Sample records for valtellina di tirano

  1. Interdisciplinary approach for disaster risk reduction in Valtellina Valley, northern Italy

    NASA Astrophysics Data System (ADS)

    Garcia, Carolina; Blahut, Jan; Luna, Byron Quan; Poretti, Ilaria; Camera, Corrado; de Amicis, Mattia; Sterlacchini, Simone

    2010-05-01

    Inside the framework of the European research network Mountain Risks, an interdisciplinary research group has been working in the Consortium of Mountain Municipalities of Valtellina di Tirano (northern Italy). This area has been continuously affected by several mountain hazards such as landslides, debris flows and floods that directly affect the population, and in some cases caused several deaths and million euros of losses. An aim of the interdisciplinary work in this study area, is to integrate different scientific products of the research group, in the areas of risk assessment, management and governance, in order to generate, among others, risk reduction tools addressed to general public and stakeholders. Two types of phenomena have been particularly investigated: debris flows and floods. The scientific products range from modeling to mapping of hazard and risk, emergency planning based on real time decision support systems, surveying for the evaluation of risk perception and preparedness, among others. Outputs from medium scale hazard and risk modeling could be used for decision makers and spatial planners as well as civil protection authorities to have a general overview of the area and indentify hot spots for further detailed analysis. Subsequently, local scale analysis is necessary to define possible events and risk scenarios for emergency planning. As for the modeling of past events and new scenarios of debris flows, physical outputs were used as inputs into physical vulnerability assessment and quantitative risk analysis within dynamic runout models. On a pilot zone, the physical damage was quantified for each affected structure within the context of physical vulnerability and different empirical vulnerability curves were obtained. Prospective economic direct losses were estimated. For floods hazard assessment, different approaches and models are being tested, in order to produce flood maps for various return periods, and related to registered rainfalls

  2. Debris flow risk mapping on medium scale and estimation of prospective economic losses

    NASA Astrophysics Data System (ADS)

    Blahut, Jan; Sterlacchini, Simone

    2010-05-01

    Delimitation of potential zones affected by debris flow hazard, mapping of areas at risk, and estimation of future economic damage provides important information for spatial planners and local administrators in all countries endangered by this type of phenomena. This study presents a medium scale (1:25 000 - 1: 50 000) analysis applied in the Consortium of Mountain Municipalities of Valtellina di Tirano (Italian Alps, Lombardy Region). In this area a debris flow hazard map was coupled with the information about the elements at risk to obtain monetary values of prospective damage. Two available hazard maps were obtained from GIS medium scale modelling. Probability estimations of debris flow occurrence were calculated using existing susceptibility maps and two sets of aerial images. Value to the elements at risk was assigned according to the official information on housing costs and land value from the Territorial Agency of Lombardy Region. In the first risk map vulnerability values were assumed to be 1. The second risk map uses three classes of vulnerability values qualitatively estimated according to the debris flow possible propagation. Risk curves summarizing the possible economic losses were calculated. Finally these maps of economic risk were compared to maps derived from qualitative evaluation of the values of the elements at risk.

  3. Fungal biodiversity in the periglacial soil of Dosdè Glacier (Valtellina, Northern Italy).

    PubMed

    Rodolfi, Marinella; Longa, Claudia Maria Oliveira; Pertot, Ilaria; Tosi, Solveig; Savino, Elena; Guglielminetti, Maria; Altobelli, Elisa; Del Frate, Giuseppe; Picco, Anna Maria

    2016-03-01

    Periglacial areas are one of the least studied habitats on Earth, especially in terms of their fungal communities. In this work, both molecular and culture-dependent methods have been used to analyse the microfungi in soils sampled on the front of the East Dosdè Glacier (Valtellina, Northern Italy). Although this survey revealed a community that was rich in fungal species, a distinct group of psychrophilic microfungi has not been detected. Most of the isolated microfungi were mesophiles, which are well adapted to the sensitive climatic changes that occur in this alpine environment. A discrepancy in the results that were obtained by means of the two diagnostic approaches suggests that the used molecular methods cannot entirely replace traditional culture-dependent methods, and vice versa. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. [Radon levels in interiors in Valtellina, on the Angera hills and in the high valley of the Cervo river].

    PubMed

    Facchini, U; Valli, G; Vecchi, R; Dezzuto, C; Lainati, D; Trabucchi, M T; Bonetti, R; Capra, L

    1992-10-01

    The results are reported of an investigation carried out from 1988 to 1990 in many houses in various sites in Lombardy and Piedmont. Measurements were actually carried out in Valtellina, in Angera--on the Lombard side of lake Maggiore--and in the high valley of the river Cervo, north of Biella. The patterns of radon immission in houses due to buildings materials and also to soil emissions are described. Average values of radon levels were obtained using track-etch detectors, whereas fluctuations were recorded daily with a unit capable of detecting alpha particles in real time. Some of the values obtained in 28 Valtellina towns were quite high--e.g., about 1,000 Bq/m3 in towns along the Insubrica fault. The area around Bormio and the Masino valley did not exhibit high radioactivity levels. A total number of nearly 100 houses were investigated in Angera; the highest radon concentrations were observed in cellars and especially in the areas where fractures are bigger and more diffuse. One particular house was accurately examined with real-time analysis of radon fluctuations. Four small towns in the pluton area were investigated in the valley of the river Cervo. In this instance, values were generally high (mean concentration: 842 Bq/m3); the highest concentrations were found in cellars and in ground-floor rooms.

  5. The "green stones" of Valtellina and Valchiavenna (central Alps, northern Italy)

    NASA Astrophysics Data System (ADS)

    Cavallo, Alessandro

    2015-04-01

    Valtellina and Val Chiavenna (Sondrio, Central Alps, northern Italy) are traditionally areas of production of building and ornamental stones (e.g. Serizzo Ghiandone, Serizzo Valmasino, San Fedelino Granite), and among these the "green stones" have a leading position. These stones had an extensive use in Lombardy, as well as abroad (e.g Switzerland). The "green stones" are related to the two mafic-ultramafic bodies of Valmalenco and Chiavenna, where the two largest quarrying districts of the Province of Sondrio are located. Until the early decades of the XX century, serpentinites (and other lithologies from Valtellina) were also extracted from the erratic boulders of Brianza (north of Milan), but at present time the law protects the few remaining boulders. The extracted and processed materials are various: serpentinites, ophicalcites, soapstones. Even the "Stone of Tresivio", used in the past in important monuments of Valtellina, could be classified among the "green stones" in a broad sense: it is a green chloritic schist with scarce and thin ferriferous calcitic veins, pertaining to the sedimentary "Servino" Formation. In recent times, the ancient quarries of this stone were rediscovered near the homonymous village, a few kilometers from Sondrio. There are also historic reports about other "green stones", used in ancient times, such as the "Stone of Grosio", a chloritic schist, and the "Bormio Prasinite". Currently the extraction and processing of "green stones" occurs mostly in Valmalenco, with 22 active serpentinite quarries and a gross volume of 70000 m3 extracted per year, with a yield of about 50%. The Malenco serpentinite (interpreted as sub-continental mantle rocks) forms a 1-2 km thick tabular body, outcropping over an area of about 170 km2, almost entirely confined within the boundaries of the valley. The antigoritic serpentinites (with variable amounts of olivine, clinopyroxene, chlorite and magnetite) are moderately up to strongly foliated, sometimes

  6. A coupled distributed hydrological-stability analysis on a terraced slope of Valtellina (northern Italy)

    NASA Astrophysics Data System (ADS)

    Camera, C.; Apuani, T.; Masetti, M.

    2013-02-01

    The aim of this work was to understand and reproduce the hydrological dynamics of a slope, which was terraced using dry-stone retaining walls and its response to these processes in terms of stability at the slope scale. The slope studied is located in Valtellina (northern Italy), near the village of Tresenda, and in the last 30 yr has experienced several soil slip/debris flow events. In 1983 alone, such events caused the death of 18 people. Direct observation of the events of 1983 enabled the principal triggering cause of these events to be recognized in the formation of an overpressure at the base of a dry-stone wall, which caused its failure. To perform the analyses it is necessary to include the presence of dry-stone walls, considering the importance they have in influencing hydrological and geotechnical processes at the slope scale. This requires a very high resolution DEM (1 m × 1 m because the walls are from 0.60 m to 1.0 m wide) that has been appositely derived. A hydrogeological raster-based model, which takes into account both the unsaturated and saturated flux components, was applied. This was able to identify preferential infiltration zones and was rather precise in the prediction of maximum groundwater levels, providing valid input for the distributed stability analysis. Results of the hydrogeological model were used for the successive stability analysis. Sections of terrace were identified from the downslope base of a retaining wall to the top of the next downslope retaining wall. Within each section a global method of equilibrium was applied to determine its safety factor. The stability model showed a general tendency to overestimate the amount of unstable areas. An investigation of the causes of this unexpected behavior was, therefore, also performed in order to progressively improve the reliability of the model.

  7. Decision Support Systems and Early Warning Solutions: a review in European context.

    NASA Astrophysics Data System (ADS)

    Cortes, V. J.; Frigerio, S.; Schenato, L.; Sterlacchini, S.; Pasuto, A.

    2012-04-01

    strategies and tools by ICT (Information & Communication Technology) for preparedness and response activities in the field of Civil Protection. The test experience was a joint development between CNR -IDPA and CNRS & University of Strasbourg for the Consortium of Mountain Municipalities Valtellina di Tirano, (Lombardia region, Italy)and the ONF-RTM Service of Barcelonnette (French South Alps).

  8. Soils evolution and treeline fluctuations under late Holocene climatic changes: a case study from Upper Valtellina (European Alps, Italy)

    NASA Astrophysics Data System (ADS)

    Masseroli, Anna; Leonelli, Giovanni; Pelfini, Manuela; Trombino, Luca

    2016-04-01

    High-altitude areas in the European Alps have been widely investigated through time for reconstructing the Holocene climate fluctuations, by analyzing both biological and abiological indicators. In high-altitude areas the ongoing temperature increase caused some effects in the natural environments such as the upward shift of the vegetation belts and, in particular, of the treeline. In fact, the treeline is considered a sensitive climate indicator; in high-altitude areas, the vegetation growth and dynamics are strongly influenced not only by climate but also by abiotic factors, like geomorphological processes and soil development. The aim of this study is the reconstruction of late Holocene soil evolution and environmental changes at the treeline on the SW slope of the Monte Confinale in the Upper Valtellina, Central Italian Alps. We performed a detailed reconstruction of the treeline altitudinal dynamics together with the field and laboratory characterization of a transect of nine soil profiles developing at an altitude ranging from 1800 m a.s.l. (closed forest) to 2600 m a.s.l. (species line), in order to understand the relationship between colonization by arboreal vegetation and soil development. The upward shift of the treeline was assessed analyzing tree age distribution on the slope by means of a tree-ring based approach. The treeline elevation over time (based on the years in which the trees reached 2 m in height) increased from 2505 m a.s.l. (period 1990-1999) to 2531 m (period 2000-2009) to 2545 m (in 2013) with a rate of upward shift of up to 2.6 m/y in the period 2000-2009. The investigated soils showed a decreasing development with increasing altitude, in fact at higher altitude we found less developed soils (i.e. Ranker), on the contrary in the forest area (about 2000 m a.s.l.) we found a more developed soil (i.e. Podzol). Moreover, the soil development may also be affected by the conditions of the slope, characterized by broad alpine grasslands that

  9. Comparison of the results of different scale hydrogeological models on a terraced slope of Valtellina (Northern Italy)

    NASA Astrophysics Data System (ADS)

    Camera, C.; Apuani, T.; Masetti, M.; Mele, M.

    2012-04-01

    The aim of this work was to understand and reproduce the hydrological dynamics of a slope that is terraced by dry-stone retaining walls. At first, the processes of interest were analyzed with a classical 2D unsaturated-saturated finite elements analysis, reproducing the geometry of a single terrace. In a second moment, a raster analysis at the slope scale was performed. The studied slope is located in Valtellina (Northern Italy), near the village of Tresenda, and in the last 30 years it experienced several soil slip/debris flow events that in 1983 caused 18 victims. Direct observation of the events of 1983 permitted to recognize the principal triggering cause of these events in the formation of an overpressure at the base of a dry-stone wall, that caused its failure. Using field tests and monitoring activity as input and calibration data respectively, the 2D model is able to explain the mechanisms of rainfall infiltration that can lead to the formation and evolution of a perched groundwater table at the contact between the bedrock and the walls backfill soil. Once calibrated and validated the model has been used to investigate the influence of different parameters on the studied processes, such as walls height, bedrock slope angle, and changes of both isotropic and anisotropic saturated hydraulic conductivity of soil and wall. From this sensitivity analysis, one of the most interesting results is the ability of the model to well differentiate the behaviour of a well maintained wall with an higher hydraulic conductivity than soil, from a poorly maintained wall that has lost part of its drainage capacity. In fact, only in this latter circumstance significant pore-water pressures can form at the base of the retaining structure. Moving the problem to the slope scale, although the used raster-model takes into account both the unsaturated and saturated components of flux as the 2D model, it is less precise in the description of the processes involved in the formation of

  10. Debris flow reconstruction - geomorphologic and numerical approach. A case study from the Selvetta event in Valtellina, Italy, July 2008

    NASA Astrophysics Data System (ADS)

    Blahut, J.; Luna, B. Quan; Akbas, S. O.; van Westen, C. J.

    2009-04-01

    On Sunday morning of 13th July 2008, after more than two days of intense rainfall, several debris and mud flows were released in the central part of Valtellina valley between Morbegno and Berbenno. One of the largest debris flows occurred in Selvetta, a fraction of Colorina municipality. The debris flow event was reconstructed after extensive field work and interviews with local inhabitants and civil protection teams. At first several rock blocks about 2 m3 in size fell down from the direction of the torrent. The blocks were followed by a wave of debris and mud that immediately destroyed one building and caused damage to other nine houses. A stream flow following the debris flow consisting of fine mud with high water content that partially washed away the accumulation of deposits from the debris phase could also be distinguished. Geomorphologic investigations allowed identification of five main sections of the flow: 1) the proper scarp; 2) path in the forested area; 3) path on the alpine meadows; 4) accelerating section; 5) accumulation area. The initiation area of the flow is situated at 1760 m. a.s.l. (1480 m above the deposition zone) in a coniferous forest. The proper scarp consisted of an area of approximately 20 m2 in size, and a height of about 0.8 m. The final volume of the debris was estimated by field mapping to be between 12 000 and 15 000 m3. It was observed that erosion and entrainment played an important role in the development of the debris flow. The Selvetta event was modelled with the FLO2D program. FLO2D is an Eulerian formulation with a finite differences numerical scheme that requires the specification of an input hydrograph. The internal stresses are isotropic and the basal shear stresses are calculated using a quadratic model. Entrainment was modeled at each section of the flow, and different hydrographs were produced in agreement with the behavior of the debris flow during its course. The significance of calculated values of pressure and

  11. Toluidine blue-O is a Nissl bright-field counterstain for lipophilic fluorescent tracers Di-ASP, DiI and DiO.

    PubMed

    Chelvanayagam, D K; Beazley, L D

    1997-03-01

    The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.

  12. Sviluppi di Ricevitori E di Componentistica Per Banda 3 mm Ad INAF-OA Cagliari

    NASA Astrophysics Data System (ADS)

    Navarrini, Alessandro

    2017-11-01

    L'INAF-OA Cagliari (OACa) sta sviluppando un ricevitore criogenico a basso rumore basato su un mixer SSB (Single Side Band) a superconduttore SIS (Superconductor-Insulator-Superconductor) per la banda 3 mm. Il ricevitore, acquistato da IRAM, è stato fortemente modificato per essere adattato al fuoco Gregoriano di SRT (Sardinia Radio Telescope). Lo strumento è caratterizzato da una nuova criogenia a ciclo chiuso 4 K (per evitare l'uso di elio liquido in antenna), da un nuovo oscillatore locale (di tipo ALMA Banda 3) e da un nuovo sistema di controllo e di monitoraggio basato su schede Raspberry ed Arduino sviluppato ad OACa. Verranno presentati i recenti sviluppi sul ricevitore, inclusi i risultati preliminari della misura della temperatura di rumore, che raggiunge un valore pari a Trec=66 K alla frequenza di 86 GHz, nonostante la criogenia non sia ancora ottimizzata. L'INAF-OACa è coinvolto nel progetto AETHRA (Advanced European Technologies for Heterodyne Receivers for Astronomy) nel quadro del programma Radionet/Horizon2020 per il quale sta contribuendo al WP1 (Work Package 1). Lo scopo del WP1 è di sviluppare e costruire un dimostratore di un array di ricevitori a doppia polarizzazione per la banda 3 mm basato su amplificatori criogenici a basso rumore (LNA) in tecnologia a semiconduttore MMIC. Nell'ambito del WP1 l'OACa ha in carico il progetto di un OrthomodeTransducer (OMT) in guida d'onda o in tecnologia planare per la banda 72-116 GHz che sia integrabile con amplificatori MMICs ed adatto all'integrazione in un array da installare nel piano focale di un radiotelescopio. Verranno presentati i design preliminari degli OMT per AETHRA, che sono basati su prototipi sviluppati in passato da OACa.

  13. Nicholas DiOrio | NREL

    Science.gov Websites

    Engineering Intern, NREL, Golden, CO, 2013 Featured Publications N. DiOrio, A. Dobos, S. Janzou, A. Nelson and Renewable Energy Laboratory, Golden, CO. N. DiOrio, A. Dobos and S. Janzou. 2015. "Economic Analysis . C. Christensen, J. Maguire, J. Burch, N. DiOrio. "Simplified Solar Water Heater Simulation

  14. [Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

    PubMed

    Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

  15. Trasforiiazioni Termoelastiche Finite di Solidi Incomprimibili

    NASA Astrophysics Data System (ADS)

    Signorini, A.

    Queste lezlioni hanno come direttiva una sintesi di quanto si trova sistematicamente sviluppato in una mia Memoria sulle trasformazioni termoelastiche finite di solidi incomprimibili, in corso di stampa negli Annali di Matematica pura e applicata t. XXXIX ( 1955) pp. 147-201 , Verranno anche esposti, come necessaria premessa, alcuni d ei risultati di due precedenti Memorie degli stessi Annali. Invece, per motivo di brevità, non potrò dare neppure un cenno delle ulteriori ricerche svilup pate dal prof. T. Manacorda in tre recentissimi suoi lavori:

  16. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    PubMed

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and

  17. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense

    PubMed Central

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark

    2017-01-01

    ABSTRACT Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense, c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and

  18. [La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

    PubMed

    Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

  19. Crystal structures of isomeric 3,5-di-chloro-N-(2,3-di-methyl-phen-yl)benzene-sulfonamide, 3,5-di-chloro-N-(2,6-di-methyl-phen-yl)benzene-sulfonamide and 3,5-di-chloro-N-(3,5-di-methyl-phen-yl)benzene-sulfonamide.

    PubMed

    Shakuntala, K; Naveen, S; Lokanath, N K; Suchetan, P A

    2017-05-01

    The crystal structures of three isomeric compounds of formula C 14 H 13 Cl 2 NO 2 S, namely 3,5-di-chloro- N -(2,3-di-methyl-phen-yl)-benzene-sulfonamide (I), 3,5-di-chloro- N -(2,6-di-methyl-phen-yl)benzene-sulfonamide (II) and 3,5-di-chloro- N -(3,5-di-methyl-phen-yl)benzene-sulfonamide (III) are described. The mol-ecules of all the three compounds are U-shaped with the two aromatic rings inclined at 41.3 (6)° in (I), 42.1 (2)° in (II) and 54.4 (3)° in (III). The mol-ecular conformation of (II) is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. The crystal structure of (I) features N-H⋯O hydrogen-bonded R 2 2 (8) loops inter-connected via C (7) chains of C-H⋯O inter-actions, forming a three-dimensional architecture. The structure also features π-π inter-actions [ Cg ⋯ Cg = 3.6970 (14) Å]. In (II), N-H⋯O hydrogen-bonded R 2 2 (8) loops are inter-connected via π-π inter-actions [inter-centroid distance = 3.606 (3) Å] to form a one-dimensional architecture running parallel to the a axis. In (III), adjacent C (4) chains of N-H⋯O hydrogen-bonded mol-ecules running parallel to [010] are connected via C-H⋯π inter-actions, forming sheets parallel to the ab plane. Neighbouring sheets are linked via offset π-π inter-actions [inter-centroid distance = 3.8303 (16) Å] to form a three-dimensional architecture.

  20. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

  1. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

  2. 40 CFR 721.10325 - Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...

  3. [La combinazione di gemcitabina e oxaliplatino (GEMOX) nel trattamento del carcinoma pancreatico in fase avanzata di malattia: le notizie sulla mia morte sono state esagerate?

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2017-12-01

    Riassunto. L'analisi è stata condotta al fine di valutare l'effetto sia sulla sopravvivenza globale (OS) sia sulla sopravvivenza libera da progressione di malattia (PFS) della chemioterapia di combinazione in prima linea per il carcinoma pancreatico in fase avanzata di malattia. La presente analisi è limitata agli studi randomizzati controllati (RCT) di fase III. Successivamente è stata applicata la European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) agli RCT di fase III analizzati per ricavare uno score relativo all'entità del beneficio clinico ottenuto per ciascun RCT. Sono state calcolate inoltre le differenze in termini di PFS tra i diversi bracci di trattamento rapportandole con i costi dei farmaci necessari per ottenere il beneficio di PFS. La nostra analisi ha valutato 11 RCT di fase III, per un totale di 4572 pazienti. Combinando i costi della terapia con la misura dell'efficacia espressa dalla PFS, è stato ottenuto un costo di 74,12 euro (€) per mese di vita guadagnato in termini di PFS con la combinazione di 5-fluorouracil, leucovorin, irinotecan e oxaliplatino (FOLFIRINOX), 90,14 € per la combinazione di gemcitabina e oxaliplatino (GEMOX) e 4708,7 € per la combinazione di nab-paclitaxel e gemcitabina. Da questo punto di vista riteniamo che l'utilizzo delle "vecche chemioterapie di combinazione" (per es., GEMOX) non dovrebbe essere completamente abbandonato, ma valutato sul singolo paziente, sulla base di diversi fattori (età, ECOG PS, comorbilità, carico di malattia), al fine di ottenere una reale "tailored therapy".

  4. Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms

    PubMed Central

    2015-01-01

    ABSTRACT Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms. PMID:26055114

  5. Di(hydroxyphenyl)- benzimidazole monomers

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

    1993-01-01

    Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

  6. Meningococco B: controllo di due focolai epidemici mediante vaccinazione

    PubMed Central

    2014-01-01

    Riassunto La problematica di un efficace approccio vaccinale nei confronti del Meningococco B (MenB) è stata superata identificando con la metodica della "reverse vaccinology" alcuni antigeni capaci di indurre una risposta verso la maggior parte dei ceppi di MenB circolanti nel mondo. Il nuovo vaccino MenB a 4 componenti (4CMenB) è stato autorizzato in Europa, Australia e Canada, ed è entrato nei calendari di immunizzazione pediatrica internazionali: Australia, Canada, UK. In Italia, le prime regioni che hanno raccomandato la vaccinazione contro il MenB sono state Basilicata e Puglia. La gestione di epidemie/focolai epidemici richiede la messa in atto di una risposta rapida da parte delle autorità sanitarie nei confronti di una emergenza sanitaria ad elevato impatto, anche emotivo, sulla popolazione, come recentemente dimostrato in due università americane. Alla dichiarazione di focolaio epidemico in atto, in entrambi i contesti si è attivata una procedura per l'uso del vaccino 4CMenB non ancora autorizzato negli USA. È stato così possibile organizzare gli interventi di profilassi attiva nei due campus universitari, adottando il primo impiego su larga scala del nuovo vaccino 4CMenB e conseguendo, in tempi relativamente brevi, elevati tassi di copertura vaccinale. A fronte di circa 14000 studenti immunizzati con almeno una dose, non è stata segnalata alcuna problematica di eventi avversi conseguenti all'immunizzazione; ad oggi non si sono verificati casi nei soggetti che hanno ricevuto il vaccino. Come conseguenza dei due focolai descritti, è oggi in corso la valutazione da parte dell'FDA per l'estensione dell'uso del vaccino 4CMenB negli Stati Uniti negli adolescenti e giovani adulti. PMID:25916017

  7. URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS

    EPA Science Inventory

    Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...

  8. DI: An interactive debugging interpreter for applicative languages

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Skedzielewski, S.K.; Yates, R.K.; Oldehoeft, R.R.

    1987-03-12

    The DI interpreter is both a debugger and interpreter of SISLAL programs. Its use as a program interpreter is only a small part of its role; it is designed to be a tool for studying compilation techniques for applicative languages. DI interprets dataflow graphs expressed in the IF1 and IF2 languages, and is heavily instrumented to report the activity of dynamic storage activity, reference counting, copying and updating of structured data values. It also aids the SISAL language evaluation by providing an interim execution vehicle for SISAL programs. DI provides determinate, sequential interpretation of graph nodes for sequential and parallelmore » operations in a canonical order. As a debugging aid, DI allows tracing, breakpointing, and interactive display of program data values. DI handles creation of SISAL and IF1 error values for each data type and propagates them according to a well-defined algebra. We have begun to implement IF1 optimizers and have measured the improvements with DI.« less

  9. Enzymatic Production of c-di-GMP Using a Thermophilic Diguanylate Cyclase.

    PubMed

    Venkataramani, Prabhadevi; Liang, Zhao-Xun

    2017-01-01

    C-di-GMP has emerged as a prevalent bacterial messenger that controls a multitude of bacterial behaviors. Having access to milligram or gram quantities of c-di-GMP is essential for the biochemical and structural characterization of enzymes and effectors involved in c-di-GMP signaling. Although c-di-GMP can be synthesized using chemical methods, diguanylate cyclases (DGC)-based enzymatic synthesis is the most efficient method of preparing c-di-GMP today. Many DGCs are not suitable for c-di-GMP production because of poor protein stability and the presence of a c-di-GMP-binding inhibitory site (I-site) in most DGCs. We have identified and engineered a thermophilic DGC for efficient production of c-di-GMP for characterizing c-di-GMP signaling proteins and riboswitches. Importantly, residue replacement in the inhibitory I-site of the thermophilic DGC drastically relieved product inhibition to enable the production of hundreds of milligrams of c-di-GMP using 5-10 mg of this robust biocatalyst.

  10. DiGeorge syndrome and unilateral symbrachydactyly.

    PubMed

    Devriendt, K; De Smet, L; De Boeck, K; Fryns, J P

    1997-01-01

    We describe a child with DiGeorge syndrome due to a del22(q11) and a symbrachydactyly of the left hand. The underlying cardiovascular malformations in DiGeorge syndrome may lead to an increased susceptibility to vascular disruptions, giving further support to the subclavian-artery-disruption-sequence theory.

  11. Di-codon Usage for Gene Classification

    NASA Astrophysics Data System (ADS)

    Nguyen, Minh N.; Ma, Jianmin; Fogel, Gary B.; Rajapakse, Jagath C.

    Classification of genes into biologically related groups facilitates inference of their functions. Codon usage bias has been described previously as a potential feature for gene classification. In this paper, we demonstrate that di-codon usage can further improve classification of genes. By using both codon and di-codon features, we achieve near perfect accuracies for the classification of HLA molecules into major classes and sub-classes. The method is illustrated on 1,841 HLA sequences which are classified into two major classes, HLA-I and HLA-II. Major classes are further classified into sub-groups. A binary SVM using di-codon usage patterns achieved 99.95% accuracy in the classification of HLA genes into major HLA classes; and multi-class SVM achieved accuracy rates of 99.82% and 99.03% for sub-class classification of HLA-I and HLA-II genes, respectively. Furthermore, by combining codon and di-codon usages, the prediction accuracies reached 100%, 99.82%, and 99.84% for HLA major class classification, and for sub-class classification of HLA-I and HLA-II genes, respectively.

  12. Di-hadron production at Jefferson Lab

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anefalos Pereira, Sergio; et. al.,

    Semi-inclusive deep inelastic scattering (SIDIS) has been used extensively in recent years as an important testing ground for QCD. Studies so far have concentrated on better determination of parton distribution functions, distinguishing between the quark and antiquark contributions, and understanding the fragmentation of quarks into hadrons. Hadron pair (di-hadron) SIDIS provides information on the nucleon structure and hadronization dynamics that complement single hadron SIDIS. Di-hadrons allow the study of low- and high-twist distribution functions and Dihadron Fragmentation Functions (DiFF). Together with the twist-2 PDFs ( f1, g1, h1), the Higher Twist (HT) e and hL functions are very interesting becausemore » they offer insights into the physics of the largely unexplored quark-gluon correlations, which provide access into the dynamics inside hadrons. The CLAS spectrometer, installed in Hall-B at Jefferson Lab, has collected data using the CEBAF 6 GeV longitudinally polarized electron beam on longitudinally polarized solid NH3 targets. Preliminary results on di-hadron beam-, target- and double-spin asymmetries will be presented.« less

  13. [Trattamento della dipendenza da alcol. Alcol e giovani: punto di vista sociale].

    PubMed

    Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Lombardo, Giuseppe; De Rosa, Francesca; Messina, Marisa Patrizia; Vitali, Mario; Pisciotta, Fabiola; Nanut, Miriana; Attilia, Maria Luisa; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. Gli adolescenti rappresentano la fascia di età più vulnerabile ai danni causati dall'abuso di alcol, in quanto iniziare a bere in giovane età è associato a un aumento del rischio di dipendenza da alcolici in età adulta. I giovani tendono a bere grandi quantità di alcolici al fine di ricercare forti emozioni e nel tentativo di raggiungere il divertimento a ogni costo, tramite le proprietà psicotrope degli alcolici. Le cause che li inducono ad assumere questi comportamenti sono da ricercare nella non conoscenza degli effetti dannosi dell'alcol, nel rito di convivialità sociale (evenienza per la quale si attribuisce all'alcol la funzione di facilitatore dell'aggregazione tra giovani), nella mancanza di interessi personali, nella scarsità dei controlli e nelle abitudini familiari. Le azioni da intraprendere per limitare o arrestare il consumo nocivo di alcol nei giovani si devono basare su interventi finalizzati a ritardare l'età del primo contatto con le bevande alcoliche, mediante la realizzazione di campagne educazionali rivolte ai giovani stessi, ai loro familiari e alla società intera.

  14. Structural Basis of Ligand Binding by a C-di-GMP Riboswitch

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, K.; Lipchock, S; Ames, T

    2009-01-01

    The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structuralmore » data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.« less

  15. An experiment of formation of charmoni states in annihilation P-Pbarra. Un esperimento di formazione di stati del charmonio in annichilazione P-Pbarra (in Italian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pallavicini, Marco

    1995-01-01

    Oggetto di questa tesi e la misura di alcune caratteristiche fisiche (massa, larghezza, e larghezza parziale in p -more » $$\\bar{p}$$) degli stati 3P 1 e 3P 2 del charmonio, -ovvero del sistema legato di un quark "charm" e del suo antiquark-, nell'amito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab.« less

  16. Misura della sezione d'urto totale e Dello scattering elastico all'energia Nel centro di massa di $$\\sqrt{s}=1.8$$ TeV (in Italian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paoletti, Riccardo

    La produzione di eventi elastici è stata misurata al Collider Tevatron del Fermi National Accelerator Laboratory (Batavia. 11.~ U .S.A.) alla energia nel centro di massa. di √s = 1800 GeV, nell'intervallo 0.06 < I t I< 0.24. Sono forniti dettagli sull'esperimento CDF che ha compiuto la misura e sui criteri di selezione degli eventi.

  17. Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.

    PubMed

    Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M

    2013-05-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis.

  18. Cyclic Di-GMP Modulates the Disease Progression of Erwinia amylovora

    PubMed Central

    Edmunds, Adam C.; Castiblanco, Luisa F.; Sundin, George W.

    2013-01-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis. PMID:23475975

  19. Enhanced healing of full-thickness burn wounds using di-rhamnolipid

    PubMed Central

    Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

    2006-01-01

    The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213

  20. 40 CFR 721.10261 - Oxime, di-Me silane (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

  1. 40 CFR 721.10261 - Oxime, di-Me silane (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...

  2. [Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].

    PubMed

    Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro

    2018-01-01

    RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.

  3. RATE CONSTANTS FOR THE REACTIONS OF OH RADICALS AND CL ATOMS WITH DI-N-PROPYL ETHER AND DI-N-BUTYL ETHER AND THEIR DEUTERATED ANALOGS. (R825252)

    EPA Science Inventory

    Using relative rate methods, rate constants for the gas-phase reactions of OH radicals and Cl atoms with di-n-propyl ether, di-n-propyl ether-d14, di-n-butyl ether and di-n-butyl ether-d18 have been measured at 296 ? 2 K and atmos...

  4. Conditional transgenesis using Dimerizable Cre (DiCre).

    PubMed

    Jullien, Nicolas; Goddard, Isabelle; Selmi-Ruby, Samia; Fina, Jean-Luc; Cremer, Harold; Herman, Jean-Paul

    2007-12-26

    Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin associated protein), respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activity, and presents a low background activity together with a high efficiency of recombination following dimerization. To test the in vivo performance of this system, we have, in the present work, knocked-in DiCre into the Rosa26 locus of mice. To evaluate the performance of the DiCre system, mice have been mated with indicator mice (Z/EG or R26R) and Cre-induced recombination was examined following activation of DiCre by rapamycin during embryonic development or after birth of progenies. No recombination could be observed in the absence of treatment of the animals, indicating a lack of background activity of DiCre in the absence of rapamycin. Postnatal rapamycin treatment (one to five daily injection, 10 mg/kg i.p) induced recombination in a number of different tissues of progenies such as liver, heart, kidney, muscle, etc. On the other hand, recombination was at a very low level following in utero treatment of DiCrexR26R mice. In conclusion, DiCre has indeed the potentiality to be used to establish conditional Cre-deleter mice. An added advantage of this system is that, contrary to other modulatable Cre systems, it offers the possibility of obtaining regulated recombination in a combinatorial manner, i.e. induce recombination at

  5. Riboswitches in eubacteria sense the second messenger c-di-AMP

    PubMed Central

    Nelson, James W.; Sudarsan, Narasimhan; Furukawa, Kazuhiro; Weinberg, Zasha; Wang, Joy X.; Breaker, Ronald R.

    2013-01-01

    Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial second messenger implicated in the control of cell wall metabolism, osmotic stress responses, and sporulation. However, the mechanisms by which c-di-AMP triggers these physiological responses have remained largely unknown. Intriguingly, a candidate riboswitch class called ydaO associates with numerous genes involved in these same processes. Although a representative ydaO motif RNA recently was reported to weakly bind ATP, we report that numerous members of this noncoding RNA class selectively respond to c-di-AMP with sub-nanomolar affinity. Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP. PMID:24141192

  6. From Civil Protection Plan to Disaster Management. PETer evolution from GIS tool to multi-area Emergency Management System

    NASA Astrophysics Data System (ADS)

    Frigerio, Simone; Sterlacchini, Simone; Malet, Jean-Philippe; Glade, Thomas

    2010-05-01

    information was managed at different levels, linking all people in decision-making roles: crews in the field, the mobile command post and the control room. The tool automatically performs organizational and operational activities within a Civil Protection plan, in line with enforceable regulations. It couples: data processing capabilities by GIS; workflow management modules by DSS and communication systems by the ICT. More specifically, the work presents the overall concept and the system architecture of a generic decision-support system in progress of development, displaying the aims of emergency management and then shows a DSS first of all for Civil Protection Plan within Disaster Preparedness and Response framework in a Consortium of Mountain Municipalities (Valtellina di Tirano, Central Alps, Northern Italy). A multi-area approach (involving the management of disaster scenarios at the La Valette landslide in the Barcelonnette Basin, South French Alps) has been introduced to calibrate the platform, to compare available dataset, information details, laws in force in different countries, stakeholders' responsibility and end-users' background. Work in progress involves multi-task tools useful in emergency situation, to enforce open-communication devices (SMS automatic platform, SKYPE interface, visual video), integrate existing monitoring system and web-service to tailor open-sharing information with emergency management demand.

  7. Cyclic di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions.

    PubMed

    Zeden, Merve S; Schuster, Christopher F; Bowman, Lisa; Zhong, Qiyun; Williams, Huw D; Gründling, Angelika

    2018-03-02

    Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such as Staphylococcus aureus However, the exact role of this molecule has not been identified. dacA , the S. aureus gene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that an S. aureus dacA mutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality of dacA were identified in alsT and opuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in S. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained in hepS, hemB, ctaA, and qoxB, coding proteins required for respiration. Furthermore, we show that dacA is dispensable for growth in anaerobic conditions. Together, these findings reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration in S. aureus . © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Severe dystrophy in DiGeorge syndrome

    PubMed Central

    Rózsai, Barnabás; Kiss, Ákos; Csábi, Györgyi; Czakó, Márta; Decsi, Tamás

    2009-01-01

    We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow’s milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome. PMID:19294771

  9. Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein–protein interaction

    PubMed Central

    Steiner, Samuel; Lori, Christian; Boehm, Alex; Jenal, Urs

    2013-01-01

    In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein–protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria. PMID:23202856

  10. The oxidation of 2,6-di-tert-butyl-4-methylphenol

    USGS Publications Warehouse

    Yohe, G.R.; Dunbar, J.E.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.

    1956-01-01

    The products formed in the oxidation of 2,6-di-tert-butyl-4-methylphenol with oxygen and sodium hydroxide at about 100?? are 3,5-di-tert-butyl-4-hydroxybenzaldehyde, trimethylacetic acid, an acidic compound C14H22O3, and probably 2,6-di-tert-butylbenzoquinone (which was actually isolated in the similar oxidation of the above-named benzaldehyde), in addition to compounds previously reported. Some of the properties of C14H22O3 are given, and the oxidation of it to 2,3-di-tert-butylsuccinic anhydride is described, but assignment of structure is reserved pending the completion of more experimental work.

  11. Limb anomalies in DiGeorge and CHARGE syndromes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prasad, C.; Quackenbush, E.J.; Whiteman, D.

    1997-01-20

    Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with CHARGE syndrome. Our first patient had a bifid left thumb, Tetralogy of Fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with CHARGE syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies. 14 refs., 4 figs.

  12. Di-n-butyl Phthalate (DNBP) and Diisobutyl Phthalate (DiBP) Metabolism in a Human Volunteer after Single Oral Doses [Journal Article

    EPA Science Inventory

    An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...

  13. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

  14. 40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...

  15. Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome.

    PubMed

    Shefi, Shai; Raviv, Gil; Rienstein, Shlomit; Barkai, Gad; Aviram-Goldring, Ayala; Levron, Jacob

    2009-07-01

    To report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome. Case report. Academic referral center. A 32 year-old female affected by DiGeorge syndrome. History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization. Avoidance of pregnancy with embryo affected by DiGeorge syndrome. Termination of pregnancy with an affected embryo followed by fluorescence in-situ hybridization based preimplantation genetic diagnosis and delivery of healthy offspring. The combination of preimplantation genetic diagnosis with fluorescence in-situ hybridization is recommended to prevent pregnancies with DiGeorge syndrome affected embryos in properly selected patients.

  16. Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

    PubMed Central

    Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.

    2013-01-01

    ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760

  17. Interdisciplinary investigations in support of project DI-MOD

    NASA Technical Reports Server (NTRS)

    Starks, Scott A.

    1991-01-01

    Interdisciplinary investigations in support of project DI-MOD are discussed. The following subject areas were covered: (1) potential extensions of Project DI-MOD to additional sites in Central America; (2) human migration patterns and their impact on malaria transmission; and (3) an investigation into possible computer-based approaches to the analysis of remotely sensed multispectral data.

  18. Di-hadron production at Jefferson Laboratory

    NASA Astrophysics Data System (ADS)

    Anefalos Pereira, Sergio; CLAS Collaboration

    2015-04-01

    Semi-inclusive deep inelastic scattering (SIDIS) has been used extensively in recent years as an important testing ground for QCD. Studies so far have concentrated on better determination of parton distribution functions, distinguishing between the quark and antiquark contributions, and understanding the fragmentation of quarks into hadrons. Pair of hadrons (di-hadron) SIDIS provides information on the nucleon structure and hadronization dynamics that complements single-hadron SIDIS. The study of di-hadrons allow us to study higher twist distribution functions and Dihadron Fragmentation Functions (DiFF). Together with the twist-2 PDFs (f 1, g 1, h 1), the Higher Twist (HT) e and hL functions are very interesting because they offer insights into the physics of the largely unexplored quark-gluon correlations which provide direct and unique insights into the dynamics inside hadrons. The CLAS spectrometer, installed in Hall-B at Jefferson Lab, has collected data using the CEBAF 6 GeV longitudinally polarized electron beam on longitudinally polarized solid NH3 targets. Preliminary results on beam-, target- and double-spin asymmetries will be presented.

  19. Upper limb malformations in DiGeorge syndrome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cormier-Daire, V.; Iserin, L.; Sidi, D.

    1995-03-13

    We report on upper limb anomalies in two children with a complete DiGeorge sequence: conotruncal defects, hypocalcemia, thymic aplasia, and facial anomalies. One child had preaxial polydactyly, and the other had club hands with hypoplastic first metacarpal. In both patients, molecular analysis documented a 22q11 deletion. To our knowledge, limb anomalies have rarely been reported in DiGeorge syndrome, and they illustrate the variable clinical expression of chromosome 22q11 deletions. 13 refs., 2 figs.

  20. Di(2-ethylhexyl)adipate

    Integrated Risk Information System (IRIS)

    Di ( 2 - ethylhexyl ) adipate ; CASRN 103 - 23 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Non

  1. Molecular studies on di-sodium tartrate molecule

    NASA Astrophysics Data System (ADS)

    Divya, P.; Jayakumar, S.; George, Preethamary; Shubashree, N. S.; Ahmed. M, Anees

    2015-06-01

    Structural characterization is important for the development of new material. The acoustical parameters such as Free Length, Internal Pressure have been measured from ultrasonic velocity, density for di sodium tartrate an optically active molecule at different temperatures using ultrasonic interferometer of frequency (2MHZ). The ultrasonic velocity increases with increase in concentration there is an increase in solute-solvent interaction. The stability constant had been calculated. SEM with EDAX studies has been done for Di-sodium tartrate an optically active molecule.

  2. Di(hydroxyphenyl)- 1,2,4-triazole monomers

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

    1993-01-01

    The di(hydroxyphenyl)- 1,2,4-triazole monomers were first synthesized by reacting bis (4-hydroxyphenyl) hydrazide with aniline hydrochloride at 250 C in the melt and also by reacting 1,3 or 1,4-bis- (4-hydroxyphenyl)- phenylene- dihydrazide with 2 moles of aniline hydrochloride in the melt. Purification of the di(hydroxyphenyl)- 1,2,4-triazole monomers was accomplished by recrystallization. Poly (1,2,4-triazoles) (PT) were prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)- 1,2,4-triazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions were carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. This synthetic route has provided high molecular weight PT of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides.

  3. DiOlistic Labeling of Neurons in Tissue Slices: A Qualitative and Quantitative Analysis of Methodological Variations.

    PubMed

    Staffend, Nancy A; Meisel, Robert L

    2011-01-01

    Fine neuronal morphology, such as dendritic spines, classically has been studied using the Golgi technique; however, Golgi staining is difficult to combine with other histological techniques. With the increasing popularity of fluorescent imaging, a number of fluorescent dyes have been developed that enable the coupling of multiple fluorescent labels in a single preparation. These fluorescent dyes include the lipophilic dialkylcarbocyanine, DiI; traditionally used for anterograde and retrograde neuronal tracing. More recently, DiI labeling has been used in combination with the Gene Gun for "DiOlistic" labeling of neurons in slice preparations. DiI sequesters itself within and diffuses laterally along the neuronal membrane, however once the cell is permeabilized, the DiI begins to leak from the cell membrane. A DiI derivative, Cell Tracker™ CM-DiI, increases dye stability and labeling half-life in permeabilized tissue, however at much greater expense. Here, the DiI and CM-DiI DiOlistic labeling techniques were tested in side-by-side experiments evaluating dye stability within dendritic architecture in medium spiny neurons of the dorsal stratum in both non-permeabilized and permeabilized tissue sections. In tissue sections that were not permeabilized, spine density in DiI labeled sections was higher than in CM-DiI labeling. In contrast, tissue sections that were permeabilized had higher spine densities in CM-DiI labeled neurons. These results suggest that for experiments involving non-permeabilized tissue, traditional DiI will suffice, however for experiments involving permeabilized tissue CM-DiI provides more consistent data. These experiments provide the first quantitative analyses of the impact of methodological permutations on neuronal labeling with DiI.

  4. URINARY AND AMNIOTIC FLUID LEVELS OF PHTHALATE MONOESTERS IN RATS AFTER THE ORAL ADMINISTRATION OF DI(2-ETHYLHEXYL) PHTHALATE AND DI-N-BUTYL PHTHALATE

    EPA Science Inventory

    Two studies were designed to examine amniotic fluid and maternal urine concentrations of the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethylhexyl) phthalate (MEHP) and the di-n-butyl phthalate (DBP) metabolite monobutyl phthalate (MBP) after administration of DEHP and D...

  5. c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

    PubMed Central

    Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

    2009-01-01

    Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

  6. Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis.

    PubMed

    Kalia, Dimpy; Merey, Gökçe; Nakayama, Shizuka; Zheng, Yue; Zhou, Jie; Luo, Yiling; Guo, Min; Roembke, Benjamin T; Sintim, Herman O

    2013-01-07

    For an organism to survive, it must be able to sense its environment and regulate physiological processes accordingly. Understanding how bacteria integrate signals from various environmental factors and quorum sensing autoinducers to regulate the metabolism of various nucleotide second messengers c-di-GMP, c-di-AMP, cGMP, cAMP and ppGpp, which control several key processes required for adaptation is key for efforts to develop agents to curb bacterial infections. In this review, we provide an update of nucleotide signaling in bacteria and show how these signals intersect or integrate to regulate the bacterial phenotype. The intracellular concentrations of nucleotide second messengers in bacteria are regulated by synthases and phosphodiesterases and a significant number of these metabolism enzymes had been biochemically characterized but it is only in the last few years that the effector proteins and RNA riboswitches, which regulate bacterial physiology upon binding to nucleotides, have been identified and characterized by biochemical and structural methods. C-di-GMP, in particular, has attracted immense interest because it is found in many bacteria and regulate both biofilm formation and virulence factors production. In this review, we discuss how the activities of various c-di-GMP effector proteins and riboswitches are modulated upon c-di-GMP binding. Using V. cholerae, E. coli and B. subtilis as models, we discuss how both environmental factors and quorum sensing autoinducers regulate the metabolism and/or processing of nucleotide second messengers. The chemical syntheses of the various nucleotide second messengers and the use of analogs thereof as antibiofilm or immune modulators are also discussed.

  7. Cyclic di-GMP-dependent Signaling Pathways in the Pathogenic Firmicute Listeria monocytogenes

    PubMed Central

    Chen, Li-Hong; Köseoğlu, Volkan K.; Güvener, Zehra T.; Myers-Morales, Tanya; Reed, Joseph M.; D'Orazio, Sarah E. F.; Miller, Kurt W.; Gomelsky, Mark

    2014-01-01

    We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase genes (ΔpdeB/C/D) or expression of a heterologous diguanylate cyclase stimulated production of a previously unknown exopolysaccharide. The synthesis of this exopolysaccharide was attributed to the pssA-E (lmo0527-0531) gene cluster. The last gene of the cluster encodes the fourth listerial GGDEF domain protein, PssE, that functions as an I-site c-di-GMP receptor essential for exopolysaccharide synthesis. The c-di-GMP-inducible exopolysaccharide causes cell aggregation in minimal medium and impairs bacterial migration in semi-solid agar, however, it does not promote biofilm formation on abiotic surfaces. The exopolysaccharide also greatly enhances bacterial tolerance to commonly used disinfectants as well as desiccation, which may contribute to survival of L. monocytogenes on contaminated food products and in food-processing facilities. The exopolysaccharide and another, as yet unknown c-di-GMP-dependent target, drastically decrease listerial invasiveness in enterocytes in vitro, and lower pathogen load in the liver and gallbladder of mice infected via an oral route, which suggests that elevated c-di-GMP levels play an overall negative role in listerial virulence. PMID:25101646

  8. Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose

    PubMed Central

    Zorraquino, Violeta; García, Begoña; Latasa, Cristina; Echeverz, Maite; Toledo-Arana, Alejandro; Valle, Jaione

    2013-01-01

    Cyclic di-GMP (c-di-GMP) is a secondary messenger that controls a variety of cellular processes, including the switch between a biofilm and a planktonic bacterial lifestyle. This nucleotide binds to cellular effectors in order to exert its regulatory functions. In Salmonella, two proteins, BcsA and YcgR, both of them containing a c-di-GMP binding PilZ domain, are the only known c-di-GMP receptors. BcsA, upon c-di-GMP binding, synthesizes cellulose, the main exopolysaccharide of the biofilm matrix. YcgR is dedicated to c-di-GMP-dependent inhibition of motility through its interaction with flagellar motor proteins. However, previous evidences indicate that in the absence of YcgR, there is still an additional element that mediates motility impairment under high c-di-GMP levels. Here we have uncovered that cellulose per se is the factor that further promotes inhibition of bacterial motility once high c-di-GMP contents drive the activation of a sessile lifestyle. Inactivation of different genes of the bcsABZC operon, mutation of the conserved residues in the RxxxR motif of the BcsA PilZ domain, or degradation of the cellulose produced by BcsA rescued the motility defect of ΔycgR strains in which high c-di-GMP levels were reached through the overexpression of diguanylate cyclases. High c-di-GMP levels provoked cellulose accumulation around cells that impeded flagellar rotation, probably by means of steric hindrance, without affecting flagellum gene expression, exportation, or assembly. Our results highlight the relevance of cellulose in Salmonella lifestyle switching as an architectural element that is both essential for biofilm development and required, in collaboration with YcgR, for complete motility inhibition. PMID:23161026

  9. Remote Sensing Global Surface Air Pressure Using Differential Absorption BArometric Radar (DiBAR)

    NASA Technical Reports Server (NTRS)

    Lin, Bing; Harrah, Steven; Lawrence, Wes; Hu, Yongxiang; Min, Qilong

    2016-01-01

    Tropical storms and severe weathers are listed as one of core events that need improved observations and predictions in World Meteorological Organization and NASA Decadal Survey (DS) documents and have major impacts on public safety and national security. This effort tries to observe surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at the 50-55 gigahertz O2 absorption band. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 4 millibars (approximately 1 millibar under all weather conditions). With these sea level pressure measurements, the forecasts of severe weathers such as hurricanes will be significantly improved. Since the development of the DiBAR concept about a decade ago, NASA Langley DiBAR research team has made substantial progress in advancing the concept. The feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. The team has developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.

  10. Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

    PubMed Central

    Galperin, Michael Y.; Gomelsky, Mark

    2013-01-01

    SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger. PMID:23471616

  11. Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway

    PubMed Central

    Russell, Matthew H.; Bible, Amber N.; Fang, Xin; Gooding, Jessica R.; Campagna, Shawn R.; Gomelsky, Mark; Alexandre, Gladys

    2013-01-01

    ABSTRACT Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors. PMID:23512960

  12. QM/MM structural and spectroscopic analysis of the di-iron(II) and di-iron(III) ferroxidase site in M ferritin.

    PubMed

    Harris, Travis V; Morokuma, Keiji

    2013-08-05

    Ferritins are cage-like proteins composed of 24 subunits that take up iron(II) and store it as an iron(III) oxide mineral core. A critical step is the ferroxidase reaction, in which oxygen reacts with a di-iron(II) site, proceeding through a peroxo intermediate, to form μ-oxo/hydroxo-bridged di-iron(III) products. The recent crystal structures of copper(II)- and iron(III)-bound frog M ferritin at 2.8 Å resolution [Bertini; et al. J. Am. Chem. Soc. 2012, 134, 6169-6176] provided an opportunity to theoretically investigate the detailed structures of the reactant state and products. In this study, the quantum mechanical/molecular mechanical ONIOM method is used to structurally optimize a series of single-subunit models with various hydration, protonation, and coordination states of the ferroxidase site. Calculated exchange coupling constants (J), Mössbauer parameters, and time-dependent density functional theoretical (TD-DFT) circular dichroism spectra with electronic embedding are compared with the available experimental data. The di-iron(II) model with the most experimentally consistent structural and spectroscopic parameters has 5-coordinate iron centers with Glu23, Glu58, His61, and two waters completing one coordination sphere, and His54, Glu58, Glu103, and Asp140 completing the other. In contrast to a previously proposed structure, Gln137 is not directly coordinated, but it is involved in hydrogen bonding with several iron ligands. For the di-iron(III) products, we find that a μ-oxo-bridged and two doubly bridged (μ-hydroxo and μ-oxo/hydroxo) species are likely coproduced. Although four quadrupole doublets were observed experimentally, we find that two doublets may arise from a single asymmetrically coordinated ferroxidase site. These proposed key structures will help to explore the pathway connecting the di-Fe(II) state to the peroxo intermediate and the branching mechanisms leading to the multiple products.

  13. Di-Adenosine Tetraphosphate (Ap4A) Metabolism Impacts Biofilm Formation by Pseudomonas fluorescens via Modulation of c-di-GMP-Dependent Pathways▿

    PubMed Central

    Monds, Russell D.; Newell, Peter D.; Wagner, Jeffrey C.; Schwartzman, Julia A.; Lu, Wenyun; Rabinowitz, Joshua D.; O'Toole, George A.

    2010-01-01

    Dinucleoside tetraphosphates are common constituents of the cell and are thought to play diverse biological roles in organisms ranging from bacteria to humans. In this study we characterized two independent mechanisms by which di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens. Null mutations in apaH, the gene encoding nucleoside tetraphosphate hydrolase, resulted in a marked increase in the cellular level of Ap4A. Concomitant with this increase, Pho regulon activation in low-inorganic-phosphate (Pi) conditions was severely compromised. As a consequence, an apaH mutant was not sensitive to Pho regulon-dependent inhibition of biofilm formation. In addition, we characterized a Pho-independent role for Ap4A metabolism in regulation of biofilm formation. In Pi-replete conditions Ap4A metabolism was found to impact expression and localization of LapA, the major adhesin regulating surface commitment by P. fluorescens. Increases in the level of c-di-GMP in the apaH mutant provided a likely explanation for increased localization of LapA to the outer membrane in response to elevated Ap4A concentrations. Increased levels of c-di-GMP in the apaH mutant were associated with increases in the level of GTP, suggesting that elevated levels of Ap4A may promote de novo purine biosynthesis. In support of this suggestion, supplementation with adenine could partially suppress the biofilm and c-di-GMP phenotypes of the apaH mutant. We hypothesize that changes in the substrate (GTP) concentration mediated by altered flux through nucleotide biosynthetic pathways may be a significant point of regulation for c-di-GMP biosynthesis and regulation of biofilm formation. PMID:20154123

  14. Di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens via modulation of c-di-GMP-dependent pathways.

    PubMed

    Monds, Russell D; Newell, Peter D; Wagner, Jeffrey C; Schwartzman, Julia A; Lu, Wenyun; Rabinowitz, Joshua D; O'Toole, George A

    2010-06-01

    Dinucleoside tetraphosphates are common constituents of the cell and are thought to play diverse biological roles in organisms ranging from bacteria to humans. In this study we characterized two independent mechanisms by which di-adenosine tetraphosphate (Ap4A) metabolism impacts biofilm formation by Pseudomonas fluorescens. Null mutations in apaH, the gene encoding nucleoside tetraphosphate hydrolase, resulted in a marked increase in the cellular level of Ap4A. Concomitant with this increase, Pho regulon activation in low-inorganic-phosphate (P(i)) conditions was severely compromised. As a consequence, an apaH mutant was not sensitive to Pho regulon-dependent inhibition of biofilm formation. In addition, we characterized a Pho-independent role for Ap4A metabolism in regulation of biofilm formation. In P(i)-replete conditions Ap4A metabolism was found to impact expression and localization of LapA, the major adhesin regulating surface commitment by P. fluorescens. Increases in the level of c-di-GMP in the apaH mutant provided a likely explanation for increased localization of LapA to the outer membrane in response to elevated Ap4A concentrations. Increased levels of c-di-GMP in the apaH mutant were associated with increases in the level of GTP, suggesting that elevated levels of Ap4A may promote de novo purine biosynthesis. In support of this suggestion, supplementation with adenine could partially suppress the biofilm and c-di-GMP phenotypes of the apaH mutant. We hypothesize that changes in the substrate (GTP) concentration mediated by altered flux through nucleotide biosynthetic pathways may be a significant point of regulation for c-di-GMP biosynthesis and regulation of biofilm formation.

  15. A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer immunotherapy.

    PubMed

    Miyabe, Hiroko; Hyodo, Mamoru; Nakamura, Takashi; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi

    2014-06-28

    Cyclic dinucleotides are of importance in the field of microbiology and immunology. They function as second messengers and are thought to participate in the signal transduction of cytosolic DNA immune responses. One such dinucleotide, cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons. Therefore c-di-GMP can be thought of as a new class of adjuvant. However, because c-di-GMP contains two phosphate groups, this prevents its use as an adjuvant because it cannot pass through the cell membrane, even though the target molecule of c-di-GMP is located in the cytoplasm. Our group has been developing a series of liposomal drug delivery systems and recently investigated YSK05 which is a synthetic, pH sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN-β in Raw264.7 cells. The induction of IFN-β from c-di-GMP liposomes was inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of IFN-β caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I. The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell activity and the inhibition of tumor growth in a mouse model. These findings indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di-GMP to the cytosol and induce an innate immune system but also as a platform for investigating the mechanism of immune sensing with cyclic dinucleotides in vitro and in vivo. Copyright

  16. High-Performance Liquid Chromatography (HPLC)-Based Detection and Quantitation of Cellular c-di-GMP.

    PubMed

    Petrova, Olga E; Sauer, Karin

    2017-01-01

    The modulation of c-di-GMP levels plays a vital role in the regulation of various processes in a wide array of bacterial species. Thus, investigation of c-di-GMP regulation requires reliable methods for the assessment of c-di-GMP levels and turnover. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis has become a commonly used approach to accomplish these goals. The following describes the extraction and HPLC-based detection and quantification of c-di-GMP from Pseudomonas aeruginosa samples, a procedure that is amenable to modifications for the analysis of c-di-GMP in other bacterial species.

  17. DiI Perfusion as a Method for Vascular Visualization in Ambystoma mexicanum.

    PubMed

    Saltman, Anna J; Barakat, May; Bryant, Donald M; Brodovskaya, Anastasia; Whited, Jessica L

    2017-06-16

    Perfusion techniques have been used for centuries to visualize the circulation of tissues. Axolotl (Ambystoma mexicanum) is a species of salamander that has emerged as an essential model for regeneration studies. Little is known about how revascularization occurs in the context of regeneration in these animals. Here we report a simple method for visualization of the vasculature in axolotl via perfusion of 1,1'-Dioctadecy-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). DiI is a lipophilic carbocyanine dye that inserts into the plasma membrane of endothelial cells instantaneously. Perfusion is done using a peristaltic pump such that DiI enters the circulation through the aorta. During perfusion, dye flows through the axolotl's blood vessels and incorporates into the lipid bilayer of vascular endothelial cells upon contact. The perfusion procedure takes approximately one hour for an eight-inch axolotl. Immediately after perfusion with DiI, the axolotl can be visualized with a confocal fluorescent microscope. The DiI emits light in the red-orange range when excited with a green fluorescent filter. This DiI perfusion procedure can be used to visualize the vascular structure of axolotls or to demonstrate patterns of revascularization in regenerating tissues.

  18. The "Bestie di Satana" murders.

    PubMed

    Birkhoff, Jutta; Candelli, Chiara; Zeroli, Stefania; La Tegola, Donatella; Carabellese, Felice

    2013-11-01

    In recent years, satanic groups have been responsible for various types and degrees of crimes. We report the case of a number of murders committed in Italy by a group of young people calling themselves the "Bestie di Satana". Forensic psychiatric assessment of the members of a satanic sect charged with the crime revealed that all the young people had a fragile, immature personality, a very low level of education and were socially disadvantaged. The trial of the members of the "Bestie di Satana" sect was concluded with the verdict of deliberate murder, and all the members were given long jail sentences. This report should lead us to explore social and cultural responses to juvenile satanism, statistically shown to be a relatively rare phenomenon but with a high criminal potential. © 2013 American Academy of Forensic Sciences.

  19. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

    PubMed Central

    Novak, Elizabeth A.; Sultan, Syed Z.; Motaleb, Md. A.

    2014-01-01

    In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease. PMID:24822172

  20. Structural Analysis of the GGDEF-EAL Domain-Containing c-di-GMP Receptor FimX

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Navarro, M.; De, N; Bae, N

    2009-01-01

    Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data andmore » crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.« less

  1. Combination of diOlistic labeling with retrograde tract tracing and immunohistochemistry.

    PubMed

    Neely, M Diana; Stanwood, Gregg D; Deutch, Ariel Y

    2009-11-15

    Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. DiOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has recently been introduced as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the restricted use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies.

  2. Combination of DiOlistic Labeling with Retrograde Tract Tracing and Immunohistochemistry

    PubMed Central

    Diana Neely, M.; Stanwood, Gregg D; Deutch, Ariel Y.

    2009-01-01

    Neuronal staining techniques have played a crucial role in the analysis of neuronal function. Several different staining techniques have been developed to allow morphological analyses of neurons. Recently diOlistic labeling, in which beads are coated with a lipophilic dye and then ballistically ejected onto brain tissue, has been developed as a useful and simple means to label neurons and glia in their entirety. Although diOlistic labeling provides detailed information on the morphology of neurons, combining this approach with other staining methods is a significant advance. We have developed protocols that result in high quality diOlistically- and retrogradely-labeled or diOlistically-immunohistochemically labeled neurons. These dual-label methods require modification of fixation parameters and the use of detergents for tissue permeabilization, and are readily applicable to a wide range of tracers and antibodies. PMID:19712695

  3. Di (2-ethylhexyl)phthalate (DEHP)

    Integrated Risk Information System (IRIS)

    Di ( 2 - ethylhexyl ) phthalate ( DEHP ) ; CASRN 117 - 81 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessme

  4. N-Nitroso-di-n-butylamine

    Integrated Risk Information System (IRIS)

    N - Nitroso - di - n - butylamine ; CASRN 924 - 16 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  5. Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

    PubMed

    Otero-Lobato, María José; Kaats-Richters, Veronica E M; Havenith, Remco W A; Jenneskens, Leonardus W; Seinen, Willem

    2004-11-14

    To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

  6. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    NASA Astrophysics Data System (ADS)

    Lu, Lu; Yu, Hua

    2018-05-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  7. DR2DI: a powerful computational tool for predicting novel drug-disease associations

    NASA Astrophysics Data System (ADS)

    Lu, Lu; Yu, Hua

    2018-04-01

    Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

  8. Propulsion Diagnostic Method Evaluation Strategy (ProDiMES) User's Guide

    NASA Technical Reports Server (NTRS)

    Simon, Donald L.

    2010-01-01

    This report is a User's Guide for the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES). ProDiMES is a standard benchmarking problem and a set of evaluation metrics to enable the comparison of candidate aircraft engine gas path diagnostic methods. This Matlab (The Mathworks, Inc.) based software tool enables users to independently develop and evaluate diagnostic methods. Additionally, a set of blind test case data is also distributed as part of the software. This will enable the side-by-side comparison of diagnostic approaches developed by multiple users. The Users Guide describes the various components of ProDiMES, and provides instructions for the installation and operation of the tool.

  9. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers

    PubMed Central

    Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2015-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

  10. [Trattamento della dipendenza da alcol. Alcol e persone senza fissa dimora: punto di vista sociale].

    PubMed

    Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Cereatti, Federica; Gencarelli, Simona; Messina, Marisa Patrizia; Vitali, Mario; De Rosa, Francesca; Ledda, Roberta; Mancini, Serena; Attilia, Maria Luisa

    2018-01-01

    RIASSUNTO. Il fenomeno delle persone senza fissa dimora sta assumendo in questi anni una rilevanza sociale devastante, con una prevalenza stimata in USA e in Europa compresa tra il 5,6% e il 13,9%. Queste persone hanno una scarsa qualità di vita, una limitata o assente vita sociale, sono spesso disoccupate o lavorano solo saltuariamente. Sono a rischio di problemi con la legge, sono spesso affette da dipendenza da droghe, da patologie psichiatriche e internistiche. L'alcol spesso non rappresenta la causa della loro condizione sociale, ma solo la conseguenza, contribuendo in questo modo al loro degrado bio-psico-sociale. Nel 2009 lo US Department of Housing and Urban Development's Homelessness Assistance Programs e nel 2010 la European Consensus Conference on Homelessness hanno segnato un grande passo avanti nella riabilitazione sociale di queste persone, utilizzando il concetto del "case management". In particolare lo Standard Case Management si è dimostrato in grado di migliorare la stabilità abitativa, di ridurre l'uso di droghe e di rimuovere le barriere lavorative. L'Assertive Community Treatment si è dimostrato, invece, in grado di migliorare la stabilità abitativa e ha un rapporto costo/beneficio migliore per i pazienti affetti da doppia diagnosi.

  11. [Donatori di Musica: when oncology meets music].

    PubMed

    Graiff, Claudio

    2014-10-01

    Donatori di Musica is a network of musicians - both physicians and volunteers - that was initially founded in 2009 with the aim to set up and coordinate classical music concerts in hospitals. This activity was initially started and led by the Oncology Departments at Carrara and Bolzano Hospitals, where high profile professional musicians make themselves available for concerts in support of Oncological in/out-patients of that specific Hospital. A live classical music performance is a deeply touching experience - particularly for those who live a critical condition like cancer. Main characteristics of Donatori di Musica concerts are: continuity (concerts are part of a regular and non-stopping music season); quality (concerts are held by well-established professional musicians); philanthropic attitude (musicians do not wear a suit and usually chat with patients; they also select an easy-to-listen program; a convivial event is usually organized after the performance with the aim of overcoming distinctions and barriers between physician and patient); no profit: musicians perform for free - travel expenses and/or overnight staying only can be claimed; concerts have free access for patients, their families and hospital staff.Patients and musicians therefore do get in close contact and music is able to merge each other experiences - with patients being treated by the beauty of music and musicians being treated theirselves by patients daily-life feedback. The Donatori di Musica experience is therefore able to help Medicine to retrieve its very first significance - the medical act regain that human and cultural dimension that seems to be abandoned in the last decades in favour of a mere technicism. This is the spirit and the deep significance of Donatori di Musica - «[…] the hope that Music can become a key support to medical treatments in every Oncology department» (by Gian Andrea Lodovici).

  12. VS2DI: Model use, calibration, and validation

    USGS Publications Warehouse

    Healy, Richard W.; Essaid, Hedeff I.

    2012-01-01

    VS2DI is a software package for simulating water, solute, and heat transport through soils or other porous media under conditions of variable saturation. The package contains a graphical preprocessor for constructing simulations, a postprocessor for displaying simulation results, and numerical models that solve for flow and solute transport (VS2DT) and flow and heat transport (VS2DH). Flow is described by the Richards equation, and solute and heat transport are described by advection-dispersion equations; the finite-difference method is used to solve these equations. Problems can be simulated in one, two, or three (assuming radial symmetry) dimensions. This article provides an overview of calibration techniques that have been used with VS2DI; included is a detailed description of calibration procedures used in simulating the interaction between groundwater and a stream fed by drainage from agricultural fields in central Indiana. Brief descriptions of VS2DI and the various types of problems that have been addressed with the software package are also presented.

  13. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.

    PubMed

    Bowman, Lisa; Zeden, Merve S; Schuster, Christopher F; Kaever, Volkhard; Gründling, Angelika

    2016-12-30

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5'-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus*

    PubMed Central

    Bowman, Lisa; Zeden, Merve S.; Kaever, Volkhard

    2016-01-01

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5′-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. PMID:27834680

  15. Biomaterial based sulphur di oxide gas sensor

    NASA Astrophysics Data System (ADS)

    Ghosh, P. K.; Sarkar, A.

    2013-06-01

    Biomaterials are getting importance in the present research field of sensors. In this present paper performance of biomaterial based gas sensor made of gum Arabica and garlic extract had been studied. Extract of garlic clove with multiple medicinal and chemical utility can be proved to be useful in sensing Sulphur di Oxide gas. On exposure to Sulphur di Oxide gas the material under observation suffers some temporary structural change, which can be observed in form of amplified potentiometric change through simple electronic circuitry. Exploiting this very property a potentiometric gas sensor of faster response and recovery time can be designed. In this work sensing property of the said material has been studied through DC conductance, FTIR spectrum etc.

  16. Enhanced di-Higgs boson production in the complex Higgs singlet model

    DOE PAGES

    Dawson, S.; Sullivan, M.

    2018-01-31

    Here, we consider the standard model (SM) extended by the addition of a complex scalar singlet, with no assumptions about additional symmetries of the potential. This model provides for resonant di-Higgs production of Higgs particles with different masses. We demonstrate that regions of parameter space allowed by precision electroweak measurements, experimental limits on single Higgs production, and perturbative unitarity allow for large di-Higgs production rates relative to the SM rates. In this scenario, the dominant production mechanism of the new scalar states is di-Higgs production. Results are presented formore » $$\\sqrt{s}$$ = 13, 27 and 100 TeV.« less

  17. Enhanced di-Higgs boson production in the complex Higgs singlet model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dawson, S.; Sullivan, M.

    Here, we consider the standard model (SM) extended by the addition of a complex scalar singlet, with no assumptions about additional symmetries of the potential. This model provides for resonant di-Higgs production of Higgs particles with different masses. We demonstrate that regions of parameter space allowed by precision electroweak measurements, experimental limits on single Higgs production, and perturbative unitarity allow for large di-Higgs production rates relative to the SM rates. In this scenario, the dominant production mechanism of the new scalar states is di-Higgs production. Results are presented formore » $$\\sqrt{s}$$ = 13, 27 and 100 TeV.« less

  18. Chromosomal heterozygosity and fertility in house mice (Mus musculus domesticus) from Northern Italy.

    PubMed

    Hauffe, H C; Searle, J B

    1998-11-01

    Following the discovery of over 40 Robertsonian (Rb) races of Mus musculus domesticus in Europe and North Africa, the house mouse has been studied extensively as an ideal model to determine the chromosomal changes that may cause or accompany speciation. Current models of chromosomal speciation are based on the assumption that heterozygous individuals have a particularly low fertility, although recent studies indicate otherwise. Despite their importance, fertility estimates for the house mouse are incomplete because traditional measurements, such as anaphase I nondisjunction and germ cell death, are rarely estimated in conjunction with litter size. In an attempt to bridge this gap, we have taken advantage of the house mouse hybrid zone in Upper Valtellina (Lombardy, Italy) in which five Rb races interbreed. We present data on the fertility of naturally occurring ("wild-caught") hybrids and of offspring from laboratory crosses of wild-caught mice ("laboratory-reared"), using various measurements. Wild-caught mice heterozygous for one fusion were more infertile than predicted from past studies, possibly due to genic hybridity; laboratory-reared heterozygotes carrying seven or eight trivalents at meiosis I and heterozygotes carrying one pentavalent also had low fertilities. These low fertilities are especially significant given the probable occurrence of a reinforcement event in Upper Valtellina.

  19. Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, K.; Lipchock, S; Livingston,

    2010-01-01

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that themore » most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 {angstrom}) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3{prime}-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.« less

  20. A novel tank for DI water reduction in MEMS manufacturing

    NASA Astrophysics Data System (ADS)

    Raccurt, O.; Tardif, F.; Kerber, L.; Lardin, T.; Vareine, T.

    2003-05-01

    A new rinsing process is proposed based on the conclusions obtained by simulations. It consists of a combination of piston flows and internal top-to-bottom recycling steps, which decreases the DI water consumption (and associated cost) for the same rinsing efficiency. This novel concept re-using the DI water in situ in the rinsing tank is demonstrated using an industrial bath recently proposed on the market.

  1. Target Search & Selection for the DI/EPOXI Spacecraft

    NASA Technical Reports Server (NTRS)

    Grebow, Daniel J.; Bhaskaran, Shyam; Chesley, Steven R.

    2012-01-01

    Upon completion of the Hartley 2 flyby in November 2010, the Deep Impact (DI) spacecraft resided in a solar orbit without possibility for gravity assist with any large body. Conservative estimates of remaining fuel were enough to provide only an 18 m/s impulse on the spacecraft. We present our method and results of our systematic scan of potential small body encounters for DI, and our criteria to narrow the selection to the asteroid 2002 GT as the target flyby body. The mission profile has two deterministic maneuvers to achieve the encounter, the first of which executed on November 25, 2011.

  2. Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

    PubMed

    Miner, Kyle D; Kurtz, Donald M

    2016-02-16

    HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

  3. Constant DI pacing suppresses cardiac alternans formation in numerical cable models

    NASA Astrophysics Data System (ADS)

    Zlochiver, S.; Johnson, C.; Tolkacheva, E. G.

    2017-09-01

    Cardiac repolarization alternans describe the sequential alternation of the action potential duration (APD) and can develop during rapid pacing. In the ventricles, such alternans may rapidly turn into life risking arrhythmias under conditions of spatial heterogeneity. Thus, suppression of alternans by artificial pacing protocols, or alternans control, has been the subject of numerous theoretical, numerical, and experimental studies. Yet, previous attempts that were inspired by chaos control theories were successful only for a short spatial extent (<2 cm) from the pacing electrode. Previously, we demonstrated in a single cell model that pacing with a constant diastolic interval (DI) can suppress the formation of alternans at high rates of activation. We attributed this effect to the elimination of feedback between the pacing cycle length and the last APD, effectively preventing restitution-dependent alternans from developing. Here, we extend this idea into cable models to study the extent by which constant DI pacing can control alternans during wave propagation conditions. Constant DI pacing was applied to ventricular cable models of up to 5 cm, using human kinetics. Our results show that constant DI pacing significantly shifts the onset of both cardiac alternans and conduction blocks to higher pacing rates in comparison to pacing with constant cycle length. We also demonstrate that constant DI pacing reduces the propensity of spatially discordant alternans, a precursor of wavebreaks. We finally found that the protective effect of constant DI pacing is stronger for increased electrotonic coupling along the fiber in the sense that the onset of alternans is further shifted to higher activation rates. Overall, these results support the potential clinical applicability of such type of pacing in improving protocols of implanted pacemakers, in order to reduce the risk of life-threatening arrhythmias. Future research should be conducted in order to experimentally validate

  4. Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma.

    PubMed

    Nakamura, Takashi; Miyabe, Hiroko; Hyodo, Mamoru; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi

    2015-10-28

    Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC-I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated within YSK05-liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c-di-GMP/YSK05-Lip induces MHC-I non-restricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Hadfield holds bubble detectors for the RaDI-N Experiment in the Columbus Module

    NASA Image and Video Library

    2013-01-25

    ISS034-E-034506 (25 Jan. 2013) --- Canadian Space Agency astronaut Chris Hadfield, Expedition 34 flight engineer, holds bubble detectors for the RaDI-N experiment in the International Space Station?s Kibo laboratory. RaDI-N measures neutron radiation levels onboard the space station. RaDI-N uses bubble detectors as neutron monitors which have been designed to only detect neutrons and ignore all other radiation.

  6. Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish.

    PubMed

    Forner-Piquer, Isabel; Maradonna, Francesca; Gioacchini, Giorgia; Santangeli, Stefania; Allarà, Marco; Piscitelli, Fabiana; Habibi, Hamid R; Di Marzo, Vincenzo; Carnevali, Oliana

    2017-10-01

    Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. Copyright © 2017 Endocrine Society.

  7. Design type air engine Di Pietro

    NASA Astrophysics Data System (ADS)

    Zwierzchowski, Jaroslaw

    The article presents a pneumatic engine constructed by Angelo Di Pietro. 3D solid models of pneumatic engine components were presented therein. A directional valve is a key element of the control system. The valve functions as a camshaft distributing air to particular engine chambers. The construction designed by Angelo Di Pietro is modern and innovative. A pneumatic engine requires low pressure to start rotary movement. With the use of CFD software, the fields of velocity vectors' distribution were determined. Moreover, the author determined the distribution of pressure values in engine inlet and outlet channels. CFD model studies on engine operation were conducted for chosen stages of operating cycles. On the basis of simulation tests that were conducted, the values of flow rates for the engine were determined. The distribution of pressure values made it possible to evaluate the torque value on the rotating shaft.

  8. TU-FG-209-08: Distribution of the Deviation Index (DI) in Digital Radiography Practices Across the United States

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jones, A; Shepard, S; Dave, J

    Purpose: To characterize the distribution of the deviation index (DI) in digital radiography practices across the United States. Methods: DI data was obtained from 10 collaborating institutions in the United States between 2012 and 2015. Each institution complied with the requirements of the Institutional Review Board at their site. DI data from radiographs of the body parts chest, abdomen, pelvis and extremity were analyzed for anteroposterior, posteroanterior, lateral, and decubitus views. The DI data was analyzed both in aggregate and stratified by exposure control method, image receptor technology, patient age, and participating site for each body part and view. Themore » number of exposures with DI falling within previously published control limits for DI and descriptive statistics were calculated. Results: DI data from 505,930 radiographic exposures was analyzed. The number of exposures with DI falling within published control limits for DI varied from 10 to 20% for adult patients and 10 to 23% for pediatric patients for different body parts and views. Mean DI values averaged over other parameters for radiographs of the abdomen, chest, pelvis, and extremities ranged from 0.3 to 1.0, −0.6 to 0.5, 0.8, and −0.9 to 0.5 for the different adult views and ranged from −1.6 to −0.1, −0.3 to 0.5, −0.1, −0.2 to 1.4 for the different pediatric views, respectively (DI data was solicited only for anteroposterior view of pelvis). Standard deviation values of DI from individual sites ranged from 1.3 to 3.6 and 1.3 to 3.0 for the different adult and pediatric views, respectively. Also of interest was that target exposure indicators varied by up to a factor of 6 between sites for certain body parts and views. Conclusion: Previously published DI control limits do not reflect the state of clinical practice in digital radiography. Mean DI and target exposure indicators are targets for quality improvement efforts in radiography.« less

  9. Monitoring Changes of Tropical Extreme Rainfall Events Using Differential Absorption Barometric Radar (DiBAR)

    NASA Technical Reports Server (NTRS)

    Lin, Bing; Harrah, Steven; Lawrence, R. Wes; Hu, Yongxiang; Min, Qilong

    2015-01-01

    This work studies the potential of monitoring changes in tropical extreme rainfall events such as tropical storms from space using a Differential-absorption BArometric Radar (DiBAR) operating at 50-55 gigahertz O2 absorption band to remotely measure sea surface air pressure. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 5 millibars (approximately 1 millibar) under all weather conditions. With these sea level pressure measurements, the forecasts, analyses and understanding of these extreme events in both short and long time scales can be improved. Severe weathers, especially hurricanes, are listed as one of core areas that need improved observations and predictions in WCRP (World Climate Research Program) and NASA Decadal Survey (DS) and have major impacts on public safety and national security through disaster mitigation. Since the development of the DiBAR concept about a decade ago, our team has made substantial progress in advancing the concept. Our feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. We have developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with our instrumentation goals. Observational system simulation experiments for space DiBAR performance show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on tropical extreme rainfall weather and climate conditions.

  10. 4-(Di­methyl­amino)­pyridinium trichlorido[4-(di­methyl­amino)­pyridine-κN]cobaltate(II)

    PubMed Central

    Guenifa, Fatiha; Hadjadj, Nasreddine; Zeghouan, Ouahida; Bendjeddou, Lamia; Merazig, Hocine

    2013-01-01

    In the anion of the title compound, (C7H11N2)[CoCl3(C7H10N2)], the CoII ion is coordinated by one N atom from a 4-(di­methyl­amino)­pyridine (DMAP) ligand and three Cl atoms, forming a CoNCl3 polyhedron with a distorted tetra­hedral geometry. In the crystal, cations and anions are linked via weak N—H⋯Cl and C—H⋯Cl hydrogen bonds. Double layers of complex anions stack along the b- axis direction, which alternate with double layers of 4-(di­methyl­amino)-pyridinium cations. PMID:24046560

  11. Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

    PubMed Central

    Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2016-01-01

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

  12. 40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...

  13. 40 CFR 721.10483 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...

  14. Studying distributed cognition of simulation-based team training with DiCoT.

    PubMed

    Rybing, Jonas; Nilsson, Heléne; Jonson, Carl-Oscar; Bang, Magnus

    2016-03-01

    Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology's usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System® simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System®. We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design.

  15. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    PubMed

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Molecular basis for the recognition of cyclic-di-AMP by PstA, a PII-like signal transduction protein.

    PubMed

    Choi, Philip H; Sureka, Kamakshi; Woodward, Joshua J; Tong, Liang

    2015-06-01

    Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized PII -like protein which has been identified as a c-di-AMP receptor. PstA is widely distributed and conserved among Gram-positive bacteria in the phylum Firmicutes. Here, we report the biochemical, structural, and functional characterization of PstA from Listeria monocytogenes. We have determined the crystal structures of PstA in the c-di-AMP-bound and apo forms at 1.6 and 2.9 Å resolution, respectively, which provide the molecular basis for its specific recognition of c-di-AMP. PstA forms a homotrimer structure that has overall similarity to the PII protein family which binds ATP. However, PstA is markedly different from PII proteins in the loop regions, and these structural differences mediate the specific recognition of their respective nucleotide ligand. The residues composing the c-di-AMP binding pocket are conserved, suggesting that c-di-AMP recognition by PstA is of functional importance. Disruption of pstA in L. monocytogenes affected c-di-AMP-mediated alterations in bacterial growth and lysis. Overall, we have defined the PstA family as a conserved and specific c-di-AMP receptor in bacteria. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  17. DiRE: identifying distant regulatory elements of co-expressed genes

    PubMed Central

    Gotea, Valer; Ovcharenko, Ivan

    2008-01-01

    Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiRE's unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org. PMID:18487623

  18. c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

    PubMed Central

    Fahmi, Tazin; Port, Gary C.

    2017-01-01

    Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an

  19. Structural Insight into the Mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tchigvintsev, A.; Xu, X.; Singer, A.

    2010-08-01

    Cyclic diguanylate (or bis-(3'-5') cyclic dimeric guanosine monophosphate; c-di-GMP) is a ubiquitous second messenger that regulates diverse cellular functions, including motility, biofilm formation, cell cycle progression, and virulence in bacteria. In the cell, degradation of c-di-GMP is catalyzed by highly specific EAL domain phosphodiesterases whose catalytic mechanism is still unclear. Here, we purified 13 EAL domain proteins from various organisms and demonstrated that their catalytic activity is associated with the presence of 10 conserved EAL domain residues. The crystal structure of the TBD1265 EAL domain was determined in free state (1.8 {angstrom}) and in complex with c-di-GMP (2.35 {angstrom}), andmore » unveiled the role of conserved residues in substrate binding and catalysis. The structure revealed the presence of two metal ions directly coordinated by six conserved residues, two oxygens of c-di-GMP phosphate, and potential catalytic water molecule. Our results support a two-metal-ion catalytic mechanism of c-di-GMP hydrolysis by EAL domain phosphodiesterases.« less

  20. A minimalist biosensor: Quantitation of cyclic di-GMP using the conformational change of a riboswitch aptamer.

    PubMed

    Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C

    2015-01-01

    Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA.

  1. Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.

    PubMed

    Li, Jiawei; Zeng, Wen; Zhang, Ye; Ko, Albert Min-Shan; Li, Chunxiang; Zhu, Hong; Fu, Qiaomei; Zhou, Hui

    2017-12-04

    Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.

  2. Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.

    PubMed

    Verri, Tiziano; Barca, Amilcare; Pisani, Paola; Piccinni, Barbara; Storelli, Carlo; Romano, Alessandro

    2017-04-01

    Solute Carrier 15 (SLC15) family, alias H + -coupled oligopeptide cotransporter family, is a group of membrane transporters known for their role in the cellular uptake of di- and tripeptides (di/tripeptides) and peptide-like molecules. Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, while SLC15A2 (PEPT2) mainly allows renal tubular reabsorption of di/tripeptides from ultrafiltration, SLC15A3 (PHT2) and SLC15A4 (PHT1) possibly interact with di/tripeptides and histidine in certain immune cells, and SLC15A5 has unknown function. Our understanding of this family in vertebrates has steadily increased, also due to the surge of genomic-to-functional information from 'non-conventional' animal models, livestock, poultry, and aquaculture fish species. Here, we review the literature on the SLC15 transporters in teleost fish with emphasis on SLC15A1 (PEPT1), one of the solute carriers better studied amongst teleost fish because of its relevance in animal nutrition. We report on the operativity of the transporter, the molecular diversity, and multiplicity of structural-functional solutions of the teleost fish orthologs with respect to higher vertebrates, its relevance at the intersection of the alimentary and osmoregulative functions of the gut, its response under various physiological states and dietary solicitations, and its possible involvement in examples of total body plasticity, such as growth and compensatory growth. By a comparative approach, we also review the few studies in teleost fish on SLC15A2 (PEPT2), SLC15A4 (PHT1), and SLC15A3 (PHT2). By representing the contribution of teleost fish to the knowledge of the physiology of di/tripeptide transport and transporters, we aim to fill the gap between higher and lower vertebrates.

  3. Target Search and Selection for the DI/EPOXI Spacecraft

    NASA Technical Reports Server (NTRS)

    Grebow, Daniel J.; Bhaskaran, Shyam; Chesley, Steven R.

    2012-01-01

    Upon completion of the Hartley 2 flyby in November 2010, the Deep Impact (DI) spacecraft resided in a solar orbit without possibility for gravity assist with any large body. Conservative estimates of remaining fuel were enough to provide only an 18 m/s impulse on the spacecraft. We present our method and results of our systematic scan of potential small body encounters for DI, and our criteria to narrow the selection to the asteroid 2002 GT as the target flyby body. The mission profile has two deterministic maneuvers to achieve the encounter, the first of which executed on November 25, 2011.

  4. Transition metal complexes of 2-amino-3,5-dihalopyridines: Syntheses, structures and magnetic properties of (3,5-diCAPH)2CuX4 and (3,5-diBAPH)2CuX4.

    PubMed

    Tremelling, Grant W; Foxman, Bruce M; Landee, Christopher P; Turnbull, Mark M; Willett, Roger D

    2009-12-21

    A family of bis(2-amino-3,5-dihalopyridinium)tetrahalocuprate(II) compounds has been synthesized, including (3,5-diCAPH)2CuCl4 (1), (3,5-diCAPH)2CuBr4 (2), (3,5-diBAPH)2CuCl4 (3), and (3,5-diBAPH)2CuBr4 (4) [3,5-diCAPH = 2-amino-3,5-dichloropyridinium; 3,5-diBAPH = 2-amino-3,5-dibromopyridinium]. These complexes have been analyzed through single crystal X-ray diffraction and temperature dependent magnetic susceptibility. Compound 1 crystallizes in the P-1 space group and the tetrachlorocuprate ion is best described as possessing a distorted square planar geometry. Compounds 2-4 are structurally similar and crystallized in the P2(1)/n, P2(1)/c, and P2(1)/n space groups respectively. The tetrahalocuprate ions are best described as distorted tetrahedra. All four compounds show antiferromagnetic interactions and were fit to the uniform chain Heisenberg model with resulting 2J/kB values of -11.71(2) K, -2.21(1) K, -12.43 (2) K, and -1.36(1) K, respectively. The exchange values correlate well with the two-halide exchange pathway parameters. The unusual observation that the chloride complexes show stronger magnetic exchange than the bromide complexes provides strong support that the exchange can be strongly dependent upon the Cu-X...X angles and Cu-X...X-Cu torsion angles.

  5. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  6. TOXICOLOGY OF MONO- AND DI-ALKYLTIN CHLORIDES.

    EPA Science Inventory

    Mono- and di-alkyltin chlorides are reactive compounds used in the production of stabilizers for polyvinyl chloride (PVC) plastics, primarily used for water distribution pipes. Health effects data were compiled or developed by the manufacturers for the EPA's HPV Challenge progra...

  7. Biofilm Formation by the Acidophile Bacterium Acidithiobacillus thiooxidans Involves c-di-GMP Pathway and Pel exopolysaccharide.

    PubMed

    Díaz, Mauricio; Castro, Matias; Copaja, Sylvia; Guiliani, Nicolas

    2018-02-21

    Acidophile bacteria belonging to the Acidithiobacillus genus are pivotal players for the bioleaching of metallic values such as copper. Cell adherence to ores and biofilm formation, mediated by the production of extracellular polymeric substances, strongly favors bioleaching activity. In recent years, the second messenger cyclic diguanylate (c-di-GMP) has emerged as a central regulator for biofilm formation in bacteria. C-di-GMP pathways have been reported in different Acidithiobacillus species; however, c-di-GMP effectors and signal transduction networks are still largely uncharacterized in these extremophile species. Here we investigated Pel exopolysaccharide and its role in biofilm formation by sulfur-oxidizing species Acidithiobacillus thiooxidans . We identified 39 open reading frames (ORFs) encoding proteins involved in c-di-GMP metabolism and signal transduction, including the c-di-GMP effector protein PelD, a structural component of the biosynthesis apparatus for Pel exopolysaccharide production. We found that intracellular c-di-GMP concentrations and transcription levels of pel genes were higher in At . thiooxidans biofilm cells compared to planktonic ones. By developing an At . thiooxidans Δ pelD null-mutant strain we revealed that Pel exopolysaccharide is involved in biofilm structure and development. Further studies are still necessary to understand how Pel biosynthesis is regulated in Acidithiobacillus species, nevertheless these results represent the first characterization of a c-di-GMP effector protein involved in biofilm formation by acidophile species.

  8. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants.

    PubMed

    Ito, Takamitsu; Fujimoto, Shunsuke; Suito, Fumiaki; Shimosaka, Makoto; Taguchi, Goro

    2017-07-01

    Citrus plants accumulate many kinds of flavonoids, including di-C-glucosyl flavonoids, which have attracted considerable attention due to their health benefits. However, the biosynthesis of di-C-glucosyl flavonoids has not been elucidated at the molecular level. Here, we identified the C-glycosyltransferases (CGTs) FcCGT (UGT708G1) and CuCGT (UGT708G2) as the primary enzymes involved in the biosynthesis of di-C-glucosyl flavonoids in the citrus plants kumquat (Fortunella crassifolia) and satsuma mandarin (Citrus unshiu), respectively. The amino acid sequences of these CGTs were 98% identical, indicating that CGT genes are highly conserved in the citrus family. The recombinant enzymes FcCGT and CuCGT utilized 2-hydroxyflavanones, dihydrochalcone, and their mono-C-glucosides as sugar acceptors and produced corresponding di-C-glucosides. The K m and k cat values of FcCGT toward phloretin were <0.5 μm and 12.0 sec -1 , and those toward nothofagin (3'-C-glucosylphloretin) were 14.4 μm and 5.3 sec -1 , respectively; these values are comparable with those of other glycosyltransferases reported to date. Transcripts of both CGT genes were found to concentrate in various plant organs, and particularly in leaves. Our results suggest that di-C-glucosyl flavonoid biosynthesis proceeds via a single enzyme using either 2-hydroxyflavanones or phloretin as a substrate in citrus plants. In addition, Escherichia coli cells expressing CGT genes were found to be capable of producing di-C-glucosyl flavonoids, which is promising for commercial production of these valuable compounds. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  9. [Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin].

    PubMed

    Zhou, Jing; Ma, Hong-yue; Fan, Xin-sheng; Xiao, Wei; Wang, Tuan-jie

    2012-10-01

    To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

  10. Measurement of q ˆ in Relativistic Heavy Ion Collisions using di-hadron correlations

    DOE PAGES

    Tannenbaum, M. J.

    2017-06-06

    The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficientmore » $$\\hat{q}$$ and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum p T, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle p Tt and associated p Ta transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, j T, is dominated by k T, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger k T in A+A than in p+p collisions. The present work introduces the observation that the k T measured in p+p collisions for di-hadrons with p Tt and p Ta must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the k T measured with the same di-hadron p Tt and p Ta in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result <$$\\hat{q}$$L>=2.1±0.6 GeV 2. This is more precise but in agreement with a theoretical calculation of <$$\\hat{q}$$L>=14$$+42\\atop{-14}$$ GeV 2 using the same data. Assuming a length ≈7 fm for central Au+Au collisions the present result gives $$\\hat{q}$$≈0.30±0.09 GeV 2/fm, in fair agreement with the JET collaboration result from single hadron suppression of $$\\hat{q}$$≈1.2±0.3 GeV 2/fm at an initial time τ 0=0.6 fm/c in Au+Au collisions at √sNN=200 GeV.« less

  11. Measurement of q ˆ in Relativistic Heavy Ion Collisions using di-hadron correlations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tannenbaum, M. J.

    The propagation of partons from hard scattering through the Quark Gluon Plasma produced in A+A collisions at RHIC and the LHC is represented in theoretical analyses by the transport coefficientmore » $$\\hat{q}$$ and predicted to cause both energy loss of the outgoing partons, observed as suppression of particles or jets with large transverse momentum p T, and broadening of the azimuthal correlations of the outgoing di-jets or di-hadrons from the outgoing parton-pair, which has not been observed. The widths of azimuthal correlations of di-hadrons with the same trigger particle p Tt and associated p Ta transverse momenta in p+p and Au+Au are so-far statistically indistinguishable as shown in recent as well as older di-hadron measurements and also with jet-hadron and hadron-jet measurements. The azimuthal width of the di-hadron correlations in p+p collisions, beyond the fragmentation transverse momentum, j T, is dominated by k T, the so-called intrinsic transverse momentum of a parton in a nucleon, which can be measured. The broadening should produce a larger k T in A+A than in p+p collisions. The present work introduces the observation that the k T measured in p+p collisions for di-hadrons with p Tt and p Ta must be reduced to compensate for the energy loss of both the trigger and away parent partons when comparing to the k T measured with the same di-hadron p Tt and p Ta in Au+Au collisions. This idea is applied to a recent STAR di-hadron measurement, with result <$$\\hat{q}$$L>=2.1±0.6 GeV 2. This is more precise but in agreement with a theoretical calculation of <$$\\hat{q}$$L>=14$$+42\\atop{-14}$$ GeV 2 using the same data. Assuming a length ≈7 fm for central Au+Au collisions the present result gives $$\\hat{q}$$≈0.30±0.09 GeV 2/fm, in fair agreement with the JET collaboration result from single hadron suppression of $$\\hat{q}$$≈1.2±0.3 GeV 2/fm at an initial time τ 0=0.6 fm/c in Au+Au collisions at √sNN=200 GeV.« less

  12. Vibrio cholerae VpsT Regulates Matrix Production and Motility by Directly Sensing Cyclic di-GMP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Krasteva, P.; Fong, J; Shikuma, N

    2010-01-01

    Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerizationmore » on c-di-GMP binding.« less

  13. 4-Bromo-N-(di-n-propyl-carbamothioyl)-benzamide.

    PubMed

    Binzet, Gün; Flörke, Ulrich; Külcü, Nevzat; Arslan, Hakan

    2009-02-04

    The synthesis of the title compound, C(14)H(19)BrN(2)OS, involves the reaction of 4-bromo-benzoyl chloride with potassium thio-cyanate in acetone followed by condensation of the resulting 4-bromo-benzoyl isothio-cyanate with di-n-propyl-amine. Typical thio-urea carbonyl and thio-carbonyl double bonds, as well as shortened C-N bonds, are observed in the title compound. The short C-N bond lengths in the centre of the mol-ecule reveal the effects of resonance in this part of the mol-ecule. The asymmetric unit of the title compound contains two crystallographically independent mol-ecules, A and B. There is very little difference between the bond lengths and angles of these mol-ecules. In mol-ecule B, one di-n-propyl group is twisted in a -anti-periplanar conformation with C-C-C-H = -179.1 (3)° and the other adopts a -synclinal conformation with C-C-C-H = -56.7 (4)°; in mol-ecule A the two di-n-propyl groups are twisted in + and -anti-periplanar conformations, with C-C-C-H = -179.9 (3) and 178.2 (3)°, respectively. In the crystal, the mol-ecules are linked into dimeric pairs via pairs of N-H⋯S hydrogen bonds.

  14. 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake.

    PubMed

    Stanford, Kristin I; Lynes, Matthew D; Takahashi, Hirokazu; Baer, Lisa A; Arts, Peter J; May, Francis J; Lehnig, Adam C; Middelbeek, Roeland J W; Richard, Jeffrey J; So, Kawai; Chen, Emily Y; Gao, Fei; Narain, Niven R; Distefano, Giovanna; Shettigar, Vikram K; Hirshman, Michael F; Ziolo, Mark T; Kiebish, Michael A; Tseng, Yu-Hua; Coen, Paul M; Goodyear, Laurie J

    2018-05-01

    Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Hooked on the nicotine addiction thesis: a response to DiFranza.

    PubMed

    Dar, Reuven; Frenk, Hanan

    2013-11-18

    DiFranza's rebuttal to our critique of the "Hooked on Nicotine" research program misconstrues our arguments beyond recognition. The grossest misrepresentation of our critique by DiFranza is that we devise (by thwarting science) to rescue "the conventional wisdom" of the "threshold model of nicotine addiction." In fact, the difference between our positions lies elsewhere: We believe that nicotine is not an addictive drug and that its contribution to the smoking habit is secondary; DiFranza believes that nicotine is so powerfully addictive that novice smokers can lose autonomy over their smoking behavior after one cigarette or even following a single puff. Our review aimed to critically examine the empirical basis of this extreme version of the nicotine "addiction" model. In this brief commentary we illustrate how the commitment to the nicotine "addiction" theory has biased the methodology and the interpretation of the data in "Hooked on Nicotine" research program.

  16. DiMeX: A Text Mining System for Mutation-Disease Association Extraction

    PubMed Central

    Mahmood, A. S. M. Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K.

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases. PMID:27073839

  17. DiMeX: A Text Mining System for Mutation-Disease Association Extraction.

    PubMed

    Mahmood, A S M Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases.

  18. Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa

    DOE PAGES

    Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.; ...

    2015-05-15

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZmore » domain fold with a dimerization mode not previously observed for this family of proteins. Moreover, calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. Our results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.« less

  19. Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Whitney, John C.; Robinson, Howard; Whitfield, Gregory B.

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZmore » domain fold with a dimerization mode not previously observed for this family of proteins. Moreover, calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. Our results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.« less

  20. Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa*

    PubMed Central

    Whitney, John C.; Whitfield, Gregory B.; Marmont, Lindsey S.; Yip, Patrick; Neculai, A. Mirela; Lobsanov, Yuri D.; Robinson, Howard; Ohman, Dennis E.; Howell, P. Lynne

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa. PMID:25817996

  1. Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

    PubMed Central

    Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Sitong; Bian, Tingwei; Han, Chunmao; Meng, Qin

    2016-01-01

    Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring. PMID:27901027

  2. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that leadmore » to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients.

  3. c-di-GMP enhances protective innate immunity in a murine model of pertussis.

    PubMed

    Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A; Gerdts, Volker

    2014-01-01

    Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required.

  4. c-di-GMP Enhances Protective Innate Immunity in a Murine Model of Pertussis

    PubMed Central

    Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G.; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A.; Gerdts, Volker

    2014-01-01

    Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required. PMID:25333720

  5. Calibrazioni a terra e prestazioni in volo di spettrometri ad immagine nel visibile e nel vicino infrarosso per l'esplorazione planetaria

    NASA Astrophysics Data System (ADS)

    Filacchione, Gianrico

    2006-10-01

    Nel corso dell’ultimo decennio l’esplorazione planetaria ha potuto beneficiare dei dati prodotti dagli spettrometri ad immagine: grazie a questa nuova classe di strumenti, realizzati per l’osservazione in remoto di superfici ed atmosfere planetarie, è possibile acquisire dati iperspettrali con elevati poteri risolutivi spaziali e spettrali. Il principale vantaggio offerto dagli spettrometri ad immagine, rispetto alle camere ed agli spettrometri puntuali, è rappresentato dalla capacità di misurare, identificare e mappare le unità composizionali delle superfici planetarie; queste informazioni permettono di investigare sia l’evoluzione geochimica delle superfici sia la dinamica e la composizione delle atmosfere. Sebbene i primi spettrometri ad immagine siano stati francesi (Phobos/ISM, Imaging Spectrometer for Mars) e statunitensi (Galileo/NIMS, Near Infrared Mapping Spectrometer), il nostro paese nel corso degli ultimi anni è stato in grado di proporre alla com unità spaziale internazionale degli strumenti dalle elevate prestazioni che sono stati infatti accettati come payload scientifici su diverse missioni interplanetarie: dai canali visibili di VIMS (Visual and Infrared Mapping Spectrometer) su Cassini (Nasa, JPL, ESA, ASI) e di OMEGA (Observatoire pour la Minéralogie, l’Eau, les Glacies et l’Activitè de Mars) su MarsExpress (ESA) ai due VIRTIS (Visible and Infrared Thermal Imaging Spectrometer) su Rosetta (ESA) e VenusExpress (ESA) fino a VIR-MS (Visible and Infrared Mapping Spectrometer) su Dawn (Nasa). In questo momento inoltre altri due spettrometri sono in avanzata fase di studio: JIRAM (Jovian InfraRed Auroral Mapper) su Juno (missione New Discovery Nasa) e VIHI (Visible and Infrared Hyperspectral Imager) integrato nel payload italiano di remote sensing SIMBIO-SYS di BepiColombo (missione cornerstone ESA). La realizzazione di uno spettrometro ad immagini da utilizzare su una missione interplanetaria richiede un’accurata analisi in fase

  6. Structural isomers of polyfluorinated di- and tri-alkylated phosphate ester surfactants present in industrial blends and in microwave popcorn bags.

    PubMed

    Trier, Xenia; Nielsen, Nikoline Juul; Christensen, Jan H

    2011-09-01

    In this study, we provide strategies for detecting and quantifying the structural isomers of polyfluorinated di- and tri-alkyl surfactants (PFAS) by mass spectrometry (MS). We specifically investigate polyfluorinated dialkylated phosphate ester surfactants (x:2/y:2 diPAPS, (F(CF(2))( x )CH(2)CH(2)O-P(O)(O)(-)-OCH(2)CH(2)(CF(2))( y )F)) and their thioether analogues (x:2/y:2 S-diPAPS, F(CF(2))( x )CH(2)CH(2)SCH(2)-C[CH(2)O)(2)P(O)(O)(-)]-CH(2)SCH(2)CH(2)(CF(2))( y )F), which are used for industrial applications, such as oil- and water-repellent coatings on paper and board. DiPAPS have been found in human blood and are metabolised to the persistent perfluoroalkyl carboxylic acids (PFCA) in rats. A microwave popcorn bag extract was analysed by ultrahigh-pressure liquid chromatography coupled to a negative electrospray ionisation-quadrupole time-of-flight MS. The extract contained S-diPAPS, diPAPS and trialkylated (triPAPS) impurities. TriPAPS were also present in industrial and synthetic diPAPS standards, and were verified with an 8:2/8:2/8:2 triPAPS standard. The eight elemental compositions (m/z's) of diPAPS in the extract represent 19 precursor ion structures, and the six S-diPAPS m/z's represent at least 13 structures. The diPAPS had [M-H](-) precursor ions of m/z 789, 889,…1,489 and the S-diPAPS of m/z 921, 1,021,…1,421, corresponding to fluorinated chains from C(6-18). Each m/z appeared as one to three chromatographic peaks of structural isomers, where, e.g. m/z 1,189 was present as 10:2/10:2, 8:2/12:2 and 6:2/14:2 diPAPS. The isomers formed different products ions, thus only half of the m/z 1,189 diPAPS concentration was measured with one precursor ion > product ion transition. In general, knowledge about structural isomers of poly-alkylated PFAS is needed for the estimation of types and amounts of perfluorinated degradation products, such as PFCA from diPAPS.

  7. DI Diesel Performance and Emissions Model

    DTIC Science & Technology

    1998-03-31

    Skeletal mechanism for NOx chemistry in Diesel engines ," SAE Paper 981450. Mori, K. (1997), "Worldwide...Based on the review discussed above, Mellor et al. (1998) postulate a skeletal mechanism for NO chemistry in DI Diesel engines . This mechanism is... mechanism for NOx chemistry in Diesel engines ," SAE Paper 981450. Various Internal Ford Reports, Ford Motor Company, Dearborn, MI. 29

  8. A C-di-GMP-proflavine-hemin supramolecular complex has peroxidase activity--implication for a simple colorimetric detection.

    PubMed

    Nakayama, Shizuka; Roelofs, Kevin; Lee, Vincent T; Sintim, Herman O

    2012-03-01

    Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) and hence provides simple colorimetric detection of c-di-GMP at low micromolar concentrations.

  9. 4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses Inflammatory Responses Through TRPV1 Activation.

    PubMed

    Kim, Yiseul; Kim, Jung Tae; Park, Joonwoo; Son, Hee Jin; Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

    2017-10-01

    Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca 2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC 50  = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. DiGeorge Syndrome: a not so rare disease.

    PubMed

    Fomin, Angela B F; Pastorino, Antonio Carlos; Kim, Chong Ae; Pereira, C A; Carneiro-Sampaio, Magda; Abe-Jacob, Cristina Miuki

    2010-01-01

    The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. Of 14 patients (8m - 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n = 12), facial abnormalities (n = 11), hypocalcemia (n = 5) and low lymphocyte count (n=2). The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up.

  11. DiTour 3.1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pelaia II, Thomas A.

    2015-06-30

    There is a need for software that allows a tour guide to present different tracks of slides and then return to the default slide show automatically upon completion. A mobile solution is needed for trade shows. DiTour is an iPad/iPhone app that pulls presentation content from a website, stores it on the device and presents it on a connected display. A tour guide can select a track to present and it will automatically return to the default track after a timeout. It offers a mobile solution which is ideal for trade shows.

  12. Corrections to di-Higgs boson production with light stops and modified Higgs couplings

    NASA Astrophysics Data System (ADS)

    Huang, Peisi; Joglekar, Aniket; Li, Min; Wagner, Carlos E. M.

    2018-04-01

    The Higgs pair production in gluon fusion is a sensitive probe of beyond-standard model (BSM) phenomena and its detection is a major goal for the LHC and higher energy hadron collider experiments. In this work we reanalyze the possible modifications of the Higgs pair production cross section within low energy supersymmetry models. We show that the supersymmetric contributions to the Higgs pair production cross section are strongly correlated with the ones of the single Higgs production in the gluon fusion channel. Motivated by the analysis of ATLAS and CMS Higgs production data, we show that the scalar superpartners' contributions may lead to significant modification of the di-Higgs production rate and invariant mass distribution with respect to the SM predictions. We also analyze the combined effects on the di-Higgs production rate of a modification of the Higgs trilinear and top-quark Yukawa couplings in the presence of light stops. In particular, we show that due to the destructive interference of the triangle and box amplitude contributions to the di-Higgs production cross section, even a small modification of the top-quark Yukawa coupling can lead to a significant increase of the di-Higgs production rate.

  13. The HD-GYP domain, cyclic di-GMP signaling, and bacterial virulence to plants.

    PubMed

    Dow, J Maxwell; Fouhy, Yvonne; Lucey, Jean F; Ryan, Robert P

    2006-12-01

    Cyclic di-GMP is an almost ubiquitous second messenger in bacteria that was first described as an allosteric activator of cellulose synthase but is now known to regulate a range of functions, including virulence in human and animal pathogens. Two protein domains, GGDEF and EAL, are implicated in the synthesis and degradation, respectively, of cyclic di-GMP. These domains are widely distributed in bacteria, including plant pathogens. The majority of proteins with GGDEF and EAL domains contain additional signal input domains, suggesting that their activities are responsive to environmental cues. Recent studies have demonstrated that a third domain, HD-GYP, is also active in cyclic di-GMP degradation. In the plant pathogen Xanthomonas campestris pv. campestris, a two-component signal transduction system comprising the HD-GYP domain regulatory protein RpfG and cognate sensor RpfC positively controls virulence. The signals recognized by RpfC may include the cell-cell signal DSF, which also acts to regulate virulence in X. campestris pv. campestris. Here, we review these recent advances in our understanding of cyclic di-GMP signaling with particular reference to one or more roles in the bacterial pathogenesis of plants.

  14. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

  15. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    PubMed Central

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; Harwood, Caroline S.; Sondermann, Holger; Navarro, Marcos V. A. S.

    2016-01-01

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs. PMID:26712005

  16. Mechanistic insights into c-di-GMP–dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa

    DOE PAGES

    Matsuyama, Bruno Y.; Krasteva, Petya V.; Baraquet, Claudine; ...

    2015-12-28

    Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ 54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response tomore » cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.« less

  17. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-12-08

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  18. Microphase separation in thin films of lamellar forming polydisperse di-block copolymers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.

    Despite the ubiquity of polydispersity in chain lengths of di-block copolymers, its effects on microphase separation in thin films have eluded a clear understanding. In this paper, we have studied effects of polydispersity on the microphase separation in thin films of lamellar forming di-block copolymers using self-consistent field theory (SCFT) and neutron reflectivity experiments. Di-block copolymers containing a polydisperse block of poly(glycidylmethacrylate) (PGMA) connected to a near-monodisperse block poly(2-vinyl-4,4-dimethyl-d 6 azlactone) (PVDMA-d 6) are considered in this work. Effects of chain length polydispersity, film thickness, substrate–monomer and monomer–monomer interactions on the microphase segregation are studied using SCFT. The theoretical studymore » reveals that in comparison to a film created with monodisperse di-block copolymers, an increase in polydispersity tends to decrease the number of lamellar strata that can be packed in a film of given thickness. This is a direct consequence of an increase in lamellar domain spacing with an increase in polydispersity index. Furthermore, it is shown that polydispersity induces conformational asymmetry and an increase in the polydispersity index leads to an increase in the effective Kuhn segment length of the polydisperse blocks. It is shown that the conformational asymmetry effects, which are entropic in origin and of increasing importance as film thickness decreases, drive the polydisperse blocks to the middle of the films despite favorable substrate interactions. These predictions are verified by results from neutron reflectivity experiments on thin films made from moderately polydisperse PGMA-PVDMA-d 6 di-block copolymer deposited on silicon substrates. In conclusion, results from SCFT are used to predict neutron reflectivity profiles, providing a facile and robust route to obtain useful physical insights into the structure of polydisperse diblock copolymers at interfaces.« less

  19. Microphase separation in thin films of lamellar forming polydisperse di-block copolymers

    DOE PAGES

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.; ...

    2015-02-03

    Despite the ubiquity of polydispersity in chain lengths of di-block copolymers, its effects on microphase separation in thin films have eluded a clear understanding. In this paper, we have studied effects of polydispersity on the microphase separation in thin films of lamellar forming di-block copolymers using self-consistent field theory (SCFT) and neutron reflectivity experiments. Di-block copolymers containing a polydisperse block of poly(glycidylmethacrylate) (PGMA) connected to a near-monodisperse block poly(2-vinyl-4,4-dimethyl-d 6 azlactone) (PVDMA-d 6) are considered in this work. Effects of chain length polydispersity, film thickness, substrate–monomer and monomer–monomer interactions on the microphase segregation are studied using SCFT. The theoretical studymore » reveals that in comparison to a film created with monodisperse di-block copolymers, an increase in polydispersity tends to decrease the number of lamellar strata that can be packed in a film of given thickness. This is a direct consequence of an increase in lamellar domain spacing with an increase in polydispersity index. Furthermore, it is shown that polydispersity induces conformational asymmetry and an increase in the polydispersity index leads to an increase in the effective Kuhn segment length of the polydisperse blocks. It is shown that the conformational asymmetry effects, which are entropic in origin and of increasing importance as film thickness decreases, drive the polydisperse blocks to the middle of the films despite favorable substrate interactions. These predictions are verified by results from neutron reflectivity experiments on thin films made from moderately polydisperse PGMA-PVDMA-d 6 di-block copolymer deposited on silicon substrates. In conclusion, results from SCFT are used to predict neutron reflectivity profiles, providing a facile and robust route to obtain useful physical insights into the structure of polydisperse diblock copolymers at interfaces.« less

  20. Microphase separation in thin films of lamellar forming polydisperse di-block copolymers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Rajeev; Lokitz, Bradley S.; Sides, Scott W.

    Despite the ubiquity of polydispersity in chain lengths of di-block copolymers, its effects on microphase separation in thin films have eluded a clear understanding. In this work, we have studied effects of polydispersity on the microphase separation in thin films of lamellar forming di-block copolymers using self-consistent field theory (SCFT) and neutron reflectivity experiments. Di-block copolymers containing a polydisperse block of poly(glycidylmethacrylate) (PGMA) connected to a near-monodisperse block poly(2-vinyl-4,4-dimethyl-d6 azlactone) (PVDMA-d6) are considered in this work. Effects of chain length polydispersity, film thickness, substrate-monomer and monomer-monomer interactions on the microphase segregation are studied using SCFT. The theoretical study reveals thatmore » in comparison to a film created with monodisperse di-block copolymers, an increase in polydispersity tends to decrease the number of lamellar strata that can be packed in a film of given thickness. This is a direct consequence of an increase in lamellar domain spacing with an increase in polydispersity index. Furthermore, it is shown that polydispersity induces conformational asymmetry and an increase in the polydispersity index leads to an increase in the effective Kuhn segment length of the polydisperse blocks. It is shown that the conformational asymmetry effects, which are entropic in origin and of increasing importance as film thickness decreases, drive the polydisperse blocks to the middle of the films despite favorable substrate interactions. These predictions are verified by results from neutron reflectivity experiments on thin films made from moderately polydisperse PGMA-PVDMA-d6 di-block copolymer deposited on silicon substrates. Finally, results from SCFT are used to predict neutron reflectivity profiles, providing a facile and robust route to obtain useful physical insights into the structure of polydisperse diblock copolymers at interfaces.« less

  1. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    PubMed Central

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  2. Distributed Timing and Localization (DiGiTaL)

    NASA Technical Reports Server (NTRS)

    D'Amico, Simone; Hunter, Roger C.; Baker, Christopher

    2017-01-01

    The Distributed Timing and Localization (DiGiTaL) system provides nano satellite formations with unprecedented,centimeter-level navigation accuracy in real time and nanosecond-level time synchronization. This is achieved through the integration of a multi-constellation Global Navigation Satellite System (GNSS) receiver, a Chip-Scale Atomic Clock (CSAC), and a dedicated Inter-Satellite Link (ISL). In comparison, traditional single spacecraft GNSS navigation solutions are accurate only to the meter-level due to the sole usage of coarse pseudo-range measurements. To meet the strict requirements of future miniaturized distributed space systems, DiGiTaL uses powerful error-cancelling combinations of raw carrier-phase measurements which are exchanged between the swarming nano satellites through a decentralized network. A reduced-dynamics estimation architecture on board each individual nano satellite processes the resulting millimeter-level noise measurements to reconstruct the fullformation state with high accuracy.

  3. The HADES-RICH upgrade using Hamamatsu H12700 MAPMTs with DiRICH FEE + Readout

    NASA Astrophysics Data System (ADS)

    Patel, V.; Traxler, M.

    2018-03-01

    The High Acceptance Di-Electron Spectrometer (HADES) is operational since the year 2000 and uses a hadron blind RICH detector for electron identification. The RICH photon detector is currently replaced by Hamamatsu H12700 MAPMTs with a readout system based on the DiRICH front-end module. The electronic readout chain is being developed as a joint effort of the HADES-, CBM- and PANDA collaborations and will also be used in the photon detectors for the upcoming Compressed Baryonic Matter (CBM) and PANDA experiments at FAIR . This article gives a brief overview on the photomultipliers and their quality assurance test measurements, as well as first measurements of the new DiRICH front-end module in final configurations.

  4. Comparison of high speed DI-LIGBT structures

    NASA Astrophysics Data System (ADS)

    Sunkavalli, Ravishankar; Baliga, B. Jayant

    1997-12-01

    The performance of the DI segmented collector (SC)-LIGBT is compared to the collector shorted (CS)-LIGBT. The SC-LIGBT allows for adjusting the tradeoff between switching speed and on-state voltage drop by simply changing the P+ collector segment width during device layout. In contrast to previously reported junction isolated (JI) devices, the DI SC-LIGBT was observed to have a turnoff speed similar to the CS-LIGBT with a higher forward drop than the conventional LIGBT. The on-state performance of the integral diodes of the SC-LIGBTs was found to be superior to the integral diode of the CS-LIGBT. The integral diodes of both the CS and the SC-LIGBTs were found to have much superior switching characteristics compared to a lateral PiN diode at the expense of a higher on-state voltage drop. Thus, the superior switching characteristics of the integral diode in the SC-LIGBT complements its fast switching behavior making this device attractive for compact, high frequency, high efficient, power ICs.

  5. Progress in high performance DI-BSCCO wire

    NASA Astrophysics Data System (ADS)

    Kikuchi, M.; Ayai, N.; Fujikami, J.; Kobayashi, S.; Yamazaki, K.; Yamade, S.; Ishida, T.; Kato, T.; Hayashi, K.; Sato, K.; Hata, R.; Iihara, J.; Yamaguchi, K.; Kumakura, H.; Kitaguchi, H.; Osamura, K.; Shimoyama, J.

    2008-03-01

    The high performances of Dynamically Innovative BSCCO (DI-BSCCO) wire have been reviewed. Critical current (Ic) has reached 210 A (77 K and self-field), which is equivalent 500 A per 10 mm width, by total optimization of whole manufacturing process including Controlled Over Pressure (CT-OP) sintering. The further higher Ic value will be available on preferable oxide filaments with the improved c-axis orientation of Bi2223 grains, the minimized non-superconducting phases, and so on. The Ic of long length wires has been reached 203 A of 42 m 180 A of 1,400 m. Ic in the magnetic field at low temperature has showed great improvements in comparison with the past 150 A class wire. The mechanical performances has been improved due to the densification of the Bi2223 filaments up to 100% by CT-OP process, moreover have been dynamically improved by reinforcement with stainless steel tapes or brass tapes. These results can enable DI-BSCCO wire to be applied for the cryogenic applications such as motors, magnets, cables and so on.

  6. DiGeorge Syndrome: a not so rare disease

    PubMed Central

    Fomin, Angela BF; Pastorino, Antonio Carlos; Kim, Chong Ae; Pereira, Alexandre C; Carneiro‐Sampaio, Magda; Abe Jacob, Cristina Miuki

    2010-01-01

    INTRODUCTION: The DiGeorge Syndrome was first described in 1968 as a primary immunodeficiency resulting from the abnormal development of the third and fourth pharyngeal pouches during embryonic life. It is characterized by hypocalcemia due to hypoparathyroidism, heart defects, and thymic hypoplasia or aplasia. Its incidence is 1:3000 live births and, despite its high frequency, little is known about its natural history and progression. ←This is probably due to diagnostic difficulties and the great variety of names used to describe it, such as velocardiofacial, Shprintzen, DiGeorge, and CATCH 22 Syndromes, as well as conotruncal facial anomaly. All represent the same genetic condition, chromosome 22q11.2 deletion, which might have several clinical expressions. OBJECTIVES: To describe clinical and laboratorial data and phenotypic characteristics of patients with DiGeorge Syndrome. METHODS: Patients underwent standard clinical and epidemiological protocol and tests to detect heart diseases, facial abnormalities, dimorphisms, neurological or behavioral disorders, recurrent infections and other comorbidities. RESULTS: Of 14 patients (8m – 18y11m), only one did not have 22q11.2 deletion detected. The main findings were: conotruncal malformation (n  =  12), facial abnormalities (n  =  11), hypocalcemia (n  =  5) and low lymphocyte count (n = 2). CONCLUSION: The authors pointed out the necessity of DGS suspicion in all patient presenting with heart defects, facial abnormalities (associated or not with hypocalcemia), and immunological disorders because although frequency of DGS is high, few patients with a confirmed diagnosis are followed up. PMID:21049214

  7. Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

    PubMed

    Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

    2015-01-01

    Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

  8. Development and characterization of novel 8-plex DiLeu isobaric labels for quantitative proteomics and peptidomics

    PubMed Central

    Frost, Dustin C.; Greer, Tyler; Xiang, Feng; Liang, Zhidan; Li, Lingjun

    2015-01-01

    Rationale Relative quantification of proteins via their enzymatically digested peptide products determines disease biomarker candidate lists in discovery studies. Isobaric label-based strategies using TMT and iTRAQ allow for up to 10 samples to be multiplexed in one experiment, but their expense limits their use. The demand for cost-effective tagging reagents capable of multiplexing many samples led us to develop an 8-plex version of our isobaric labeling reagent, DiLeu. Methods The original 4-plex DiLeu reagent was extended to an 8-plex set by coupling isotopic variants of dimethylated leucine to an alanine balance group designed to offset the increasing mass of the label’s reporter group. Tryptic peptides from a single protein digest, a protein mixture digest, and Saccharomyces cerevisiae lysate digest were labeled with 8-plex DiLeu and analyzed via nanoLC-MS2 on a Q-Exactive Orbitrap mass spectrometer. Characteristics of 8-plex DiLeu-labeled peptides, including quantitative accuracy and fragmentation, were examined. Results An 8-plex set of DiLeu reagents with 1 Da-spaced reporters was synthesized at a yield of 36%. The average cost to label eight 100 μg peptide samples was calculated to be approximately $15. Normalized collision energy tests on the Q-Exactive revealed that a higher-energy collisional dissociation value of 27 generated the optimum number of high-quality spectral matches. Relative quantification of DiLeu-labeled peptides yielded normalized median ratios accurate to within 12% of their expected values. Conclusions Cost-effective 8-plex DiLeu reagents can be synthesized and applied to relative peptide and protein quantification. These labels increase the multiplexing capacity of our previous 4-plex implementation without requiring high-resolution instrumentation to resolve reporter ion signals. PMID:25981542

  9. Oxidation of 2,6-di-tert-butyl-4-methylphenol. The structure of C14H22O3

    USGS Publications Warehouse

    Yohe, G.R.; Dunbar, J.E.; Lansford, M.W.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.

    1959-01-01

    The acidic compound C14H22O3, previously reported without assignment of structure as an oxidation product of 2,6-di-tert-butyl-4-methylphenol, is now believed to be DL-trans-5,6-di-tert-butyl-2-hydroxy-1,4-diketo-2-cyclohexene (I). Chemical properties are described and infrared spectra are presented in support of this structure. This structure is of interest in relation to the problem of the existence of o-di-tert-alkylbenzene derivatives. The relatively easy racemization of optically active I suggests that its completely enolized form, 5,6-di-tert-butyl-1,2,4-trihydroxybenzene, is capable of transitory existence.

  10. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

  11. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6...-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92-343 and P-92-344) are subject to...

  12. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

  13. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

  14. 40 CFR 721.9730 - 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,3,5-Triazin-2-amine, 4-di-meth-yl-a... New Uses for Specific Chemical Substances § 721.9730 1,3,5-Triazin-2-amine, 4-di-meth-yl-a-mino-6... substances generically identified as 1,3,5-triazin-2-amine, 4-di-meth-yl-a-mino-6-substituted- (PMN Nos. P-92...

  15. DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

    PubMed Central

    Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

    2014-01-01

    Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

  16. Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

    PubMed Central

    Bui, Tuan V; Stifani, Nicolas; Akay, Turgay; Brownstone, Robert M

    2016-01-01

    The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery. DOI: http://dx.doi.org/10.7554/eLife.21715.001 PMID:27977000

  17. Big Data from Europe's Natural Science Collections through DiSSCo

    NASA Astrophysics Data System (ADS)

    Addink, Wouter; Koureas, Dimitris; Casino, Ana

    2017-04-01

    DiSSCo, a Distributed System of Scientific Collections, will be a Research Infrastructure delivering big data describing the history of Planet Earth. Approximately 1.5 billion biological and geological specimens, representing the last 300 years of scientific study on the natural world, reside in collections all over Europe. These span 4.5 billion years of history, from the formation of the solar system to the present day. In the European landscape of environmental Research Infrastructures, different projects and landmarks describe services that aim at aggregating, monitoring, analysing and modelling geo-diversity information. The effectiveness of these services, however, is based on the quality and availability of primary reference data that today is scattered and uncomplete. DiSSCo provides the required bio-geographical, taxonomic and species trait data at the level of precision and accuracy required to enable and speed up research for the rapidly growing seven grand societal challenges that are priorities of the Europe 2020 strategy. DiSSCo enables better connections between collection data and observations in biodiversity observation networks, such as EU BON and GEOBON. This supports research areas like long term ecological research, for which the continuity and long term research is a strength of biological collections.

  18. DI Diesel Performance and Emissions Models

    DTIC Science & Technology

    2003-06-11

    Skeletal mechanism for NOx chemistry in diesel engines ,” SAE Paper 981450, 1998 SAE Transactions, Vol. 107, Sect. 4, J. Fuels and... mechanism for NOx chemistry proposed by Mellor et al. (1998a) is incorporated in an engine simulation code. The two-zone model, also proposed by Mellor et...34Dynamic Application of a Skeletal Mechanism for DI Diesel NOx Emissions," SAE Paper 2001-01-1984, SAE Trans., J. Fuels & Lubricants,

  19. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

    PubMed Central

    Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs

    2017-01-01

    ABSTRACT The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli. This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. PMID:28928205

  20. [Un processo che può gettare luce sulla cosiddetta 'paura di sé' nel disturbo ossessivo-compulsivo: l'Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni].

    PubMed

    Mannino, Gherardo; Guerini, Rossella

    2018-01-01

    RIASSUNTO. Al fine di comprendere meglio la psicopatologia del disturbo ossessivo-compulsivo (DOC), in anni recenti è stata prestata una crescente attenzione alla cosiddetta "paura di sé" (fear of self), vale a dire la paura che le persone con DOC nutrono di ospitare dentro di sé aspetti inaccettabili. Tuttavia, l'esatta dinamica di questo fenomeno ancora non è chiara: di conseguenza, allo scopo di delucidarla meglio, sarà qui descritto uno specifico processo psicologico denominato Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni (IRMI). Quando un paziente con DOC valuta in qualche modo come inaccettabile una propria esperienza interna (pensieri, emozioni, immagini mentali, ecc.) o un proprio comportamento, identificherà retrospettivamente le presunte motivazioni/inclinazioni negative che sarebbero state all'origine di quell'esperienza o comportamento. L'IRMI non solo aiuta a comprendere meglio il fenomeno della "paura di sé", ma possiede anche importanti implicazioni per la terapia.

  1. PLCs, DI, & RTI: A Tapestry for School Change

    ERIC Educational Resources Information Center

    Stoehr, Judy; Banks, Maria; Allen, Linda

    2011-01-01

    Rather than buying individual books about professional learning communities (PLCs), differentiated instruction (DI), and Response to Intervention (RTI), invest wisely in one resource that synthesizes all three. The text uses a tapestry analogy to weave together these critical topics to form a comprehensive framework for achieving continuous school…

  2. Experiences on the development of a Community Based Early Warning System for mountain risks in northern Italy

    NASA Astrophysics Data System (ADS)

    Garcia, Carolina; Sterlacchini, Simone; de Amicis, Mattia; Fontana, Michele; Trozzi, Arianna; Frigerio, Ivan

    2010-05-01

    In the framework of the European project Mountain Risks (http://mountain-risks.eu/), one of the projects currently developed is a methodology to integrate risk management and evacuation emergency plans, focused on prevention as a key element for disaster risk reduction, applied in the Mountain Community Valtellina of Tirano, an area recurrently affected by several mountain hazards. Taking into account the actual state of disaster risk reduction initiatives in the study area, including the existence of a real time emergency plan based on GIS (Geographical Information Systems), DSS (Decision Support Systems), and ICT (Information & Communication Technology), but knowing the lack involvement of the general community in any of the preparation activities developed until the present and the lack of divulgation of the current emergency plan, it was decided that the methodology that could better adapt to the actual conditions of the study area would be a non structural Community Based Early Warning System (CBEWS). A CBEWS has been recognized by institutions as the UN and the INSDR, as an effective and important strategy for disaster risk reduction. This strategy is broadly used especially in developing countries and has proved its effectiveness in many disasters crisis all over the world. In spite of that, possibly for political and social reasons, there are really few applications of CBEWS in developed countries which has made the elaboration of this research project a particularly difficult process due to the lack of previous references with similar conditions to the one in the study area. Difficulties related to any multidisciplinary work which also involves the general community have been faced during the development of the project such as the differences in language (both the technical jargon of the different disciplines and the native language), time restrictions, the process of learning and adapting to different social structures, the process of contacting several

  3. AraC-like transcriptional activator CuxR binds c-di-GMP by a PilZ-like mechanism to regulate extracellular polysaccharide production

    PubMed Central

    Schäper, Simon; Steinchen, Wieland; Krol, Elizaveta; Altegoer, Florian; Skotnicka, Dorota; Bange, Gert; Becker, Anke

    2017-01-01

    Cyclic dimeric GMP (c-di-GMP) has emerged as a key regulatory player in the transition between planktonic and sedentary biofilm-associated bacterial lifestyles. It controls a multitude of processes including production of extracellular polysaccharides (EPSs). The PilZ domain, consisting of an N-terminal “RxxxR” motif and a β-barrel domain, represents a prototype c-di-GMP receptor. We identified a class of c-di-GMP–responsive proteins, represented by the AraC-like transcription factor CuxR in plant symbiotic α-proteobacteria. In Sinorhizobium meliloti, CuxR stimulates transcription of an EPS biosynthesis gene cluster at elevated c-di-GMP levels. CuxR consists of a Cupin domain, a helical hairpin, and bipartite helix-turn-helix motif. Although unrelated in sequence, the mode of c-di-GMP binding to CuxR is highly reminiscent to that of PilZ domains. c-di-GMP interacts with a conserved N-terminal RxxxR motif and the Cupin domain, thereby promoting CuxR dimerization and DNA binding. We unravel structure and mechanism of a previously unrecognized c-di-GMP–responsive transcription factor and provide insights into the molecular evolution of c-di-GMP binding to proteins. PMID:28559336

  4. c-di-GMP can form remarkably stable G-quadruplexes at physiological conditions in the presence of some planar intercalators.

    PubMed

    Nakayama, Shizuka; Kelsey, Ilana; Wang, Jingxin; Sintim, Herman O

    2011-04-28

    The ubiquitous bacterial biofilm regulator, c-di-GMP can form G-quadruplexes at physiological conditions in the presence of some aromatic compounds, such as acriflavine and proflavine. The fluorescence of these compounds is quenched upon c-di-GMP binding and some of the formed c-di-GMP G-quadruplexes are stable even at 75 °C. © The Royal Society of Chemistry 2011

  5. Manufacture of Fior di Latte cheese by incorporation of probiotic lactobacilli.

    PubMed

    Minervini, F; Siragusa, S; Faccia, M; Dal Bello, F; Gobbetti, M; De Angelis, M

    2012-02-01

    This work aimed to select heat-resistant probiotic lactobacilli to be added to Fior di Latte (high-moisture cow milk Mozzarella) cheese. First, 18 probiotic strains belonging to Lactobacillus casei, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus reuteri were screened. Resistance to heating (65 or 55°C for 10 min) varied markedly between strains. Adaptation at 42°C for 10 min increased the heat resistance at 55°C for 10 min of all probiotic lactobacilli. Heat-adapted L. delbrueckii ssp. bulgaricus SP5 (decimal reduction time at 55°C of 227.4 min) and L. paracasei BGP1 (decimal reduction time at 55°C of 40.8 min) showed the highest survival under heat conditions that mimicked the stretching of the curd and were used for the manufacture of Fior di Latte cheese. Two technology options were chosen: chemical (addition of lactic acid to milk) or biological (Streptococcus thermophilus as starter culture) acidification with or without addition of probiotics. As determined by random amplified polymorphic DNA-PCR and 16S rRNA gene analyses, the cell density of L. delbrueckii ssp. bulgaricus SP5 and L. paracasei BGP1 in chemically or biologically acidified Fior di Latte cheese was approximately 8.0 log(10)cfu/g. Microbiological, compositional, biochemical, and sensory analyses (panel test by 30 untrained judges) showed that the use of L. delbrueckii ssp. bulgaricus SP5 and L. paracasei BGP1 enhanced flavor formation and shelf-life of Fior di Latte cheeses. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  6. Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions.

    PubMed

    Eison, A S; Iversen, S D; Sandberg, B E; Watson, S P; Hanley, M R; Iversen, L L

    1982-01-08

    A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.

  7. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-12-08

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The background visual shows the biosphere with data from a NASA satellite instrument called the Sea-viewing Wide Field-of-View Sensor (SeaWiFS). svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=10704 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  8. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-12-08

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The visual shows Hurricane Sandy. The visual uses data from Goddard Earth Observing System Model, Version 5 (GEOS-5) to simulate surface wind speeds across the Atlantic during Sandy’s lifecycle. svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=30465 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  9. 10 Tips for Turning DI Theory into Practice

    ERIC Educational Resources Information Center

    Ducey, Melissa N.; Key, Shirley

    2009-01-01

    At the core of differentiated instruction (DI) is the belief that because all children are different, their learning needs and abilities are different, and therefore must be approached differently. Differentiating instruction allows teachers to meet the students where they are academically and bring them forward. Although one continues to grow in…

  10. Efficacy of the Direct Instruction Language for Learning (DI-LL) Program to Promote Expressive and Receptive Language in Children with Autism Spectrum Disorder

    DTIC Science & Technology

    2017-07-01

    spectrum disorder. However, DI-LL has not yet been carefully studied in children with ASD. As in ABA, the DI-LL curriculum incorporates immediate... study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of DI-LL in a six-month randomized trial in...fading. To date, there is only one small study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of

  11. Functional characterization of dI6 interneurons in the neonatal mouse spinal cord.

    PubMed

    Dyck, Jason; Lanuza, Guillermo M; Gosgnach, Simon

    2012-06-01

    Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior.

  12. Functional characterization of dI6 interneurons in the neonatal mouse spinal cord

    PubMed Central

    Dyck, Jason; Lanuza, Guillermo M.

    2012-01-01

    Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior. PMID:22442567

  13. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

    PubMed

    Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

    2017-09-19

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several

  14. Supra­molecular inter­actions in 2,6-di­amino-4-chloro­pyrimidin-1-ium 5-chloro­salicylate and bis­(2,6-di­amino-4-chloro­pyrimidin-1-ium) naphthalene-1,5-di­sulfonate

    PubMed Central

    Swinton Darious, Robert; Thomas Muthiah, Packianathan

    2018-01-01

    The crystals of two new salts, 2,6-di­amino-4-chloro­pyrimidin-1-ium 5-chloro­salicylate, C4H6ClN4 +·C7H4ClO3 −, (I), and bis­(2,6-di­amino-4-chloro­pyrimidin-1-ium) naphthalene-1,5-di-sulfonate, 2C4H6ClN4 +·C10H6O6S2 2−, (II), have been synthesized and characterized by single-crystal X-ray diffraction. In both compounds, the N atom of the pyrimidine group in between the amino substituents is protonated and the pyrimidinium cation forms a pair of N—H⋯O hydrogen bonds with the carboxyl­ate/sulfonate ion, leading to a robust R 2 2(8) motif (supra­molecular heterosynthon). In compound (I), a self-complementary base pairing involving the other pyrimidinium ring nitro­gen atom and one of the amino groups via a pair of N—H⋯N hydrogen bonds [R 2 2(8) homosynthon] is also present. In compound (II), the crystallographic inversion centre coincides with the inversion centre of the naphthalene-1,5-di­sulfonate ion and all the sulfonate O atoms are hydrogen-bond acceptors, generating fused-ring motifs and a quadruple DDAA array. A halogen-bond (Cl⋯Cl) inter­action is present in (I) with a distance and angle of 3.3505 (12) Å and 151.37 (10)°, respectively. In addition, a C—Cl⋯π inter­action and a π–π inter­action in (I) and a π–π inter­action in (II) further stabilize these crystal structures. PMID:29850062

  15. Mapping training needs for dissemination and implementation research: lessons from a synthesis of existing D&I research training programs.

    PubMed

    Chambers, David A; Proctor, Enola K; Brownson, Ross C; Straus, Sharon E

    2017-09-01

    With recent growth in the field of dissemination and implementation (D&I) research, multiple training programs have been developed to build capacity, including summer training institutes, graduate courses, degree programs, workshops, and conferences. While opportunities for D&I research training have expanded, course organizers acknowledge that available slots are insufficient to meet demand within the scientific and practitioner community. In addition, individual programs have struggled to best fit various needs of trainees, sometimes splitting coursework between specific D&I content and more introductory grant writing material. This article, stemming from a 2013 NIH workshop, reviews experiences across multiple training programs to align training needs, career stage and role, and availability of programs. We briefly review D&I needs and opportunities by career stage and role, discuss variations among existing training programs in format, mentoring relationships, and other characteristics, identify challenges of mapping needs of trainees to programs, and present recommendations for future D&I research training.

  16. Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella

    PubMed Central

    Solano, Cristina; García, Begoña; Latasa, Cristina; Toledo-Arana, Alejandro; Zorraquino, Violeta; Valle, Jaione; Casals, Joan; Pedroso, Enrique; Lasa, Iñigo

    2009-01-01

    Bacteria have developed an exclusive signal transduction system involving multiple diguanylate cyclase and phosphodiesterase domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) that modulate the levels of the same diffusible molecule, 3′-5′-cyclic diguanylic acid (c-di-GMP), to transmit signals and obtain specific cellular responses. Current knowledge about c-di-GMP signaling has been inferred mainly from the analysis of recombinant bacteria that either lack or overproduce individual members of the pathway, without addressing potential compensatory effects or interferences between them. Here, we dissected c-di-GMP signaling by constructing a Salmonella strain lacking all GGDEF-domain proteins and then producing derivatives, each restoring 1 protein. Our analysis showed that most GGDEF proteins are constitutively expressed and that their expression levels are not interdependent. Complete deletion of genes encoding GGDEF-domain proteins abrogated virulence, motility, long-term survival, and cellulose and fimbriae synthesis. Separate restoration revealed that 4 proteins from Salmonella and 1 from Yersinia pestis exclusively restored cellulose synthesis in a c-di-GMP–dependent manner, indicating that c-di-GMP produced by different GGDEF proteins can activate the same target. However, the restored strain containing the STM4551-encoding gene recovered all other phenotypes by means of gene expression modulation independently of c-di-GMP. Specifically, fimbriae synthesis and virulence were recovered through regulation of csgD and the plasmid-encoded spvAB mRNA levels, respectively. This study provides evidence that the regulation of the GGDEF-domain proteins network occurs at 2 levels: a level that strictly requires c-di-GMP to control enzymatic activities directly, restricted to cellulose synthesis in our experimental conditions, and another that involves gene regulation for which c-di-GMP synthesis can be dispensable. PMID:19416883

  17. Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5.

    PubMed

    Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin

    2016-05-01

    The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical diagnosis. Confirmatory factor analyses found a better fit against a DSM-5 model than a DSM-IV-TR model of ASD. Exploration of the content validity of the 3Di-sv for the DSM-5 revealed some construct underrepresentation, therefore we obtained data from a panel of 3Di-trained clinicians from ASD-specialized centers to recommend items to fill these gaps. Taken together, the 3Di-sv provides a solid basis to create a similar instrument suitable for DSM-5. Concrete recommendations are provided to improve DSM-5 compatibility.

  18. Analysis of tomographic mineralogical data using YaDiV—Overview and practical case study

    NASA Astrophysics Data System (ADS)

    Friese, Karl-Ingo; Cichy, Sarah B.; Wolter, Franz-Erich; Botcharnikov, Roman E.

    2013-07-01

    We introduce the 3D-segmentation and -visualization software YaDiV to the mineralogical application of rock texture analysis. YaDiV has been originally designed to process medical DICOM datasets. But due to software advancements and additional plugins, this open-source software can now be easily used for the fast quantitative morphological characterization of geological objects from tomographic datasets. In this paper, we give a summary of YaDiV's features and demonstrate the advantages of 3D-stereographic visualization and the accuracy of 3D-segmentation for the analysis of geological samples. For this purpose, we present a virtual and a real use case (here: experimentally crystallized and vesiculated magmatic rocks, corresponding to the composition of the 1991-1995 Unzen eruption, Japan). Especially the spacial representation of structures in YaDiV allows an immediate, intuitive understanding of the 3D-structures, which may not become clear by only looking on 2D-images. We compare our results of object number density calculations with the established classical stereological 3D-correction methods for 2D-images and show that it was possible to achieve a seriously higher quality and accuracy. The methods described in this paper are not dependent on the nature of the object. The fact, that YaDiV is open-source and users with programming skills can create new plugins themselves, may allow this platform to become applicable to a variety of geological scenarios from the analysis of textures in tiny rock samples to the interpretation of global geophysical data, as long as the data are provided in tomographic form.

  19. Descriptive sensory analysis of Aceto Balsamico Tradizionale di Modena DOP and Aceto Balsamico Tradizionale di Reggio Emilia DOP.

    PubMed

    Zeppa, Giuseppe; Gambigliani Zoccoli, Mario; Nasi, Enrico; Masini, Giovanni; Meglioli, Giuseppe; Zappino, Matteo

    2013-12-01

    Aceto Balsamico Tradizionale (ABT) is a typical Italian vinegar available in two different forms: Aceto Balsamico Tradizionale di Modena DOP (ABTM) and Aceto Balsamico Tradizionale di Reggio Emilia DOP (ABTRE). ABT is obtained by alcoholic fermentation and acetic bio-oxidation of cooked grape must and aged at least 12 years in wooden casks and is known and sold around the world. Despite this widespread recognition, data on sensory characteristics of these products are very scarce. Therefore a descriptive analysis was conducted to define a lexicon for the ABT sensory profile and to create a simple, stable and reproducible synthetic ABT for training panellists. A lexicon of 20 sensory parameters was defined and validated and a synthetic ABT was prepared as standard reference. Simple standards for panellist training were also defined and the sensory profiles of ABTM and ABTRE were obtained. The obtained results confirm that descriptive analysis can be used for the sensory characterisation of ABT and that the sensory profiles of ABTM and ABTRE are very different. Furthermore, the results demonstrate that a lexicon and proper standard references are essential for describing the sensory qualities of ABT both for technical purposes and to protect the product from commercial fraud. © 2013 Society of Chemical Industry.

  20. Braccio di Ferro: a new haptic workstation for neuromotor rehabilitation.

    PubMed

    Casadio, Maura; Sanguineti, Vittorio; Morasso, Pietro G; Arrichiello, Vincenzo

    2006-01-01

    This technical note describes a new robotic workstation for neurological rehabilitation, shortly named Braccio di Ferro. It has been designed by having in mind the range of forces and the frequency bandwidth that characterize the interaction between a patient and a physical therapist, as well as a number of requirements that we think are essential for allowing a natural haptic interaction: back-driveability, very low friction and inertia, mechanical robustness, the possibility to operate in different planes, and an open software environment, which allows the operator to add new functionalities and design personalized rehabilitation protocols. Braccio di Ferro is an open system and, in the spirit of open source design, is intended to foster the dissemination of robot therapy. Moreover, its combination of features is not present in commercially available systems.

  1. Detection of intramyocardially injected DiR-labeled mesenchymal stem cells by optical and optoacoustic tomography.

    PubMed

    Berninger, Markus T; Mohajerani, Pouyan; Wildgruber, Moritz; Beziere, Nicolas; Kimm, Melanie A; Ma, Xiaopeng; Haller, Bernhard; Fleming, Megan J; Vogt, Stephan; Anton, Martina; Imhoff, Andreas B; Ntziachristos, Vasilis; Meier, Reinhard; Henning, Tobias D

    2017-06-01

    The distribution of intramyocardially injected rabbit MSCs, labeled with the near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbo-cyanine-iodide (DiR) using hybrid Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) and Multispectral Optoacoustic Tomography (MSOT) imaging technologies, was investigated. Viability and induction of apoptosis of DiR labeled MSCs were assessed by XTT- and Caspase-3/-7-testing in vitro . 2 × 10 6 , 2 × 10 5 and 2 × 10 4 MSCs labeled with 5 and 10 μg DiR/ml were injected into fresh frozen rabbit hearts. FMT-XCT, MSOT and fluorescence cryosection imaging were performed. Concentrations up to 10 μg DiR/ml did not cause apoptosis in vitro (p > 0.05). FMT and MSOT imaging of labeled MSCs led to a strong signal. The imaging modalities highlighted a difference in cell distribution and concentration correlated to the number of injected cells. Ex-vivo cryosectioning confirmed the molecular fluorescence signal. FMT and MSOT are sensitive imaging techniques offering high-anatomic resolution in terms of detection and distribution of intramyocardially injected stem cells in a rabbit model.

  2. Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis.

    PubMed

    Ren, Gai-Xian; Fan, Sai; Guo, Xiao-Peng; Chen, Shiyun; Sun, Yi-Cheng

    2016-01-01

    Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in Y. pestis. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments.

  3. URINARY METABOLITES OF DI-N-OCTYL PHTHALATE IN RATS

    EPA Science Inventory

    Di-n-octyl phthalate (DnOP) is a plasticizer used in polyvinyl chloride plastics, cellulose esters, and polystyrene resins. The metabolism of DnOP results in the hydrolysis of one ester linkage to produce mono-n-octyl phthalate (MnOP), which subsequently metabolizes to form oxida...

  4. LtmA, a novel cyclic di-GMP-responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis

    PubMed Central

    Li, Weihui; He, Zheng-Guo

    2012-01-01

    In a bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport and metabolism genes. c-di-GMP could enhance the ability of Ms6479 to bind to its target DNA. Furthermore, our results establish Ms6479 as a global activator that positively regulates the expression of diverse target genes. Overexpression of Ms6479 in M. smegmatis significantly reduced the permeability of the cell wall to crystal violet and increased mycobacterial resistance to anti-tuberculosis antibiotics. Interestingly, Ms6479 lacks the previously reported c-di-GMP binding motifs. Our findings introduce Ms6479 (here designated LtmA for lipid transport and metabolism activator) as a new c-di-GMP-responsive regulator. PMID:23047950

  5. Measurement of threshold temperature effects in dissociative electron attachment to HI and DI

    NASA Technical Reports Server (NTRS)

    Chutjian, A.; Alajajian, S. H.; Man, K.-F.

    1990-01-01

    From accurate spectroscopic constants it is found that the thermal dissociative-attachment process (DA) in DI should be exothermic only for rotational levels J greater than 8 in v = O. Here, measurement of an enhancement of DA with rotational temperature T in the range 298-468 K is reported. The effect is easily accounted for by the increase in total fractional population of excited J levels in DI relative to HI. The effect affords a rotational analog to the use of vibrationally excited molecules (e.g., HCl) in a plasma to control electron conduction.

  6. Probing Electroweak Phase Transition via Enhanced Di-Higgs Production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carena, Marcela; Liu, Zhen; Riembau, Marc

    2018-01-02

    We consider a singlet extension of the Standard Model (SM) with a spontaneousmore » $$Z_2$$ breaking and study the gluon-gluon fusion production of the heavy scalar, with subsequent decay into a pair of SM-like Higgs bosons. We find that an on-shell interference effect can notably enhance the resonant di-Higgs production rate up to 40\\%. In addition, consistently taking into account both the on-shell and off-shell interference effects between the heavy scalar and the SM di-Higgs diagrams significantly improves the HL-LHC and HE-LHC reach in this channel. As an example, within an effective field theory analysis in an explicitly $$Z_2$$ breaking scenario, we further discuss the potential to probe the parameter region compatible with a first order electroweak phase transition. Our analysis is applicable for general potentials of the singlet extension of the SM as well as for more general resonance searches.« less

  7. Probing Electroweak Phase Transition via Enhanced Di-Higgs Production

    DOE PAGES

    Carena, Marcela; Liu, Zhen; Riembau, Marc

    2018-05-24

    We consider a singlet extension of the Standard Model (SM) with a spontaneousmore » $$Z_2$$ breaking and study the gluon-gluon fusion production of the heavy scalar, with subsequent decay into a pair of SM-like Higgs bosons. We find that an on-shell interference effect can notably enhance the resonant di-Higgs production rate up to 40\\%. In addition, consistently taking into account both the on-shell and off-shell interference effects between the heavy scalar and the SM di-Higgs diagrams significantly improves the HL-LHC and HE-LHC reach in this channel. As an example, within an effective field theory analysis in an explicitly $$Z_2$$ breaking scenario, we further discuss the potential to probe the parameter region compatible with a first order electroweak phase transition. Our analysis is applicable for general potentials of the singlet extension of the SM as well as for more general resonance searches.« less

  8. Leonardo DiCaprio visited Goddard Saturday to discuss Earth science with Piers Sellers

    NASA Image and Video Library

    2017-12-08

    Academy Award®- winning actor and environmental activist Leonardo DiCaprio visited NASA’s Goddard Space Flight Center in Greenbelt, Maryland on Saturday, April 23, 2016. During his visit, Mr. DiCaprio interviewed Dr. Piers Sellers, an Earth scientist, former astronaut and current deputy director of Goddard’s Sciences and Exploration Directorate. The two discussed the different missions NASA has underway to study changes in the Earth’s atmosphere, water and land masses for a climate change documentary that Mr. DiCaprio has in production. Using a wall-size, high-definition display system that shows visual representations based on actual science data, Mr. DiCaprio and Dr. Sellers discussed data results from NASA’s fleet of satellites in Earth’s orbit. The background image showing global sea surface circulation colored by temperature where reds are warm areas (32 degrees Celsius) and blues are cold regions (0 degrees Celsius). The data used for this visual is a joint MIT/JPL project called Estimating the Circulation and Climate of the Ocean, Phase II (ECCO2). For more info on this visual, svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=3912 During his visit, Mr. DiCaprio also visited the facility holding NASA’s James Webb Space Telescope that is being developed as a large infrared telescope with a 6.5-meter primary mirror. The telescope will be launched on an Ariane 5 rocket from French Guiana in October of 2018, and will be a premier observatory of the next decade, serving thousands of astronomers worldwide. Credit: NASA/Goddard/Rebecca Roth NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  9. 40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and Silicones, di-Me, Me... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as Siloxanes and Silicones...

  10. 40 CFR 721.10482 - Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and Silicones, di-Me, Me... Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with silica. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as Siloxanes and Silicones...

  11. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal..., reaction products with polyethylene-polypropylene glycol Bu glycidal ether. (a) Chemical substance and... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

  12. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene glycol Bu glycidal..., reaction products with polyethylene-polypropylene glycol Bu glycidal ether. (a) Chemical substance and... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

  13. Difference gel electrophoresis (DiGE) identifies differentially expressed proteins in endoscopically-collected pancreatic fluid

    PubMed Central

    Paulo, Joao A.; Lee, Linda S.; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

    2012-01-01

    Alterations in the pancreatic fluid proteome of individuals with chronic pancreatitis may offer insights into the development and progression of the disease. The endoscopic pancreas function test (ePFT) can safely collect large volumes of pancreatic fluid that are potentially amenable to proteomic analyses using difference gel electrophoresis (DiGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pancreatic fluid was collected endoscopically using the ePFT method following secretin stimulation from three individuals with severe chronic pancreatitis and three chronic abdominal pain controls. The fluid was processed to minimize protein degradation and the protein profiles of each cohort, as determined by DiGE and LC-MS/MS, were compared. This DiGE-LC-MS/MS analysis reveals proteins that are differentially expressed in chronic pancreatitis compared to chronic abdominal pain controls. Proteins with higher abundance in pancreatic fluid from chronic pancreatitis individuals include: actin, desmoplankin, alpha-1-antitrypsin, SNC73, and serotransferrin. Those of relatively lower abundance include carboxypeptidase B, lipase, alpha-1-antichymotrypsin, alpha-2-macroglobulin, Arp2/3 subunit 4, glyceraldehyde-3-phosphate dehydrogenase, and protein disulfide isomerase. Endoscopic collection (ePFT) in tandem with DiGE-LC-MS/MS is a suitable approach for pancreatic fluid proteome analysis, however, further optimization of our protocol, as outlined herein, may improve proteome coverage in future analyses. PMID:21792986

  14. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tetraethylene glycol di-(2-ethylhexoate). 178.3940 Section 178.3940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  15. Migration of cyclo-diBA from coatings into canned food: method of analysis, concentration determined in a survey and in silico hazard profiling.

    PubMed

    Biedermann, Sandra; Zurfluh, Michael; Grob, Koni; Vedani, Angelo; Brüschweiler, Beat J

    2013-08-01

    Cyclo-diBA, the cyclic product formed from bisphenol A and bisphenol A diglycidyl ether during production of epoxy resins, was measured in canned food using reversed phase HPLC with fluorescence detection. Half (9 of 17) of the samples of canned fish in oil collected in April 2010 contained cyclo-diBA with an average concentration of 1025 μg/kg and a maximum of 1980 μg/kg. In September 2012, cyclo-diBA was detectable (>25 μg/kg) in merely 13 from 44 such products; the average concentration in these was 807 μg/kg and the maximum now reached 2640 μg/kg. Fish in brine contained far less cyclo-diBA. The majority of the canned meat products contained cyclo-diBA at a mean concentration of 477 μg/kg and a maximum of 1050 μg/kg. All prepared meals, such as ravioli or soups, contained cyclo-diBA, with a mean at 287 μg/kg. In canned tomatoes, peas and other vegetables in water or fruits in syrup, no cyclo-diBA was detected (<25 μg/kg). Since no experimental toxicity data are available except for its cytotoxicity, an in silico hazard profiling was performed. Cyclo-diBA seems to be stable and of low reactivity. There is indication for considerable oral bioavailability and for the potential to accumulate in the human body. Cyclo-diBA can be metabolized into cyclic and acyclic compounds. Based on SAR assessment for cyclo-diBA and read-across from BADGE to linear cyclo-diBA metabolites, genotoxic effects are improbable. Specific binding of cyclo-diBA to nuclear receptors, such as ERβ, can be predicted, indicating a potential endocrine-disrupting potency. The limit by the EFSA guidelines of 50 μg/person/d for compounds shown not to be genotoxic as well as the TTC-based Cramer structural class III value of 90 μg/person/d could be exceeded several fold by high consumers of canned fish in oil with high brand loyalty. As a consequence, risk reduction measures were taken. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Pharmacokinetic Study of Di-Phenyl-Di-(2,4-Difluobenzohydroxamato)Tin(IV): Novel Metal-Based Complex with Promising Antitumor Potential

    PubMed Central

    Li, Yunlan; Gao, Zhuyan; Guo, Pu; Li, Qingshan

    2012-01-01

    Di-phenyl-di-(2,4-difluobenzohydroxamato)tin(IV)(DPDFT), a new metal-based arylhydroxamate antitumor complex, showed high in vivo and in vitro antitumor activity with relative low toxicity, but no data was reported regarding its pharmacokinetics and dependent toxicity. In this paper, a rapid, sensitive, and reproducible HPLC method in vivo using Diamonsil ODS column with a mixture of methanol and phosphoric acid in water (30 : 70, V/V, pH 3.0) as mobile phase was developed and validated for the determination of DPDFT. The plasma was deproteinized with methanol that contained acetanilide as the internal standard (I.S.). The photodiode array detector was set at a wavelength of 228 nm at room temperature and a linear curve over the concentration range 0.1~25 μg·mL−1 (r = 0.9993) was obtained. The method was used to determine the concentration-time profiles for DPDFT in the plasma after single intravenous administration with doses of 5, 10, 15 mg·kg−1 to rats. The pharmacokinetics parameter calculations and modeling were carried out using the 3p97 software. The results showed that the concentration-time curves of DPDFT in rat plasma could be fitted to two-compartment model. PMID:22400014

  17. Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease.

    PubMed

    Paul, Jodi R; Munir, Hira A; van Groen, Thomas; Gamble, Karen L

    2018-06-01

    Disruption of circadian rhythms is commonly reported in individuals with Alzheimer's disease (AD). Neurons in the primary circadian pacemaker, the suprachiasmatic nucleus (SCN), exhibit daily rhythms in spontaneous neuronal activity which are important for maintaining circadian behavioral rhythms. Disruption of SCN neuronal activity has been reported in animal models of other neurodegenerative disorders; however, the effect of AD on SCN neurophysiology remains unknown. In this study we examined circadian behavioral and electrophysiological changes in a mouse model of AD, using male mice from the Tg-SwDI line which expresses human amyloid precursor protein with the familial Swedish (K670N/M671L), Dutch (E693Q), Iowa (D694N) mutations. The free-running period of wheel-running behavior was significantly shorter in Tg-SwDI mice compared to wild-type (WT) controls at all ages examined (3, 6, and 10 months). At the SCN level, the day/night difference in spike rate was significantly dampened in 6-8 month-old Tg-SwDI mice, with decreased AP firing during the day and an increase in neuronal activity at night. The dampening of SCN excitability rhythms in Tg-SwDI mice was not associated with changes in input resistance, resting membrane potential, or action potential afterhyperpolarization amplitude; however, SCN neurons from Tg-SwDI mice had significantly reduced A-type potassium current (I A ) during the day compared to WT cells. Taken together, these results provide the first evidence of SCN neurophysiological disruption in a mouse model of AD, and highlight I A as a potential target for AD treatment strategies in the future. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Focusing the lens of language experience: perception of Ma'di stops by Greek and English bilinguals and monolinguals.

    PubMed

    Antoniou, Mark; Best, Catherine T; Tyler, Michael D

    2013-04-01

    Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek-English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals' discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group.

  19. ProDiGe: Prioritization Of Disease Genes with multitask machine learning from positive and unlabeled examples

    PubMed Central

    2011-01-01

    Background Elucidating the genetic basis of human diseases is a central goal of genetics and molecular biology. While traditional linkage analysis and modern high-throughput techniques often provide long lists of tens or hundreds of disease gene candidates, the identification of disease genes among the candidates remains time-consuming and expensive. Efficient computational methods are therefore needed to prioritize genes within the list of candidates, by exploiting the wealth of information available about the genes in various databases. Results We propose ProDiGe, a novel algorithm for Prioritization of Disease Genes. ProDiGe implements a novel machine learning strategy based on learning from positive and unlabeled examples, which allows to integrate various sources of information about the genes, to share information about known disease genes across diseases, and to perform genome-wide searches for new disease genes. Experiments on real data show that ProDiGe outperforms state-of-the-art methods for the prioritization of genes in human diseases. Conclusions ProDiGe implements a new machine learning paradigm for gene prioritization, which could help the identification of new disease genes. It is freely available at http://cbio.ensmp.fr/prodige. PMID:21977986

  20. Interlayer neurones in the rat superior colliculus: a tracer study using Dil/Di-ASP.

    PubMed

    Hilbig, H; Schierwagen, A

    1994-01-12

    Five different populations of interlayer neurones (ILNs) can be described after DiI/Di-ASP tracing in rat superior colliculus (SC). All of these labelled neurones preferentially lay in the rostro-medial part of the SC. Most of them are located in the stratum opticum and in the stratum griseum superficiale. Our results indicate that ILNs represent a minority of neurones in the superficial layers but may constitute a substantial population of neurones in the stratum opticum connecting the visual and the multimodal collicular layers.

  1. The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS.

    PubMed

    Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C; Greaves-Lord, Kirstin

    2015-06-01

    The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3 Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3 Di and ADOS, in 186 children referred to six mental health centers. The parent report showed excellent correspondence to an ASD classification according to the 3 Di and both the 3 Di and ADOS. The teacher report added significantly to the screening accuracy over and above the parent report when compared with the ADOS classification. Findings support the screening utility of the parent-reported SRS among clinically referred children and indicate that different informants may provide unique information relevant for ASD assessment.

  2. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang

    Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant micemore » that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.« less

  3. Synthesis and Chemistry of Organic Geminal Di- and Triazides.

    PubMed

    Häring, Andreas P; Kirsch, Stefan F

    2015-11-06

    This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections.

  4. 21 CFR 178.3940 - Tetraethylene glycol di-(2-ethylhexoate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Tetraethylene glycol di-(2-ethylhexoate). 178.3940 Section 178.3940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... to be used for tying meat provided the twine fibers are produced from nylon resins complying with...

  5. High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

    PubMed

    Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

    2016-05-01

    The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour. © 2015 THE AUTHORS MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

  6. Ancient DNA evidence supports the contribution of Di-Qiang people to the han Chinese gene pool.

    PubMed

    Zhao, Yong-Bin; Li, Hong-Jie; Li, Sheng-Nan; Yu, Chang-Chun; Gao, Shi-Zhu; Xu, Zhi; Jin, Li; Zhu, Hong; Zhou, Hui

    2011-02-01

    Han Chinese is the largest ethnic group in the world. During its development, it gradually integrated with many neighboring populations. To uncover the origin of the Han Chinese, ancient DNA analysis was performed on the remains of 46 humans (1700 to 1900 years ago) excavated from the Taojiazhai site in Qinghai province, northwest of China, where the Di-Qiang populations had previously lived. In this study, eight mtDNA haplogroups (A, B, D, F, M*, M10, N9a, and Z) and one Y-chromosome haplogroup (O3) were identified. All analyses show that the Taojiazhai population presents close genetic affinity to Tibeto-Burman populations (descendants of Di-Qiang populations) and Han Chinese, suggesting that the Di-Qiang populations may have contributed to the Han Chinese genetic pool. 2010 Wiley-Liss, Inc.

  7. PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

    The plasticizer Di (2-ethylhexyl) phtha...

  8. High-Resolution Enabled 12-Plex DiLeu Isobaric Tags for Quantitative Proteomics

    PubMed Central

    2015-01-01

    Multiplex isobaric tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ)) are a valuable tool for high-throughput mass spectrometry based quantitative proteomics. We have developed our own multiplex isobaric tags, DiLeu, that feature quantitative performance on par with commercial offerings but can be readily synthesized in-house as a cost-effective alternative. In this work, we achieve a 3-fold increase in the multiplexing capacity of the DiLeu reagent without increasing structural complexity by exploiting mass defects that arise from selective incorporation of 13C, 15N, and 2H stable isotopes in the reporter group. The inclusion of eight new reporter isotopologues that differ in mass from the existing four reporters by intervals of 6 mDa yields a 12-plex isobaric set that preserves the synthetic simplicity and quantitative performance of the original implementation. We show that the new reporter variants can be baseline-resolved in high-resolution higher-energy C-trap dissociation (HCD) spectra, and we demonstrate accurate 12-plex quantitation of a DiLeu-labeled Saccharomyces cerevisiae lysate digest via high-resolution nano liquid chromatography–tandem mass spectrometry (nanoLC–MS2) analysis on an Orbitrap Elite mass spectrometer. PMID:25405479

  9. Mechanism of di-tert-butylsilylene transfer from a silacyclopropane to an alkene.

    PubMed

    Driver, Tom G; Woerpel, K A

    2003-09-03

    Kinetic and thermodynamic studies of the reactions of cyclohexene silacyclopropane 1 and monosubstituted alkenes suggested a possible mechanism for di-tert-butylsilylene transfer. The kinetic order in cyclohexene silacyclopropane 1 and cyclohexene were determined to be 1 and -1, respectively. Saturation kinetic behavior in monosubstituted alkene concentration was observed. Competition experiments between substituted styrenes and a deficient amount of di-tert-butylsilylene from 1 correlated well with the Hammett equation and provided a rho value of -0.666 +/- 0.008, using sigma(p) constants. These data supported a two-step mechanism involving reversible di-tert-butylsilylene extrusion from 1, followed by irreversible concerted electrophilic attack of the silylene on the monosubstituted alkene. Eyring activation parameters were found to be DeltaH++ = 22.1 +/- 0.9 kcal.mol(-1) and DeltaS++ = -15 +/- 2 eu. Competition experiments between cycloalkenes and allylbenzene determined cycloalkenes to be more efficient silylene traps (k(rel) =1.3, DeltaDeltaG++ = 0.200 kcal.mol(-1)). A summary of the data resulted in a postulated reaction coordinate diagram. The mechanistic studies enabled rational modification of reaction conditions that improved the synthetic utility of silylene transfer. Removal of the volatile cyclohexene from the reaction mixture into an evacuated headspace led to the formation of previously inaccessible cyclohexene-derived silacyclopropanes.

  10. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

  11. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

  12. 40 CFR 721.9516 - Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and silicones, 3-[(2... Specific Chemical Substances § 721.9516 Siloxanes and silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me... silicones, 3-[(2-aminoethyl) amino]propyl Me, di-Me, reaction products with polyethylene-polypropylene...

  13. 32 CFR 644.336 - Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Notices to Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development (HUD). 644.336 Section 644.336... Departments of Interior (DI); Health and Human Resources (HHR); Education; and Housing and Urban Development...

  14. Design, Synthesis and Evaluation of Novel Isoxazolines/Oxime Sulfonates of 2‧(2‧,6‧)-(Di)Chloropodophyllotoxins as Insecticidal Agents

    NASA Astrophysics Data System (ADS)

    Yu, Mingqiao; Liu, Guangci; Zhang, Yuanyuan; Feng, Tao; Xu, Ming; Xu, Hui

    2016-09-01

    A series of 2‧(2‧,6‧)-(di)halogeno-isoxazolopodophyllic acids-based esters, and oxime sulfonates of 2‧(2‧,6‧)-(di)halogenopodophyllones were prepared by structural modifications of podophyllotoxin as insecticidal agents against Mythimna separata Walker. It was found that when 2‧(2‧,6‧)-(di)halogenopodophyllones or 2‧(2‧,6‧)-(di)chloropicropodophyllones reacted with hydroxylamine hydrochloride, the desired products were related with the configuration of their lactones. Three key single-crystal structures of Ie, IIe and IIIb were determined by X-ray diffraction. Especially compounds IIc and Vc showed the highest insecticidal activity. Moreover, some interesting results of structure-insecticidal activity relationships of tested compounds were also observed.

  15. Using Stage- and Slit-Scanning to Improve Contrast and Optical Sectioning in Dual-View Inverted Light Sheet Microscopy (diSPIM)

    PubMed Central

    KUMAR, ABHISHEK; CHRISTENSEN, RYAN; GUO, MIN; CHANDRIS, PANOS; DUNCAN, WILLIAM; WU, YICONG; SANTELLA, ANTHONY; MOYLE, MARK; WINTER, PETER W.; COLÓN-RAMOS, DANIEL; BAO, ZHIRONG; SHROFF, HARI

    2017-01-01

    Dual-view inverted selective plane illumination microscopy (diSPIM) enables high-speed, long-term, fourdimensional (4D) imaging with isotropic spatial resolution. It is also compatible with conventional sample mounting on glass coverslips. However, broadening of the light sheet at distances far from the beam waist and sample-induced scattering degrades diSPIM contrast and optical sectioning. We describe two simple improvements that address both issues and entail no additional hardware modifications to the base diSPIM. First, we demonstrate improved diSPIM sectioning by keeping the light sheet and detection optics stationary, and scanning the sample through the stationary light sheet (rather than scanning the broadening light sheet and detection plane through the stationary sample, as in conventional diSPIM). This stage-scanning approach allows a thinner sheet to be used when imaging laterally extended samples, such as fixed microtubules or motile mitochondria in cell monolayers, and produces finer contrast than does conventional diSPIM. We also used stage-scanning diSPIM to obtain high-quality, 4D nuclear datasets derived from an uncompressed nematode embryo, and performed lineaging analysis to track 97% of cells until twitching. Second, we describe the improvement of contrast in thick, scattering specimens by synchronizing light-sheet synthesis with the rolling, electronic shutter of our scientific complementary metal-oxide-semiconductor (sCMOS) detector. This maneuver forms a virtual confocal slit in the detection path, partially removing out-of-focus light. We demonstrate the applicability of our combined stage- and slit-scanning-methods by imaging pollen grains and nuclear and neuronal structures in live nematode embryos. All acquisition and analysis code is freely available online. PMID:27638693

  16. ∑s-∑s as a di-baryonic molecule

    NASA Astrophysics Data System (ADS)

    Rathaud, D. P.; Rai, Ajay Kumar

    2018-05-01

    We study the ∑s-∑s, as a possible di-baryonic molecule in the potential model framework. We approximated the binding mechanism mainly as One Boson Exchange (QBE) plus screen type Yukawa potential. We predict the ∑s-∑s bound state molecule with I(Jp)=0(0+) and 0(1+) possible quantum numbers.

  17. MedSynDiKATe--design considerations for an ontology-based medical text understanding system.

    PubMed Central

    Hahn, U.; Romacker, M.; Schulz, S.

    2000-01-01

    MedSynDiKATe is a natural language processor for automatically acquiring knowledge from medical finding reports. The content of these documents is transferred to formal representation structures which constitute a corresponding text knowledge base. The general system architecture we present integrates requirements from the analysis of single sentences, as well as those of referentially linked sentences forming cohesive texts. The strong demands MedSynDiKATe poses to the availability of expressive knowledge sources are accounted for by two alternative approaches to (semi)automatic ontology engineering. PMID:11079899

  18. The crystal structure of a new ferrocenyl P,N ligand: 1-[(2,2-di-methyl-hydrazin-1-yl-idene)meth-yl]-1'-(di-phenyl-phospho-rothio-yl)ferrocene.

    PubMed

    Mouas, Toma Nardjes; Daran, Jean-Claude; Merazig, Hocine; Manoury, Eric

    2018-02-01

    The asymmetric unit of the title compound, [Fe(C 8 H 11 N 2 )(C 17 H 14 PS)], contains two independent mol-ecules ( A and B ) with very similar conformations. Each mol-ecule is built up from a ferrocene unit substituted in the 1 and 1' positions by a protected sulfur di-phenyl-phosphine and by a di-methyl-hydrazine, -C(H)=N-N(CH 3 ) 2 , fragment. The two independent mol-ecules are linked by a C-H⋯N hydrogen bond. In the crystal, the A - B dimer is linked by a pair of C-H⋯S hydrogen bonds, forming a centrosymmetric four-mol-ecule arrangement. These units are linked by C-H⋯π inter-actions, forming a supra-molecular three-dimensional structure.

  19. The extremophile Acidithiobacillus ferrooxidans possesses a c-di-GMP signalling pathway that could play a significant role during bioleaching of minerals.

    PubMed

    Ruiz, L M; Castro, M; Barriga, A; Jerez, C A; Guiliani, N

    2012-02-01

      The primary goal of this study was to characterize the existence of a functional c-di-GMP pathway in the bioleaching bacterium Acidithiobacillus ferrooxidans.   A bioinformatic search revealed that the genome sequence of At. ferrooxidans ATCC 23270 codes for several proteins involved in the c-di-GMP pathway, including diguanylate cyclases (DGC), phosphodiesterases and PilZ effector proteins. Overexpression in Escherichia coli demonstrated that four At. ferrooxidans genes code for proteins containing GGDEF/EAL domains with functional DGC activity. MS/MS analysis allowed the identification of c-di-GMP in nucleotide preparations obtained from At. ferrooxidans cells. In addition, c-di-GMP levels in cells grown on the surface of solid energetic substrates such as sulfur prills or pyrite were higher than those measured in ferrous iron planktonic cells.   At. ferrooxidans possesses a functional c-di-GMP pathway that could play a key role in At. ferrooxidans biofilm formation during bioleaching processes.   This is the first global study about the c-di-GMP pathway in an acidophilic bacterium of great interest for the biomining industry. It opens a new way to explore the regulation of biofilm formation by biomining micro-organisms during the bioleaching process. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

  20. Evaluation of a di-O-methylated glycan as a potential antigenic target for the serodiagnosis of human toxocariasis.

    PubMed

    Elefant, G R; Roldán, W H; Seeböck, A; Kosma, P

    2016-04-01

    Serodiagnosis of human toxocariasis is based on the detection of specific IgG antibodies by the enzyme-linked immunosorbent assay (ELISA) using Toxocara larvae excretory-secretory (TES) antigens, but its production is a laborious and time-consuming process being also limited by the availability of adult females of T. canis as source for ova to obtain larvae. Chemical synthesis of the di-O-methylated (DiM) glycan structure found in the TES antigens has provided material for studying the antibody reactivity in a range of mammalian hosts, showing reactivity with human IgM and IgG. In this study, we have evaluated the performance of the DiM glycan against a panel of sera including patients with toxocariasis (n = 60), patients with other helminth infections (n = 75) and healthy individuals (n = 94), showing that DiM is able to detect IgG antibodies with a sensitivity and specificity of 91·7% and 94·7%, respectively, with a very good agreement with the TES antigens (kappa = 0·825). However, cross-reactivity was observed in some sera from patients with ascariasis, hymenolepiasis and fascioliasis. These results show that the DiM glycan could be a promising antigenic tool for the serodiagnosis of human toxocariasis. © 2016 John Wiley & Sons Ltd.

  1. In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli in Response to Zinc Overload.

    PubMed

    Yeo, Jongchan; Dippel, Andrew B; Wang, Xin C; Hammond, Ming C

    2018-01-09

    Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP. Specifically, we demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are repressed with excess zinc, but not with other divalent metals. Furthermore, in both flow cytometry and fluorescence microscopy setups, we monitor the dynamic increase in cellular cyclic di-GMP levels upon zinc depletion and show that this response is due to de-repression of the endogenous diguanylate cyclase DgcZ. In the presence of zinc, cells exhibit enhanced cell motility and increased sensitivity to antibiotics due to inhibited biofilm formation. Taken together, these results showcase the application of RBF biosensors in visualizing single-cell dynamic changes in cyclic di-GMP signaling in direct response to environmental cues such as zinc and highlight our ability to assess whether observed phenotypes are related to specific signaling enzymes and pathways.

  2. Focusing the lens of language experience: Perception of Ma'di stops by Greek and English bilinguals and monolinguals

    PubMed Central

    Antoniou, Mark; Best, Catherine T.; Tyler, Michael D.

    2013-01-01

    Monolingual listeners are constrained by native language experience when categorizing and discriminating unfamiliar non-native contrasts. Are early bilinguals constrained in the same way by their two languages, or do they possess an advantage? Greek–English bilinguals in either Greek or English language mode were compared to monolinguals on categorization and discrimination of Ma'di stop-voicing distinctions that are non-native to both languages. As predicted, English monolinguals categorized Ma'di prevoiced plosive and implosive stops and the coronal voiceless stop as English voiced stops. The Greek monolinguals categorized the Ma'di short-lag voiceless stops as Greek voiceless stops, and the prevoiced implosive stops and the coronal prevoiced stop as Greek voiced stops. Ma'di prenasalized stops were uncategorized. Greek monolinguals discriminated the non-native voiced-voiceless contrasts very well, whereas the English monolinguals did poorly. Bilinguals were given all oral and written instructions either in English or in Greek (language mode manipulation). Each language mode subgroup categorized Ma'di stop-voicing comparably to the corresponding monolingual group. However, the bilinguals’ discrimination was unaffected by language mode: both subgroups performed intermediate to the monolinguals for the prevoiced-voiceless contrast. Thus, bilinguals do not possess an advantage for unfamiliar non-native contrasts, but are nonetheless uniquely configured language users, differing from either monolingual group. PMID:23556605

  3. "DI Days:" Differentiating Instruction through Student Choice. Classroom Tips

    ERIC Educational Resources Information Center

    Hammond, Donald J.

    2011-01-01

    To better meet the needs of the author's high school students, who have a variety of abilities, interests and engagement levels, he often differentiates instruction through the use of "DI Days." On these days, students use a choice board to select from a wide range of activities offered in learning centers. Each center offers content-focused…

  4. Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

    PubMed

    Sharma, Parveen; Ignatchenko, Vladimir; Grace, Kevin; Ursprung, Claudia; Kislinger, Thomas; Gramolini, Anthony O

    2010-07-09

    Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase, which transports Ca(2+) into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation. Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO) annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins. We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

  5. Infusion of di-2-ethylhexylphthalate for neonates: a review of potential health risk.

    PubMed

    Jaeger, Rudolph J; Weiss, Arlene L; Brown, Karen

    2005-01-01

    Plasticizers leach from polyvinyl chloride medical devices into infusion fluids. One plasticizer frequently found is di-2-ethylhexylphthalate. The Food and Drug Administration estimates that di-2-ethylhexylphthalate exposure exceeding a daily tolerable intake of 0.6 mg/kg per day may harm newborns, especially males. Exposure 20 times the tolerable intake or more may be given daily to certain infants, neonates, and premature infants in the neonatal intensive care unit. Currently, scant data exist on the exact dosage to this population. Furthermore, the exact potential for harm, either subtle or overt, is unknown or disputed. Thus, the recording of exposure history and "dose" in the medical record is warranted.

  6. The Tumor Suppressor DiRas3 Forms a Complex with H-Ras and C-RAF Proteins and Regulates Localization, Dimerization, and Kinase Activity of C-RAF*

    PubMed Central

    Baljuls, Angela; Beck, Matthias; Oenel, Ayla; Robubi, Armin; Kroschewski, Ruth; Hekman, Mirko; Rudel, Thomas; Rapp, Ulf R.

    2012-01-01

    The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down-regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic effect of DiRas3 is achieved through several mechanisms, including inhibition of cell proliferation, motility, and invasion, as well as induction of apoptosis and autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling through Ras/MAPK and PI3K. Despite intensive research, the mode of interference of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of speculation. In this study, we show that DiRas3 associates with the H-Ras oncogene and that activation of H-Ras enforces this interaction. Furthermore, while associated with DiRas3, H-Ras is able to bind to its effector protein C-RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H-Ras is more stable than the two protein complexes H-Ras·C-RAF or H-Ras·DiRas3, respectively. The consequence of this complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID:22605333

  7. DNA Replication Origin Function Is Promoted by H3K4 Di-methylation in Saccharomyces cerevisiae

    PubMed Central

    Rizzardi, Lindsay F.; Dorn, Elizabeth S.; Strahl, Brian D.; Cook, Jeanette Gowen

    2012-01-01

    DNA replication is a highly regulated process that is initiated from replication origins, but the elements of chromatin structure that contribute to origin activity have not been fully elucidated. To identify histone post-translational modifications important for DNA replication, we initiated a genetic screen to identify interactions between genes encoding chromatin-modifying enzymes and those encoding proteins required for origin function in the budding yeast Saccharomyces cerevisiae. We found that enzymes required for histone H3K4 methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase Bre1, are required for robust growth of several hypomorphic replication mutants, including cdc6-1. Consistent with a role for these enzymes in DNA replication, we found that both Set1 and Bre1 are required for efficient minichromosome maintenance. These phenotypes are recapitulated in yeast strains bearing mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains lacking specific COMPASS complex members or containing H2B mutations that differentially affect H3K4 methylation states, we determined that these replication defects were due to loss of H3K4 di-methylation. Furthermore, histone H3K4 di-methylation is enriched at chromosomal origins. These data suggest that H3K4 di-methylation is necessary and sufficient for normal origin function. We propose that histone H3K4 di-methylation functions in concert with other histone post-translational modifications to support robust genome duplication. PMID:22851644

  8. DNA replication origin function is promoted by H3K4 di-methylation in Saccharomyces cerevisiae.

    PubMed

    Rizzardi, Lindsay F; Dorn, Elizabeth S; Strahl, Brian D; Cook, Jeanette Gowen

    2012-10-01

    DNA replication is a highly regulated process that is initiated from replication origins, but the elements of chromatin structure that contribute to origin activity have not been fully elucidated. To identify histone post-translational modifications important for DNA replication, we initiated a genetic screen to identify interactions between genes encoding chromatin-modifying enzymes and those encoding proteins required for origin function in the budding yeast Saccharomyces cerevisiae. We found that enzymes required for histone H3K4 methylation, both the histone methyltransferase Set1 and the E3 ubiquitin ligase Bre1, are required for robust growth of several hypomorphic replication mutants, including cdc6-1. Consistent with a role for these enzymes in DNA replication, we found that both Set1 and Bre1 are required for efficient minichromosome maintenance. These phenotypes are recapitulated in yeast strains bearing mutations in the histone substrates (H3K4 and H2BK123). Set1 functions as part of the COMPASS complex to mono-, di-, and tri-methylate H3K4. By analyzing strains lacking specific COMPASS complex members or containing H2B mutations that differentially affect H3K4 methylation states, we determined that these replication defects were due to loss of H3K4 di-methylation. Furthermore, histone H3K4 di-methylation is enriched at chromosomal origins. These data suggest that H3K4 di-methylation is necessary and sufficient for normal origin function. We propose that histone H3K4 di-methylation functions in concert with other histone post-translational modifications to support robust genome duplication.

  9. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  10. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  11. 40 CFR 721.2275 - N,N,N′,N′-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false N,N,Nâ²,Nâ²-Tetrakis(oxi-ranyl- methyl)-1,3-cyclohexane di-meth-anamine. 721.2275 Section 721.2275 Protection of Environment ENVIRONMENTAL...-cyclohexane di-meth-anamine. (a) Chemical substances and significant new uses subject to reporting. (1) The...

  12. DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE

    EPA Science Inventory

    DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE. JE Andrews, H Nichols, and ES Hunter. Reproductive Toxicology Division, NHEERL, USEPA, RTP, NC.

    Disinfection of drinking water with chlorine results in numerous chlorinated byprodu...

  13. Palladium(II) complexes bearing di-(2-picolyl)amine functionalized chrysin fragments. An experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    González-Montiel, Simplicio; Valdez-Calderón, Alejandro; Vásquez-Pérez, J. Manuel; Torres-Valencia, J. Martín; Martínez-Otero, Diego; López, Jorge A.; Cruz-Borbolla, Julián

    2017-10-01

    A new series of chrysin derivatives containing the di-(2-picolyl)amine (2a-d) moiety have been designed, synthesized, and treated with PdCl2·2CH3CN allowing the preparation of new cationic Palladium(II) complexes (3a-d). Solution-phase studies by 1H NMR spectroscopy of 3a-d revealed that the protons of the methylene groups of the di(2-picolyl)amine fragment are diasterotopic. GIAO/DFT studies were performed to predict the molecular structures of 3a-d by comparing the experimental and theoretical 1H-NMR chemical shifts. The molecular structure of 3c was determined by X-ray crystallographic analysis revealing that di-(2-picolyl)amine fragment is coordinated to the palladium center in a κ3-N,N,N-tridentate fashion in an overall square-planar geometry completed with a chloride atom.

  14. On-line process analysis innovation: DiComp (tm) shunting dielectric sensor technology

    NASA Technical Reports Server (NTRS)

    Davis, Craig R.; Waldman, Frank A.

    1993-01-01

    The DiComp Shunting Dielectric Sensor (SDS) is a new patent-pending technology developed under the Small Business Innovation Research Program (SBIR) for NASA's Kennedy Space Center. The incorporation of a shunt electrode into a conventional fringing field dielectric sensor makes the SDS uniquely sensitive to changes in material dielectric properties in the KHz to MHz range which were previously detectable only at GHz measurement frequencies. The initial NASA application of the SDS for Nutrient Delivery Control has demonstrated SDS capabilities for thickness and concentration measurement of Hoagland nutrient solutions. The commercial introduction of DiComp SDS technology for concentration and percent solids measurements in dispersions, emulsions and solutions represents a new technology for process measurements for liquids in a variety of industries.

  15. The effect of real and virtual photons in the di-lepton channel at the LHC

    NASA Astrophysics Data System (ADS)

    Accomando, Elena; Fiaschi, Juri; Hautmann, Francesco; Moretti, Stefano; Shepherd-Themistocleous, Claire H.

    2017-07-01

    We present a study of di-lepton production at the CERN Large Hadron Collider with a particular focus on the contribution resulting from both real and virtual photons in the initial state. We discuss the region of phase space in which the invariant mass of the lepton pair is of the order of several TeV, where searches for new physics phenomena yielding a di-lepton signature are presently carried out. We study both the yield and associated uncertainties for all possible topologies in photon-induced di-lepton production and compare these with what is expected in the standard Drell-Yan channel, where quark-antiquark pairs are responsible for the production of lepton pairs. We analyse the impact of these QED contributions on the expected Standard Model background and on searches for new physics. In this latter case, we use the production of an extra heavy Z‧-boson predicted by the Sequential Standard Model (SSM) as a benchmark process.

  16. Carbon Nanofiber Incorporated Silica Based Aerogels with Di-Isocyanate Cross-Linking

    NASA Technical Reports Server (NTRS)

    Vivod, Stephanie L.; Meador, Mary Ann B.; Capadona, Lynn A.; Sullivan, Roy M.; Ghosn, Louis J.; Clark, Nicholas; McCorkle, Linda

    2008-01-01

    Lightweight materials with excellent thermal insulating properties are highly sought after for a variety of aerospace and aeronautic applications. (1) Silica based aerogels with their high surface area and low relative densities are ideal for applications in extreme environments such as insulators for the Mars Rover battery. (2) However, the fragile nature of aerogel monoliths prevents their widespread use in more down to earth applications. We have shown that the fragile aerogel network can be cross-linked with a di-isocyanate via amine decorated surfaces to form a conformal coating. (3) This coating reinforces the neck regions between secondary silica particles and significantly strengthens the aerogels with only a small effect on density or porosity. Scheme 1 depicts the cross-linking reaction with the di-isocyanate and exhibits the stages that result in polymer cross-linked aerogel monoliths.

  17. A rare positively charged nicotinic acid di­sulfide: 2,2′-di­thio­dinicotinic acid hydro­chloride monohydrate

    PubMed Central

    McGuire, Chad M.; Albrecht-Schmitt, Thomas E.

    2018-01-01

    The title compound {systematic name: 3-carb­oxy-2-[2-(3-carb­oxy­pyridin-2-yl)disulfan-1-yl)]pyridin-1-ium chloride monohydrate}, C12H9N2O4S2 +·Cl−·H2O, crystallizes in the triclinic space group P . A pair of 2-mercaptonicotinic acid moieties is connected by a 2,2′-di­sulfide bond with a dihedral angle of 78.79 (3)°. One of the N atom is protonated, as are both carboxyl­ate groups, resulting in an overall +1 charge on the dimer. The structure comprises a zigzagging layer of the dimerized di­thio­dinicotinic acid rings, with charge-balancing chloride ions and water mol­ecules between the layers. Hydrogen bonding between the chloride and water sites with the dimer appears to hold the structure together. Nearest neighbor nicotinic acid rings are offset when viewed down the a axis, suggesting no added stability from ring stacking. The asymmetric unit corresponds to the empirical formula of the compound, and it packs with two formula units per unit cell.

  18. c-di-GMP Turn-Over in Clostridium difficile Is Controlled by a Plethora of Diguanylate Cyclases and Phosphodiesterases

    PubMed Central

    Bordeleau, Eric; Fortier, Louis-Charles; Malouin, François; Burrus, Vincent

    2011-01-01

    Clostridium difficile infections have become a major healthcare concern in the last decade during which the emergence of new strains has underscored this bacterium's capacity to cause persistent epidemics. c-di-GMP is a bacterial second messenger regulating diverse bacterial phenotypes, notably motility and biofilm formation, in proteobacteria such as Vibrio cholerae, Pseudomonas aeruginosa, and Salmonella. c-di-GMP is synthesized by diguanylate cyclases (DGCs) that contain a conserved GGDEF domain. It is degraded by phosphodiesterases (PDEs) that contain either an EAL or an HD-GYP conserved domain. Very little is known about the role of c-di-GMP in the regulation of phenotypes of Gram-positive or fastidious bacteria. Herein, we exposed the main components of c-di-GMP signalling in 20 genomes of C. difficile, revealed their prevalence, and predicted their enzymatic activity. Ectopic expression of 31 of these conserved genes was carried out in V. cholerae to evaluate their effect on motility and biofilm formation, two well-characterized phenotype alterations associated with intracellular c-di-GMP variation in this bacterium. Most of the predicted DGCs and PDEs were found to be active in the V. cholerae model. Expression of truncated versions of CD0522, a protein with two GGDEF domains and one EAL domain, suggests that it can act alternatively as a DGC or a PDE. The activity of one purified DGC (CD1420) and one purified PDE (CD0757) was confirmed by in vitro enzymatic assays. GTP was shown to be important for the PDE activity of CD0757. Our results indicate that, in contrast to most Gram-positive bacteria including its closest relatives, C. difficile encodes a large assortment of functional DGCs and PDEs, revealing that c-di-GMP signalling is an important and well-conserved signal transduction system in this human pathogen. PMID:21483756

  19. Di-jet Hadron Correlations in Central Au+Au Collisions at √{sNN} = 200 GeV at STAR

    NASA Astrophysics Data System (ADS)

    Elsey, Nicholas; STAR Collaboration

    2017-09-01

    Jets and their modifications due to partonic energy loss provide a powerful tool to study the properties of the QGP created in ultrarelativistic heavy-ion collisions. For jets reconstructed with the anti-kT algorithm with resolution parameter R = 0.4 , previous measurements of the di-jet asymmetry AJ at STAR) indicate that the observed imbalance of an initial ``hard-core'' di-jet selection with pTconst > 2.0 GeV/c, pTlead > 20.0 GeV/c and pTsub > 10.0 GeV/c is restored to the balance of the pp reference when soft constituents are included. The lost energy recovered with soft constituents suggests soft gluon radiation by high pT partons. Jet-hadron correlations with respect to di-jets allow a differential assessment of the kinematic properties of the soft gluon radiation spectrum induced by partonic energy loss in the QGP. We present charged hadron correlations with respect to the di-jets found in the above AJ analysis, and compare to similar measurements using a jet trigger at RHIC.

  20. Efficient detection of differentially methylated regions using DiMmeR.

    PubMed

    Almeida, Diogo; Skov, Ida; Silva, Artur; Vandin, Fabio; Tan, Qihua; Röttger, Richard; Baumbach, Jan

    2017-02-15

    Epigenome-wide association studies (EWAS) generate big epidemiological datasets. They aim for detecting differentially methylated DNA regions that are likely to influence transcriptional gene activity and, thus, the regulation of metabolic processes. The by far most widely used technology is the Illumina Methylation BeadChip, which measures the methylation levels of 450 (850) thousand cytosines, in the CpG dinucleotide context in a set of patients compared to a control group. Many bioinformatics tools exist for raw data analysis. However, most of them require some knowledge in the programming language R, have no user interface, and do not offer all necessary steps to guide users from raw data all the way down to statistically significant differentially methylated regions (DMRs) and the associated genes. Here, we present DiMmeR (Discovery of Multiple Differentially Methylated Regions), the first free standalone software that interactively guides with a user-friendly graphical user interface (GUI) scientists the whole way through EWAS data analysis. It offers parallelized statistical methods for efficiently identifying DMRs in both Illumina 450K and 850K EPIC chip data. DiMmeR computes empirical P -values through randomization tests, even for big datasets of hundreds of patients and thousands of permutations within a few minutes on a standard desktop PC. It is independent of any third-party libraries, computes regression coefficients, P -values and empirical P -values, and it corrects for multiple testing. DiMmeR is publicly available at http://dimmer.compbio.sdu.dk . diogoma@bmb.sdu.dk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  1. Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

    PubMed

    Castro, Matías; Deane, Shelly M; Ruiz, Lina; Rawlings, Douglas E; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

  2. Diguanylate Cyclase Null Mutant Reveals That C-Di-GMP Pathway Regulates the Motility and Adherence of the Extremophile Bacterium Acidithiobacillus caldus

    PubMed Central

    Castro, Matías; Deane, Shelly M.; Ruiz, Lina; Rawlings, Douglas E.; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process. PMID:25689133

  3. Stereoselective Formation of Mono- and Di-Hydroxylated Polychlorinated Biphenyls by Rat Cytochrome P450 2B1

    PubMed Central

    Lehmler, Hans-Joachim; Wong, Charles S.

    2013-01-01

    Changes in atropisomer composition of chiral polychlorinated biphenyls (PCBs) and their mono- and di- hydroxylated metabolites (OH- and diOH-PCBs) via rat cytochrome P450 2B1 (CYP2B1) mediated biotransformation were investigated in vitro. Rat CYP2B1 could stereoselectively biotransform chiral PCBs to generate meta-OH-PCBs as the major metabolites after 60 min incubations. Non-racemic enantiomer fractions (EFs: concentration ratios of the (+)-atropisomer or the first-eluting atropisomer over the total concentrations of two atropisomers) of 5-OH-PCBs, were 0.17, 0.20, 0.85, 0.77 and 0.41 for incubations with PCBs 91, 95, 132, 136 and 149, respectively. CYP-mediated stereoselective formation of diOH-PCBs from OH-PCBs was observed for the first time. After 60 min stereoselective biotransformation, the EFs of both 4-OH-PCB 95 and 5-OH-PCB 95 changed from racemic (i.e., 0.50) to 0.62 and 0.46, respectively. These transformations generated statistically non-racemic 4,5-diOH-PCB 95, with EFs of 0.53 and 0.58 for 4-OH-PCB 95 and 5-OH-PCB 95 incubations, respectively. Biotransformation of PCBs 91 and 136 also generated 4,5-diOH-PCB 91 and 4,5-diOH-PCB 136, respectively. These in vitro results were consistent with that observed for stereoselective PCB biotransformation by rat liver microsomes and in vivo. Biotransformation interference between two atropisomers of PCB 136 was investigated for the first time in this study. The biotransformation process of (−)-PCB 136 was significantly disrupted by the presence of (+)-PCB 136, but not the other way around. Thus, stereoselective metabolism of chiral PCBs and OH-PCBs by CYPs is a major mechanism for atropisomer composition change of PCBs and their metabolites in the environment, with the degree of composition change dependent, at least in part, on stereoselective interference of atropisomers with each other at the enzyme level. PMID:24060104

  4. DiAs User Interface: A Patient-Centric Interface for Mobile Artificial Pancreas Systems

    PubMed Central

    Keith-Hynes, Patrick; Guerlain, Stephanie; Mize, Benton; Hughes-Karvetski, Colleen; Khan, Momin; McElwee-Malloy, Molly; Kovatchev, Boris P.

    2013-01-01

    Background Recent in-hospital studies of artificial pancreas (AP) systems have shown promising results in improving glycemic control in patients with type 1 diabetes mellitus. The next logical step in AP development is to conduct transitional outpatient clinical trials with a mobile system that is controlled by the patient. In this article, we present the user interface (UI) of the Diabetes Assistant (DiAs), an experimental smartphone-based mobile AP system, and describe the reactions of a round of focus groups to the UI. This work is an initial inquiry involving a relatively small number of potential users, many of whom had never seen an AP system before, and the results should be understood in that light. Methods We began by considering how the UI of an AP system could be designed to make use of the familiar touch-based graphical UI of a consumer smartphone. After developing a working prototype UI, we enlisted a human factors specialist to perform a heuristic expert analysis. Next we conducted a formative evaluation of the UI through a series of three focus groups with N = 13 potential end users as participants. The UI was modified based upon the results of these studies, and the resulting DiAs system was used in transitional outpatient AP studies of adults in the United States and Europe. Results The DiAs UI was modified based on focus group feedback from potential users. The DiAs was subsequently used in JDRF- and AP@Home-sponsored transitional outpatient AP studies in the United States and Europe by 40 subjects for 2400 h with no adverse events. Conclusions Adult patients with type 1 diabetes mellitus are able to control an AP system successfully using a patient-centric UI on a commercial smartphone in a transitional outpatient environment. PMID:24351168

  5. Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

    PubMed

    Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

    2015-01-01

    DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

  6. Probing the electroweak phase transition via enhanced di-Higgs boson production

    NASA Astrophysics Data System (ADS)

    Carena, Marcela; Liu, Zhen; Riembau, Marc

    2018-05-01

    We consider a singlet extension of the standard model (SM) with a spontaneous Z2 breaking and study the gluon-gluon fusion production of the heavy scalar, with subsequent decay into a pair of SM-like Higgs bosons. We find that an on-shell interference effect can notably enhance the resonant di-Higgs production rate up to 40%. In addition, consistently taking into account both the on-shell and off-shell interference effects between the heavy scalar and the SM di-Higgs diagrams significantly improves the HL-LHC and HE-LHC reach in this channel. As an example, within an effective field theory analysis in an explicitly Z2 breaking scenario, we further discuss the potential to probe the parameter region compatible with a first-order electroweak phase transition. Our analysis is applicable for general potentials of the singlet extension of the SM as well as for more general resonance searches.

  7. Congo Red Stain Identifies Matrix Overproduction and Is an Indirect Measurement for c-di-GMP in Many Species of Bacteria.

    PubMed

    Jones, Christopher J; Wozniak, Daniel J

    2017-01-01

    Congo red is a diazo textile dye that has been used to visualize the production of amyloid fibers for nearly a century. Microbiological applications were later developed, especially in identifying strains that produce amyloid appendages called curli and overexpressing polysaccharides in the biofilm matrix. The second messenger cyclic diguanylate (c-di-GMP) regulates the production of biofilm matrix polysaccharides, and therefore Congo red staining of samples can be utilized as an indirect measurement of elevated c-di-GMP production in bacteria. Congo red allows the identification of strains producing high c-di-GMP in an inexpensive, quantitative, and high-throughput manner.

  8. Di- or polysulphide-bound biomarkers in sulphur-rich geomacromolecules as revealed by selective chemolysis

    NASA Astrophysics Data System (ADS)

    Kohnen, Math E. l.; Sinninghe Damsté, Jaap S.; Kock-van Dalen, A. c.; Jan, W. De Leeuw

    1991-05-01

    Three types of sulphur-rich high-molecular-weight material in the alkylsulphide, the polar, and the asphaltene fractions isolated from the bitumen of an immature bituminous shale from the Vena del Gesso basin (Italy) were desulphurised using Raney Ni and were treated with MeLi/MeI, a chemical degradation method which cleaves selectively and quantitatively di- or polysulphide linkages. The products formed were characterised by gas chromatography-mass spectrometry. Raney Ni desulphurisation revealed that these S-rich macromolecules are in substantial part composed of sulphur-linked biomarkers with linear, branched, isoprenoid, steroid, hopanoid, and carotenoid carbon skeletons. MeLi/Mel treatment provided evidence that a major part of the total amount of macromolecularly bound biomarkers are linked via di- or polysulphide moieties to the macromolecular network. Since the di- or polysulphide linkages are attached at specific positions of the bound biomarkers it is proposed that they are formed by intermolecular incorporation reactions of HS x- into low-molecular-weight functionalised biological lipids during early diagenesis. The different properties (solubility and molecular weight) of the sulphur-rich macromolecules in the alkylsulphide, the resin, and the asphaltene fractions can be explained simply by differences in degree of sulphur cross-linking.

  9. A Basic Behavior of CNG DI Combustion in a Spark-Ignited Rapid Compression Machine

    NASA Astrophysics Data System (ADS)

    Huang, Zuohua; Shiga, Seiichi; Ueda, Takamasa; Jingu, Nobuhisa; Nakamura, Hisao; Ishima, Tsuneaki; Obokata, Tomio; Tsue, Mitsuhiro; Kono, Michikata

    A basic characteristics of compressed natural gas direct-injection (CNG DI) combustion was studied by using a rapid compression machine. Results show that comparing with homogeneous mixture, CNG DI has short combustion duration, high pressure rise due to combustion, and high rate of heat release, which are considered to come from the charge stratification and the gas flow generated by the fuel injection. CNG DI can realize extremely lean combustion which reaches 0.03 equivalence ratio, φ. Combustion duration, maximum pressure rise due to combustion and combustion efficiency are found to be insensitive to the injection modes. Unburned methane showed almost the same level as that of homogeneous mixture combustion. CO increased steeply with the increase in φ when φ was greater than 0.8 due to the excessive stratification, and NOx peak value shifted to the region of lower φ. Combustion inefficiency maintains less than 0.08 in the range of φ from 0.1 to 0.9 and increases at very low φ due to bulk quenching and at higher φ due to excessive stratification. The combustion efficiency estimated from combustion products shows good agreement with that of heat release analysis.

  10. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

    PubMed

    Lopez-Rivera, Esther; Liu, Yangfan P; Verbitsky, Miguel; Anderson, Blair R; Capone, Valentina P; Otto, Edgar A; Yan, Zhonghai; Mitrotti, Adele; Martino, Jeremiah; Steers, Nicholas J; Fasel, David A; Vukojevic, Katarina; Deng, Rong; Racedo, Silvia E; Liu, Qingxue; Werth, Max; Westland, Rik; Vivante, Asaf; Makar, Gabriel S; Bodria, Monica; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Maiorana, Mariarosa; Petrey, Donald S; Honig, Barry; Lozanovski, Vladimir J; Salomon, Rémi; Heidet, Laurence; Carpentier, Wassila; Gaillard, Dominique; Carrea, Alba; Gesualdo, Loreto; Cusi, Daniele; Izzi, Claudia; Scolari, Francesco; van Wijk, Joanna A E; Arapovic, Adela; Saraga-Babic, Mirna; Saraga, Marijan; Kunac, Nenad; Samii, Ali; McDonald-McGinn, Donna M; Crowley, Terrence B; Zackai, Elaine H; Drozdz, Dorota; Miklaszewska, Monika; Tkaczyk, Marcin; Sikora, Przemyslaw; Szczepanska, Maria; Mizerska-Wasiak, Malgorzata; Krzemien, Grazyna; Szmigielska, Agnieszka; Zaniew, Marcin; Darlow, John M; Puri, Prem; Barton, David; Casolari, Emilio; Furth, Susan L; Warady, Bradley A; Gucev, Zoran; Hakonarson, Hakon; Flogelova, Hana; Tasic, Velibor; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Allegri, Landino; Wong, Craig S; Drummond, Iain A; D'Agati, Vivette; Imamoto, Akira; Barasch, Jonathan M; Hildebrandt, Friedhelm; Kiryluk, Krzysztof; Lifton, Richard P; Morrow, Bernice E; Jeanpierre, Cecile; Papaioannou, Virginia E; Ghiggeri, Gian Marco; Gharavi, Ali G; Katsanis, Nicholas; Sanna-Cherchi, Simone

    2017-02-23

    The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10 -14 ). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

  11. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

    PubMed Central

    Lopez-Rivera, E.; Liu, Y.P.; Verbitsky, M.; Anderson, B.R.; Capone, V.P.; Otto, E.A.; Yan, Z.; Mitrotti, A.; Martino, J.; Steers, N.J.; Fasel, D.A.; Vukojevic, K.; Deng, R.; Racedo, S.E.; Liu, Q.; Werth, M.; Westland, R.; Vivante, A.; Makar, G.S.; Bodria, M.; Sampson, M.G.; Gillies, C.E.; Vega-Warner, V.; Maiorana, M.; Petrey, D.S.; Honig, B.; Lozanovski, V.J.; Salomon, R.; Heidet, L.; Carpentier, W.; Gaillard, D.; Carrea, A.; Gesualdo, L.; Cusi, D.; Izzi, C.; Scolari, F.; van Wijk, J.A.E.; Arapovic, A.; Saraga-Babic, M.; Saraga, M.; Kunac, N.; Samii, A.; McDonald-McGinn, D.M.; Crowley, T.B.; Zackai, E.H.; Drozdz, D.; Miklaszewska, M.; Tkaczyk, M.; Sikora, P.; Szczepanska, M.; Mizerska-Wasiak, M.; Krzemien, G.; Szmigielska, A.; Zaniew, M.; Darlow, J.M.; Puri, P.; Barton, D.; Casolari, E.; Furth, S.L.; Warady, B.A.; Gucev, Z.; Hakonarson, H.; Flogelova, H.; Tasic, V.; Latos-Bielenska, A.; Materna-Kiryluk, A.; Allegri, L.; Wong, C.S.; Drummond, I.A.; D’Agati, V.; Imamoto, A.; Barasch, J.M.; Hildebrandt, F.; Kiryluk, K.; Lifton, R.P.; Morrow, B.E.; Jeanpierre, C.; Papaioannou, V.E.; Ghiggeri, G.M.; Gharavi, A.G.; Katsanis, N.; Sanna-Cherchi, S.

    2017-01-01

    BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.) PMID:28121514

  12. Poly[[nona­aqua­bis­(μ-5-hy­droxy­benzene-1,3-di­carboxyl­ato)(5-hy­droxy­benzene-1,3-di­carboxyl­ato)dicerium(III)] hexa­hydrate

    PubMed Central

    Fan, Xiao; Daiguebonne, Carole; Guillou, Olivier; Camara, Magatte

    2014-01-01

    In the title coordination polymer, {[Ce2(C8H4O5)3(H2O)9]·6H2O}n, the asymmetric unit is formed by two CeIII atoms, three 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands, nine coordinating water mol­ecules and six water mol­ecules of crystallization. The two CeIII atoms are bridged by 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands acting in a bis-bidentate coordination mode, generating infinite chains along [101]. Both independent metal atoms are nine-coordinated, one by four O atoms from the carboxyl­ate groups of two bridging 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligands and five O atoms from water mol­ecules, generating a tricapped trigonal–prismatic geometry. The coordination around the second CeIII atom is similar, except that one of the water mol­ecules is replaced by an O atom from an additional 5-hy­droxy­benzene-1,3-di­carboxyl­ate ligand acting in a monodentate coordination mode and forming a capped square-anti­prismatic geometry. PMID:24860313

  13. Forward di-jet production in p+Pb collisions in the small-x improved TMD factorization framework

    DOE PAGES

    van Hameren, A.; Kotko, P.; Kutak, K.; ...

    2016-12-12

    We study the production of forward di-jets in proton-lead and proton-proton collisions at the Large Hadron Collider. Such configurations, with both jets produced in the forward direction, impose a dilute-dense asymmetry which allows to probe the gluon density of the lead or proton target at small longitudinal momentum fractions. Even though the jet momenta are always much bigger than the saturation scale of the target, Qs, the transverse momentum imbalance of the di-jet system may be either also much larger than Qs, or of the order Qs, implying that the small-x QCD dynamics involved is either linear or non-linear, respectively.more » The small-x improved TMD factorization framework deals with both situations in the same formalism. In the latter case, which corresponds to nearly back-to-back jets, we find that saturation effects induce a significant suppression of the forward di-jet azimuthal correlations in proton-lead versus proton-proton collisions.« less

  14. Microwave-assisted synthesis of 3,6-di(pyridin-2-yl)pyridazines: unexpected ketone and aldehyde cycloadditions.

    PubMed

    Hoogenboom, Richard; Moore, Brian C; Schubert, Ulrich S

    2006-06-23

    3,6-Di(pyridin-2-yl)pyridazines are an interesting class of compounds because of their metal-coordinating ability resulting in the self-assembly into [2x2] gridlike metal complexes with copper(I) or silver(I) ions. These and other substituted pyridazines can be prepared by the inverse-electron-demand Diels-Alder reactions between acetylenes and 1,2,4,5-tetrazines. In this contribution, the effect of (superheated) microwave conditions on these generally slow cycloadditions is described. The cycloaddition of acetylenes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine could be accelerated from several days reflux in toluene or N,N-dimethylformamide to several hours in dichloromethane at 150 degrees C. In addition, the unexpected cycloaddition of the enol tautomers of various ketones and aldehydes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine is described in detail providing an alternative route for the synthesis of (substituted) pyridazines.

  15. Forward di-jet production in p+Pb collisions in the small-x improved TMD factorization framework

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    van Hameren, A.; Kotko, P.; Kutak, K.

    We study the production of forward di-jets in proton-lead and proton-proton collisions at the Large Hadron Collider. Such configurations, with both jets produced in the forward direction, impose a dilute-dense asymmetry which allows to probe the gluon density of the lead or proton target at small longitudinal momentum fractions. Even though the jet momenta are always much bigger than the saturation scale of the target, Qs, the transverse momentum imbalance of the di-jet system may be either also much larger than Qs, or of the order Qs, implying that the small-x QCD dynamics involved is either linear or non-linear, respectively.more » The small-x improved TMD factorization framework deals with both situations in the same formalism. In the latter case, which corresponds to nearly back-to-back jets, we find that saturation effects induce a significant suppression of the forward di-jet azimuthal correlations in proton-lead versus proton-proton collisions.« less

  16. Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate

    PubMed Central

    Tanser, A. R.; Bourke, M. P.; Blandford, A. G.

    1973-01-01

    Tanser, A. R., Bourke, M. P., and Blandford, A. G. (1973).Thorax, 28, 596-600. Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate. We investigated 57 employees of a factory where diphenyl-methane di-isocyanate (MDI) was used to prepare the materials for making rigid polyurethane foam. Four employees had developed hypersensitivity to MDI. Two had severe, and one moderate asthma, while the fourth had symptoms resembling the delayed hypersensitivity type of reaction. Ten other employees had experienced unpleasant, mainly respiratory, irritant effects from MDI vapour. A past history of bronchitis or of allergy was found more commonly in those with symptoms from MDI than in those without symptoms. It is not known if MDI causes permanent damage to the respiratory tract. The most severely affected cases in the present series had normal spirometric values after recovery, and no persisting symptoms. MDI is safer than other isocyanates used in industry but may cause both major and minor illness. It should be handled with the same precautions as those used with the more toxic compounds. PMID:4784381

  17. MONO-(3-CARBOXYPROPYL) PHTHALATE, A METABOLITE OF DI-N-OCTYL PHTHALATE

    EPA Science Inventory

    Di-n-octyl phthalate (DnOP) is found as a component of mixed C6–C10 linear-chain phthalates used as plasticizers in various polyvinyl chloride applications, including flooring and carpet tiles. Following exposure and absorption, DnOP is metabolized to its hydrolytic monoester, mo...

  18. Probing the electroweak phase transition via enhanced di-Higgs boson production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carena, Marcela; Liu, Zhen; Riembau, Marc

    Here, we consider a singlet extension of the Standard Model (SM) with a spontaneousmore » $$Z_2$$ breaking and study the gluon-gluon fusion production of the heavy scalar, with subsequent decay into a pair of SM-like Higgs bosons. We find that an on-shell interference effect can notably enhance the resonant di-Higgs production rate up to 40\\%. In addition, consistently taking into account both the on-shell and off-shell interference effects between the heavy scalar and the SM di-Higgs diagrams significantly improves the HL-LHC and HE-LHC reach in this channel. As an example, within an effective field theory analysis in an explicitly $$Z_2$$ breaking scenario, we further discuss the potential to probe the parameter region compatible with a first order electroweak phase transition. Our analysis is applicable for general potentials of the singlet extension of the SM as well as for more general resonance searches.« less

  19. Probing the electroweak phase transition via enhanced di-Higgs boson production

    DOE PAGES

    Carena, Marcela; Liu, Zhen; Riembau, Marc

    2018-05-24

    Here, we consider a singlet extension of the Standard Model (SM) with a spontaneousmore » $$Z_2$$ breaking and study the gluon-gluon fusion production of the heavy scalar, with subsequent decay into a pair of SM-like Higgs bosons. We find that an on-shell interference effect can notably enhance the resonant di-Higgs production rate up to 40\\%. In addition, consistently taking into account both the on-shell and off-shell interference effects between the heavy scalar and the SM di-Higgs diagrams significantly improves the HL-LHC and HE-LHC reach in this channel. As an example, within an effective field theory analysis in an explicitly $$Z_2$$ breaking scenario, we further discuss the potential to probe the parameter region compatible with a first order electroweak phase transition. Our analysis is applicable for general potentials of the singlet extension of the SM as well as for more general resonance searches.« less

  20. VizieR Online Data Catalog: Algol-type binaries. VIII. DI Peg & AF Gem (Yang+, 2014)

    NASA Astrophysics Data System (ADS)

    Yang, Y.-G.; Yang, Y.; Li, S.-Z.

    2014-10-01

    In the 2012-2013 observing season, DI Peg and AF Gem were observed using the 60cm telescope and the 85cm telescope at Xinglong station (XLs) of National Astronomical Observatories of Chinese (NAOC). The standard Johnson-Cousins UBVRcIc photometric systems were mounted upon two small telescopes. On five consecutive nights from 2012 October 9 to 13, the multi-color photometry of DI Peg was made with the 60cm telescope. The other variable star, AF Gem, was observed using the 85cm telescope on 7 nights from 2013 January 1 to 7. (5 data files).

  1. Utility of the 3Di Short Version for the Diagnostic Assessment of Autism Spectrum Disorder and Compatibility with DSM-5

    ERIC Educational Resources Information Center

    Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C.; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin

    2016-01-01

    The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical…

  2. Hydrophobic Materials Based on Salts of Di(2-ethylhexyl)phosphoric Acid

    NASA Astrophysics Data System (ADS)

    Kizim, N. F.; Golubina, E. N.

    2018-03-01

    Interfacial formations of material based on metals di(2-ethylhexyl)phosphates of various metals exhibit hydrophobic properties. The contact angle of the surface, modified by the interfacial formations materials, could reach up to 140° depending on the nature of the solvent, the metal salt, the number of applications.

  3. Growth and antioxidant defense responses of wheat seedlings to di-n-butyl phthalate and di (2-ethylhexyl) phthalate stress.

    PubMed

    Gao, Minling; Dong, Youming; Zhang, Ze; Song, Wenhua; Qi, Yun

    2017-04-01

    Phthalate acid esters (PAEs) are vital environmental hormone-like chemicals that are noxious to plants, animals, and human beings. In this study, the influences of di-n-butyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) on the seed germination, root morphology, and various physiological changes of wheat seedlings were investigated by analyzing superoxide anion (O 2 - ) accumulation, antioxidant enzyme activity, and lipid peroxidation. DBP and DEHP were found to obviously inhibit germination only at high concentrations, but significantly affected root morphology even at lower concentrations. Their toxic effects were the most severe on root elongation, followed by shoot elongation, and were the least severe on germination rate, indicating that root elongation was the best index for evaluating DBP and DEHP eco-toxicity. DBP and DEHP also enhanced O 2 - and malondialdehyde levels and membrane permeability, as well as produced changes in the antioxidant status and PAE content in the stem and leaf (combined tissues, hereafter shoot) and root tissues. The activities of superoxide dismutase, catalase, and peroxidase increased at low and medium DBP and DEHP concentrations, but declined at high PAE concentrations. These results indicated that PAEs could exert oxidative damage in the early development stage of wheat, particularly at higher concentrations. DBP and DEHP accumulation was higher in the roots than in the shoot tissues, and their levels in these tissues increased with increasing PAE concentrations, supporting their more-serious toxic effects on roots than those on shoots. Further, the physicochemical properties of DBP rendered it more harmful than DEHP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

  5. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

  6. The Screening Accuracy of the Parent and Teacher-Reported Social Responsiveness Scale (SRS): Comparison with the 3Di and ADOS

    ERIC Educational Resources Information Center

    Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C.; Greaves-Lord, Kirstin

    2015-01-01

    The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3Di and ADOS, in 186 children referred to…

  7. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

  8. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

  9. 40 CFR 721.6900 - Polymer of bisphenol A di-glyc-i-dal ether, substituted al-kenes, and but-a-diene.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of bisphenol A di-glyc-i-dal... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6900 Polymer of bisphenol A di-glyc-i... subject to reporting. (1) The chemical substances identified generically as polymer of bisphenol A...

  10. Pseudosymmetric fac-di-aqua-trichlorido[(di-methyl-phosphor-yl)methanaminium-κO]manganese(II).

    PubMed

    Reiss, Guido J

    2013-05-01

    In the title compound, [Mn(C3H11NOP)Cl3(H2O)2], the Mn(II) metal center has a distorted o-cta-hedral geometry, coordinated by the three chloride ligands showing a facial arrangement. Two water mol-ecules and the O-coordinated dpmaH cation [dpmaH = (di-methyl-phosphor-yl)methanaminium] complete the coordination sphere. Each complex mol-ecule is connected to its neighbours by O-H⋯Cl and N-H⋯Cl hydrogen bonds. Two of the chloride ligands and the two water ligands form a hydrogen-bonded polymeric sheet in the ab plane. Furthermore, these planes are connected to adjacent planes by hydrogen bonds from the aminium function of cationic dpmaH ligand. A pseudo-mirror plane perpendicular to the b axis in the chiral space group P21 is observed together with inversion twinning [ratio = 0.864 (5):0.136 (5)].

  11. DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.

    PubMed

    Gándara, Carolina; Alonso, Juan C

    2015-03-01

    Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true 4-Hydroxymethyl-2,6-di-tert-butylphenol. 178.2550 Section 178.2550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  13. 21 CFR 178.2550 - 4-Hydroxymethyl-2,6-di-tert-butylphenol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false 4-Hydroxymethyl-2,6-di-tert-butylphenol. 178.2550 Section 178.2550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND...

  14. Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area induces reinstatement of cocaine-seeking behaviour in rats.

    PubMed

    Placenza, Franca M; Fletcher, Paul J; Rotzinger, Susan; Vaccarino, Franco J

    2004-12-01

    The mesocorticolimbic dopamine (DA) system is critically involved in mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a neuropeptide that significantly interacts with the mesocorticolimbic system, therefore suggesting a possible role for the SP system in the mediation of relapse. This study examined the effects of injections of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of cocaine-seeking behaviour, as well as on locomotor activity in rats. Additionally, this study examined whether these effects are DA-dependent. Rats were trained to self-administer cocaine for 15 days followed by 15 days of extinction. Reinstatement of cocaine-seeking behaviour was then measured in response to bilateral intra-VTA microinjections of DiMe-C7 (0, 0.1, 0.5 and 2.5 microg). In a separate group of rats, locomotor activity was measured in response to intra-VTA injections of DiMe-C7 (0, 0.5, 1.5 and 3 microg). The effects of pre-treatment with DA receptor antagonists on DiMe-C7-induced reinstatement and locomotor activity were also examined. Animals were pre-treated with the D(1) and D(2) receptor antagonists, SCH23390 and haloperidol (0, 0.01 and 0.03 mg/kg, IP), respectively, prior to receiving intra-VTA injections of DiMe-C7 (0 and 2.5 microg). Infusion of DiMe-C7 into the VTA increased locomotor activity and induced reinstatement of cocaine-seeking behaviour. Both SCH23390 and haloperidol blocked intra-VTA DiMe-C7-induced locomotor activation. In addition, SCH23390 attenuated DiMe-C7-induced reinstatement of cocaine-seeking behaviour, while haloperidol had no effect. These results suggest that interactions between SP and the mesocorticolimbic DA system may play a role in mediating reinstatement of cocaine-seeking behaviour and that the involvement of these interactions in reinstatement are dependent upon D(1) receptor mechanisms.

  15. EFFECTS OF SEWAGE SLUDGE ON DI-(2-ETHYLHEXYL) PHTHALATE UPTAKE BY PLANTS

    EPA Science Inventory

    Di-(2-ethylhexyl) phthalate (DEHP) is a priority organic pollutant frequently found in municipal sludges. reenhouse study was conducted to determine the effects of sludge on plant uptake of 14 C-DEHP (carbonyl labeled). lants grown included three food chain crops, lettuce (Lactuc...

  16. Mechanosensing of shear by Pseudomonas aeruginosa leads to increased levels of the cyclic-di-GMP signal initiating biofilm development

    PubMed Central

    Rodesney, Christopher A.; Roman, Brian; Dhamani, Numa; Cooley, Benjamin J.; Katira, Parag; Touhami, Ahmed; Gordon, Vernita D.

    2017-01-01

    Biofilms are communities of sessile microbes that are phenotypically distinct from their genetically identical, free-swimming counterparts. Biofilms initiate when bacteria attach to a solid surface. Attachment triggers intracellular signaling to change gene expression from the planktonic to the biofilm phenotype. For Pseudomonas aeruginosa, it has long been known that intracellular levels of the signal cyclic-di-GMP increase upon surface adhesion and that this is required to begin biofilm development. However, what cue is sensed to notify bacteria that they are attached to the surface has not been known. Here, we show that mechanical shear acts as a cue for surface adhesion and activates cyclic-di-GMP signaling. The magnitude of the shear force, and thereby the corresponding activation of cyclic-di-GMP signaling, can be adjusted both by varying the strength of the adhesion that binds bacteria to the surface and by varying the rate of fluid flow over surface-bound bacteria. We show that the envelope protein PilY1 and functional type IV pili are required mechanosensory elements. An analytic model that accounts for the feedback between mechanosensors, cyclic-di-GMP signaling, and production of adhesive polysaccharides describes our data well. PMID:28533383

  17. An ab initio molecular dynamics study of thermal decomposition of 3,6-di(azido)-1,2,4,5-tetrazine.

    PubMed

    Wu, Qiong; Zhu, Weihua; Xiao, Heming

    2014-10-21

    Ab initio molecular dynamics simulations were performed to study the thermal decomposition of isolated and crystal 3,6-di(azido)-1,2,4,5-tetrazine (DiAT). During unimolecular decomposition, the three different initiation mechanisms were observed to be N-N2 cleavage, ring opening, and isomerization, respectively. The preferential initial decomposition step is the homolysis of the N-N2 bond in the azido group. The release mechanisms of nitrogen gas are found to be very different in the early and later decomposition stages of crystal DiAT. In the early decomposition, DiAT decomposes very fast and drastically without forming any stable long-chains or heterocyclic clusters, and most of the nitrogen gases are released through rapid rupture of nitrogen-nitrogen and carbon-nitrogen bonds. But in the later decomposition stage, the release of nitrogen gas is inhibited due to low mobility, long distance from each other, and strong carbon-nitrogen bonds. To overcome the obstacles, the nitrogen gases are released through slow formation and disintegration of polycyclic networks. Our simulations suggest a new decomposition mechanism for the organic polyazido initial explosive at the atomistic level.

  18. The cyclic-di-GMP phosphodiesterase BinA negatively regulates cellulose-containing biofilms in Vibrio fischeri.

    PubMed

    Bassis, Christine M; Visick, Karen L

    2010-03-01

    Bacteria produce different types of biofilms under distinct environmental conditions. Vibrio fischeri has the capacity to produce at least two distinct types of biofilms, one that relies on the symbiosis polysaccharide Syp and another that depends upon cellulose. A key regulator of biofilm formation in bacteria is the intracellular signaling molecule cyclic diguanylate (c-di-GMP). In this study, we focused on a predicted c-di-GMP phosphodiesterase encoded by the gene binA, located directly downstream of syp, a cluster of 18 genes critical for biofilm formation and the initiation of symbiotic colonization of the squid Euprymna scolopes. Disruption or deletion of binA increased biofilm formation in culture and led to increased binding of Congo red and calcofluor, which are indicators of cellulose production. Using random transposon mutagenesis, we determined that the phenotypes of the DeltabinA mutant strain could be disrupted by insertions in genes in the bacterial cellulose biosynthesis cluster (bcs), suggesting that cellulose production is negatively regulated by BinA. Replacement of critical amino acids within the conserved EAL residues of the EAL domain disrupted BinA activity, and deletion of binA increased c-di-GMP levels in the cell. Together, these data support the hypotheses that BinA functions as a phosphodiesterase and that c-di-GMP activates cellulose biosynthesis. Finally, overexpression of the syp regulator sypG induced binA expression. Thus, this work reveals a mechanism by which V. fischeri inhibits cellulose-dependent biofilm formation and suggests that the production of two different polysaccharides may be coordinated through the action of the cellulose inhibitor BinA.

  19. Evaluation of in vitro properties of di-tri-octahedral smectite on clostridial toxins and growth.

    PubMed

    Weese, J S; Cote, N M; deGannes, R V G

    2003-11-01

    Clostridial colitis and endotoxaemia of intestinal origin are significant causes of morbidity and mortality in horses. Intestinal adsorbents are available for treatment of these conditions; however, little information exists supporting their use. To evaluate the ability of di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C. perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions of metronidazole in vitro. Clostridium difficile toxins, C. perfringens enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octahedral smectite, then tested for the presence of clostridial toxins or endotoxin using commercial tests. Serial dilutions of smectite were tested for the ability to inhibit growth of C. perfringens in culture broth, and to interfere with the effect of metronidazole on growth of C. perfringens in culture broth. Clostridium difficile toxins A and B, and C. perfringens enterotoxin were completely bound at dilutions of 1:2 to 1:16. Partial binding of C. difficile toxins occurred at dilutions up to 1:256 while partial binding of C. perfringens enterotoxin occurred up to a dilution of 1:128. Greater than 99% binding of endotoxin occurred with dilutions 1:2 to 1:32. No inhibition of growth of C. difficile or C. perfringens was present at any dilution, and there was no effect on the action of metronidazole. Di-tri-octahedral smectite possesses the ability to bind C. difficile toxins A and B, C. perfringens enterotoxin and endotoxin in vivo while having no effect on bacterial growth or the action of metronidazole. In vivo studies are required to determine whether di-tri-octahedral smectite might be a useful adjunctive treatment of clostridial colitis and endotoxaemia in horses.

  20. Principles of diet therapy in ancient Chinese medicine: 'Huang Di Nei Jing'.

    PubMed

    Ho, Z C

    1993-06-01

    Huang Di Nei Jing, the first systematic Chinese medical book, was compiled from the observations of imperial herbal doctors in the Qin and Han periods (221 BC - 220 AD). From this classic traditional source may be derived the concept of a balanced and complete diet and probably the world's first dietary guidelines. Basic to the tradition are han, re, wen and bu foods, respectively 'cold', 'hot', 'neutral', 'strengthening'. Basic to Chinese cuisine are jan and tsai- 'cereal' (the rice staple and main meal) and 'dishes' to accompany the rice. Chinese traditional medicine, as in Huang Di Nei Jing, considers the nourishment of body and mind. It also emphasises that herbal medicine and food have the same origin. Diet was essential to the prevention of disease which a glossary of Chinese terms is given at the end of the paper in the Chinese tradition, was superior to treatment.

  1. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM ...

    EPA Pesticide Factsheets

    this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet. Raw data file from our published studies on DIBP specifically requested (6/14/2016) by NCEA scientists for analysis and inclusion in their assessment of this chemical.

  2. The Instructional Instrument SL-EDGE Student Library-Educational DiGital Environment.

    ERIC Educational Resources Information Center

    Kyriakopoulou, Antonia; Kalamboukis, Theodore

    An educational digital environment that will provide appropriate methods and techniques for the support and enhancement of the educational and learning process is a valuable tool for both educators and learners. In the context of such a mission, the educational tool SL-EDGE (Student Library-Educational DiGital Environment) has been developed. The…

  3. Di(phenylpropylamino)gossypol: a derivative of the dimeric natural product gossypol

    USDA-ARS?s Scientific Manuscript database

    Di(phenylpropylamino)gossypol [2,2'-bis(1,6-dihydroxy,-5-isopropyl,-8-methineaminopropylbenzene-3-methyl)-naphthylene-7-one, C48H52N2O6] is formed by reaction of the dimeric natural product gossypol with 3-phenyl-1-propylamine. When crystallized from diethyl ether, the compound has monoclinic (P21/c...

  4. DEVELOPMENTAL EXPOSURE TO DI-N-BUTYLTIN DICHLORIDE (DBTC): IMMUNOTOXIC AND NEUROTOXIC EVALUATION

    EPA Science Inventory

    Organotins are incorporated as stabilizers in PVC water supply pipe. Particularly when new, mono- and di-substituted methyl- and butyltins leach from the pipe and are thus of regulatory concern to EPA. These contaminants have adverse effects on both the immune and nervous systems...

  5. Gelling Mechanism of Aluminum Di-Soaps in Oils

    NASA Astrophysics Data System (ADS)

    Wang, Xiaorong; Rackaitis, Mindaugas

    2009-03-01

    This work demonstrates that aluminum di-soaps form nano-sized spherical micelles in the oils and that the aggregation of these micelles forms a network that gives rise to a gel formation -- thereby refuting a long-held belief that the gel formation was the result of linear polymeric chains of aluminum association. The discovery of such aluminum nano-particles could expand application of these materials to new technologies because these materials are chemically inert, odorless and nontoxic, and have been widely used in greases, paints, gels, cosmetics, drugs and foods.

  6. Production of aromatics from di- and polyoxygenates

    DOEpatents

    Beck, Taylor; Blank, Brian; Jones, Casey; Woods, Elizabeth; Cortright, Randy

    2016-08-02

    Methods, catalysts, and reactor systems for producing in high yield aromatic chemicals and liquid fuels from a mixture of oxygenates comprising di- and polyoxygenates are disclosed. Also disclosed are methods, catalysts, and reactor systems for producing aromatic chemicals and liquid fuels from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like; and methods, catalysts, and reactor systems for producing the mixture of oxygenates from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like. The disclosed catalysts for preparing the mixture of oxygenates comprise a Ni.sub.nSn.sub.m alloy and a crystalline alumina support.

  7. Production of aromatics from di- and polyoxygenates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beck, Taylor; Blank, Brian; Jones, Casey

    Methods, catalysts, and reactor systems for producing in high yield aromatic chemicals and liquid fuels from a mixture of oxygenates comprising di- and polyoxygenates are disclosed. Also disclosed are methods, catalysts, and reactor systems for producing aromatic chemicals and liquid fuels from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like; and methods, catalysts, and reactor systems for producing the mixture of oxygenates from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like. The disclosed catalysts for preparing the mixture of oxygenates comprise a Ni.sub.nSn.sub.m alloy and a crystalline aluminamore » support.« less

  8. Production of aromatics from di- and polyoxygenates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beck, Taylor; Blank, Brian; Jones, Casey

    Methods, catalysts, and reactor systems for producing in high yield aromatic chemicals and liquid fuels from a mixture of oxygenates comprising di- and polyoxygenates are disclosed. Also disclosed are methods, catalysts, and reactor systems for producing aromatic chemicals and liquid fuels from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like; and methods, catalysts, and reactor systems for producing the mixture of oxygenates from oxygenated hydrocarbons such as carbohydrates, sugars, sugar alcohols, sugar degradation products, and the like. The disclosed catalysts for preparing the mixture of oxygenates comprise a Group VIII metal and a crystallinemore » alumina support.« less

  9. DECHLORINATION ACTIVITY (CROSS-ACCLIMATION) OF FRESHWATER SEDIMENTS ADAPTED TO MONO- AND DI-CHLOROPHENOLS

    EPA Science Inventory

    The reductive dechlorination of chlorophenols (CPs) in sediment slurries (10% solids) adapted to dechlorinate mono- and di-CPs (DCP) was investigated to define the regiospecificity of the dechlorination reaction. nadapted sediment slurries amended with various ortho-substituted C...

  10. MODULATION OF RAT LEYDIG CELL STEROIDOGENIC FUNCTION BY DI(2-ETHYLHEXYL)PHTHALATE

    EPA Science Inventory

    Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate.

    Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, Zirkin BR, Hardy MP.

    Center for Biomedical Research, Population Council, New York, New York 10021, USA. benson@popcbr...

  11. Partial attenuation of Marek's disease virus by manipulation of Di-codon bias

    USDA-ARS?s Scientific Manuscript database

    All species studied to date demonstrate a preference for certain codons over other synonymous codons (codon bias), a preference which is also observed for pairs of codons (di-codon bias). Previous studies using poliovirus and influenza virus as models have demonstrated the ability to cause attenuat...

  12. DiAlert: a prevention program for overweight first degree relatives of type 2 diabetes patients: results of a pilot study to test feasibility and acceptability.

    PubMed

    Heideman, Wieke H; de Wit, Maartje; Middelkoop, Barend J C; Nierkens, Vera; Stronks, Karien; Verhoeff, Arnoud P; Snoek, Frank J

    2012-09-27

    Prevalence of type 2 diabetes mellitus is increasing due to lifestyle changes, particularly affecting those genetically at risk. We developed DiAlert as a targeted group-based intervention aimed to promote intrinsic motivation and action planning for lifestyle changes and weight loss in first degree relatives of patients with type 2 diabetes mellitus.The main objective of the pilot of the DiAlert intervention was to assess fidelity, feasibility and acceptability prior to starting the randomized controlled trial. Individuals with a family history of type 2 diabetes mellitus were self-identified and screened for eligibility. DiAlert consists of two group sessions. Feasibility, fidelity, acceptability and self-reported perceptions and behavioral determinants were evaluated in a pre-post study using questionnaires and observations. Determinants of behavior change were analyzed using paired-samples t tests and Wilcoxon signed rank tests. DiAlert was delivered to two groups of first degree relatives of patients with type 2 diabetes mellitus (N = 9 and N = 12). Feasibility and fidelity were confirmed. Overall, the DiAlert group sessions were positively evaluated (8.0 on a scale of 1 to 10) by participants. The intervention did not impact perceived susceptibility or worry about personal diabetes risk. Action planning with regard to changing diet and physical activity increased. DiAlert proved feasible and was well-accepted by participants. Positive trends in action planning indicate increased likelihood of actual behavior change following DiAlert. Testing the effectiveness in a randomized controlled trial is imperative. Netherlands National Trial Register (NTR): NTR2036.

  13. Localization of the human mitochondrial citrate transporter protein gene to chromosome 22q11 in the DiGeorge syndrome critical region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heisterkamp, N.; Hoeve, J.T.; Groffen, J.

    A high percentage of patients with DiGeorge syndrome and velo-cardio-facial syndrome have interstitial deletions on chromosome 22q11. The shortest region of overlap is currently estimated to be around 500 kb. Two segments of DNA from chromosome 22q11, located 160 kb apart, were cloned because they contained NotI restriction enzyme sites. In the current study we demonstrate that these segments are absent from chromosomes 22 carrying microdeletions of two different DiGeorge patients. Fluorescence in situ and Southern blot hybridization was further used to show that this locus is within the DiGeorge critical region. Phylogenetically conserved sequences adjacent to one of themore » two NotI sites hybridized to mRNAs in different human cell lines. cDNAs isolated with a probe from this segment showed it to contain the gene for the human mitochondrial citrate transporter protein. Deletion of this gene in DiGeorge may contribute to the mental deficiency seen in the patients. 35 refs., 5 figs.« less

  14. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L.

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOFmore » and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.« less

  15. Crystal structure of benzyl (E)-2-(3,4-di-meth-oxy-benzyl-idene)hydrazine-1-carbodi-thio-ate.

    PubMed

    Tan, Yew-Fung; Break, Mohammed Khaled Bin; Tahir, M Ibrahim M; Khoo, Teng-Jin

    2015-02-01

    The title compound, C17H18N2O2S2, synthesized via a condensation reaction between S-benzyl di-thio-carbazate and 3,4-di-meth-oxy-benzaldehyde, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. Both mol-ecules have an L-shape but differ in the orientation of the benzyl ring with respect to the 3,4-di-meth-oxy-benzyl-idine ring, this dihedral angle is 65.59 (8)° in mol-ecule A and 73.10 (8)° in mol-ecule B. In the crystal, the A and B mol-ecules are linked via pairs of N-H⋯S hydrogen bonds, forming dimers with an R 2 (2)(8) ring motif. The dimers are linked via pairs of C-H⋯O hydrogen bonds, giving inversion dimers of dimers. These units are linked by C-H⋯π inter-actions, forming ribbons propagating in the [100] direction.

  16. The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control

    PubMed Central

    Lindenberg, Sandra; Klauck, Gisela; Pesavento, Christina; Klauck, Eberhard; Hengge, Regine

    2013-01-01

    C-di-GMP—which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)—is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and—by direct and specific interaction—activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling. PMID:23708798

  17. MECHANISTIC CONSIDERATIONS FOR HUMAN RELEVANCE OF CANCER HAZARD OF DI(2-ETHYLHEXYL) PHTHALATE

    EPA Science Inventory

    Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and enviro...

  18. 40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

  19. 40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

  20. 40 CFR 721.10395 - Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...., polymers with adipic acid and triethanolamine, di-Me sulfate-quaternized. 721.10395 Section 721.10395... Fatty acids, C14-18 and C16-18 unsatd., polymers with adipic acid and triethanolamine, di-Me sulfate... sulfate-quaternized (PMN P-10-458; CAS No. 1211825-32-9) is subject to reporting under this section for...

  1. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  2. Mechanisms of Decreased Moisture Uptake in ortho- Methylated Di(Cyanate Esters)

    DTIC Science & Technology

    2014-10-01

    Distribution A: Approved for public release; distribution is unlimited. 1 Mechanisms of Decreased Moisture Uptake in ortho- Methylated Di(Cyanate...when analogous networks containing a single methyl group ortho- to each aryl- cyanurate linkage were prepared by reduction and acid-catalyzed coupling...of salicylic acid followed by treatment with cyanogen bromide and subsequent cyclotrimerization. The differences in water uptake were observed

  3. Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome

    PubMed Central

    Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva

    2015-01-01

    A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0–120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome. PMID:26783479

  4. Numerical evaluation of magnetic absolute measurements with arbitrarily distributed DI-fluxgate theodolite orientations

    NASA Astrophysics Data System (ADS)

    Brunke, Heinz-Peter; Matzka, Jürgen

    2018-01-01

    At geomagnetic observatories the absolute measurements are needed to determine the calibration parameters of the continuously recording vector magnetometer (variometer). Absolute measurements are indispensable for determining the vector of the geomagnetic field over long periods of time. A standard DI (declination, inclination) measuring scheme for absolute measurements establishes routines in magnetic observatories. The traditional measuring schema uses a fixed number of eight orientations (Jankowski et al., 1996).

    We present a numerical method, allowing for the evaluation of an arbitrary number (minimum of five as there are five independent parameters) of telescope orientations. Our method provides D, I and Z base values and calculated error bars of them.

    A general approach has significant advantages. Additional measurements may be seamlessly incorporated for higher accuracy. Individual erroneous readings are identified and can be discarded without invalidating the entire data set. A priori information can be incorporated. We expect the general method to also ease requirements for automated DI-flux measurements. The method can reveal certain properties of the DI theodolite which are not captured by the conventional method.

    Based on the alternative evaluation method, a new faster and less error-prone measuring schema is presented. It avoids needing to calculate the magnetic meridian prior to the inclination measurements.

    Measurements in the vicinity of the magnetic equator are possible with theodolites and without a zenith ocular.

    The implementation of the method in MATLAB is available as source code at the GFZ Data Center Brunke (2017).

  5. [Synthesis and spectral characteristics of novel di-schiff base derivatives incorporting oxadiazole ring].

    PubMed

    Chen, Tong-bin; Zhang, Xiong-lu; Fan, Xiao-lin; Li, Xun

    2008-12-01

    4-nitrobenzoic acid and hydraxine sulfate were cyclized with H3PO4/P2O5 to afford 2,5-bis(4-nitrophenyl)-1, 3,4-oxadiazole(1), then(1)was reduced to 2,5-bis(4-aminophenyl)-1,3,4-oxadiazole using Zn/CaCl2 as reduction reagent, and at last, a series of novel di-schiff base derivatives containing oxadiazole ring were obtained by the reaction of 2,5-bis(4-aminophenyl)-1, 3,4-oxadiazole with aromatic aldehydes (yield: 65%-81%). The structures of these compounds were confirmed by 1H NMR, FTIR and MS. Their UV-Vis spectra as well as fluorescence spectra were studied and the electrochemical properties were tested with cyclic voltammetry. The UV-Vis spectroscopy results show that the characteristic absorption peaks of 1, 3, 4-oxadiazole unit and di-schiff base unit disappeared. The maximum absorption wavelength was detected at 345-357 nm because conjugation effect made the two energy bands partially hybrid and form a new energy band structure. Fluorescence spectroscopy results show that they emit strong blue and purple fluorescence, and the emission maximum wavelengths of di-schiff base are from 390 to 407 nm. Electrochemical properties results show that they have higher affinity energy (2.36-3.04 eV) and ionic potential (5.35-6.06 eV), which indicated that they have better electron-transporting properties than PBD except 3 a and 3 h. The results give a reference to further application to organic electroluminescent devices of the target compound.

  6. Kinetic Measurements of Di- and Tripeptide and Peptidomimetic Drug Transport in Different Kidney Regions Using the Fluorescent Membrane Potential-Sensitive Dye, DiS-C3-(3).

    PubMed

    Alghamdi, Othman A; King, Nicola; Jones, Graham L; Moens, Pierre D J

    2017-12-01

    Tri- and dipeptides are transported in the kidney by PEPT1 and PEPT2 isoforms. The aim of this study was to investigate differences in transport kinetics between renal brush border (BBMV) and outer medulla (OMMV) membrane vesicles (where PEPT1 and PEPT2 are sequentially available) for a range of di- and tripeptides and peptidomimetic drugs. This was accomplished through the use of the potential-sensitive fluorescent dye 3,3'-dipropylthiacarbocyanine iodide [DiS-C 3 -(3)]. BBMV and OMMV were prepared from the rat kidney using standard techniques. The presence of PEPT1 in BBMV and PEPT2 in OMMV was confirmed using Western blotting. Fluorescence changes were measured when extravesicular medium at pH 6.6 containing 0-1 mM substrates was added to a cuvette containing vesicles pre-equilibrated at pH 7.4 and 2.71 μM DiS-C 3 -(3). An increase in fluorescence intensity occurred upon substrate addition reflecting the expected positive change in membrane potential difference. Of the range of substrates studied, OMMV manifested the highest affinity to cefadroxil and valacyclovir (K m 4.3 ± 1.2 and 11.7 ± 3.2 µM, respectively) compared to other substrates, whilst the BBMV showed a higher affinity to Gly-His (K m 15.4 ± 3.1 µM) compared to other substrates. In addition, OMMV showed higher affinity and capacity to Gly-Gln (K m 47.1 ± 9.8 µM, 55.5 ± 2.8 ΔF/s/mg protein) than BBMV (K m 78.1 ± 13.3 µM and 35.5 ± 1.7 ΔF/s/mg protein, respectively). In conclusion, this study successfully separated the expression of PEPT1 and PEPT2 into different vesicle preparations inferring their activity in different regions of the renal proximal tubule.

  7. Comparison of stabilization by Vitamin E and 2,6-di-tert-butylphenols during polyethylene radio-thermal-oxidation

    NASA Astrophysics Data System (ADS)

    Richaud, Emmanuel

    2014-10-01

    This paper reports a compilation of data for PE+Vitamin E and 2,6-di-tert-butylphenols oxidation in radio-thermal ageing. Data unambiguously show that Vitamin E reacts with Prad and POOrad whereas 2,6-di-tert-butyl phenols only react with POOrad. Kinetic parameters of the stabilization reactions for both kinds of antioxidants were tentatively extracted from phenol depletion curves, and discussed regarding the structure of the stabilizer. They were also used for completing an existing kinetic model used for predicting the stabilization by antioxidants. This one permits to compare the efficiency of stabilizer with dose rate or sample thickness.

  8. Dose Reconstruction of Di-2-Ethylhexyl Phthalate Using a Simple Pharmacokinetic Model [Manuscript

    EPA Science Inventory

    Background In 2005, eight adults provided full volumes and times of urine voids during one normal work week. These samples were analyzed for four di-2-ethylhexyl phthalate (DEHP) metabolites. Participants also provided diary information on their diet, driving, and out¬door a...

  9. VITELLOGENIN GENE EXPRESSION IN MALE FATHEAD MINNOWS EXPOSED TO DI(2-ETHYLHEXYL)PHTHALATE

    EPA Science Inventory

    Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used extensively in the plastics industry. DEHP has been shown to be ubiquitous in the environment and has been detected in ground and surface waters, sediment sludge and at several Superfund sites. Previous studies using rats ...

  10. Analysis of proton wires in the enzyme active site suggests a mechanism of c-di-GMP hydrolysis by the EAL domain phosphodiesterases.

    PubMed

    Grigorenko, Bella L; Knyazeva, Marina A; Nemukhin, Alexander V

    2016-11-01

    We report for the first time a hydrolysis mechanism of the cyclic dimeric guanosine monophosphate (c-di-GMP) by the EAL domain phosphodiesterases as revealed by molecular simulations. A model system for the enzyme-substrate complex was prepared on the base of the crystal structure of the EAL domain from the BlrP1 protein complexed with c-di-GMP. The nucleophilic hydroxide generated from the bridging water molecule appeared in a favorable position for attack on the phosphorus atom of c-di-GMP. The most difficult task was to find a pathway for a proton transfer to the O3' atom of c-di-GMP to promote the O3'P bond cleavage. We show that the hydrogen bond network extended over the chain of water molecules in the enzyme active site and the Glu359 and Asp303 side chains provides the relevant proton wires. The suggested mechanism is consistent with the structural, mutagenesis, and kinetic experimental studies on the EAL domain phosphodiesterases. Proteins 2016; 84:1670-1680. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. A Search for Supersymmetric Higgs Bosons in the Di-tau Decay Mode in Proton - Anti-proton Collisions at 1.8 TeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Connolly, Amy Lynn

    A search for directly produced Supersymmetric Higgs Bosons has been performed in the di-tau decay channel in 86.3 ± 3.5 pb -1 of data collected by CDF during Run1b at the Tevatron. They search for events where one tau decays to an electron and the other tau decays hadronically. They perform a counting experiment and set limits on the cross section for Higgs production in the high tan β region of the m A-tan β plane. For a benchmark parameter space point where m A = 100 and tan β = 50, they set a 95% confidence level upper limitmore » at 891 pb compared to the theoretically predicted cross section of 122 pb. For events where the tau candidates are not back-to-back, they utilize a di-tau mass reconstruction technique for the first time on hadron collider data. Limits based on a likelihood binned in di-tau mass from non-back-to-back events alone are weaker than the limits obtained from the counting experiment using the full di-tau sample.« less

  12. DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

    PubMed Central

    Scornik, Fabiana S.; Bucciero, Ronald S.; Wu, Yuesheng; Selga, Elisabet; Bosch Calero, Cristina; Brugada, Ramon

    2013-01-01

    The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK) channel activator with selectivity for its β1- or β4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming α-subunit and a smooth muscle-abundant regulatory β1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the β1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its α-subunit. We studied BK channels from wild-type and transgenic β1-knockout mice in excised patches. BK channels from brain arteries, with or without the β1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) (∼30 μM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as −300 mV. This “sweet spot” for persistent activation is independent of Ca2+ and/or the β1–4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. PMID:23542916

  13. The RNA binding protein CsrA controls c-di-GMP metabolism by directly regulating the expression of GGDEF proteins

    PubMed Central

    Jonas, Kristina; Edwards, Adrianne N.; Simm, Roger; Romeo, Tony; Römling, Ute; Melefors, Öjar

    2009-01-01

    Summary The carbon storage regulator CsrA is an RNA binding protein that controls carbon metabolism, biofilm formation and motility in various eubacteria. Nevertheless, in Escherichia coli only five target mRNAs have been shown to be directly regulated by CsrA at the post-transcriptional level. Here we identified two new direct targets for CsrA, ycdT and ydeH, both of which encode proteins with GGDEF domains. A csrA mutation caused mRNA levels of ycdT and ydeH to increase more than 10-fold. RNA mobility shift assays confirmed the direct and specific binding of CsrA to the mRNA leaders of ydeH and ycdT. Overexpression of ycdT and ydeH resulted in a more than 20-fold increase in the cellular concentration of the second messenger c-di-GMP, implying that both proteins possess diguanylate cyclase activity. Phenotypic characterization revealed that both proteins are involved in the regulation of motility in a c-di-GMP dependent manner. CsrA was also found to regulate the expression of five additional GGDEF/EAL proteins and a csrA mutation led to modestly increased cellular levels of c-di-GMP. All together, these data demonstrate a global role for CsrA in the regulation of c-di-GMP metabolism by regulating the expression of GGDEF proteins at the post-transcriptional level. PMID:18713317

  14. Analysis of the Borrelia burgdorferi Cyclic-di-GMP-Binding Protein PlzA Reveals a Role in Motility and Virulence ▿

    PubMed Central

    Pitzer, Joshua E.; Sultan, Syed Z.; Hayakawa, Yoshihiro; Hobbs, Gerry; Miller, Michael R.; Motaleb, Md A.

    2011-01-01

    The cyclic-dimeric-GMP (c-di-GMP)-binding protein PilZ has been implicated in bacterial motility and pathogenesis. Although BB0733 (PlzA), the only PilZ domain-containing protein in Borrelia burgdorferi, was reported to bind c-di-GMP, neither its role in motility or virulence nor it's affinity for c-di-GMP has been reported. We determined that PlzA specifically binds c-di-GMP with high affinity (dissociation constant [Kd], 1.25 μM), consistent with Kd values reported for c-di-GMP-binding proteins from other bacteria. Inactivation of the monocistronically transcribed plzA resulted in an opaque/solid colony morphology, whereas the wild-type colonies were translucent. While the swimming pattern of mutant cells appeared normal, on swarm plates, mutant cells exhibited a significantly reduced swarm diameter, demonstrating a role of plzA in motility. Furthermore, the plzA mutant cells were significantly less infectious in experimental mice (as determined by 50% infectious dose [ID50]) relative to wild-type spirochetes. The mutant also had survival rates in fed ticks lower than those of the wild type. Consequently, plzA mutant cells failed to complete the mouse-tick-mouse infection cycle, indicating plzA is essential for the enzootic life cycle of B. burgdorferi. All of these defects were corrected when the mutant was complemented in cis. We propose that failure of plzA mutant cells to infect mice was due to altered motility; however, the possibility that an unidentified factor(s) contributed to interruption of the B. burgdorferi enzootic life cycle cannot yet be excluded. PMID:21357718

  15. A computational investigation on the antioxidant potential of myricetin 3,4'-di-O-α-L-rhamnopyranoside.

    PubMed

    Mendes, Rodrigo A; Almeida, Shawan K C; Soares, Iuri N; Barboza, Cristina A; Freitas, Renato G; Brown, Alex; de Souza, Gabriel L C

    2018-05-11

    In this work, we present a computational study on the antioxidant potential of myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside (Compound M). A density functional theory (DFT) approach with the B3LYP and LC-ωPBE functionals and with both the 6-311G(d,p) and 6-311+G(d,p) basis sets was used. The focus of the investigation was on the structural and energetic parameters including both bond dissociation enthalpies (BDEs) and ionization potentials (IPs), which provide information on the potential antioxidant activity. The properties computed were compared with BDEs and IPs available in the literature for myricetin, a compound well known for presenting antioxidant activity (and the parent molecule of the compound of interest in the present work). Myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside presented the lowest BDE to be 79.13 kcal/mol (as determined using B3LYP/6-311G(d,p) in water) while myricetin has a quite similar value (within 3.4 kcal/mol). IPs computed in the gas phase [B3LYP/6-311G(d,p)] are 157.18 and 161.4 kcal/mol for myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside and myricetin, respectively. As the values of BDEs are considerably lower than the ones probed for IPs (in the gas phase or in any given solvent environment), the hydrogen atom transfer mechanism is preferred over the single electron transfer mechanism. The BDEs obtained suggest that myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside can present antioxidant potential as good as the parent molecule myricetin (a well-known antioxidant). Therefore, experimental tests on the antioxidant activity of Compound M are encouraged.

  16. Mechanism of silver-mediated di-tert-butylsilylene transfer from a silacyclopropane to an alkene.

    PubMed

    Driver, Tom G; Woerpel, K A

    2004-08-18

    Kinetic studies of the reactions of cyclohexene silacyclopropane 1 and monosubstituted alkenes in the presence of 5 mol % of (Ph3P)2AgOTf suggested a possible mechanism for silver-mediated di-tert-butylsilylene transfer. The kinetic order in cyclohexene silacyclopropane 1 was determined to be one. Inverse kinetic saturation behavior (rate inhibition) was observed in monosubstituted alkene and cyclohexene concentrations. Saturation kinetic behavior in catalyst concentration was observed. A reactive intermediate, a silylsilver complex, was observed using low temperature 29Si NMR spectroscopy. Competition experiments between substituted styrenes and a deficient amount of 1 correlated well with the Hammett equation and provided a rho value of -0.62 +/- 0.02 using sigmap constants. These data support a mechanism involving reversible silver-promoted di-tert-butylsilylene extrusion from 1 followed by irreversible concerted electrophilic attack of the silylsilver intermediate on the alkene.

  17. Traceability of 'Limone di Siracusa PGI' by a multidisciplinary analytical and chemometric approach.

    PubMed

    Amenta, M; Fabroni, S; Costa, C; Rapisarda, P

    2016-11-15

    Food traceability is increasingly relevant with respect to safety, quality and typicality issues. Lemon fruits grown in a typical lemon-growing area of southern Italy (Siracusa), have been awarded the PGI (Protected Geographical Indication) recognition as 'Limone di Siracusa'. Due to its peculiarity, consumers have an increasing interest about this product. The detection of potential fraud could be improved by using the tools linking the composition of this production to its typical features. This study used a wide range of analytical techniques, including conventional techniques and analytical approaches, such as spectral (NIR spectra), multi-elemental (Fe, Zn, Mn, Cu, Li, Sr) and isotopic ((13)C/(12)C, (18)O/(16)O) marker investigations, joined with multivariate statistical analysis, such as PLS-DA (Partial Least Squares Discriminant Analysis) and LDA (Linear Discriminant Analysis), to implement a traceability system to verify the authenticity of 'Limone di Siracusa' production. The results demonstrated a very good geographical discrimination rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Selective identification of specialized pro-resolving lipid mediators from their biosynthetic double di-oxygenation isomers.

    PubMed

    Hansen, Trond V; Dalli, Jesmond; Serhan, Charles N

    The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions. Most often the different families among these mediators are chemically characterized by two or three chiral, secondary alcohols, separated by either an E,E,Z -triene or an E,Z,E,E -tetraenemoiety. The lipoxygenases also form other oxygenated polyunsaturated natural products, coined double di-oxygenation products, that are constitutional isomers of the protectin and maresin families of specialized pro-resolving lipid mediators. Very often these products exhibit similar chromatographic properties and mass spectrometrical fragment ions as the pro-resolving mediators. In addition, the double di-oxygenation products are sometimes formed in larger amounts than the specialized pro-resolving lipid mediators. Thus, it is not always possible to distinguish between the specialized pro-resolving mediators and their double di-oxygenation isomers in biological systems, using LC/MS-based techniques. Herein, a convenient and easy-to-use protocol to meet this challenge is presented.

  19. [The Istituto di Storia della Medicina archive and video collection].

    PubMed

    Aruta, Alessandro; De Angelis, Elio

    2006-01-01

    The Istituto di Storia della Medicina at Rome University was to a certain extent a one-man achievement. Founded by Adalberto Pazzini in 1937, its collections comprehended books, objects, as well as photographs, movies, and other didactic video. The Istituto was also a center for publications, conferences and meetings. The archival sources that document its activity have been re-evaluated and restored in recent years, together with the collections housed in the Library and in the Museum.

  20. Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs

    PubMed Central

    Yip, W. S. Vincent; Shigematsu, Hideki; Taylor, David W.; Baserga, Susan J.

    2016-01-01

    Ribosomal RNA (rRNA) modifications are essential for ribosome function in all cellular organisms. Box C/D small (nucleolar) ribonucleoproteins [s(no)RNPs] catalyze 2′-O-methylation, one rRNA modification type in Eukarya and Archaea. Negatively stained electron microscopy (EM) models of archaeal box C/D sRNPs have demonstrated the dimeric sRNP (di-sRNP) architecture, which has been corroborated by nuclear magnetic resonance (NMR) studies. Due to limitations of the structural techniques, the orientation of the box C/D sRNAs has remained unclear. Here, we have used cryo-EM to elucidate the sRNA orientation in a M. jannaschii box C/D di-sRNP. The cryo-EM reconstruction suggests a parallel orientation of the two sRNAs. Biochemical and structural analyses of sRNPs assembled with mutant sRNAs indicate a potential interaction between the sRNA stem ends. Our results suggest that the parallel arrangement of the sRNAs juxtaposes their stem ends into close proximity to allow for a stabilizing interaction that helps maintain the di-sRNP architecture. PMID:27342279

  1. New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity.

    PubMed

    Quiliano, Miguel; Pabón, Adriana; Ramirez-Calderon, Gustavo; Barea, Carlos; Deharo, Eric; Galiano, Silvia; Aldana, Ignacio

    2017-04-15

    We report the design (in silico ADMET criteria), synthesis, cytotoxicity studies (HepG-2 cells), and biological evaluation of 15 hydrazine/hydrazide quinoxaline 1,4-di-N-oxide derivatives against the 3D7 chloroquine sensitive strain and FCR-3 multidrug resistant strain of Plasmodium falciparum and Leishmania infantum (axenic amastigotes). Fourteen of derivatives are novel quinoxaline 1,4-di-N-oxide derivatives. Compounds 18 (3D7 IC 50 =1.40μM, FCR-3 IC 50 =2.56μM) and 19 (3D7 IC 50 =0.24μM, FCR-3 IC 50 =2.8μM) were identified as the most active against P. falciparum, and they were the least cytotoxic (CC 50 -values>241μM) and most selective (SI>86). None of the compounds tested against L. infantum were considered to be active. Additionally, the functional role of the hydrazine and hydrazide structures were studied in the quinoxaline 1,4-di-N-oxide system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying, E-mail: yygcn@163.com, E-mail: yangyg@chnu.edu.cn, E-mail: yangy818@yeah.net

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periodsmore » for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.« less

  3. Crystal structure of mer-tris-{2,6-di-fluoro-3-[5-(2-fluoro-phen-yl)pyridin-2-yl-κN]pyridin-4-yl-κC4}iridium(III) di-chloro-methane hemisolvate n-hexane hemisolvate.

    PubMed

    Kang, Youngjin; Park, Ki-Min; Kim, Jinho

    2017-12-01

    The asymmetric unit of the title compound, [Ir(C 17 H 11 F 2 N 2 ) 3 ]·0.5CH 3 (CH 2 ) 4 CH 3 ·0.5CH 2 Cl 2 , comprises one Ir III atom, three 2,6-di-fluoro-3-[5-(2-fluoro-phen-yl)pyridin-2-yl]pyridin-4-yl ligands and half each of an n -hexane and a di-chloro-methane solvent mol-ecule located about crystallographic inversion centres. The Ir III atom displays a distorted octa-hedral coordination geometry, having three C , N -chelating 2,6-di-fluoro-3-[5-(2-fluoro-phen-yl)pyridin-2-yl]pyridin-4-yl ligands arranged in a meridional manner. The Ir III ion lies almost in the equatorial plane [deviation = 0.0069 (15) Å]. The average distance [2.041 (3) Å] of Ir-C bonds is slightly shorter than that [2.076 (3) Å] of Ir-N bonds. A variety of intra- and inter-molecular C-H⋯F and C-H⋯π hydrogen bonds, as well as inter-molecular C-F⋯π inter-actions, contribute to the stabilization of the mol-ecular and crystal structures, and result in the formation of a two-dimensional network parallel to the ab plane. No inter-actions between n -hexane solvent mol-ecules and the other components in the title compound are observed.

  4. Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.

    PubMed

    Békés, Miklós; van der Heden van Noort, Gerbrand J; Ekkebus, Reggy; Ovaa, Huib; Huang, Tony T; Lima, Christopher D

    2016-05-19

    Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Method of dissolving metal oxides with di- or polyphosphonic acid and a redundant

    DOEpatents

    Horwitz, Earl P.; Chiarizia, Renato

    1996-01-01

    A method of dissolving metal oxides using a mixture of a di- or polyphosphonic acid and a reductant wherein each is present in a sufficient amount to provide a synergistic effect with respect to the dissolution of metal oxides and optionally containing corrosion inhibitors and pH adjusting agents.

  6. A Versatile Room-Temperature Route to Di- and Trisubstituted Allenes Using Flow-Generated Diazo Compounds**

    PubMed Central

    Poh, Jian-Siang; Tran, Duc N; Battilocchio, Claudio; Hawkins, Joel M; Ley, Steven V

    2015-01-01

    A copper-catalyzed coupling reaction between flow-generated unstabilized diazo compounds and terminal alkynes provides di- and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups. PMID:26013774

  7. Defective interfering particles of poliovirus: mapping of the deletion and evidence that the deletions in the genomes of DI(1), (2), and (3) are located in the same region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nomoto, A.; Jacobson, A.; Lee, Y.F.

    1979-01-01

    The deletions in RNAs of three defective interfering (DI) particles of poliovirus type 1 have been located and their approximate extent determined by three methods. (1) Digestion with RNase III of DI RNAs yields the same 3'-terminal fragments as digestion wth RNase III of standard virus RNA. The longest 3'-terminal located in the 5'-terminal half of the polio genome. (2) Fingerprints of RNase T/sub 1/-resistant oligonucleotides of all three DI RNAs are identical and lack four large oligonucleotides as compared to the fingerprints of standard virus, an observation suggesting that the deletions in all three DI RNAs are located inmore » the same reregion of the viral genome. The deletion-specific oligonucleotides have also been shown to be within the 5'-terminal half of the viral genome by alkali fragmentation of the RNA and fingerprinting poly(A)-linked (3'-terminal) fragments of decreasing size. (3) Virion RNA of DI(2) particles was annealed with denatured double-stranded RNA (RF) of standard virus and the hybrid heteroduplex molcules examined in the electron microscope. A single loop, approximately 900 nucleotides long and 20% from one end of the molecules, was observed. Both the size and extent of individual deletions is somewhat variable in different hetereoduplex molecules, an observation suggesting heterogeneity in the size of the deletion in RNA of the DI(2) population. Our data show that the DI RNAs of poliovirus contain an internal deletion in that region of the viral genome known to specify the capsid polypeptides. This result provides an explanation as to why poliovirus DI particles are unable to synthesize viral coat proteins.« less

  8. Genome-Based Comparison of Cyclic Di-GMP Signaling in Pathogenic and Commensal Escherichia coli Strains

    PubMed Central

    Povolotsky, Tatyana L.

    2015-01-01

    ABSTRACT The ubiquitous bacterial second messenger cyclic di-GMP (c-di-GMP) has recently become prominent as a trigger for biofilm formation in many bacteria. It is generated by diguanylate cyclases (DGCs; with GGDEF domains) and degraded by specific phosphodiesterases (PDEs; containing either EAL or HD-GYP domains). Most bacterial species contain multiples of these proteins with some having specific functions that are based on direct molecular interactions in addition to their enzymatic activities. Escherichia coli K-12 laboratory strains feature 29 genes encoding GGDEF and/or EAL domains, resulting in a set of 12 DGCs, 13 PDEs, and four enzymatically inactive “degenerate” proteins that act by direct macromolecular interactions. We present here a comparative analysis of GGDEF/EAL domain-encoding genes in 61 genomes of pathogenic, commensal, and probiotic E. coli strains (including enteric pathogens such as enteroaggregative, enterohemorrhagic, enteropathogenic, enterotoxigenic, and adherent and invasive Escherichia coli and the 2011 German outbreak O104:H4 strain, as well as extraintestinal pathogenic E. coli, such as uropathogenic and meningitis-associated E. coli). We describe additional genes for two membrane-associated DGCs (DgcX and DgcY) and four PDEs (the membrane-associated PdeT, as well as the EAL domain-only proteins PdeW, PdeX, and PdeY), thus showing the pangenome of E. coli to contain at least 35 GGDEF/EAL domain proteins. A core set of only eight proteins is absolutely conserved in all 61 strains: DgcC (YaiC), DgcI (YliF), PdeB (YlaB), PdeH (YhjH), PdeK (YhjK), PdeN (Rtn), and the degenerate proteins CsrD and CdgI (YeaI). In all other GGDEF/EAL domain genes, diverse point and frameshift mutations, as well as small or large deletions, were discovered in various strains. IMPORTANCE Our analysis reveals interesting trends in pathogenic Escherichia coli that could reflect different host cell adherence mechanisms. These may either benefit from or be

  9. Genome-Based Comparison of Cyclic Di-GMP Signaling in Pathogenic and Commensal Escherichia coli Strains.

    PubMed

    Povolotsky, Tatyana L; Hengge, Regine

    2016-01-01

    The ubiquitous bacterial second messenger cyclic di-GMP (c-di-GMP) has recently become prominent as a trigger for biofilm formation in many bacteria. It is generated by diguanylate cyclases (DGCs; with GGDEF domains) and degraded by specific phosphodiesterases (PDEs; containing either EAL or HD-GYP domains). Most bacterial species contain multiples of these proteins with some having specific functions that are based on direct molecular interactions in addition to their enzymatic activities. Escherichia coli K-12 laboratory strains feature 29 genes encoding GGDEF and/or EAL domains, resulting in a set of 12 DGCs, 13 PDEs, and four enzymatically inactive "degenerate" proteins that act by direct macromolecular interactions. We present here a comparative analysis of GGDEF/EAL domain-encoding genes in 61 genomes of pathogenic, commensal, and probiotic E. coli strains (including enteric pathogens such as enteroaggregative, enterohemorrhagic, enteropathogenic, enterotoxigenic, and adherent and invasive Escherichia coli and the 2011 German outbreak O104:H4 strain, as well as extraintestinal pathogenic E. coli, such as uropathogenic and meningitis-associated E. coli). We describe additional genes for two membrane-associated DGCs (DgcX and DgcY) and four PDEs (the membrane-associated PdeT, as well as the EAL domain-only proteins PdeW, PdeX, and PdeY), thus showing the pangenome of E. coli to contain at least 35 GGDEF/EAL domain proteins. A core set of only eight proteins is absolutely conserved in all 61 strains: DgcC (YaiC), DgcI (YliF), PdeB (YlaB), PdeH (YhjH), PdeK (YhjK), PdeN (Rtn), and the degenerate proteins CsrD and CdgI (YeaI). In all other GGDEF/EAL domain genes, diverse point and frameshift mutations, as well as small or large deletions, were discovered in various strains. Our analysis reveals interesting trends in pathogenic Escherichia coli that could reflect different host cell adherence mechanisms. These may either benefit from or be counteracted by the c-di

  10. Archaeomagnetic dating of Copper Age furnaces at Croce di Papa village and relations on Vesuvius and Phlegraean Fields volcanic activity

    NASA Astrophysics Data System (ADS)

    Principe, Claudia; Gogichaishvili, Avto; Arrighi, Simone; Devidze, Marina; La Felice, Sonia; Paolillo, Annarita; Giordano, Daniele; Morales, Juan

    2018-01-01

    Metallurgic furnaces, discovered in the archaeological site of Croce di Papa, Nola, at 15 km NE from the Vesuvius summit, were dated here by using archaeomagnetic technique. They are positioned between the deposits of the Vesuvius eruption of Pomici di Avellino and of the Phlegraean eruption of Agnano-Monte Spina. A revision of available age data and associated uncertainties for these two eruptions was carried out in order to provide constraints on the Croce di Papa furnaces age determination. The adopted archaeomagnetic technique provides an accurate age of 3136-3027 BCE corresponding to 5085 to 4976 a BP that represents the upper age limit of the Agnano-Monte Spina eruption. This study provides evidences for the existence of human settlements in the Campanian Plain in the first century of the forth millennium BC and allow to assess the limited impact of the Agnano-Monte Spina eruption on climate and human settlement.

  11. Detecting and measuring deprivation in primary care: development, reliability and validity of a self-reported questionnaire: the DiPCare-Q

    PubMed Central

    Bischoff, Thomas; Diserens, Esther-Amélie; Herzig, Lilli; Meystre-Agustoni, Giovanna; Panese, Francesco; Favrat, Bernard; Sass, Catherine; Bodenmann, Patrick

    2012-01-01

    Objectives Advances in biopsychosocial science have underlined the importance of taking social history and life course perspective into consideration in primary care. For both clinical and research purposes, this study aims to develop and validate a standardised instrument measuring both material and social deprivation at an individual level. Methods We identified relevant potential questions regarding deprivation using a systematic review, structured interviews, focus group interviews and a think-aloud approach. Item response theory analysis was then used to reduce the length of the 38-item questionnaire and derive the deprivation in primary care questionnaire (DiPCare-Q) index using data obtained from a random sample of 200 patients during their planned visits to an ambulatory general internal medicine clinic. Patients completed the questionnaire a second time over the phone 3 days later to enable us to assess reliability. Content validity of the DiPCare-Q was then assessed by 17 general practitioners. Psychometric properties and validity of the final instrument were investigated in a second set of patients. The DiPCare-Q was administered to a random sample of 1898 patients attending one of 47 different private primary care practices in western Switzerland along with questions on subjective social status, education, source of income, welfare status and subjective poverty. Results Deprivation was defined in three distinct dimensions: material (eight items), social (five items) and health deprivation (three items). Item consistency was high in both the derivation (Kuder-Richardson Formula 20 (KR20) =0.827) and the validation set (KR20 =0.778). The DiPCare-Q index was reliable (interclass correlation coefficients=0.847) and was correlated to subjective social status (rs=−0.539). Conclusion The DiPCare-Q is a rapid, reliable and validated instrument that may prove useful for measuring both material and social deprivation in primary care. PMID:22307103

  12. The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.

    PubMed

    Chen, Hui-Jie; Li, Na; Luo, Ye; Jiang, Yong-Liang; Zhou, Cong-Zhao; Chen, Yuxing; Li, Qiong

    2018-04-09

    The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian c G MP-regulated phosphodiesterases, Anabaena a denylyl cyclases and Escherichia coli transcription activator F hlA) domain containing bifunctional enzyme DcpA ( d iguanylate c yclase and p hosphodiesterase A ) that catalyzes the synthesis and hydrolysis of c-di-GMP . Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  13. The EIPeptiDi tool: enhancing peptide discovery in ICAT-based LC MS/MS experiments.

    PubMed

    Cannataro, Mario; Cuda, Giovanni; Gaspari, Marco; Greco, Sergio; Tradigo, Giuseppe; Veltri, Pierangelo

    2007-07-15

    Isotope-coded affinity tags (ICAT) is a method for quantitative proteomics based on differential isotopic labeling, sample digestion and mass spectrometry (MS). The method allows the identification and relative quantification of proteins present in two samples and consists of the following phases. First, cysteine residues are either labeled using the ICAT Light or ICAT Heavy reagent (having identical chemical properties but different masses). Then, after whole sample digestion, the labeled peptides are captured selectively using the biotin tag contained in both ICAT reagents. Finally, the simplified peptide mixture is analyzed by nanoscale liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nevertheless, the ICAT LC-MS/MS method still suffers from insufficient sample-to-sample reproducibility on peptide identification. In particular, the number and the type of peptides identified in different experiments can vary considerably and, thus, the statistical (comparative) analysis of sample sets is very challenging. Low information overlap at the peptide and, consequently, at the protein level, is very detrimental in situations where the number of samples to be analyzed is high. We designed a method for improving the data processing and peptide identification in sample sets subjected to ICAT labeling and LC-MS/MS analysis, based on cross validating MS/MS results. Such a method has been implemented in a tool, called EIPeptiDi, which boosts the ICAT data analysis software improving peptide identification throughout the input data set. Heavy/Light (H/L) pairs quantified but not identified by the MS/MS routine, are assigned to peptide sequences identified in other samples, by using similarity criteria based on chromatographic retention time and Heavy/Light mass attributes. EIPeptiDi significantly improves the number of identified peptides per sample, proving that the proposed method has a considerable impact on the protein identification process and, consequently, on

  14. catena-Poly[(E)-4,4′-(ethene-1,2-di­yl)dipyridinium [[bis­(thio­cyanato-κN)ferrate(II)]-di-μ-thio­cyanato-κ2 N:S;κ2 S:N

    PubMed Central

    Wöhlert, Susanne; Wriedt, Mario; Jess, Inke; Näther, Christian

    2010-01-01

    In the title compound, {(C12H12N2)[Fe(NCS)4]}n, each FeII cation is coordinated by four N-bonded and two S-bonded thio­cyanate anions in an octa­hedral coordination mode. The asymmetric unit consists of one FeII cation, located on a center of inversion, as well as one protonated (E)-4,4′-(ethene-1,2-di­yl)dipyridinium dication and two thio­cyanate anions in general positions. The crystal structure consists of Fe—(NCS)2—Fe chains extending along the a axis, in which two further thio­cyanate anions are only terminally bonded via nitro­gen. Non-coordinating (E)-4,4′-(ethene-1,2-di­yl)dipyrid­inium cations are found between the chains. PMID:21587404

  15. ChIP-Seq and RNA-Seq Reveal an AmrZ-Mediated Mechanism for Cyclic di-GMP Synthesis and Biofilm Development by Pseudomonas aeruginosa

    PubMed Central

    Jones, Christopher J.; Newsom, David; Kelly, Benjamin; Irie, Yasuhiko; Jennings, Laura K.; Xu, Binjie; Limoli, Dominique H.; Harrison, Joe J.; Parsek, Matthew R.; White, Peter; Wozniak, Daniel J.

    2014-01-01

    The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, the global effect of AmrZ on gene expression remains unknown, and therefore, AmrZ may directly regulate many additional genes that are crucial for infection. Compared to the wild type strain, a ΔamrZ mutant exhibits a rugose colony phenotype, which is commonly observed in variants that accumulate the intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic di-GMP is produced by diguanylate cyclases (DGC) and degraded by phosphodiesterases (PDE). We hypothesized that AmrZ limits the intracellular accumulation of c-di-GMP through transcriptional repression of gene(s) encoding a DGC. In support of this, we observed elevated c-di-GMP in the ΔamrZ mutant compared to the wild type strain. Consistent with other strains that accumulate c-di-GMP, when grown as a biofilm, the ΔamrZ mutant formed larger microcolonies than the wild-type strain. This enhanced biofilm formation was abrogated by expression of a PDE. To identify potential target DGCs, a ChIP-Seq was performed and identified regions of the genome that are bound by AmrZ. RNA-Seq experiments revealed the entire AmrZ regulon, and characterized AmrZ as an activator or repressor at each binding site. We identified an AmrZ-repressed DGC-encoding gene (PA4843) from this cohort, which we named AmrZ dependent cyclase A (adcA). PAO1 overexpressing adcA accumulates 29-fold more c-di-GMP than the wild type strain, confirming the cyclase activity of AdcA. In biofilm reactors, a ΔamrZ ΔadcA double mutant formed smaller microcolonies than the single ΔamrZ mutant, indicating adcA is responsible for the hyper biofilm phenotype of the ΔamrZ mutant. This study combined the techniques of ChIP-Seq and RNA-Seq to define the comprehensive regulon of a bifunctional transcriptional regulator. Moreover, we identified a c-di-GMP mediated mechanism for Amr

  16. ViDiT-CACTUS: an inexpensive and versatile library preparation and sequence analysis method for virus discovery and other microbiology applications.

    PubMed

    Verhoeven, Joost Theo Petra; Canuti, Marta; Munro, Hannah J; Dufour, Suzanne C; Lang, Andrew S

    2018-04-19

    High-throughput sequencing (HTS) technologies are becoming increasingly important within microbiology research, but aspects of library preparation, such as high cost per sample or strict input requirements, make HTS difficult to implement in some niche applications and for research groups on a budget. To answer these necessities, we developed ViDiT, a customizable, PCR-based, extremely low-cost (<5 US dollars per sample) and versatile library preparation method, and CACTUS, an analysis pipeline designed to rely on cloud computing power to generate high-quality data from ViDiT-based experiments without the need of expensive servers. We demonstrate here the versatility and utility of these methods within three fields of microbiology: virus discovery, amplicon-based viral genome sequencing and microbiome profiling. ViDiT-CACTUS allowed the identification of viral fragments from 25 different viral families from 36 oropharyngeal-cloacal swabs collected from wild birds, the sequencing of three almost complete genomes of avian influenza A viruses (>90% coverage), and the characterization and functional profiling of the complete microbial diversity (bacteria, archaea, viruses) within a deep-sea carnivorous sponge. ViDiT-CACTUS demonstrated its validity in a wide range of microbiology applications and its simplicity and modularity make it easily implementable in any molecular biology laboratory, towards various research goals.

  17. Heat transfer and pressure drop studies of TiO2/DI water nanofluids in helically corrugated tubes using spiraled rod inserts

    NASA Astrophysics Data System (ADS)

    Anbu, S.; Venkatachalapathy, S.; Suresh, S.

    2018-05-01

    An experimental study on the convective heat transfer and friction factor characteristics of TiO2/DI water nanofluids in uniformly heated plain and helically corrugated tubes (HCT) with and without spiraled rod inserts (SRI) under laminar flow regime is presented in this paper. TiO2 nanoparticles with an average size of 32 nm are dispersed in deionized (DI) water to form stable suspensions containing 0.1, 0.15, 0.2, and 0.25% volume concentrations of nanoparticles. It is found that the inclusion of nanoparticles to DI water ameliorated Nusselt number which increased with nanoparticles concentration upto 0.2%. Two spiraled rod inserts made of copper with different pitches (pi = 50 mm and 30 mm) are inserted in both plain and corrugated tubes and it is found that the addition of these inserts increased the Nusselt number substantially. For Helically corrugated tube with lower pitch and maximum height of corrugation (pc = 8 mm, hc = 1 mm) with 0.2% volume concentration of nanoparticles, a maximum enhancement of 15% in Nusselt number is found without insert and with insert having lower pitch (pi = 30 mm) the enhancement is 34% when compared to DI water in plain tube. The results on friction factor show a maximum penalty of about 53.56% for the above HCT.

  18. A Novel Dark-Inducible Protein, LeDI-2, and Its Involvement in Root-Specific Secondary Metabolism in Lithospermum erythrorhizon1

    PubMed Central

    Yazaki, Kazufumi; Matsuoka, Hideaki; Shimomura, Koichiro; Bechthold, Andreas; Sato, Fumihiko

    2001-01-01

    Lithospermum erythrorhizon produces red naphthoquinone pigments that are shikonin derivatives. They are accumulated exclusively in the roots of this plant. The biosynthesis of shikonin is strongly inhibited by light, even though other environmental conditions are optimized. Thus, L. erythrorhizon dark-inducible genes (LeDIs) were isolated to investigate the regulatory mechanism of shikonin biosynthesis. LeDI-2, showing the strict dark-specific expression, was further characterized by use of cell suspension cultures and hairy root cultures as model systems. Its mRNA accumulation showed a similar pattern with that of shikonin. In the intact plants LeDI-2 expression was observed solely in the root, and the longitudinal distribution of its mRNA was also in accordance to that of shikonin. LeDI-2 encoded a very hydrophobic polypeptide of 114 amino acids that shared significant similarities with some root-specific polypeptides such as ZRP3 (maize) and RcC3 (rice). Reduction of LeDI-2 expression by its antisense DNA in hairy roots of L. erythrorhizon decreased the shikonin accumulation, whereas other biosynthetic enzymes, e.g. p-hydroxybenzoic acid:geranyltransferase, which catalyzed a critical biosynthetic step, showed similar activity as the wild-type clone. This is the first report of the gene that is involved in production of secondary metabolites without affecting biosynthetic enzyme activities. PMID:11299363

  19. Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP

    PubMed Central

    Okegbe, Chinweike; Fields, Blanche L.; Cole, Stephanie J.; Beierschmitt, Christopher; Morgan, Chase J.; Price-Whelan, Alexa; Stewart, Richard C.; Lee, Vincent T.; Dietrich, Lars E. P.

    2017-01-01

    Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3′,5′)-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain–containing regulatory proteins found in complex eukaryotes. PMID:28607054

  20. Effect of Diethylene Glycol Monomethyl Ether (DiEGME) and Triethylene Glycol Monomethyl Ether (TriEGME) on Microbial Contaminants in Aviation Fuel

    DTIC Science & Technology

    2010-03-01

    still be effective at controlling microbial growth. DiEGME and TriEGME’s ability to inhibit biofilm growth is also demonstrated. TriEGME is shown to...MO) with DiEGME or TriEGME added as appropriate. Fuel was filtered with a 0.45µm hydrophobic cellulose nitrate filter (Nalge Nunc, Rochester, NY... biofilm formation. However, no numerical standards have been universally accepted which define a particular colony count level as problematic (27). This

  1. An easy one-pot synthesis of diverse 2,5-di(2-pyridyl)pyrroles: a versatile entry point to metal complexes of functionalised, meridial and tridentate 2,5-di(2-pyridyl)pyrrolato ligands.

    PubMed

    McSkimming, Alex; Diachenko, Vera; London, Rachel; Olrich, Kiara; Onie, C Jessica; Bhadbhade, Mohan M; Bucknall, Martin P; Read, Roger W; Colbran, Stephen B

    2014-09-01

    A wide variety of 2,5-di(2-pyridyl)pyrroles (dppHs) substituted at the C3 and C4 positions of the pyrrole core were obtained by direct condensation of a 2-pyridylcarboxaldehyde (2 equiv), an α-methylene ketone with at least one electron-withdrawing substituent and ammonium acetate. A novel 2,5-di(1,10-phenanthrolin-2-yl)pyrrole was also characterised. The dppHs provide a direct, quick entry to dipyridylpyrrolato (dpp(-) )-metal complexes. The meridial tridentate dpp(-) ligand is a useful anionic analogue of the terpyridyl ligand. The first (dpp)Ru complexes are described; the 3,4-substitution of the central pyrrole significantly perturbs the potentials of the redox processes of these complexes. A [(dpp)Ru(bpy)(MeCN)](+) (bpy=2,2'-bipyridine) complex is an electrocatalyst for the reductive disproportionation of carbon dioxide to carbon monoxide and the carbonate ion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. X-ray Radiative Transfer in Protoplanetary Disks with ProDiMo

    NASA Astrophysics Data System (ADS)

    Rab, Christian; Woitke, Peter; Güdel, Manuel; Min, Michiel; Diana Team

    2013-07-01

    X-ray emission is a common property of YSOs. T Tauri stars show X-ray luminosities up to 10^32 erg/s but also Herbig Ae/Be stars can have moderate X-ray emission in the range of 10^28 to 10^31 erg/s. We want to investigate the impact of X-ray radiation on the thermal and chemical structure of protoplanetary discs around these YSOs. Therefore we have added a new X-ray Radiative Transfer module to the radiation thermo-chemical code ProDiMo (Protoplanetary Disc Modeling) extending the existing implementation of X-ray chemistry implemented by Aresu et al. This new module considers gas and dust opacities (including scattering) and a possible X-ray background field. Further we added a new set of FUV - photoreactions to the X-ray chemistry module of ProDiMo as fast electrons created in X-ray ionisation can produce a significant secondary FUV radiation field by exciting atomic or molecular hydrogen. We discuss the importance of these processes on the thermal and chemical structure of the protoplanetary disc, and present them on the basis of a typical T Tauri disc model. This work is performed in the context of the EU FP7-project DIANA (www.diana-project.com).

  3. Sensitivity and specificity of the Akena Visual Depression Inventory (AViDI-18) in Kampala (Uganda) and Cape Town (South Africa).

    PubMed

    Akena, Dickens; Joska, John; Stein, Dan J

    2018-05-01

    Visual scales may be particularly useful in screening for depression in patients with low literacy. However, few have been validated and none are in common use.AimModification and validation of a visual scale to screen for depression in low literacy settings. We assessed the validity, reliability and factor loading of a 28-item visual depression inventory using pictorial items depicting depression signs and symptoms. We validated a revised scale comprised of 18 items known as the Akena Visual Depression Inventory (AViDI-18) against a structured diagnostic interview (Mini-International Neuropsychiatric Inventory) in 343 patients in Kampala (Uganda) and Cape Town (South Africa). The 18 pictorial items had acceptable validity and reliability. The area under the curve (AUC) score of the AViDI-18 was 0.9. AUC scores were not significantly associated with sociodemographic variables. The AViDI-18 is a valid screen for depression in patients with low literacy.Declaration of interestNone.

  4. Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.

    PubMed

    Jonas, Kristina; Edwards, Adrianne N; Ahmad, Irfan; Romeo, Tony; Römling, Ute; Melefors, Ojar

    2010-02-01

    Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.

  5. The evolution of active Lavina di Roncovetro landslides by multi-temporal high-resolution topographic data

    NASA Astrophysics Data System (ADS)

    Isola, Ilaria; Fornaciai, Alessandro; Favalli, Massimiliano; Gigli, Giovanni; Nannipieri, Luca; Mucchi, Lorenzo; Intrieri, Emanuele; Pizziolo, Marco; Bertolini, Giovanni; Trippi, Federico; Casagli, Nicola; Schina, Rosa; Carnevale, Ennio

    2017-04-01

    High-resolution topographic data has been collected over the Lavina di Roncovetro active landslide (Reggio Emilia, Italy) for about 3 years by using various methods and technologies. Tha Lavina di Roncovetro landslide can be considered as a fluid-viscous mudflow, which can reach a down flow maximum rate of 10 m/day. The landslide started between the middle and the end of the XIX century and since then it has had a rapid evolution mainly characterized by the rapid retrogression of the crown to the extent that now reaches the top of Mount Staffola. In the frame of EU Wireless Sensor Network for Ground Instability Monitoring - Wi-GIM project (LIFE12ENV/IT/001033) the Lavina di Roncovetro landslide has been periodically tracked using technologies that span from the LiDAR, both terrestrial and aerial, to the Structure from Motion (SfM) photogrammetry method based on Unmanned Aerial Vehicle (UAV) and aerial survey. These data are used to create six high-resolution Digital Terrain Models (DEMs), which imaged the landslide surface on March 2014, October 2014, June 2015, July 2015, January 2016 and December 2016. Multi-temporal high-resolution topographic data have been used for qualitative and quantitative morphometric analysis and topographic change detection of the landslide with the aim to estimate and map the volume of removed and/or accumulated material, the average rates of vertical and horizontal displacement and the deformation structures affecting the landslide over the investigated period.

  6. (Carbonato-κO,O')bis-(di-2-pyridyl-amine-κN,N')cobalt(III) bromide.

    PubMed

    Czapik, Agnieszka; Papadopoulos, Christos; Lalia-Kantouri, Maria; Gdaniec, Maria

    2011-04-01

    In the title compound, [Co(CO(3))(C(10)H(9)N(3))(2)]Br, a distorted octa-hedral coordination of the Co(III) atom is completed by four N atoms of the two chelating di-2-pyridyl-amine ligands and two O atoms of the chelating carbonate anion. The di-2-pyridyl-amine ligands are nonplanar and the dihedral angles between the 2-pyridyl groups are 29.11 (9) and 37.15 (12)°. The coordination cation, which has approximate C(2) symmetry, is connected to the bromide ion via an N-H⋯Br(-) hydrogen bond. The ionic pair thus formed is further assembled into a dimer via N-H⋯O inter-actions about an inversion centre. A set of weaker C-H⋯O and C-H⋯Br(-) inter-actions connect the dimers into a three-dimensional network.

  7. Crystal structure of bis­[trans-di­chlorido­bis(propane-1,3-di­amine-κ2 N,N′)chromium(III)] dichromate from synchrotron data

    PubMed Central

    Moon, Dohyun; Ryoo, Keon Sang; Choi, Jong-Ha

    2016-01-01

    The structure of the title compound, [CrCl2(tn)2]2[Cr2O7] (tn = propane-1,3-di­amine; C3H10N2), has been determined from synchrotron data. The asymmetric unit contains one CrIII complex cation and half a [Cr2O7]2− anion. In the complex cation, the CrIII ion is coordinated by the four N atoms of two propane-1,3-di­amine (tn) ligands in the equatorial plane and by two Cl atoms in a trans configuration, displaying a distorted octa­hedral coordination sphere. The two six-membered rings in the complex cation have an anti chair–chair conformation with respect to each other. The mean Cr—N(tn) and Cr—Cl bond lengths are 2.09 (1) and 2.320 (2) Å, respectively. The slightly bent dichromate anion is disordered over two sets of sites (occupancy ratio = 0.7:0.3) and has a staggered conformation. The crystal structure is stabilized by inter­molecular hydrogen bonds involving the NH2 groups of the tn ligands as donors and the O atoms of the [Cr2O7]2− anion and chlorido ligands as acceptors. PMID:27920920

  8. Synthesis of di-functional ligand and fluorescently labeling SiO2 microspheres

    NASA Astrophysics Data System (ADS)

    Chen, Kexu; Kang, Ming; Liu, Min; Shen, Simin; Sun, Rong

    2018-05-01

    In order to complete the fluorescent labeling of SiO2 microspheres, a kind of di-functional ligand was synthesized and purified, which could not only coordinate rare earth ions but also react with the active groups to bond host materials with an alkoxysilane groups. Fourier transform infrared spectroscopy (FT-IR), 1H NMR spectra, MS spectra, field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and luminescence spectrophotometer were used to study the structure of di-functional ligand and properties of fluorescent coupling agent and fluorescent labeled SiO2 microspheres. The optimal experiment conditions were acquired as follows: molar ratio as 1: 4 (MDBM: MICPTES), reaction time at 6 h and reaction temperature as 65 °C (yield up to 40%) through the orthogonal experiment and purification process. The results indicated that fluorescent coupling agent presented red photoluminesence of Eu3+ ions at 610 nm, and the absolute quantum yield was 11%. On the other hand, the hydrolysis of the coupling agent reacted on the surface of SiO2 microspheres and presented fluorescent labeling homogeneously.

  9. Crystal structures of three lead(II) acetate-bridged di-amino-benzene coordination polymers.

    PubMed

    Geiger, David K; Parsons, Dylan E; Zick, Patricia L

    2014-12-01

    Poly[tris-(acetato-κ(2) O,O')(μ2-acetato-κ(3) O,O':O)tetra-kis-(μ3-acetato-κ(4) O,O':O:O')bis-(benzene-1,2-di-amine-κN)tetra-lead(II)], [Pb4(CH3COO)8(C6H8N2)2] n , (I), poly[(acetato-κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(4-chloro-benzene-1,2-diamine-κN)lead(II)], [Pb(CH3COO)2(C6H7ClN2)] n , (II), and poly[(κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(3,4-di-amino-benzo-nitrile-κN)lead(II)], [Pb(CH3COO)2(C7H7N3)] n , (III), have polymeric structures in which monomeric units are joined by bridging acetate ligands. All of the Pb(II) ions exhibit hemidirected coordination. The repeating unit in (I) is composed of four Pb(II) ions having O6, O6N, O7 and O6N coordination spheres, respectively, where N represents a monodentate benzene-1,2-di-amine ligand and O acetate O atoms. Chains along [010] are joined by bridging acetate ligands to form planes parallel to (10-1). (II) and (III) are isotypic and have one Pb(II) ion in the asymmetric unit that has an O6N coordination sphere. Pb2O2 units result from a symmetry-imposed inversion center. Polymeric chains parallel to [100] exhibit hydrogen bonding between the amine and acetate ligands. In (III), additional hydrogen bonds between cyano groups and non-coordinating amines join the chains by forming R 2 (2)(14) rings.

  10. Box C/D sRNA stem ends act as stabilizing anchors for box C/D di-sRNPs.

    PubMed

    Yip, W S Vincent; Shigematsu, Hideki; Taylor, David W; Baserga, Susan J

    2016-10-14

    Ribosomal RNA (rRNA) modifications are essential for ribosome function in all cellular organisms. Box C/D small (nucleolar) ribonucleoproteins [s(no)RNPs] catalyze 2'-O-methylation, one rRNA modification type in Eukarya and Archaea. Negatively stained electron microscopy (EM) models of archaeal box C/D sRNPs have demonstrated the dimeric sRNP (di-sRNP) architecture, which has been corroborated by nuclear magnetic resonance (NMR) studies. Due to limitations of the structural techniques, the orientation of the box C/D sRNAs has remained unclear. Here, we have used cryo-EM to elucidate the sRNA orientation in a M. jannaschii box C/D di-sRNP. The cryo-EM reconstruction suggests a parallel orientation of the two sRNAs. Biochemical and structural analyses of sRNPs assembled with mutant sRNAs indicate a potential interaction between the sRNA stem ends. Our results suggest that the parallel arrangement of the sRNAs juxtaposes their stem ends into close proximity to allow for a stabilizing interaction that helps maintain the di-sRNP architecture. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Mono- and di-bromo platinum(IV) prodrugs via oxidative bromination: synthesis, characterization, and cytotoxicity.

    PubMed

    Xu, Zoufeng; Wang, Zhigang; Yiu, Shek-Man; Zhu, Guangyu

    2015-12-14

    Platinum(IV)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(IV) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(II) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(IV) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(IV) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(IV) prodrugs and provides with a convenient strategy to obtain brominated platinum(IV) complexes.

  12. Direct labeling and visualization of blood vessels with lipophilic carbocyanine dye DiI

    PubMed Central

    Li, Yiwen; Song, Ying; Zhao, Lian; Gaidosh, Gabriel; Laties, Alan M; Wen, Rong

    2009-01-01

    We describe a protocol to rapidly and reliably visualize blood vessels in experimental animals. Blood vessels are directly labeled by cardiac perfusion using a specially formulated aqueous solution containing 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), a lipophilic carbocyanine dye, which incorporates into endothelial cell membranes upon contact. By lateral diffusion, DiI also stains membrane structures, including angiogenic sprouts and pseudopodial processes that are not in direct contact. Tissues can be immediately examined by conventional and confocal fluorescence microscopy. High-quality serial optical sections using confocal microscopy are obtainable from thick tissue sections, especially at low magnification, for three-dimensional reconstruction. It takes less than 1 h to stain the vasculature in a whole animal. Compared with alternative techniques to visualize blood vessels, including space-occupying materials such as India ink or fluorescent dye-conjugated dextran, the corrosion casting technique, endothelial cell-specific markers and lectins, the present method simplifies the visualization of blood vessels and data analysis. PMID:18846097

  13. Yield and economics of shallow subsurface drip irrigation (S3DI) and furrow diking

    USDA-ARS?s Scientific Manuscript database

    A shallow subsurface drip irrigation (S3DI) was installed yearly in conjunction with furrow diking to document yield and economic benefit of these techniques on peanut (Arachis hypogaea L.), cotton (Gossypium hirsutum L.), and corn (Zea mays L.). This research was conducted for three years from 2005...

  14. Bound states via Higgs exchanging and heavy resonant di-Higgs

    NASA Astrophysics Data System (ADS)

    Kang, Zhaofeng

    2017-08-01

    The existence of Higgs boson h predicted by the standard model (SM) was established and hunting for clues to new physics (NP) hidden in h has become the top priority in particle physics. In this paper we explore an intriguing phenomenon that prevails in NP associated with h, bound state (Bh, referring to the ground state only) of relatively heavy particles ϕ out of NP via interchanging h. This is well-motivated due to the intrinsic properties of h: It has zero spin and light mass, capable of mediating Yukawa interactions; moreover, it may be strongly coupled to ϕ in several important contexts, from addressing the naturalness problem by compositeness/supersymmetry (SUSY)/classical scale invariance to understanding neutrino mass origin radiatively and matter asymmetry by electroweak baryogensis. The new resonance Bh, being a neutral scalar boson, has important implications to the large hadron collider (LHC) di-Higgs search because it yields a clear resonant di-Higgs signature at the high mass region (≳ 1 TeV). In other words, searching for Bh offers a new avenue to probe the hidden sector with a Higgs-portal. For illustration in this paper we concentrate on two examples, the stop sector in SUSY and an inert Higgs doublet from a radiative neutrino model. In particular, h-mediation opens a new and wide window to probe the conventional stoponium and the current date begins to have sensitivity to stoponium around TeV.

  15. Big Data Sensors of Organic Advocacy: The Case of Leonardo DiCaprio and Climate Change.

    PubMed

    Leas, Eric C; Althouse, Benjamin M; Dredze, Mark; Obradovich, Nick; Fowler, James H; Noar, Seth M; Allem, Jon-Patrick; Ayers, John W

    2016-01-01

    The strategies that experts have used to share information about social causes have historically been top-down, meaning the most influential messages are believed to come from planned events and campaigns. However, more people are independently engaging with social causes today than ever before, in part because online platforms allow them to instantaneously seek, create, and share information. In some cases this "organic advocacy" may rival or even eclipse top-down strategies. Big data analytics make it possible to rapidly detect public engagement with social causes by analyzing the same platforms from which organic advocacy spreads. To demonstrate this claim we evaluated how Leonardo DiCaprio's 2016 Oscar acceptance speech citing climate change motivated global English language news (Bloomberg Terminal news archives), social media (Twitter postings) and information seeking (Google searches) about climate change. Despite an insignificant increase in traditional news coverage (54%; 95%CI: -144 to 247), tweets including the terms "climate change" or "global warming" reached record highs, increasing 636% (95%CI: 573-699) with more than 250,000 tweets the day DiCaprio spoke. In practical terms the "DiCaprio effect" surpassed the daily average effect of the 2015 Conference of the Parties (COP) and the Earth Day effect by a factor of 3.2 and 5.3, respectively. At the same time, Google searches for "climate change" or "global warming" increased 261% (95%CI, 186-335) and 210% (95%CI 149-272) the day DiCaprio spoke and remained higher for 4 more days, representing 104,190 and 216,490 searches. This increase was 3.8 and 4.3 times larger than the increases observed during COP's daily average or on Earth Day. Searches were closely linked to content from Dicaprio's speech (e.g., "hottest year"), as unmentioned content did not have search increases (e.g., "electric car"). Because these data are freely available in real time our analytical strategy provides substantial lead time

  16. Big Data Sensors of Organic Advocacy: The Case of Leonardo DiCaprio and Climate Change

    PubMed Central

    Althouse, Benjamin M.; Dredze, Mark; Obradovich, Nick; Fowler, James H.; Noar, Seth M.; Allem, Jon-Patrick

    2016-01-01

    The strategies that experts have used to share information about social causes have historically been top-down, meaning the most influential messages are believed to come from planned events and campaigns. However, more people are independently engaging with social causes today than ever before, in part because online platforms allow them to instantaneously seek, create, and share information. In some cases this “organic advocacy” may rival or even eclipse top-down strategies. Big data analytics make it possible to rapidly detect public engagement with social causes by analyzing the same platforms from which organic advocacy spreads. To demonstrate this claim we evaluated how Leonardo DiCaprio’s 2016 Oscar acceptance speech citing climate change motivated global English language news (Bloomberg Terminal news archives), social media (Twitter postings) and information seeking (Google searches) about climate change. Despite an insignificant increase in traditional news coverage (54%; 95%CI: -144 to 247), tweets including the terms “climate change” or “global warming” reached record highs, increasing 636% (95%CI: 573–699) with more than 250,000 tweets the day DiCaprio spoke. In practical terms the “DiCaprio effect” surpassed the daily average effect of the 2015 Conference of the Parties (COP) and the Earth Day effect by a factor of 3.2 and 5.3, respectively. At the same time, Google searches for “climate change” or “global warming” increased 261% (95%CI, 186–335) and 210% (95%CI 149–272) the day DiCaprio spoke and remained higher for 4 more days, representing 104,190 and 216,490 searches. This increase was 3.8 and 4.3 times larger than the increases observed during COP’s daily average or on Earth Day. Searches were closely linked to content from Dicaprio’s speech (e.g., “hottest year”), as unmentioned content did not have search increases (e.g., “electric car”). Because these data are freely available in real time our

  17. The Theory behind the Theory in DCT and SCDT: A Response to Rigazio-DiGilio.

    ERIC Educational Resources Information Center

    Terry, Linda L.

    1994-01-01

    Responds to previous article by Rigazio-DiGilio on Developmental Counseling and Therapy and Systemic Cognitive-Developmental Therapy as two integrative models that unify individual, family, and network treatment within coconstructive-developmental framework. Discusses hidden complexities in cognitive-developmental ecosystemic integration and…

  18. Bis(1,3-di-tert-butylimidazolin-2-iminato) titanium complexes as effective catalysts for the monodisperse polymerization of propylene.

    PubMed

    Sharma, Manab; Yameen, Haneen Simaan; Tumanskii, Boris; Filimon, Sabina-Alexandra; Tamm, Matthias; Eisen, Moris S

    2012-10-17

    The use of bis(1,3-di-tert-butylimidazolin-2-iminato) titanium dichloride (1) and dimethyl (2) complexes in the polymerization of propylene is presented. The complexes were activated using different amounts of methylalumoxane (MAO), giving in each case a very active catalytic mixture and producing polymers with a narrow molecular weight distribution (polydispersity = 1.10). The use of the cocatalyst triphenylcarbenium (trityl) tetra(pentafluorophenyl)borate totally inhibits the reaction, producing the corresponding bis(1,3-di-tert-butylimidazolin-2-iminato) titanium(III) methyl complex, the trityl radical ((•)CPh(3)), the anionic MeB(C(6)F(5))(4)(-), B(C(6)F(5))(3), and the bis(1,3-di-tert-butylimidazolin-2-iminato) titanium(IV) dimethyl·B(C(6)F(5))(3) complex. The use of a combination of physical methods such as NMR, ESR-C(60), and MALDI-TOF analyses enabled us to propose a plausible mechanism for the polymerization of propylene, presenting that the polymerization is mainly carried out in a living fashion. In addition, we present a slow equilibrium toward a small amount of a dormant species responsible for 2,1-misinsertions and chain transfer processes.

  19. The crystal structure of a new ferrocenyl P,N ligand: 1-[(2,2-di­methyl­hydrazin-1-yl­idene)meth­yl]-1′-(di­phenyl­phospho­rothio­yl)ferrocene

    PubMed Central

    Mouas, Toma Nardjes; Daran, Jean-Claude; Merazig, Hocine

    2018-01-01

    The asymmetric unit of the title compound, [Fe(C8H11N2)(C17H14PS)], contains two independent mol­ecules (A and B) with very similar conformations. Each mol­ecule is built up from a ferrocene unit substituted in the 1 and 1′ positions by a protected sulfur di­phenyl­phosphine and by a di­methyl­hydrazine, –C(H)=N—N(CH3)2, fragment. The two independent mol­ecules are linked by a C—H⋯N hydrogen bond. In the crystal, the A–B dimer is linked by a pair of C—H⋯S hydrogen bonds, forming a centrosymmetric four-mol­ecule arrangement. These units are linked by C—H⋯π inter­actions, forming a supra­molecular three-dimensional structure. PMID:29850039

  20. Shallow subsurface drip irrigation (S3DI) for small irregular-shaped fields in the southeast

    USDA-ARS?s Scientific Manuscript database

    Field tests were conducted using S3DI on cotton (Gossypium hirsutum, L.), corn (Zea mays, L.), and peanut (Arachis hypogeae, L.) rotations to investigate yield potential and economic sustainability of this irrigation system. Drip tubing was installed in alternate row middles, strip tillage was used ...

  1. 3D-DIVIMP(HC) code modeling of DIII-D DiMES porous plug injector experiments

    NASA Astrophysics Data System (ADS)

    Mu, Y.; Elder, J. D.; Stangeby, P. C.; McLean, A. G.

    2011-08-01

    A Porous Plug Injector (PPI) system for the Divertor Material Evaluation System (DiMES) on DIII-D has been employed for in situ study of chemical erosion in the tokamak divertor environment. The 3D-DIVIMP(HC) code has been applied to the interpretation of the CI, CII and other spectroscopic measurements made at the PPI location, for (a) the synthetic source due to injection of CH4 through the PPI, and (b) the natural emission from the PPI head itself, which was inserted above surrounding graphite tiles by ˜0.3 mm.The code successfully replicated the MDS (spectrometer)-measured absolute emissions of CH, CI, CII 427 nm, 514 nm, and 658 nm [1] and the DiMES TV-measured spatial shapes of the CH, CI, and CII 514 nm [1] emission "clouds" to within the combined uncertainties. It is thus concluded that the most important physics and chemistry of chemical sputtering have most likely been included in the model.

  2. 40 CFR 721.9675 - Titanate [Ti6O13 (2-)], di-po-tas-sium.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9675 Titanate [Ti6O13 (2-)], di-po-tas-sium. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as titanate [Ti6O13 (2-)], dipotassium (CAS No...

  3. 40 CFR 721.9675 - Titanate [Ti6O13 (2-)], di-po-tas-sium.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9675 Titanate [Ti6O13 (2-)], di-po-tas-sium. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as titanate [Ti6O13 (2-)], dipotassium (CAS No...

  4. On the lost portrait of Galileo by the Tuscan painter Santi di Tito

    NASA Astrophysics Data System (ADS)

    Molaro, Paolo

    2016-12-01

    We study here the first established image of Galileo from the engraving made by Giuseppe Calendi at the end of the eighteenth century after a lost portrait of 1601 by Santi di Tito. We show that the engraving cannot be an exact copy, as it contains several inaccuracies which are unlikely to have been present in the original painting. A recent claim of the discovery of the painting by Santi di Tito is examined, and some reasons for suspecting it to be a forgery are outlined. As an alternative, we suggest a connection between the engraving and a portrait attributed to Tintoretto (which is currently in the collection of the Padua Civic Museum). The engraving and the Padua painting look quite different but can be traced to a common origin if we assume that Calendi added the half body, copied the painting onto copper plate directly, and adjusted the shading slightly. In this way, several features and details of the engraving find a plausible explanation. Finally, we note a remarkable similarity between the Padua portrait and a figure included in a Cologne painting by Rubens dating to about 1602-1604, which was suggested by Huemer to be Galileo.

  5. DiMES PMI research at DIII-D in support of ITER and beyond

    DOE PAGES

    Rudakov, Dimitry L.; Abrams, Tyler; Ding, Rui; ...

    2017-03-27

    An overview of recent Plasma-Material Interactions (PMI) research at the DIII-D tokamak using the Divertor Material Evaluation System (DiMES) is presented. The DiMES manipulator allows for exposure of material samples in the lower divertor of DIII-D under well-diagnosed ITER-relevant plasma conditions. Plasma parameters during the exposures are characterized by an extensive diagnostic suite including a number of spectroscopic diagnostics, Langmuir probes, IR imaging, and Divertor Thomson Scattering. Post-mortem measurements of net erosion/deposition on the samples are done by Ion Beam Analysis, and results are modelled by the ERO and REDEP/WBC codes with plasma background reproduced by OEDGE/DIVIMP modelling based onmore » experimental inputs. This article highlights experiments studying sputtering erosion, re-deposition and migration of high-Z elements, mostly tungsten and molybdenum, as well as some alternative materials. Results are generally encouraging for use of high-Z PFCs in ITER and beyond, showing high redeposition and reduced net sputter erosion. Two methods of high-Z PFC surface erosion control, with (i) external electrical biasing and (ii) local gas injection, are also discussed. Furthermore, these techniques may find applications in the future devices.« less

  6. Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components.

    PubMed Central

    Rock, G; Labow, R S; Tocchi, M

    1986-01-01

    In order to impart flexibility, plastic medical devices incorporate liquid plasticizers into their structure. Data from several laboratories, including ours, have shown that these compounds leach from blood bags and tubing during collection of blood, storage of various blood components and during kidney dialysis and cell and plasma apheresis procedures. After the plasticizer di(2-ethylhexyl) phthalate leaches from poly(vinyl chloride) blood packs, it is converted by a plasma enzyme to a more toxic metabolite, mono(2-ethylhexyl) phthalate. Blood fractionation products from outdated plasma contain mono(2-ethylhexyl) phthalate, the highest level being found in normal serum albumin. Recently, we have reported that di(2-ethylhexyl) phthalate actually binds to the red blood cell membrane and reduces its osmotic fragility. Current methods of red cells storage, which permit utilization up to 35 days after collection, are not possible without this membrane stabilization. Platelets are now stored for 5 days in the Fenwal PL 732 polyolefin bag. Although stated to be essentially free of liquid plasticizers, a significant level of leaching from this bag into the extracts of stored platelet concentrates was observed. PMID:3709456

  7. Modeling of material erosion and redeposition for dedicated DiMES experiments on DIII-D

    NASA Astrophysics Data System (ADS)

    Ding, R.; Abrams, T.; Chrobak, C. P.; Guo, H. Y.; Snyder, P. B.; Chan, V. S.; Rudakov, D. L.; Stangeby, P. C.; Elder, J. D.; Tskhakaya, D.; Wampler, W. R.; Kirschner, A.; McLean, A. G.

    2015-11-01

    Erosion and redeposition of plasma facing materials is a key issue for high-power, long pulse tokamak operation. A series of experiments has been carried out on DIII-D in which well-characterized samples of different materials were exposed to divertor plasma using DiMES. Such experiments provide a good benchmark for PMI codes, such as ERO. It was found that the erosion and redeposition are strongly determined by the impurity content in the plasma and sheath properties near the surface. The principal experimental results (net erosion rate and profile, net/gross erosion ratio) are reproduced by ERO simulations to within the uncertainties, indicating that the controlling physics has likely been identified. New techniques suggested by modeling such as external biasing and local gas injection for suppressing material erosion are planned to be tested in DiMES/DIII-D experiments. Work supported by US DOE DE-FC02-04ER54698, DE-AC52-07NA27344, DE-AC04-94AL85000, DE-AC52-07NA27344.

  8. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence.

    PubMed

    Davies, Bryan W; Bogard, Ryan W; Young, Travis S; Mekalanos, John J

    2012-04-13

    The function of the Vibrio 7(th) pandemic island-1 (VSP-1) in cholera pathogenesis has remained obscure. Utilizing chromatin immunoprecipitation sequencing and RNA sequencing to map the regulon of the master virulence regulator ToxT, we identify a TCP island-encoded small RNA that reduces the expression of a previously unrecognized VSP-1-encoded transcription factor termed VspR. VspR modulates the expression of several VSP-1 genes including one that encodes a novel class of di-nucleotide cyclase (DncV), which preferentially synthesizes a previously undescribed hybrid cyclic AMP-GMP molecule. We show that DncV is required for efficient intestinal colonization and downregulates V. cholerae chemotaxis, a phenotype previously associated with hyperinfectivity. This pathway couples the actions of previously disparate genomic islands, defines VSP-1 as a pathogenicity island in V. cholerae, and implicates its occurrence in 7(th) pandemic strains as a benefit for host adaptation through the production of a regulatory cyclic di-nucleotide. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Di-Isocyanate Crosslinked Aerogels with 1, 6-Bis (Trimethoxysilyl) Hexane Incorporated in Silica Backbone

    NASA Technical Reports Server (NTRS)

    Vivod, Stephanie L.; Meador, Mary Ann B.; Nguyen, Baochau N.; Quade, Derek; Randall, Jason; Perry, Renee

    2008-01-01

    Silica aerogels are desirable materials for many applications that take advantage of their light weight and low thermal conductivity. Addition of a conformal polymer coating which bonds with the amine decorated surface of the silica network improves the strength of the aerogels by as much as 200 times. Even with vast improvement in strength they still tend to undergo brittle failure due to the rigid silica backbone. We hope to increase the flexibility and elastic recovery of the silica based aerogel by altering the silica back-bone by incorporation of more flexible hexane links. To this end, we investigated the use of 1,6-bis(trimethoxysilyl)hexane (BTMSH), a polysilsesquioxane precursor3, as an additional co-reactant to prepare silica gels which were subsequently cross-linked with di-isocyanate. Previously, this approach of adding flexibility by BTMSH incorporation was demonstrated with styrene cross-linked aerogels. In our study, we varied silane concentration, mol % of silicon from BTMSH and di-isocyanate concentration by weight percent to attempt to optimize both the flexibility and the strength of the aerogels.

  10. [Adalberto Pazzini and the origins of the Istituto di Storia della Medicina].

    PubMed

    Conforti, Maria

    2006-01-01

    The first part of the paper deals with the Italian tradition of medical history in the 1930s, when Adalberto Pazzini became the most successful medical historian in Italy. Its second part deals with the founding and renovation (1938 and 1954 respectively) of the Istituto di Storia della Medicina at Rome University, with a description of the innovative--and largely utopian--planning of the Library and of the Museum and didactic collections by Pazzini.

  11. Aqueous infrared carboxylate absorbances: Aliphatic di-acids

    USGS Publications Warehouse

    Cabaniss, S.E.; Leenheer, J.A.; McVey, I.F.

    1998-01-01

    Aqueous attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra of 18 aliphatic di-carboxylic acids are reported as a function of pH. The spectra show isosbestic points and intensity changes which indicate that Beer's law is obeyed, and peak frequencies lie within previously reported ranges for aqueous carboxylates and pure carboxylic acids. Intensity sharing from the symmetric carboxylate stretch is evident in many cases, so that bands which are nominally due to alkyl groups show increased intensity at higher pH. The asymmetric stretch of the HA- species is linearly related to the microscopic acidity constant of the H2A species, with ??pK 2 intervening atoms). The results suggest that aqueous ATR-FTIR may be able to estimate 'intrinsic' pKa values of carboxylic acids, in addition to providing quantitative estimates of ionization. ?? 1998 Elsevier Science B.V. All rights reserved.

  12. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  13. Method for separating mono- and di-octylphenyl phosphoric acid esters

    DOEpatents

    Arnold, Jr., Wesley D.

    1977-01-01

    A method for separating mono-octylphenyl phosphoric acid ester and di-octylphenyl phosphoric acid ester from a mixture thereof comprises reacting the ester mixture with a source of lithium or sodium ions to form a mixture of the phosphate salts; contacting the salt mixture with an organic solvent which causes the dioctylphenyl phosphate salt to be dissolved in the organic solvent phase and the mono-octylphenyl phosphate salt to exist in a solid phase; separating the phases; recovering the phosphate salts from their respective phases; and acidifying the recovered salts to form the original phosphoric acid esters.

  14. Genetic Modifiers of the Physical Malformations in Velo-Cardio-Facial Syndrome/DiGeorge Syndrome

    ERIC Educational Resources Information Center

    Aggarwal, Vimla S.; Morrow, Bernice E.

    2008-01-01

    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid, and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that "Tbx1", a…

  15. La meridiana di Egnazio Danti nella Torre dei Venti in Vaticano: un'icona della riforma Gregoriana del calendario

    NASA Astrophysics Data System (ADS)

    Sigismondi, Costantino

    2014-05-01

    La Torre dei Venti domina l’angolo Sud Ovest del cortile della Pigna (nell'area dei Musei Vaticani), ed è inclusa negli ambienti dell'Archivio Segreto Vaticano. Non è aperta al pubblico, ma è universalmente nota per la fama che da oltre quattrocento anni la circonda, legata alle vicende della riforma Gregoriana del calendario. La meridiana tracciata da padre Egnazio Danti (1536-1586) nella torre dei Venti, fu visitata anche da Gregorio XIII, probabilmente il 21 marzo 1581 come suppone il padre Stein, per convincersi dell'anticipo ormai arrivato a dieci giorni dell'equinozio di primavera sulla data che il concilio di Nicea aveva fissato al 21 marzo per il computo pasquale. La ricognizione astrometrica del febbraio-marzo 2009 fatta dall'autore viene qui presentata.

  16. BACE1 Protein Endocytosis and Trafficking Are Differentially Regulated by Ubiquitination at Lysine 501 and the Di-leucine Motif in the Carboxyl Terminus*

    PubMed Central

    Kang, Eugene L.; Biscaro, Barbara; Piazza, Fabrizio; Tesco, Giuseppina

    2012-01-01

    β-Site amyloid precursor protein-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals present in their carboxyl-terminal fragment with specific trafficking molecules. The BACE1 carboxyl-terminal fragment contains a di-leucine sorting signal (495DDISLL500) and a ubiquitination site at Lys-501. Here, we report that lack of ubiquitination at Lys-501 (BACE1K501R) does not affect the rate of endocytosis but produces BACE1 stabilization and accumulation of BACE1 in early and late endosomes/lysosomes as well as at the cell membrane. In contrast, the disruption of the di-leucine motif (BACE1LLAA) greatly impairs BACE1 endocytosis and produces a delayed retrograde transport of BACE1 to the trans-Golgi network (TGN) and a delayed delivery of BACE1 to the lysosomes, thus decreasing its degradation. Moreover, the combination of the lack of ubiquitination at Lys-501 and the disruption of the di-leucine motif (BACE1LLAA/KR) produces additive effects on BACE1 stabilization and defective internalization. Finally, BACE1LLAA/KR accumulates in the TGN, while its levels are decreased in EEA1-positive compartments indicating that both ubiquitination at Lys-501 and the di-leucine motif are necessary for the trafficking of BACE1 from the TGN to early endosomes. Our studies have elucidated a differential role for the di-leucine motif and ubiquitination at Lys-501 in BACE1 endocytosis, trafficking, and degradation and suggest the involvement of multiple adaptor molecules. PMID:23109336

  17. Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes

    PubMed Central

    Ajit, Deepa; Simonyi, Agnes; Li, Runting; Chen, Zihong; Hannink, Mark; Fritsche, Kevin L.; Mossine, Valeri V.; Smith, Robert E.; Dobbs, Thomas K.; Luo, Rensheng; Folk, William R.; Gu, Zezong; Lubahn, Dennis B.; Weisman, Gary A.; Sun, Grace Y.

    2016-01-01

    The increase in oxidative stress and inflammatory responses associated with neurodegenerative diseases has drawn considerable attention towards understanding the transcriptional signaling pathways involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Nrf2 (Nuclear Factor Erythroid 2-like 2). Our recent studies with immortalized murine microglial cells (BV-2) demonstrated effects of botanical polyphenols to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) and enhance Nrf2-mediated antioxidant responses (Sun et al., 2015). In this study, an immortalized rat astrocyte (DI TNC1) cell line expressing a luciferase reporter driven by the NF-κB or the Nrf2/Antioxidant Response Element (ARE) promoter was used to assess regulation of these two pathways by phytochemiscals such as quercetin, rutin, cyanidin, cyanidin-3-O-glucoside, as well as botanical extracts from Withania somnifera (Ashwagandha), Sutherlandia frutescens (Sutherlandia) and Euterpe oleracea (Açaí). Quercetin effectively inhibited LPS-induced NF-κB reporter activity and stimulated Nrf2/ARE reporter activity in DI TNC1 astrocytes. Cyanidin and the glycosides showed similar effects but only at much higher concentrations. All three botanical extracts effectively inhibited LPS-induced NF-κB reporter activity. These extracts were capable of enhancing ARE activity by themselves and further enhanced ARE activity in the presence of LPS. Quercetin and botanical extracts induced Nrf2 and HO-1 protein expression. Interestingly, Ashwagandha extract was more active in inducing Nrf2 and HO-1 expression in DI TNC1 astrocytes as compared to Sutherlandia and Açaí extracts. In summary, this study demonstrated NF-kB and Nrf2/ARE promotor activities in DI TNC1 astrocytes, and further showed differences in ability for specific botanical polyphenols and extracts to down-regulate LPS-induced NF-kB and up-regulate the NRF2/ARE activities in these cells. PMID:27166148

  18. The carbocyanine dye DiD labels in vitro and in vivo neural stem cells of the subventricular zone as well as myelinated structures following in vivo injection in the lateral ventricle.

    PubMed

    Carradori, Dario; Barreau, Kristell; Eyer, Joël

    2016-02-01

    Carbocyanines are fluorescent lipophilic cationic dyes used since the early 1980s as neuronal tracers. Several applications of these compounds have been developed thanks to their low cell toxicity, lateral diffusion within the cellular membranes, and good photostability. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine 4-chlorobenzenesulfonate (DiD) is an interesting component of this family because, in addition to the classic carbocyanine properties, it has a longer wavelength compared with its analogues. That makes DiD an excellent carbocyanine for labeling cells and tissues with significant intrinsic fluorescence. Drug encapsulation, drug delivery, and cellular transplantation are also fields using DiD-based systems where having detailed knowledge about its behavior as a single entity is important. Recently, promising studies concerned neural stem cells from the subventricular zone of the lateral ventricle in the brain (their natural niche) and their potential therapeutic use. Here, we show that DiD is able to label these stem cells in vitro and present basilar information concerning its pharmacokinetics, concentrations, and microscope protocols. Moreover, when DiD is injected in vivo in the cerebrospinal fluid present in the lateral ventricle of rat, it also labels stem cells as well as myelinated structures of the caudoputamen. This analysis provides a database to consult when planning experiments concerning DiD and neural stem cells from the subventricular zone. © 2015 Wiley Periodicals, Inc.

  19. Geomorphology and age of the Marocche di Dro rock avalanches (Trentino, Italy)

    NASA Astrophysics Data System (ADS)

    Ivy-Ochs, S.; Martin, S.; Campedel, P.; Hippe, K.; Alfimov, V.; Vockenhuber, C.; Andreotti, E.; Carugati, G.; Pasqual, D.; Rigo, M.; Viganò, A.

    2017-08-01

    The Marocche di Dro deposits in the lower Sarca Valley are some of the most distinctive rock avalanche deposits of the Alps. We use geomorphology and cosmogenic 36Cl exposure dating of boulders to divide the Marocche di Dro deposits into two rock avalanche bodies; the Marocca Principale to the north and the Kas to the south. The deposits were previously undated and had been mapped as up to five different events. The largest event Marocca Principale, which comprises an estimated 1000 106 m3 of predominantly Rotzo Formation limestones, occurred 5300 ± 860 yr ago. The release area is located mainly in the alcove between Mt. Casale and Mt. Granzoline, but likely extends all the way to Mt. Brento. The Kas event took place 1080 ± 160 yr ago with detachment below Mt. Brento. The Kas debris, with an estimated volume of 300 106 m3, buried the southern third of the Marocca Principale deposit. Kas presents a barren, stark landscape dominated by house-sized Tovel Member Rotzo Formation boulders bearing distinctive chert lenses. Both the extreme relief of the rock wall (more than 1300 m) and the tectonic setting predispose the range front to massive failure. For the two events, initially translational movement likely quickly evolved into complex failure and massive collapse. Run-out across the valley of several kilometers and run-up on the opposite slope of hundreds of meters followed. A summary of all dated and large historical landslides in the Alps underlines the periods of enhanced slope activity discussed in the literature: 10-9 kyr, 5-3 kyr, and 2-1 kyr, the latter especially for the Southern Alps. No deposits of the first temporal cluster are found at Marocche di Dro. The age of Marocca Principale at 5300 ± 860 yr suggests occurrence during the second period. Failure may have been related to the shift to wetter, colder climate at the transition from the middle to the late Holocene. Nevertheless, a seismic trigger cannot be ruled out. For the Kas rock avalanche at 1080

  20. Marina di Ravenna Tide Gauge (Italy): rescue of the initial 23 years of data (1873-1896)

    NASA Astrophysics Data System (ADS)

    Bruni, S.; Zerbini, S.; Raicich, F.; Errico, M.; Santi, E.

    2017-12-01

    The tide gauge of Marina di Ravenna, formerly Porto Corsini, Italy, has been first installed in August 1873, but its oldest records, currently available through public archives, only date back to 1896. We found historical documents reporting that the earlier data should have been preserved in the historical archives of the Istituto Geografico Militare (IGM), Florence, Italy. Even if we did not find the original tidal charts in the IGM archives, we were able to retrieve six hand-written volumes reporting the readings of the high and low waters for the period 1873-1922. These volumes and the relevant documents contain important information which allowed clarifying existing doubts on the tide gauge reference levels and constants. The 1873-1922 data were digitized, the quality was assessed as well as the reference to a common datum. With the addition of these initial 23 years of data (1873-1896), the time series of the Marina di Ravenna tide gauge spans now 144 years. The area of Marina di Ravenna was and is affected by subsidence, due to both natural and anthropogenic causes. The effects of human activities started to be noticeable since the 1920s, when the area was interested by reclamation works; during the 60s and 70s, ground-fluid extraction was responsible for subsidence rates up to several cm/year. The newly retrieved records are then particularly valuable for assessing the local sea-level trend in a period when only natural subsidence was affecting the tide-gauge observations.

  1. Reinforcing properties of the substance P C-fragment analog DiMe-C7 in Carassius auratus.

    PubMed

    Mattioli, R; Coelho, J; Martins, A

    1996-04-01

    The aim of the present study was to investigate whether two substance P (SP) fragments have reinforcing effects in Carassius auratus when the fish were tested in a place-preference experimental model. Fish were placed in a 3-compartment box in which one compartment gives access to two others that are not connected. The time spent in each compartment was recorded for 10 min in order to determine which one was preferred. Twenty-four hours later the fish were given one of the following ip treatments: 1) group VEH (N = 12), injected with teleost saline, 2) group DiMe-C7 (N = 12), injected with 33 micrograms/kg DiMe-C7, and 3) group SP1-7 (N = 12), injected with 167 micrograms/kg SP1-7. Immediately after treatment the fish were kept for 30 min in the compartment that was the least preferred on the day before and this procedure was repeated for 3 days. On the fifth day the fish were retested for 10 min to determine the time spent in each compartment. Two-way analysis of variance with treatments and testing as factors indicated a main effect (P < 0.0025) as well as a testing effect (P < 0.009). The post-hoc Scheffé multiple comparison test indicated that only the DiMe-C7 group presented an increase in the time spent in the paired compartment after treatment. We suggest that the C-terminal fragment of SP has reinforcing effects in Carassius auratus.

  2. Mixed (phthalocyaninato)(Schiff-base) di-dysprosium sandwich complexes. Effect of magnetic coupling on the SMM behavior.

    PubMed

    Wang, Hailong; Liu, Chenxi; Liu, Tao; Zeng, Suyuan; Cao, Wei; Ma, Qi; Duan, Chunying; Dou, Jianmin; Jiang, Jianzhuang

    2013-11-21

    Reaction between Schiff-base ligand and half-sandwich complex M(Pc)(acac) led to the isolation of new sandwich-type mixed (phthalocyaninato)(Schiff-base) di-lanthanide compounds M2(Pc)2(L)H2O (M = Dy, Gd) (1, 2) [H2Pc = metal free phthalocyanine, Hacac = acetylacetone, H2L = N,N'-bis(3-methyloxysalicylidene)benzene-1,2-diamine] with the triple-decker molecular structure clearly revealed by single crystal X-ray diffraction analysis. For the comparative studies, sandwich triple-decker analogues with pure Schiff-base ligand M2(L)3H2O (M = Dy, Gd) (3, 4) were also prepared. Dynamic magnetic measurement result reveals the single-molecule magnet (SMM) nature of the di-dysprosium derivative 1, while the static magnetic investigation over both pure and the diamagnetic diluted samples of this compound discloses the interionic ferromagnetic coupling between the two dysprosium ions, which in turn effectively suppresses the QTM and enhances the energy barrier of this SMM. Nevertheless, comparative studies over the static magnetic properties of the di-dysprosium triple-decker complexes 1 and 3 indicate the stronger magnetic coupling between the two lanthanide ions in mixed (phthalocyaninato)(Schiff-base) species than in the pure Schiff-base triple-decker analogue, suggesting the special coordination sphere around the dysprosium ions in the former compound over the latter one on the more intense inter-ionic ferromagnetic coupling. As a very small step towards understanding the structure-property relationship, the present result will be surely helpful for the design and synthesis of the multinuclear lanthanide-based SMMs with good properties.

  3. Antioxidant and cytotoxic activity of new di- and polyamine caffeine analogues.

    PubMed

    Jasiewicz, Beata; Sierakowska, Arleta; Jankowski, Wojciech; Hoffmann, Marcin; Piorońska, Weronika; Górnicka, Agnieszka; Bielawska, Anna; Bielawski, Krzysztof; Mrówczyńska, Lucyna

    2018-04-18

    A series of new di- and polyamine-caffeine analogues were synthesized and characterized by NMR, FT-IR and MS spectroscopic methods. To access stability of the investigated caffeine analogues Molecular Dynamic simulations were performed in NAMD 2.9 assuming CHARMM36 force field. To evaluate the antioxidant capacity of new compounds, three different antioxidant assays were used, namely 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH • ) scavenging activity, ferrous ions (Fe 2+ ) chelating activity and Fe 3+ →Fe 2+ reducing ability. In vitro, the ability of new derivatives to protect human erythrocytes against oxidative haemolysis induced by free radical from 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) was estimated. The cytotoxic activity was tested using MCF-7 breast cancer cells and human erythrocytes. All compounds showed the antioxidant capacity depending mostly on their ferrous ions chelating activity. In the presence of AAPH, some derivatives were able to effectively inhibit the oxidative haemolysis. Two derivatives, namely 8-(methyl(2-(methylamino)ethyl)-amino)caffeine and 8-(methyl(3-(methylamino)propyl)amino)caffeine, showed cytotoxic activity against MCF-7 breast cancer cells but not against human erythrocytes. Therefore, it is concluded that the selected di- and polyamine caffeine analogues, depending on their chemical structure, were able to minimize the oxidative stress and to inhibit the tumour cell grow. The confirmed antioxidant and cytotoxic properties of some caffeine derivatives make them attractive for potential applications in food or pharmaceutical industries.

  4. From grape berries to wine: population dynamics of cultivable yeasts associated to "Nero di Troia" autochthonous grape cultivar.

    PubMed

    Garofalo, Carmela; Tristezza, Mariana; Grieco, Francesco; Spano, Giuseppe; Capozzi, Vittorio

    2016-04-01

    The aim of this work was to study the biodiversity of yeasts isolated from the autochthonous grape variety called "Uva di Troia", monitoring the natural diversity from the grape berries to wine during a vintage. Grapes were collected in vineyards from two different geographical areas and spontaneous alcoholic fermentations (AFs) were performed. Different restriction profiles of ITS-5.8S rDNA region, corresponding to Saccharomyces cerevisiae, Issatchenkia orientalis, Metschnikowia pulcherrima, Hanseniaspora uvarum, Candida zemplinina, Issatchenkia terricola, Kluyveromyces thermotolerans, Torulaspora delbrueckii, Metschnikowia chrysoperlae, Pichia fermentans, Hanseniaspora opuntiae and Hanseniaspora guilliermondii, were observed. The yeast occurrences varied significantly from both grape berries and grape juices, depending on the sampling location. Furthermore, samples collected at the end of AF revealed the great predominance of Saccharomyces cerevisiae, with a high intraspecific biodiversity. This is the first report on the population dynamics of 'cultivable' microbiota diversity of "Uva di Troia" cultivar from the grape to the corresponding wine ("Nero di Troia"), and more general for Southern Italian oenological productions, allowing us to provide the basis for an improved management of wine yeasts (with both non-Saccharomyces and Saccharomyces) for the production of typical wines with desired unique traits. A certain geographical-dependent variability has been reported, suggesting the need of local based formulation for autochthonous starter cultures, especially in the proportion of the different species/strains in the design of mixed microbial preparations.

  5. A low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits

    PubMed

    Marum, Ana Paula; Moreira, Cátia; Tomas-Carus, Pablo; Saraiva, Fernando; Guerreiro, Catarina Sousa

    2017-06-05

    Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgiasymptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the "Diet adherence" (85%). "Satisfaction with improvement of symptoms" (76%), showed correlating with "diet adherence" (r = 0.65; p < 0.01). Results are highly encouraging

  6. Bromine Incorporation in Regulated and Emerging DBPs and the Relative Predominance of Mono, Di and Trihalogenated DBPs - SLIDES

    EPA Science Inventory

    Examination of bromine incorporation in emerging DBPs vs that of regulated DBPs Study of predominance of di- vs trihalogenated species in different DBP classes Better understand and characterize exposure to DBPs of health concern

  7. Mass spectrometry-based phytochemical screening for hypoglycemic activity of Fagioli di Sarconi beans (Phaseolus vulgaris L.).

    PubMed

    Pascale, Raffaella; Bianco, Giuliana; Cataldi, Tommaso R I; Kopplin, Philippe-Schmitt; Bosco, Federica; Vignola, Lisiana; Uhl, Jenny; Lucio, Marianna; Milella, Luigi

    2018-03-01

    The present study deals with the evaluation of antidiabetic activities of Fagioli di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the European Union with the mark PGI (i.e., Protected Geographical Indication), and cultivated in Basilicata (southern Italy). For this purpose, α-glucosidase and α-amylase assays were assessed; among all bean ecotypes, the tight green seed colour of Verdolino extracts exhibited the highest α-glucosidase and α-amylase inhibitory activity with IC 50 =1.1±0.1μg/ml and IC 50 =19.3±1.1μg/ml, respectively. Phytochemical compound screening of all Fagioli di Sarconi beans performed by flow injection-electrospray ionization-ultrahigh resolution mass spectrometry (uHRMS) and based on the calculation of elemental formulas from accurate m/z values, was helpful to annotate specific compounds, such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely responsible for their biological activity. Copyright © 2017. Published by Elsevier Ltd.

  8. The Baia-Fondi di Baia eruption at Campi Flegrei: stratigraphy and dynamics of a multi-stage caldera reactivation event

    NASA Astrophysics Data System (ADS)

    Pistolesi, Marco; Bertagnini, Antonella; Di Roberto, Alessio; Isaia, Roberto; Vona, Alessandro; Cioni, Raffaello; Giordano, Guido

    2017-09-01

    The Baia-Fondi di Baia eruption is one of the sporadic events that have occurred in the western sector of the Campi Flegrei caldera. It dates back to 9525-9696 bp and opened Epoch 2 of the caldera activity after a 1000-year-long period of quiescence. Although relatively small in terms of erupted volume with respect to most of the events of the past 15 ka, the Baia-Fondi di Baia eruption was characterized by a complex series of events, which have led to different interpretations in the literature. We present a detailed stratigraphic study of 40 outcrops in a sector of about 90 km2, coupled with sedimentological (grain size, componentry), physical (density, vesicularity), textural, and compositional analyses of the erupted deposits. Based on these data, we interpret the stratigraphic succession as being related to two distinct eruptive episodes (Baia and Fondi di Baia). These were separated by a short time interval, and each was characterized by different eruptive phases. The Baia eruptive episode started in a shallow-water environment with an explosive vent-opening phase that formed a breccia deposit (Unit I), rapidly followed by alternating fallout activity and dense, pyroclastic density current deposits generation (Unit II). Sedimentological features and pumice textural analyses suggest that deposition of Unit II coincided with the intensity peak of the eruption, with the fallout deposit being characterized by a volume of 0.06 ± 0.008 km3 (corresponding to a total erupted mass of 4.06 ± 0.5 × 1010 kg), a column height of 17 km, and a corresponding mass flow rate of 1.8 × 107 kg s-1. The associated tephra also shows the highest vesicularity (up to 81 vol.%) the highest vesicle number density (1.01 × 108 cm-3) and decompression rate (0.69 MPa s-1). This peak phase waned to turbulent, surge-like activity possibly associated with Vulcanian explosions and characterized by progressively lower intensity, as shown by density/vesicularity and textural properties of

  9. Role of cyclic di-GMP in Xylella fastidiosa biofilm formation, plant virulence, and insect transmission.

    PubMed

    Chatterjee, Subhadeep; Killiny, Nabil; Almeida, Rodrigo P P; Lindow, Steven E

    2010-10-01

    Xylella fastidiosa must coordinately regulate a variety of traits contributing to biofilm formation, host plant and vector colonization, and transmission between plants. Traits such as production of extracellular polysaccharides (EPS), adhesins, extracellular enzymes, and pili are expressed in a cell-density-dependent fashion mediated by a cell-to-cell signaling system involving a fatty acid diffusible signaling factor (DSF). The expression of gene PD0279 (which has a GGDEF domain) is downregulated in the presence of DSF and may be involved in intracellular signaling by modulating the levels of cyclic di-GMP. PD0279, designated cyclic di-GMP synthase A (cgsA), is required for biofilm formation, plant virulence, and vector transmission. cgsA mutants exhibited a hyperadhesive phenotype in vitro and overexpressed gumJ, hxfA, hxfB, xadA, and fimA, which promote attachment of cells to surfaces and, hence, biofilm formation. The mutants were greatly reduced in virulence to grape albeit still transmissible by insect vectors, although at a reduced level compared with transmission rates of the wild-type strain, despite the fact that similar numbers of cells of the cgsA mutant were acquired by the insects from infected plants. High levels of EPS were measured in cgsA mutants compared with wild-type strains, and scanning electron microscopy analysis also revealed a thicker amorphous layer surrounding the mutants. Overexpression of cgsA in a cgsA-complemented mutant conferred the opposite phenotypes in vitro. These results suggest that decreases of cyclic di-GMP result from the accumulation of DSF as cell density increases, leading to a phenotypic transition from a planktonic state capable of colonizing host plants to an adhesive state that is insect transmissible.

  10. Pseudosymmetric fac-di­aqua­trichlorido[(di­methyl­phosphor­yl)methanaminium-κO]manganese(II)

    PubMed Central

    Reiss, Guido J.

    2013-01-01

    In the title compound, [Mn(C3H11NOP)Cl3(H2O)2], the MnII metal center has a distorted o­cta­hedral geometry, coordinated by the three chloride ligands showing a facial arrangement. Two water mol­ecules and the O-coordinated dpmaH cation [dpmaH = (di­methyl­phosphor­yl)methanaminium] complete the coordination sphere. Each complex mol­ecule is connected to its neighbours by O—H⋯Cl and N—H⋯Cl hydrogen bonds. Two of the chloride ligands and the two water ligands form a hydrogen-bonded polymeric sheet in the ab plane. Furthermore, these planes are connected to adjacent planes by hydrogen bonds from the aminium function of cationic dpmaH ligand. A pseudo-mirror plane perpendicular to the b axis in the chiral space group P21 is observed together with inversion twinning [ratio = 0.864 (5):0.136 (5)]. PMID:23723764

  11. An automatic DI-flux at the Livingston Island geomagnetic observatory, Antarctica: requirements and lessons learned

    NASA Astrophysics Data System (ADS)

    Marsal, Santiago; José Curto, Juan; Torta, Joan Miquel; Gonsette, Alexandre; Favà, Vicent; Rasson, Jean; Ibañez, Miquel; Cid, Òscar

    2017-07-01

    The DI-flux, consisting of a fluxgate magnetometer coupled with a theodolite, is used for the absolute manual measurement of the magnetic field angles in most ground-based observatories worldwide. Commercial solutions for an automated DI-flux have recently been developed by the Royal Meteorological Institute of Belgium (RMI), and are practically restricted to the AutoDIF and its variant, the GyroDIF. In this article, we analyze the pros and cons of both instruments in terms of its suitability for installation at the partially manned geomagnetic observatory of Livingston Island (LIV), Antarctica. We conclude that the GyroDIF, even if it is less accurate and more power demanding, is more suitable than the AutoDIF for harsh conditions due to the simpler infrastructure that is necessary. Power constraints in the Spanish Antarctic Station Juan Carlos I (ASJI) during the unmanned season require an energy-efficient design of the thermally regulated box housing the instrument as well as thorough power management. Our experiences can benefit the geomagnetic community, which often faces similar challenges.

  12. Physicochemical characterization of 3,6-diHydroxyflavone binding BSA immobilized on PEG-coated silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Voicescu, Mariana; Ionescu, Sorana; Calderon-Moreno, Jose M.; Nistor, Cristina L.

    2017-02-01

    Studies based on silver nanoparticles (SNPs) and polyethylene glycols (PEGs) are mainly in the pharmaceutical field, with PEG as good "vehicle" to transport protein-based drugs. In this work, physicochemical characteristics of 3,6-diHydroxyflavone (3,6-diHF) binding bovine serum albumin (BSA) on PEG (Tween20, L64, and Myrj52)-coated SNPs have been investigated by steady-state and time-resolved fluorescence spectroscopy. These interactions give rise to the formation of intermolecular and intramolecular H bonds. As a subject of interest, the effect of temperature (30-60 °C) on the H bonds was studied by steady-state fluorescence. The size distribution and zeta potential of SNPs were determined by dynamic light scattering (DLS). Scanning electron microscopy (SEM) analysis revealed the spherical nature of particles with average diameter 40-80 nm. The structure, stability, dynamics, and conformational changes in adsorbed BSA protein on the PEG-coated SNPs surface have been also investigated by steady-state/lifetime fluorescence and circular dichroism spectroscopy. The results have relevance in the oxidative stress and drug delivery processes.

  13. Crystal structure of {2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ3N,C1,N'}(bromido/chlorido)-mercury(II).

    PubMed

    Gupta, Anand; Singh, Harkesh B; Butcher, Ray J

    2017-11-01

    In the mol-ecular structure of the title compound, {2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ 3 N , C 1 , N '}[bromido/chlorido-(0.30/0.70)]mercury(II)-{2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κ 3 N , C 1 , N '}[bromido/chlorido-(0.24/0.76)]mer-cury(II) (1/1), [HgBr 0.30 Cl 0.70 (C 12 H 19 N 2 )]·[HgBr 0.24 Cl 0.76 (C 12 H 19 N 2 )], there are two mol-ecules in the asymmetric unit of formula L Hg X { L = 2,6-bis-[(di-methyl-amino)-meth-yl]phenyl and X = Cl/Br}. In each mol-ecule, the halide site is mixed Cl/Br, with occupancies of 0.699 (7):0.301 (7) and 0.763 (7):0.237 (7), respectively. The two mol-ecules are linked into dimers by a combination of Hg⋯Hg [Hg⋯Hg = 3.6153 (3) Å] and C-H⋯Cl and C-H⋯π inter-actions.

  14. Short communication: Chemical and sensory characteristics of Canestrato di Moliterno cheese manufactured in spring.

    PubMed

    Trani, A; Gambacorta, G; Loizzo, P; Cassone, A; Faccia, M

    2016-08-01

    Canestrato di Moliterno is an Italian Protected Geographical Indication hard cheese, made in winter and spring from a mixture of ewe and goat milks, that has been poorly investigated. The present study was aimed at characterizing the cheese made in the warm season. Two series of samples, ripened in traditional rooms called fondaco as indicated in the official protocol of production, were taken from the main certified producers. The cheeses were analyzed for gross composition; proteolysis and lipolysis; volatile fraction; and organoleptic features. Gross composition was not completely homogeneous among the samples, but primary proteolysis and lipolysis were quite uniform. We observed variations in secondary proteolysis, likely caused by fluctuations in environmental conditions in the fondaco. The sensory profiles of the samples were homogeneous: the cheese was soluble, greasy, and adhesive, with a sheepfold and buttery odor. The main taste attributes were fermented, pungent, and bitter. Overall, the results of this study provide an initial contribution to the characterization of Canestrato di Moliterno, and could be used to improve marketing strategies. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Internuclear Genetic Transfer in Vegetative Dikaryons of SCHIZOPHYLLUM COMMUNE: I. Di-Mon Mating Analysis

    PubMed Central

    Leonard, Thomas J.; Dick, Stanley; Gaber, Richard F.

    1978-01-01

    A series of hemi-compatible dikaryon x monokaryon (di-mon) matings was designed to determine whether there was any genetic interaction between the dikaryotic nuclei. One of the nuclei in each dikaryon was known to carry a recessive gene (mnd) that promoted the development of an abnormal growth form, mound. Dikaryons containing both mnd + and mnd nuclei produced mosaic colonies that consisted of three distinct kinds of hyphae: mound, fruiting body, and vegetative (devoid of any multihyphal structure). When dikaryotic hyphae from each of these morphological regions were used in di-mon matings, the genetic and developmental characteristics of the selected nuclear types were examined in the resulting derived dikaryons. The results showed that fruiting-body and vegetative cells contained the expected mnd and mnd+ nuclei. Dikaryotic mound hyphae, however, contained only mnd nuclei. In a manner as yet unresolved, but clearly dependent on the presence of the mnd allele, the mnd + allele of a wild nucleus was altered to, or acquired, the mnd allele. A number of hypotheses were considered to explain the genetic event(s) that generates [mnd + mnd*] dikaryotic cells from [mnd+ + mnd] cells, but none was found to be entirely satisfactory. PMID:17248788

  16. Three cyanobacteriochromes work together to form a light color-sensitive input system for c-di-GMP signaling of cell aggregation.

    PubMed

    Enomoto, Gen; Ni-Ni-Win; Narikawa, Rei; Ikeuchi, Masahiko

    2015-06-30

    Cyanobacteriochromes (CBCRs) are cyanobacterial photoreceptors that have diverse spectral properties and domain compositions. Although large numbers of CBCR genes exist in cyanobacterial genomes, no studies have assessed whether multiple CBCRs work together. We recently showed that the diguanylate cyclase (DGC) activity of the CBCR SesA from Thermosynechococcus elongatus is activated by blue-light irradiation and that, when irradiated, SesA, via its product cyclic dimeric GMP (c-di-GMP), induces aggregation of Thermosynechococcus vulcanus cells at a temperature that is suboptimum for single-cell viability. For this report, we first characterize the photobiochemical properties of two additional CBCRs, SesB and SesC. Blue/teal light-responsive SesB has only c-di-GMP phosphodiesterase (PDE) activity, which is up-regulated by teal light and GTP. Blue/green light-responsive SesC has DGC and PDE activities. Its DGC activity is enhanced by blue light, whereas its PDE activity is enhanced by green light. A ΔsesB mutant cannot suppress cell aggregation under teal-green light. A ΔsesC mutant shows a less sensitive cell-aggregation response to ambient light. ΔsesA/ΔsesB/ΔsesC shows partial cell aggregation, which is accompanied by the loss of color dependency, implying that a nonphotoresponsive DGC(s) producing c-di-GMP can also induce the aggregation. The results suggest that SesB enhances the light color dependency of cell aggregation by degrading c-di-GMP, is particularly effective under teal light, and, therefore, seems to counteract the induction of cell aggregation by SesA. In addition, SesC seems to improve signaling specificity as an auxiliary backup to SesA/SesB activities. The coordinated action of these three CBCRs highlights why so many different CBCRs exist.

  17. Evaluation of a Salmonella Strain Lacking the Secondary Messenger C-di-GMP and RpoS as a Live Oral Vaccine

    PubMed Central

    García, Begoña; Gil, Carmen; García-Ona, Enrique; Burgui, Saioa; Casares, Noelia; Hervás-Stubbs, Sandra; Lasarte, Juan José; Lasa, Iñigo

    2016-01-01

    Salmonellosis is one of the most important bacterial zoonotic diseases transmitted through the consumption of contaminated food, with chicken and pig related products being key reservoirs of infection. Although numerous studies on animal vaccination have been performed in order to reduce Salmonella prevalence, there is still a need for an ideal vaccine. Here, with the aim of constructing a novel live attenuated Salmonella vaccine candidate, we firstly analyzed the impact of the absence of cyclic-di-GMP (c-di-GMP) in Salmonella virulence. C-di-GMP is an intracellular second messenger that controls a wide range of bacterial processes, including biofilm formation and synthesis of virulence factors, and also modulates the host innate immune response. Our results showed that a Salmonella multiple mutant in the twelve genes encoding diguanylate cyclase proteins that, as a consequence, cannot synthesize c-di-GMP, presents a moderate attenuation in a systemic murine infection model. An additional mutation of the rpoS gene resulted in a synergic attenuating effect that led to a highly attenuated strain, referred to as ΔXIII, immunogenic enough to protect mice against a lethal oral challenge of a S. Typhimurium virulent strain. ΔXIII immunogenicity relied on activation of both antibody and cell mediated immune responses characterized by the production of opsonizing antibodies and the induction of significant levels of IFN-γ, TNF-α, IL-2, IL-17 and IL-10. ΔXIII was unable to form a biofilm and did not survive under desiccation conditions, indicating that it could be easily eliminated from the environment. Moreover, ΔXIII shows DIVA features that allow differentiation of infected and vaccinated animals. Altogether, these results show ΔXIII as a safe and effective live DIVA vaccine. PMID:27537839

  18. [Application of multiplex PCR for the screening of genotyping system for the rare blood groups Fy(a-), s-,k-,Di(b-) and Js(b-)].

    PubMed

    Jiao, Wei; Xie, Li; Li, Hailan; Lan, Jiao; Mo, Zhuning; Yang, Ziji; Liu, Fei; Xiao, Ruiping; He, Yunlei; Ye, Luyi; Zhu, Ziyan

    2014-04-01

    To screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population. Sequence-specific primers were designed based on single nucleotide polymorphism (SNP) sites of blood group antigens Fy(b) and s. A specific multiplex PCR system I was established. Multiplex PCR system II was applied to detect alleles antigens Di(b), k, Js(b)1910 and Js(b) 2019 at the same time. The two systems was were used to screen for rare blood group antigens in 4490 randomly selected healthy donors of Guangxi Zhuang ethnic origin. We successfully made the multiplex PCR system I. We detected the rare blood group antigens using the two PCR system. There are five Fy(a-), three s(-), two Di(b-) in 4490 Guangxi zhuang random samples. The multiplex PCR system I has achieved good accuracy and stability. With multiplex PCR systems I and II, 4490 samples were screened. Five Fy(a-), three s(-) and two Di(b-) samples were discovered. Multiplex PCR is an effective methods, which can be used for high throughput screening of rare blood groups. The rare blood types of Guangxi Zhuang ethnic origin obtained through the screening can provide valuable information for compatible blood transfusion. Through screening we obtained precious rare blood type materials which can be used to improve the capability of compatible infusion and reduce the transfusion reactions.

  19. Achromobactor denitrificans SP1 produces pharmaceutically active 25C prodigiosin upon utilizing hazardous di(2-ethylhexyl)phthalate

    USDA-ARS?s Scientific Manuscript database

    Achromobacter denitrificans SP1 isolated from soil sludge heavily contaminated with plastic waste produced a novel pharmaceutically-active 25C prodigiosin analog during growth in a simple mineral salt medium supplemented with hazardous di(2-ethylhexyl)phthalate (DEHP) blended PVC plastics (in situ) ...

  20. Di-isodityrosine is the intermolecular cross-link of isodityrosine-rich extensin analogs cross-linked in vitro.

    PubMed

    Held, Michael A; Tan, Li; Kamyab, Abdolreza; Hare, Michael; Shpak, Elena; Kieliszewski, Marcia J

    2004-12-31

    Extensins are cell wall hydroxyproline-rich glycoproteins that form covalent networks putatively involving tyrosyl and lysyl residues in cross-links catalyzed by one or more extensin peroxidases. The precise cross-links remain to be chemically identified both as network components in muro and as enzymic products generated in vitro with native extensin monomers as substrates. However, some extensin monomers contain variations within their putative cross-linking motifs that complicate cross-link identification. Other simpler extensins are recalcitrant to isolation including the ubiquitous P3-type extensin whose major repetitive motif, Hyp)(4)-Ser-Hyp-Ser-(Hyp)(4)-Tyr-Tyr-Tyr-Lys, is of particular interest, not least because its Tyr-Tyr-Tyr intramolecular isodityrosine cross-link motifs are also putative candidates for further intermolecular cross-linking to form di-isodityrosine. Therefore, we designed a set of extensin analogs encoding tandem repeats of the P3 motif, including Tyr --> Phe and Lys --> Leu variations. Expression of these P3 analogs in Nicotiana tabacum cells yielded glycoproteins with virtually all Pro residues hydroxylated and subsequently arabinosylated and with likely galactosylated Ser residues. This was consistent with earlier analyses of P3 glycopeptides isolated from cell wall digests and the predictions of the Hyp contiguity hypothesis. The tyrosine-rich P3 analogs also contained isodityrosine, formed in vivo. Significantly, these isodityrosine-containing analogs were further cross-linked in vitro by an extensin peroxidase to form the tetra-tyrosine intermolecular cross-link amino acid di-isodityrosine. This is the first identification of an inter-molecular cross-link amino acid in an extensin module and corroborates earlier suggestions that di-isodityrosine represents one mechanism for cross-linking extensins in muro.

  1. Resonant di-Higgs boson production in the b b ¯ W W channel: Probing the electroweak phase transition at the LHC

    DOE PAGES

    Huang, T.; No, J. M.; Pernié, L.; ...

    2017-08-11

    Here, we analyze the prospects for resonant di-Higgs production searches at the LHC in themore » $$b\\bar{b}$$W +W − (W +→ℓ +ν ℓ, W −→ℓ −$$\\bar{v}$$ ℓ) channel, as a probe of the nature of the electroweak phase transition in Higgs portal extensions of the Standard Model. In order to maximize the sensitivity in this final state, we develop a new algorithm for the reconstruction of the $$b\\bar{b}$$W +W − invariant mass in the presence of neutrinos from the W decays, building from a technique developed for the reconstruction of resonances decaying to τ +τ − pairs. We show that resonant di-Higgs production in the $$b\\bar{b}$$W +W − channel could be a competitive probe of the electroweak phase transition already with the data sets to be collected by the CMS and ATLAS experiments in run 2 of the LHC. The increase in sensitivity with larger amounts of data accumulated during the high-luminosity LHC phase can be sufficient to enable a potential discovery of the resonant di-Higgs production in this channel.« less

  2. Resonant di-Higgs boson production in the b b ¯ W W channel: Probing the electroweak phase transition at the LHC

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, T.; No, J. M.; Pernié, L.

    Here, we analyze the prospects for resonant di-Higgs production searches at the LHC in themore » $$b\\bar{b}$$W +W − (W +→ℓ +ν ℓ, W −→ℓ −$$\\bar{v}$$ ℓ) channel, as a probe of the nature of the electroweak phase transition in Higgs portal extensions of the Standard Model. In order to maximize the sensitivity in this final state, we develop a new algorithm for the reconstruction of the $$b\\bar{b}$$W +W − invariant mass in the presence of neutrinos from the W decays, building from a technique developed for the reconstruction of resonances decaying to τ +τ − pairs. We show that resonant di-Higgs production in the $$b\\bar{b}$$W +W − channel could be a competitive probe of the electroweak phase transition already with the data sets to be collected by the CMS and ATLAS experiments in run 2 of the LHC. The increase in sensitivity with larger amounts of data accumulated during the high-luminosity LHC phase can be sufficient to enable a potential discovery of the resonant di-Higgs production in this channel.« less

  3. Complex Structure and Biochemical Characterization of the Staphylococcus aureus Cyclic Diadenylate Monophosphate (c-di-AMP)-binding Protein PstA, the Founding Member of a New Signal Transduction Protein Family*

    PubMed Central

    Campeotto, Ivan; Zhang, Yong; Mladenov, Miroslav G.; Freemont, Paul S.; Gründling, Angelika

    2015-01-01

    Signaling nucleotides are integral parts of signal transduction systems allowing bacteria to cope with and rapidly respond to changes in the environment. The Staphylococcus aureus PII-like signal transduction protein PstA was recently identified as a cyclic diadenylate monophosphate (c-di-AMP)-binding protein. Here, we present the crystal structures of the apo- and c-di-AMP-bound PstA protein, which is trimeric in solution as well as in the crystals. The structures combined with detailed bioinformatics analysis revealed that the protein belongs to a new family of proteins with a similar core fold but with distinct features to classical PII proteins, which usually function in nitrogen metabolism pathways in bacteria. The complex structure revealed three identical c-di-AMP-binding sites per trimer with each binding site at a monomer-monomer interface. Although distinctly different from other cyclic-di-nucleotide-binding sites, as the half-binding sites are not symmetrical, the complex structure also highlighted common features for c-di-AMP-binding sites. A comparison between the apo and complex structures revealed a series of conformational changes that result in the ordering of two anti-parallel β-strands that protrude from each monomer and allowed us to propose a mechanism on how the PstA protein functions as a signaling transduction protein. PMID:25505271

  4. The cyclic-di-GMP diguanylate cyclase CdgA has a role in biofilm formation and exopolysaccharide production in Azospirillum brasilense.

    PubMed

    Ramírez-Mata, Alberto; López-Lara, Lilia I; Xiqui-Vázquez, Ma Luisa; Jijón-Moreno, Saúl; Romero-Osorio, Angelica; Baca, Beatriz E

    2016-04-01

    In bacteria, proteins containing GGDEF domains are involved in production of the second messenger c-di-GMP. Here we report that the cdgA gene encoding diguanylate cyclase A (CdgA) is involved in biofilm formation and exopolysaccharide (EPS) production in Azospirillum brasilense Sp7. Biofilm quantification using crystal violet staining revealed that inactivation of cdgA decreased biofilm formation. In addition, confocal laser scanning microscopy analysis of green-fluorescent protein-labeled bacteria showed that, during static growth, the biofilms had differential levels of development: bacteria harboring a cdgA mutation exhibited biofilms with considerably reduced thickness compared with those of the wild-type Sp7 strain. Moreover, DNA-specific staining and treatment with DNase I, and epifluorescence studies demonstrated that extracellular DNA and EPS are components of the biofilm matrix in Azospirillum. After expression and purification of the CdgA protein, diguanylate cyclase activity was detected. The enzymatic activity of CdgA-producing cyclic c-di-GMP was determined using GTP as a substrate and flavin adenine dinucleotide (FAD(+)) and Mg(2)(+) as cofactors. Together, our results revealed that A. brasilense possesses a functional c-di-GMP biosynthesis pathway. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  5. A near-infrared light responsive c-di-GMP module-based AND logic gate in Shewanella oneidensis.

    PubMed

    Hu, Yidan; Wu, Yichao; Mukherjee, Manisha; Cao, Bin

    2017-01-31

    A novel, biofilm-based AND logic gate was constructed in Shewanella oneidensis through a near-infrared (NIR) light responsive c-di-GMP module. The logic gate was demonstrated in microbial fuel cells with isopropyl β-d-thiogalactoside (IPTG) and NIR light as the inputs and electrical signals as the output.

  6. German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results.

    PubMed

    Thümer, Leonore; Adler, Kerstin; Bonifacio, Ezio; Hofmann, Frank; Keller, Manfred; Milz, Christine; Munte, Axel; Ziegler, Anette-Gabriele

    2010-01-01

    Diabetes incidence in childhood and youth is increasing worldwide, including autoimmune and non-autoimmune cases. Recent findings suggest that there is a larger than expected proportion of type 2 diabetes in youth, and potential cases of intermediate diabetes phenotypes. Most pediatric diabetes registries focus on type 1 diabetes. Also, there is an absence of reliable data on type 2 diabetes incidence in youth. The DiMelli study aims to establish a diabetes incidence cohort registry of patients in Germany, diagnosed with diabetes mellitus before age 20 years. It will be used to characterize diabetes phenotypes by immunologic, metabolic, and genetic markers. DiMelli will assess the contribution of obesity and socio-demographic factors to the development of diabetes in childhood and youth. Recruitment of patients started in 2009, and is expected to continue at a rate of 250 patients per year. 84% of the 216 patients recruited within the first year were positive for multiple islet autoantibodies, 12% for one islet autoantibody, and 4% were islet autoantibody-negative. Patients with multiple islet autoantibodies were younger and had lower fasting C-peptide levels, compared to islet autoantibody-negative patients (median age 10.0 vs. 14.1 years, p < 0.01). Results from the first year of the study show that DiMelli will help to reveal new knowledge on the etiology of diabetes, and the contribution of genetic predisposition and environmental risk factors to the different types of diabetes.

  7. Sponsor gnomonici di 2000 anni fa nelle Dolomiti e a Pompei

    NASA Astrophysics Data System (ADS)

    del Favero, Enrico

    2003-01-01

    The author describes two memorial tablets of the Roman age, probably dating back to the first Century AD, which were discovered in Belluno province, in the towns of Valle di Cadore and Castellavazzo. They are concerned with sundials donated to the local communities by coeval sponsors. After brief recalling how people measured the time during the Roman age, the meaning of a similar tablet found in Pompeii is examined. This last tablet is included - inter alia - in the Michael T. Bragg's website on Pompeii, which has been found thanks to the so-called Roth's sundials list.

  8. The 1:1 co-crystal of 2-bromo-naphthalene-1,4-dione and 1,8-di-hydroxy-anthracene-9,10-dione: crystal structure and Hirshfeld surface analysis.

    PubMed

    Tonin, Marlon D L; Garden, Simon J; Jotani, Mukesh M; Wardell, Solange M S V; Wardell, James L; Tiekink, Edward R T

    2017-05-01

    The asymmetric unit of the title co-crystal, C 10 H 5 BrO 2 ·C 14 H 8 O 4 [systematic name: 2-bromo-1,4-di-hydro-naphthalene-1,4-dione-1,8-dihy-droxy-9,10-di-hydro-anthracene-9,10-dione (1/1)], features one mol-ecule of each coformer. The 2-bromo-naphtho-quinone mol-ecule is almost planar [r.m.s deviation of the 13 non-H atoms = 0.060 Å, with the maximum deviations of 0.093 (1) and 0.099 (1) Å being for the Br atom and a carbonyl-O atom, respectively]. The 1,8-di-hydroxy-anthra-quinone mol-ecule is planar (r.m.s. deviation for the 18 non-H atoms is 0.022 Å) and features two intra-molecular hy-droxy-O-H⋯O(carbon-yl) hydrogen bonds. Dimeric aggregates of 1,8-di-hydroxy-anthra-quinone mol-ecules assemble through weak inter-molecular hy-droxy-O-H⋯O(carbon-yl) hydrogen bonds. The mol-ecular packing comprises stacks of mol-ecules of 2-bromo-naphtho-quinone and dimeric assembles of 1,8-di-hydroxy-anthra-quinone with the shortest π-π contact within a stack of 3.5760 (9) Å occurring between the different rings of 2-bromo-naphtho-quinone mol-ecules. The analysis of the Hirshfeld surface reveals the importance of the inter-actions just indicated but, also the contribution of additional C-H⋯O contacts as well as C=O⋯π inter-actions to the mol-ecular packing.

  9. Hexaquark states as possible candidates for di-baryonic molecular states with Yukawa potential in a semi-relativistic scheme

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patel, Smruti J., E-mail: fizix.smriti@gmail.com; Vinodkumar, P. C.

    2016-05-06

    We study the mass spectra of hexaquark states as di-hadronic molecules with Yukawa potential in a semi-relativistic scheme. We have solved numerically the relevant equation using mathematica notebook of Range-Kutta method including effective Yukawa like potential between two baryons to model the two-body interaction and have calculated their masses and binding energy. We have been able to assign the J{sup P} values for many of the exotic states according to their compositions. We have predicted some of the di-baryonic exotic states for which experimental as well as theoretical data are not available and we look forward to see the experimentalmore » support in favour of our predictions. So in the absence of such results our predictions can be used as guidelines for future experimental and theoretical analysis of exotic states.« less

  10. A Unique β-1,2-Mannosyltransferase of Thermotoga maritima That Uses Di-myo-Inositol Phosphate as the Mannosyl Acceptor▿

    PubMed Central

    Rodrigues, Marta V.; Borges, Nuno; Almeida, Carla P.; Lamosa, Pedro; Santos, Helena

    2009-01-01

    In addition to di-myo-inositol-1,3′-phosphate (DIP), a compatible solute widespread in hyperthermophiles, the organic solute pool of Thermotoga maritima comprises 2-(O-β-d-mannosyl)-di-myo-inositol-1,3′-phosphate (MDIP) and 2-(O-β-d-mannosyl-1,2-O-β-d-mannosyl)-di-myo-inositol-1,3′-phosphate (MMDIP), two newly identified β-1,2-mannosides. In cells grown under heat stress, MDIP was the major solute, accounting for 43% of the total pool; MMDIP and DIP accumulated to similar levels, each corresponding to 11.5% of the total pool. The synthesis of MDIP involved the transfer of the mannosyl group from GDP-mannose to DIP in a single-step reaction catalyzed by MDIP synthase. This enzyme used MDIP as an acceptor of a second mannose residue, yielding the di-mannosylated compound. Minor amounts of the tri-mannosylated form were also detected. With a genomic approach, putative genes for MDIP synthase were identified in the genome of T. maritima, and the assignment was confirmed by functional expression in Escherichia coli. Genes with significant sequence identity were found only in the genomes of Thermotoga spp., Aquifex aeolicus, and Archaeoglobus profundus. MDIP synthase of T. maritima had maximal activity at 95°C and apparent Km values of 16 mM and 0.7 mM for DIP and GDP-mannose, respectively. The stereochemistry of MDIP was characterized by isotopic labeling and nuclear magnetic resonance (NMR): DIP selectively labeled with carbon 13 at position C1 of the l-inositol moiety was synthesized and used as a substrate for MDIP synthase. This β-1,2-mannosyltransferase is unrelated to known glycosyltransferases, and within the domain Bacteria, it is restricted to members of the two deepest lineages, i.e., the Thermotogales and the Aquificales. To our knowledge, this is the first β-1,2-mannosyltransferase characterized thus far. PMID:19648237

  11. Transport and thermodynamic properties of hydrous melts in the system An-Di.

    NASA Astrophysics Data System (ADS)

    Giordano, D.; Potuzak, M.; Romano, C.; Russell, J. K.; Nowak, M.; Dingwell, D. B.

    2006-12-01

    The thermodynamic and transport properties hydrous silicate melts are of fundamental importance for characterization of the dynamics and energetics associated with silicate melts in the Earth. The literature concerning the transport and calorimetric properties of hydrous silicate melts remains scarce. With few exceptions little has been effectively done in order to provide chemical models that bridge the gap between the description of both complex and simple systems. The An-Di system is of general interest to geochemists as well as petrologists because it serves as a simple analogue for basaltic compositions. It was chosen here due to the combination of its simple chemical description and the presence of an extensive database of published experimental data on both its transport and thermodynamic properties. We have measured the viscosity (η)), the glass transition temperatures (Tg) and the heat capacity (Cp) of silicate melts in the An-Di system containing up to 3 wt.% of dissolved H2O. Viscosity data were obtained by using the dilatometric method of micropenetration, whereas a differential scanning calorimeter (DSC) was employed to determine the glass transition temperatures and the heat capacities. In order to characterize the well-known cooling/heating rate dependence of the glass transition temperatures the calorimetric measurements were performed at heating/cooling rate of 5, 10, 15 and 20 K/min. These results together with those of previous experimental studies have been used to provide a compositional model capable of calculating the Newtonian viscosity of melts as well as the Tg and Cp values for the An- Di+H2O system. The non-Arrhenian T-dependence of viscosity is accounted for by the Vogel-Fulcher- Tammann (VFT) and the Adam Gibbs (AG) equations. Our optimizations assume a common, high-T limit (A) for silicate melt viscosity, consistent with values provided by both theoretical and experimental studies. In particular, we also show that glass transition

  12. Overview of the recent DiMES and MiMES experiments in DIII-D

    NASA Astrophysics Data System (ADS)

    Rudakov, D. L.; Wong, C. P. C.; Litnovsky, A.; Wampler, W. R.; Boedo, J. A.; Brooks, N. H.; Fenstermacher, M. E.; Groth, M.; Hollmann, E. M.; Jacob, W.; Krasheninnikov, S. I.; Krieger, K.; Lasnier, C. J.; Leonard, A. W.; McLean, A. G.; Marot, M.; Moyer, R. A.; Petrie, T. W.; Philipps, V.; Smirnov, R. D.; Stangeby, P. C.; Watkins, J. G.; West, W. P.; Yu, J. H.

    2009-12-01

    Divertor and midplane material evaluation systems (DiMES and MiMES) in the DIII-D tokamak are used to address a variety of plasma-material interaction (PMI) issues relevant to ITER. Among the topics studied are carbon erosion and re-deposition, hydrogenic retention in the gaps between plasma-facing components (PFCs), deterioration of diagnostic mirrors from carbon deposition and techniques to mitigate that deposition, and dynamics and transport of dust. An overview of the recent experimental results is presented.

  13. Mono-, di-, and tri- tert-butyl ethers of glycerol . A molecular spectroscopic study

    NASA Astrophysics Data System (ADS)

    Jamróz, Małgorzata E.; Jarosz, Małgorzata; Witowska-Jarosz, Janina; Bednarek, Elżbieta; Tęcza, Witold; Jamróz, Michał H.; Dobrowolski, Jan Cz.; Kijeński, Jacek

    2007-07-01

    MS, NMR, IR and Raman molecular spectroscopy techniques were applied to characterize 3- tert-butoxy-propane-1,2-diol, 1,3-di- tert-butoxy-propan-2-ol, and 1,2,3-tri- tert-butoxy-propane. These ethers are the main products of glycerol etherification reaction and are excellent oxygen additives for diesel fuel. Computational DFT/ B3LYP/6-31G ** studies were performed to support and rationalize both vibrational spectroscopy analysis and the isomer ratio.

  14. Development of mono- and di-AcO substituted BODIPYs on the boron center.

    PubMed

    Jiang, Xin-Dong; Zhang, Jian; Furuyama, Taniyuki; Zhao, Weili

    2012-01-06

    Mono- and di-AcO substituted BODIPYs (1 and 2) were synthesized from TM-BDP. The structures of 1 and 2 were supported by single crystal X-ray analysis. Both 1 and 2 possess a large absorption coefficient, high fluorescence quantum yield, and high light stability. Compound 2 has much improved water solubility which is highly desirable for biological applications. Theoretical calculation supports our observations in X-ray analysis, absorption, and cyclic voltammetry. © 2011 American Chemical Society

  15. Demethylation of 5,n-di-tert-butyl-8,n-dimethoxy[2.n]metacyclophane-1-ynes with BBr3 to afford novel [n]benzofuranophanes

    NASA Astrophysics Data System (ADS)

    Akther, Thamina; Islam, Md Monarul; Matsumoto, Taisuke; Tanaka, Junji; Feng, Xing; Redshaw, Carl; Yamato, Takehiko

    2016-10-01

    Novel [n]benzofuranophanes (n = 8 & 10) 2a-b have been prepared by successive intramolecular cyclization from 5,19-di-tert-butyl-8,22-dimethoxy[n]metacyclophane-1-yne (syn-1a-b) by treatment with BBr3 in CH2Cl2 at room temperature for 8h. [2.n]Benzofuranophanes 2a-b were also obtained by treatment of 1,2-di-endo-bromo-5,19-di-tert-butyl-8,22-dimethoxy[n]metacyclophane (meso-3a-b) with BBr3 in CH2Cl2 by using the same reaction conditions. 1H NMR spectra of 2a-b reveals the formation of intramolecular hydrogen bonding between hydroxyl proton with the oxygen of the furan moiety and X-ray analysis shows that the lengths between H (OH) and O (furan) are 1.981 and 1.823 Å̊, respectively. The conformation of [8]benzofuranophane 2a in solution is rigid with restricted rotation around the diaryl linkage rather than [10]benzofuranophane 2b because of weak intramolecular hydrogen bonding and the short length of the cross-linking chain.

  16. Crystal structures of three 3-chloro-3-methyl-2,6-di­aryl­piperidin-4-ones

    PubMed Central

    Arulraj, R.; Sivakumar, S.; Kaur, Manpreet; Jasinski, Jerry P.

    2017-01-01

    The syntheses and crystal structure of 3-chloro-3-methyl-r-2,c-6-di­phenyl­piperidin-4-one, C18H18ClNO, (I), 3-chloro-3-methyl-r-2,c-6-di-p-tolyl­piperidin-4-one, C20H22ClNO, (II), and 3-chloro-3-methyl-r-2,c-6-bis­(4-chloro­phen­yl)piperidin-4-one, C18H16Cl3NO, (III), are described. In each structure, the piperidine ring adopts a chair conformation and dihedral angles between the mean planes of the phenyl rings are 58.4 (2), 73.5 (5) and 78.6 (2)° in (I), (II) and (III), respectively. In the crystals, mol­ecules are linked into C(6) chains by weak N—H⋯O hydrogen bonds and C—H⋯π inter­actions are also observed. PMID:28217321

  17. Double Spin Asymmetries, ALL, for Di-hadrons in PHENIX

    NASA Astrophysics Data System (ADS)

    McKinney, Cameron

    2010-11-01

    The Relativistic Heavy Ion Collider (RHIC), through its polarized proton-proton collisions, provides leading order access to δG, the gluon contribution to the proton spin. Previous measurements have shown δG(x) dx to be consistent with zero in the Bjorken-x range of 0.05 to 0.2, whereas there is presently no measurement constraining δG (x) for x below or above this range. The Muon Piston Calorimeter provides the opportunity to expand the constrained range by allowing measurements of double spin asymmetries for azimuthally-separated pairs of 0̂'s at forward rapidity, 3.1<=|η|<=3.9, for √s=200 GeV and 500 GeV data taken in 2009. We present PYTHIA simulations studying the kinematics and possible asymmetries from di-hadron production at RHIC.

  18. An alternatively spliced heat shock transcription factor, OsHSFA2dI, functions in the heat stress-induced unfolded protein response in rice.

    PubMed

    Cheng, Q; Zhou, Y; Liu, Z; Zhang, L; Song, G; Guo, Z; Wang, W; Qu, X; Zhu, Y; Yang, D

    2015-03-01

    As sessile organisms, plants have evolved a wide range of defence pathways to cope with environmental stress such as heat shock. However, the molecular mechanism of these defence pathways remains unclear in rice. In this study, we found that OsHSFA2d, a heat shock transcriptional factor, encodes two main splice variant proteins, OsHSFA2dI and OsHSFA2dII in rice. Under normal conditions, OsHSFA2dII is the dominant but transcriptionally inactive spliced form. However, when the plant suffers heat stress, OsHSFA2d is alternatively spliced into a transcriptionally active form, OsHSFA2dI, which participates in the heat stress response (HSR). Further study found that this alternative splicing was induced by heat shock rather than photoperiod. We found that OsHSFA2dI is localised to the nucleus, whereas OsHSFA2dII is localised to the nucleus and cytoplasm. Moreover, expression of the unfolded protein response (UNFOLDED PROTEIN RESPONSE) sensors, OsIRE1, OsbZIP39/OsbZIP60 and the UNFOLDED PROTEIN RESPONSE marker OsBiP1, was up-regulated. Interestingly, OsbZIP50 was also alternatively spliced under heat stress, indicating that UNFOLDED PROTEIN RESPONSE signalling pathways were activated by heat stress to re-establish cellular protein homeostasis. We further demonstrated that OsHSFA2dI participated in the unfolded protein response by regulating expression of OsBiP1. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  19. Social dataset analysis and mapping tools for Risk Perception: resilience, people preparation and communication tools

    NASA Astrophysics Data System (ADS)

    Peters-Guarin, Graciela; Garcia, Carolina; Frigerio, Simone

    2010-05-01

    Perception has been identified as resource and part of the resilience of a community to disasters. Risk perception, if present, may determine the potential damage a household or community experience. Different levels of risk perception and preparedness can influence directly people's susceptibility and the way they might react in case of an emergency caused by natural hazards. In spite of the profuse literature about risk perception, works to spatially portray this feature are really scarce. The spatial relationship to danger or hazard is being recognised as an important factor of the risk equation; it can be used as a powerful tool either for better knowledge or for operational reasons (e.g. management of preventive information). Risk perception and people's awareness when displayed in a spatial format can be useful for several actors in the risk management arena. Local authorities and civil protection can better address educational activities to increase the preparation of particularly vulnerable groups of clusters of households within a community. It can also be useful for the emergency personal in order to optimally direct the actions in case of an emergency. In the framework of the Marie Curie Research Project, a Community Based Early Warning System (CBEWS) it's been developed in the Mountain Community Valtellina of Tirano, northern Italy. This community has been continuously exposed to different mass movements and floods, in particular, a large event in 1987 which affected a large portion of the valley and left 58 dead. The actual emergency plan for the study area is composed by a real time, highly detailed, decision support system. This emergency plan contains detailed instructions for the rapid deployment of civil protection and other emergency personal in case of emergency, for risk scenarios previously defined. Especially in case of a large event, where timely reaction is crucial for reducing casualties, it is important for those in charge of emergency

  20. 40 CFR 721.1725 - Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1725 Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The...

  1. 40 CFR 721.1725 - Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1725 Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The...

  2. 40 CFR 721.1725 - Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1725 Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester. (a) Chemical substance and significant new uses subject to reporting. (1) The...

  3. Crystal structure of tetra-aqua-bis(3,5-di-amino-4H-1,2,4-triazol-1-ium)cobalt(II) bis-[bis-(pyridine-2,6-di-carboxyl-ato)cobaltate(II)] dihydrate.

    PubMed

    Johnson, Atim; Mbonu, Justina; Hussain, Zahid; Loh, Wan-Sin; Fun, Hoong-Kun

    2015-06-01

    The asymmetric unit of the title compound, [Co(C2H6N5)2(H2O)4][Co(C7H3NO4)2]2·2H2O, features 1.5 Co(II) ions (one anionic complex and one half cationic complex) and one water mol-ecule. In the cationic complex, the Co(II) atom is located on an inversion centre and is coordinated by two triazolium cations and four water mol-ecules, adopting an octa-hedral geometry where the N atoms of the two triazolium cations occupy the axial positions and the O atoms of the four water mol-ecules the equatorial positions. The two triazole ligands are parallel offset (with a distance of 1.38 Å between their planes). In the anionic complex, the Co(II) ion is six-coordinated by two N and four O atoms of the two pyridine-2,6-di-carboxyl-ate anions, exhibiting a slightly distorted octa-hedral coordination geometry in which the mean plane of the two pyridine-2,6-di-carboxyl-ate anions are almost perpendicular to each other, making a dihedral angle of 85.87 (2)°. In the crystal, mol-ecules are linked into a three-dimensional network via C-H⋯O, C-H⋯N, O-H⋯O and N-H⋯O hydrogen bonds.

  4. Improving proton conduction pathways in di- and triblock copolymer membranes: Branched versus linear side chains

    NASA Astrophysics Data System (ADS)

    Dorenbos, G.

    2017-06-01

    Phase separation within a series of polymer membranes in the presence of water is studied by dissipative particle dynamics. Each polymer contains hydrophobic A beads and hydrophilic C beads. Three parent architectures are constructed from a backbone composed of connected hydrophobic A beads to which short ([C]), long ([A3C]), or symmetrically branched A5[AC][AC] side chains spring off. Three di-block copolymer derivatives are constructed by covalently bonding an A30 block to each parent architecture. Also three tri-blocks with A15 blocks attached to both ends of each parent architecture are modeled. Monte Carlo tracer diffusion calculations through the water containing pores for 1226 morphologies reveal that water diffusion for parent architectures is slowest and diffusion through the di-blocks is fastest. Furthermore, diffusion increases with side chain length and is highest for branched side chains. This is explained by the increase of water pore size with , which is the average number of bonds that A beads are separated from a nearest C bead. Optimization of within the amphiphilic parent architecture is expected to be essential in improving proton conduction in polymer electrolyte membranes.

  5. Approach to the study of flavone di-C-glycosides by high performance liquid chromatography-tandem ion trap mass spectrometry and its application to characterization of flavonoid composition in Viola yedoensis.

    PubMed

    Cao, Jie; Yin, Chengle; Qin, Yan; Cheng, Zhihong; Chen, Daofeng

    2014-10-01

    The mass spectrometric (MS) analysis of flavone di-C-glycosides has been a difficult task due to pure standards being unavailable commercially and to that the reported relative intensities of some diagnostic ions varied with MS instruments. In this study, five flavone di-C-glycoside standards from Viola yedoensis have been systematically studied by high performance liquid chromatography-electrospray ionization-tandem ion trap mass spectrometry (HPLC-ESI-IT-MS(n)) in the negative ion mode to analyze their fragmentation patterns. A new MS(2) and MS(3) hierarchical fragmentation for the identification of the sugar nature (hexoses or pentoses) at C-6 and C-8 is presented based on previously established rules of fragmentation. Here, for the first time, we report that the MS(2) and MS(3) structure-diagnostic fragments about the glycosylation types and positions are highly dependent on the configuration of the sugars at C-6 and C-8. The base peak ((0,2) X1 (0,2) X(2)(-) ion) in MS(3) spectra of di-C-glycosides could be used as a diagnostic ion for flavone aglycones. These newly proposed fragmentation behaviors have been successfully applied to the characterization of flavone di-C-glycosides found in V. yedoensis. A total of 35 flavonoid glycosides, including 1 flavone mono-C-hexoside, 2 flavone 6,8-di-C-hexosides, 11 flavone 6,8-di-C-pentosides, 13 flavone 6,8-C-hexosyl-C-pentosides, 5 acetylated flavone C-glycosides and 3 flavonol O-glycosides, were identified or tentatively identified on the base of their UV profiles, MS and MS(n) (n = 5) data, or by comparing with reference substances. Among these, the acetylated flavone C-glycosides were reported from V. yedoensis for the first time. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Mosaic tetraploidy in a liveborn infant with features of the DiGeorge anomaly.

    PubMed

    Wullich, B; Henn, W; Groterath, E; Ermis, A; Fuchs, S; Zankl, M

    1991-11-01

    We report on a liveborn male infant with mosaic tetraploidy who presented with multiple congenital anomalies including features of the DiGeorge anomaly (type I truncus arteriosus with other cardiovascular malformations, thymic hypoplasia, hypocalcemia). No structural chromosome aberrations, namely of chromosome 22, were detected. These findings contribute to the variability of symptoms of the polyploid phenotype. Additionally, the cytogenetic studies in our case emphasize the necessity of investigating fibroblasts in order to evaluate the relevant proportion of aberrant cells in mosaicism.

  7. VaDiR: an integrated approach to Variant Detection in RNA.

    PubMed

    Neums, Lisa; Suenaga, Seiji; Beyerlein, Peter; Anders, Sara; Koestler, Devin; Mariani, Andrea; Chien, Jeremy

    2018-02-01

    Advances in next-generation DNA sequencing technologies are now enabling detailed characterization of sequence variations in cancer genomes. With whole-genome sequencing, variations in coding and non-coding sequences can be discovered. But the cost associated with it is currently limiting its general use in research. Whole-exome sequencing is used to characterize sequence variations in coding regions, but the cost associated with capture reagents and biases in capture rate limit its full use in research. Additional limitations include uncertainty in assigning the functional significance of the mutations when these mutations are observed in the non-coding region or in genes that are not expressed in cancer tissue. We investigated the feasibility of uncovering mutations from expressed genes using RNA sequencing datasets with a method called Variant Detection in RNA(VaDiR) that integrates 3 variant callers, namely: SNPiR, RVBoost, and MuTect2. The combination of all 3 methods, which we called Tier 1 variants, produced the highest precision with true positive mutations from RNA-seq that could be validated at the DNA level. We also found that the integration of Tier 1 variants with those called by MuTect2 and SNPiR produced the highest recall with acceptable precision. Finally, we observed a higher rate of mutation discovery in genes that are expressed at higher levels. Our method, VaDiR, provides a possibility of uncovering mutations from RNA sequencing datasets that could be useful in further functional analysis. In addition, our approach allows orthogonal validation of DNA-based mutation discovery by providing complementary sequence variation analysis from paired RNA/DNA sequencing datasets.

  8. A major QTL controlling apple skin russeting maps on the linkage group 12 of 'Renetta Grigia di Torriana'.

    PubMed

    Falginella, Luigi; Cipriani, Guido; Monte, Corinne; Gregori, Roberto; Testolin, Raffaele; Velasco, Riccardo; Troggio, Michela; Tartarini, Stefano

    2015-06-19

    Russeting is a disorder developed by apple fruits that consists of cuticle cracking followed by the replacement of the epidermis by a corky layer that protects the fruit surface from water loss and pathogens. Although influenced by many environmental conditions and orchard management practices, russeting is under genetic control. The difficulty in classifying offspring and consequent variable segregation ratios have led several authors to conclude that more than one genetic determinant could be involved, although some evidence favours a major gene (Ru). In this study we report the mapping of a major genetic russeting determinant on linkage group 12 of apple as inferred from the phenotypic observation in a segregating progeny derived from 'Renetta Grigia di Torriana', the construction of a 20 K Illumina SNP chip based genetic map, and QTL analysis. Recombination analysis in two mapping populations restricted the region of interest to approximately 400 Kb. Of the 58 genes predicted from the Golden Delicious sequence, a putative ABCG family transporter has been identified. Within a small set of russeted cultivars tested with markers of the region, only six showed the same haplotype of 'Renetta Grigia di Torriana'. A major determinant (Ru_RGT) for russeting development putatively involved in cuticle organization is proposed as a candidate for controlling the trait. SNP and SSR markers tightly co-segregating with the Ru_RGT locus may assist the breeder selection. The observed segregations and the analysis of the 'Renetta Grigia di Torriana' haplotypic region in a panel of russeted and non-russeted cultivars may suggest the presence of other determinants for russeting in apple.

  9. Adsorptive effects of di-tri-octahedral smectite on Clostridium perfringens alpha, beta, and beta-2 exotoxins and equine colostral antibodies.

    PubMed

    Lawler, Jacquelin Boggs; Hassel, Diana M; Magnuson, Roberta J; Hill, Ashley E; McCue, Patrick M; Traub-Dargatz, Josie L

    2008-02-01

    To determine the adsorptive capability of di-tri-octahedral smectite (DTOS) on Clostridium perfringens alpha, beta, and beta-2 exotoxins and equine colostral antibodies. 3 C perfringens exotoxins and 9 colostral samples. Alpha, beta, and beta-2 exotoxins were individually co-incubated with serial dilutions of DTOS or bismuth subsalicylate, and the amount of toxin remaining after incubation was determined via toxin-specific ELISAs. Colostral samples from healthy mares were individually co-incubated with serial dilutions of DTOS, and colostral IgG concentrations were determined via single radial immunodiffusion assay. Di-tri-octahedral smectite decreased the amount of each C perfringens exotoxin in co-incubated samples in a dose-dependent manner and was more effective than bismuth subsalicylate at reducing exotoxins in vitro. Decreases in the concentration of IgG were detected in samples of colostrum that were combined with DTOS at 1:4 through 1:16 dilutions, whereas no significant decrease was evident with DTOS at the 1:32 dilution. Di-tri-octahedral smectite effectively adsorbed C perfringens exotoxins in vitro and had a dose-dependent effect on the availability of equine colostral antibodies. Results suggested that DTOS may be an appropriate adjunctive treatment in the management of neonatal clostridiosis in horses. In vivo studies are necessary to fully assess the clinical efficacy of DTOS treatment.

  10. Thiol oxidation and di-tyrosine formation in human plasma proteins induced by inflammatory concentrations of hypochlorous acid.

    PubMed

    Colombo, Graziano; Clerici, Marco; Altomare, Alessandra; Rusconi, Francesco; Giustarini, Daniela; Portinaro, Nicola; Garavaglia, Maria Lisa; Rossi, Ranieri; Dalle-Donne, Isabella; Milzani, Aldo

    2017-01-30

    In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics. Mass spectrometry (MS) analysis was performed to elucidate the protein composition of HMW aggregates. α1-antitrypsin, transthyretin, and haptoglobin showed thiol oxidation at HOCl concentrations higher than those causing complete oxidation of albumin. At the highest HOCl concentrations, formation of carbonylated and di-tyrosine cross-linked HMW protein aggregates also occurred. MS analysis identified fibrinogen, complement C3 and apolipoprotein A-I as components of HMW protein aggregates. These results could be relevant for human diseases characterized by inflammatory conditions in which myeloperoxidase and HOCl are involved. In this study we evaluated the oxidative damage occurring on plasma proteins when reconstituted human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). Pathophysiological concentrations of HOCl are able to induce different modifications on plasma proteins such as carbonylation, sulfhydryl oxidation and formation of high molecular weight (HMW) protein aggregates characterized by di-tyrosine fluorescence. There are two relevant aspects emerging from this paper. The first one consists on identifying low abundant proteins undergoing sulfhydryl oxidation by biotin-maleimide derivatization followed by MALDI-TOF mass spectrometry. This approach suggests three low-abundant proteins undergoing HOCl-induced oxidation: transthyretin, α1-antitrypsin, and haptoglobin. In addition, we analysed HMW protein aggregates forming after HOCl exposure

  11. USSAERO version D computer program development using ANSI standard FORTRAN 77 and DI-3000 graphics

    NASA Technical Reports Server (NTRS)

    Wiese, M. R.

    1986-01-01

    The D version of the Unified Subsonic Supersonic Aerodynamic Analysis (USSAERO) program is the result of numerous modifications and enhancements to the B01 version. These changes include conversion to ANSI standard FORTRAN 77; use of the DI-3000 graphics package; removal of the overlay structure; a revised input format; the addition of an input data analysis routine; and increasing the number of aeronautical components allowed.

  12. Synthesis and liquid crystalline properties of mono-, di- and tri-O-alkyl pentaerythritol derivatives bearing tri-, di- or monogalactosyl heads: the effects of curvature of molecular packing on mesophase formation.

    PubMed

    Dumoulin, Fabienne; Lafont, Dominique; Huynh, Thai-Lê; Boullanger, Paul; Mackenzie, Grahame; West, Jon J; Goodby, John W

    2007-01-01

    Self-organisation and self-assembly are critical to the stability of synthetic and biological membranes. Of particular importance is consideration of the packing arrangements of the various molecular species. Both phospho- and glycolipids can pack in ways in which curvature can be introduced into self-organised or self-assembled systems. For instance, it is known that the degree of curvature can affect the structures of any condensed phases that are formed. In this article we report on a systematic study in which we have varied the shapes of glycolipids and examined the condensed phases that they form. In doing so, we have also unified the shape dependency of lyotropic liquid crystals with those of thermotropic liquid crystals. In order to undertake this systematic study a range of different pentaerythritol derivatives was synthesized, which covers combinations of one to three alkyl chains of different lengths (6,7,9,10,11,12,14,16 carbon atoms) and three to one galactosyl heads. Mono- and di-O-galactosyl derivatives were prepared directly by glycosylation of the corresponding alcohols using 2,3,4,6-tetra-O-benzoyl or acetyl-alpha-D-galactopyranosyl trichloroacetimidate or bromide as the donors; the tri-O-galactosyl derivatives were synthesized from O-alkyl-O-benzyl di-O-galactosyl pentaerythritol intermediates, followed by de-O-benzylation and glycosylation steps. All of the fully deprotected products were obtained by standard methods, and their self-organising and self-assembling properties examined.

  13. Di-p-xylylene polymer and method for making the same

    DOEpatents

    Jahn, Randy K.; Liepins, Raimond

    1985-01-01

    A method and apparatus for forming an improved poly-p-xylylene film. Solid di-para-xylylene dimer is sublimed in a sublimation furnace at approximately 100.degree. to 200.degree. C. and subsequently conducted to a pyrolysis furnace where it is pyrolyzed to the diradical p-xylylene monomer while in the vapor state at approximately 600 degrees C. The diradical monomer is then introduced into a deposition chamber for deposition onto a suitable substrate. The deposition chamber includes electrodes for producing a low pressure plasma through which the diradical monomer passes prior to deposition. The interaction of the diradical monomer with the low pressure plasma results in the formation of poly-p-xylylene film which is exceptionally hard and thermally stable.

  14. Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview

    PubMed Central

    2018-01-01

    Di-2-ethylhexyl phthalate (DEHP) is extensively used as a plasticizer in many products, especially medical devices, furniture materials, cosmetics, and personal care products. DEHP is noncovalently bound to plastics, and therefore, it will leach out of these products after repeated use, heating, and/or cleaning of the products. Due to the overuse of DEHP in many products, it enters and pollutes the environment through release from industrial settings and plastic waste disposal sites. DEHP can enter the body through inhalation, ingestion, and dermal contact on a daily basis, which has raised some concerns about its safety and its potential effects on human health. The main aim of this review is to give an overview of the endocrine, testicular, ovarian, neural, hepatotoxic, and cardiotoxic effects of DEHP on animal models and humans in vitro and in vivo. PMID:29682520

  15. Azide and acetate complexes plus two iron-depleted crystal structures of the di-iron enzyme delta9 stearoyl-acyl carrier protein desaturase. Implications for oxygen activation and catalytic intermediates.

    PubMed

    Moche, Martin; Shanklin, John; Ghoshal, Alokesh; Lindqvist, Ylva

    2003-07-04

    Delta9 stearoyl-acyl carrier protein (ACP) desaturase is a mu-oxo-bridged di-iron enzyme, which belongs to the structural class I of large helix bundle proteins and that catalyzes the NADPH and O2-dependent formation of a cis-double bond in stearoyl-ACP. The crystal structures of complexes with azide and acetate, respectively, as well as the apoand single-iron forms of Delta9 stearoyl-ACP desaturase from Ricinus communis have been determined. In the azide complex, the ligand forms a mu-1,3-bridge between the two iron ions in the active site, replacing a loosely bound water molecule. The structure of the acetate complex is similar, with acetate bridging the di-iron center in the same orientation with respect to the di-iron center. However, in this complex, the iron ligand Glu196 has changed its coordination mode from bidentate to monodentate, the first crystallographic observation of a carboxylate shift in Delta9 stearoyl-ACP desaturase. The two complexes are proposed to mimic a mu-1,2 peroxo intermediate present during catalytic turnover. There are striking structural similarities between the di-iron center in the Delta9 stearoyl-ACP desaturase-azide complex and in the reduced rubrerythrin-azide complex. This suggests that Delta9 stearoyl-ACP desaturase might catalyze the formation of water from exogenous hydrogen peroxide at a low rate. From the similarity in iron center structure, we propose that the mu-oxo-bridge in oxidized desaturase is bound to the di-iron center as in rubrerythrin and not as reported for the R2 subunit of ribonucleotide reductase and the hydroxylase subunit of methane monooxygenase. The crystal structure of the one-iron depleted desaturase species demonstrates that the affinities for the two iron ions comprising the di-iron center are not equivalent, Fe1 being the higher affinity site and Fe2 being the lower affinity site.

  16. Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators.

    PubMed

    Nesper, Jutta; Hug, Isabelle; Kato, Setsu; Hee, Chee-Seng; Habazettl, Judith Maria; Manfredi, Pablo; Grzesiek, Stephan; Schirmer, Tilman; Emonet, Thierry; Jenal, Urs

    2017-11-01

    The flagellar motor is a sophisticated rotary machine facilitating locomotion and signal transduction. Owing to its important role in bacterial behavior, its assembly and activity are tightly regulated. For example, chemotaxis relies on a sensory pathway coupling chemical information to rotational bias of the motor through phosphorylation of the motor switch protein CheY. Using a chemical proteomics approach, we identified a novel family of CheY-like (Cle) proteins in Caulobacter crescentus , which tune flagellar activity in response to binding of the second messenger c-di-GMP to a C-terminal extension. In their c-di-GMP bound conformation Cle proteins interact with the flagellar switch to control motor activity. We show that individual Cle proteins have adopted discrete cellular functions by interfering with chemotaxis and by promoting rapid surface attachment of motile cells. This study broadens the regulatory versatility of bacterial motors and unfolds mechanisms that tie motor activity to mechanical cues and bacterial surface adaptation.

  17. Geophysical investigations of the Olonium Roman site (Northern Como Lake)

    NASA Astrophysics Data System (ADS)

    Arlsan, Ermanno; Biella, Giancarlo; Boniolo, Graziano; Caporusso, Donatella; de Franco, Roberto; Lozej, Alfredo; Veronese, Luigi

    1999-03-01

    The study area is located at S. Agata (Gera Lario), a small center at the northern end of Como Lake, near the junction of Valchiavenna and Valtellina Valleys. This site played a strategic role since ancient times, providing the control on the communications routes to both the Como Lake and the Spluga and Septimer alpine passes. Since the end of the last century archaeological findings are reported in literature, also supported, from the early XI century, by archival documents confirming the existence of the `Olonium' settlement, an administrative and fiscal center of primary importance, as well as a parish amongst the most influential in the Como Lake area. Within an area of 45,000 m 2 an electrical survey has been carried out in conjunction with magnetic and GPR investigations. These studies have indicated the presence of a number of sub-areas characterized by significant anomalies defined by the overlapping of the results obtained from two or more geophysical methods. In two of such sub-areas, excavation tests have been conducted, which have brought to light a number of archaeological findings of interest. In one of the two sub-areas, which is characterized by the superimposition of electrical and radar anomalies, a deposit of large pebbles has been found. The origin of this deposit has not been ascertained, whether it is of fluvial origin, related to the deviation of the Adda river in the Pian di Spagna region in Roman times, or it is part of reclamation works, still of Roman times, of paleolacustrine marshes. The overlapping stratigraphy, however, suggests the development of fluvial channels between Roman and Low-Medieval times. In the other sub-area, excavations were carried out on sites defined by electrical and radar anomalies, and confirmed by the results from magnetic survey. The excavations brought to light, below the fluvial deposits, a large medieval edifice, which could be identified as the S. Stefano church abandoned in 1444. The church is built on

  18. Dynamics of glass-forming di-n-butyl phthalate as studied by NMR.

    PubMed

    Szcześniak, E; Głowinkowski, S; Suchański, W; Jurga, S

    1997-04-01

    Spin-lattice relaxation times T1 and nuclear Overhauser effect (NOE) enhancement factors for the individual ring carbons in di-n-butyl phthalate (DBF) show that the reorientational correlation function corresponding to the global dynamics in supercooled liquid can be described by a Davidson-Cole distribution. Measurements of proton spin-lattice relaxation times T1 and T1p, as well as 1H NMR spectra at temperatures below the glass transition temperature, Tg, reveal that the same distribution holds also for description of local dynamics in glassy DBF. The activation parameters of the motions detected are derived.

  19. Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

    PubMed

    Altier, N; Stewart, J

    1993-11-19

    Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

  20. Reaction Electronic Flux Perspective on the Mechanism of the Zimmerman Di-π-methane Rearrangement.

    PubMed

    Matute, Ricardo A; Pérez, Patricia; Chamorro, Eduardo; Villegas-Escobar, Nery; Cortés-Arriagada, Diego; Herrera, Barbara; Gutiérrez-Oliva, Soledad; Toro-Labbé, Alejandro

    2018-06-01

    The reaction electronic flux (REF) offers a powerful tool in the analysis of reaction mechanisms. Noteworthy, the relationship between aromaticity and REF can eventually reveal subtle electronic events associated with reactivity in aromatic systems. In this work, this relationship was studied for the triplet Zimmerman di-π-methane rearrangement. The aromaticity loss and gain taking place during the reaction is well acquainted by the REF, thus shedding light on the electronic nature of reactions involving dibenzobarrelenes.

  1. Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

    PubMed

    Sirima, S B; Durier, C; Kara, L; Houard, S; Gansane, A; Loulergue, P; Bahuaud, M; Benhamouda, N; Nebié, I; Faber, B; Remarque, E; Launay, O

    2017-10-27

    Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. ClinicalTrials.gov NCT02014727; PACTR201402000719423. Copyright © 2017. Published by Elsevier Ltd.

  2. Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4.

    PubMed

    Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

    2014-12-01

    In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)--producing the biofilm-promoting second messenger c-di-GMP--that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4

    PubMed Central

    Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

    2014-01-01

    In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)—producing the biofilm-promoting second messenger c-di-GMP—that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. PMID:25361688

  4. dSet1 Is the Main H3K4 Di- and Tri-Methyltransferase Throughout Drosophila Development

    PubMed Central

    Hallson, Graham; Hollebakken, Robert E.; Li, Taosui; Syrzycka, Monika; Kim, Inho; Cotsworth, Shawn; Fitzpatrick, Kathleen A.; Sinclair, Donald A. R.; Honda, Barry M.

    2012-01-01

    In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a “global” or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans. PMID:22048023

  5. Average structure and M2 site configurations in C2/c clinopyroxenes along the Di-En join

    NASA Astrophysics Data System (ADS)

    Tribaudino, M.; Benna, P.; Bruno, E.

    1989-12-01

    In order to clarify the structural configurations observed in Diss in the Ca-rich region of the Di-En join (in which TEM observations show neither exsolution microstructures nor evidence of spinodal decomposition) single crystals large enough for X-ray diffraction analyses, with composition (Ca0.66Mg0.34)MgSi2O6, have been equilibrated close to the solvus at T=1350° C for 317 h, and quenched at room temperature. The refinement in C2/c space group shows that in the M2 site Ca and Mg are fully ‘ordered’ in two split positions (M2occ: 0.66 Ca; M2'occ: 0.34 Mg). Since the average structure shows a relevant elongation of anisotropic thermal ellipsoids of the O2 and O3 oxygen atoms, the refinement has been carried out according to a split model for O2 and O3 atoms: Ca appears 8-coordinated (as in diopside) and Mg shows a sixfold coordination similar to that of high-pigeonite. This coordination for Mg is significantly different from the fourfold coordination (Zn-like in Zn-cpx) proposed previously and it is a more probable coordination for Mg from a crystalchemical point of view. The same results were obtained refining a Di80En20 cpx, equilibrated at T=1230° C, according to the same O-split model. The data support the coexistence of a Di-like configuration for Ca and of a highPig-like configuration for Mg away from the solvus also. At T very near to T solidus the different configurations, observed at room temperature in the quenched samples, should converge and Ca and Mg should retain a single disordered configuration in the M2 site.

  6. Diabetes risk reduction in overweight first degree relatives of type 2 diabetes patients: effects of a low-intensive lifestyle education program (DiAlert) A randomized controlled trial.

    PubMed

    Heideman, Wieke H; de Wit, Maartje; Middelkoop, Barend J C; Nierkens, Vera; Stronks, Karien; Verhoeff, Arnoud P; Snoek, Frank J

    2015-04-01

    To test the efficacy of a low-intensive lifestyle education program (DiAlert) for overweight first degree relatives of type 2 diabetes patients aimed at reducing diabetes risk. Overweight first degree relatives of type 2 diabetes patients were randomly assigned to the DiAlert intervention (N=45) or control group who received leaflets (N=51). DiAlert consists of two group sessions and newsletters. Assessments were scheduled at baseline, three and nine months, with weight loss as primary outcome. Secondary outcomes included anthropometric, metabolic, behavioral and psychological measures. Comparisons were made over time and between groups. Both groups showed modest weight loss with no difference between randomization groups. However, after DiAlert significantly more participants lost 5% of their weight compared to controls (P=0.03). Significant improvement of waist circumference sustained after 9 months in the intervention group (intervention: -4.33cm, P<0.01/control: -1.25cm, P=0.08). Systolic blood pressure improved within the intervention group (intervention: -8.77mmHg, P<0.01/control: -1.03mmHg, P=0.60). No effect was observed for biomedical and psychosocial outcomes. Our low-intensive structured lifestyle education program helps overweight relatives to improve waist circumference and supports relevant weight loss. The family approach provides opportunities to reach and engage relatives at risk in diabetes prevention education. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Identification and geochemical significance of cyclic di-and trisulphides with linear and acyclic isoprenoid carbon skeletons in immature sediments

    NASA Astrophysics Data System (ADS)

    Kohnen, Math E. L.; Sinninghe Damsté, Jaap S.; ten Haven, H. L.; Van Dalen, A. C. Kock; Schouten, Stefan; De Leeuw, Jan W.

    1991-12-01

    Homologous series (C 15-C 24) of novel 3- n-alkyl-1,2-dithianes and 3- n-alkyl-6-methyl-1,2-di-thianes have been identified in immature sediments. The identification of these compounds was based on comparison of mass spectra and Chromatographie data with those of synthesized 3-methyl-6-tridecyll, 2-dithiane. In addition, 4-methyl-3-(3,7,11-trimethyldodecyl)-1,2-dithiane, 4-(4,8,12-trimethyltridecyl)-1,2-dithiane, 5-methyl-4-(3,7,11-trimethyldodecyl)-1,2,3-trithiepane, and a 1,2-dithiane possessing a pentakishomohopane carbon skeleton were tentatively assigned on the basis of mass spectral characteristics, selective chemolysis, and desulphurisation. The occurrence of these cyclic di-and trisulphides with linear, acyclic isoprenoid and hopanoid carbon skeletons in thermally immature sediments indicates that inorganic polysulphides are incorporated into functionalised lipids during the early stages of diagenesis.

  8. (Carbonato-κ2 O,O′)bis­(di-2-pyridyl­amine-κ2 N,N′)cobalt(III) bromide

    PubMed Central

    Czapik, Agnieszka; Papadopoulos, Christos; Lalia-Kantouri, Maria; Gdaniec, Maria

    2011-01-01

    In the title compound, [Co(CO3)(C10H9N3)2]Br, a distorted octa­hedral coordination of the CoIII atom is completed by four N atoms of the two chelating di-2-pyridyl­amine ligands and two O atoms of the chelating carbonate anion. The di-2-pyridyl­amine ligands are nonplanar and the dihedral angles between the 2-pyridyl groups are 29.11 (9) and 37.15 (12)°. The coordination cation, which has approximate C 2 symmetry, is connected to the bromide ion via an N—H⋯Br− hydrogen bond. The ionic pair thus formed is further assembled into a dimer via N—H⋯O inter­actions about an inversion centre. A set of weaker C—H⋯O and C—H⋯Br− inter­actions connect the dimers into a three-dimensional network. PMID:21753946

  9. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

    PubMed

    Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

    2006-11-01

    Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

  10. Molecular dynamics study of di-CF4 based reverse micelles in supercritical CO2.

    PubMed

    Liu, Bing; Tang, Xinpeng; Fang, Wenjing; Li, Xiaoqi; Zhang, Jun; Zhang, Zhiliang; Shen, Yue; Yan, Youguo; Sun, Xiaoli; He, Jianying

    2016-10-26

    Reverse micelles (RMs) in supercritical CO 2 (scCO 2 ) are promising alternatives for organic solvents, especially when both polar and non-polar components are involved. Fluorinated surfactants, particularly double-chain fluorocarbon surfactants, are able to form well-structured RMs in scCO 2 . The inherent self-assembly mechanisms of surfactants in scCO 2 are still subject to discussion. In this study, molecular dynamics simulations are performed to investigate the self-aggregation behavior of di-CF4 based RMs in scCO 2 , and stable and spherical RMs are formed. The dynamics process and the self-assembly structure in the RMs reveal a three-step mechanism to form the RMs, that is, small RMs, rod-like RMs and fusion of the rod-like RMs. Hydrogen-bonds between headgroups and water molecules, and salt bridges linking Na + ions, headgroups and water molecules enhance the interfacial packing efficiency of the surfactant. The results show that di-CF4 molecules have a high surfactant coverage at the RM interface, implying a high CO 2 -philicity. This mainly results from bending of the short chain (C-COO-CH 2 -(CF2) 3 -CF3) due to the flexible carboxyl group. The microscopic insight provided in this study is helpful in understanding surfactant self-assembly phenomena and designing new CO 2 -philic surfactants.

  11. Um satélite brasileiro para observação do diâmetro solar

    NASA Astrophysics Data System (ADS)

    Emilio, M.; Leister, N. V.; Benevides Soares, P.; Teixeira, R.; Kuhn, J.

    2003-08-01

    Propomos uma missão espacial para medir a forma e o diâmetro solar com o objetivo de ajudar a determinar o potencial gravitacional do Sol e a sua rotação com precisão, testar modelos teóricos de variação de energia e pela primeira vez medir os modos g de oscilação. As observações serão obtidas através do instrumento denominado APT (Astrometric and Photometric Telescope) descrito por Kuhn(1983). A sensibilidade do instrumento é de 0,2 mas em 27 dias para as observações do diâmetro solar feitas a cada minuto. Esta é uma missão de três anos de duração e pode complementar as medidas que serão feitas pelo satélite PICARD (a ser lançado em 2007). Outros parâmetros físicos podem ser obtidos com as mesmas imagens o que certamente interessará à comunidade de física solar. Um primeiro contato foi realizado com a agência espacial brasileira que pretende lançar um satélite científico a cada dois anos.

  12. Effect of Mono and Di-rhamnolipids on Biofilms Pre-formed by Bacillus subtilis BBK006.

    PubMed

    De Rienzo, Mayri A Díaz; Martin, Peter J

    2016-08-01

    Different microbial inhibition strategies based on the planktonic bacterial physiology have been known to have limited efficacy on the growth of biofilms communities. This problem can be exacerbated by the emergence of increasingly resistant clinical strains. Biosurfactants have merited renewed interest in both clinical and hygienic sectors due to their potential to disperse microbial biofilms. In this work, we explore the aspects of Bacillus subtilis BBK006 biofilms and examine the contribution of biologically derived surface-active agents (rhamnolipids) to the disruption or inhibition of microbial biofilms produced by Bacillus subtilis BBK006. The ability of mono-rhamnolipids (Rha-C10-C10) produced by Pseudomonas aeruginosa ATCC 9027 and the di-rhamnolipids (Rha-Rha-C14-C14) produced by Burkholderia thailandensis E264, and phosphate-buffered saline to disrupt biofilm of Bacillus subtilis BBK006 was evaluated. The biofilm produced by Bacillus subtilis BBK006 was more sensitive to the di-rhamnolipids (0.4 g/L) produced by Burkholderia thailandensis than the mono-rhamnolipids (0.4 g/L) produced by Pseudomonas aeruginosa ATCC 9027. Rhamnolipids are biologically produced compounds safe for human use. This makes them ideal candidates for use in new generations of bacterial dispersal agents and useful for use as adjuvants for existing microbial suppression or eradication strategies.

  13. An Investigation of Pun Translatability in English Translations of Sa'di's Ghazals Based on Delabastita's Proposed Model

    ERIC Educational Resources Information Center

    Koochacki, Fahime

    2016-01-01

    The rich cultural connotations behind puns and the distinctive features of the puns' form, sound and meanings pose great challenges to the translator. Furthermore, given puns' non-negligible effects in Persian literary texts, it has been the aim of the present study to analyze and measure how puns in Sa'di's Ghazals have actually been treated in…

  14. Diagnosing Autism in Adults with Intellectual Disability: Validation of the DiBAS-R in an Independent Sample

    ERIC Educational Resources Information Center

    Heinrich, Manuel; Böhm, Julia; Sappok, Tanja

    2018-01-01

    The study assessed the diagnostic validity of the diagnostic behavioral assessment for autism spectrum disorders-revised (DiBAS-R; 19-item screening scale based on ratings by caregivers) in a clinical sample of 381 adults with ID. Analysis revealed a sensitivity of 0.82 and a specificity of 0.67 in the overall sample (70.3% agreement). Sensitivity…

  15. Assessing Autism in Adults: An Evaluation of the Developmental, Dimensional and Diagnostic Interview-Adult Version (3Di-Adult)

    ERIC Educational Resources Information Center

    Mandy, William; Clarke, Kiri; McKenner, Michele; Strydom, Andre; Crabtree, Jason; Lai, Meng-Chuan; Allison, Carrie; Baron-Cohen, Simon; Skuse, David

    2018-01-01

    We developed a brief, informant-report interview for assessing autism spectrum conditions (ASC) in adults, called the Developmental, Dimensional and Diagnostic Interview-Adult Version (3Di-Adult); and completed a preliminary evaluation. Informant reports were collected for participants with ASC (n = 39), a non-clinical comparison group (n = 29)…

  16. Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4''-carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin.

    PubMed

    Ma, Shutao; Ma, Ruixin; Liu, Zhaopeng; Ma, Chenchen; Shen, Xuecui

    2009-10-01

    4''-Carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin were designed, synthesized and evaluated. The 4''-carbamate analogs retained excellent activity against erythromycin-susceptible Staphylococcus pneumoniae and showed improved activity against erythromycin-resistant Staphylococcus pneumoniae. Compared with 4''-carbamate analogs, 11,12-cyclic carbonate-4''-carbamate analogs exhibited improved activity against erythromycin-resistant Staphylococcus pneumoniae encoded by the mef gene or the erm and mef genes, and 11,4''-di-O-arylalkylcarbamoyl analogs showed greatly improved activity (0.25-0.5 microg/mL) against erythromycin-resistant Staphylococcus pneumoniae encoded by the erm gene. Among them, the novel series of 11,4''-di-O-arylalkylcarbamoyl analogs 7a-k exhibited potent and balanced activity against susceptible and resistant bacteria. In particular, compounds 7f and 7k were the most effective against susceptible bacteria and resistant bacteria encoded by the erm gene or the mef gene.

  17. Three Antagonistic Cyclic di-GMP-Catabolizing Enzymes Promote Differential Dot/Icm Effector Delivery and Intracellular Survival at the Early Steps of Legionella pneumophila Infection

    PubMed Central

    Allombert, Julie; Lazzaroni, Jean-Claude; Baïlo, Nathalie; Gilbert, Christophe; Charpentier, Xavier; Doublet, Patricia

    2014-01-01

    Legionella pneumophila is an intracellular pathogen which replicates within protozoan cells and can accidently infect alveolar macrophages, causing an acute pneumonia in humans. The second messenger cyclic di-GMP (c-di-GMP) has been shown to play key roles in the regulation of various bacterial processes, including virulence. While investigating the function of the 22 potential c-di-GMP-metabolizing enzymes of the L. pneumophila Lens strain, we found three that directly contribute to its ability to infect both protozoan and mammalian cells. These three enzymes display diguanylate cyclase (Lpl0780), phosphodiesterase (Lpl1118), and bifunctional diguanylate cyclase/phosphodiesterase (Lpl0922) activities, which are all required for the survival and intracellular replication of L. pneumophila. Mutants with deletions of the corresponding genes are efficiently taken up by phagocytic cells but are partially defective for the escape of the Legionella-containing vacuole (LCV) from the host degradative endocytic pathway and result in lower survival. In addition, Lpl1118 is required for efficient endoplasmic reticulum recruitment to the LCV. Trafficking and biogenesis of the LCV are dependent upon the orchestrated actions of several type 4 secretion system Dot/Icm effectors proteins, which exhibit differentially altered translocation in the three mutants. While translocation of some effectors remained unchanged, others appeared over- and undertranslocated. A general translocation offset of the large repertoire of Dot/Icm effectors may be responsible for the observed defects in the trafficking and biogenesis of the LCV. Our results suggest that L. pneumophila uses cyclic di-GMP signaling to fine-tune effector delivery and ensure effective evasion of the host degradative pathways and establishment of a replicative vacuole. PMID:24379287

  18. Genetic modifiers of Velo- cardio- facial syndrome/DiGeorge syndrome

    PubMed Central

    Aggarwal, Vimla S.; Morrow, Bernice E.

    2009-01-01

    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid and thymic defects as well as cardiac outflow tract malformations. Most patients have a similar hemizygous 3 million base pair deletion on 22q11.2. Studies in mouse have shown that Tbx1, a T- box containing transcription factor present on the deleted region, is likely responsible for the etiology of the syndrome. Furthermore, mutations in TBX1 have been found in rare non-deleted patients. Despite having the same sized deletion, most VCFS/DGS patients exhibit significant clinical variability. Stochastic, environmental and genetic factors likely modify the phenotype of patients with the disorder. Here, we review mouse genetics studies which may help identify genetic modifiers for VCFS/DGS. PMID:18636633

  19. [Chiral separation of five beta-blockers using di-n-hexyl L-tartrate-boric acid complex as mobile phase additive by reversed-phase liquid chromatography].

    PubMed

    Yang, Juan; Wang, Lijuan; Guo, Qiaoling; Yang, Gengliang

    2012-03-01

    A reversed-phase high performance liquid chromatographic (HPLC) method using the di-n-hexyl L-tartrate-boric acid complex as a chiral mobile phase additive was developed for the enantioseparation of five beta-blockers including propranolol, esmolol, metoprolol, bisoprolol and sotalol. In order to obtain a better enantioseparation, the influences of concentrations of di-n-butyl L-tartrate and boric acid, the type, concentration and pH of the buffer, methanol content as well as the molecular structure of analytes were extensively investigated. The separation of the analytes was performed on a Venusil MP-C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase was 15 mmol/L ammonium acetate-methanol containing 60 mmol/L boric acid, 70 mmol/L di-n-hexyl L-tartrate (pH 6.00). The volume ratios of 15 mmol/L ammonium acetate to methanol were 20: 80 for propranolol, esmolol, metoprolol, bisoprolol and 30: 70 for sotalol. The flow rate was 0.5 mL/min and the detection wavelength was set at 214 nm. Under the optimized conditions, baseline enantioseparation was obtained separately for the five pairs of analytes.

  20. Serpentinite-driven Exhumation of the UHP Lago di Cignana Unit in the Fossil Alpine Plate Interface

    NASA Astrophysics Data System (ADS)

    Scambelluri, M.; Gilio, M.; Angiboust, S.; Godard, M.; Pettke, T.

    2015-12-01

    The Lago di Cignana Unit (LCU) is a coesite- [1] and diamond-bearing [2] slice of oceanic-derived eclogites and metasediments recording Alpine UHP metamorphism at 600 °C-3.2 GPa (~110 km depth) [3]. The LCU is tectonically sandwiched between the eclogitic Zermatt-Saas Zone (ZSZ; 540 °C-3.2 GPa) [4] and the blueschist Combin Zone (400 °C-0.9 GPa) [5] along a tectonic structure joining HP units recording a ~1.2 GPa (40 km) pressure difference. So far, the ZSZ has been attributed to normal HP conditions and the mechanism driving exhumation and accretion of the LCU in its present structural position is not fully understood.We performed petrography and bulk-rock trace element analyses of rocks from LCU and ZSZ serpentinites. We observed that, while serpentinites in the core of the ZSZ show normal subduction zone trace elements and REE's patterns, the Ol+Ti-chu+Chl veins and host serpentinites enveloping the LCU are strongly enriched in sediment-derived fluid-mobile elements (U, Th, Nb, Ta, Ce, Y, As, Sb) and REE's: their patterns well match those of the closely associated LCU-UHP rocks.The presence of extremely enriched Ol+Ti-chu+Chl veins in the serpentinites at direct contact with the UHP Lago di Cignana Unit suggests that fluid exchange between serpentinite and LCU crustal rocks occurred at peak metamorphic conditions. Their coupling therefore occurred during subduction burial and/or peak UHP conditions. As such, the buoyancy force originating from the relatively light serpentinites fuelled the exhumation of the Lago di Cignana Unit. In this contest, the tectonic contact between the Zermatt-Saas Zone and the Combin Zone evolved into a true tectonic plate interface surface.1. Reinecke (1998). Lithos 42(3), 147-189; 2. Frezzotti et al. (2011). Nat. Geosci. 4(10), 703-706; 3. Groppo et al. (2009). J. Metam. Geol. 27(3), 207-231; 4. Angiboust et al. (2009). Terra Nova 21(3), 171-180; 5. Reddy et al. (1999). J. Metam. Geol. 17, 573-590.

  1. Experimental Determination of Solubilities of Sodium Polyborates In MgCl 2 Solutions: Solubility Constant of Di-Sodium Hexaborate Tetrahydrate, and Implications For the Diagenetic Formation of Ameghinite

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiong, Yongliang; Kirkes, Leslie; KNOX, Jandi

    In this paper, solubility measurements were conducted for sodium polyborates in MgCl 2 solutions at 22.5 ± 0.5 °C. According to solution chemistry and XRD patterns, di-sodium tetraborate decahydrate (borax) dissolves congruently, and is the sole solubility-controlling phase, in a 0.01 mol/kg MgCl 2 solution: Na 2B 4O 7•10H 2O(cr) ⇌ 2Na + + 4B(OH) 4 + 2H + + H 2O(l). However, in a 0.1 mol/kg MgCl 2 solution borax dissolves incongruently and is in equilibrium with di-sodium hexaborate tetrahydrate: 2Na 2B 6O 10•4H 2O(cr) + 2Na + + 23H 2O(l) ⇌ 3Na 2B 4O 7•10H 2O(cr) + 2Hmore » +. In this study, the equilibrium constant (log K 0) for Reaction 2 at 25 °C and infinite dilution was determined to be –16.44 ± 0.13 (2σ) based on the experimental data and the Pitzer model for calculations of activity coefficients of aqueous species. In accordance with the log K 0 for Reaction 1 from a previous publication from this research group, and log K 0 for Reaction 2 from this study, the equilibrium constant for dissolution of di-sodium hexaborate tetrahydrate at 25 °C and at infinite dilution, Na 2B 6O 10•4H 2O(cr) + 10H 2O(l) ⇌ 2Na + + 6B(OH) 4 - + 4H + was derived to be –45.42 ± 0.16 (2σ). The equilibrium constants determined in this study can find applications in many fields. For example, in the field of nuclear waste management, the formation of di-sodium hexaborate tetrahydrate in brines containing magnesium will decrease borate concentrations, making less borate available for interactions with Am(III). In the field of experimental investigations, based on the equilibrium constant for Reaction 2, the experimental systems can be controlled in terms of acidity around neutral pH by using the equilibrium assemblage of borax and di-sodium hexaborate tetrahydrate at 25 °C. As salt lakes and natural brines contain both borate and magnesium as well as sodium, the formation of sodium hexaborate tetrahydrate may influence the chemical evolution of salt lakes

  2. Experimental Determination of Solubilities of Sodium Polyborates In MgCl 2 Solutions: Solubility Constant of Di-Sodium Hexaborate Tetrahydrate, and Implications For the Diagenetic Formation of Ameghinite

    DOE PAGES

    Xiong, Yongliang; Kirkes, Leslie; KNOX, Jandi; ...

    2017-11-01

    In this paper, solubility measurements were conducted for sodium polyborates in MgCl 2 solutions at 22.5 ± 0.5 °C. According to solution chemistry and XRD patterns, di-sodium tetraborate decahydrate (borax) dissolves congruently, and is the sole solubility-controlling phase, in a 0.01 mol/kg MgCl 2 solution: Na 2B 4O 7•10H 2O(cr) ⇌ 2Na + + 4B(OH) 4 + 2H + + H 2O(l). However, in a 0.1 mol/kg MgCl 2 solution borax dissolves incongruently and is in equilibrium with di-sodium hexaborate tetrahydrate: 2Na 2B 6O 10•4H 2O(cr) + 2Na + + 23H 2O(l) ⇌ 3Na 2B 4O 7•10H 2O(cr) + 2Hmore » +. In this study, the equilibrium constant (log K 0) for Reaction 2 at 25 °C and infinite dilution was determined to be –16.44 ± 0.13 (2σ) based on the experimental data and the Pitzer model for calculations of activity coefficients of aqueous species. In accordance with the log K 0 for Reaction 1 from a previous publication from this research group, and log K 0 for Reaction 2 from this study, the equilibrium constant for dissolution of di-sodium hexaborate tetrahydrate at 25 °C and at infinite dilution, Na 2B 6O 10•4H 2O(cr) + 10H 2O(l) ⇌ 2Na + + 6B(OH) 4 - + 4H + was derived to be –45.42 ± 0.16 (2σ). The equilibrium constants determined in this study can find applications in many fields. For example, in the field of nuclear waste management, the formation of di-sodium hexaborate tetrahydrate in brines containing magnesium will decrease borate concentrations, making less borate available for interactions with Am(III). In the field of experimental investigations, based on the equilibrium constant for Reaction 2, the experimental systems can be controlled in terms of acidity around neutral pH by using the equilibrium assemblage of borax and di-sodium hexaborate tetrahydrate at 25 °C. As salt lakes and natural brines contain both borate and magnesium as well as sodium, the formation of sodium hexaborate tetrahydrate may influence the chemical evolution of salt lakes

  3. Biophysical and transfection studies of the diC(14)-amidine/DNA complex.

    PubMed Central

    Cherezov, Vadim; Qiu, Hong; Pector, Veronique; Vandenbranden, Michel; Ruysschaert, Jean-Marie; Caffrey, Martin

    2002-01-01

    Liposomes of the synthetic cationic lipid, N-t-butyl-N'-tetradecylamino-propionamidine (diC(14)-amidine), efficiently ports DNA into mammalian cells in the absence of other (neutral) lipids. The compositional simplicity of this transfection mix makes it attractive from a formulation perspective. We have used low- and wide-angle x-ray diffraction and polarized light microscopy to characterize the thermotropic phase behavior and microstructure of diC(14)-amidine and of the lipid/DNA (circular plasmid, 5.4 kb) complex with a view to understanding the structure of the complex and its role in transfection. Upon heating, the lipid in buffer undergoes a lamellar crystalline (L(c), d(001) = 41.7 A)-to-lamellar liquid crystal (L(c)(alpha), d(001) depends on hydration and T) transition at approximately 40 degrees C. Sonicated lipid vesicles with a reported transition temperature of approximately 23 degrees C complex with DNA. Complex formation is complete at a DNA/lipid mole ratio (rho) of 0.8. Adding DNA to the lipid causes d(001) of the multilayered complex to drop from 52 to 49 A as rho rises from 0.03 to 1.64. The minimal DNA-DNA duplex separation observed is 26 A, consistent with the close packing of B-DNA. Lipid bilayers in the complex undergo a lamellar gel (L(c)(beta))-to-L(c)(alpha) (superscript c refers to complex) transition at approximately 23 degrees C. Transfection efficiency was maximized at rho = 0.4. The structure and transfection data combined suggest that densely packaged DNA in a net positively charged complex is essential for transfection. PMID:12023234

  4. Di-iso-Butyl Phthalate MATERNAL AND FETAL DATA FROM THE LE GRAY RESEARCH TEAM FOR NCEA June 15 2016

    EPA Science Inventory

    this file contains the raw data on the effects of in utero administration of di-iso-butyl phthalate on maternal weight gain during dosing and the numbers of fetuses and fetal resorptions. The data have all been previously published, as described on the file metadata sheet.

  5. The Effects of DI Flashcards and Math Racetrack on Multiplication Facts for Two Elementary Students with Learning Disabilities

    ERIC Educational Resources Information Center

    Lund, Kaitlyn; McLaughlin, T. F.; Neyman, Jen; Everson, Mary

    2012-01-01

    The purpose of this study was to evaluate the effects of a Direct Instruction (DI) flashcard system paired with a math racetrack to teach basic multiplication facts to two elementary students diagnosed with learning disabilities. The study was conducted in a resource room which served intermediate aged elementary students. The school was located…

  6. Crystal structure and Hirshfield analysis of the 4-(di-methyl-amino)-pyridine adduct of 4-meth-oxy-phenyl-borane.

    PubMed

    Shooter, Jesse; Allen, Caleb J; Tinsley, Colby W K; Zakharov, Lev N; Abbey, Eric R

    2017-11-01

    The title compound [systematic name: 4-(di-methyl-amino)-pyridine-4-meth-oxy-phenyl-borane (1/1)], C 14 H 19 BN 2 O, contains two independent mol-ecules in the asymmetric unit. Both molecules exhibit coplanar, mostly sp 2 -hybridized meth-oxy and di-methyl-amino substituents on their respective aromatic rings, consistent with π-donation into the aromatic systems. The B-H groups exhibit an intra-molecular close contact with a C-H group of the pyridine ring, which may be evidence of electrostatic attraction between the hydridic B-H and the electropositive aromatic C-H. There appears to be weak C-H⋯π(arene) inter-actions between two of the H atoms of an amino-methyl group and the meth-oxy-substituted benzene ring of the other independent mol-ecule, and another C-H⋯π (arene) inter-action between one of the pyridine ring H atoms and the same benzene ring.

  7. Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.

    PubMed

    Maruyama, Takahisa; Yamamoto, Yasuo; Kano, Yuko; Kurazono, Mizuyo; Shitara, Eiki; Iwamatsu, Katsuyoshi; Atsumi, Kunio

    2009-01-15

    A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility.

  8. Measurements of the center-of-mass energies at BESIII via the di-muon process

    DOE PAGES

    Ablikim, M.; Achasov, M. N.; Ai, X. C.; ...

    2016-06-01

    From 2011 to 2014, the BESIII experiment collected about 5 fb -1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing the di-muon process e +e - → γ ISR/FSRμ +μ -, the center-of-mass energies of the data samples are measured with a precision of 0.8 MeV. The center-of-mass energy is found to be stable for most of the time during data taking.

  9. 40 CFR 721.1725 - Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.1725 Benzoic acid, 3,3′-methyl-enebis [6 amino..., Benzoic acid, 3,3′-methylenebis [6 amino-, di-2-propenyl ester. (2) The significant new uses are: (i) Any... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzoic acid, 3,3â²-methyl-enebis [6...

  10. 40 CFR 721.1725 - Benzoic acid, 3,3′-methyl-enebis [6 amino-, di-2-propenyl ester.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.1725 Benzoic acid, 3,3′-methyl-enebis [6 amino..., Benzoic acid, 3,3′-methylenebis [6 amino-, di-2-propenyl ester. (2) The significant new uses are: (i) Any... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzoic acid, 3,3â²-methyl-enebis [6...

  11. Flash Pyrolysis of t-Butyl Hydroperoxide and Di-t-butyl Peroxide: Evidence of Roaming in the Decomposition of Organic Hydroperoxides.

    PubMed

    Jones, Paul J; Riser, Blake; Zhang, Jingsong

    2017-10-19

    Thermal decomposition of t-butyl hydroperoxide and di-t-butyl peroxide was investigated using flash pyrolysis (in a short reaction time of <100 μs) and vacuum-ultraviolet (λ = 118.2 nm) single-photon ionization time-of-flight mass spectrometry (VUV-SPI-TOFMS) at temperatures up to 1120 K and quantum computational methods. Acetone and methyl radical were detected as the predominant products in the initial decomposition of di-t-butyl peroxide via O-O bond fission. In the initial dissociation of t-butyl hydroperoxide, acetone, methyl radical, isobutylene, and isobutylene oxide products were identified. The novel detection of the unimolecular formation of isobutylene oxide, as supported by the computational study, was found to proceed via a roaming hydroxyl radical facilitated by a hydrogen-bonded intermediate. This new pathway could provide a new class of reactions to consider in the modeling of the low temperature oxidation of alkanes.

  12. SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme

    PubMed Central

    Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P. C.; Ovaa, Huib; Drag, Marcin; Lima, Christopher D.; Huang, Tony T.

    2015-01-01

    Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15-conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a “mono-distributive” manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a “di-distributive” cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses. PMID:25764917

  13. SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme.

    PubMed

    Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P C; Ovaa, Huib; Drag, Marcin; Lima, Christopher D; Huang, Tony T

    2015-06-01

    Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co-opted Ub-ISG15 conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated host proteins. In the present study, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle East respiratory syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the intrinsic DUB activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a minimal recognition element using a 'di-distributive' cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP (Ub-specific protease)-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help to identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.

  14. The new concept of the Disruption Index (DI) as an indicator to measure cascading effects in urban areas

    NASA Astrophysics Data System (ADS)

    Oliveira, C. S.; Ferreira, M. A.

    2015-12-01

    Apart from the loss of lives, injuries and homeless resulting from an earthquake, not only the economy and physical landscape are altered, but also the lives of citizens and their places of work are dramatically altered. If critical services and functions are disrupted for more than a reasonable time period, consequences can be severe. All communities are at risk and face potential disaster, if unprepared. The Disruption Index (DI) is a tool that allows the representation of a complex, multidimensional, situation in a concise and easier way, providing institutions and communities with a way to identify the global earthquake impact in a geographical area, the elements at risk, and the means to reduce it. Understanding how the loss and cascading effects across a number of areas might be correlated during a single earthquake is critical to evaluate risk. The application of this tool, prior-to a catastrophe, assumes a huge importance for earthquake risk professionals and planners to understand their impacts and to start building earthquake resilient cities. Post-to an event, this tool provides an assessment of its extent and impact considering the propagation effects, developed in a Geographic Information System (GIS) environment. The DI was already tested, calibrated after several earthquakes and applied in Portugal, Italy, Spain and Iceland. The next step in this research is to implement this tool directly into web portals or websites as well as PAGER or GDACS platforms to: - Rapidly assess an earthquake impact in a region following significant events. Nowadays the institutions used the shake maps; it's an important tool but cannot reflect the impact on livelihoods and the cascade effects. The DI maps can be used by state and local organizations, both public and private, for post-earthquake response and recovery, public and scientific information.

  15. Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

    PubMed Central

    Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

    2006-01-01

    Background Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Objective Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Results Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). Conclusion We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers. PMID:17107847

  16. The Epoxidation of 2,5-Di-tert-butyl-1,4-benzoquinone: A Consecutive Reaction for the Physical Chemistry Laboratory.

    ERIC Educational Resources Information Center

    Hairfield, E. M.; And Others

    1985-01-01

    Reports a consecutive first-order reaction for which the concentrations of reactant, intermediate, and products can be determined simulataneously. This reaction is the epoxidation of 2,5-di-tert-butyl-1,4-benzoquinone (I) by alkaline hydroperoxidation using tert-butyl hydroperoxide and benzyltrimethylammonium hydroxide (Triton B) catalyst.…

  17. A Bayes Factor Meta-Analysis of Recent Extrasensory Perception Experiments: Comment on Storm, Tressoldi, and Di Risio (2010)

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Morey, Richard D.; Province, Jordan M.

    2013-01-01

    Psi phenomena, such as mental telepathy, precognition, and clairvoyance, have garnered much recent attention. We reassess the evidence for psi effects from Storm, Tressoldi, and Di Risio's (2010) meta-analysis. Our analysis differs from Storm et al.'s in that we rely on Bayes factors, a Bayesian approach for stating the evidence from data for…

  18. A Versatile Room-Temperature Route to Di- and Trisubstituted Allenes Using Flow-Generated Diazo Compounds.

    PubMed

    Poh, Jian-Siang; Tran, Duc N; Battilocchio, Claudio; Hawkins, Joel M; Ley, Steven V

    2015-06-26

    A copper-catalyzed coupling reaction between flow-generated unstabilized diazo compounds and terminal alkynes provides di- and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  19. Applying a New Model for Sharing Population Health Data to National Syndromic Influenza Surveillance: DiSTRIBuTE Project Proof of Concept, 2006 to 2009.

    PubMed

    Olson, Donald R; Paladini, Marc; Lober, William B; Buckeridge, David L

    2011-08-02

    The Distributed Surveillance Taskforce for Real-time Influenza Burden Tracking and Evaluation (DiSTRIBuTE) project began as a pilot effort initiated by the International Society for Disease Surveillance (ISDS) in autumn 2006 to create a collaborative electronic emergency department (ED) syndromic influenza-like illness (ILI) surveillance network based on existing state and local systems and expertise. DiSTRIBuTE brought together health departments that were interested in: 1) sharing aggregate level data; 2) maintaining jurisdictional control; 3) minimizing barriers to participation; and 4) leveraging the flexibility of local systems to create a dynamic and collaborative surveillance network. This approach was in contrast to the prevailing paradigm for surveillance where record level information was collected, stored and analyzed centrally. The DiSTRIBuTE project was created with a distributed design, where individual level data remained local and only summarized, stratified counts were reported centrally, thus minimizing privacy risks. The project was responsive to federal mandates to improve integration of federal, state, and local biosurveillance capabilities. During the proof of concept phase, 2006 to 2009, ten jurisdictions from across North America sent ISDS on a daily to weekly basis year-round, aggregated data by day, stratified by local ILI syndrome, age-group and region. During this period, data from participating U.S. state or local health departments captured over 13% of all ED visits nationwide. The initiative focused on state and local health department trust, expertise, and control. Morbidity trends observed in DiSTRIBuTE were highly correlated with other influenza surveillance measures. With the emergence of novel A/H1N1 influenza in the spring of 2009, the project was used to support information sharing and ad hoc querying at the state and local level. In the fall of 2009, through a broadly collaborative effort, the project was expanded to enhance

  20. Ester of Quinoxaline-7-carboxylate 1,4-di-N-oxide as Apoptosis Inductors in K-562 Cell Line: An in vitro, QSAR and DFT Study.

    PubMed

    Rivera, Gildardo; Andrade-Ochoa, Sergio; Romero, Manolo S Ortega; Palos, Isidro; Monge, Antonio; Sanchez-Torres, Luvia Enid

    2017-01-01

    Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives on K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models. Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor activity on K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms. Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.