa) or subgenotype A1, this subgenotype is found in South Africa, Malawi, Uganda, Tanzania, Somalia, Yemen, India, Nepal, the Philippines and Brazil. The relatively higher mean nucleotide divergence of subgenotype A1 suggests that it has been endemic and has a long evolutionary history in the populations where it prevails. Distinctive sequence characteristics could account for the high hepatitis B e-antigen (HBeAg) negativity and low HBV DNA levels in carriers of this subgenotype. Substitutions or mutations can reduce HBeAg expression at three levels: (i) 1762T1764A atthe transcriptional level; (ii) substitutions at nt 1809-1812 at the translational level; and (iii) 1862T at the post-translational level. Co-existence of 1762T1764A and nt 1809-1812 mutations reduces HBeAg expression in an additive manner. In addition, subgenotype A1 has unique sequence alterations in the transcriptional regulatory elements and the polymerase coding region. The distinct sequence characteristics of subgenotype A1 may contribute to the 4.5-fold increased risk of heptocellular carcinoma in HBV carriers infected with genotype A, which is entirely attributable to subgenotype A1.

  1. Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma

    Directory of Open Access Journals (Sweden)

    Joao McONeil Plancher

    2015-06-01

    Full Text Available With this case report, we would like to heighten the awareness of clinicians about COL4A1 as a single-gene disorder causing cerebral small vessel disease and describe a previously unreported pathogenic missense substitution in COL4A1 (p.Gly990Val and a new clinical presentation. We identified a heterozygous putatively pathogenic mutation of COL4A1 in a 50-year-old female with a history of congenital cataracts and glaucoma who presented with multiple diffusion-positive infarcts and areas of contrast enhancement following mild head trauma. We believe that this presentation of multiple areas of acute brain and vascular injury in the setting of mild head trauma is a new manifestation of this genetic disorder. Imaging findings of multiple acute infarcts and regions of contrast enhancement with associated asymptomatic old deep microhemorrhages and leukomalacia in adults after head trauma should raise a high suspicion for a COL4A1 genetic disorder. Radiographic patterns of significant leukoaraiosis and deep microhemorrhages can also be seen in patients with long-standing vasculopathy associated with hypertension, which our patient lacked. Our findings demonstrate the utility of genetic screening for COL4A1 mutations in young patients who have small vessel vasculopathy on brain imaging but who do not have significant cardiovascular risk factors.

  2. Global identification of hnRNP A1 binding sites for SSO-based splicing modulation

    DEFF Research Database (Denmark)

    Bruun, Gitte H; Doktor, Thomas K; Borch-Jensen, Jonas

    2016-01-01

    for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing...... regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif. We find that hnRNP A1 binding in proximal introns may be important for repressing exons. We show that inclusion of the alternative cassette exon 3 in SKA2 can be significantly increased by SSO-based treatment which blocks an i...... downstream of the 5' splice site can be blocked by SSOs to activate the exon. CONCLUSIONS: The hnRNP A1 binding map can be used to identify potential targets for SSO-based therapy. Moreover, together with the hnRNP A1 consensus binding motif, the binding map may be used to predict whether disease...

  3. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

    DEFF Research Database (Denmark)

    Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

    2013-01-01

    seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

  4. MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

    Science.gov (United States)

    Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

    2017-11-01

    Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

  5. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease.

    Science.gov (United States)

    Kobayashi, Yodai; Sugahara, Hirosuke; Shimada, Kousuke; Mitsuyama, Eri; Kuhara, Tetsuya; Yasuoka, Akihito; Kondo, Takashi; Abe, Keiko; Xiao, Jin-Zhong

    2017-10-18

    It has previously been shown that the consumption of probiotics may have beneficial effects not only on peripheral tissues but also on the central nervous system and behavior via the microbiota-gut-brain axis, raising the possibility that treatment with probiotics could be an effective therapeutic strategy for managing neurodegenerative disorders. In this study, we investigated the effects of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on behavior and physiological processes in Alzheimer's disease (AD) model mice. We found that administration of B. breve A1 to AD mice reversed the impairment of alternation behavior in a Y maze test and the reduced latency time in a passive avoidance test, indicating that it prevented cognitive dysfunction. We also demonstrated that non-viable components of the bacterium or its metabolite acetate partially ameliorated the cognitive decline observed in AD mice. Gene profiling analysis revealed that the consumption of B. breve A1 suppressed the hippocampal expressions of inflammation and immune-reactive genes that are induced by amyloid-β. Together, these findings suggest that B. breve A1 has therapeutic potential for preventing cognitive impairment in AD.

  6. Reconstitution of β-carotene hydroxylase activity of thermostable CYP175A1 monooxygenase

    International Nuclear Information System (INIS)

    Momoi, Kyoko; Hofmann, Ute; Schmid, Rolf D.; Urlacher, Vlada B.

    2006-01-01

    CYP175A1 is a thermostable P450 Monooxygenase from Thermus thermophilus HB27, demonstrating in vivo activity towards β-carotene. Activity of CYP175A1 was reconstituted in vitro using artificial electron transport proteins. First results were obtained in the mixture with a crude Escherichia coli cell extract at 37 o C. In this system, β-carotene was hydroxylated to β-cryptoxanthin. The result indicated the presence of electron transport enzymes among the E. coli proteins, which are suitable for CYP175A1. However, upon in vitro reconstitution of CYP175A1 activity with purified recombinant flavodoxin and flavodoxin reductase from E. coli, only very low β-cryptoxanthin production was observed. Remarkably, with another artificial electron transport system, putidaredoxin and putidaredoxin reductase from Pseudomonas putida, purified CYP175A1 enzyme hydroxylated β-carotene at 3- and also 3'-positions, resulting in β-cryptoxanthin and zeaxanthin. Under the optimal reaction conditions, the turnover rate of the enzyme reached 0.23 nmol β-cryptoxanthin produced per nmol P450 per min

  7. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

    Science.gov (United States)

    Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

    2017-06-01

    Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Thirtieth anniversary of reactor accident in A-1 Nuclear Power Plant Jaslovske Bohunice

    International Nuclear Information System (INIS)

    Kuruc, J.; Matel, L.

    2007-01-01

    The facts about reactor accidents in A-1 Nuclear Power Plant Jaslovske Bohunice, Slovakia are presented. There was the reactor KS150 (HWGCR) cooled with carbon dioxide and moderated with heavy water. A-1 NPP was commissioned on December 25, 1972. The first reactor accident happened on January 5, 1976 during fuel loading. This accident has not been evaluated according to the INES scale up to the present time. The second serious accident in A-1 NPP occurred on February 22, 1977 also during fuel loading. This INES level 4 of reactor accident resulted in damaged fuel integrity with extensive corrosion damage of fuel cladding and release of radioactivity into the plant area. The A-1 NPP was consecutively shut down and is being decommissioned in the present time. Both reactor accidents are described briefly. Some radioecological and radiobiological consequences of accidents and contamination of area of A-1 NPP as well as of Manivier Canal and Dudvah River as result of flooding during the decommissioning are presented (authors)

  9. Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

    Science.gov (United States)

    Kleine, J P; Camargo-Kosugi, C M; Carvalho, C V; Silva, F C; Silva, I D C G

    2015-12-29

    The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.

  10. Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.

    Directory of Open Access Journals (Sweden)

    Lotta von Ossowski

    Full Text Available Recent studies indicate that glutamatergic signaling involves, and is regulated by, thiol modifying and redox-active compounds. In this study, we examined the role of a reactive cysteine residue, Cys-893, in the cytosolic C-terminal tail of GluA1 AMPA receptor as a potential regulatory target. Elimination of the thiol function by substitution of serine for Cys-893 led to increased steady-state expression level and strongly reduced interaction with SAP97, a major cytosolic interaction partner of GluA1 C-terminus. Moreover, we found that of the three cysteine residues in GluA1 C-terminal tail, Cys-893 is the predominant target for S-nitrosylation induced by exogenous nitric oxide donors in cultured cells and lysates. Co-precipitation experiments provided evidence for native association of SAP97 with neuronal nitric oxide synthase (nNOS and for the potential coupling of Ca2+-permeable GluA1 receptors with nNOS via SAP97. Our results show that Cys-893 can serve as a molecular target for regulatory thiol modifications of GluA1 receptors, including the effects of nitric oxide.

  11. Sibling sRNA RyfA1 Influences Shigella dysenteriae Pathogenesis

    Directory of Open Access Journals (Sweden)

    Megan E. Fris

    2017-01-01

    Full Text Available Small regulatory RNAs (sRNAs of Shigella dysenteriae and other pathogens are vital for the regulation of virulence-associated genes and processes. Here, we characterize RyfA1, one member of a sibling pair of sRNAs produced by S. dysenteriae. Unlike its nearly identical sibling molecule, RyfA2, predicted to be encoded almost exclusively by non-pathogenic species, the presence of a gene encoding RyfA1, or a RyfA1-like molecule, is strongly correlated with virulence in a variety of enteropathogens. In S. dysenteriae, the overproduction of RyfA1 negatively impacts the virulence-associated process of cell-to-cell spread as well as the expression of ompC, a gene encoding a major outer membrane protein important for the pathogenesis of Shigella. Interestingly, the production of RyfA1 is controlled by a second sRNA, here termed RyfB1, the first incidence of one regulatory small RNA controlling another in S. dysenteriae or any Shigella species.

  12. S1(1A1)<--S0(1A1) transition of benzo[g,h,i]perylene in supersonic jets and rare gas matrices.

    Science.gov (United States)

    Rouillé, G; Arold, M; Staicu, A; Krasnokutski, S; Huisken, F; Henning, Th; Tan, X; Salama, F

    2007-05-07

    The study of the S1(1A1)argon matrices. The comparison of the redshifts determined for either transition reveals that the polarizability of BghiP is larger in its S2 than in its S1 state. Bandwidths of 2.7 cm-1 measured in supersonic jets, which provide conditions relevant for astrophysics, are similar to those of most diffuse interstellar bands. The electronic transitions of BghiP are found to lie outside the ranges covered by present databases. From the comparison between experimental spectra and theoretical computations, it is concluded that the accuracy of empirical and ab initio approaches in predicting electronic energies is still not sufficient to identify astrophysically interesting candidates for spectroscopic laboratory studies.

  13. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez

    2017-12-16

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  14. Solvent extraction of uranium (VI) by Amberlite Lsub(A-1)

    International Nuclear Information System (INIS)

    Kim, S.S.

    1977-01-01

    The effects of uranium, amine and sulfuric acid concentrate, and temperature on the extraction of uranium(VI) from acidic sulphate solutions by Amberlite Lsub(A-1) in benzene was studied. The extraction of sulfuric acid by Amberlite Lsub(A-1) in benzene was also examined. It was found that 92 to 98 percent extraction was obtained for a uranyl sulphate solution of 5g/1 concentrate containing of 0.2M to 0.3M sulfuric acid, a Amberlite Lsub(A-1) of 5 to 10 percent (weight) in benzene, at a temperature of less than 20 0 C. The mechanism of uranium extraction was discussed on the basis of the resluts obtained. (author)

  15. Ranked solutions of the matric equation A1X1=A2X2

    Directory of Open Access Journals (Sweden)

    A. Duane Porter

    1980-01-01

    Full Text Available Let GF(pz denote the finite field of pz elements. Let A1 be s×m of rank r1 and A2 be s×n of rank r2 with elements from GF(pz. In this paper, formulas are given for finding the number of X1,X2 over GF(pz which satisfy the matric equation A1X1=A2X2, where X1 is m×t of rank k1, and X2 is n×t of rank k2. These results are then used to find the number of solutions X1,…,Xn, Y1,…,Ym, m,n>1, of the matric equation A1X1…Xn=A2Y1…Ym.

  16. Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

    DEFF Research Database (Denmark)

    Calanna, S; Scicali, R; Di Pino, A

    2014-01-01

    BACKGROUND AND AIMS: We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. METHODS AND RESULTS: Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5...... of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels......, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood...

  17. A novel COL11A1 missense mutation in siblings with non-ocular Stickler syndrome.

    Science.gov (United States)

    Kohmoto, Tomohiro; Tsuji, Atsumi; Morita, Kei-Ichi; Naruto, Takuya; Masuda, Kiyoshi; Kashimada, Kenichi; Enomoto, Keisuke; Morio, Tomohiro; Harada, Hiroyuki; Imoto, Issei

    2016-01-01

    Stickler syndrome (STL) is an autosomal, dominantly inherited, clinically variable and genetically heterogeneous connective tissue disorder characterized by ocular, auditory, orofacial and skeletal abnormalities. We conducted targeted resequencing using a next-generation sequencer for molecular diagnosis of a 2-year-old girl who was clinically suspected of having STL with Pierre Robin sequence. We detected a novel heterozygous missense mutation, NM_001854.3:n.4838G>A [NM_001854.3 (COL11A1_v001):c.4520G>A], in COL11A1, resulting in a Gly to Asp substitution at position 1507 [NM_001854.3(COL11A1_i001)] within one of the collagen-like domains of the triple helical region. The same mutation was detected in her 4-year-old brother with cleft palate and high-frequency sensorineural hearing loss.

  18. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez; de Sessions, Paola Florez; Moon, Robert W.; Grainger, Munira; Holder, Anthony A; Blackman, Michael J.; Roper, Cally; Drakeley, Christopher J.; Pain, Arnab; Sutherland, Colin J.; Hibberd, Martin L.; Campino, Susana; Clark, Taane G

    2017-01-01

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  19. Positive selection in the SLC11A1 gene in the family Equidae

    DEFF Research Database (Denmark)

    Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan

    2016-01-01

    Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes...... a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans...... and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence...

  20. A 1-day course to improve the teaching effectiveness of health professions faculty members.

    Science.gov (United States)

    Stein, Susan M; Fujisaki, Brad S; Davis, Shawn E; Maclean, Linda Garrelts

    2012-02-10

    To determine the effect of a 1-day teaching-methods course for pharmacy and nursing faculty members on teaching proficiency and perceptions of effective teaching. A 1-day teaching-methods course was created and presented to 12 pharmacy and nursing faculty members. Participants' teaching sessions were video-recorded pre- and post-course. A panel of educators evaluated pre- and post-course video-recorded teaching presentations to assess teaching effectiveness. Participants completed pre- and post-course self-evaluations and surveys. Panelists' assessments confirmed significant improvement in 7 of 10 domains. Perceptions of teaching efficacy and proficiency to teach effectively improved after completion of the course. A 1-day teaching-methods course, requiring minimal resources, is a valuable development resource that can improve teaching effectiveness through enhanced communication and teaching techniques. Because effective teaching is positively correlated with students' learning, training seminars can be integral to comprehensive quality improvement.

  1. KADAR HbA1c DAN RASIO LIPID PADA WANITA DEWASA DENGAN OBESITAS SENTRAL

    Directory of Open Access Journals (Sweden)

    Lisa Sudaryanto

    2016-06-01

    Full Text Available Central obesity was accumulation of fat in the abdominal region. Many studies showed correlations between central obesity and cardiovascular diseases, e.g. diabetes and dyslipidemia.  This study was conducted to know the difference between HbA1c and lipid profil between the women with and without central obesity. This study was an analytic observational study with cross-sectional design. Subjects of 52 respondents were healthy adult women staff in campus I, II, III Sanata Dharma University in Yogyakarta and selected using purposive sampling technique. The data of waist circumference, pelvic/hip circumference, HbA1c and lipid profile were collected among the subjects and analyzed with computer with 95% confidence interval. The results of this study showed HbA1c levels and lipid profile were different between the women with and without central obesity, although the difference was not statistically significant.

  2. QCD and resonance physics. The π-p-A1 system

    International Nuclear Information System (INIS)

    Shifman, M.A.; Vainshtein, A.I.; Zakharov, V.I.

    1978-01-01

    The QCD sum rules derived earlier are applied to evaluate the leptonic widths and masses of the π, rho, A 1 mesons (the very existence of resonances is taken as granted, however). The mass scale is set by the power corrections to asymptotic freedom which are due to nonperturbative effects in QCD. The main results are expressions for the p → e + e - and π → μν decay widths and a relation between the mass and the power corrections. Estimates of the A 1 leptonic width are also presented. It is argued that the observed difference in the spectra in the in the vector and axial-vector channels (π - rho - A 1 system) provides a very clean test of the power corrections

  3. New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2018-03-01

    Full Text Available Medullary thyroid cancer (MTC is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1 plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K, which is the key enzyme in the mammalian target of rapamycin (mTOR pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53-sestrins-AMPK-mTOR signaling pathway.

  4. Expression study of CYP19A1 gene in a cohort of Iranian leiomyoma patients

    Directory of Open Access Journals (Sweden)

    Leila Emrahi

    2018-07-01

    Full Text Available Background: CYP19A1 gene encodes aromatase, a microsomal key enzyme that catalyzes the synthesis of estrogens from androgens. Accumulating evidence has revealed that aromatase plays an important role in the pathogenesis of leiomyoma through increasing local concentration of estrogens. In this study, we examined the levels of CYP19A1 mRNA to determine the impact of aromatase overexpression in uterine leiomyoma growth. Subjects and methods: Tissues were obtained via myomectomy or hysterectomy from 30 patients. Total RNA was extracted and cDNA was synthesized from each frozen sample. Using SYBR Green dye, Real-time PCR assay was performed by sequence-specific primers. Relative mRNA expression was normalized to the mean of the Ct values determined for HPRT1. Gene expression ratio in each sample was determined relative to the mean ΔCt value of tumor-free margin samples. Results: PCR efficiencies for amplification reactions of HPRT1, and CYP19A genes were calculated as 0.93 and 0.96, respectively. Regression coefficients (R for standard curves were above 0.90. The obtained data revealed that the mean fold increase of CYP19A1 gene expression in leiomyoma samples relative to normal samples was 3.551 (95% CI: 0.04–6.64, S.E., 0.29–5.35. Conclusions: Our results were in accordance with previous studies and imply that up-regulation of CYP19A1 is correlated with the pathogenesis of leiomyoma tumors. We also observed that expression level of CYP19A1 was not linked to the tumor size or localization. It can be concluded that; up-regulation of aromatase is a key factor in the initiation of tumor development as well as tumor growth. Keywords: Leiomyoma, CYP19A1, Real-time PCR, Gene expression study

  5. Hemoglobin A1c and arterial and ventricular stiffness in older adults.

    Directory of Open Access Journals (Sweden)

    Susan J Zieman

    Full Text Available Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE are implicated in this stiffening pathophysiology. We examined the association between HbA(1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.Baseline HbA(1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG with like measures.HbA(1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP, carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM. FG levels were positively associated with systolic, diastolic and PP and LVM.In this sample of older adults without diabetes, HbA(1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

  6. A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

    Science.gov (United States)

    Lemieux, Bruno; Blanchette, Marco; Monette, Anne; Mouland, Andrew J; Wellinger, Raymund J; Chabot, Benoit

    2015-01-01

    The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

  7. A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

    Directory of Open Access Journals (Sweden)

    Bruno Lemieux

    Full Text Available The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

  8. HbA1c levels in individuals heterozygous for hemoglobin variants.

    Science.gov (United States)

    Tavares, Ricardo Silva; Souza, Fábio Oliveira de; Francescantonio, Isabel Cristina Carvalho Medeiros; Soares, Weslley Carvalho; Mesquita, Mauro Meira

    2017-04-01

    To evaluate the levels of glycated hemoglobin (HbA1c) in patients heterozygous for hemoglobin variants and compare the results of this test with those of a control group. This was an experimental study based on the comparison of HbA1c tests in two different populations, with a test group represented by individuals heterozygous for hemoglobin variants (AS and AC) and a control group consisting of people with electrophoretic profile AA. The two populations were required to meet the following inclusion criteria: Normal levels of fasting glucose, hemoglobin, urea and triglycerides, bilirubin > 20 mg/dL and non-use of acetylsalicylic acid. 50 heterozygous subjects and 50 controls were evaluated between August 2013 and May 2014. The comparison of HbA1c levels between heterozygous individuals and control subjects was performed based on standard deviation, mean and G-Test. The study assessed a test group and a control group, both with 39 adults and 11 children. The mean among heterozygous adults for HbA1c was 5.0%, while the control group showed a rate of 5.74%. Heterozygous children presented mean HbA1c at 5.11%, while the controls were at 5.78%. G-Test yielded p=0.93 for children and p=0.89 for adults. Our study evaluated HbA1c using ion exchange chromatography resins, and the patients heterozygous for hemoglobin variants showed no significant difference from the control group.

  9. Alternate site testing for HbA1c using the Primus CLC330 GHb analyzer.

    Science.gov (United States)

    Phillipov, G; Charles, P; Beng, C; Phillips, P J

    1997-04-01

    To determine whether the Primus high-pressure liquid chromatography (HPLC) is suited to alternate site testing (AST) for HbA1c in a hospital diabetes outpatient clinic. Patients were attending the clinic for routine management of their diabetes. A number of diabetic patients with uremia (n = 11) were also investigated. HbA1c levels were measured in the outpatient setting by the Primus HPLC and in a more limited study the DCA-2000 instrument using the new 6-min assay cartridge. HbA1c measurements were also performed with Pierce affinity minicolumns and a Bio-Rad Variant HPLC. The Primus HPLC assay had low imprecision of 2.3, 1.6, and 1.0% for HbA1c levels of 4.7, 7.3, and 11.1%, respectively, and was not prone to interference by carbamylated hemoglobin as found for the ion-exchange Variant HPLC method. Method comparison studies showed that the bias and proportional error between the Pierce affinity minicolumn procedure (standardized with respect to an external quality control program) and the Primus HPLC (Y) was -0.4 and 1.2% respectively (n = 32). Similarly the bias and proportional error between the Primus and DCA-2000 methods was 0.7 and -2.5%. The Primus was shown to give falsely elevated HbA1c concentrations if the time between sequential injections was > 28 min. The Primus HPLC has a decided advantage over specialty AST instruments, like the DCA-2000, in not only meeting AST requirements but also allowing rapid automated batch processing of all laboratory HbA1c samples.

  10. 125I-labeled 8-phenylxanthine derivatives: antagonist radioligands for adenosine A1 receptors

    International Nuclear Information System (INIS)

    Linden, J.; Patel, A.; Earl, C.Q.; Craig, R.H.; Daluge, S.M.

    1988-01-01

    A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 adenosine receptors of bovine and rat brain and A2 receptors of human platelets was examined. The addition of arylamine or photosensitive aryl azide groups to the 3-position of xanthine had little effect on A1 binding affinity with or without iodination, whereas substitutions at the 1-position caused greatly reduced A1 binding affinity. The addition of an aminobenzyl group to the 3-position of the xanthine had little effect on A2 binding affinity, but 3-aminophenethyl substitution decreased A2 binding affinity. Two acidic 3-(arylamino)-8-phenylxanthine derivatives were labeled with 125 I and evaluated as A1 receptor radioligands. The new radioligands bound to A1 receptors with KD values of 1-1.25 nM. Specific binding represented over 80% of total binding. High concentrations of NaCl or other salts increased the binding affinity of acidic but not neutral antagonists, suggesting that interactions between ionized xanthines and receptors may be affected significantly by changes in ionic strength. On the basis of binding studies with these antagonists and isotope dilution with the agonist [ 125 I]N6-(4-amino-3-iodobenzyl)adenosine, multiple agonist affinity states of A1 receptors have been identified

  11. K2-EDTA and K3-EDTA Greiner Tubes for HbA1c Measurement.

    Science.gov (United States)

    Vrtaric, Alen; Filipi, Petra; Hemar, Marina; Nikolac, Nora; Simundic, Ana-Maria

    2016-02-01

    To determine whether K2-ethylenediaminetetraacetic acid (EDTA) and K3-EDTA Greiner tubes could be used interchangeably for glycosylated hemoglobin, type A1C (HbA1c) measurement via the Abbott Laboratories ARCHITECT chemiluminescent microparticle HbA1c assay on the ARCHITECT i2000SR immunoanalyzer at our university hospital. We drew blood from a total of 45 outpatients into plastic Greiner Vacuette tubes, some of which were lined with K2-EDTA and others with K3-EDTA anticoagulant. Data are presented as median and interquartile range values. We used the Wilcoxon test and Passing-Bablok regression for tube comparison. For K2-EDTA tubes median HbA1c concentration was 54 mmol/mol (41 to 71 mmol/mol) and for K3-EDTA tubes 56 mmol/mol (43 to 69 mmol/mol). There was no statistically significant difference between K2-EDTA and K3-EDTA (bias= -1.29 mmol/mol; P = 0.24). Passing-Bablok regression showed that there is no constant and proportional error: y = -0.23 (95% CI[-3.52 to 0.69]) + 1.00( 95% CI[0.98 to 1.06]) x. In this study, we provide evidence for the lack of any clinically and statistically significant bias between K2-EDTA and K3-EDTA HbA1c measurements. Thus, Greiner tubes lined with K2-EDTA and those lined with K3-EDTA can safely be used interchangeably to measure HbA1c via the Abbott Laboratories ARCHITECT assay. © American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.

    Science.gov (United States)

    Zhang, Lei; Liu, Wen; Wang, Qun; Li, Qinpei; Wang, Huijuan; Wang, Jun; Teng, Tieshan; Chen, Mingliang; Ji, Ailing; Li, Yanzhang

    2018-03-02

    Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K), which is the key enzyme in the mammalian target of rapamycin (mTOR) pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53)-sestrins-AMPK-mTOR signaling pathway.

  13. Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian populations

    Science.gov (United States)

    FUJIMAKI, TETSUO; KATO, KIMIHIKO; OGURI, MITSUTOSHI; YOHIDA, TETSURO; HORIBE, HIDEKI; YOKOI, KIYOSHI; WATANABE, SACHIRO; SATOH, KEI; AOYAGI, YUKITOSHI; TANAKA, MASASHI; YOSHIDA, HIROTO; SHINKAI, SHOJI; NOZAWA, YOSHINORI; SHIN, DONG-JIK; LEE, JONG HO; JANG, YANGSOO; YAMADA, YOSHIJI

    2011-01-01

    We previously identified rs6929846 of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) as a susceptibility locus for myocardial infarction in Japanese individuals by a genome-wide association study. The aim of the present study was to examine the relation of the rs6929846 polymorphism of BTN2A1 to dyslipidemia in Japanese and Korean populations, given that dyslipidemia is an important risk factor for myocardial infarction. A total of 10,953 individuals from three independent subject panels were examined. The relations of the rs6929846 polymorphism of BTN2A1 to serum concentrations of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were examined in each subject panel. The C→T polymorphism (rs6929846) of BTN2A1 was significantly associated with serum concentrations of triglycerides in Japanese subject panels A (P=0.0004) and B (P=0.0010), and in the Korean population (P=0.0095), with the minor T allele being related to an increased serum concentration of triglycerides. The rs6929846 was associated with serum concentrations of HDL-cholesterol in Japanese subject panels A (P=0.0047) and B (P=0.0015), with the T allele being related to a decreased serum concentration of HDL-cholesterol, but not in the Korean population. This polymorphism was associated with the serum concentration of LDL-cholesterol only in Japanese subject panel B (P=0.0059), with the T allele being related to an increased serum concentration of LDL-cholesterol. The results suggest that BTN2A1 may be a susceptibility gene for hypertriglyceridemia in East Asian populations and for low serum HDL-cholesterol in the Japanese population. PMID:22977569

  14. Test Specification of A1-1 Test for OECD-ATLAS Project

    International Nuclear Information System (INIS)

    Kang, Kyoung-Ho; Moon, Sang-Ki; Lee, Seung-Wook; Choi, Ki-Yong; Song, Chul-Hwa

    2014-01-01

    In the OECD-ATLAS project, design extension conditions (DECs) such as a station blackout (SBO) and a total loss of feed water (TLOFW) will be experimentally investigated to meet the international interests in the multiple high-risk DECs raised after the Fukushima accident. The proposed test matrix for the OECD-ATLAS project is summarized in Table 1.. In this study, detailed specification of the first test named as A1-1 in the OECD-ATLAS project was described. The target scenario of the A1-1 test is a prolonged SBO with delayed supply of turbine-driven auxiliary feedwater to only SG number 2 (SG-2). A SBO is one of the most important DECs in that without any proper operator actions, a total loss of heat sink leads to core uncover, to core damage, and ultimately a core melt-down scenario under high pressure. Due to this safety importance, a SBO is considered to be a base test item of the OECD-ATLAS project. A detailed specification of the first test named as A1-1 in the OECD-ATLAS project was described. The target scenario of the A1-1 test is a prolonged SBO with delayed supply of turbine-driven auxiliary feedwater to only SG-2 in order to consider an accident mitigation measure. The pre-test analysis using MARS code was performed with an aim of setting up the detailed test procedures for A1-1 test and also gaining the physical insights for a prolonged SBO transient. In the A1-1 test, a prolonged SBO transient will be simulated with two temporal phases: Phase (I) for conservative SBO transient without supply of turbine-driven auxiliary feedwater and Phase (II) for asymmetric cooling via single trained supply of turbine-driven auxiliary feedwater

  15. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

    International Nuclear Information System (INIS)

    Kitkumthorn, Nakarin; Mutirangura, Apiwat; Yanatatsanajit, Pattamawadee; Kiatpongsan, Sorapop; Phokaew, Chureerat; Triratanachat, Surang; Trivijitsilp, Prasert; Termrungruanglert, Wichai; Tresukosol, Damrong; Niruthisard, Somchai

    2006-01-01

    The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

  16. Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments.

    Science.gov (United States)

    Barratt, Daniel T; Coller, Janet K; Somogyi, Andrew A

    2006-06-05

    The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

  17. Hb variants in Korea: effect on HbA1c using five routine methods.

    Science.gov (United States)

    Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

    2017-07-26

    Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

  18. Cooperation of the SKODA Works in physical starting of the A-1 nuclear power plant

    International Nuclear Information System (INIS)

    Zbytovsky, A.

    1974-01-01

    Co-ordinated research and development efforts of the SKODA Works in the construction, commissioning and start-up of the A-1 nuclear power plant at Jaslovske Bohunice are described. The share of the SKODA Works in the cooperation with allied institutions in the USSR and with two Czechoslovak institutions, i.e., the Nuclear Research Institute at Rez and the Nuclear Power Plant at Bohunice, is detailed and documented by a schedule of experiments aimed at verifying the A-1 calculated parameters in actual operation. (L.O.)

  19. Empirically establishing blood glucose targets to achieve HbA1c goals.

    Science.gov (United States)

    Wei, Nancy; Zheng, Hui; Nathan, David M

    2014-04-01

    OBJECTIVE To determine the average fasting, postprandial, and bedtime self-monitored blood glucose (SMBG) concentrations associated with specified HbA1c levels using data from the A1c-Derived Average Glucose (ADAG) study. RESEARCH DESIGN AND METHODS The ADAG study was a multicenter observational study that used continuous glucose monitoring and SMBG testing to determine the relationship between mean average glucose and HbA1c. We used the SMBG data from 470 of the ADAG study participants (237 with type 1 diabetes and 147 with type 2 diabetes) to determine the average fasting, premeal, 90-min postmeal, and bedtime blood glucose (BG) for predefined target HbA1c groups between 5.5 and 8.5% (37-69 mmol/mol). t Tests were used to compare mean BG values between type 1 and type 2 diabetes groups. RESULTS The average fasting BG needed to achieve predefined HbA1c target levels of 5.5-6.49% (37-47 mmol/mol), 6.5-6.99% (48-52 mmol/mol), 7.0-7.49% (52-58 mmol/mol), 7.5-7.99% (58-64 mmol/mol), and 8.0-8.5% (64-69 mmol/mol) were 122 mg/dL with 95% CI 117-127, 142 mg/dL (135-150), 152 mg/dL (143-162), 167 mg/dL (157-177), and 178 mg/dL (164-192), respectively. Postmeal BG to achieve the HbA1c level of 6.5-6.99% (48-52 mmol/mol) and 7.0-7.49% (52-58 mmol/mol) were 139 mg/dL (134-144) and 152 mg/dL (147-157), respectively. Bedtime BG was 153 mg/dL (145-161) and 177 mg/dL (166-188), respectively. CONCLUSIONS We have determined the average BG at premeal, postmeal, and bedtime to achieve a variety of HbA1c targets. These results, based on empirical data, will help patients and providers set realistic day-to-day SMBG targets to achieve individualized HbA1c goals.

  20. Entsymaattisen Abbott Architect c8000 HbA1c -menetelmän validointi

    OpenAIRE

    Karjalainen, Laura

    2013-01-01

    Opinnäytetyö suoritettiin THL:n Tautiriskiyksikön analyyttisen biokemian laboratoriossa (TLAB). Työssä validoitiin uusi entsymaattinen Abbott Architect c8000 HbA1c -menetelmä, jota käytetään diabetekseen liittyvissä tutkimuksissa. Validoinnilla haluttiin varmistaa uuden mittaustekniikaltaan erilaisen menetelmän toimivuus. Menetelmävertailussa komparatiivisena menetelmänä oli laboratoriossa rutiinikäytössä ollut Abbottin immunoturbidimetrinen HbA1c-menetelmä. Uusi entsymaattinen menetelmä peru...

  1. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

    Science.gov (United States)

    Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

    2016-11-01

    Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI

    NARCIS (Netherlands)

    Vermeulen, R. J.; Peeters-Scholte, C.; van Vugt, J. J. M.; van Vught, J. J. M. G.; Barkhof, F.; Rizzu, P.; van der Schoor, S. R. D.; van der Knaap, M. S.

    2011-01-01

    Mutations in the gene COL4A1, encoding collagen IV A1, are associated with familial porencephaly. Previously, COL4A1 mutation-associated antenatal hemorrhages have been suggested by early post-natal imaging. We describe 2 children with fetal intracerebral hemorrhages and a COL4A1 mutation. There was

  3. Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation.

    Science.gov (United States)

    Tomotaki, Seiichi; Mizumoto, Hiroshi; Hamabata, Takayuki; Kumakura, Akira; Shiota, Mitsutaka; Arai, Hiroshi; Haginoya, Kazuhiro; Hata, Daisuke

    2016-12-01

    We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal-fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present. Copyright © 2014. Published by Elsevier B.V.

  4. Analysis of storm runoff-sediment yield of a 1st order stream basin in ...

    African Journals Online (AJOL)

    Analysis of storm runoff-sediment yield of a 1st order stream basin in Obafemi Awolowo University, Ile-Ife, southwestern Nigeria. ... The findings of this study will aid programme in soil erosion controls designed by the governments and individuals in forested watersheds. Key Words: Storm flow discharge, storm sediment ...

  5. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins

    DEFF Research Database (Denmark)

    Moore, J.S.; Kulhavy, R.; Tomana, M.

    2007-01-01

    , VV reacted with sugars of both IgA subclasses and IgG, indicating that it also recognized N-linked glycans without GalNAc. Furthermore, HAA and HPA from several manufacturers differed in their ability to bind various IgA1 myeloma proteins and other GalNAc-containing glycoproteins in ELISA and Western...

  6. AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor.

    Science.gov (United States)

    Dai, Tongcheng; Li, Na; Han, Fajun; Zhang, Hua; Zhang, Yuanxing; Liu, Qin

    2016-03-01

    Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Hemoglobin A1c measurement for the diagnosis of Type 2 diabetes in children

    Directory of Open Access Journals (Sweden)

    Kapadia Chirag

    2012-12-01

    Full Text Available Abstract Laboratory measurements of hemoglobin A1c above 6.5% were approved as an additional diagnostic criteria for diabetes mellitus by the American Diabetes Association in 2010. Several recent pediatric studies have cast HbA1c measurement in children in an unfavorable light in the pediatric population, by comparing HbA1c measurements to results on oral glucose tolerance test (OGTT or fasting plasma glucose (FPG. However, many of these studies do not recognize that diabetes diagnostic criteria are based upon long-term health outcomes. In this sense, OGTT and FPG have themselves never been validated in the pediatric population. Studies to validate diagnostic tests for diabetes in pediatric populations may take a substantial period of time, and may prove unfeasible. However, studies that tie diagnostic results as a child to diagnostic results as an adult may be more feasible and may provide the data needed to determine which pediatric diagnostic criteria to use. Thus, for the time being, except for cases of hemoglobinopathy, cystic fibrosis, and a few other exceptions, describing HbA1c as ‘lacking in sensitivity or specificity’ in the pediatric population because of lack of correlation with OGTT is not scientifically sound.

  8. Predictors of HbA1c levels in patients initiating metformin

    NARCIS (Netherlands)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra

    2016-01-01

    Objective: The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. Research design and methods: We conducted a cohort study including type 2 diabetes patients who received

  9. Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1

    NARCIS (Netherlands)

    Lodder, E. M.; Hoogeboom, A. J. M.; Coert, J. H.; de Graaff, E.

    2008-01-01

    Brachydactyly type A1 is a limb malformation characterized by a uniform shortening of the middle phalanges in all digits. Mutations in the Indian hedgehog (IHH) gene were shown to be the cause of this autosomal dominant disorder. The IHH protein is known to be an important signaling molecule

  10. 26 CFR 1.641(a)-1 - Imposition of tax; application of tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Imposition of tax; application of tax. 1.641(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.641(a)-1 Imposition of tax; application of tax. For taxable years beginning after December 31, 1970, section 641 prescribes...

  11. Occipital lobe seizures related to marked elevation of hemoglobin A1C: report of two cases.

    Science.gov (United States)

    Hung, Wan-Ling; Hsieh, Peiyuan F; Lee, Yi-Chung; Chang, Ming-Hong

    2010-07-01

    Occipital lobe seizures caused by nonketotic hyperglycemia (NKH) have been reported in only a few cases and are not fully characterized. We report two cases of NKH-related occipital lobe seizures with high hemoglobin A1C (HbA1C), epileptiform electroencephalograph (EEG) and MRI abnormalities. Both patients had moderate hyperglycemia (310-372 mg/dl) and mildly elevated serum osmolarity (295-304 mOsm/kg) but markedly elevated HbA1C (13.8-14.4%). One patient had a clinico-EEG seizure originating from the right occipital region during sleep. The other patient had an interictal epileptiform discharge consisting of unilateral occipital beta activity in sleep. None of the previously reported cases fulfilled the criteria of a nonketotic hyperglycemic hyperosmolar (NKHH) state, or showed any interictal beta paroxysms, spikes, sharp waves, or spike/sharp-slow wave complexes. We suggest that prolonged exposure to uncontrolled hyperglycemia, as indicated by HbA1C, rather than an acute NKHH state is crucial in the development of this peculiar seizure. We also suggest clinicians look for the presence of interictal focal beta paroxysms in addition to the usual epileptiform discharges while reading the EEG of these patients. 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. A 1Σ+ → X 1Σ+ bands of the isotopic lithium hydrides

    International Nuclear Information System (INIS)

    Li, K.C.; Stwalley, W.C.

    1977-01-01

    In order to obtain a better understanding of the X 1 Σ + ground state and the A 1 Σ + state potential energy curves of lithium hydride and to examine in detail the concept of ''mass-reduced quantum numbers'' for both an ordinary (X 1 Σ + ) and an anomalous (A 1 Σ + ) electronic state, the emission spectra of the A 1 Σ + → X 1 Σ + bands of the isotopic lithium hydrides and deuterides ere photographed in the 3000 to 5000A region with a 3.4 meter Ebert Spectrograph. The bands found involved v'' = 0 to 7 to various v' = 0 to 17 for 6 LiH, and v'' = 0 to 7 to various v' = 1 to 16 for 6 LiD. Additional bands involving v'' = 4 and 5 were also found for 7 LiH. The vibrational-rotational spectroscopic analysis of 7 LiH, 6 LiH and 6 LiD are reported here, as are the reanalyses of the 7 LiH and 7 LiD data reported by Crawford and Jorgensen. New Rydberg-Klein-Rees (RKR) A 1 Σ + and X 1 Σ + potential curves have been constructed for each individual molecule and are reported, but detailed isotopic comparisons will be reported in subsequent publications

  13. Prevalence and gene frequencies of A1A2BO and Rh(D) blood ...

    African Journals Online (AJOL)

    Ruqaiya Hussain

    2012-08-03

    Aug 3, 2012 ... Human Genetics and Toxicology Lab, Section of Genetics, Department of Zoology ... alence and gene frequencies of A1A2BO and Rh(D) blood groups among the Muslim populations of ..... The principal bio-clinical significance of the erythrocytic ... (CST), UP, which funded the major project, titled '' Genomic.

  14. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

    DEFF Research Database (Denmark)

    Mills, Philippa B; Footitt, Emma J; Mills, Kevin A

    2010-01-01

    Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-alpha-aminoadipic semialdehyde/L-Delta1-piperideine 6-carboxylate. However, whilst t...

  15. Supercurrents and hydrodynamic modes in 3He-A1 in an electric field

    International Nuclear Information System (INIS)

    Makhlin, Yu.G.

    1994-01-01

    The authors consider the supercurrent in superfluid 3 He in an electric field. The possibility to generate hydrodynamic modes (first and second sound) in the A 1 -phase by an oscillating electric field is proposed. It is shown that the resonance technique can amplify the small amplitude of the second-sound wave. The possibility of measurement is also discussed

  16. Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR

    Directory of Open Access Journals (Sweden)

    Cheng Qian

    2017-12-01

    Full Text Available AIM: To investigate the correlation of matrix metalloproteinase -9(MMP-9, glycated albumin(GA, glycosylated hemoglobin(HbA1cand adipokines(including visfatin, resistin and leptinwith diabetic retinopathy(DR. METHODS: From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients(80 eyeswith non proliferative diabetic retinopathy(NPDRand 34 patients(68 eyeswith proliferative diabetic retinopathy(PDR, and diabetes mellitus 40 patients(80 eyeswith non DR(NDRand 40 healthy volunteers(80 eyeswere selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected. RESULTS: PDR group visfatin was 4.41±0.82ng/mL, was significantly lower than the NPDR group, NDR group and control group(PPPPrs=0.523, 0.461 and 0.414, Prs=-0.433, Prs=0.401 and 0.460, PCONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

  17. High mobility group A1 enhances tumorigenicity of human cholangiocarcinoma and confers resistance to therapy

    DEFF Research Database (Denmark)

    Quintavalle, Cristina; Burmeister, Katharina; Piscuoglio, Salvatore

    2017-01-01

    High mobility group A1 (HMGA1) protein has been described to play an important role in numerous types of human carcinoma. By the modulation of several target genes HMGA1 promotes proliferation and epithelial-mesenchymal transition of tumor cells. However, its role in cholangiocarcinoma (CCA) has...

  18. Supporting a 1:1 Program with a Student Technology Team

    Science.gov (United States)

    Peterson, Lana; Scharber, Cassandra

    2017-01-01

    Purpose: The purpose of this paper is to describe the practice of using student technology teams (STTs) offered at a high school within a 1:1 district. Design/methodology/approach: This qualitative case study (Merriam, 1998, 2009) documents how an STT program functioned in 2015-2016 academic year. Findings: Findings show the STT provided a rich…

  19. A rational route to SCM materials based on a 1-D cobalt selenocyanato coordination polymer.

    Science.gov (United States)

    Boeckmann, Jan; Näther, Christian

    2011-07-07

    Thermal annealing of a discrete complex with terminal SeCN anions and monodentate coligands enforces the formation of a 1D cobalt selenocyanato coordination polymer that shows slow relaxation of the magnetization. Therefore, this approach offers a rational route to 1D materials that might show single chain magnetic behaviour. This journal is © The Royal Society of Chemistry 2011

  20. TLR2 Controls Intestinal Carcinogen Detoxication by CYP1A1

    DEFF Research Database (Denmark)

    Do, Khoa; Fink, Lisbeth Nielsen; Jensen, Thomas Elbenhardt

    2012-01-01

    of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance...

  1. Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention

    International Nuclear Information System (INIS)

    Androutsopoulos, Vasilis P; Tsatsakis, Aristidis M; Spandidos, Demetrios A

    2009-01-01

    CYP1A1 is one of the main cytochrome P450 enzymes, examined extensively for its capacity to activate compounds with carcinogenic properties. Continuous exposure to inhalation chemicals and environmental carcinogens is thought to increase the level of CYP1A1 expression in extrahepatic tissues, through the aryl hydrocarbon receptor (AhR). Although the latter has long been recognized as a ligand-induced transcription factor, which is responsible for the xenobiotic activating pathway of several phase I and phase II metabolizing enzymes, recent evidence suggests that the AhR is involved in various cell signaling pathways critical to cell cycle regulation and normal homeostasis. Disregulation of these pathways is implicated in tumor progression. In addition, it is becoming increasingly evident that CYP1A1 plays an important role in the detoxication of environmental carcinogens, as well as in the metabolic activation of dietary compounds with cancer preventative activity. Ultimately the contribution of CYP1A1 to cancer progression or prevention may depend on the balance of procarcinogen activation/detoxication and dietary natural product extrahepatic metabolism

  2. 26 CFR 1.860A-1 - Effective dates and transition rules.

    Science.gov (United States)

    2010-04-01

    ... and ending before January 1, 1990. (2) Tax avoidance rules—(i) Transfers of certain residual interests... TAX (CONTINUED) INCOME TAXES Real Estate Investment Trusts § 1.860A-1 Effective dates and transition... inclusions accrue in an amount sufficient to satisfy the taxes on the excess inclusions. (iii) Residual...

  3. Small-angle scattering instruments on a 1 MW long pulse spallation source

    International Nuclear Information System (INIS)

    Olah, G.A.; Hjelm, R.P.; Seeger, P.A.

    1995-01-01

    We have designed and optimized two small-angle neutron scattering instruments for installation at a 1 MW long pulse spallation source. The first of these instruments measures a Q-domain from 0.002 to 0.44 A -1 , and the second instrument from 0.00069-0.17 A -1 , Design characteristics were determined and optimization was done using a Monte Carlo instrument simulation package under development at Los alamos. A performance comparison was made between these instruments with D11 at the ILL by evaluating the scattered intensity and rms resolution for the instrument response function at different Q values for various instrument configurations needed to spn a Q-range of 0.0007-0.44 A -1 . We concluded that the first of these instruments outperforms D11 in both intensity and resolution over most of the Q-domain and that the second is comparable to D11. Comparisons were also made of the performance of the optimized long pulse instruments with different reflectors and with a short pulse source, from which we concluded that there is an optimal moderator-reflector combination, and that a short pulse does not substantially improve the instrument performance. (author) 7 figs., 2 tabs., 9 refs

  4. Structural analysis of a 1kW Darrieus turbine spoke

    DEFF Research Database (Denmark)

    Belloni, Federico; Bedon, Gabriele; Castelli, Marco Raciti

    A structural study of a 1 kW Darrieus turbine spoke was performed in order to study stress distribution on the piece and make it more light. The VAWT turbine, originally intended for urban operation, is provided with 3 blades and 6 spokes. Since turbine initial tests showed relevant balancing...

  5. Stabilization of 5A1 urease by covalent attachement to wool | Ahmed ...

    African Journals Online (AJOL)

    The investigation of five bacterial strains for urease production referred that Bacillus licheniformis 5A1 had the highest urease activity (10.3U/ml/min) after 24h. The enzyme was covalently coupled to different carriers via glutaraldehyde, and wool gave the highest immobilization yield (76.4%) and retained 85% of the original ...

  6. Pyridoxine-dependent epilepsy owing to antiquitin deficiency - mutation in the ALDH7A1 gene

    NARCIS (Netherlands)

    Jagadeesh, S.; Suresh, B.; Murugan, V.; Suresh, S.; Salomons, G.S.; Struys, E.A.; Jacobs, C.

    2013-01-01

    Pyridoxine-dependent epilepsy (PDE) is an inborn error of metabolism resulting from antiquitin deficiency. There is marked elevation of a-amino adipic semi-aldehyde (aAASA), piperidine-6-carboxylate (P6C) and pipecolic acid. The diagnosis can be confirmed by identifying the mutation in the ALDH7A1

  7. Refractive index sensor based on a 1D photonic crystal in a microfluidic channel

    DEFF Research Database (Denmark)

    Rodrigues de Sousa Nunes, Pedro André; Mortensen, Asger; Kutter, Jörg Peter

    2010-01-01

    A refractive index sensor has been fabricated in silicon oxynitride by standard UV lithography and dry etching processes. The refractive index sensor consists of a 1D photonic crystal (PhC) embedded in a microfluidic channel addressed by fiber-terminated planar waveguides. Experimental...

  8. A maximum power point tracking scheme for a 1kw stand-alone ...

    African Journals Online (AJOL)

    A maximum power point tracking scheme for a 1kw stand-alone solar energy based power supply. ... Nigerian Journal of Technology ... A method for efficiently maximizing the output power of a solar panel supplying a load or battery bus under ...

  9. Annexin A1 expression in a pooled breast cancer series : Association with tumor subtypes and prognosis

    NARCIS (Netherlands)

    Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H.; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M.; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid Raza; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Phillips, Kelly Anne; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F.; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K.; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Bankier, Agnes; Bastick, Patti; Beesley, Jonathan; Beilby, John; Bennett, Barbara; Bennett, Ian; Berry, Geoffrey; Blackburn, Anneke; Bogwitz, Michael; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burgess, Matthew; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chauhan, Deepa; Chauhan, Manisha; Christian, Alice; Clarke, Christine; Colley, Alison; Cotton, Dick; Crook, Ashley; Cui, James; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah Jane; deFazio, Anna; Delatycki, Martin; Dickson, Rebecca; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Edwards, Stacey; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Fellows, Andrew; Fenton, Georgina; Field, Michael; Firgaira, Frank; Flanagan, James; Fleming, Jean; Fong, Peter; Forbes, John; Fox, Stephen; French, Juliet; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Hardie, Kate; Harris, Marion; Hart, Stewart; Hayward, Nick; Healey, Sue; Heiniger, Louise; Hopper, John; Humphrey, Evelyn; Hunt, Clare; James, Paul; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kidd, Alexa; Kiely, Belinda; Kirk, Judy; Koehler, Jessica; Kollias, James; Kovalenko, Serguei; Lakhani, Sunil; Leaming, Amanda; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Mann, Graham; Marsh, Deborah; McLachlan, Sue Anne; Meiser, Bettina; Meldrum, Cliff; Milne, Roger; Mitchell, Gillian; Newman, Beth; Niedermayr, Eveline; Nightingale, Sophie; O'Connell, Shona; O'Loughlin, Imelda; Osborne, Richard; Pachter, Nick; Patterson, Briony; Peters, Lester; Phillips, Kelly; Price, Melanie; Purser, Lynne; Reeve, Tony; Reeve, Jeanne; Richards, Robert; Rickard, Edwina; Robinson, Bridget; Rudzki, Barney; Saleh, Mona; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Saunus, Jodi; Sayer, Robyn; Scott, Elizabeth; Scott, Rodney; Scott, Clare; Seshadri, Ram; Sexton, Adrienne; Sharma, Raghwa; Shelling, Andrew; Simpson, Peter; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Sykes, Pamela; Tassell, Margaret; Taylor, Donna; Taylor, Jessica; Thierry, Benjamin; Thomas, Susan; Thompson, Ella; Thorne, Heather; Townshend, Sharron; Trainer, Alison; Tran, Lan; Tucker, Kathy; Tyler, Janet; Visvader, Jane; Walker, Logan; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Wu, Kathy; Young, Mary Ann; Bowtell, D.; Green, A.; Webb, P.; de Fazio, A.; Gertig, D.

    2015-01-01

    Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2

  10. [Assays of HbA1c and Amadori products in human biology].

    Science.gov (United States)

    Gillery, P

    2014-09-01

    Different Amadori products, formed during the early steps of the non-enzymatic glycation of proteins, may be assayed in current practice in human biology. The most important marker is HbA1c, resulting from the binding of glucose to the N-terminal extremity of HbA beta chains. HbA1c may be evaluated by various techniques (ion exchange or affinity high performance liquid chromatography, capillary electrophoresis, immunoassay, enzymatic technique) and is considered the best marker of diabetic patient survey. Due to its irreversible and cumulative formation, it provides a retrospective information on the glycemic balance over the four to eight weeks preceding blood collection. It benefits from an international standardization, based on a reference method using liquid chromatography coupled to capillary electrophoresis or mass spectrometry, maintained by an international network of reference laboratories. When HbA1c assay cannot be used (anemia, hemolysis, hemoglobinopathy) or when a shorter period of glycemic equilibrium must be evaluated (child and adolescent, pregnancy, therapeutic changes), other Amadori products may be assayed, like plasma fructosamine (all plasma glycated proteins) or glycated albumin. Nevertheless, these assays are less used in practice, because their semiological value has been less evidenced. Besides, fructosamine assay lacks specificity, and glycated albumin assay has been described recently. An expanding use of HbA1c assay is expected, especially for the diagnosis of diabetes mellitus and the evaluation of other risks, especially cardiovascular ones. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric ...

  12. The renal urate transporter SLC17A1 locus: confirmation of association with gout.

    Science.gov (United States)

    Hollis-Moffatt, Jade E; Phipps-Green, Amanda J; Chapman, Brett; Jones, Gregory T; van Rij, Andre; Gow, Peter J; Harrison, Andrew A; Highton, John; Jones, Peter B; Montgomery, Grant W; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2012-04-27

    Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

  13. 26 CFR 1.989(a)-1 - Definition of a qualified business unit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Definition of a qualified business unit. 1.989... definition of the term “qualified business unit” (QBU) within the meaning of section 989. (2) Effective date... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Export Trade Corporations § 1.989(a)-1 Definition of a...

  14. Peroxisomicine A1 (plant toxin-514) affects normal peroxisome assembly in the yeast Hansenula polymorpha

    NARCIS (Netherlands)

    Vargas-Zapata, Rigoberto; Torres-González, Vladimira; Sepúlveda-Saavedra, Julio; Piñeyro-López, Alfredo; Rechinger, Karl B.; Keizer-Gunnink, Ineke; Kiel, Jan A.K.W.; Veenhuis, Marten

    Previously we demonstrated that peroxisomicine A1 (T-514), a plant toxin isolated from Karwinskia species, has a deteriorating effect on the integrity of peroxisomes of methylotrophic yeasts. Here we describe two strains of Hansenula polymorpha, affected in the normal utilization of methanol as sole

  15. Detection of Helicobacter pylori vacA, cagA and iceA1 virulence ...

    African Journals Online (AJOL)

    Ahmed El-Shenawy

    related genes in different age group patients with ... vacA and iceA1 genotypes of H. pylori strains recovered from patients with dyspepsia. Subjects and methods: ..... many decades in the absence of antimicrobial treatment. Longitu- dinal studies ...

  16. 17 CFR 240.11a1-4(T) - Bond transactions on national securities exchanges.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bond transactions on national....11a1-4(T) Bond transactions on national securities exchanges. A transaction in a bond, note, debenture, or other form of indebtedness effected on a national securities exchange by a member for its own...

  17. CYP19A1 fine-mapping and Mendelian randomization

    DEFF Research Database (Denmark)

    Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M

    2016-01-01

    Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant associat...

  18. Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts

    Directory of Open Access Journals (Sweden)

    Victor J. Thannickal

    2013-09-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi can affect gene expression, and some, such as suberoylanilide hydroxamic acid (SAHA, are US FDA approved for cancer treatment. In this study, we investigated SAHA’s effects on the expression of collagen III alpha 1 (COL3A1 in primary human IPF fibroblasts and in a murine model of pulmonary fibrosis. We observed that increased COL3A1 expression in IPF fibroblasts can be substantially reduced by SAHA treatment at the level of transcription as detected by RT-PCR; collagen III protein level was also reduced, as detected by Western blots and immunofluorescence. The deacetylation inhibitor effect of SAHA was verified by observing higher acetylation levels of both histone H3 and H4 in treated IPF cells. Chromatin immunoprecipitation (ChIP experiments demonstrated that the reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. In our murine model of bleomycin-induced pulmonary fibrosis, the SAHA treated group demonstrated significantly less collagen III, as detected by immunohistochemistry. Our data indicate that the HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression.

  19. Evaluation of the hemoglobin A1c-analyzer TOSOH HLC-723 G7.

    Science.gov (United States)

    Gremmels, Heinz-Detlef; Richter, Anja; Watzke, Ivonne

    2003-01-01

    The TOSOH HLC-723 G7 is a compact analyzer designed for the measurement of HbA1c under routine laboratory conditions. The analyzer has an automatic blood tube supply and positive sample identification. Samples are transported automatically via racks in a continuous-load mode, cap piercing is optional. Tests devoted to the assessment of reproducibility and accuracy of analytical results indicated that over a test period of 17 days, the intra-assay variation (CV) was 1.79%, and the inter-assay variation 2.60%, respectively. A comparison with the predecessor model G5 showed a very good correlation (r = 0.997, y = 1.0041x - 0.00172; n = 149). The presence of high triglyceride, bilirubin or urea concentrations in patient samples did not influence the analytical precision. The labile HbA1c fraction (L-A1c) is clearly separated during chromatography and thus does not compromise HbA1c analysis. With a protocol of 1.2 minutes, the TOSOH G7 is a very fast analyzer, designed for laboratories with a high throughput of samples.

  20. A 1.5 GeV high brilliance synchrotron light source with combined function lattice

    International Nuclear Information System (INIS)

    Eriksson, M.; Lindgren, L.J.; Andersson, Aa.; Roejsel, P.; Werin, S.

    1988-01-01

    A 1.5 GeV synchrotron light source with a combined function lattice is studied. The light source will offer X-ray radiation with λc=1.0 angstrom from a superconducting wiggler and high brilliance VUV-radiation from undulators. The magnet lattice, magnet design and ring performance is discussed. (authors)

  1. Is hemoglobin A1c level effective in predicting the prognosis of Fournier gangrene?

    Science.gov (United States)

    Sen, Haluk; Bayrak, Omer; Erturhan, Sakip; Borazan, Ersin; Koc, Mustafa Nihat

    2016-01-01

    To evaluate the effect of immune failure and/or diabetes mellitus (DM) association on the mortality and morbidity of the Fournier's Gangrene (FG), and interrelatedly, the usability of HbA1c level in the prediction of prognosis. The data of 38 patients with the diagnosis of FG were investigated retrospectively. The patients were divided into two groups as patients with DM (Group 1, n = 18) and non-diabetics (Group 2, n = 20). The patients in group 1 were also divided into two subgroups as patients with HbA1c value ≥7 (Group 1a) and HbA1c value 38°C) (n = 22, 57.8%), purulent discharge from genital or perineal areas (n = 13, 34.2%), skin bruises (n = 11, 28.9%) and general state disorder in five patients that were admitted from day care center (13.1%). DM, as the most often comorbid disease, was detected in 18 patients (47.3%). Six patients (15.7%) were deceased during the follow-up period. In the present study, the researchers determined that diabetic patients with HbA1c level of 7 or higher had worse prognosis, and increased mortality.

  2. Population haplotype analysis and evolutionary relations of the COL2A1 gene

    NARCIS (Netherlands)

    Meulenbelt, I.; Williams, G.J.; Koppele, J.M.T.E.; Giessen, G.C.D.E. van; Slagboom, P.E.

    1996-01-01

    We have determined the allele frequencies mad pairwise linkage disequilibria of restriction fragment length polymorphisms (RFLPs) distributed over the entire COL2A1 gene (spanning 23 · 6 kb) in a population of unrelated Dutch Caucasians. Pairwise linkage disequilibrium analysis of RFLP sites between

  3. Prompt γ-ray data evaluation of thermal-neutron capture for A = 1-25

    International Nuclear Information System (INIS)

    Zhou Chunmei

    1999-01-01

    The method of prompt γ-ray data evaluation for thermal-neutron capture has been briefly presented. The prompt capture γ-ray data of stable nuclei for A = 1 - 25 are evaluated. The evaluated data have been changed into the ENSDF format and the checks of physics and format have been made

  4. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

    NARCIS (Netherlands)

    Mills, P.B.; Footitt, E.J.; Mills, K.A.; Tuschl, K.; Aylett, S.; Varadkar, S.; Hemingway, C.; Marlow, N.; Rennie, J.; Baxter, P.; Dulac, O.; Nabbout, R.; Craigen, W.J.; Schmitt, B.; Feillet, F.; Christensen, E.; de Lonlay, P.; Pike, M.G.; Hughes, M.I.; Struijs, E.A.; Jakobs, C.; Zuberi, S.M.; Clayton, P.T.

    2010-01-01

    Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-α-aminoadipic semialdehyde/l-Δ

  5. Data of evolutionary structure change: 1A96A-1VDMG [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1A96A-1VDMG 1A96 1VDM A G -EKYIVTWDMLQIHARKLASRLMPSEQWKGIIAVSRGGL...VPGALLARELGIRHVDTVCISSY-----NQRELKVLKRAEGDGEG--FIVIDDLVDTGGTAVAIREMYP-----KAHFVTIFAKPAGRPLVDDYVVDIPQDTWIEQPWDMG...U CA 180 1VDM G 1VDMG...entryChain> 1VDM G 1VDMG IEEVKKLG...index> 1VDM G 1VDMG

  6. 26 CFR 1.925(a)-1T - Temporary regulations; transfer pricing rules for FSCs.

    Science.gov (United States)

    2010-04-01

    ... the FSC) by its choice of the three transfer pricing methods described in paragraphs (c)(2), (3), and... income method (the administrative pricing rules) of section 925(a)(1) and (2), respectively, and the...), any, or all, of the transfer pricing methods may be used in the same taxable year of the FSC for...

  7. Pyridoxine-Dependent Epilepsy in Zebrafish Caused by Aldh7a1 Deficiency

    NARCIS (Netherlands)

    Pena, Izabella A; Roussel, Yann; Daniel, Kate; Mongeon, Kevin; Johnstone, Devon; Weinschutz Mendes, Hellen; Bosma, Marjolein; Saxena, Vishal; Lepage, Nathalie; Chakraborty, Pranesh; Dyment, David A; van Karnebeek, Clara D M; Verhoeven-Duif, Nanda; Bui, Tuan Vu; Boycott, Kym M.; Ekker, Marc; MacKenzie, Alex

    2017-01-01

    Pyridoxine-dependent epilepsy (PDE) is a rare disease characterized by mutations in the lysine degradation gene ALDH7A1 leading to recurrent neonatal seizures, which are uniquely alleviated by high doses of pyridoxine or pyridoxal 5'-phosphate (vitamin B6 vitamers). Despite treatment,

  8. Welding electrode for peripheral welds of A-1 reactor pressure vessel

    International Nuclear Information System (INIS)

    Lakatos, L.

    1975-01-01

    The properties are outlined of the VUZ-AC1-52 welding electrode used in welding the Bohunice A-1 reactor pressure vessel. The mechanical properties of welded joints after the final thermal treatment are summed up. (J.K.)

  9. Twenty years from the start-up of A-1, the first Czechoslovak nuclear power plant

    International Nuclear Information System (INIS)

    Komarek, A.

    1992-01-01

    On the occasion of the 20th anniversary of the start-up of A-1, the first Czechoslovak nuclear power plant, some less widely known data concerning the background of its development and construction, its importance for Czechoslovak engineering, and some conclusions for the future development of the Czechoslovak power industry are presented. (author) 3 figs

  10. The reduction of retinene1 to vitamina A1 in vitro.

    Science.gov (United States)

    WALD, G; HUBBARD, R

    1949-01-01

    In the surviving vertebrate retina the retinene(1) liberated by bleaching rhodopsin is converted quantitatively to vitamin A(1). Recent chemical studies have indicated that in this process the aldehyde group of retinene(1) is reduced to the primary alcohol group of vitamin A(1) (Morton; Wald). Some time ago we brought this reaction into a cell-free brei prepared from cattle retinas. The retinas were frozen, desiccated, ground, and exhaustively extracted with petroleum ether; the resulting powder, stirred in neutral buffer solution and exposed to light, converted its retinene(1) completely to vitamin A(1). Some time ago also we observed that fresh rhodopsin solutions exhibit a special type of fading in darkness following exposure to light, which is absent from the same solutions after aging. We have confirmed Bliss's identification of this reaction as the conversion of retinene(1) to vitamin A(1). The system which reduces retinene(1) is fractionated anatomically in the retinal rods. The outer segments of the rods, broken off from the underlying retinal tissue, are unable to convert their retinene(1) to vitamin A(1). In the presence of a water extract of crushed retina they do perform this conversion. On the other hand the retinal tissue from which a water extract was taken has lost this capacity. Such washed retinal tissue is reactivated by returning the washings to the solid material. The activating effect of retinal washings on isolated outer limbs or washed retina is duplicated by a boiled muscle juice. This in turn can be replaced by reduced cozymase (reduced coenzyme I; DPN-H(2)); or by a mixture of DPN and fructosediphosphate. The conversion of retinene(1) to vitamin A(1) is therefore a reduction in which two atoms of hydrogen are transferred to retinene(1) from reduced cozymase. It is assumed that this reaction is catalyzed by an apoenzyme, retinene(1) reductase, present in the rod outer limb. This process is coupled with a second system in the outer segment

  11. A rare encounter with very massive stars in NGC 3125-A1

    Energy Technology Data Exchange (ETDEWEB)

    Wofford, Aida [UPMC-CNRS, UMR7095, Institut d' Astrophysique de Paris, F-75014 Paris (France); Leitherer, Claus [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Chandar, Rupali [University of Toledo, Department of Physics and Astronomy, Toledo, OH 43606 (United States); Bouret, Jean-Claude, E-mail: wofford@iap.edu [Aix Marseille Universite, CNRS, LAM (Laboratoire d' Astrophysique de Marseille) UMR 7326, F-13388 Marseille (France)

    2014-02-01

    Super star cluster A1 in the nearby starburst galaxy NGC 3125 is characterized by broad He II λ1640 emission (FWHM ∼ 1200 km s{sup –1}) of unprecedented strength (equivalent width, EW = 7.1 ± 0.4 Å). Previous attempts to characterize the massive star content in NGC 3125-A1 were hampered by the low resolution of the UV spectrum and the lack of co-spatial panchromatic data. We obtained far-UV to near-IR spectroscopy of the two principal emitting regions in the galaxy with the Space Telescope Imaging Spectrograph and the Cosmic Origins Spectrograph on board the Hubble Space Telescope. We use these data to study three clusters in the galaxy, A1, B1, and B2. We derive cluster ages of 3-4 Myr, intrinsic reddenings of E(B – V) = 0.13, 0.15, and 0.13, and cluster masses of 1.7 × 10{sup 5}, 1.4 × 10{sup 5}, and 1.1 × 10{sup 5} M {sub ☉}, respectively. A1 and B2 show O V λ1371 absorption from massive stars, which is rarely seen in star-forming galaxies, and have Wolf-Rayet (WR) to O star ratios of N(WN5-6)/N(O) = 0.23 and 0.10, respectively. The high N(WN5-6)/N(O) ratio of A1 cannot be reproduced by models that use a normal initial mass function (IMF) and generic WR star line luminosities. We rule out that the extraordinary He II λ1640 emission and O V λ1371 absorption of A1 are due to an extremely flat upper IMF exponent, and suggest that they originate in the winds of very massive (>120 M {sub ☉}) stars. In order to reproduce the properties of peculiar clusters such as A1, the present grid of stellar evolution tracks implemented in Starburst99 needs to be extended to masses >120 M {sub ☉}.

  12. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yongsheng, E-mail: yongshengtanwhu@126.com; Li, Yan, E-mail: liyansd2@163.com

    2015-10-23

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 {sup low} and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96{sup ®}Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 {sup low}, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases

  13. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

    International Nuclear Information System (INIS)

    Tan, Yongsheng; Li, Yan

    2015-01-01

    This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 "l"o"w and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96"®Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 "l"o"w, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases expression of NR4A1

  14. Measurements of the Double-Spin Asymmetry A1 on Helium-3: Toward a Precise Measurement of the Neutron A1

    International Nuclear Information System (INIS)

    Parno, Diana Seymour

    2011-01-01

    The spin structure of protons and neutrons has been an open question for nearly twenty-five years, after surprising experimental results disproved the simple model in which valence quarks were responsible for nearly 100% of the nucleon spin. Diverse theoretical approaches have been brought to bear on the problem, but a shortage of precise data - especially on neutron spin structure - has prevented a thorough understanding. Experiment E06-014, conducted in Hall A of Jefferson Laboratory in 2009, presented an opportunity to add to the world data set for the neutron in the poorly covered valence-quark region. Jefferson Laboratory's highly polarized electron beam, combined with Hall A's facilities for a high-density, highly polarized 3 He target, allowed a high-luminosity double-polarized experiment, while the large acceptance of the BigBite spectrometer gave coverage over a wide kinematic range: 0.15 2 2 . From these data, we extract the longitudinal asymmetry in virtual photon-nucleon scattering, A 1 , on the 3 He nucleus. Combined with the remaining E06-014 data, this will form the basis of a measurement of the neutron asymmetry A n 1 that will extend the kinematic range of the data available to test models of spin-dependent parton distributions in the nucleon

  15. DRD2 A1 allele and P300 abnormalities in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Blum, K. [Univ. of Texas Health Science Center, San Antonio, TX (United States)]|[PATH Foundation, Princeton, NJ (United States); Wood, R.; Sheridan, L.P.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1994-09-01

    Obesity is a heterogeneous and prevalent disorder having both inheritable and environmental components. The role of the dopamine system in P300 has been implicated. We genotyped 193 neuropsychiatrically ill patients with and without comorbid drug and alcohol/abuse/dependence and obesity for the prevalence of the A1 allele of the DRD2 gene. We found a significant linear trend ({chi}{sup 2} = 40.4, df=1, p<0.00001) where the percent prevalence of the A1 increased with increasing polysubstance abuse. Where the A1 allele was found in 44% of 40 obese subjects, the A1 allele prevalence was found in as much as 91% of 11 obese subjects with comorbid polysubstance abuse. 53 obese subjects having a mean body weight (BMI) of 34.6{+-}8.2 were mapped for brain electrical activity and compared with 15 controls with a BMI of 22.3{+-}3.0 (P<.001). The P3 amplitude was significantly different (two tailed; t=3.24, df=16.2, P = 0.005), whereas P3 latency was not significant. Preliminarily, we found a significant decreased P3 amplitude correlated with parental polysubstance abuse (p=0.4) with prolongation of P3 latency correlated with the three risk factors of parental substance abuse, chemical dependency and carbohydrate bingeing (P<0.02). Finally, in a small sample, the A1 allele was present in 25% of probands having 0 risk compared to 66% in those obese subjects with any risk. This work represents the first electrophysiological data to implicate P3 abnormalities in a subset of obesity and further confirms an association of the DRD2 gene and a electrophysiological marker previously indicated to have predictive value in vulnerability to addictive behaviors.

  16. Bilirubin glucuronidation revisited: proper assay conditions to estimate enzyme kinetics with recombinant UGT1A1.

    Science.gov (United States)

    Zhou, Jin; Tracy, Timothy S; Remmel, Rory P

    2010-11-01

    Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. However, the instability of bilirubin and its glucuronides presents substantial technical challenges to conduct in vitro bilirubin glucuronidation assays. Furthermore, because bilirubin can be diglucuronidated through a sequential reaction, establishment of initial rate conditions can be problematic. To address these issues, a robust high-performance liquid chromatography assay to measure both bilirubin mono- and diglucuronide conjugates was developed, and the incubation conditions for bilirubin glucuronidation by human embryonic kidney 293-expressed UGT1A1 were carefully characterized. Our results indicated that bilirubin glucuronidation should be assessed at very low protein concentrations (0.05 mg/ml protein) and over a short incubation time (5 min) to assure initial rate conditions. Under these conditions, bilirubin total glucuronide formation exhibited a hyperbolic (Michaelis-Menten) kinetic profile with a K(m) of ∼0.2 μM. In addition, under these initial rate conditions, the relative proportions between the total monoglucuronide and the diglucuronide product were constant across the range of bilirubin concentration evaluated (0.05-2 μM), with the monoglucuronide being the predominant species (∼70%). In conclusion, establishment of appropriate incubation conditions (i.e., very low protein concentrations and short incubation times) is necessary to properly characterize the kinetics of bilirubin glucuronidation in a recombinant UGT1A1 system.

  17. Expression of enzymatically inactive wasp venom phospholipase A1 in Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Irina Borodina

    Full Text Available Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification.Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect on growth of the yeast cells. To overcome the problem we introduced three different point mutations at the critical points of the active site, where serine137, aspartate165 or histidine229 were replaced by alanine (S137A, D165A and H229A. All the three mutated forms could be expressed in P. pastoris. The H229A mutant did not have any detectable phospholipase A1 activity and was secreted at the level of several mg/L in shake flask culture. The protein was purified by nickel-affinity chromatography and its identity was confirmed by MALDI-TOF mass spectrometry. The protein could bind IgE antibodies from wasp venom allergic patients and could inhibit the binding of wasp venom to IgE antibodies specific for phospholipase A1 as shown by Enzyme Allergo-Sorbent Test (EAST. Moreover, the recombinant protein was allergenic in a biological assay as demonstrated by its capability to induce histamine release of wasp venom-sensitive basophils.The recombinant phospholipase A1 presents a good candidate for wasp venom immunotherapy.

  18. Effects of Sleep Disorders on Hemoglobin A1c Levels in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Ahmet Keskin

    2015-01-01

    Full Text Available Background: Studies have reported the presence of sleep disorders in approximately 50-70% of diabetic patients, and these may contribute to poor glycemic control, diabetic neuropathy, and overnight hypoglycemia. The aim of this study was to determine the frequency of sleep disorders in diabetic patients, and to investigate possible relationships between scores of these sleep disorders and obstructive sleep apnea syndrome (OSAS and diabetic parameters (fasting blood glucose, glycated hemoglobin A1c [HbA1c], and lipid levels. Methods: We used the Berlin questionnaire (BQ for OSAS, the Epworth Sleepiness Scale (ESS, and the Pittsburgh Sleep Quality Index (PSQI to determine the frequency of sleep disorders and their possible relationships with fasting blood glucose, HbA1c, and lipid levels. Results: The study included 585 type 2 diabetic patients admitted to family medicine clinics between October and December 2014. Sleep, sleep quality, and sleep scores were used as the dependent variables in the analysis. The ESS scores showed that 54.40% of patients experienced excessive daytime sleepiness, and according to the PSQI, 64.30% experienced poor-quality sleep. The BQ results indicated that 50.20% of patients were at high-risk of OSAS. HbA1c levels correlated significantly with the ESS and PSQI results (r = 0.23, P < 0.001 and r = 0.14, P = 0.001, respectively, and were significantly higher in those with high-risk of OSAS as defined by the BQ (P < 0.001. These results showed that HbA1c levels were related to sleep disorders. Conclusions: Sleep disorders are common in diabetic patients and negatively affect the control of diabetes. Conversely, poor diabetes control is an important factor disturbing sleep quality. Addressing sleep disturbances in patients who have difficulty controlling their blood glucose has dual benefits: Preventing diabetic complications caused by sleep disturbance and improving diabetes control.

  19. Age-dependent changes of presynaptic neuromodulation via A1-adenosine receptors in rat hippocampal slices.

    Science.gov (United States)

    Sperlágh, B; Zsilla, G; Baranyi, M; Kékes-Szabó, A; Vizi, E S

    1997-10-01

    The presynaptic neuromodulation of stimulation-evoked release of [3H]-acetylcholine by endogenous adenosine, via A1-adenosine receptors, was studied in superfused hippocampal slices taken from 4-, 12- and 24-month-old rats. 8-Cyclopentyl-1,3-dimethylxanthine (0.25 microM), a selective A1-receptor antagonist, increased significantly the electrical field stimulation-induced release of [3H]-acetylcholine in slices prepared from 4- and 12-month-old rats, showing a tonic inhibitory action of endogenous adenosine via stimulation of presynaptic A1-adenosine receptors. In contrast, 8-cyclopentyl-1,3-dimethylxanthine had no effect in 24-month-old rats. 2-Chloroadenosine (10 microM), an adenosine receptor agonist decreased the release of [3H]-acetylcholine in slices taken from 4- and 12-month-old rats, and no significant change was observed in slices taken from 24-month-old rats. In order to show whether the number/or affinity of the A1-receptors was affected in aged rats, [3H]-8-cyclopentyl-1,3-dimethylxanthine binding was studied in hippocampal membranes prepared from rats of different ages. Whereas the Bmax value was significantly lower in 2-year-old rats than in younger counterparts, the dissociation constant (Kd) was not affected by aging, indicating that the density rather than the affinity of adenosine receptors was altered. Endogenous adenosine levels present in the extracellular space were also measured in the superfusate by high performance liquid chromatography (HPLC) coupled with ultraviolet detection, and an age-related increase in the adenosine level was found. In summary, our results indicate that during aging the level of adenosine in the extracellular fluid is increased in the hippocampus. There is a downregulation and reduced responsiveness of presynaptic adenosine A1-receptors, and it seems likely that these changes are due to the enhanced adenosine level in the extracellular space.

  20. SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Emma V. Jones

    2018-02-01

    Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

  1. A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.

    Directory of Open Access Journals (Sweden)

    Elaine Fernanda da Silva

    Full Text Available Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS infusion in non-anesthetized rats. Male Wistar rats (280-340 g received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1 or free saporin (sham, 0.021 ng.nL(-1 into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2 and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1, b.wt., for longer than 1 min. In the sham-group (n = 8, HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline. Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group, and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg. Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05. In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

  2. [Diagnostic agreement between two glycosylated a1b hemoglobin methods in Primary Care].

    Science.gov (United States)

    Villar-del-Campo, M C; Rodríguez-Caravaca, G; Gil-Yonte, P; Cidoncha-Calderón, E; García-Cruces Méndez, J; Donnay-Pérez, S

    2014-01-01

    Several methods are available for measuring glycosylated A1c hemoglobin (HbA1c), all rapid methods for point of care use in a clinical or laboratory setting. This study attempts to compare the diagnostic agreement between two methods for detection of HbA1c. A descriptive cross-sectional study of diagnostic agreement was carried out in the Los Carmenes Health Centre. Two groups of patients -with and without type 2 diabetes- were consecutively included. A method for point-of-care use in a Primary Care Clinic setting (DCA(TM) Systems Siemens(®)) was compared with a laboratory test (chromatographic analysis). An analysis was made of the mean concentration of HbA1c, the agreement between methods, using the intra-class correlation coefficient (CCLA1) and the Bland-Altman method. A total of 102 patients were included, 62 diabetic (60.8%) and 40 non-diabetic (39.2%). The overall mean HbA1c was 6.46% (SD=0.88) in the analysis using capillary blood in the clinic with the DCA™ system, and 6.44% (SD=0.86) using the laboratory test (P>.05). The degree of agreement between the two tests was 0.975 (95% CI: 0.963-0.983). The mean of the differences between the results of the two assessed tests was 0.024 (SD=0.27). The percentage of points outside the limits of optimal agreement, as defined in the Bland-Altman graph, was 2.5%. Diagnostic agreement between a method for point-of-care use in a Primary Health Care Clinic and a laboratory test was very high. Detection at the point-of-care allows a quick and simple assessment of HbA1c. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  3. Polymorphisms of CYP17A1, CYP19, and androgen in Brazilian women with uterine leiomyomas

    DEFF Research Database (Denmark)

    Rosa, Fabíola Encinas; Canevari, Renata de Azevedo; Ambrosio, Eliane Papa

    2008-01-01

    BACKGROUND: Uterine leiomyomas are common, benign, smooth muscle tumors representing a significant public health problem. The aim of this study was to investigate CYP17A1, CYP19, and androgen (AR) polymorphisms, their relative risks for uterine leiomyomas and possible associations with clinical...... parameters. METHODS: Uterine leiomyoma tissues and blood samples were obtained from 87 patients, as were peripheral blood samples from 68 control women. Clinical data were recorded in both groups. The CYP17A1 (rs743572) polymorphism was analyzed by PCR-RFLP, and the CYP19 [TTTA](n) repeat and AR [CAG...... were exclusive to the leiomyoma group. The LOH assay showed allele losses at AR locus in four informative tumors and X chromosome inactivation analysis revealed that these tumors retained the active allele. CONCLUSIONS: The overall lack of association between uterine leiomyomas with polymorphisms...

  4. Citrullinemia type I and hypertrophic pyloric stenosis in a 1-month old male infant

    Directory of Open Access Journals (Sweden)

    Yoona Rhee

    2013-01-01

    Full Text Available Citrullinemia type I (CTLN1 is an inherited urea cycle disorder, now included in most newborn screening panels in the US and Europe. Due to argininosuccinate synthetase deficiency, CTLN1 can lead to recurrent hyperammonemic crisis that may result in permanent neurologic sequelae. Vomiting in patients with urea cycle disorders may either be the result or cause of acute hyperammonemia, particularly if due to an illness that leads to catabolism. Therefore, age-appropriate common etiologies of vomiting must be considered when evaluat- ing these patients. We present a 1-month old male infant with CTLN1 who had a 1-week history of vomiting and was discovered to have hypertrophic pyloric stenosis. This is the first documented case of an infant with CTLN1 who was later diagnosed with hypertrophic pyloric stenosis, and only the second case of concomitant disease.

  5. Genetic variation in statin intolerance and a possible protective role for UGT1A1.

    Science.gov (United States)

    V Willrich, Maria Alice; Kaleta, Erin J; Bryant, Sandra C; Spears, Grant M; Train, Laura J; Peterson, Sandra E; Lennon, Vanda A; Kopecky, Stephen L; Baudhuin, Linnea M

    2018-01-01

    The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance. Creatine kinase activity, lipid profiles and genetic analyses were performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3 sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1 c.3435C>T, ABCG2 c.421C>A and GATM rs9806699. Although lipids were higher in cases, genetic variant minor allele frequencies were similar between cases and controls, except for UGT1A1*28, which was less prevalent in cases than controls.

  6. Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Florio, C.; Rosati, A.M.; Traversa, U.; Vertua, R. (Univ. of Trieste (Italy))

    1991-01-01

    In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-({sup 3}H)adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system.

  7. Hot-Fire Testing of a 1N AF-M315E Thruster

    Science.gov (United States)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  8. Immunological comparison of basic encephalitogen and histone F2A1

    International Nuclear Information System (INIS)

    Bustin, M.; Teitelbaum, D.; Webb, C.

    1975-01-01

    The extent of immunological cross-reaction between basic encephalitogen and histone F2A1 on both the humoral antibody level and on the cellular level has been established. The extent of humoral cross-reaction was tested by direct complement fixation employing both anti-histone F2A1 and antisera to basic encephalitogen, by inhibition of complement fixation, by radioimmunoassay and by passive cutaneous anaphylaxis. The data obtained failed to reveal immunological cross-reaction between the proteins on the humoral antibody level. The extent of cross-reaction at the cellular level was tested by the lymphocyte stimulation technique in rabbits and guinea pigs, by inhibition of lymphocyte stimulation and by delayed hypersensitivity skin reactions. It is concluded that the immunological studies provide limited evidence that the two proteins share antigenic determinants. (orig./GSE) [de

  9. Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex

    International Nuclear Information System (INIS)

    Florio, C.; Rosati, A.M.; Traversa, U.; Vertua, R.

    1991-01-01

    In order to investigate diurnal variation in adenosine A1 receptors binding parameters, Bmax and Kd values of specifically bound N6-cyclohexyl-[ 3 H]adenosine were determined in the cerebral cortex of mice that had been housed under controlled light-dark cycles for 4 weeks. Significant differences were found for Bmax values measured at 3-hr intervals across a 24-h period, with low Bmax values during the light period and high Bmax values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%. No substantial rhythm was found in the Kd values. It is suggested that the changes in the density of A1 receptors could reflect a physiologically-relevant mechanism by which adenosine exerts its modulatory role in the central nervous system

  10. Evidence for quark-hadron duality in the proton spin asymmetry A1

    International Nuclear Information System (INIS)

    Airapetian, A.; Akopov, N.; Akopov, Z.; Avakian, R.; Avetissian, A.; Avetissian, E.; Elbakian, G.; Gharibyan, V.; Marukyan, H.; Rostomyan, A.; Taroian, S.; Zohrabian, H.; Amarian, M.; Ammosov, V.V.; Gapienko, V.; Aschenauer, E.C.; Boettcher, H.; Ehrenfried, M.; Ellinghaus, F.; Jung, P.

    2003-01-01

    Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry A 1 . Longitudinally polarized positrons were scattered off a longitudinally polarized hydrogen target for values of Q 2 between 1.2 and 12 GeV 2 and values of W 2 between 1 and 4 GeV 2 . The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable x. This finding implies that the description of A 1 in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of Q 2 above 1.6 GeV 2

  11. Expression of Enzymatically Inactive Wasp Venom Phospholipase A1 in Pichia pastoris

    DEFF Research Database (Denmark)

    Borodina, Irina; Jensen, Bettina M.; Wagner, Tim

    2011-01-01

    Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain...... and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form...... in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification.Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect...

  12. Expression of enzymatically inactive wasp venom phospholipase A1 in Pichia pastoris

    DEFF Research Database (Denmark)

    Borodina, Irina; Jensen, Bettina M.; Wagner, Tim

    Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain...... and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form...... in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification. Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect...

  13. Expression of enzymatically inactive wasp venom phospholipase A1 in Pichia pastoris

    DEFF Research Database (Denmark)

    Borodina, Irina; Jensen, Bettina M; Wagner, Tim

    2011-01-01

    Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain...... and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form...... in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification.Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect...

  14. Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions

    DEFF Research Database (Denmark)

    Bonomo, Silvia; Jorgensen, Flemming Steen; Olsen, Lars

    2017-01-01

    Cytochrome P450 17A1 (CYP17A1) catalyzes C17 hydroxylation of pregnenolone and progesterone and the subsequent C17–C20 bond cleavage (lyase reaction) to form androgen precursors. Compound I (Cpd I) and peroxo anion (POA) are the heme-reactive species underlying the two reactions. We have characte...... the concept that the selectivity of the steroidogenic CYPs is ruled by direct interactions with the enzyme, in contrast to the selectivity of drug-metabolizing CYPs, where the reactivity of the substrates dominates....... characterized the reaction path for both the hydroxylase and lyase reactions using density functional theory (DFT) calculations and the enzyme–substrate interactions by molecular dynamics (MD) simulations. Activation barriers for positions subject to hydroxylase reaction have values close to each other and span...

  15. MAIZE: a 1 MA LTD-Driven Z-Pinch at The University of Michigan

    International Nuclear Information System (INIS)

    Gilgenbach, R. M.; Gomez, M. R.; Zier, J. C.; Tang, W. W.; French, D. M.; Lau, Y. Y.; Mazarakis, M. G.; Cuneo, M. E.; Johnston, M. D.; Oliver, B. V.; Mehlhorn, T. A.; Kim, A. A.; Sinebryukhov, V. A.

    2009-01-01

    Researchers at The University of Michigan have constructed and tested a 1-MA Linear Transformer Driver (LTD), the first of its type to reach the USA. The Michigan Accelerator for Inductive Z-pinch Experiments, (MAIZE), is based on the LTD developed at the Institute of High Current Electronics in collaboration with Sandia National Labs and UM. This LTD utilizes 80 capacitors and 40 spark gap switches, arranged in 40 ''bricks,'' to deliver a 1 MA, 100 kV pulse with 100 ns risetime into a matched resistive load. Preliminary resistive-load test results are presented for the LTD facility.Planned experimental research programs at UM include: a) Studies of Magneto-Raleigh-Taylor instability of planar foils, and b) Vacuum convolute studies including cathode and anode plasma.

  16. A 1MeV, 1A negative ion accelerator test facility

    International Nuclear Information System (INIS)

    Hanada, M.; Dairaku, M.; Inoue, T.; Miyamoto, K.; Ohara, Y.; Okumura, Y.; Watanabe, K.; Yokoyama, K.

    1995-01-01

    For the Proof-of-Principle test of negative ion acceleration up to 1 MeV, the beam energy required for ITER, a negative ion test facility named MeV Test Facility (MTF) and an ion source/accelerator have been designed and constructed. They are designed to produce a 1 MeV H- beam at a low source pressure of 0.13Pa. The MTF has a power supply system, which constituts of a 1MV, 1A, 60 s Cockcroft-Walton type dc high energy generator and power supplies for negative ion generation and extraction (ion source power supplies). The negative ion source/accelerator is composed of a cesiated volume source and a 5-stage, multi-aperture, electrostatic accelerator. The MTF and the ion source/accelerator have been completed, and the accelertion test up to 1 MeV of the H- ions has started. (orig.)

  17. Oscillations and waves in a spatially distributed system with a 1/f spectrum

    Science.gov (United States)

    Koverda, V. P.; Skokov, V. N.

    2018-02-01

    A spatially distributed system with a 1/f power spectrum is described by two nonlinear stochastic equations. Conditions for the formation of auto-oscillations have been found using numerical methods. The formation of a 1/f and 1/k spectrum simultaneously with the formation and motion of waves under the action of white noise has been demonstrated. The large extreme fluctuations with 1/f and 1/k spectra correspond to the maximum entropy, which points to the stability of such processes. It is shown that on the background of formation and motion of waves at an external periodic action there appears spatio-temporal stochastic resonance, at which one can observe the expansion of the region of periodic pulsations under the action of white noise.

  18. Polarization labelling spectroscopy of the A 1Σ+sub(u) band of Na2

    International Nuclear Information System (INIS)

    Itoh, H.; Hayakawa, M.; Fukuda, Y.; Matsuoka, M.

    1981-01-01

    A result of the polarization labelling spectroscopy of the A 1 Σ + sub(u) band of sodium dimer for the high vibrational quantum number upsilon' > 20 is reported. The frequency difference Δν = νsub(o)sub(b)sub(s)-νsub(c)sub(a)sub(l) is found to decrease from 2 to -3 cm -1 as the rotational levels (upsilon' = 27-30), where νsub(c)sub(a)sub(l) is the calculated transition frequency using the Dunham coefficients of Demtroeder and Stock for the X 1 Σ + sub(g) band and of Kusch and Hessel for the A 1 Σ + sub(u) band. (orig.)

  19. Global map of lithosphere thermal thickness on a 1 deg x 1 deg grid - digitally available

    DEFF Research Database (Denmark)

    Artemieva, Irina

    2014-01-01

    with no or low quality heat flow data. This analysis requires knowledge oflithosphere age globally.A compilation of tectono-thermal ages of lithospheric terranes on a 1 deg 1 deg grid forms the basis forthe statistical analysis. It shows that, statistically, lithospheric thermal thickness z (in km) depends......This presentation reports a 1 deg 1 deg global thermal model for the continental lithosphere (TC1). The modelis digitally available from the author’s web-site: www.lithosphere.info.Geotherms for continental terranes of different ages (early Archean to present) are constrained by reliabledata...... on borehole heat flow measurements (Artemieva and Mooney, 2001), checked with the original publicationsfor data quality, and corrected for paleo-temperature effects where needed. These data are supplemented bycratonic geotherms based on xenolith data.Since heat flow measurements cover not more than half...

  20. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures

    Science.gov (United States)

    Carvill, Gemma L.; McMahon, Jacinta M.; Schneider, Amy; Zemel, Matthew; Myers, Candace T.; Saykally, Julia; Nguyen, John; Robbiano, Angela; Zara, Federico; Specchio, Nicola; Mecarelli, Oriano; Smith, Robert L.; Leventer, Richard J.; Møller, Rikke S.; Nikanorova, Marina; Dimova, Petia; Jordanova, Albena; Petrou, Steven; Helbig, Ingo; Striano, Pasquale; Weckhuysen, Sarah; Berkovic, Samuel F.; Scheffer, Ingrid E.; Mefford, Heather C.

    2015-01-01

    GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutations in seven individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). We describe two truncations and four missense alterations, all of which most likely lead to loss of function of GAT-1 and thus reduced GABA re-uptake from the synapse. These individuals share many of the electrophysiological properties of Gat1-deficient mice, including spontaneous spike-wave discharges. Overall, pathogenic mutations occurred in 6/160 individuals with MAE, accounting for ∼4% of unsolved MAE cases. PMID:25865495

  1. Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study

    DEFF Research Database (Denmark)

    Madsbad, Sten; Kilhovd, B; Lager, I

    2001-01-01

    AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI...... with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.......) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS...

  2. Phenotypic Plasticity, CYP19A1 Pleiotropy, and Maladaptive Selection in Developmental Disorders

    Directory of Open Access Journals (Sweden)

    J. Patrick Malone

    2013-05-01

    Full Text Available The contribution of evolutionary psychology to the study of development and psychopathology depends on adherence to the principles of evolutionary biology. The human brain evolved because selection favored neither size nor complexity but instead the phenotypic plasticity supporting cognitive flexibility. Cell proliferation, migration, elongation, synaptogenesis, synaptic pruning, apoptosis, and myelination occur at varying rates during asynchronous phases of development throughout the brain. Developmentally sensitive periods result from phenotypic plasticity and are vital for adaptation to the environment. The biological systems surrounding the CYP19A1 gene provide mechanisms for neuroprotection and targeted neuronal debridement in response to environmental stress, uniting selection with developmental biology. Updates to Dunbar’s original hypothesis with current primatological data, inclusion of total brain mass, and the introduction of CYP19A1 orthology from nine primate species yields a linear regression, R 2 = .994, adjusted R 2 = .989, F(3, 5 = 143.758, p < .001.

  3. 26 CFR 1.1402(a)-1 - Definition of net earnings from self-employment.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Definition of net earnings from self-employment... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(a)-1 Definition of net earnings from self-employment. (a) Subject to the special rules set forth in §§ 1.1402(a)-3...

  4. ALARA radiation protection applications at NPP A1 decommissioning using VISPLAN planning tool

    International Nuclear Information System (INIS)

    Slavik, O.; Kucharova, D.; Listjak, M.

    2005-01-01

    The SCK.CEN developed during the BR3 reactor decommissioning a graphical interfaced 3D dose assessment tool aimed at the above mentioned dose optimization problems. The tool was improved further and commercialized under the name VISIPLAN 3D ALARA planning tool. The use of VISIPLAN tool at NPP A1 decommissioning was advised by EDF within the IAEA TCP SLR/4008 project missions as a component of a 3D technological chain ensuring acquisition and evaluation of digitized information leading to ALARA optimisation of the developed decommissioning working procedures (see Fig. 1). VISIPLAN license was purchased by IAEA and granted to VUJE and NPP A1 within the IAEA TCP project SLR/4008, covering also the necessary basic and advanced training (at NPP A1 real decommissioning environment), and is currently used by VUJE analysts at NPP A1 decommissioning as an ALARA tool for intervention planning and optimisation. The VISIPLAN allows a fast dose assessment for work planned in a radioactive environment. The calculations are based on a 3D model of the work place. This PC-based tool is user friendly and calculates a detailed dose account for different work scenarios defined by the ALARA analyst, taking into account worker position, work duration and subsequent geometry and source distribution changes. The VISIPLAN methodology is described. The VISIPLAN tool was applied to several ALARA studies carried out by the VUJE within development and analysis of various Work Programs for NPP Al decommissioning tasks. The applications ranged from simpler to complex ALARA planning tasks covering simple shielding applications to selection of the most suitable order of complex working procedures. Removal of inner liners from underground reservoirs 6/1 and 6/2 as well as Dismantling of pipes and components from a (hostile) 60 m corridor are described. (authors)

  5. Applied research into direct numerical control of A-1 reactor temperature

    International Nuclear Information System (INIS)

    Karpeta, C.; Volf, K.

    1974-01-01

    Partial results of research efforts aimed at applying modern control theory in the control of the reactor of the A-1 nuclear power station are presented. A mathematical model of the process dynamics was developed. Some parameters of the model were determined using the results of an experimentally performed reactor scram. The optimal stochastic discrete regulator was determined and closed-loop transients were studied. The possibilities of implementing control routines were investigated using the RPP-16 computer. (author)

  6. "SERUM FERRITIN IN TYPE 2 DIABETES MELLITUS AND ITS RELATIONSHIP WITH HbA1c"

    Directory of Open Access Journals (Sweden)

    F. Sharifi Sh. Sazandeh

    2004-06-01

    Full Text Available Diabetes mellitus (DM type 2 is one of the most common endocrine disorders affecting more than 135 million people in the world. The etiology of the disease is not fully understood, but recently subclinical hemochromatosis has been considered as one of the probable causes of DM. This study was carried out to examine the relationship between serum ferritin as a marker of iron overload with DM and HbA1c. This study was conducted on 97 patients with type 2 DM who were referred to Zanjan Diabetes Clinic. Ninety-four normal age-matched individuals were included in the study as the control group. Ferritin, hemoglobin, HbA1c, and fasting blood sugar were measured in blood samples. Exclusion criteria included anemia, or any other disease or drug that could affect ferritin levels. Results were analyzed statistically by Chi-square test, t-test and Pearson regression coefficient test. One hundred ninety-one cases including 97 diabetics (37 males and 60 females and 94 normal individuals were studied. There were no significant differences between the two groups regarding age, hemoglobin and body mass index. Mean serum ferritin was significantly higher in diabetics than in the control group (101±73 mg/ml vs. 43.5+42 mg/ml, p<0.001. There was no correlation between serum ferritin and HbA1c in diabetic patients of either sex. Ferritin levels in patients with DM is high, but not related to levels of HbA1c and blood glucose control.

  7. Analysis of shutdown and aftercooling cycles of the A-1 nuclear power plant

    International Nuclear Information System (INIS)

    Mueller, V.; Vopatril, M.

    1977-01-01

    A new concept is described of the emergency shut-down and after-cooling of the A-1 reactor based on the elimination of pressure shock and minimization of thermal shock. After-cooling is effected by all circulators which had not been defective before shut-down. During shut-down the pumps run at reduced speed. A diesel generator is used as a self-contained power supply. The after-cooling is classified into three types depending on the machinery power consumption, i.e., normal, emergency and super-emergency. The selection of the power supply and the after-cooling conditions proceeds automatically. A mathematical model is described of A-1 reactor behaviour during different accidents requiring the shut-down and after-cooling. Computer programmes are briefly indicated for the analysis of transients in the primary coolant circuit (ZVJE-73-23, SHOCK A-1), for the analysis of transients resulting from a neutron power controller failure or from a circulator failure (HAZARD), for the analysis of after-cooling processes (DENDEL), and programme SAULIS as an auxiliary programme for processing the results and for the print-out of the DENDEL programme. Steady-state parameters before the failure were found as initial conditions for the calculation of transients. The mathematical model was solved using a system of three computer programmes linked by interprogramme communication. The analysis is described of the cooperation of reactor safety circuits and of the automatic equipment for the reduction of thermal shock in the primary coolant circuit, as is the analysis of reactor accidents related to reactor control and to the safety circuits. Theoretical results are compared with experimental values obtained during the experimental A-1 reactor shut-down and after-cooling. The accuracy of the calculated value for the cooling gas temperature at the central and marginal channel outputs is -10 to +15% during the first 30 s of after-cooling. (J.P.)

  8. Finite difference approximation of control via the potential in a 1-D Schrodinger equation

    Directory of Open Access Journals (Sweden)

    K. Kime

    2000-04-01

    Full Text Available We consider the problem of steering given initial data to given terminal data via a time-dependent potential, the control, in a 1-D Schrodinger equation. We determine a condition for existence of a transferring potential within our approximation. Using Maple, we give equations for the control and also examples in which the potential is restricted to be centralized and to be a step potential.

  9. Hemoglobin A1c, Diabetes Mellitus, Diabetic Nephropathy and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alicia G. Cercado

    2017-12-01

    To prevent, diagnose and treat DM, DN and CKD, it is essential to have state-of-theart tools available to all people. In our region, access to trials, equipment and laboratories within HbA1c standardization programs, internationally accepted, is a pending task. Millions of individuals from the present and future generations of South America will suffer from DM, DN and CKD, so we need to take the voice of science to these people through the daily "doing".

  10. Perubahan Sel Imun Pulpitis Akibat Biomodulasi Laser GaA1As

    OpenAIRE

    Nugrohowati Nugrohowati

    2015-01-01

    The objective of this study was to disclose the effect of GaA1As laser biomodulation on pulpitis immune response. The use of laser is still disputable, because of the biomodulation effect of laser remains unclear, particularly on immune response of pulpitis. Laser is  astressor because it produces stress wave that may cause stress on pulp. Modulation of immune system occurred in each variable of immune system component was considred to be GAS (General Adaptation Syndrome). The applied design ...

  11. Experimental Results of A1.2 Test for OECD-ATLAS Project

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kyoung-Ho; Bae, Byoung-Uhn; Park, Yu-Sun; Kim, Jong-Rok; Choi, Nam-Hyun; Choi, Ki-Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    In order to meet the international interests in the multiple high-risk design extension conditions (DECs) raised after the Fukushima accident, KAERI (Korea Atomic Energy Research Institute) is operating an OECD/NEA project (hereafter, OECD-ATLAS project) by utilizing a thermal-hydraulic integral effect test facility, ATLAS (Advanced Thermal-hydraulic Test Loop for Accident Simulation). As for a prolonged SBO transient of the OECD-ATLAS project, two tests, named A1.1 and A1.2, were determined to be performed. In particular, passive safety systems are considered as the most promising alternatives to reinforce the safety and reliability of an ultimate heat removal system without any operator actions in the SBO transients. As one of the new safety improvement concepts to mitigate an SBO accident efficiently, a cooling and operational performance of the passive auxiliary feedwater system (PAFS) is investigated in the framework of the OECD-ATLAS project to produce clearer knowledge of the actual phenomena and to provide the best guidelines for accident management. As the second test of the OECD-ATLAS project, the A1.2 test was conducted to simulate a prolonged SBO with asymmetric secondary cooling through the supply of passive auxiliary feedwater only to SG-2. When the collapsed water level of steam generator reached a wide range of 25%, PAFS was actuated. PAFS played a key role in cooling down the primary system by the heat transfer and the natural circulation. With the actuation of PAFS, the fluid temperatures at the core inlet and outlet started to decrease without any excursion of the maximum heater surface temperature in the core. This integral effect test data of A1.2 test can be used to evaluate the prediction capability of existing safety analysis codes and identify any code deficiency for an SBO simulation with an operation of a passive system such as PAFS.

  12. A 1 + 5-dimensional gravitational-wave solution. Curvature singularity and spacetime singularity

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Zhu [Tianjin University, Department of Physics, Tianjin (China); Li, Wen-Du [Tianjin University, Department of Physics, Tianjin (China); Nankai University, Theoretical Physics Division, Chern Institute of Mathematics, Tianjin (China); Dai, Wu-Sheng [Nankai University, Theoretical Physics Division, Chern Institute of Mathematics, Tianjin (China); Nankai University and Tianjin University, LiuHui Center for Applied Mathematics, Tianjin (China)

    2017-12-15

    We solve a 1 + 5-dimensional cylindrical gravitational-wave solution of the Einstein equation, in which there are two curvature singularities. Then we show that one of the curvature singularities can be removed by an extension of the spacetime. The result exemplifies that the curvature singularity is not always a spacetime singularity; in other words, the curvature singularity cannot serve as a criterion for spacetime singularities. (orig.)

  13. An investigation of room temperature ''oxidized'' thin films of A1 for photovoltaic applications

    International Nuclear Information System (INIS)

    Adegboyega, G.A.

    1985-12-01

    Sheet resistance and transmittance changes of thin films of A1 evaporated in high vacuum were measured during sorption of oxygen at room atmosphere. An increase of both sheet resistance and transmittance with a tendency to saturation has been observed. Evaluation of various thicknesses of the films for possible use as transparent electrode material for photovoltaic applications shows that for very thin films ( = 200 A) the ''oxidized'' films are superior. (author)

  14. Structural features and dynamic investigations of the membrane-bound cytochrome P450 17A1.

    Science.gov (United States)

    Cui, Ying-Lu; Xue, Qiao; Zheng, Qing-Chuan; Zhang, Ji-Long; Kong, Chui-Peng; Fan, Jing-Rong; Zhang, Hong-Xing

    2015-10-01

    Cytochrome P450 (CYP) 17A1 is a dual-function monooxygenase with a critical role in the synthesis of many human steroid hormones. The enzyme is an important target for treatment of breast and prostate cancers that proliferate in response to estrogens and androgens. Despite the crystallographic structures available for CYP17A1, no membrane-bound structural features of this enzyme at atomic level are available. Accumulating evidence has indicated that the interactions between bounded CYPs and membrane could contribute to the recruitment of lipophilic substrates. To this end, we have investigated the effects on structural characteristics in the presence of the membrane for CYP17A1. The MD simulation results demonstrate a spontaneous insertion process of the enzyme to the lipid. Two predominant modes of CYP17A1 in the membrane are captured, characterized by the depths of insertion and orientations of the enzyme to the membrane surface. The measured heme tilt angles show good consistence with experimental data, thereby verifying the validity of the structural models. Moreover, conformational changes induced by the membrane might have impact on the accessibility of the active site to lipophilic substrates. The dynamics of internal aromatic gate formed by Trp220 and Phe224 are suggested to regulate tunnel opening motions. The knowledge of the membrane binding characteristics could guide future experimental and computational works on membrane-bound CYPs so that various investigations of CYPs in their natural, lipid environment rather than in artificially solubilized forms may be achieved. Copyright © 2015. Published by Elsevier B.V.

  15. Platanus pollen allergen, Pla a 1: quantification in the atmosphere and influence on a sensitizing population.

    Science.gov (United States)

    Fernández-González, D; González-Parrado, Z; Vega-Maray, A M; Valencia-Barrera, R M; Camazón-Izquierdo, B; De Nuntiis, P; Mandrioli, P

    2010-11-01

    The allergic response in susceptible patients does not always coincide with the presence and magnitude of airborne pollen counts. The prevalence of allergy to Platanus is currently moderate, although the percentage of monosensitized patients is low. This hinders accurate interpretation of the relationship between the amount of pollen inhaled and the patient's symptoms. This study aims to investigate the relationship between the atmospheric concentration pattern of Pla a 1 aeroallergen and the Platanus pollen. The pollen sampling was carried out using a Hirst-type volumetric trap (Burkard(©) ) for pollen grains and a Burkard Cyclone sampler (Burkard(©) ) for Pla a 1 allergen. Serum-specific IgE levels to Acer sp., Artemisia vulgaris, Betula alba, Chenopodium album, Cupressus arizonica, Cynodon dactylon, Fraxinus excelsior, Lolium perenne, Pinus sp., Plantago lanceolata, Platanus acerifolia, Populus sp., Quercus ilex and Taraxacum officinale allergens were determined using the EAST System (Hytec specific IgE EIA kit; Hycor Biomedical, Kassel, Germany). The aerobiological dynamics of Platanus pollen grains and Pla a 1 differed considerably, particularly during the Platanus pollination period. Of the 118 subjects tested, sera from 34 contained specific IgE to Platanus pollen and all of them had specific IgE to other pollen types. The presence of the aeroallergen Pla a 1 in the atmosphere appears to be independent of Platanus pollen counts over the same period, which may be contributing to allergic symptoms and sensitization. The number of polysensitized patients displaying allergy to Platanus suggested that allergic symptoms were caused by co-sensitization or cross-reactivity involving a number of allergenic particles. © 2010 Blackwell Publishing Ltd.

  16. Novel homozygous missense mutation in ALDH7A1 causes neonatal pyridoxine dependent epilepsy.

    Science.gov (United States)

    Coci, Emanuele G; Codutti, Luca; Fink, Christian; Bartsch, Sophie; Grüning, Gunnar; Lücke, Thomas; Kurth, Ingo; Riedel, Joachim

    2017-04-01

    Pyridoxine dependent epilepsy (PDE) (OMIM#266100) is a neonatal form of epilepsy, caused by dysfunction of the enzyme α-aminoadipic semialdehyde dehydrogenase (ALDH7A1 or Antiquitin). This enzyme converts α-aminoadipic semialdehyde (α-AASA) into α-aminoadipate (AAA), a critical step in the lysine metabolism of the brain. ALDH7A1 dysfunction causes an accumulation of α-AASA and δ 1 -piperideine-6-carboxylic acid (P6C), which are in equilibrium with each other. P6C binds and inactivates pyridoxal 5'-phosphate (PLP), the active form of pyridoxine. Individuals affected by ALDH7A1 deficiency show pre-natal and post-natal seizures, which respond to oral pyridoxine but not to other pediatric anti-epileptic drugs. We discovered a novel missense mutation (c.566G > A, p.Gly189Glu) in homozygous state residing in the NAD+ binding domain coding region of exon 6 and affecting an highly conserved amino acid residue. The seizures stopped under post-natal pyridoxine therapy, nevertheless a longer follow-up is needed to evaluate the intellectual development of the child, who is additionally treated with oral l-arginine since the 13th month of life. Developmental delay with or without structural cortex abnormalities were reported in several patients. A brain MRI scan revealed hyperintense white matter in the right cerebellum compatible with cerebellar gliosis. Taken together, our studies enlarge the group of missense pathogenic mutations of ALDH7A1 gene and reveal a novel cerebellar finding within the PDE patients cohort. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Analysis of glycated hemoglobin A1c by capillary electrophoresis and capillary isoelectric focusing

    Czech Academy of Sciences Publication Activity Database

    Koval, Dušan; Kašička, Václav; Cottet, H.

    2011-01-01

    Roč. 413, č. 1 (2011), s. 8-15 ISSN 0003-2697 R&D Projects: GA ČR GP203/09/P485; GA ČR(CZ) GA203/08/1428 Institutional research plan: CEZ:AV0Z40550506 Keywords : capillary zone electrophoresis * capillary isoelectric focusing * glycated hemoglobin HbA1c Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.996, year: 2011

  18. Coherent production of a1- mesons and (ρπ)- systems by antineutrinos on neon

    International Nuclear Information System (INIS)

    Marage, P.; Sacton, J.; Willocq, S.; Aderholz, M.; Wittek, W.; Allport, P.P.; Baton, J.P.; Neveu, M.; Burtovoy, V.; Clayton, E.F.; Mobayyen, M.M.; Wainstein, S.; Cooper-Sarkar, A.M.; Guy, J.; Venus, W.; Jones, G.T.; O'Neale, S.; Varvell, K.; Matsinos, E.; Simopoulou, E.; Vayaki, A.; Morrison, D.R.O.; Wachsmuth, H.; Sansum, R.A.

    1991-01-01

    The coherent production of 3π systems by charged current antineutrino interactions on neon nuclei is studied in the bubble chamber BEBC exposed to the CERN SPS wide band beam. The coherent signal is attributed mainly to (ρπ) production, where the (ρπ) system is either non-resonant or comes from the decay of a 1 mesons. The kinematical variables and the total cross section are compared with the predictions of the meson dominance model. (orig.)

  19. Missense mutation in exon 2 of SLC36A1 responsible for champagne dilution in horses.

    Directory of Open Access Journals (Sweden)

    Deborah Cook

    2008-09-01

    Full Text Available Champagne coat color in horses is controlled by a single, autosomal-dominant gene (CH. The phenotype produced by this gene is valued by many horse breeders, but can be difficult to distinguish from the effect produced by the Cream coat color dilution gene (CR. Three sires and their families segregating for CH were tested by genome scanning with microsatellite markers. The CH gene was mapped within a 6 cM region on horse chromosome 14 (LOD = 11.74 for theta = 0.00. Four candidate genes were identified within the region, namely SPARC [Secreted protein, acidic, cysteine-rich (osteonectin], SLC36A1 (Solute Carrier 36 family A1, SLC36A2 (Solute Carrier 36 family A2, and SLC36A3 (Solute Carrier 36 family A3. SLC36A3 was not expressed in skin tissue and therefore not considered further. The other three genes were sequenced in homozygotes for CH and homozygotes for the absence of the dilution allele (ch. SLC36A1 had a nucleotide substitution in exon 2 for horses with the champagne phenotype, which resulted in a transition from a threonine amino acid to an arginine amino acid (T63R. The association of the single nucleotide polymorphism (SNP with the champagne dilution phenotype was complete, as determined by the presence of the nucleotide variant among all 85 horses with the champagne dilution phenotype and its absence among all 97 horses without the champagne phenotype. This is the first description of a phenotype associated with the SLC36A1 gene.

  20. Operation of a 1.3 GHz, 10 MW Multiple Beam Klystron

    CERN Document Server

    Bohlen, H P; Cattelino, M; Cox, L; Cusick, M; Forrest, S; Friedlander, F; Staprans, A; Wright, E; Zitelli, L

    2004-01-01

    Results will be reported for a 1.3 GHz, 10 MW multiple beam klystron that is being developed for the TESLA linear accelerator facility. The design parameters for the device are 10 MW peak RF output power with 150 kW average power, 1.5 ms pulse length, 65% efficiency, 50 dB gain, and 2.0 A/cm2