Fluctuations Magnetiques des Gaz D'electrons Bidimensionnels: Application AU Compose Supraconducteur LANTHANE(2-X) Strontium(x) Cuivre OXYGENE(4)

NASA Astrophysics Data System (ADS)

Benard, Pierre

Nous presentons une etude des fluctuations magnetiques de la phase normale de l'oxyde de cuivre supraconducteur La_{2-x}Sr _{x}CuO_4 . Le compose est modelise par le Hamiltonien de Hubbard bidimensionnel avec un terme de saut vers les deuxiemes voisins (modele tt'U). Le modele est etudie en utilisant l'approximation de la GRPA (Generalized Random Phase Approximation) et en incluant les effets de la renormalisation de l'interaction de Hubbard par les diagrammes de Brueckner-Kanamori. Dans l'approche presentee dans ce travail, les maximums du facteur de structure magnetique observes par les experiences de diffusion de neutrons sont associes aux anomalies 2k _{F} de reseau du facteur de structure des gaz d'electrons bidimensionnels sans interaction. Ces anomalies proviennent de la diffusion entre particules situees a des points de la surface de Fermi ou les vitesses de Fermi sont tangentes, et conduisent a des divergences dont la nature depend de la geometrie de la surface de Fermi au voisinage de ces points. Ces resultats sont ensuite appliques au modele tt'U, dont le modele de Hubbard usuel tU est un cas particulier. Dans la majorite des cas, les interactions ne determinent pas la position des maximums du facteur de structure. Le role de l'interaction est d'augmenter l'intensite des structures du facteur de structure magnetique associees a l'instabilite magnetique du systeme. Ces structures sont souvent deja presentes dans la partie imaginaire de la susceptibilite sans interaction. Le rapport d'intensite entre les maximums absolus et les autres structures du facteur de structure magnetique permet de determiner le rapport U_ {rn}/U_{c} qui mesure la proximite d'une instabilite magnetique. Le diagramme de phase est ensuite etudie afin de delimiter la plage de validite de l'approximation. Apres avoir discute des modes collectifs et de l'effet d'une partie imaginaire non-nulle de la self-energie, l'origine de l'echelle d'energie des fluctuations magnetiques est examinee. Il est ensuite demontre que le modele a trois bandes predit les memes resultats pour la position des structures du facteur de structure magnetique que le modele a une bande, dans la limite ou l'hybridation des orbitales des atomes d'oxygene des plans Cu-O_2 et l'amplitude de sauts vers les seconds voisins sont nulles. Il est de plus constate que l'effet de l'hybridation des orbitales des atomes d'oxygene est bien modelise par le terme de saut vers les seconds voisins. Meme si ils decrivent correctement le comportement qualitatif des maximums du facteur de structure magnetique, les modeles a trois bandes et a une bande ne permettent pas d'obtenir une position de ces structures conforme avec les mesures experimentales, si on suppose que la bande est rigide, c'est-a-dire que les parametres du Hamiltonien sont independants de la concentration de strontium. Ceci peut etre cause par la dependance des parametres du Hamiltonien sur la concentration de strontium. Finalement, les resultats sont compares avec les experiences de diffusion de neutrons et les autres theories, en particulier celles de Littlewood et al. (1993) et de Q. Si et al. (1993). La comparaison avec les resultats experimentaux pour le compose de lanthane suggere que le liquide de Fermi possede une surface de Fermi disjointe, et qu'il est situe pres d'une instabilite magnetique incommensurable.

Modelisation de l'erosion et des sources de pollution dans le bassin versant Iroquois/Blanchette dans un contexte de changements climatiques

NASA Astrophysics Data System (ADS)

Coulibaly, Issa

Principale source d'approvisionnement en eau potable de la municipalite d'Edmundston, le bassin versant Iroquois/Blanchette est un enjeu capital pour cette derniere, d'ou les efforts constants deployes pour assurer la preservation de la qualite de son eau. A cet effet, plusieurs etudes y ont ete menees. Les plus recentes ont identifie des menaces de pollution de diverses origines dont celles associees aux changements climatiques (e.g. Maaref 2012). Au regard des impacts des modifications climatiques annonces a l'echelle du Nouveau-Brunswick, le bassin versant Iroquois/Blanchette pourrait etre fortement affecte, et cela de diverses facons. Plusieurs scenarios d'impacts sont envisageables, notamment les risques d'inondation, d'erosion et de pollution a travers une augmentation des precipitations et du ruissellement. Face a toutes ces menaces eventuelles, l'objectif de cette etude est d'evaluer les impacts potentiels des changements climatiques sur les risques d'erosion et de pollution a l'echelle du bassin versant Iroquois/Blanchette. Pour ce faire, la version canadienne de l'equation universelle revisee des pertes en sol RUSLE-CAN et le modele hydrologique SWAT ( Soil and Water Assessment Tool) ont ete utilises pour modeliser les risques d'erosion et de pollution au niveau dans la zone d'etude. Les donnees utilisees pour realiser ce travail proviennent de sources diverses et variees (teledetections, pedologiques, topographiques, meteorologiques, etc.). Les simulations ont ete realisees en deux etapes distinctes, d'abord dans les conditions actuelles ou l'annee 2013 a ete choisie comme annee de reference, ensuite en 2025 et 2050. Les resultats obtenus montrent une tendance a la hausse de la production de sediments dans les prochaines annees. La production maximale annuelle augmente de 8,34 % et 8,08 % respectivement en 2025 et 2050 selon notre scenario le plus optimiste, et de 29,99 % en 2025 et 29,72 % en 2050 selon le scenario le plus pessimiste par rapport a celle de 2013. Pour ce qui est de la pollution, les concentrations observees (sediment, nitrate et phosphore) connaissent une evolution avec les changements climatiques. La valeur maximale de la concentration en sediments connait une baisse en 2025 et 2050 par rapport a 2013, de 11,20 mg/l en 2013, elle passe a 9,03 mg/l en 2025 puis a 6,25 en 2050. On s'attend egalement a une baisse de la valeur maximale de la concentration en nitrate au fil des annees, plus accentuee en 2025. De 4,12 mg/l en 2013, elle passe a 1,85 mg/l en 2025 puis a 2,90 en 2050. La concentration en phosphore par contre connait une augmentation dans les annees a venir par rapport a celle de 2013, elle passe de 0,056 mg/l en 2013 a 0,234 mg/l en 2025 puis a 0,144 en 2050.

Algorithmes de couplage RANS et ecoulement potentiel

NASA Astrophysics Data System (ADS)

Gallay, Sylvain

Dans le processus de developpement d'avion, la solution retenue doit satisfaire de nombreux criteres dans de nombreux domaines, comme par exemple le domaine de la structure, de l'aerodynamique, de la stabilite et controle, de la performance ou encore de la securite, tout en respectant des echeanciers precis et minimisant les couts. Les geometries candidates sont nombreuses dans les premieres etapes de definition du produit et de design preliminaire, et des environnements d'optimisations multidisciplinaires sont developpes par les differentes industries aeronautiques. Differentes methodes impliquant differents niveaux de modelisations sont necessaires pour les differentes phases de developpement du projet. Lors des phases de definition et de design preliminaires, des methodes rapides sont necessaires afin d'etudier les candidats efficacement. Le developpement de methodes ameliorant la precision des methodes existantes tout en gardant un cout de calcul faible permet d'obtenir un niveau de fidelite plus eleve dans les premieres phases de developpement du projet et ainsi grandement diminuer les risques associes. Dans le domaine de l'aerodynamisme, les developpements des algorithmes de couplage visqueux/non visqueux permettent d'ameliorer les methodes de calcul lineaires non visqueuses en methodes non lineaires prenant en compte les effets visqueux. Ces methodes permettent ainsi de caracteriser l'ecoulement visqueux sur les configurations et predire entre autre les mecanismes de decrochage ou encore la position des ondes de chocs sur les surfaces portantes. Cette these se focalise sur le couplage entre une methode d'ecoulement potentiel tridimensionnelle et des donnees de section bidimensionnelles visqueuses. Les methodes existantes sont implementees et leurs limites identifiees. Une methode originale est ensuite developpee et validee. Les resultats sur une aile elliptique demontrent la capacite de l'algorithme a de grands angles d'attaques et dans la region post-decrochage. L'algorithme de couplage a ete compare a des donnees de plus haute fidelite sur des configurations issues de la litterature. Un modele de fuselage base sur des relations empiriques et des simulations RANS a ete teste et valide. Les coefficients de portance, de trainee et de moment de tangage ainsi que les coefficients de pression extraits le long de l'envergure ont montre un bon accord avec les donnees de soufflerie et les modeles RANS pour des configurations transsoniques. Une configuration a geometrie hypersustentatoire a permis d'etudier la modelisation des surfaces hypersustentees de la methode d'ecoulement potentiel, demontrant que la cambrure peut etre prise en compte uniquement dans les donnees visqueuses.

Modelling and Simulation as a Service: New Concepts and Service-Oriented Architectures (Modelisation et simulation en tant que service: Nouveaux concepts et architectures orientes service)

DTIC Science & Technology

2015-05-01

delivery business model where S&T activities are conducted in a NATO dedicated executive body, having its own personnel, capabilities and infrastructure ...SD-4: Design for Securability 5-4 5.3.2 Recommendations on Simulation Environment Infrastructure 5-5 5.3.2.1 Recommendation IN-1: Harmonize...Critical Data and 5-5 Algorithms 5.3.2.2 Recommendation IN-2: Establish Permanent Simulation 5-5 Infrastructure 5.3.2.3 Recommendation IN-3: Establish

Modelisation de la Propagation des Ondes Sonores dans un Environnement Naturel Complexe

NASA Astrophysics Data System (ADS)

L'Esperance, Andre

Ce travail est consacre a la propagation sonore a l'exterieur dans un environnement naturel complexe, i.e. en presence de conditions reelles de vent, de gradient de temperature et de turbulence atmospherique. Plus specifiquement ce travail comporte deux objectifs. D'une part, il vise a developper un modele heuristique de propagation sonore (MHP) permettant de prendre en consideration l'ensemble des phenomenes meteorologiques et acoustiques influencant la propagation du son a l'exterieur. D'autre part, il vise a identifier dans quelles circonstances et avec quelle importance les conditions meteorologiques interviennent sur la propagation sonore. Ce travail est divise en cinq parties. Apres une breve introduction identifiant les motivations de cette etude (chapitre 1), le chapitre 2 fait un rappel des travaux deja realises dans le domaine de la propagation du son a l'exterieur. Ce chapitre presente egalement les bases de l'acoustique geometrique a partir desquelles ont ete developpees la partie acoustique du modele heuristique de propagation. En outre, on y decrit comment les phenomenes de refraction et de turbulence atmospherique peuvent etre consideres dans la theorie des rayons. Le chapitre 3 presente le modele heuristique de propagation (MHP) developpe au cours de cet ouvrage. La premiere section de ce chapitre decrit le modele acoustique de propagation, modele qui fait l'hypothese d'un gradient de celerite lineaire et qui est base sur une solution hybride d'acoustique geometrique et de theorie des residus. La deuxieme section du chapitre 3 traite plus specifiquement de la modelisation des aspects meteorologiques et de la determination des profils de celerite et des index de fluctuation associes aux conditions meteorologiques. La section 3 de ce chapitre decrit comment les profils de celerite resultants sont linearises pour les calculs dans le modele acoustique, et finalement la section 4 donne les tendances generales obtenues par le modele. Le chapitre 4 decrit les compagnes de mesures qui ont ete realisees a Rock-Spring (Pennsylvanie, Etats -Unis) au cours de l'ete 90 et a Bouin (Vendee, France) au cours de l'automne 91. La campagne de mesure de Rock -Spring a porte plus specifiquement sur les effets de la refraction alors que la campagne de Bouin a prote plus specifiquement sur les effets de la turbulence. La section 4.1 decrit les equipements et le traitement des donnees meteorologiques realisees dans chaque cas et la section 4.2 fait de meme pour les resultats acoustiques. Finalement, le chapitre 5 compare les resultats experimentaux obtenus avec ceux donnes par le MHP, tant pour les resultats meteorologiques que pour les resultats acoustiques. Des comparaisons avec un autre modele (le Fast Field Program) sont egalement presentees.

Prediction du profil de durete de l'acier AISI 4340 traite thermiquement au laser

NASA Astrophysics Data System (ADS)

Maamri, Ilyes

Les traitements thermiques de surfaces sont des procedes qui visent a conferer au coeur et a la surface des pieces mecaniques des proprietes differentes. Ils permettent d'ameliorer la resistance a l'usure et a la fatigue en durcissant les zones critiques superficielles par des apports thermiques courts et localises. Parmi les procedes qui se distinguent par leur capacite en terme de puissance surfacique, le traitement thermique de surface au laser offre des cycles thermiques rapides, localises et precis tout en limitant les risques de deformations indesirables. Les proprietes mecaniques de la zone durcie obtenue par ce procede dependent des proprietes physicochimiques du materiau a traiter et de plusieurs parametres du procede. Pour etre en mesure d'exploiter adequatement les ressources qu'offre ce procede, il est necessaire de developper des strategies permettant de controler et regler les parametres de maniere a produire avec precision les caracteristiques desirees pour la surface durcie sans recourir au classique long et couteux processus essai-erreur. L'objectif du projet consiste donc a developper des modeles pour predire le profil de durete dans le cas de traitement thermique de pieces en acier AISI 4340. Pour comprendre le comportement du procede et evaluer les effets des differents parametres sur la qualite du traitement, une etude de sensibilite a ete menee en se basant sur une planification experimentale structuree combinee a des techniques d'analyse statistiques eprouvees. Les resultats de cette etude ont permis l'identification des variables les plus pertinentes a exploiter pour la modelisation. Suite a cette analyse et dans le but d'elaborer un premier modele, deux techniques de modelisation ont ete considerees, soient la regression multiple et les reseaux de neurones. Les deux techniques ont conduit a des modeles de qualite acceptable avec une precision d'environ 90%. Pour ameliorer les performances des modeles a base de reseaux de neurones, deux nouvelles approches basees sur la caracterisation geometrique du profil de durete ont ete considerees. Contrairement aux premiers modeles predisant le profil de durete en fonction des parametres du procede, les nouveaux modeles combinent les memes parametres avec les attributs geometriques du profil de durete pour refleter la qualite du traitement. Les modeles obtenus montrent que cette strategie conduit a des resultats tres prometteurs.

Modelling of Molecular Structures and Properties in Physical Chemistry and Biophysics, Forty-Fourth International Meeting (Modelisation des Structures et Proprietes Moleculaires en Chimie Physique et en Biophysique, Quarante- Quatrieme Reunion Internationale)

DTIC Science & Technology

1989-09-01

pyridone).Previous work on, py/ridimum, pyrazinjumn or pyrimidi im salts Koon 2 -pyrimloone and 2 - pyrimidone salts [43j have shown that some...forces. Acct . r ~[U... •K;.i. LJ , ’ 0, ’’ .t_I ..- .It . ( :.. 2 A VIBRATIONAL MOLECULAR FORCE FIELD FOR .ACROMOLECULA-R MODELLI= Gerard VERGOTENi...microscopic point of view are (1) understanding, ( 2 ) interpretation of experimental results, (3) semiquantitative estimates of experimental results and (4

Human Behaviour Representation in Constructive Modelling (Representation du comportement humain dans des modelisations creatives)

DTIC Science & Technology

2009-09-01

involved in R&T activities. RTO reports both to the Military Committee of NATO and to the Conference of National Armament Directors. It comprises a...4 11.5.3 Project Description 11-5 Chapter 12 – Technical Evaluation Report 12-1 12.1 Executive Summary 12-1 12.2 Introduction 12-2 12.3...modelling human factors has been slow over the past decade, other forums have been reporting a number of theoretical and applied papers on human behaviour

Future Modelling and Simulation Challenges (Defis futurs pour la modelisation et la simulation)

DTIC Science & Technology

2002-11-01

Language School Figure 2: Location of the simulation center within the MEC Military operations research section - simulation lab Military operations... language . This logic can be probabilistic (branching is randomised, which is useful for modelling error), tactical (a branch goes to the task with the... language and a collection of simulation tools that can be used to create human and team behaviour models to meet users’ needs. Hence, different ways of

Modelisation de l'architecture des forets pour ameliorer la teledetection des attributs forestiers

NASA Astrophysics Data System (ADS)

Cote, Jean-Francois

The quality of indirect measurements of canopy structure, from in situ and satellite remote sensing, is based on knowledge of vegetation canopy architecture. Technological advances in ground-based, airborne or satellite remote sensing can now significantly improve the effectiveness of measurement programs on forest resources. The structure of vegetation canopy describes the position, orientation, size and shape of elements of the canopy. The complexity of the canopy in forest environments greatly limits our ability to characterize forest structural attributes. Architectural models have been developed to help the interpretation of canopy structural measurements by remote sensing. Recently, the terrestrial LiDAR systems, or TLiDAR (Terrestrial Light Detection and Ranging), are used to gather information on the structure of individual trees or forest stands. The TLiDAR allows the extraction of 3D structural information under the canopy at the centimetre scale. The methodology proposed in my Ph.D. thesis is a strategy to overcome the weakness in the structural sampling of vegetation cover. The main objective of the Ph.D. is to develop an architectural model of vegetation canopy, called L-Architect (LiDAR data to vegetation Architecture), and to focus on the ability to document forest sites and to get information on canopy structure from remote sensing tools. Specifically, L-Architect reconstructs the architecture of individual conifer trees from TLiDAR data. Quantitative evaluation of L-Architect consisted to investigate (i) the structural consistency of the reconstructed trees and (ii) the radiative coherence by the inclusion of reconstructed trees in a 3D radiative transfer model. Then, a methodology was developed to quasi-automatically reconstruct the structure of individual trees from an optimization algorithm using TLiDAR data and allometric relationships. L-Architect thus provides an explicit link between the range measurements of TLiDAR and structural attributes of individual trees. L-Architect has finally been applied to model the architecture of forest canopy for better characterization of vertical and horizontal structure with airborne LiDAR data. This project provides a mean to answer requests of detailed canopy architectural data, difficult to obtain, to reproduce a variety of forest covers. Because of the importance of architectural models, L-Architect provides a significant contribution for improving the capacity of parameters' inversion in vegetation cover for optical and lidar remote sensing. Mots-cles: modelisation architecturale, lidar terrestre, couvert forestier, parametres structuraux, teledetection.

Capteur de CO{2} à fibres optiques par absorption moléculaire à 4,3 μm

NASA Astrophysics Data System (ADS)

Bendamardji, S.; Alayli, Y.; Huard, S.

1996-04-01

This paper describes a remote optical fibre sensor for the carbon dioxide detection by molecular absorption in the near infrared (4.3 μm) corresponding to fundamental mode ν3. To overcome the problem of the strong attenuation signal of optical fibre in the near infrared, we have used the opto-suppling technique which changes the working wavelength from 4.3 μm to 860 nm and permits the use of standard optical fibre 50/125. The simulation of absorption has been obtained by original modelisation of the absorption spectrum and the establishment of the calibration curves takes to the sensor to detect a partial pressures greater than 100 μbar with a minimal error margin of 100 μbar, which is acceptable considering the future use of the device. The sensor has been designed to monitor the CO{2} rate in enriched greenhouses. Cet article décrit un capteur à fibres optiques de gaz carbonique par absorption moléculaire dans l'infrarouge moyen (4,3 μm) correspondant au mode fondamental ν3. La liaison entre le site de mesure et le site de contrôle est assurée par un fibre optique standard 50/125 après une transposition de longueur d'onde de 4,3 μm à 860 nm par opto-alimentation. La simulation de l'absorption a été obtenue par modélisation originale du spectre d'absorption et l'établissement des courbes d'étalonnage prévoit une marge d'erreur minimale de 100 μbar, ce qui est suffisant pour l'application du dispositif à la régulation de taux CO{2} dans les serres agricoles enrichies par de gaz.

Etude vibroacoustique d'un systeme coque-plancher-cavite avec application a un fuselage simplifie

NASA Astrophysics Data System (ADS)

Missaoui, Jemai

L'objectif de ce travail est de developper des modeles semi-analytiques pour etudier le comportement structural, acoustique et vibro-acoustique d'un systeme coque-plancher-cavite. La connection entre la coque et le plancher est assuree en utilisant le concept de rigidite artificielle. Ce concept de modelisation flexible facilite le choix des fonctions de decomposition du mouvement de chaque sous-structure. Les resultats issus de cette etude vont permettre la comprehension des phenomenes physiques de base rencontres dans une structure d'avion. Une approche integro-modale est developpee pour calculer les caracteristiques modales acoustiques. Elle utilise une discretisation de la cavite irreguliere en sous-cavites acoustiques dont les bases de developpement sont connues a priori. Cette approche, a caractere physique, presente l'avantage d'etre efficace et precise. La validite de celle-ci a ete demontree en utilisant des resultats disponibles dans la litterature. Un modele vibro-acoustique est developpe dans un but d'analyser et de comprendre les effets structuraux et acoustiques du plancher dans la configuration. La validite des resultats, en termes de resonance et de fonction de transfert, est verifiee a l'aide des mesures experimentales realisees au laboratoire.

Human Behaviour Representation in Constructive Modelling (Representation du comportement humain dans des modelisations creatives)

DTIC Science & Technology

2009-09-01

ordination with other NATO bodies involved in R&T activities. RTO reports both to the Military Committee of NATO and to the Conference of National...Aims 11-4 11.5.2 Background 11-4 11.5.3 Project Description 11-5 Chapter 12 – Technical Evaluation Report 12-1 12.1 Executive Summary 12-1...track. Although progress in modelling human factors has been slow over the past decade, other forums have been reporting a number of theoretical and

Modelisation de la diffusion sur les surfaces metalliques: De l'adatome aux processus de croissance

NASA Astrophysics Data System (ADS)

Boisvert, Ghyslain

Cette these est consacree a l'etude des processus de diffusion en surface dans le but ultime de comprendre, et de modeliser, la croissance d'une couche mince. L'importance de bien mai triser la croissance est primordiale compte tenu de son role dans la miniaturisation des circuits electroniques. Nous etudions ici les surface des metaux nobles et de ceux de la fin de la serie de transition. Dans un premier temps, nous nous interessons a la diffusion d'un simple adatome sur une surface metallique. Nous avons, entre autres, mis en evidence l'apparition d'une correlation entre evenements successifs lorsque la temperature est comparable a la barriere de diffusion, i.e., la diffusion ne peut pas etre associee a une marche aleatoire. Nous proposons un modele phenomenologique simple qui reproduit bien les resultats des simulations. Ces calculs nous ont aussi permis de montrer que la diffusion obeit a la loi de Meyer-Neldel. Cette loi stipule que, pour un processus active, le prefacteur augmente exponentiellement avec la barriere. En plus, ce travail permet de clarifier l'origine physique de cette loi. En comparant les resultats dynamiques aux resultats statiques, on se rend compte que la barriere extraite des calculs dynamiques est essentiellement la meme que celle obtenue par une approche statique, beaucoup plus simple. On peut donc obtenir cette barriere a l'aide de methodes plus precises, i.e., ab initio, comme la theorie de la fonctionnelle de la densite, qui sont aussi malheureusement beaucoup plus lourdes. C'est ce que nous avons fait pour plusieurs systemes metalliques. Nos resultats avec cette derniere approche se comparent tres bien aux resultats experimentaux. Nous nous sommes attardes plus longuement a la surface (111) du platine. Cette surface regorge de particularites interessantes, comme la forme d'equilibre non-hexagonale des i lots et deux sites d'adsorption differents pour l'adatome. De plus, des calculs ab initio precedents n'ont pas reussi a confirmer la forme d'equilibre et surestiment grandement la barriere. Nos calculs, plus complets et dans un formalisme mieux adapte a ce genre de probleme, predisent correctement la forme d'equilibre, qui est en fait due a un relachement different du stress de surface aux deux types de marches qui forment les cotes des i lots. Notre valeur pour la barriere est aussi fortement diminuee lorsqu'on relaxe les forces sur les atomes de la surface, amenant le resultat theorique beaucoup plus pres de la valeur experimentale. Nos calculs pour le cuivre demontre en effet que la diffusion de petits i lots pendant la croissance ne peut pas etre negligee dans ce cas, mettant en doute la valeur des interpretations des mesures experimentales. (Abstract shortened by UMI.)

Modelisation de l'historique d'operation de groupes turbine-alternateur

NASA Astrophysics Data System (ADS)

Szczota, Mickael

Because of their ageing fleet, the utility managers are increasingly in needs of tools that can help them to plan efficiently maintenance operations. Hydro-Quebec started a project that aim to foresee the degradation of their hydroelectric runner, and use that information to classify the generating unit. That classification will help to know which generating unit is more at risk to undergo a major failure. Cracks linked to the fatigue phenomenon are a predominant degradation mode and the loading sequences applied to the runner is a parameter impacting the crack growth. So, the aim of this memoir is to create a generator able to generate synthetic loading sequences that are statistically equivalent to the observed history. Those simulated sequences will be used as input in a life assessment model. At first, we describe how the generating units are operated by Hydro-Quebec and analyse the available data, the analysis shows that the data are non-stationnary. Then, we review modelisation and validation methods. In the following chapter a particular attention is given to a precise description of the validation and comparison procedure. Then, we present the comparison of three kind of model : Discrete Time Markov Chains, Discrete Time Semi-Markov Chains and the Moving Block Bootstrap. For the first two models, we describe how to take account for the non-stationnarity. Finally, we show that the Markov Chain is not adapted for our case, and that the Semi-Markov chains are better when they include the non-stationnarity. The final choice between Semi-Markov Chains and the Moving Block Bootstrap depends of the user. But, with a long term vision we recommend the use of Semi-Markov chains for their flexibility. Keywords: Stochastic models, Models validation, Reliability, Semi-Markov Chains, Markov Chains, Bootstrap

Radio Wave Propagation Modeling, Prediction and Assessment (L’Evaluation, la Prevision et la Modelisation des Ondes Hertziennes)

DTIC Science & Technology

1990-01-01

modifiers and added an additional set of modifiers to adjust the average VTOP. The original DECO model made use of waveguide excitation factors and...ranges far beyond the horizon. The modified refractivity M is defined by N - N + (h/a) x 106 - N + 0.157 h (2.1) where h is the height above the earth’s...LAYEIR APPING LAVER REFRACTIVITY N MODIFIED REFRAACTIVIT M Figure 2.4. N and N profiles for an elevated duct. t /VA--’’TM tDUCT ITx IFPAT4G RELRACIVT

Modelisation des emissions de particules microniques et nanometriques en usinage

NASA Astrophysics Data System (ADS)

Khettabi, Riad

La mise en forme des pieces par usinage emet des particules, de tailles microscopiques et nanometriques, qui peuvent etre dangereuses pour la sante. Le but de ce travail est d'etudier les emissions de ces particules pour fins de prevention et reduction a la source. L'approche retenue est experimentale et theorique, aux deux echelles microscopique et macroscopique. Le travail commence par des essais permettant de determiner les influences du materiau, de l'outil et des parametres d'usinage sur les emissions de particules. E nsuite un nouveau parametre caracterisant les emissions, nomme Dust unit , est developpe et un modele predictif est propose. Ce modele est base sur une nouvelle theorie hybride qui integre les approches energetiques, tribologiques et deformation plastique, et inclut la geometrie de l'outil, les proprietes du materiau, les conditions de coupe et la segmentation des copeaux. Il ete valide au tournage sur quatre materiaux: A16061-T6, AISI1018, AISI4140 et fonte grise.

Time Sensitive Course of Action Development and Evaluation

DTIC Science & Technology

2010-10-01

Applications militaires de la modelisation humaine ). RTO-MP-HFM-202 14. ABSTRACT The development of courses of action that integrate military with...routes between the capital town C of the province and a neighboring country M. Both roads are historically significant smuggling routes. There were

Developpement D'un Modele Climatique Regional: Fizr Simulation des Conditions de Janvier de la Cote Ouest Nord Americaine

NASA Astrophysics Data System (ADS)

Goyette, Stephane

1995-11-01

Le sujet de cette these concerne la modelisation numerique du climat regional. L'objectif principal de l'exercice est de developper un modele climatique regional ayant les capacites de simuler des phenomenes de meso-echelle spatiale. Notre domaine d'etude se situe sur la Cote Ouest nord americaine. Ce dernier a retenu notre attention a cause de la complexite du relief et de son controle sur le climat. Les raisons qui motivent cette etude sont multiples: d'une part, nous ne pouvons pas augmenter, en pratique, la faible resolution spatiale des modeles de la circulation generale de l'atmosphere (MCG) sans augmenter a outrance les couts d'integration et, d'autre part, la gestion de l'environnement exige de plus en plus de donnees climatiques regionales determinees avec une meilleure resolution spatiale. Jusqu'alors, les MCG constituaient les modeles les plus estimes pour leurs aptitudes a simuler le climat ainsi que les changements climatiques mondiaux. Toutefois, les phenomenes climatiques de fine echelle echappent encore aux MCG a cause de leur faible resolution spatiale. De plus, les repercussions socio-economiques des modifications possibles des climats sont etroitement liees a des phenomenes imperceptibles par les MCG actuels. Afin de circonvenir certains problemes inherents a la resolution, une approche pratique vise a prendre un domaine spatial limite d'un MCG et a y imbriquer un autre modele numerique possedant, lui, un maillage de haute resolution spatiale. Ce processus d'imbrication implique alors une nouvelle simulation numerique. Cette "retro-simulation" est guidee dans le domaine restreint a partir de pieces d'informations fournies par le MCG et forcee par des mecanismes pris en charge uniquement par le modele imbrique. Ainsi, afin de raffiner la precision spatiale des previsions climatiques de grande echelle, nous developpons ici un modele numerique appele FIZR, permettant d'obtenir de l'information climatique regionale valide a la fine echelle spatiale. Cette nouvelle gamme de modeles-interpolateurs imbriques qualifies d'"intelligents" fait partie de la famille des modeles dits "pilotes". L'hypothese directrice de notre etude est fondee sur la supposition que le climat de fine echelle est souvent gouverne par des forcages provenant de la surface plutot que par des transports atmospheriques de grande echelle spatiale. La technique que nous proposons vise donc a guider FIZR par la Dynamique echantillonnee d'un MCG et de la forcer par la Physique du MCG ainsi que par un forcage orographique de meso-echelle, en chacun des noeuds de la grille fine de calculs. Afin de valider la robustesse et la justesse de notre modele climatique regional, nous avons choisi la region de la Cote Ouest du continent nord americain. Elle est notamment caracterisee par une distribution geographique des precipitations et des temperatures fortement influencee par le relief sous-jacent. Les resultats d'une simulation d'un mois de janvier avec FIZR demontrent que nous pouvons simuler des champs de precipitations et de temperatures au niveau de l'abri beaucoup plus pres des observations climatiques comparativement a ceux simules a partir d'un MCG. Ces performances sont manifestement attribuees au forcage orographique de meso-echelle de meme qu'aux caracteristiques de surface determinees a fine echelle. Un modele similaire a FIZR peut, en principe, etre implante sur l'importe quel MCG, donc, tout organisme de recherche implique en modelisation numerique mondiale de grande echelle pourra se doter d'un el outil de regionalisation.

Methode d'identification parametrique pour la surveillance in situ des joints a recouvrement par propagation d'ondes vibratoires

NASA Astrophysics Data System (ADS)

Francoeur, Dany

Cette these de doctorat s'inscrit dans le cadre de projets CRIAQ (Consortium de recherche et d'innovation en aerospatiale du Quebec) orientes vers le developpement d'approches embarquees pour la detection de defauts dans des structures aeronautiques. L'originalite de cette these repose sur le developpement et la validation d'une nouvelle methode de detection, quantification et localisation d'une entaille dans une structure de joint a recouvrement par la propagation d'ondes vibratoires. La premiere partie expose l'etat des connaissances sur l'identification d'un defaut dans le contexte du Structural Health Monitoring (SHM), ainsi que la modelisation de joint a recouvrements. Le chapitre 3 developpe le modele de propagation d'onde d'un joint a recouvrement endommage par une entaille pour une onde de flexion dans la plage des moyennes frequences (10-50 kHz). A cette fin, un modele de transmission de ligne (TLM) est realise pour representer un joint unidimensionnel (1D). Ce modele 1D est ensuite adapte a un joint bi-dimensionnel (2D) en faisant l'hypothese d'un front d'onde plan incident et perpendiculaire au joint. Une methode d'identification parametrique est ensuite developpee pour permettre a la fois la calibration du modele du joint a recouvrement sain, la detection puis la caracterisation de l'entaille situee sur le joint. Cette methode est couplee a un algorithme qui permet une recherche exhaustive de tout l'espace parametrique. Cette technique permet d'extraire une zone d'incertitude reliee aux parametres du modele optimal. Une etude de sensibilite est egalement realisee sur l'identification. Plusieurs resultats de mesure sur des joints a recouvrements 1D et 2D sont realisees permettant ainsi l'etude de la repetabilite des resultats et la variabilite de differents cas d'endommagement. Les resultats de cette etude demontrent d'abord que la methode de detection proposee est tres efficace et permet de suivre la progression d'endommagement. De tres bons resultats de quantification et de localisation d'entailles ont ete obtenus dans les divers joints testes (1D et 2D). Il est prevu que l'utilisation d'ondes de Lamb permettraient d'etendre la plage de validite de la methode pour de plus petits dommages. Ces travaux visent d'abord la surveillance in-situ des structures de joint a recouvrements, mais d'autres types de defauts. (comme les disbond) et. de structures complexes sont egalement envisageables. Mots cles : joint a recouvrement, surveillance in situ, localisation et caracterisation de dommages

Etude du processus de changement vecu par des familles ayant decide d'adopter volontairement des comportements d'attenuation des changements climatiques

NASA Astrophysics Data System (ADS)

Leger, Michel T.

Les activites humaines energivores telles l'utilisation intensive de l'automobile, la surconsommation de biens et l'usage excessif d'electricite contribuent aux changements climatiques et autres problemes environnementaux. Bien que plusieurs recherches rapportent que l'etre humain est de plus en plus conscient de ses impacts sur le climat de la planete, ces memes recherches indiquent qu'en general, les gens continuent a se comporter de facon non ecologique. Que ce soit a l'ecole ou dans la communaute, plusieurs chercheurs en education relative a l'environnement estiment qu'une personne bien intentionnee est capable d'adopter des comportements plus respectueux de l'environnement. Le but de cette these etait de comprendre le processus d'integration de comportements d'attenuation des changements climatiques dans des familles. A cette fin, nous nous sommes fixe deux objectifs : 1) decrire les competences et les procedes qui favorisent l'adoption de comportements d'attenuation des changements climatiques dans des familles et 2) decrire les facteurs et les dynamiques familiales qui facilitent et limitent l'adoption de comportements d'attenuation des changements climatiques dans des familles. Des familles ont ete invitees a essayer des comportements personnels et collectifs d'attenuation des changements climatiques de sorte a integrer des modes de vie plus ecologiques. Sur une periode de huit mois, nous avons suivi leur experience de changement afin de mieux comprendre comment se produit le processus de changement dans des familles qui decident volontairement d'adopter des comportements d'attenuation des changements climatiques. Apres leur avoir fourni quelques connaissances de base sur les changements climatiques, nous avons observe le vecu de changement des familles durant huit mois d'essais a l'aide de journaux reflexifs, d'entretiens d'explicitation et du journal du chercheur. La these comporte trois articles scientifiques. Dans le premier article, nous presentons une recension des ecrits sur le changement de comportement en environnement. Nous explorons egalement la famille comme systeme fonctionnel de sorte a mieux comprendre ce contexte d'action environnementale qui est, a notre connaissance, peu etudie. Dans le deuxieme article, nous presentons nos resultats de recherche concernant les facteurs d'influence observes ainsi que les competences manifestees au cours du processus d'adoption de nouveaux comportements environnementaux dans trois familles. Enfin, le troisieme article presente les resultats du cas d'une quatrieme famille ou les membres vivent depuis longtemps des modes de vie ecologique. Dans le cadre d'une demarche d'analyse par theorisation ancree, l'etude de ce cas modele nous a permis d'approfondir les categories conceptuelles identifiees dans le deuxieme article de sorte a produire une modelisation de l'integration de comportements environnementaux dans le contexte de la famille. Les conclusions degagees grace a la recension des ecrits nous ont permis d'identifier les elements qui pourraient influencer l'adoption de comportements environnementaux dans des familles. La recension a aussi permis une meilleure comprehension des divers facteurs qui peuvent affecter l'adoption de comportements environnementaux et, enfin, elle a permis de mieux cerner le phenomene de changement de comportement dans le contexte de la famille consideree comme un systeme. En appliquant un processus d'analyse inductif, a partir de nos donnees qualitatives, les resultats de notre etude multi-cas nous ont indique que deux construits conceptuels semblent influencer l'adoption de comportements environnementaux en famille : 1) les valeurs biospheriques communes au sein de la famille et 2) les competences collectivement mises a profit collectivement durant l'essai de nouveaux comportements environnementaux. Notre modelisation du processus de changement dans des familles indique aussi qu'une dynamique familiale collaborative et la presence d'un groupe de soutien exterieur sont deux elements conceptuels qui tendent a influencer les deux principaux construits et, par ce fait, tendent a augmenter les chances d'integrer de nouveaux comportements environnementaux dans des familles. En conclusion, nous presentons les limites de notre recherche ainsi que des pistes pour des recherches futures. Notamment, nous recommandons que l'ecole accueille les familles des eleves dans le cadre d'activites d'education a l'environnement ou les freres, les soeurs et les parents des eleves puissent apprendre ensemble, a l'ecole. Par exemple, nous recommandons la conduite en ERE d'une recherche action portant sur l'apprentissage intergenerationnel de nouveaux comportements dans le contexte de la famille. Mots-cles : education relative a l'environnement, comportement environnemental en famille, changement de comportement en famille, valeurs biospheriques, competences d'action.

Bellman Continuum (3rd) International Workshop (13-14 June 1988)

DTIC Science & Technology

1988-06-01

Modelling Uncertain Problem ................. 53 David Bensoussan ,---,>Asymptotic Linearization of Uncertain Multivariable Systems by Sliding Modes...K. Ghosh .-. Robust Model Tracking for a Class of Singularly Perturbed Nonlinear Systems via Composite Control ....... 93 F. Garofalo and L. Glielmo...MODELISATION ET COMMANDE EN ECONOMIE MODELS AND CONTROL POLICIES IN ECONOMICS Qualitative Differential Games : A Viability Approach ............. 117

Environmental Modeling Packages for the MSTDCL TDP: Review and Recommendations (Trousses de Modelisation Environnementale Pour le PDT DCLTCM: Revue et Recommendations)

DTIC Science & Technology

2009-09-01

frequency shallow water scenarios, and DRDC has ready access to a well-established PE model ( PECan ). In those spectral areas below 1 kHz, where the PE...PCs Personnel Computers PE Parabolic Equation PECan PE Model developed by DRDC SPADES/ICE Sensor Performance and Acoustic Detection Evaluation

Commerce de detail de l'essence automobile: Modelisation de l'impact a court terme des facteurs endogenes et exogenes sur les ventes d'essence dans les stations-service a Montreal

NASA Astrophysics Data System (ADS)

Nguimbus, Raphael

La determination de l'impact des facteurs sous controle et hors controle qui influencent les volumes de vente des magasins de detail qui vendent des produits homogenes et fortement substituables constitue le coeur de cette these. Il s'agit d'estimer un ensemble de coefficients stables et asymtotiquement efficaces non correles avec les effets specifiques aleatoires des sites d'essence dans le marche de Montreal (Quebec, Canada) durant is periode 1993--1997. Le modele econometrique qui est ainsi specifie et teste, isole un ensemble de quatre variables dont le prix de detail affiche dans un site d'essence ordinaire, la capacite de service du site pendant les heures de pointe, les heures de service et le nombre de sites concurrents au voisinage du site dans un rayon de deux kilometres. Ces quatre facteurs influencent les ventes d'essence dans les stations-service. Les donnees en panel avec les methodes d'estimation robustes (estimateur a distance minimale) sont utilisees pour estimer les parametres du modele de vente. Nous partons avec l'hypothese generale selon laquelle il se developpe une force d'attraction qui attire les clients automobilistes dans chaque site, et qui lui permet de realiser les ventes. Cette capacite d'attraction varie d'un site a un autre et cela est du a la combinaison de l'effort marketing et de l'environnement concurrentiel autour du site. Les notions de voisinage et de concurrence spatiale expliquent les comportements des decideurs qui gerent les sites. Le but de cette these est de developper un outil d'aide a la decision (modele analytique) pour permettre aux gestionnaires des chaines de stations-service d'affecter efficacement les ressources commerciales dans ies points de vente.

Modelisation numerique de l'hydrologie pour l'aide a la gestion des bassins versants, par l'utilisation conjointe des systemes d'information geographique et de la methode des elements finis un nouvel outil pour le developpement durable SAGESS

NASA Astrophysics Data System (ADS)

Bel Hadj Kacem, Mohamed Salah

All hydrological processes are affected by the spatial variability of the physical parameters of the watershed, and also by human intervention on the landscape. The water outflow from a watershed strictly depends on the spatial and temporal variabilities of the physical parameters of the watershed. It is now apparent that the integration of mathematical models into GIS's can benefit both GIS and three-dimension environmental models: a true modeling capability can help the modeling community bridge the gap between planners, scientists, decision-makers and end-users. The main goal of this research is to design a practical tool to simulate run-off water surface using Geographic design a practical tool to simulate run-off water surface using Geographic Information Systems and the simulation of the hydrological behavior by the Finite Element Method.

Comparison of different 3D wavefront sensing and reconstruction techniques for MCAO

NASA Astrophysics Data System (ADS)

Bello, Dolores; Vérinaud, Christophe; Conan, Jean-Marc; Fusco, Thierry; Carbillet, Marcel; Esposito, Simone

2003-02-01

The vertical distribution of the turbulence limits the field of view of classical adaptive optics due to the anisoplanatism. Multiconjugate adaptive optics (MCAO) uses several deformable mirrors conjugated to different layers in the atmosphere to overcome this effect. In the last few years, many studies and developments have been done regarding the analysis of the turbulence volume, and the choice of the wavefront reconstruction techniques.An extensive study of MCAO modelisation and performance estimation has been done at OAA and ONERA. The developed Monte Carlo codes allow to simulate and investigate many aspects: comparison of turbulence analysis strategies (tomography or layer oriented) and comparison of different reconstruction approaches. For instance in the layer oriented approach, the control for a given deformable mirror can be either deduced from the whole set of wavefront sensor measurements or only using the associated wavefront sensor. Numerical simulations are presented showing the advantages and disadvantages of these different options for several cases depending on the number, geometry and magnitude of the guide stars.

A Designer’s Guide to Human Performance Modelling (La Modelisation des Performances Humaines: Manuel du Concepteur).

DTIC Science & Technology

1998-12-01

failure detection, monitoring, and decision making.) moderator function. Originally, the output from these One of the best known OCM implementations, the...imposed by the tasks themselves, the information and equipment provided, the task environment, operator skills and experience, operator strategies , the...problem-solving situation, including the toward failure.) knowledge necessary to generate the right problem- solving strategies , the attention that

Etude de la dynamique des porteurs dans des nanofils de silicium par spectroscopie terahertz

NASA Astrophysics Data System (ADS)

Beaudoin, Alexandre

Ce memoire presente une etude des proprietes de conduction electrique et de la dynamique temporelle des porteurs de charges dans des nanofils de silicium sondes par rayonnement terahertz. Les cas de nanofils de silicium non intentionnellement dopes et dopes type n sont compares pour differentes configurations du montage experimental. Les mesures de spectroscopie terahertz en transmission montre qu'il est possible de detecter la presence de dopants dans les nanofils via leur absorption du rayonnement terahertz (˜ 1--12 meV). Les difficultes de modelisation de la transmission d'une impulsion electromagnetique dans un systeme de nanofils sont egalement discutees. La detection differentielle, une modification au systeme de spectroscopie terahertz, est testee et ses performances sont comparees au montage de caracterisation standard. Les instructions et des recommendations pour la mise en place de ce type de mesure sont incluses. Les resultats d'une experience de pompe optique-sonde terahertz sont egalement presentes. Dans cette experience, les porteurs de charge temporairement crees suite a l'absorption de la pompe optique (lambda ˜ 800 nm) dans les nanofils (les photoporteurs) s'ajoutent aux porteurs initialement presents et augmentent done l'absorption du rayonnement terahertz. Premierement, l'anisotropie de l'absorption terahertz et de la pompe optique par les nanofils est demontree. Deuxiemement, le temps de recombinaison des photoporteurs est etudie en fonction du nombre de photoporteurs injectes. Une hypothese expliquant les comportements observes pour les nanofils non-dopes et dopes-n est presentee. Troisiemement, la photoconductivite est extraite pour les nanofils non-dopes et dopes-n sur une plage de 0.5 a 2 THz. Un lissage sur la photoconductivite permet d'estimer le nombre de dopants dans les nanofils dopes-n. Mots-cles: nanofil, silicium, terahertz, conductivite, spectroscopie, photoconductivite.

Charge Transport in Carbon Nanotubes-Polymer Composite Photovoltaic Cells

PubMed Central

Ltaief, Adnen; Bouazizi, Abdelaziz; Davenas, Joel

2009-01-01

We investigate the dark and illuminated current density-voltage (J/V) characteristics of poly(2-methoxy-5-(2’-ethylhexyloxy)1-4-phenylenevinylene) (MEH-PPV)/single-walled carbon nanotubes (SWNTs) composite photovoltaic cells. Using an exponential band tail model, the conduction mechanism has been analysed for polymer only devices and composite devices, in terms of space charge limited current (SCLC) conduction mechanism, where we determine the power parameters and the threshold voltages. Elaborated devices for MEH-PPV:SWNTs (1:1) composites showed a photoresponse with an open-circuit voltage Voc of 0.4 V, a short-circuit current density JSC of 1 µA/cm² and a fill factor FF of 43%. We have modelised the organic photovoltaic devices with an equivalent circuit, where we calculated the series and shunt resistances.

LLR data analysis and impact on lunar dynamics from recent developments at OCA LLR Station

NASA Astrophysics Data System (ADS)

Viswanathan, Vishnu; Fienga, Agnes; Courde, Clement; Torre, Jean-Marie; Exertier, Pierre; Samain, Etienne; Feraudy, Dominique; Albanese, Dominique; Aimar, Mourad; Mariey, Hervé; Viot, Hervé; Martinot-Lagarde, Gregoire

2016-04-01

Since late 2014, OCA LLR station has been able to range with infrared wavelength (1064nm). IR ranging provides both temporal and spatial improvement in the LLR observations. IR detection also permits in densification of normal points, including the L1 and L2 retroreflectors due to better signal to noise ratio. This contributes to a better modelisation of the lunar libration. The hypothesis of lunar dust and environmental effects due to the chromatic behavior noticed on returns from L2 retroreflector is discussed. In addition, data analysis shows that the effect of retroreflector tilt and the use of calibration profile for the normal point deduction algorithm, contributes to improving the precision of normal points, thereby impacting lunar dynamical models and inner physics.

Étude de la réponse photoacoustique d'objets massifs en 3D

NASA Astrophysics Data System (ADS)

Séverac, H.; Mousseigne, M.; Franceschi, J. L.

1996-11-01

In some sectors such as microelectronics or the physics of materials, reliability is of capital importance. It is also particularly attractive to have access on informations on the material behaviour without the use of a destructive test like chemical analysis or others mechanical tests. The submitted method for non-destructive testing is based on the waves generation with a laser beam. The aim of studying the various waves in the three-dimensional space is to bring informations about materials response. Thermoelastic modelisation allowed a rigorous analytic approach and to give rise to a software written in Turbo-Pascal for a more general solution. Dans les secteurs où la fiabilité est capitale, tels la micro-électronique ou la physique des matériaux, il est particulièrement utile d'accéder aux informations sur le comportement du matériau sans avoir à utiliser une méthode destructive (analyses chimiques ou autres essais mécaniques). La méthode de contrôle non destructif présentée est basée sur la génération d'ondes par impact d'un faisceau laser focalisé à la surface d'un échantillon, sans atteindre le régime d'ablation. L'étude de la propagation des diverses ondes dans l'espace tridimensionnel permet d'apporter des mesures quantitatives sur l'analyse de la réponse des matériaux utilisés. La modélisation des phénomènes thermoélastiques a permis une approche analytique rigoureuse et donné naissance à un logiciel de simulation écrit en Turbo-Pascal pour des études plus générales.

Development of a precision multimodal surgical navigation system for lung robotic segmentectomy

PubMed Central

Soldea, Valentin; Lachkar, Samy; Rinieri, Philippe; Sarsam, Mathieu; Bottet, Benjamin; Peillon, Christophe

2018-01-01

Minimally invasive sublobar anatomical resection is becoming more and more popular to manage early lung lesions. Robotic-assisted thoracic surgery (RATS) is unique in comparison with other minimally invasive techniques. Indeed, RATS is able to better integrate multiple streams of information including advanced imaging techniques, in an immersive experience at the level of the robotic console. Our aim was to describe three-dimensional (3D) imaging throughout the surgical procedure from preoperative planning to intraoperative assistance and complementary investigations such as radial endobronchial ultrasound (R-EBUS) and virtual bronchoscopy for pleural dye marking. All cases were operated using the DaVinci SystemTM. Modelisation was provided by Visible Patient™ (Strasbourg, France). Image integration in the operative field was achieved using the Tile Pro multi display input of the DaVinci console. Our experience was based on 114 robotic segmentectomies performed between January 2012 and October 2017. The clinical value of 3D imaging integration was evaluated in 2014 in a pilot study. Progressively, we have reached the conclusion that the use of such an anatomic model improves the safety and reliability of procedures. The multimodal system including 3D imaging has been used in more than 40 patients so far and demonstrated a perfect operative anatomic accuracy. Currently, we are developing an original virtual reality experience by exploring 3D imaging models at the robotic console level. The act of operating is being transformed and the surgeon now oversees a complex system that improves decision making. PMID:29785294

Development of a precision multimodal surgical navigation system for lung robotic segmentectomy.

PubMed

Baste, Jean Marc; Soldea, Valentin; Lachkar, Samy; Rinieri, Philippe; Sarsam, Mathieu; Bottet, Benjamin; Peillon, Christophe

2018-04-01

Minimally invasive sublobar anatomical resection is becoming more and more popular to manage early lung lesions. Robotic-assisted thoracic surgery (RATS) is unique in comparison with other minimally invasive techniques. Indeed, RATS is able to better integrate multiple streams of information including advanced imaging techniques, in an immersive experience at the level of the robotic console. Our aim was to describe three-dimensional (3D) imaging throughout the surgical procedure from preoperative planning to intraoperative assistance and complementary investigations such as radial endobronchial ultrasound (R-EBUS) and virtual bronchoscopy for pleural dye marking. All cases were operated using the DaVinci System TM . Modelisation was provided by Visible Patient™ (Strasbourg, France). Image integration in the operative field was achieved using the Tile Pro multi display input of the DaVinci console. Our experience was based on 114 robotic segmentectomies performed between January 2012 and October 2017. The clinical value of 3D imaging integration was evaluated in 2014 in a pilot study. Progressively, we have reached the conclusion that the use of such an anatomic model improves the safety and reliability of procedures. The multimodal system including 3D imaging has been used in more than 40 patients so far and demonstrated a perfect operative anatomic accuracy. Currently, we are developing an original virtual reality experience by exploring 3D imaging models at the robotic console level. The act of operating is being transformed and the surgeon now oversees a complex system that improves decision making.

Study of dehydroxylated-rehydroxylated smectites by SAXS

NASA Astrophysics Data System (ADS)

Muller, F.; Pons, C.-H.; Papin, A.

2002-07-01

Montmorillonite and beidellite are dioctahedral 2:1 phyllosilicates. The weakness of the bonding between layers allows the intercalation of water molecules (disposed in layers) in the interlayer space. The samples studied are constituted of cv layers (cv for vacant octahedral sites in cis positions). They have been dehydroxylated. This is accompanied by the migration of the octahedral cations from former trans-octahedra to empty cis-sites therefore the layers become tv (vacant site in trans position). To characterize the stacking of the layers, SAXS (Small Angle X-ray Scattering) analyses have been investigated in natural (N) and after a dehydroxylation-rehydroxylation cycle (R) states. The SAXS pattern modelisation for Na -exchanged samples in the N state shows that the layers stack in particles with well defined interlayer distances d_{001}, corresponding to 0 water layer, 1 water layers and 2 water layers. The dehydroxylation-rehydroxylation cycle increases the proportion of interlayer distances with zero water layer and the disorder in the stacking. The decreasing of the disorder parameter with the proportion of tetrahedral charge in the N and R sample shows that the distribution of the water layers depend on the localization of the deficit of charge. Les montmorillonites et les smectites sont des phyllosilicates 2:1 dioctaédriques. Les liaisons entre feuillets sont suffisamment faibles pour permettre l'insertion, dans l'espace interfoliaire, de molécules d'eau qui se disposent en couches. Les échantillons étudiés ont des feuillets cis-vacants (le site octaédrique inoccupé est en une des deux positions “cis”). Ils ont été deshydroxylés. Ceci s'accompagne d'une migration cationique, à l'intérieur des couches octaédriques, des sites trans vers les sites cis et le feuillet devient trans-vacant. Des expériences de Diffusion X aux Petits Angles (DPA) ont permis de caractériser l'empilement des feuillets. La modélisation des diagrammes de DPAX met en évidence, pour les échantillons sodique non traités, des empilements de feuillets formant des particules avec des distances interlamellaires à 0, 1 et 2 couches d'eau. Après le cycle de déshydroxylation-réhydroxylation, la proportion de feuillets avec une distance interlamellaire correspondante à zéro couche d'eau et le désordre dans l'empi lement des feuillets augmentent. La décroissance du paramètre de désordre avec la proportion de charges tetraédriques montre que l'organi sation des couches d'eau dépend de la localisation du déficit de charge.

Etude de la transmission sonore a travers un protecteur de type "coquilles" : modelisation numerique et validation experimentale

NASA Astrophysics Data System (ADS)

Boyer, Sylvain

On estime que sur les 3,7 millions des travailleurs au Quebec, plus de 500 000 sont exposes quotidiennement a des niveaux de bruits pouvant causer des lesions de l'appareil auditif. Lorsqu'il n'est pas possible de diminuer le niveau de bruit environnant, en modifiant les sources de bruits, ou en limitant la propagation du son, le port de protecteurs auditifs individualises, telles que les coquilles, demeure l'ultime solution. Bien que vue comme une solution a court terme, elle est communement employee, du fait de son caractere peu dispendieux, de sa facilite d'implantation et de son adaptabilite a la plupart des operations en environnement bruyant. Cependant les protecteurs auditifs peuvent etre a la fois inadaptes aux travailleurs et a leur environnement et inconfortables ce qui limite leur temps de port, reduisant leur protection effective. Afin de palier a ces difficultes, un projet de recherche sur la protection auditive intitule : " Developpement d'outils et de methodes pour ameliorer et mieux evaluer la protection auditive individuelle des travailleur ", a ete mis sur pied en 2010, associant l'Ecole de technologie superieure (ETS) et l'Institut de recherche Robert-Sauve en sante et en securite du travail (IRSST). S'inscrivant dans ce programme de recherche, le present travail de doctorat s'interesse specifiquement a la protection auditive au moyen de protecteurs auditifs " passifs " de type coquille, dont l'usage presente trois problematiques specifiques presentees dans les paragraphes suivants. La premiere problematique specifique concerne l'inconfort cause par exemple par la pression statique induite par la force de serrage de l'arceau, qui peut reduire le temps de port recommande pour limiter l'exposition au bruit. Il convient alors de pouvoir donner a l'utilisateur un protecteur confortable, adapte a son environnement de travail et a son activite. La seconde problematique specifique est l'evaluation de la protection reelle apportee par le protecteur. La methode des seuils auditifs REAT (Real Ear Attenuation Threshold) aussi vu comme un "golden standard" est utilise pour quantifier la reduction du bruit mais surestime generalement la performance des protecteurs. Les techniques de mesure terrains, telles que la F-MIRE (Field Measurement in Real Ear) peuvent etre a l'avenir de meilleurs outils pour evaluer l'attenuation individuelle. Si ces techniques existent pour des bouchons d'oreilles, elles doivent etre adaptees et ameliorees pour le cas des coquilles, en determinant l'emplacement optimal des capteurs acoustiques et les facteurs de compensation individuels qui lient la mesure microphonique a la mesure qui aurait ete prise au tympan. La troisieme problematique specifique est l'optimisation de l'attenuation des coquilles pour les adapter a l'individu et a son environnement de travail. En effet, le design des coquilles est generalement base sur des concepts empiriques et des methodes essais/erreurs sur des prototypes. La piste des outils predictifs a ete tres peu etudiee jusqu'a present et meriterait d'etre approfondie. L'utilisation du prototypage virtuel, permettrait a la fois d'optimiser le design avant production, d'accelerer la phase de developpement produit et d'en reduire les couts. L'objectif general de cette these est de repondre a ces differentes problematiques par le developpement d'un modele de l'attenuation sonore d'un protecteur auditif de type coquille. A cause de la complexite de la geometrie de ces protecteurs, la methode principale de modelisation retenue a priori est la methode des elements finis (FEM). Pour atteindre cet objectif general, trois objectifs specifiques ont ete etablis et sont presentes dans les trois paragraphes suivants. (Abstract shortened by ProQuest.).

Modelisation 0D/1D des emissions de particules de suie dans les turbines a gaz aeronautiques

NASA Astrophysics Data System (ADS)

Bisson, Jeremie

Because of more stringent regulations of aircraft particle emissions as well as strong uncertainties about their formation and their effects on the atmosphere, a better understanding of particle microphysical mechanisms and their interactions with the engine components is required. This thesis focuses on the development of a 0D/1D combustion model with soot production in an aeronautical gas turbine. A major objective of this study is to assess the quality of soot particle emission predictions for different flight configurations. The model should eventually allow performing parametric studies on current or future engines with a minimal computation time. The model represents the combustor as well as turbines and nozzle with a chemical reactor network (CRN) that is coupled with a detailed combustion chemistry for kerosene (Jet A-1) and a soot particle dynamics model using the method of moments. The CRN was applied to the CFM56-2C1 engine during flight configurations of the LTO cycle (Landing-Take-Off) as in the APEX-1 study on aircraft particle emissions. The model was mainly validated on gas turbine thermodynamic data and pollutant concentrations (H2O, COX, NOx, SOX) which were measured in the same study. Once the first validation completed, the model was subsequently used for the computation of mass and number-based emissions indices of the soot particulate population and average diameter. Overall, the model is representative of the thermodynamic conditions and succeeds in predicting the emissions of major pollutants, particularly at high power. Concerning soot particulate emissions, the model's ability to predict simultaneously the emission indices as well as mean diameter has been partially validated. Indeed, the mass emission indices have remained higher than experimental results particularly at high power. These differences on particulate emission index may be the result of uncertainties on thermodynamic parameters of the CRN and mass air flow distribution in the combustion chamber. The analysis of the number-based emission index profile along the CRN also highlights the need to review the nucleation model that has been used and to consider in the future the implementation of a particle aggregation mechanism.

Comparison of ensemble post-processing approaches, based on empirical and dynamical error modelisation of rainfall-runoff model forecasts

NASA Astrophysics Data System (ADS)

Chardon, J.; Mathevet, T.; Le Lay, M.; Gailhard, J.

2012-04-01

In the context of a national energy company (EDF : Electricité de France), hydro-meteorological forecasts are necessary to ensure safety and security of installations, meet environmental standards and improve water ressources management and decision making. Hydrological ensemble forecasts allow a better representation of meteorological and hydrological forecasts uncertainties and improve human expertise of hydrological forecasts, which is essential to synthesize available informations, coming from different meteorological and hydrological models and human experience. An operational hydrological ensemble forecasting chain has been developed at EDF since 2008 and is being used since 2010 on more than 30 watersheds in France. This ensemble forecasting chain is characterized ensemble pre-processing (rainfall and temperature) and post-processing (streamflow), where a large human expertise is solicited. The aim of this paper is to compare 2 hydrological ensemble post-processing methods developed at EDF in order improve ensemble forecasts reliability (similar to Monatanari &Brath, 2004; Schaefli et al., 2007). The aim of the post-processing methods is to dress hydrological ensemble forecasts with hydrological model uncertainties, based on perfect forecasts. The first method (called empirical approach) is based on a statistical modelisation of empirical error of perfect forecasts, by streamflow sub-samples of quantile class and lead-time. The second method (called dynamical approach) is based on streamflow sub-samples of quantile class and streamflow variation, and lead-time. On a set of 20 watersheds used for operational forecasts, results show that both approaches are necessary to ensure a good post-processing of hydrological ensemble, allowing a good improvement of reliability, skill and sharpness of ensemble forecasts. The comparison of the empirical and dynamical approaches shows the limits of the empirical approach which is not able to take into account hydrological dynamic and processes, i. e. sample heterogeneity. For a same streamflow range corresponds different processes such as rising limbs or recession, where uncertainties are different. The dynamical approach improves reliability, skills and sharpness of forecasts and globally reduces confidence intervals width. When compared in details, the dynamical approach allows a noticeable reduction of confidence intervals during recessions where uncertainty is relatively lower and a slight increase of confidence intervals during rising limbs or snowmelt where uncertainty is greater. The dynamic approach, validated by forecaster's experience that considered the empirical approach not discriminative enough, improved forecaster's confidence and communication of uncertainties. Montanari, A. and Brath, A., (2004). A stochastic approach for assessing the uncertainty of rainfall-runoff simulations. Water Resources Research, 40, W01106, doi:10.1029/2003WR002540. Schaefli, B., Balin Talamba, D. and Musy, A., (2007). Quantifying hydrological modeling errors through a mixture of normal distributions. Journal of Hydrology, 332, 303-315.

Development and modelisation of a hydro-power conversion system based on vortex induced vibration

NASA Astrophysics Data System (ADS)

Lefebure, David; Dellinger, Nicolas; François, Pierre; Mosé, Robert

2016-11-01

The Vortex Induced Vibration (VIV) phenomenon leads to mechanical issues concerning bluff bodies immerged in fluid flows and have therefore been studied by numerous authors. Moreover, an increasing demand for energy implies the development of alternative, complementary and renewable energy solutions. The main idea of EauVIV project consists in the use of VIV rather than its deletion. When rounded objects are immerged in a fluid flow, vortices are formed and shed on their downstream side, creating a pressure imbalance resulting in an oscillatory lift. A convertor modulus consists of an elastically mounted, rigid cylinder on end-springs, undergoing flow- induced motion when exposed to transverse fluid-flow. These vortices induce cyclic lift forces in opposite directions on the circular bar and cause the cylinder to vibrate up and down. An experimental prototype was developed and tested in a free-surface water channel and is already able to recover energy from free-stream velocity between 0.5 and 1 m.s -1. However, the large number of parameters (stiffness, damping coefficient, velocity of fluid flow, etc.) associated with its performances requires optimization and we choose to develop a complete tridimensionnal numerical model solution. A 3D numerical model has been developed in order to represent the real system behavior and improve it through, for example, the addition of parallel cylinders. The numerical model build up was carried out in three phases. The first phase consists in establishing a 2D model to choose the turbulence model and quantify the dependence of the oscillations amplitudes on the mesh size. The second corresponds to a 3D simulation with cylinder at rest in first time and with vertical oscillation in a second time. The third and final phase consists in a comparison between the experimental system dynamic behavior and its numerical model.

The Second NATO Modelling and Simulation Conference(Deuxieme conference OTAN sur la modelisation et la simulation)

DTIC Science & Technology

2001-07-01

Major General A C Figgures, Capability Manager (Manœuvre) UK MOD, provided the Conference with a fitting end message encouraging the SE and M&S...SESSION Welcoming Address - ‘Synthetic Environments - Managing the Breakout’ WA by M. Markin Opening Address for NATO M&S Conference OA by G. Sürsal...Keynote Address KN by G.J. Burrows Industry’s Role IR† by M. Mansell The RMCS SSEL I by J.R. Searle SESSION 1: POLICY, STRATEGY & MANAGEMENT A Strategy

Models for Aircrew Safety Assessment: Uses, Limitations and Requirements (la Modelisation des conditions de securite des equipages: applications, limitations et cahiers des charges)

DTIC Science & Technology

1999-08-01

immediately, re- ducing venous return artifacts during the first beat of the simulation. tn+1 - W+ on c+ / \\ W_ on c_ t 1 Xi-l Xi+1 Figure 4...s) Figure 5: The effect of network complexity. The aortic pressure is shown in Figure 5 during the fifth beat for the networks with one and three...Mechanical Engineering Department, Uni- versity of Victoria. [19] Huyghe J.M., 1986, "Nonlinear Finite Element Models of The Beating Left

Propagation Modelling and Decision Aids for Communications, Radar and Navigation Systems (La Modelisation de la Propagation et Aides a la Decision Pour les Sysemes de elecommunicaions, de Radar et de Navigation)

DTIC Science & Technology

1994-09-01

the refractive index i. can be density, temperature , ion composition, ionospheric determined from a simplified form of the Appleton- electric field...see Cannon 119941. the electron density profile is based upon the underlying neutral composition. temperature and wind together with electric field...in many of the newer HF predictions decision software , NSSDC/WDC-A-R&S 90-19, National Space aids. They also provide a very useful stand alone

Evaluation d'un ecosysteme pastoral sahelien: Apport de la geomatique (Oursi, Burkina Faso)

NASA Astrophysics Data System (ADS)

Kabore, Seraphine Sawadogo

L'objectif principal de cette recherche est la mise au point d'une architecture d'integration de donnees socio-bio-geographiques et de donnees satellitales dans un Systeme d'Information Geographique (SIG) en vue d'une aide a la prise de decisions dans un environnement semi-aride au nord du Burkina Faso. Elle repond a la question fondamentale de l'interpretation des effets des facteurs climatiques et socioeconomiques sur le milieu pastoral. La recherche s'est appuyee sur plusieurs hypotheses de travail: possibilite d'utilisation de modele de simulation, d'approche multicritere et de donnees de teledetection dans un cadre de systeme d'information geographique. L'evolution spatiotemporelle des parametres de productivite du milieu a ete evaluee par approche dynamique selon le modele de Wu et al. (1996) qui modelise les interactions entre le climat, le milieu physique, le vegetal et l'animal pour mieux quantifier la biomasse primaire. A ce modele, quatre parametres ont ete integres par approche floue et multicritere afin de prendre en compte la dimension socioeconomique de la productivite pastorale (apport majeur de la recherche): la sante, l'education, l'agriculture et l'eau. La teledetection (imagerie SPOT) a permis de definir la production primaire a partir de laquelle les simulations ont ete realisees sur 10 annees. Les resultats obtenus montrent une bonne correlation entre biomasse primaire in situ et celle calculee pour les deux modeles, avec toutefois une meilleure efficacite du modele modifie (4 fois plus) dans les zones de forte productivite ou l'on note un taux de surexploitation agricole eleve. A cause de la variabilite spatiale de la production primaire in situ, les erreurs des resultats de simulation (8 a 11%) sont acceptables et montrent la pertinence de l'approche grace a l'utilisation des SIG pour la spatialisation et l'integration des differents parametres des modeles. Les types de production secondaire preconises (production de lait pendant 7 mois ou de viande pendant 6 mois) sont bases sur les besoins de l'UBT et le disponible fourrager qui est de qualite mediocre en saison seche. Dans les deux cas de figure, un deficit fourrager est observe. Deux types de transhumance sont proposes afin d'assurer une production durable selon deux scenarios: exploitation rationnelle des unites pastorales selon un plan de rotation annuelle et mise en defens a moyen terme des zones degradees pour une regeneration. Les zones potentielles pour la transhumance ont ete determinees selon les limites acceptables des criteres d'exploitation durable des milieux saheliens definis par Kessler (1994) soit 0,2 UBT.ha-1.

Modelisation and distribution of neutron flux in radium-beryllium source (226Ra-Be)

NASA Astrophysics Data System (ADS)

Didi, Abdessamad; Dadouch, Ahmed; Jai, Otman

2017-09-01

Using the Monte Carlo N-Particle code (MCNP-6), to analyze the thermal, epithermal and fast neutron fluxes, of 3 millicuries of radium-beryllium, for determine the qualitative and quantitative of many materials, using method of neutron activation analysis. Radium-beryllium source of neutron is established to practical work and research in nuclear field. The main objective of this work was to enable us harness the profile flux of radium-beryllium irradiation, this theoretical study permits to discuss the design of the optimal irradiation and performance for increased the facility research and education of nuclear physics.

Guide to Modelling & Simulation (M&S) for NATO Network-Enabled Capability (M&S for NNEC) (Guide de la modelisation et de la simulation (M&S) pour las NATO network-enabled capability (M&S de la NNEC))

DTIC Science & Technology

2010-02-01

interdependencies, and then modifying plans according to updated projections. This is currently an immature area where further research is required. The...crosscutting.html. [7] Zeigler, B.P. and Hammonds, P. (2007). “Modelling and Simulation- Based Data Engineering: Introducing Pragmatics and Ontologies for...the optimum benefit to be obtained and while immature , ongoing research needs to be maintained. 20) Use of M&S to support complex operations needs

Modelisation geometrique par NURBS pour le design aerodynamique des ailes d'avion

NASA Astrophysics Data System (ADS)

Bentamy, Anas

The constant evolution of the computer science gives rise to many research areas especially in computer aided design. This study is part, of the advancement of the numerical methods in engineering computer aided design, specifically in aerospace science. The geometric modeling based on NURBS has been applied successfully to generate a parametric wing surface for aerodynamic design while satisfying manufacturing constraints. The goal of providing a smooth geometry described with few parameters has been achieved. In that case, a wing design including ruled surfaces at the leading edge slat and at the flap, and, curved central surfaces with intrinsic geometric property coming from conic curves, necessitates 130 control points and 15 geometric design variables. The 3D character of the wing need to be analyzed by techniques of investigation of surfaces in order to judge conveniently the visual aspect and detect any sign inversion in both directions of parametrization u and nu. Color mapping of the Gaussian curvature appears to be a very effective tools in visualization. The automation of the construction has been attained using an heuristic optimization algorithm, simulated annealing. The relative high speed of convergence to the solutions confirms its practical interest in engineering problems nowadays. The robustness of the geometric model has been tested successfully with an academic inverse design problem. The results obtained allow to foresee multiple possible applications from an extension to a complete geometric description of an airplane to the interaction with others disciplines belonging to a preliminary aeronautical design process.

Modelisation of an unspecialized quadruped walking mammal.

PubMed

Neveu, P; Villanova, J; Gasc, J P

2001-12-01

Kinematics and structural analyses were used as basic data to elaborate a dynamic quadruped model that may represent an unspecialized mammal. Hedgehogs were filmed on a treadmill with a cinefluorographic system providing trajectories of skeletal elements during locomotion. Body parameters such as limb segments mass and length, and segments centre of mass were checked from cadavers. These biological parameters were compiled in order to build a virtual quadruped robot. The robot locomotor behaviour was compared with the actual hedgehog to improve the model and to disclose the necessary changes. Apart from use in robotics, the resulting model may be useful to simulate the locomotion of extinct mammals.

Determination des Parametres Atmospheriques des Etoiles Naines Blanches de Type DB

NASA Astrophysics Data System (ADS)

Beauchamp, Alain

1995-01-01

Les etoiles naines blanches dont les spectres visibles sont domines par des raies fortes d'helium neutre sont subdivisees en trois classes, DB (raies d'helium neutre seulement), DBA (raies d'helium neutre et d'hydrogene) et DBZ (raies d'helium neutre et d'elements lourds). Nous analysons trois echantillons de spectres observes de ces types de naines blanches. Les echantillons consistent, respectivement, de 48 spectres dans le domaine du visible (3700-5100 A). 24 dans l'ultraviolet (1200-3100 A) et quatre dans la partie rouge du visible (5100-6900) A). Parmi les objets de l'echantillon visible, nous identifions quatre nouvelles DBA, ainsi que deux nouvelles DBZ, auparavant classees DB. L'analyse nous permet de determiner spectroscopiquement les parametres atmospheriques, soit la temperature effective, la gravite de surface, ainsi que l'abondance relative de l'hydrogene, N(H)/N(He), dans le cas des DBA. Pour les objets plus chauds que ~15,000 K, la gravite de surface determinee est fiable, et nous obtenons les masses stellaires avec une relation masse -rayon theorique. Les exigences propres a l'analyse de ces objets ont requis d'importantes ameliorations dans la modelisation de leurs atmospheres et distributions de flux de radiation emis par ces derniers. Nous avons inclus dans les modeles d'atmospheres, pour la premiere fois a notre connaissance, les effets dus a la molecule He_sp{2 }{+}, ainsi que l'equation d'etat de Hummer et Mihalas (1988), qui tient compte des perturbations entre particules dans le calcul des populations des differents niveaux atomiques. Nous traitons la convection dans le cadre de la theorie de la longueur de melange. Trois grilles de modeles d'atmospheres a l'ETL (equilibre thermodynamique local) ont ete produites, pour un ensemble de temperatures effectives, gravites de surface et abondances d'hydrogene couvrant les proprietes des etoiles de nos echantillons; elles sont caracterisees par differentes parametrisations appelees, respectivement, ML1, ML2 et ML3, de la theorie de longueur de melange. Nous avons calcule une grille de spectres synthetiques avec les memes parametrisations que la grille de modeles d'atmospheres. Notre traitement de l'elargissement des raies de l'helium neutre a ete ameliore de facon significative par rapport aux etudes precedentes. D'une part, nous tenons compte de l'elargissement des raies produit par les interactions entre l'emetteur et les particules neutres (elargissements par resonance et de van der Waals) en plus de celui par les particules chargees (elargissement Stark). D'autre part, nous avons calcule nous-memes les profils Stark avec les meilleures theories d'elargissement disponibles pour la majorite des raies observees; ces profils depassent en qualite ce qui a ete publie jusqu'a ce jour. Nous avons calcule la distribution de masse des etoiles DB plus chaudes que 15,000 K. La distribution de masse des DB est tres etroite, avec environ les trois quarts des etoiles incluses dans l'intervalle 0.55-0.65 Modot. La masse moyenne des etoiles DB est de 0.58 M_⊙ avec sigma = 0.07. La difference principale entre les distributions de masse des DB et DA est la faible proportion de DB dans les ailes de la distribution, ce qui implique que les DA moins massives que ~0.4 M odot et plus massives que ~0.8 M_⊙ ne se convertissent pas en DB. Les objets les plus massifs de notre echantillon sont de type DBA, ce qui suggere que la masse elevee favorise la visibilite de l'hydrogene. (Abstract shortened by UMI.).

Ground observations and remote sensing data for integrated modelisation of water budget in the Merguellil catchment, Tunisia

NASA Astrophysics Data System (ADS)

Mougenot, Bernard

2016-04-01

The Mediterranean region is affected by water scarcity. Some countries as Tunisia reached the limit of 550 m3/year/capita due overexploitation of low water resources for irrigation, domestic uses and industry. A lot of programs aim to evaluate strategies to improve water consumption at regional level. In central Tunisia, on the Merguellil catchment, we develop integrated water resources modelisations based on social investigations, ground observations and remote sensing data. The main objective is to close the water budget at regional level and to estimate irrigation and water pumping to test scenarios with endusers. Our works benefit from French, bilateral and European projects (ANR, MISTRALS/SICMed, FP6, FP7…), GMES/GEOLAND-ESA) and also network projects as JECAM and AERONET, where the Merguellil site is a reference. This site has specific characteristics associating irrigated and rainfed crops mixing cereals, market gardening and orchards and will be proposed as a new environmental observing system connected to the OMERE, TENSIFT and OSR systems respectively in Tunisia, Morocco and France. We show here an original and large set of ground and remote sensing data mainly acquired from 2008 to present to be used for calibration/validation of water budget processes and integrated models for present and scenarios: - Ground data: meteorological stations, water budget at local scale: fluxes tower, soil fluxes, soil and surface temperature, soil moisture, drainage, flow, water level in lakes, aquifer, vegetation parameters on selected fieds/month (LAI, height, biomass, yield), land cover: 3 times/year, bare soil roughness, irrigation and pumping estimations, soil texture. - Remote sensing data: remote sensing products from multi-platform (MODIS, SPOT, LANDSAT, ASTER, PLEIADES, ASAR, COSMO-SkyMed, TerraSAR X…), multi-wavelength (solar, micro-wave and thermal) and multi-resolution (0.5 meters to 1 km). Ground observations are used (1) to calibrate soil-vegetation-atmosphere models at field scale on different compartment and irrigated and rainfed land during a limited time (seasons or set of dry and wet years), (2) to calibrate and validate particularly evapotranspiration derived from multi-wavelength satellite data at watershed level in relationships with the aquifer conditions: pumping and recharge rate. We will point out some examples.

Elaboration de nouvelles approches micromecaniques pour l'optimisation des performances mecaniques des materiaux heterogenes

NASA Astrophysics Data System (ADS)

Aboutajeddine, Ahmed

Les modeles micromecaniques de transition d'echelles qui permettent de determiner les proprietes effectives des materiaux heterogenes a partir de la microstructure sont consideres dans ce travail. L'objectif est la prise en compte de la presence d'une interphase entre la matrice et le renforcement dans les modeles micromecaniques classiques, de meme que la reconsideration des approximations de base de ces modeles, afin de traiter les materiaux multiphasiques. Un nouveau modele micromecanique est alors propose pour tenir compte de la presence d'une interphase elastique mince lors de la determination des proprietes effectives. Ce modele a ete construit grace a l'apport de l'equation integrale, des operateurs interfaciaux de Hill et de la methode de Mori-Tanaka. Les expressions obtenues pour les modules globaux et les champs dans l'enrobage sont de nature analytique. L'approximation de base de ce modele est amelioree par la suite dans un nouveau modele qui s'interesse aux inclusions enrobees avec un enrobage mince ou epais. La resolution utilisee s'appuie sur une double homogeneisation realisee au niveau de l'inclusion enrobee et du materiau. Cette nouvelle demarche, permettra d'apprehender completement les implications des approximations de la modelisation. Les resultats obtenus sont exploites par la suite dans la solution de l'assemblage de Hashin. Ainsi, plusieurs modeles micromecaniques classiques d'origines differentes se voient unifier et rattacher, dans ce travail, a la representation geometrique de Hashin. En plus de pouvoir apprecier completement la pertinence de l'approximation de chaque modele dans cette vision unique, l'extension correcte de ces modeles aux materiaux multiphasiques est rendue possible. Plusieurs modeles analytiques et explicites sont alors proposee suivant des solutions de differents ordres de l'assemblage de Hashin. L'un des modeles explicite apparait comme une correction directe du modele de Mori-Tanaka, dans les cas ou celui ci echoue a donner de bons resultats. Finalement, ce modele de Mori-Tanaka corrige est utilise avec les operateurs de Hill pour construire un modele de transition d'echelle pour les materiaux ayant une interphase elastoplastique. La loi de comportement effective trouvee est de nature incrementale et elle est conjuguee a la relation de la plasticite de l'interphase. Des simulations d'essais mecaniques pour plusieurs proprietes de l'interphase plastique a permis de dresser des profils de l'enrobage octroyant un meilleur comportement au materiau.

Les mousses adaptatives pour l'amelioration de l'absorption acoustique: Modelisation, mise en oeuvre, mecanismes de controle

NASA Astrophysics Data System (ADS)

Leroy, Pierre

The objective of this thesis is to conduct a thorough numerical and experimental analysis of the smart foam concept, in order to highlight the physical mechanisms and the technological limitations for the control of acoustic absorption. A smart foam is made of an absorbing material with an embedded actuator able to complete the lack of effectiveness of this material in the low frequencies (<500Hz). In this study, the absorbing material is a melamine foam and the actuator is a piezoelectric film of PVDF. A 3D finite element model coupling poroelastic, acoustic, elastic and piezoelectric fields is proposed. The model uses volume and surface quadratic elements. The improved formulation (u,p) is used. An orthotropic porous element is proposed. The power balance in the porous media is established. This model is a powerful and general tool allowing the modeling of all hybrid configurations using poroelastic and piezoelectric fields. Three smart foams prototypes have been built with the aim of validating the numerical model and setting up experimental active control. The comparison of numerical calculations and experimental measurements shows the validity of the model for passive aspects, transducer behaviors and also for control configuration. The active control of acoustic absorption is carried out in normal incidence with the assumption of plane wave in the frequency range [0-1500Hz]. The criterion of minimization is the reflected pressure measured by an unidirectional microphone. Three control cases were tested: off line control with a sum of pure tones, adaptive control with the nFX-LMS algorithm for a pure tone and for a random broad band noise. The results reveal the possibility of absorbing a pressure of 1.Pa at 1.00Hz with 100V and a broad band noise of 94dB with a hundred Vrms starting from 250Hz. These results have been obtained with a mean foam thickness of 4cm. The control ability of the prototypes is directly connected to the acoustic flow. An important limitation for the broad band control comes from the high distortion level through the system in the low and high frequency range (<500Hz, > 1500Hz). The use of the numerical model, supplemented by an analytical study made it possible to clarify the action mode and the dissipation mechanisms in smart foams. The PVDF moves with the same phase and amplitude of the residual incidental pressure which is not dissipated in the foam. Viscous effect dissipation is then very weak in the low frequencies and becomes more important in the high frequencies. The wave which was not been dissipated in the porous material is transmitted by the PVDF in the back cavity. The outlooks of this study are on the one hand, the improvement of the model and the prototypes and on the other hand, the widening of the field of research to the control of the acoustic transmission and the acoustic radiation of surfaces. The model could be improved by integrating viscoelastic elements able to account for the behavior of the adhesive layer between the PVDF and foam. A modelisation of electro-elastomers materials would also have to be implemented in the code. This new type of actuator could make it possible to exceed the PVDF displacement limitations. Finally it would be interesting for the industrial integration prospects to seek configurations able to maximize acoustic absorption and to limit the transmission and the radiation of surfaces at the same time.

Modelisation et optimisation des systemes energetiques a l'aide d'algorithmes evolutifs

NASA Astrophysics Data System (ADS)

Hounkonnou, Sessinou M. William

Optimization of thermal and nuclear plant has many economics advantages as well as environmentals. Therefore new operating points research and use of new tools to achieve those kind of optimization are the subject of many studies. In this momentum, this project is intended to optimize energetic systems precisely the secondary loop of Gentilly 2 nuclear plant using both the extraction of the high and low pressure turbine as well as the extraction of the mixture coming from the steam generator. A detailed thermodynamic model of the various equipment of the secondary loop such as the feed water heaters, the moisture separator-reheater, the dearator, the condenser and the turbine is carried out. We use Matlab software (version R2007b, 2007) with the library for the thermodynamic properties of water and steam (XSteam pour Matlab, Holmgren, 2006). A model of the secondary loop is than obtained thanks to the assembly of the different equipments. A simulation of the equipment and the complete cycle enabled us to release two objectifs functions knowing as the net output and the efficiency which evolve in an opposite way according to the variation of the extractions. Due to the complexity of the problem, we use a method based on the genetic algorithms for the optimization. More precisely we used a tool which was developed at the "Institut de genie nucleaire" named BEST (Boundary Exploration Search Technique) developed in VBA* (Visual BASIC for Application) for its ability to converge more quickly and to carry out a more exhaustive search at the border of the optimal solutions. The use of the DDE (Dynamic Data Exchange) enables us to link the simulator and the optimizer. The results obtained show us that they still exists several combinations of extractions which make it possible to obtain a better point of operation for the improvement of the performance of Gentilly 2 power station secondary loop. *Trademark of Microsoft

Modelisations et inversions tri-dimensionnelles en prospections gravimetrique et electrique

NASA Astrophysics Data System (ADS)

Boulanger, Olivier

The aim of this thesis is the application of gravity and resistivity methods for mining prospecting. The objectives of the present study are: (1) to build a fast gravity inversion method to interpret surface data; (2) to develop a tool for modelling the electrical potential acquired at surface and in boreholes when the resistivity distribution is heterogeneous; and (3) to define and implement a stochastic inversion scheme allowing the estimation of the subsurface resistivity from electrical data. The first technique concerns the elaboration of a three dimensional (3D) inversion program allowing the interpretation of gravity data using a selection of constraints such as the minimum distance, the flatness, the smoothness and the compactness. These constraints are integrated in a Lagrangian formulation. A multi-grid technique is also implemented to resolve separately large and short gravity wavelengths. The subsurface in the survey area is divided into juxtaposed rectangular prismatic blocks. The problem is solved by calculating the model parameters, i.e. the densities of each block. Weights are given to each block depending on depth, a priori information on density, and density range allowed for the region under investigation. The present code is tested on synthetic data. Advantages and behaviour of each method are compared in the 3D reconstruction. Recovery of geometry (depth, size) and density distribution of the original model is dependent on the set of constraints used. The best combination of constraints experimented for multiple bodies seems to be flatness and minimum volume for multiple bodies. The inversion method is tested on real gravity data. The second tool developed in this thesis is a three-dimensional electrical resistivity modelling code to interpret surface and subsurface data. Based on the integral equation, it calculates the charge density caused by conductivity gradients at each interface of the mesh allowing an exact estimation of the potential. Modelling generates a huge matrix made of Green's functions which is stored by using the method of pyramidal compression. The third method consists to interpret electrical potential measurements from a non-linear geostatistical approach including new constraints. This method estimates an analytical covariance model for the resistivity parameters from the potential data. (Abstract shortened by UMI.)

Caracterisation et modelisation de la degradation des proprietes fonctionnelles des AMF soumis a un chargement cyclique

NASA Astrophysics Data System (ADS)

Paradis, Alexandre

The principal objective of the present thesis is to elaborate a computational model describing the mechanical properties of NiTi under different loading conditions. Secondary objectives are to build an experimental database of NiTi under stress, strain and temperature in order to validate the versatility of the new model proposed herewith. The simulation model used presently at Laboratoire sur les Alliage a Memoire et les Systemes Intelligents (LAMSI) of ETS is showing good behaviour in quasi-static loading. However, dynamic loading with the same model do not allows one to include degradation. The goal of the present thesis is to build a model capable of describing such degradation in a relatively accurate manner. Some experimental testing and results will be presented. In particular, new results on the behaviour of NiTi being paused during cycling are presented in chapter 2. A model is developed in chapter 3 based on Likhachev's micromechanical model. Good agreement is found with experimental data. Finally, an adaptation of the model is presented in chapter 4, allowing it to be eventually implemented into a finite-element commercial software.

Etude des phenomenes dynamiques ultrarapides et des caracteristiques impulsionnelles d'emission terahertz du supraconducteur YBCO

NASA Astrophysics Data System (ADS)

Savard, Stephane

Les premieres etudes d'antennes a base de supraconducteurs a haute temperature critique emettant une impulsion electromagnetique dont le contenu en frequence se situe dans le domaine terahertz remontent a 1996. Une antenne supraconductrice est formee d'un micro-pont d'une couche mince supraconductrice sur lequel un courant continu est applique. Un faisceau laser dans le visible est focalise sur le micro-pont et place le supraconducteur dans un etat hors-equilibre ou des paires sont brisees. Grace a la relaxation des quasiparticules en surplus et eventuellement de la reformation des paires supraconductrices, nous pouvons etudier la nature de la supraconductivite. L'analyse de la cinetique temporelle du champ electromagnetique emis par une telle antenne terahertz supraconductrice s'est averee utile pour decrire qualitativement les caracteristiques de celle-ci en fonction des parametres d'operation tels que le courant applique, la temperature et la puissance d'excitation. La comprehension de l'etat hors-equilibre est la cle pour comprendre le fonctionnement des antennes terahertz supraconductrices a haute temperature critique. Dans le but de comprendre ultimement cet etat hors-equilibre, nous avions besoin d'une methode et d'un modele pour extraire de facon plus systematique les proprietes intrinseques du materiau qui compose l'antenne terahertz a partir des caracteristiques d'emission de celle-ci. Nous avons developpe une procedure pour calibrer le spectrometre dans le domaine temporel en utilisant des antennes terahertz de GaAs bombarde aux protons H+ comme emetteur et detecteur. Une fois le montage calibre, nous y avons insere une antenne emettrice dipolaire de YBa 2Cu3O7-delta . Un modele avec des fonctions exponentielles de montee et de descente du signal est utilise pour lisser le spectre du champ electromagnetique de l'antenne de YBa 2Cu3O7-delta, ce qui nous permet d'extraire les proprietes intrinseques de ce dernier. Pour confirmer la validite du modele choisi, nous avons mesure les proprietes intrinseques du meme echantillon de YBa2Cu3O7- delta avec la technique pompe-visible et sonde-terahertz donnant, elle aussi, acces aux temps caracteristiques regissant l'evolution hors-equilibre de ce materiau. Dans le meilleur scenario, ces temps caracteristiques devraient correspondre a ceux evalues grace a la modelisation des antennes. Un bon controle des parametres de croissance des couches minces supraconductrices et de fabrication du dispositif nous a permis de realiser des antennes d'emission terahertz possedant d'excellentes caracteristiques en terme de largeur de bande d'emission (typiquement 3 THz) exploitables pour des applications de spectroscopie resolue dans le domaine temporel. Le modele developpe et retenu pour le lissage du spectre terahertz decrit bien les caracteristiques de l'antenne supraconductrice pour tous les parametres d'operation. Toutefois, le lien avec la technique pompe-sonde lors de la comparaison des proprietes intrinseques n'est pas direct malgre que les deux techniques montrent que le temps de relaxation des porteurs augmente pres de la temperature critique. Les donnees en pompe-sonde indiquent que la mesure du temps de relaxation depend de la frequence de la sonde, ce qui complique la correspondance des proprietes intrinseques entre les deux techniques. De meme, le temps de relaxation extrait a partir du spectre de l'antenne terahertz augmente en s'approchant de la temperature critique (T c) de YBa2Cu 3O7-delta. Le comportement en temperature du temps de relaxation correspond a une loi de puissance qui est fonction de l'inverse du gap supraconducteur avec un exposant 5 soit 1/Delta 5(T). Le travail presente dans cette these permet de mieux decrire les caracteristiques des antennes supraconductrices a haute temperature critique et de les relier aux proprietes intrinseques du materiau qui les compose. De plus, cette these presente les parametres a ajuster comme le courant applique, la puissance de la pompe, la temperature d'operation, etc, afin d'optimiser l'emission et les performances de ces antennes supraconductrices entre autres pour maximiser leur etendue en frequence dans une perspective d'application en spectroscopie terahertz. Cependant, plusieurs des resultats obtenus soulevent la difficulte de decrire l'etat hors-equilibre et la necessite de developper une theorie pour le supraconducteur YBa2 Cu3O7-delta

Transport de paires EPR dans des structures mesoscopiques

NASA Astrophysics Data System (ADS)

Dupont, Emilie

Dans cette these, nous nous sommes particulierement interesses a la propagation de paires EPR1 delocalisees et localisees, et a l'influence d'un supraconducteur sur le transport de ces paires. Apres une introduction de cette etude, ainsi que du cadre scientifique qu'est l'informatique quantique dans lequel elle s'inscrit, nous allons dans le chapitre 1 faire un rappel sur le systeme constitue de deux points quantiques normaux entoures de deux fils supraconducteurs. Cela nous permettra d'introduire une methode de calcul qui sera reutilisee par la suite, et de trouver egalement le courant Josephson produit par ce systeme transforme en SQUID-dc par l'ajout d'une jonction auxiliaire. Le SQUID permet de mesurer l'etat de spin (singulet ou triplet), et peut etre forme a partir d'autres systemes que nous etudierons ensuite. Dans le chapitre 2, nous rappellerons l'etude detaillee d'un intricateur d'Andreev faite par un groupe de Bale. La matrice T, permettant d'obtenir le courant dans les cas ou les electrons sont separes spatialement ou non, sera etudiee en detail afin d'en faire usage au chapitre suivant. Le chapitre 3 est consacre a l'etude de l'influence du bruit sur le fonctionnement de l'intricateur d'Andreev. Ce bruit modifie la forme du courant jusqu'a aboutir a d'autres conditions de fonctionnement de l'intricateur. En effet, le bruit present sur les points quantiques peut perturber le transport des paires EPR par l'intermediaire des degres de liberte. Nous montrerons que, du fait de l'"intrication" entre la charge de la paire et le bruit, la paire est detruite pour des temps longs. Cependant, le resultat le plus important sera que le bruit perturbe plus le transport des paires delocalisees, qui implique une resonance de Breit-Wigner a deux particules. Le transport parasite n'implique pour sa part qu'une resonance de Breit-Wigner a une particule. Dans le chapitre 4, nous reviendrons au systeme constitue de deux points quantiques entoures de deux fils supraconducteurs, mais ici, les deux points quantiques seront aussi supraconducteurs. On obtiendra alors l'hamiltonien effectif de la meme maniere que precedemment ainsi que la forme du courant. Dans le cas ou la tension entre les deux fils est nulle, nous ferons une comparaison avec l'experience et nous verrons que les resultats obtenus sont plus en accord avec celle-ci si on fait l'hypothese de la presence d'un bain, qui va modeliser le bruit sur l'un des fils. Enfin, dans le dernier chapitre, nous utiliserons a la fois un qubit de charge et un qubit de spin entoures par deux fils supraconducteurs. Nous pourrons alors mesurer l'influence du supraconducteur et voir s'il est possible de creer ici des paires d'electrons intriques et d'aboutir a un pendule quantique. 1Il existe des systemes qui produisent des paires de particules ejectees simultanement dans des directions opposees et qui permettent de tester le paradoxe d' Einstein, Podolsky, Rosen. Chaque particule de la paire est dans un etat indetermine. Si on mesure les etats respectifs des deux particules, on obtient systematiquement des resultats complementaires, soit de facon aleatoire: 0-1 ou 1-0. La mecanique quantique explique que les deux particules ainsi produites constituent un seul systeme, une paire EPR.

Etude energetique et modelisation d'un Systeme Hybride Eolien-Diesel avec stockage d'Air Comprime (SHEDAC)

NASA Astrophysics Data System (ADS)

Martinez, Nicolas

Actuellement le Canada et plus specialement le Quebec, comptent une multitude de sites isoles dont !'electrification est assuree essentiellement par des generatrices diesel a cause, principalement, de l'eloignement du reseau central de disuibution electrique. Bien que consideree comme une source fiable et continue, 1 'utilisation des generatrices diesel devient de plus en plus problematique d'un point de vue energetique, economique et environnemental. Dans le but d'y resoudre et de proposer une methode d'approvisionnement plus performante, mains onereuse et plus respectueuse de l'environnement, l'usage des energies renouvelables est devenu indispensable. Differents travaux ont alors demontre que le couplage de ces energies avec des generauices diesel, formant des systemes hybrides, semble etre une des meilleures solutions. Parmi elles, le systeme hybride eolien-diesel avec stockage par air comprime (SHEDAC) se presente comme une configuration optimale pour 1 'electrification des sites isoles. En effet, differentes etudes ont permis de mettre en avant l'efficacite du stockage par air comprime, par rapport a d'autres technologies de stockage, en complement d'un systeme hybride eolien-diesel. Plus precisement, ce systeme se compose de sous-systemes qui sont: des eoliennes, des generatrices diesel et une chaine de compression et de stockage d'air comprime qui est ensuite utilisee pour suralimenter les generatrices. Ce processus permet ainsi de reduire Ia consommation en carburant tout en agrandissant la part d'energie renouvelable dans Ia production electrique. A ce jour, divers travaux de recherche ont pennis de demontrer I' efficacite d 'un tel systeme et de presenter une variete de configurations possibles. A travers ce memoire, un logiciel de dimensionnement energetique y est elabore dans le but d'unifom1iser !'approche energetique de cette technologie. Cet outil se veut etre une innovation dans le domaine puisqu'il est actuellement impossible de dimensionner un SHEDAC avec les outils existants. Un etat de l'art specifique associe a une validation des resultats a ete realise dans le but de proposer un logiciel fiable et performant. Dans une logique visant !'implantation d'un SHEDAC sur un site isole du Nord-du-Quebec, le logiciel developpe a ete, ensuite, utilise pour realiser une etude energetique permettant d' en degager la solution optimale a mettre en place. Enfin, a l' aide des outils et des resultats obtenus precedemment, !'elaboration de nouvelles strategies d'operation est presentee dans le but de demontrer comment le systeme pourrait etre optimise afm de repondre a differentes contraintes techniques. Le contenu de ce memoire est presente sous forme de trois articles originaux, soumis a des joumaux scientifiques avec cornite de lecture, et d'un chapitre specifique presentant les nouvelles strategies d 'operation. Ils relatent des travaux decrits dans le paragraphe precedent et permettent d'en deduire un usage concluant et pertinent du SHEDAC dans un site isole nordique.

Developpement d'une methode calorimetrique de mesure des pertes ac pour des rubans supraconducteurs a haute temperature critique

NASA Astrophysics Data System (ADS)

Dolez, Patricia

Le travail de recherche effectue dans le cadre de ce projet de doctorat a permis la mise au point d'une methode de mesure des pertes ac destinee a l'etude des supraconducteurs a haute temperature critique. Pour le choix des principes de cette methode, nous nous sommes inspires de travaux anterieurs realises sur les supraconducteurs conventionnels, afin de proposer une alternative a la technique electrique, presentant lors du debut de cette these des problemes lies a la variation du resultat des mesures selon la position des contacts de tension sur la surface de l'echantillon, et de pouvoir mesurer les pertes ac dans des conditions simulant la realite des futures applications industrielles des rubans supraconducteurs: en particulier, cette methode utilise la technique calorimetrique, associee a une calibration simultanee et in situ. La validite de la methode a ete verifiee de maniere theorique et experimentale: d'une part, des mesures ont ete realisees sur des echantillons de Bi-2223 recouverts d'argent ou d'alliage d'argent-or et comparees avec les predictions theoriques donnees par Norris, nous indiquant la nature majoritairement hysteretique des pertes ac dans nos echantillons; d'autre part, une mesure electrique a ete realisee in situ dont les resultats correspondent parfaitement a ceux donnes par notre methode calorimetrique. Par ailleurs, nous avons compare la dependance en courant et en frequence des pertes ac d'un echantillon avant et apres qu'il ait ete endommage. Ces mesures semblent indiquer une relation entre la valeur du coefficient de la loi de puissance modelisant la dependance des pertes avec le courant, et les inhomogeneites longitudinales du courant critique induites par l'endommagement. De plus, la variation en frequence montre qu'au niveau des grosses fractures transverses creees par l'endommagement dans le coeur supraconducteur, le courant se partage localement de maniere a peu pres equivalente entre les quelques grains de matiere supraconductrice qui restent fixes a l'interface coeur-enveloppe, et le revetement en alliage d'argent. L'interet d'une methode calorimetrique par rapport a la technique electrique, plus rapide, plus sensible et maintenant fiable, reside dans la possibilite de realiser des mesures de pertes ac dans des environnements complexes, reproduisant la situation presente par exemple dans un cable de transport d'energie ou dans un transformateur. En particulier, la superposition d'un courant dc en plus du courant ac habituel nous a permis d'observer experimentalement, pour la premiere fois a notre connaissance, un comportement particulier des pertes ac en fonction de la valeur du courant dc decrit theoriquement par LeBlanc. Nous avons pu en deduire la presence d'un courant d'ecrantage Meissner de 16 A, ce qui nous permet de determiner les conditions dans lesquelles une reduction du niveau de pertes ac pourrait etre obtenue par application d'un courant dc, phenomene denomme "vallee de Clem".

Etude de l'impact de la valorisation energetique de pneus hors d'usage, dans une cimenterie, sur les emissions gazeuses par modelisation de la dispersion atmospherique

NASA Astrophysics Data System (ADS)

Bredin, Nathalie

La génération incéssante de déchets nécessite le développement de nouvelles technologies, telle que la valorisation énergétique, pour en disposer. Une filière appropriée pour valoriser énergétiquement les déchets est le procédé cimentier. L'industrie du ciment est une des grandes consommatrices d'énergie. La température nécessaire à la préparation du ciment se situe aux environs de 1450°C pour faire réagir la matière première (cru) qui est sous forme poudreuse et constituée principalement de roches calcaires, argileuses, schisteuses,... Les gaz de combustion ont un long temps de résidence dans les fours. De plus, le mode de fonctionnement des fours est responsable d'un effet de lessivage des gaz acides par le cru alcalin. Ces propriétés font du procédé cimentier un bon candidat pour la valorisation énergétique des déchets. Les déchets interessants pour les cimenteries sont, entre autres, les huiles usées, les solvants usés et les pneus usés qui ont un pouvoir calorifique équivalent à celui du charbon. Les rejets à l'atmosphère des cimenteries sont principalement des émissions gazeuses. Ainsi, l'impact de la valorisation de pneus usés sur les émissions gazeuses de la cimenterie Saint-Laurent de Joliette a été étudié, à l'aide de l'outil qu'est la modélisation de la dispersion atmosphérique. Le modèle utilisé ISC-ST2, Industrial Source Complex-Short Term, est de type gaussien. L'analyse des concentrations maximales horaires et moyennes sur différentes périodes de temps (1 heure, 8 heures, ..., 1 an) des émissions gazeuses dans l'air ambiant montre que celles-ci sont en deçà des normes émises par le gouvernement québécois et par la Communauté Urbaine de Montréal. L'étude de la distribution géographique des polluants, d'après les concentrations annuelles, dans un rayon de 5 km autour de la cimenterie montre que le fait d'utiliser des pneus comme combustible de substitution n'a qu'un faible impact sur la concentration des contaminants au niveau du sol. L'étude du modèle gaussien de dispersion a permis de mettre au point un nouvel outil: la corrélation existant entre les concentrations latérales et verticales des polluants dans le panache. Cet outil utilisé pour étudier les schémas de dispersion atmosphérique de Turner en milieu rural, et de Briggs en milieux urbain et rural, montre que, en milieu rural, le schéma de dispersion proposé par Briggs présente une dispersion plus importante que celui de Turner pour les classes neutres et instables et moins importantes pour les classes stables. La comparaison des schémas de Briggs (rural et urbain) confirme que la dispersion en milieu urbain est plus importante qu'en milieu rural.

Application d'une technique de modelisation aerodynamique conceptuelle sur la simulation d'un pilote automatique a commande optimale pour un avion d'affaires

NASA Astrophysics Data System (ADS)

Pollender-Moreau, Olivier

Ce document présente, dans le cadre d'un contexte conceptuel, une méthode d'enchaînement servant à faire le lien entre les différentes étapes qui permettent de réaliser la simulation d'un aéronef à partir de ses données géométriques et de ses propriétés massiques. En utilisant le cas de l'avion d'affaires Hawker 800XP de la compagnie Hawker Beechcraft, on démontre, via des données, un processus de traitement par lots et une plate-forme de simulation, comment (1) modéliser la géométrie d'un aéronef en plusieurs surfaces, (2) calculer les forces aérodynamiques selon une technique connue sous le nom de Vortex Lattice Method, (3) construire un modèle de vol servant à la simulation des aéronefs pour leur enveloppe de vol en ajoutant des fonctions supplémentaires, (4) construire un modèle de turbosoufflante simplifié, (5) développer un algorithme d'équilibre (trim) du mouvement longitudinal, (6) développer des algorithmes de contrôle à commande moderne, (7) développer certaines fonctions d'un système de pilotage automatique, et (8) rassembler le tout sous une même plate-forme de simulation. Afin de supporter ce travail, une application publique Matlab, connue sous le nom de Tornado, est utilisée conjointement avec d'autres fonctions pour la conception du modèle de vol aérodynamique. D'ailleurs, il sera démontré que le modèle de vol, quoiqu'il soit quand même crédible, ne concorde pas tout à fait avec les données de référence. Par contre, puisque le modèle des moteurs fonctionne bien, que l'algorithme d'équilibrage du mouvement longitudinal fonctionne bien et que les pôles des systèmes dynamiques concordent avec la littérature, les tests dynamiques effectués au sein de la plate-forme de simulation permettent d'obtenir des résultats fonctionnels et crédibles. D'ailleurs, deux systèmes d'augmentation de la stabilité basés sur la méthode de contrôle moderne LQR et couvrant l'enveloppe de vol de l'aéronef via un système d'ordonnancement des gains sont implémentés respectivement selon les mouvements longitudinal et latéral. Ces fonctions fonctionnent bien et permettent de rencontrer les qualités de vol requises pour un avion d'affaires. Finalement, certaines fonctions concernant un système de pilotage automatique sont implémentées. Dans le cas du mouvement latéral, ces fonctions sont basées sur les méthodes de contrôle modernes et couvrent la totalité de l'enveloppe de vol; mais en ce qui concerne le mouvement longitudinal, elles sont basées sur des algorithmes d'équilibre difficile à gérer pour implémenter sur toute l'enveloppe de vol, c'est pourquoi les tests présentés sont limités à des scénarios bien précis. Dans les deux cas, les essais effectués donnent d'assez bons résultats.

Evaluation de la qualite osseuse par les ondes guidees ultrasonores =

NASA Astrophysics Data System (ADS)

Abid, Alexandre

La caracterisation des proprietes mecaniques de l'os cortical est un domaine d'interet pour la recherche orthopedique. En effet, cette caracterisation peut apporter des informations primordiales pour determiner le risque de fracture, la presence de microfractures ou encore depister l'osteoporose. Les deux principales techniques actuelles de caracterisation de ces proprietes sont le Dual-energy X-ray Absorptiometry (DXA) et le Quantitative Computed Tomogaphy (QCT). Ces techniques ne sont pas optimales et presentent certaines limites, ainsi l'efficacite du DXA est questionnee dans le milieu orthopedique tandis que le QCT necessite des niveaux de radiations problematiques pour en faire un outil de depistage. Les ondes guidees ultrasonores sont utilisees depuis de nombreuses annees pour detecter les fissures, la geometrie et les proprietes mecaniques de cylindres, tuyaux et autres structures dans des milieux industriels. De plus, leur utilisation est plus abordable que celle du DXA et n'engendrent pas de radiation ce qui les rendent prometteuses pour detecter les proprietes mecaniques des os. Depuis moins de dix ans, de nombreux laboratoires de recherche tentent de transposer ces techniques au monde medical, en propageant les ondes guidees ultrasonores dans les os. Le travail presente ici a pour but de demontrer le potentiel des ondes guidees ultrasonores pour determiner l'evolution des proprietes mecaniques de l'os cortical. Il commence par une introduction generale sur les ondes guidees ultrasonores et une revue de la litterature des differentes techniques relatives a l'utilisation des ondes guidees ultrasonores sur les os. L'article redige lors de ma maitrise est ensuite presente. L'objectif de cet article est d'exciter et de detecter certains modes des ondes guides presentant une sensibilite a la deterioration des proprietes mecaniques de l'os cortical. Ce travail est realise en modelisant par elements finis la propagation de ces ondes dans deux modeles osseux cylindriques. Ces deux modeles sont composes d'une couche peripherique d'os cortical et remplis soit d'os trabeculaire soit de moelle osseuse. Ces deux modeles permettent d'obtenir deux geometries, chacune propice a la propagation circonferentielle ou longitudinale des ondes guidees. Les resultats, ou trois differents modes ont pu etre identifies, sont compares avec des donnees experimentales obtenues avec des fantomes osseux et theoriques. La sensibilite de chaque mode pour les differents parametres des proprietes mecaniques est alors etudiee ce qui permet de conclure sur le potentiel de chaque mode quant a la prediction de risque de fracture ou de presence de microfractures.

Contribution to study of interfaces instabilities in plane, cylindrical and spherical geometry

NASA Astrophysics Data System (ADS)

Toque, Nathalie

1996-12-01

This thesis proposes several experiments of hydrodynamical instabilities which are studied, numerically and theoretically. The experiments are in plane and cylindrical geometry. Their X-ray radiographies show the evolution of an interface between two solid media crossed by a detonation wave. These materials are initially solid. They become liquide under shock wave or stay between two phases, solid and liquid. The numerical study aims at simulating with the codes EAD and Ouranos, the interfaces instabilities which appear in the experiments. The experimental radiographies and the numerical pictures are in quite good agreement. The theoretical study suggests to modelise a spatio-temporal part of the experiments to obtain the quantitative development of perturbations at the interfaces and in the flows. The models are linear and in plane, cylindrical and spherical geometry. They preceed the inoming study of transition between linear and non linear development of instabilities in multifluids flows crossed by shock waves.

Generation of 238U Covariance Matrices by Using the Integral Data Assimilation Technique of the CONRAD Code

NASA Astrophysics Data System (ADS)

Privas, E.; Archier, P.; Bernard, D.; De Saint Jean, C.; Destouche, C.; Leconte, P.; Noguère, G.; Peneliau, Y.; Capote, R.

2016-02-01

A new IAEA Coordinated Research Project (CRP) aims to test, validate and improve the IRDF library. Among the isotopes of interest, the modelisation of the 238U capture and fission cross sections represents a challenging task. A new description of the 238U neutrons induced reactions in the fast energy range is within progress in the frame of an IAEA evaluation consortium. The Nuclear Data group of Cadarache participates in this effort utilizing the 238U spectral indices measurements and Post Irradiated Experiments (PIE) carried out in the fast reactors MASURCA (CEA Cadarache) and PHENIX (CEA Marcoule). Such a collection of experimental results provides reliable integral information on the (n,γ) and (n,f) cross sections. This paper presents the Integral Data Assimilation (IDA) technique of the CONRAD code used to propagate the uncertainties of the integral data on the 238U cross sections of interest for dosimetry applications.

Conception, elaboration et mise a l'essai d'un simulateur interactif permettant une approche modelisante: Application aux lois de la genetique mendelienne

NASA Astrophysics Data System (ADS)

Lasri, Abdel-Halim

Dans cette recherche-developpement, nous avons concu, developpe et mis a l'essai un simulateur interactif pour favoriser l'apprentissage des lois probabilistes impliqees dans la genetique mendelienne. Cet environnement informatise devra permettre aux etudiants de mener des experiences simulees, utilisant les statistiques et les probebilites comme outils mathematiques pour modeliser le phenomene de la transmission des caracteres hereditaires. L'approche didactique est essentiellement orientee vers l'utilisation des methodes quantitatives impliquees dans l'experimentation des facteurs hereditaires. En incorporant au simulateur le principe de la "Lunette cognitive" de Nonnon (1986), l'etudiant fut place dans une situation ou il a pu synchroniser la perception de la representation iconique (concrete) et symbolique (abstraite) des lois probabilistes de Mendel. A l'aide de cet environnement, nous avons amene l'etudiant a identifier le(s) caractere(s) hereditaire(s) des parents a croiser, a predire les frequences phenotypiques probables de la descendance issue du croisement, a observer les resultats statistiques et leur fluctuation au niveau de l'histogramme des frequences, a comparer ces resultats aux predictions anticipees, a interpreter les donnees et a selectionner en consequence d'autres experiences a realiser. Les etapes de l'approche inductive sont privilegiees du debut a la fin des activites proposees. L'elaboration, du simulateur et des documents d'accompagnement, a ete concue a partir d'une vingtaine de principes directeurs et d'un modele d'action. Ces principes directeurs et le modele d'action decoulent de considerations theoriques psychologiques, didactiques et technologiques. La recherche decrit la structure des differentes parties composant le simulateur. L'architecture de celui-ci est construite autour d'une unite centrale, la "Principale", dont les liens et les ramifications avec les autres unites confere a l'ensemble du simulateur sa souplesse et sa facilite d'utilisation. Le simulateur "Genetique", a l'etat de prototype, et la documentation qui lui est afferente ont ete soumis a deux mises a l'essai: l'une fonctionnelle, l'autre empirique. La mise a l'essai fonctionnelle, menee aupres d'un groupe d'enseignants experts, a permis d'identifier les lacunes du materiel elabore afin de lui apporter les reajustements qui s'imposaient. La mise a l'essai empirique, conduite par un groupe de onze (11) etudiants de niveau secondaire, avait pour but, d'une part, de tester la facilite d'utilisation du simulateur "Genetique" ainsi que les documents d'accompagnement et, d'autre part, de verifier si les participants retiraient des avantages pedagogiques de cet environnement. Trois techniques furent exploitees pour recolter les donnees de la mise a l'essai empirique. L'analyse des resultats a permis de faire un retour critique sur les productions concretes de cette recherche et d'apporter les modifications necessaires tant au simulateur qu'aux documents d'accompagnement. Cette analyse a permis egalement de conclure que notre simulateur interactif favorise une approche inductive permettant aux etudiants de s'approprier les lois probabilistes de Mendel. Enfin, la conclusion degage des pistes de recherches destinees aux etudes ulterieures, plus particulierement celles qui s'interessent a developper des simulateurs, afin d'integrer a ceux-ci des representations concretes et abstraites presentees en temps reel. Les disquettes du simulateur "Genetique" et les documents d'accompagnement sont annexes a la presente recherche.

POD and PPP with multi-frequency processing

NASA Astrophysics Data System (ADS)

Roldán, Pedro; Navarro, Pedro; Rodríguez, Daniel; Rodríguez, Irma

2017-04-01

Precise Orbit Determination (POD) and Precise Point Positioning (PPP) are methods for estimating the orbits and clocks of GNSS satellites and the precise positions and clocks of user receivers. These methods are traditionally based on processing the ionosphere-free combination. With this combination, the delay introduced in the signal when passing through the ionosphere is removed, taking advantage of the dependency of this delay with the square of the frequency. It is also possible to process the individual frequencies, but in this case it is needed to properly model the ionospheric delay. This modelling is usually very challenging, as the electron content in the ionosphere experiences important temporal and spatial variations. These two options define the two main kinds of processing: the dual-frequency ionosphere-free processing, typically used in the POD and in certain applications of PPP, and the single-frequency processing with estimation or modelisation of the ionosphere, mostly used in the PPP processing. In magicGNSS, a software tool developed by GMV for POD and PPP, a hybrid approach has been implemented. This approach combines observations from any number of individual frequencies and any number of ionosphere-free combinations of these frequencies. In such a way, the observations of ionosphere-free combination allow a better estimation of positions and orbits, while the inclusion of observations from individual frequencies allows to estimate the ionospheric delay and to reduce the noise of the solution. It is also possible to include other kind of combinations, such as geometry-free combination, instead of processing individual frequencies. The joint processing of all the frequencies for all the constellations requires both the estimation or modelisation of ionospheric delay and the estimation of inter-frequency biases. The ionospheric delay can be estimated from the single-frequency or dual-frequency geometry-free observations, but it is also possible to use a-priori information based on ionospheric models, on external estimations and on the expected behavior of the ionosphere. The inter-frequency biases appear because the delay of the signal inside the transmitter and the receiver strongly depends on its frequency. However, it is possible to include constraints in the estimator regarding these delays, assuming small variations over time. By using different types of combinations, all the available information from GNSS systems can be included in the processing. This is especially interesting for the case of Galileo satellites, which transmit in several frequencies, and the GPS IIF satellites, which transmit in L5 in addition to the traditional L1 and L2. Several experiments have been performed, to assess the improvement on performance of POD and PPP when using all the constellations and all the available frequencies for each constellation. This paper describes the new approach of multi-frequency processing, including the estimation of biases and ionospheric delays impacting on GNSS observations, and presents the results of the performed experimentation activities to assess the benefits in POD and PPP algorithms.

Regard epistemique sur une evolution conceptuelle en physique au secondaire

NASA Astrophysics Data System (ADS)

Potvin, Patrice

The thesis, which is in continuity with Legendre's (1993) work, deals with qualitative understanding of physics notions at the secondary level. It attempts to identify and to label, in the verbalizations of 12 to 16 year-old students, the tendencies that guide their cognitive itineraries through the exploration of problem-situations. The hypotheses of work are about modelisations, conceptions and p-prims. These last objects are seen, in DiSessa's epistemological perspective, as a type of habit that influences the determination of links between the parameters of a problem. In other words, they coordinate logically and mathematically. Methodology is based on explicitation interviews. This type of interview authorizes verbalizations that involve an "intuitive sense" of mechanics. Twenty students are invited to share their evocations as they explore the logics of a computerized microworld. This microworld has been programmed on the "Interactive Physics(TM)" software and is made of five different situations that involve speed, acceleration, mass, force and inertia. The situations are presented to the students from the least to the most complex. An analysis of the verbalizations of the five students shows the existence of elements that play a role in modelisation and qualitative construction of comprehension as well as in its qualitative/quantitative articulation. Results indicate the presence of coordinative habits easily discernible. P-prims appear to play an important part in the construction of models and in the determination of links between the variables of a problem. The analysis of the results allows to see that conceptions are not so important pieces in comprehension. As such, they seem phenotypic. Also, analysis allows to recognize the difficulty to understand properly the inverse relation (1/x) and its asymptotic nature. The "p-prim" analysis also establishes the possibility to analyze not only efficient and inefficient intuitions, but also the cognitive itineraries of students working to construct the logic of the movement of a "ball" as a whole. Implications of the thesis are, among others, at the praxic level; it becomes possible to imagine sequences of learning and teaching physics that are based on the consideration of p-prims despite the implicit nature of these objects. This is a truly constructivist practice which establishes bridges between novice and expert knowledge because there are p-prims in both of them. As so, the thesis acknowledges a perspective of learning inscribed in "continuity". It also proposes a fertile theoretical ground for the comprehension of physics.

Modelisation, conception et simulation des performances d'un collecteur solaire aeraulique a tubes sous vide en milieu nordique

NASA Astrophysics Data System (ADS)

Paradis, Pierre-Luc

The global energy consumption is still increasing year after year even if different initiatives are set up to decrease fossil fuel dependency. In Canada 80% of the energy is used for space heating and domestic hot water heating in residential sector. This heat could be provided by solar thermal technologies despite few difficulties originating from the cold climate. The aim of this project is to design a solar evacuated tube thermal collector using air as the working fluid. Firstly, needs and specifications of the product are established in a clear way. Then, three concepts of collector are presented. The first one relies on the standard evacuated tube. The second one uses a new technology of tubes; both sides are open. The third one uses heat pipe to extract the heat from the tubes. Based on the needs and specification as criteria, the concept involving tubes with both sides open has been selected as the best idea. In order to simulate the performances of the collector, a model of the heat exchanges in an evacuated tube was developed in 4 steps. The first step is a model in steady state intended to calculate the stagnation temperature of the tube for a fixed solar radiation, outside temperature and wind speed. As a second step, the model is generalised to transient condition in order to validate it with an experimental setup. A root mean square error of 2% is then calculated. The two remainder steps are intended to calculate the temperature of airflow leaving the tube. In the same way, a first model in steady state is developed and then generalised to the transient mode. Then, the validation with an experimental setup gave a difference of 0.2% for the root mean square error. Finally, a preindustrial prototype intended to work in open loop for preheating of fresh air is presented. During the project, explosion of the both sides open evacuated tube in overheating condition blocked the construction of a real prototype for the test. Different path for further work are also identified. One of these is in relation with CFD simulation of the uniformity of the airflow inside of the collector. Another one is the analysis of the design with a design of experiment plan.

Le niobate de lithium a haute temperature pour les applications ultrasons =

NASA Astrophysics Data System (ADS)

De Castilla, Hector

L'objectif de ce travail de maitrise en sciences appliquees est de trouver puis etudier un materiau piezoelectrique qui est potentiellement utilisable dans les transducteurs ultrasons a haute temperature. En effet, ces derniers sont actuellement limites a des temperatures de fonctionnement en dessous de 300°C a cause de l'element piezoelectrique qui les compose. Palier a cette limitation permettrait des controles non destructifs par ultrasons a haute temperature. Avec de bonnes proprietes electromecaniques et une temperature de Curie elevee (1200°C), le niobate de lithium (LiNbO 3) est un bon candidat. Mais certaines etudes affirment que des processus chimiques tels que l'apparition de conductivite ionique ou l'emergence d'une nouvelle phase ne permettent pas son utilisation dans les transducteurs ultrasons au-dessus de 600°C. Cependant, d'autres etudes plus recentes ont montre qu'il pouvait generer des ultrasons jusqu'a 1000°C et qu'aucune conductivite n'etait visible. Une hypothese a donc emerge : une conductivite ionique est presente dans le niobate de lithium a haute temperature (>500°C) mais elle n'affecte que faiblement ses proprietes a hautes frequences (>100 kHz). Une caracterisation du niobate de lithium a haute temperature est donc necessaire afin de verifier cette hypothese. Pour cela, la methode par resonance a ete employee. Elle permet une caracterisation de la plupart des coefficients electromecaniques avec une simple spectroscopie d'impedance electrochimique et un modele reliant de facon explicite les proprietes au spectre d'impedance. Il s'agit de trouver les coefficients du modele permettant de superposer au mieux le modele avec les mesures experimentales. Un banc experimental a ete realise permettant de controler la temperature des echantillons et de mesurer leur impedance electrochimique. Malheureusement, les modeles actuellement utilises pour la methode par resonance sont imprecis en presence de couplages entre les modes de vibration. Cela implique de posseder plusieurs echantillons de differentes formes afin d'isoler chaque mode principal de vibration. De plus, ces modeles ne prennent pas bien en compte les harmoniques et modes en cisaillement. C'est pourquoi un nouveau modele analytique couvrant tout le spectre frequentiel a ete developpe afin de predire les resonances en cisaillement, les harmoniques et les couplages entre les modes. Neanmoins, certains modes de resonances et certains couplages ne sont toujours pas modelises. La caracterisation d'echantillons carres a pu etre menee jusqu'a 750°C. Les resultats confirment le caractere prometteur du niobate de lithium. Les coefficients piezoelectriques sont stables en fonction de la temperature et l'elasticite et la permittivite ont le comportement attendu. Un effet thermoelectrique ayant un effet similaire a de la conductivite ionique a ete observe ce qui ne permet pas de quantifier l'impact de ce dernier. Bien que des etudes complementaires soient necessaires, l'intensite des resonances a 750°C semble indiquer que le niobate de lithium peut etre utilise pour des applications ultrasons a hautes frequences (>100 kHz).

Recent and upcoming observations of the CARacterisation et Modelisation de l'ENvironnement (CARMEN) mission

NASA Astrophysics Data System (ADS)

Ecoffet, Robert; Maget, Vincent; Rolland, Guy; Lorfevre, Eric; Bourdarie, Sébastien; Boscher, Daniel

2016-07-01

We have developed a series of instruments for energetic particle measurements, associated with component test beds "MEX". The aim of this program is to check and improve space radiation engineering models and techniques. The first series of instruments, "ICARE" has flown on the MIR space station (SPICA mission), the ISS (SPICA-S mission) and the SAC-C low Earth polar orbiting satellite (ICARE mission 2001-2011) in cooperation with the Argentinian space agency CONAE. A second series of instruments "ICARE-NG" was and is flown as: - CARMEN-1 mission on CONAE's SAC-D, 650 km, 98°, 2011-2015, along with three "SODAD" space micro-debris detectors - CARMEN-2 mission on the JASON-2 satellite (CNES, JPL, EUMETSAT, NOAA), 1336 km, 66°, 2008-now, along with JAXA's LPT energetic particle detector - CARMEN-3 mission on the JASON-3 satellite in the same orbit as JASON-2, launched 17 January 2016, along with a plasma detector "AMBRE", and JAXA's LPT again. The ICARE-NG is spectrometer composed of a set of three fully depleted silicon solid state detectors used in single and coincident mode. The on-board measurements consist in accumulating energy loss spectra in the detectors over a programmable accumulation period. The spectra are generated through signal amplitude classification using 8 bit ADCs and resulting in 128/256 channels histograms. The discriminators reference levels, amplifier gain and accumulation time for the spectra are programmable to provide for possible on-board tuning optimization. Ground level calibrations have been made at ONERA-DESP using radioactive source emitting alpha particles in order to determine the exact correspondence between channel number and particle energy. To obtain the response functions to particles, a detailed sectoring analysis of the satellite associated with GEANT-4/MCNP-X calculations has been performed to characterize the geometrical factors of the each detector for p+ as well as for e- with different energies. The component test bed "MEX" is equipped with two different types of active dosimeters, P-MOS silicon dosimeters and OSL (optically stimulated luminescence). Those dosimeters provide independent measurements of ionizing and displacement damage doses and consolidate spectrometers' observations. The data sets obtained cover more than one solar cycle. Dynamics of the radiation belts, effects of solar particle events, coronal mass ejections and coronal holes were observed. Spectrometer measurements and dosimeter readings were used to evaluate current engineering models, and helped in developing improved ones, along with "space weather" radiation belt indices. The presentation will provide a comprehensive review of detector features and mission results.

Contributions de la geographie et de la modelisation predictive a une etude de potentiel archeologique prehistorique en Gaspesie

NASA Astrophysics Data System (ADS)

Desrosiers, Marc

La Gaspésie, région péninsulaire à l'extrême est du Québec, possède un héritage archéologique préhistorique riche qui s'étend de 9 000 ans jusqu'à 450 ans avant aujourd'hui. L'archéologie a livré de nombreux sites préhistoriques dans la région, surtout dans le nord de la péninsule, un constat en partie attribuable à la présence de sources de matières premières lithiques, d'axes de circulation potentielles, mais aussi à la répartition spatiale inégale des efforts de recherche. L'étude du potentiel archéologique préhistorique gaspésien, c'est la première étape de la démarche archéologique, est donc nécessaire pour orienter les travaux futurs dans cette région. Trois secteurs représentatifs de la Gaspésie ont été étudiés pour développer une nouvelle approche d'étude de potentiel : Sainte-Anne-des-Monts, le lac Sainte-Anne et New Richmond. Ensemble, ces secteurs s'étirent au travers de la péninsule sur un axe nord-sud et correspondent à un possible axe de circulation préhistorique. L'évaluation du potentiel archéologique de ces aires d'étude dépend notamment de contexte géographique gaspésien. Celui-ci est complexe, particulièrement depuis la déglaciation qui a engendré une succession de transformations du paysage. Les variations du niveau marin relatif, le passage de la toundra à un milieu forestier et d'autres changements environnementaux ont conditionné la façon dont les populations préhistoriques se sont adaptées au territoire. L'étude de potentiel dépend également des connaissances archéologiques existantes pour la région, car elles conditionnent la sélection de variables environnementales représentatives des sites connus. À partir de la confrontation des données géographiques et archéologiques, nous avons proposé des schèmes d'établissement pour les périodes chronoculturelles de la préhistoire gaspésienne. Ces patrons informationnels permettent d'illustrer la façon dont les populations préhistoriques occupaient le territoire gaspésien. C'est en appliquant ces schèmes d'établissement dans un SIG (Système d'Information Géographique) qu'il est alors possible de modéliser l'occupation potentielle du territoire au cours des périodes de la préhistoire gaspésienne. Les résultats de la modélisation sont prometteurs car les sites archéologiques connus dans le secteur de Sainte-Anne-des-Monts correspondent aux secteurs à potentiel élevé proposés par la modélisation, bien qu'une validation géomorphologique de la modélisation soit nécessaire à une étape ultérieure. Les deux autres secteurs ne présentaient pas de sites archéologiques datés qui permettaient de valider la modélisation à ces endroits. L'outil proposé est d'autant plus intéressant qu'il permet d'étudier rapidement de vastes territoires au potentiel archéologique mal évalué, comme c'est le cas de la Gaspésie.

Etude aerodynamique d'un jet turbulent impactant une paroi concave

NASA Astrophysics Data System (ADS)

LeBlanc, Benoit

Etant donne la demande croissante de temperatures elevees dans des chambres de combustion de systemes de propulsions en aerospatiale (turbomoteurs, moteur a reaction, etc.), l'interet dans le refroidissement par jets impactant s'est vu croitre. Le refroidissement des aubes de turbine permet une augmentation de temperature de combustion, ce qui se traduit en une augmentation de l'efficacite de combustion et donc une meilleure economie de carburant. Le transfert de chaleur dans les au bages est influence par les aspects aerodynamiques du refroidissement a jet, particulierement dans le cas d'ecoulements turbulents. Un manque de comprehension de l'aerodynamique a l'interieur de ces espaces confinees peut mener a des changements de transfert thermique qui sont inattendus, ce qui augmente le risque de fluage. Il est donc d'interet pour l'industrie aerospatiale et l'academie de poursuivre la recherche dans l'aerodynamique des jets turbulents impactant les parois courbes. Les jets impactant les surfaces courbes ont deja fait l'objet de nombreuses etudes. Par contre des conditions oscillatoires observees en laboratoire se sont averees difficiles a reproduire en numerique, puisque les structures d'ecoulements impactants des parois concaves sont fortement dependantes de la turbulence et des effets instationnaires. Une etude experimentale fut realisee a l'institut PPRIME a l'Universite de Poitiers afin d'observer le phenomene d'oscillation dans le jet. Une serie d'essais ont verifie les conditions d'ecoulement laminaires et turbulentes, toutefois le cout des essais experimentaux a seulement permis d'avoir un apercu du phenomene global. Une deuxieme serie d'essais fut realisee numeriquement a l'Universite de Moncton avec l'outil OpenFOAM pour des conditions d'ecoulement laminaire et bidimensionnel. Cette etude a donc comme but de poursuivre l'enquete de l'aerodynamique oscillatoire des jets impactant des parois courbes, mais pour un regime d'ecoulement transitoire, turbulent, tridimensionnel. Les nombres de Reynolds utilises dans l'etude numerique, bases sur le diametre du jet lineaire observe, sont de Red = 3333 et 6667, consideres comme etant en transition vers la turbulence. Dans cette etude, un montage numerique est construit. Le maillage, le schema numerique, les conditions frontiere et la discretisation sont discutes et choisis. Les resultats sont ensuite valides avec des donnees turbulentes experimentales. En modelisation numerique de turbulence, les modeles de Moyennage Reynolds des Equations Naviers Stokes (RANS) presentent des difficultes avec des ecoulements instationnaires en regime transitionnel. La Simulation des Grandes Echelles (LES) presente une solution plus precise, mais au cout encore hors de portee pour cette etude. La methode employee pour cette etude est la Simulation des Tourbillons Detaches (DES), qui est un hybride des deux methodes (RANS et LES). Pour analyser la topologie de l'ecoulement, la decomposition des modes propres (POD) a ete egalement ete effectuee sur les resultats numeriques. L'etude a demontre d'abord le temps de calcul relativement eleve associe a des essais DES pour garder le nombre de Courant faible. Les resultats numeriques ont cependant reussi a reproduire correctement le basculement asynchrone observe dans les essais experimentaux. Le basculement observe semble etre cause par des effets transitionnels, ce qui expliquerait la difficulte des modeles RANS a correctement reproduire l'aerodynamique de l'ecoulement. L'ecoulement du jet, a son tour, est pour la plupart du temps tridimensionnel et turbulent sauf pour de courtes periodes de temps stable et independant de la troisieme dimension. L'etude topologique de l'ecoulement a egalement permit la reconaissances de structures principales sousjacentes qui etaient brouillees par la turbulence. Mots cles : jet impactant, paroi concave, turbulence, transitionnel, simulation des tourbillons detaches (DES), OpenFOAM.

Magnetophotoluminescence de dyades d'azote uniques dans le gallium arsenide

NASA Astrophysics Data System (ADS)

Ouellet-Plamondon, Clauderic

On the goal to achieve an efficient quantum light source, there are many possibilities ranging from lasers to quantum dots. One of those candiate is to use a single nitrogen dyad in GaAs. This nanostructure is composed of two nitrogen atoms in nearest neigbors subsituting for two arsenic atoms. Since both of those atoms have the same valence, the combined effet of the electronegativity and the small size of the nitrogen atoms form a potential well which attracts an electron. A hole is then bound to the electron via coulomb interaction, creating a bound exciton at the dyad from which the luminescence can be studied. In this work, we present an experimental study of the fine structure of the emission from single nitrogen dyads. The photoluminescence measurements are realised using a high resolution confocal microscope and under a magnetic field of up to 7 T. The spatial resolution combined with the sample's surface density of nitrogen dyads allows studying the properties of individual dyads. Since the C2v symmetry of the dyad lifts the degeneracy of the excitonic levels without magnetic field, four or five transitions are observed, depending on the orientation of the dyad with respect to the observation axis. Using a Hamiltonian taking into account the exchange interaction, the local crystal field and the Zeeman effect, the energie of excitonic states as well as their transition probabilites are modelised. This model reproduce the linear polarization of the emmited photons and is used to determine a range of acceptable value for the g-factor of the bound electron as well as the isotropic and anisotropic factors of the interaction of the weakly-bound hole with the magnetic field. Furthermore, from the diamagnetic shift, the radius of the wavefunction of the electron is evalutated at 16.2 °A, confirming that it is strongly localized to the dyad. Of all the dyads studied, a certain number of them had an emission strickingly different from the ones usually observed. In a first case, the environment perturbed the excitonic states making only the two states at higher energy observable. In a second case, an additional depolarised transition is observed at lower energy. We show that this transition is associated to a charged exciton, indicating for the first time that these nanotructures can bind multiple charges like their larger epitaxial and colloidal counterpart. This work gives a better comprehension of excitons bound to a nitrogen dyad and opens the way to many applications.

La conception, la modelisation et la simulation du systeme VSC-HVDC offshore

NASA Astrophysics Data System (ADS)

Benhalima, Seghir

Wind energy is recognized worldwide as a proven technology to meet the growing demands of green sustainable energy. To exploit this stochastic energy source and put together with the conventional energy sources without affecting the performance of existing electrical grids, several research projects have been achieved. In addition, at ocean level, wind energy has a great potential. It means that the production of this energy will increase in the world. The optimal extraction of this energy source needs to be connected to the grid via a voltage source converter which plays the role of interface. To minimise losses due to the transport of energy at very long distances, the technology called High Voltage Direct Current based on Voltage Source Converter (VSC-HVDC) is used. To achieve this goal, a new topology is designed with a new control algorithm based on control of power generated by the wind farm, the DC voltage regulation and the synchronization between wind farm and VSC-HVDC (based on NPC). The proposed topology and its control technique are validated using the "MATLAB/Simulink program". The results are promising, because the THD is less than 5% and the power factor is close to one.

MONET: multidimensional radiative cloud scene model

NASA Astrophysics Data System (ADS)

Chervet, Patrick

1999-12-01

All cloud fields exhibit variable structures (bulge) and heterogeneities in water distributions. With the development of multidimensional radiative models by the atmospheric community, it is now possible to describe horizontal heterogeneities of the cloud medium, to study these influences on radiative quantities. We have developed a complete radiative cloud scene generator, called MONET (French acronym for: MOdelisation des Nuages En Tridim.) to compute radiative cloud scene from visible to infrared wavelengths for various viewing and solar conditions, different spatial scales, and various locations on the Earth. MONET is composed of two parts: a cloud medium generator (CSSM -- Cloud Scene Simulation Model) developed by the Air Force Research Laboratory, and a multidimensional radiative code (SHDOM -- Spherical Harmonic Discrete Ordinate Method) developed at the University of Colorado by Evans. MONET computes images for several scenario defined by user inputs: date, location, viewing angles, wavelength, spatial resolution, meteorological conditions (atmospheric profiles, cloud types)... For the same cloud scene, we can output different viewing conditions, or/and various wavelengths. Shadowing effects on clouds or grounds are taken into account. This code is useful to study heterogeneity effects on satellite data for various cloud types and spatial resolutions, and to determine specifications of new imaging sensor.

Hidden Markov random field model and Broyden-Fletcher-Goldfarb-Shanno algorithm for brain image segmentation

NASA Astrophysics Data System (ADS)

Guerrout, EL-Hachemi; Ait-Aoudia, Samy; Michelucci, Dominique; Mahiou, Ramdane

2018-05-01

Many routine medical examinations produce images of patients suffering from various pathologies. With the huge number of medical images, the manual analysis and interpretation became a tedious task. Thus, automatic image segmentation became essential for diagnosis assistance. Segmentation consists in dividing the image into homogeneous and significant regions. We focus on hidden Markov random fields referred to as HMRF to model the problem of segmentation. This modelisation leads to a classical function minimisation problem. Broyden-Fletcher-Goldfarb-Shanno algorithm referred to as BFGS is one of the most powerful methods to solve unconstrained optimisation problem. In this paper, we investigate the combination of HMRF and BFGS algorithm to perform the segmentation operation. The proposed method shows very good segmentation results comparing with well-known approaches. The tests are conducted on brain magnetic resonance image databases (BrainWeb and IBSR) largely used to objectively confront the results obtained. The well-known Dice coefficient (DC) was used as similarity metric. The experimental results show that, in many cases, our proposed method approaches the perfect segmentation with a Dice Coefficient above .9. Moreover, it generally outperforms other methods in the tests conducted.

Multi-scale properties of large eddy simulations: correlations between resolved-scale velocity-field increments and subgrid-scale quantities

NASA Astrophysics Data System (ADS)

Linkmann, Moritz; Buzzicotti, Michele; Biferale, Luca

2018-06-01

We provide analytical and numerical results concerning multi-scale correlations between the resolved velocity field and the subgrid-scale (SGS) stress-tensor in large eddy simulations (LES). Following previous studies for Navier-Stokes equations, we derive the exact hierarchy of LES equations governing the spatio-temporal evolution of velocity structure functions of any order. The aim is to assess the influence of the subgrid model on the inertial range intermittency. We provide a series of predictions, within the multifractal theory, for the scaling of correlation involving the SGS stress and we compare them against numerical results from high-resolution Smagorinsky LES and from a-priori filtered data generated from direct numerical simulations (DNS). We find that LES data generally agree very well with filtered DNS results and with the multifractal prediction for all leading terms in the balance equations. Discrepancies are measured for some of the sub-leading terms involving cross-correlation between resolved velocity increments and the SGS tensor or the SGS energy transfer, suggesting that there must be room to improve the SGS modelisation to further extend the inertial range properties for any fixed LES resolution.

Modelisation numerique d'un actionneur plasma de type decharge a barriere dielectrique par la methode de derive-diffusion

NASA Astrophysics Data System (ADS)

Xing, Jacques

Dielectric barrier discharge (DBD) plasma actuator is a proposed device for active for control in order to improve the performances of aircraft and turbomachines. Essentially, these actuators are made of two electrodes separated by a layer of dielectric material and convert electricity directly into flow. Because of the high costs associated with experiences in realistic operating conditions, there is a need to develop a robust numerical model that can predict the plasma body force and the effects of various parameters on it. Indeed, this plasma body force can be affected by atmospheric conditions (temperature, pressure, and humidity), velocity of the neutral flow, applied voltage (amplitude, frequency, and waveform), and by the actuator geometry. In that respect, the purpose of this thesis is to implement a plasma model for DBD actuator that has the potential to consider the effects of these various parameters. In DBD actuator modelling, two types of approach are commonly proposed, low-order modelling (or phenomenological) and high-order modelling (or scientific). However a critical analysis, presented in this thesis, showed that phenomenological models are not robust enough to predict the plasma body force without artificial calibration for each specific case. Moreover, there are based on erroneous assumptions. Hence, the selected approach to model the plasma body force is a scientific drift-diffusion model with four chemical species (electrons, positive ions, negative ions, and neutrals). This model was chosen because it gives consistent numerical results comparatively with experimental data. Moreover, this model has great potential to include the effect of temperature, pressure, and humidity on the plasma body force and requires only a reasonable computational time. This model was independently implemented in C++ programming language and validated with several test cases. This model was later used to simulate the effect of the plasma body force on the laminar-turbulent transition on airfoil in order to validate the performance of this model in practical CFD simulation. Numerical results show that this model gives a better prediction of the effect of the plasma on the fluid flow for a practical case in aerospace than a phenomenological model.

Processus de modelisation et etude des orages geomagnetiques dans les reseaux electriques: Impact sur le reseau de transport d'Hydro-Quebec

NASA Astrophysics Data System (ADS)

Abdellaoui, Amr

This research project presents a complete modelling process of the effects of GIC on Hydro-Quebec power system network for system planning studies. The advantage of the presented method is that it enables planning engineers to simulate the effects of geomagnetic disturbances on the Hydro-Quebec System under different conditions and contingencies within reasonable calculation time frame. This modelling method of GIC in electric power systems has been applied to the Hydro-Quebec System. An equivalent HQ DC model has been achieved. A numerical calculation method of DC sources from a non-uniform geoelectric field has been developed and implemented on HQ DC model. Harmonics and increased reactive power losses of saturated transformers have been defined as a function of GIC through a binary search algorithm using a chosen HQ magnetization curve. The evolution in time of each transformer saturation according to its effective GIC has been evaluated using analytical formulas. The reactive power losses of saturated transformers have been modeled in PSS/E[1] HQ network as constant reactive current loads assigned to the corresponding transformer buses. Finally, time domain simulations have been performed with PSS/E taking into account transformer saturation times. This has been achieved by integrating HQ DC model results and analytical calculations results of transformer saturation times into an EMTP load model. An interface has been used to link EMTP load model to HQ PSS/E network. Different aspects of GIC effects on the Hydro-Quebec system have been studied, including the influence of uniform and non-uniform geoelectric fields, the comparison of reactive power losses of the 735kV HQ system with those of Montreal network, the risks to voltage levels and the importance of reactive power dynamic reserve. This dissertation presents a new GIC modelling approach for power systems for planning and operations purposes. This methodology could be further enhanced, particularly, the aspect regarding the transformer saturation times. Hence more research remains to be pursued in this area.

Utilization of the multiple scattering model for the conception of heterogeneous materials with specific electromagnetic properties

NASA Astrophysics Data System (ADS)

Vignéras-Lefebvre, V.; Miane, J. L.; Parneix, J. P.

1993-03-01

A modelisation of the behaviour of heterogeneous structures, made with spherical particles, submitted to microwave fields, using multiple scattering, is presented. First of all, we expose the principle of scattering by a single sphere, using Mie's equations represented in the form of a transfer matrix. This matrix, generalized to a distribution of particles, allows the translation of an average behaviour of the material. As part of the limit of Rayleigh, the value of the effective permittivity thus obtained is compared to experimental results. Une modélisation du comportement de structures hétérogènes composées de particules sphériques, soumises à des champs hyperfréquences, utilisant la multidiffusion, est présentée. Dans un premier temps, nous exposons le principe de la diffusion par une seule sphère en utilisant les équations de Mie représentées sous forme matricielle. Cette matrice généralisée à une distribution de particules permet de traduire un comportement moyen du matériau. Dans le cadre de l'approximation de Rayleigh, la valeur de la permittivité ainsi calculée est comparée à des résultats expérimentaux.

Formulation, caracterisation, modelisation et prevision du comportement thermomecanique des pieces plastiques et composites de fibres de bois : Application aux engrenages =

NASA Astrophysics Data System (ADS)

Mijiyawa, Faycal

Cette etude permet d'adapter des materiaux composites thermoplastiques a fibres de bois aux engrenages, de fabriquer de nouvelles generations d'engrenages et de predire le comportement thermique de ces engrenages. Apres une large revue de la litterature sur les materiaux thermoplastiques (polyethylene et polypropylene) renforces par les fibres de bois (bouleau et tremble), sur la formulation et l'etude du comportement thermomecanique des engrenages en plastique-composite; une relation a ete etablie avec notre presente these de doctorat. En effet, beaucoup d'etudes sur la formulation et la caracterisation des materiaux composites a fibres de bois ont ete deja realisees, mais aucune ne s'est interessee a la fabrication des engrenages. Les differentes techniques de formulation tirees de la litterature ont facilite l'obtention d'un materiau composite ayant presque les memes proprietes que les materiaux plastiques (nylon, acetal...) utilises dans la conception des engrenages. La formulation des materiaux thermoplastiques renforces par les fibres de bois a ete effectuee au Centre de recherche en materiaux lignocellulosiques (CRML) de l'Universite du Quebec a Trois-Rivieres (UQTR), en collaboration avec le departement de Genie Mecanique, en melangeant les composites avec deux rouleaux sur une machine de type Thermotron-C.W. Brabender (modele T-303, Allemand) ; puis des pieces ont ete fabriquees par thermocompression. Les thermoplastiques utilises dans le cadre de cette these sont le polypropylene (PP) et le polyethylene haute densite (HDPE), avec comme renfort des fibres de bouleau et de tremble. A cause de l'incompatibilite entre la fibre de bois et le thermoplastique, un traitement chimique a l'aide d'un agent de couplage a ete realise pour augmenter les proprietes mecaniques des materiaux composites. Pour les composites polypropylene/bois : (1) Les modules elastiques et les contraintes a la rupture en traction des composites PP/bouleau et PP/tremble evoluent lineairement en fonction du taux de fibres, avec ou sans agent de couplage (Maleate de polypropylene MAPP). De plus, l'adherence entre les fibres de bois et le plastique est amelioree en utilisant seulement 3 % MAPP, entrainant donc une augmentation de la contrainte maximale bien qu'aucun effet significatif ne soit observe sur le module d'elasticite. (2) Les resultats obtenus montrent que, en general, les proprietes en traction des composites polypropylene/bouleau, polypropylene/tremble et polypropylene/bouleau/ tremble sont tres semblables. Les composites plastique-bois (WPCs), en particulier ceux contenant 30 % et 40 % de fibres, ont des modules elastiques plus eleves que certains plastiques utilises dans l'application des engrenages (ex. Nylon). Pour les composites polyethylene/bois, avec 3%Maleate de polyethylene (MAPE): (1) Tests de traction : le module elastique passe de 1.34 GPa a 4.19 GPa pour le composite HDPE/bouleau, alors qu'il passe de 1.34 GPa a 3.86 GPa pour le composite HDPE/tremble. La contrainte maximale passe de 22 MPa a 42.65 MPa pour le composite HDPE/bouleau, alors qu'elle passe de 22 MPa a 43.48 MPa pour le composite HDPE/tremble. (2) Tests de flexion : le module elastique passe de 1.04 GPa a 3.47 GPa pour le composite HDPE/bouleau et a 3.64 GPa pour le composite HDPE/tremble. La contrainte maximale passe de 23.90 MPa a 66.70 MPa pour le composite HDPE/bouleau, alors qu'elle passe a 59.51 MPa pour le composite HDPE/tremble. (3) Le coefficient de Poisson determine par impulsion acoustique est autour de 0.35 pour tous les composites HDPE/bois. (4) Le test de degradation thermique TGA nous revele que les materiaux composites presentent une stabilite thermique intermediaire entre les fibres de bois et la matrice HDPE. (5) Le test de mouillabilite (angle de contact) revele que l'ajout de fibres de bois ne diminue pas de facon significative les angles de contact avec de l'eau parce que les fibres de bois (bouleau ou tremble) semblent etre enveloppees par la matrice sur la surface des composites, comme le montrent des images prises au microscope electronique a balayage MEB. (6) Le modele de Lavengoof-Goettler predit mieux le module elastique du composite thermoplastique/bois. (7) Le HDPE renforce par 40 % de bouleau est mieux adapte pour la fabrication des engrenages, car le retrait est moins important lors du refroidissement au moulage. La simulation numerique semble mieux predire la temperature d'equilibre a la vitesse de 500 tr/min; alors qu'a 1000 tr/min, on remarque une divergence du modele. (Abstract shortened by ProQuest.). None None None None None None None None

On the connection between financial processes with stochastic volatility and nonextensive statistical mechanics

NASA Astrophysics Data System (ADS)

Queirós, S. M. D.; Tsallis, C.

2005-11-01

The GARCH algorithm is the most renowned generalisation of Engle's original proposal for modelising returns, the ARCH process. Both cases are characterised by presenting a time dependent and correlated variance or volatility. Besides a memory parameter, b, (present in ARCH) and an independent and identically distributed noise, ω, GARCH involves another parameter, c, such that, for c=0, the standard ARCH process is reproduced. In this manuscript we use a generalised noise following a distribution characterised by an index qn, such that qn=1 recovers the Gaussian distribution. Matching low statistical moments of GARCH distribution for returns with a q-Gaussian distribution obtained through maximising the entropy Sq=1-sumipiq/q-1, basis of nonextensive statistical mechanics, we obtain a sole analytical connection between q and left( b,c,qnright) which turns out to be remarkably good when compared with computational simulations. With this result we also derive an analytical approximation for the stationary distribution for the (squared) volatility. Using a generalised Kullback-Leibler relative entropy form based on Sq, we also analyse the degree of dependence between successive returns, zt and zt+1, of GARCH(1,1) processes. This degree of dependence is quantified by an entropic index, qop. Our analysis points the existence of a unique relation between the three entropic indexes qop, q and qn of the problem, independent of the value of (b,c).

Towards self-consistent plasma modelisation in presence of neoclassical tearing mode and sawteeth: effects on transport coefficients

NASA Astrophysics Data System (ADS)

Basiuk, V.; Huynh, P.; Merle, A.; Nowak, S.; Sauter, O.; Contributors, JET; the EUROfusion-IM Team

2017-12-01

The neoclassical tearing modes (NTM) increase the effective heat and particle radial transport inside the plasma, leading to a flattening of the electron and ion temperature and density profiles at a given location depending on the safety factor q rational surface (Hegna and Callen 1997 Phys. Plasmas 4 2940). In burning plasma such as in ITER, this NTM-induced increased transport could reduce significantly the fusion performance and even lead to a disruption. Validating models describing the NTM-induced transport in present experiment is thus important to help quantifying this effect on future devices. In this work, we apply an NTM model to an integrated simulation of current, heat and particle transport on JET discharges using the European transport simulator. In this model, the heat and particle radial transport coefficients are modified by a Gaussian function locally centered at the NTM position and characterized by a full width proportional to the island size through a constant parameter adapted to obtain the best simulations of experimental profiles. In the simulation, the NTM model is turned on at the same time as the mode is triggered in the experiment. The island evolution is itself determined by the modified Rutherford equation, using self-consistent plasma parameters determined by the transport evolution. The achieved simulation reproduces the experimental measurements within the error bars, before and during the NTM. A small discrepancy is observed on the radial location of the island due to a shift of the position of the computed q = 3/2 surface compared to the experimental one. To explain such small shift (up to about 12% with respect to the position observed from the experimental electron temperature profiles), sensitivity studies of the NTM location as a function of the initialization parameters are presented. First results validate both the transport model and the transport modification calculated by the NTM model.

Mechanical behavior and modelisation of Ti-6Al-4V titanium sheet under hot stamping conditions

NASA Astrophysics Data System (ADS)

Sirvin, Q.; Velay, V.; Bonnaire, R.; Penazzi, L.

2017-10-01

The Ti-6Al-4V titanium alloy is widely used for the manufacture of aeronautical and automotive parts (solid parts). In aeronautics, this alloy is employed for its excellent mechanical behavior associated with low density, outstanding corrosion resistance and good mechanical properties up to 600°C. It is especially used for the manufacture of fuselage frames, on the pylon for carrying out the primary structure (machining forged blocks) and the secondary structure in sheet form. In this last case, the sheet metal forming can be done through various methods: at room temperature by drawing operation, at very high temperature (≃900°C) by superplastic forming (SPF) and at intermediate temperature (≥750°C) by hot forming (HF). In order to reduce production costs and environmental troubles, the cycle times reduction associated with a decrease of temperature levels are relevant. This study focuses on the behavior modelling of Ti-6Al-4V alloy at temperatures above room temperature to obtained greater formability and below SPF condition to reduce tools workshop and energy costs. The displacement field measurement obtained by Digital Image Correlation (DIC) is based on innovative surface preparation pattern adapted to high temperature exposures. Different material parameters are identified to define a model able to predict the mechanical behavior of Ti-6Al-4V alloy under hot stamping conditions. The hardening plastic model identified is introduced in FEM to simulate an omega shape forming operation.

Scaling forecast models for wind turbulence and wind turbine power intermittency

NASA Astrophysics Data System (ADS)

Duran Medina, Olmo; Schmitt, Francois G.; Calif, Rudy

2017-04-01

The intermittency of the wind turbine power remains an important issue for the massive development of this renewable energy. The energy peaks injected in the electric grid produce difficulties in the energy distribution management. Hence, a correct forecast of the wind power in the short and middle term is needed due to the high unpredictability of the intermittency phenomenon. We consider a statistical approach through the analysis and characterization of stochastic fluctuations. The theoretical framework is the multifractal modelisation of wind velocity fluctuations. Here, we consider three wind turbine data where two possess a direct drive technology. Those turbines are producing energy in real exploitation conditions and allow to test our forecast models of power production at a different time horizons. Two forecast models were developed based on two physical principles observed in the wind and the power time series: the scaling properties on the one hand and the intermittency in the wind power increments on the other. The first tool is related to the intermittency through a multifractal lognormal fit of the power fluctuations. The second tool is based on an analogy of the power scaling properties with a fractional brownian motion. Indeed, an inner long-term memory is found in both time series. Both models show encouraging results since a correct tendency of the signal is respected over different time scales. Those tools are first steps to a search of efficient forecasting approaches for grid adaptation facing the wind energy fluctuations.

A Simplified and Reliable Damage Method for the Prediction of the Composites Pieces

NASA Astrophysics Data System (ADS)

Viale, R.; Coquillard, M.; Seytre, C.

2012-07-01

Structural engineers are often faced to test results on composite structures largely tougher than predicted. By attempting to reduce this frequent gap, a survey of some extensive synthesis works relative to the prediction methods and to the failure criteria was led. This inquiry dealts with the plane stress state only. All classical methods have strong and weak points wrt practice and reliability aspects. The main conclusion is that in the plane stress case, the best usaul industrial methods give predictions rather similar. But very generally they do not explain the often large discrepancies wrt the tests, mainly in the cases of strong stress gradients or of bi-axial laminate loadings. It seems that only the methods considering the complexity of the composites damages (so-called physical methods or Continuum Damage Mechanics “CDM”) bring a clear mending wrt the usual methods..The only drawback of these methods is their relative intricacy mainly in urged industrial conditions. A method with an approaching but simplified representation of the CDM phenomenology is presented. It was compared to tests and other methods: - it brings a fear improvement of the correlation with tests wrt the usual industrial methods, - it gives results very similar to the painstaking CDM methods and very close to the test results. Several examples are provided. In addition this method is really thrifty wrt the material characterization as well as for the modelisation and the computation efforts.

[Relapse: causes and consequences].

PubMed

Thomas, P

2013-09-01

Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Codigestion of solid wastes: a review of its uses and perspectives including modeling.

PubMed

Mata-Alvarez, Joan; Dosta, Joan; Macé, Sandra; Astals, Sergi

2011-06-01

The last two years have witnessed a dramatic increase in the number of papers published on the subject of codigestion, highlighting the relevance of this topic within anaerobic digestion research. Consequently, it seems appropriate to undertake a review of codigestion practices starting from the late 1970s, when the first papers related to this concept were published, and continuing to the present day, demonstrating the exponential growth in the interest shown in this approach in recent years. Following a general analysis of the situation, state-of-the-art codigestion is described, focusing on the two most important areas as regards publication: codigestion involving sewage sludge and the organic fraction of municipal solid waste (including a review of the secondary advantages for wastewater treatment plant related to biological nutrient removal), and codigestion in the agricultural sector, that is, including agricultural - farm wastes, and energy crops. Within these areas, a large number of oversized digesters appear which can be used to codigest other substrates, resulting in economic and environmental advantages. Although the situation may be changing, there is still a need for good examples on an industrial scale, particularly with regard to wastewater treatment plants, in order to extend this beneficial practice. In the last section, a detailed analysis of papers addressing the important aspect of modelisation is included. This analysis includes the first codigestion models to be developed as well as recent applications of the standardised anaerobic digestion model ADM1 to codigestion. (This review includes studies ranging from laboratory to industrial scale.).

Long-term analyses of snow dynamics within the french Alps on the 1900-2100 period. Analyses of historical snow water equivalent observations, modelisations and projections of a hundred of snow courses.

NASA Astrophysics Data System (ADS)

Mathevet, T.; Joel, G.; Gottardi, F.; Nemoz, B.

2017-12-01

The aim of this communication is to present analyses of climate variability and change on snow water equivalent (SWE) observations, reconstructions (1900-2016) and scenarii (2020-2100) of a hundred of snow courses dissiminated within the french Alps. This issue became particularly important since a decade, in regions where snow variability had a large impact on water resources availability, poor snow conditions in ski resorts and artificial snow production. As a water resources manager in french mountainuous regions, EDF (french hydropower company) has developed and managed a hydrometeorological network since 1950. A recent data rescue research allowed to digitize long term SWE manual measurments of a hundred of snow courses within the french Alps. EDF have been operating an automatic SWE sensors network, complementary to the snow course network. Based on numerous SWE observations time-series and snow accumulation and melt model (Garavaglia et al., 2017), continuous daily historical SWE time-series have been reconstructed within the 1950-2016 period. These reconstructions have been extented to 1900 using 20 CR reanalyses (ANATEM method, Kuentz et al., 2015) and up to 2100 using GIEC Climate Change scenarii. Considering various mountainous areas within the french Alps, this communication focuses on : (1) long term (1900-2016) analyses of variability and trend of total precipitation, air temperature, snow water equivalent, snow line altitude, snow season length , (2) long term variability of hydrological regime of snow dominated watersheds and (3) future trends (2020 -2100) using GIEC Climate Change scenarii. Comparing historical period (1950-1984) to recent period (1984-2016), quantitative results within a region in the north Alps (Maurienne) shows an increase of air temperature by 1.2 °C, an increase of snow line height by 200m, a reduction of SWE by 200 mm/year and a reduction of snow season length by 15 days. These analyses will be extended from north to south of the Alps, on a region spanning 200 km. Caracterisation of the increase of snow line height and SWE reduction are particularly important at a local and watershed scale. This long term change of snow dynamics within moutainuous regions both impacts snow resorts and artificial snow production developments and multi-purposes dam reservoirs managments.

Modelisation agregee de chauffe-eau electriques commandes par champ moyen pour la gestion des charges dans un reseau

NASA Astrophysics Data System (ADS)

Losseau, Romain

The ongoing energy transition is about to entail important changes in the way we use and manage energy. In this view, smart grids are expected to play a significant part through the use of intelligent storage techniques. Initiated in 2014, the SmartDesc project follows this trend to create an innovative load management program by exploiting the thermal storage associated with electric water heaters existing in residential households. The device control algorithms rely on the recent theory of mean field games to achieve a decentralized control of the water heaters temperatures producing an aggregate optimal trajectory, designed to smooth the electric demand of a neighborhood. Currently, this theory does not include power and temperature constraints due to the tank heating system or necessary for the user's safety and comfort. Therefore, a trajectory violating these constraints would not be feasible and would not induce the forecast load smoothing. This master's thesis presents a method to detect the non-feasability, of a target trajectory based on the Kolmogorov equations associated with the controlled electric water heaters and suggests a way to correct it so as to make it achievable under constraints. First, a partial differential equations based model of the water heaters under temperature constraints is presented. Subsequently, a numerical scheme is developed to simulate it, and applied to the mean field control. The results of the mean field control with and without constraints are compared, and non-feasabilities of the target trajectory are highlighted upon violations. The last part of the thesis is dedicated to developing an accelerated version of the mean field and a method of correcting the target trajectory so as to enlarge as much as possible the set of achievable profiles.

Modelling a radiology department service using a VDL integrated approach.

PubMed

Guglielmino, Maria Gabriella; Celano, Giovanni; Costa, Antonio; Fichera, Sergio

2009-01-01

The healthcare industry is facing several challenges such as the reduction of costs and quality improvement of the provided services. Engineering studies could be very useful in supporting organizational and management processes. Healthcare service efficiency depends on a strong collaboration between clinical and engineering experts, especially when it comes to analyzing the system and its constraints in detail and subsequently, when it comes to deciding on the reengineering of some key activities. The purpose of this paper is to propose a case study showing how a mix of representation tools allow a manager of a radiology department to solve some human and technological resource re-organizational issues, which have to be faced due to the introduction of a new technology and a new portfolio of services. In order to simulate the activities within the radiology department and examine the relationship between human and technological resources, different visual diagrammatic language (VDL) techniques have been implemented to get knowledge about the heterogeneous factors related to the healthcare service delivery. In particular, flow charts, IDEFO diagrams and Petri nets have been integrated each other with success as a modelisation tools. The simulation study performed through the application of the aforementioned VDL techniques suggests the opportunity of re-organizing the nurse activities within the radiology department. The re-organization of a healthcare service and in particular of a radiology department by means of joint flow charts, IDEF0 diagrams and Petri nets is a poorly investigated topic in literature. This paper demonstrates how flow charts and IDEF0 can help people working within the department to understand the weak points of their organization and constitute an efficient base of knowledge for the implementation of a Petri net aimed at improving the departmental performance.

Geographical variation of overweight, obesity and related risk factors: Findings from the European Health Examination Survey in Luxembourg, 2013-2015.

PubMed

Samouda, Hanen; Ruiz-Castell, Maria; Bocquet, Valery; Kuemmerle, Andrea; Chioti, Anna; Dadoun, Frédéric; Kandala, Ngianga-Bakwin; Stranges, Saverio

2018-01-01

The analyses of geographic variations in the prevalence of major chronic conditions, such as overweight and obesity, are an important public health tool to identify "hot spots" and inform allocation of funding for policy and health promotion campaigns, yet rarely performed. Here we aimed at exploring, for the first time in Luxembourg, potential geographic patterns in overweight/obesity prevalence in the country, adjusted for several demographic, socioeconomic, behavioural and health status characteristics. Data came from 720 men and 764 women, 25-64 years old, who participated in the European Health Examination Survey in Luxembourg (2013-2015). To investigate the geographical variation, geo-additive semi-parametric mixed model and Bayesian modelisations based on Markov Chain Monte Carlo techniques for inference were performed. Large disparities in the prevalence of overweight and obesity were found between municipalities, with the highest rates of obesity found in 3 municipalities located in the South-West of the country. Bayesian approach also underlined a nonlinear effect of age on overweight and obesity in both genders (significant in men) and highlighted the following risk factors: 1. country of birth for overweight in men born in a non-European country (Posterior Odds Ratio (POR): 3.24 [1.61-8.69]) and women born in Portugal (POR: 2.44 [1.25-4.43]), 2. low educational level (secondary or below) for overweight (POR: 1.66 (1.06-2.72)] and obesity (POR:2.09 [1.05-3.65]) in men, 3. single marital status for obesity in women (POR: 2.20 [1.24-3.91]), 4.fair (men: POR: 3.19 [1.58-6.79], women: POR: 2.24 [1.33-3.73]) to very bad health perception (men: POR: 15.01 [2.16-98.09]) for obesity, 5. sleeping more than 6 hours for obesity in unemployed men (POR: 3.66 [2.02-8.03]). Protective factors highlighted were: 1. single marital status against overweight (POR: [0.60 (0.38-0.96)]) and obesity (POR: 0.39 [0.16-0.84]) in men, 2. the fact to be widowed against overweight in women (POR: [0.30 (0.07-0.86)], as well as a non European country of birth (POR: 0.49 [0.19-0.98]), tertiary level of education (POR: 0.34 [0.18-0.64]), moderate alcohol consumption (POR: 0.54 [0.36-0.90]) and aerobic physical activity practice (POR: 0.44 [0.27-0.77]) against obesity in women. A double burden of environmental exposure due to historic mining and industrial activities and past economic vulnaribility in the South-West of the country may have participated to the higher prevalence of obesity found in this region. Other demographic, socioeconomic, behavioural and health status covariates could have been involved as well.

Approches pour la reduction de l'impact de defaut dans le transport d'energie du parc eolien offshore via VSC-HVDC =

NASA Astrophysics Data System (ADS)

Benadja, Mounir

Dans ce travail est presente un systeme de generation d'energie d'un parc eolien offshore et un systeme de transport utilisant les stations VSC-HVDC connectees au reseau principal AC onshore. Trois configurations ont ete etudiees, modelisees et validees par simulation. Dans chacune des configurations, des contributions ameliorant les cotes techniques et economiques sont decrites ci-dessous : La premiere contribution concerne un nouvel algorithme MPPT (Maximum Power Point Tracking) utilise pour l'extraction de la puissance maximale disponible dans les eoliennes des parcs offshores. Cette technique d'extraction du MPPT ameliore le rendement energetique de la chaine de conversion des energies renouvelables notamment l'energie eolienne a petite et a grande echelles (parc eolien offshore) qui constitue un probleme pour les constructeurs qui se trouvent confrontes a developper des dispositifs MPPT simples, moins couteux, robustes, fiables et capable d'obtenir un rendement energetique maximal. La deuxieme contribution concerne la reduction de la taille, du cout et de l'impact des defauts electriques (AC et DC) dans le systeme construit pour transporter l'energie d'un parc eolien offshore (OWF) vers le reseau principal AC onshore via deux stations 3L-NPC VSCHVDC. La solution developpee utilise des observateurs non-lineaires bases sur le filtre de Kalman etendu (EKF). Ce filtre permet d'estimer la vitesse de rotation et la position du rotor de chacune des generatrices du parc eolien offshore et de la tension du bus DC de l'onduleur DC-AC offshore et des deux stations 3L-NPC-VSC-HVDC (offshore et onshore). De plus, ce developpement du filtre de Kalman etendu a permis de reduire l'impact des defauts AC et DC. Deux commandes ont ete utilisees, l'une (commande indirect dans le plan abc) avec EKF integre destinee pour controler le convertisseur DC-AC offshore et l'autre (commande d-q) avec EKF integre pour controler les convertisseurs des deux stations AC-DC et DC-AC tout en tenant compte des entrees de chacune des stations. L'integration des observateurs non-lineaires (EKF) dans le controle des convertisseurs permet de resoudre le probleme des incertitudes de mesure, des incertitudes dans la modelisation, en cas du dysfonctionnement ou de panne des capteurs de mesure ainsi que le probleme de l'impact des defauts (AC et DC) sur la qualite d'energie dans les systemes de transmission. Ces estimations contribuent a rendre le cout global du systeme moins cher et sa taille moins encombrante ainsi que la reduction de l'impact des defauts (AC et DC) sur le systeme. La troisieme contribution concerne la reduction de la taille, du cout et de l'impact des defauts electriques (AC et DC) dans le systeme construit pour transporter l'energie d'un parc eolien offshore (OWF) vers le reseau principal AC onshore via deux stations VSC-HVDC. La solution developpee utilise des observateurs non-lineaires bases sur le filtre de Kalman etendu (EKF). Ce filtre permet d'estimer la vitesse de rotation et la position du rotor de chacune des generatrices du parc eolien et de la tension du bus DC de l'onduleur DC-AC offshore. La contribution porte surtout sur le developpement des deux commandes des deux stations. La premiere, la commande non-lineaire modifiee pour controler le premier convertisseur de la station VSC-HVDC offshore assurant le transfert de la puissance generee par le parc eolien vers la station VSC-HVDC onshore. La deuxieme commande non-lineaire modifiee avec integration de la regulation de la tension du bus DC et de la commande a modele de reference adaptative (MRAC) pour la compensation des surintensites et surtensions durant les defauts AC et DC. On peut constater que lors d'un defaut AC au PCC (Point of Common Coupling) du cote reseau onshore, la profondeur de l'impact du defaut AC sur l'amplitude des courants du reseau principal AC onshore qui etait reduit a 60% par les travaux de recherche (Erlich, Feltes et Shewarega, 2014), comparativement a la nouvelle commande proposee MRAC qui reduit la profondeur de l'impact a 35%. Lors de l'apparition des defauts AC et DC, une reduction de l'impact des defauts sur l'amplitude des courants de reseau AC terrestre et du temps de reponse a ete observee et la stabilite du systeme a ete renforcee par l'utilisation de la commande adaptative basee sur le modele de reference MRAC. La quatrieme contribution concerne une nouvelle commande basee sur le mode de glissement (SM) appliquee pour la station VSC-HVDC qui relie le parc eolien offshore (OWF) au reseau principal AC. Ce parc est compose de dix eoliennes basees sur des generatrices synchrones a aimant permanent (VSWT/PMSGs) connectees en parallele et chacune est controlee par son propre convertisseur DC-DC. Une comparaison des performances entre la commande SM et de la commande non-lineaire avec des controleurs PI pour les deux conditions (presence et absence de defaut DC) a ete analysee et montre la superiorite de la commande par SM. Un prototype du systeme etudie a echelle reduite a ete realise et teste au laboratoire GREPCI en utilisant la carte dSPACE-DS1104 pour la validation experimentale. L'analyse et la simulation des systemes etudies sont developpees sous l'environnement Matlab/Simulink/Simpowersystem. Les resultats obtenus a partir des configurations developpees sont valides par simulation et par experimentation. Les performances sont tres satisfaisantes du point de vue reponse dynamique, reponse en regime permanent, stabilite du systeme et qualite de l'energie.

NASA TEERM Hexavalent Chrome Alternatives Projects

DTIC Science & Technology

2011-08-18

1 N2-2 N3-2 N4-2 N5-2 N6-2 N7-2 N8-2 N9-2 N10-2 N11-2 N12-2 N13-2 H H2-1 H3-1 H4-1 H5-1 H6-1 H7-1 H8-1 H9-1 H10-1 H11-1 H12-1 H13 -1 H2-2 H3-2 H4-2...H5-2 H6-2 H7-2 H8-2 H9-2 H10-2 H11-2 H12-2 H13 -2 D D2-1 D3-1 D4-1 D5-1 D6-1 D7-1 D8-1 D9-1 D10-1 D11-1 D12-1 D13-1 D2-2 D3-2 D4-2 D5-2 D6-2 D7-2...Color, Adhesion, Impact , Flexibility, Fluid Resistance, Filiform Corrosion, Salt-Spray Corrosion, Artificial Weathering, Stripability, Restoration

Optimum Aeroelastic Characteristics for Composite Supermaneuverable Aircraft.

DTIC Science & Technology

1986-07-31

1󈨌D22 1 k 16 ’ cD 22YI Y6 WL k 17 ’ cD 22 Y, Y7 k 18 ’ -2cD 26YI1 Y6 gi 0 k19 : -2cD26Y I y 7 k1,10 12 2c Bo 10 1 󈧐D22 1 10 22 cD22 (y2 )2 k23 -2cD...2 6y1Y2 k24 -2cD 2 6 Y2Y 2 3 ,, 11 10 k -S-D + 2cD a 25 12 D22 5 2 12 5 2 k26 cD22 Y2 Y6 k27 cD22 y2 Y7 28 -2cD 2 6 Y2 Y6 k29 -2cD 26Y2 Y7 k’ "" 0y

Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

PubMed

Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

2016-04-14

There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial.

PubMed

Hammami, Muhammad M; Yusuf, Ahmed

2017-02-24

Vitamin D (D) supplements are indispensable for its world-wide deficiency. Controversy continues on ergocalciferol (D2) and cholecalciferol (D3) relative potency as well as on dosing-schedule and sex role in raising 25-hydroxy D (25(OH)D) level, the best indicator of D status. We randomized 279 adults to daily D2, D3, D2/D3, or placebo; 2-weekly D2 or D3; or 4-weekly D2 or D3 (250,000 IU over/140 days). Randomization sequence, stratified by body-mass-index (BMI) and sex, was concealed from study coordinators and participants who were then blinded to capsules' content. D2, D3, 25(OH)D2, and 25(OH)D3 Serum levels were determined blindly on days 0,1,2,3,4,7,14, and 2-weekly thereafter by high performance liquid chromatography assay. The results of 269 participants were available for analysis. Primary endpoint was area-under-the-curve (AUC) of 25(OH)D (25(OH)D2 + 25(OH)D3) adjusted for sex, BMI, and baseline 25(OH)D level. Mean(SD) age was 33.0(8.5) year, 41% were males, and 85% completed follow-up. Baseline 25(OH)D level was 39.8(11.9) and increased by 3.3(11.6) and 28.6(16.3) nmol/L, in the placebo and active-treatment groups, respectively. AUC from day 0 to 140 (AUC 140 ) of 25(OH)D was 40% (D3 daily) to 55% (D3 2-weekly) higher with active-treatment than placebo (p < 0.001). 25(OH)D2 AUC 140 was higher in daily than 2-weekly (17%, p = 0.006) and 4-weekly (20%, p = 0.001) D2-treated groups. 25(OH)D3 AUC 140 was lower in daily than 2-weekly (11%, p = 0.002) and 4-weekly D3-treated groups (10%, p = 0.008). In D2-treated groups, there was 16.4 nmol/L decrease in 25(OH)D3 level that correlated (p < 0.001) with 25(OH)D2 level increase (r = 0.48) and baseline 25(OH)D level (r = 0.58), in one participant with measurable baseline 25(OH)D2 level, D3 caused a similar decrease in 25(OH)D2 level, while in the D2/D3-treated group, 25(OH)D3 level didn't increase. Incremental AUC from day 0 to 7 (AUC 7 ) of D3 and 25(OH)D3 in D3-treated groups were 118-243% higher and 31-39% lower, respectively, than incremental AUC 7 of D2 and 25(OH)D2 in D2-treated groups. Incremental AUC 7 of D3 and 25(OH)D3 in D3-treated groups and D2 and 25(OH)D2 in D2-treated groups were higher in females than males (55, 13, 64, and 28%, respectively). Baseline 25(OH)D level predicted response to D2 and D3 (p < 0.001), whereas, BMI was significant predictor only for early response to D2. Effects of D2 and D3 supplements on 25 (OH)D level may be dosing-schedule and sex-dependent. D2-associated reduction in 25(OH)D3 level may be related to total 25(OH)D level rather than being D2-specific. D2 may be 25-hydroxylated faster than D3. ClinicalTrial.gov identifier: NCT01170494 (registered July 25, 2010).

The agreement between 3D, standard 2D and triplane 2D speckle tracking: effects of image quality and 3D volume rate.

PubMed

Trache, Tudor; Stöbe, Stephan; Tarr, Adrienn; Pfeiffer, Dietrich; Hagendorff, Andreas

2014-12-01

Comparison of 3D and 2D speckle tracking performed on standard 2D and triplane 2D datasets of normal and pathological left ventricular (LV) wall-motion patterns with a focus on the effect that 3D volume rate (3DVR), image quality and tracking artifacts have on the agreement between 2D and 3D speckle tracking. 37 patients with normal LV function and 18 patients with ischaemic wall-motion abnormalities underwent 2D and 3D echocardiography, followed by offline speckle tracking measurements. The values of 3D global, regional and segmental strain were compared with the standard 2D and triplane 2D strain values. Correlation analysis with the LV ejection fraction (LVEF) was also performed. The 3D and 2D global strain values correlated good in both normally and abnormally contracting hearts, though systematic differences between the two methods were observed. Of the 3D strain parameters, the area strain showed the best correlation with the LVEF. The numerical agreement of 3D and 2D analyses varied significantly with the volume rate and image quality of the 3D datasets. The highest correlation between 2D and 3D peak systolic strain values was found between 3D area and standard 2D longitudinal strain. Regional wall-motion abnormalities were similarly detected by 2D and 3D speckle tracking. 2DST of triplane datasets showed similar results to those of conventional 2D datasets. 2D and 3D speckle tracking similarly detect normal and pathological wall-motion patterns. Limited image quality has a significant impact on the agreement between 3D and 2D numerical strain values.

How to anticipate the assessment of the public health benefit of new medicines?

PubMed

Massol, Jacques; Puech, Alain; Boissel, Jean-Pierre

2007-01-01

The Public Health Benefit (PHB) of new medicines is a recent and French-specific criterion (October 1999 decree) which is often only partially documented in the transparency files due to a lack of timely information. At the time of the first reimbursement application for a new medicine to the "Transparency Committee", the file is exclusively based on data from randomised clinical trials. These data are generated from a global clinical development plan which was designed a long time before the new medicine's submission for reimbursement. And this plan does not systematically provide the data needed to assess the PHB. Thus, one easily understands the difficulty to anticipate and document this recent French criterion. In France, the PHB is both one of the necessary criteria for the reimbursement submission and an indicator for the national health policy management. Its assessment also helps to identify the needs and objectives of the post-registration studies (nowadays in the scope of responsibilities of the "Drug Economics Committee"). The assessment of the PHB criterion is carried through after the marketing authorization process and is an addition to it. To understand how to anticipate the assessment of the new medicines' PHB, one needs to consider how it differs from the preliminary step of the marketing authorization process. Whereas the evaluation for marketing authorization seeks to determine if the new medicine could be useful in a specific indication, the PHB assessment aims at quantifying the therapeutic benefit in a population, taking into account the reference treatments in this population. A new medicine receives a marketing authorization based on the data of the registration file which provides information on the clinical benefit of the new medicine in the populations of the trials and in the context of the trials. On the other side, the PHB looks at the effects of the new medicine at the scale of the general population, in real practice. The PHB components of a new medicine at first submission are the expected response of this new medicine to a public health need, the expected benefit on the health status of the population and ultimately the expected impact on the health care system. The benefit of a new medicine on the health status of a population is based on public health criteria which can be morbi-mortality or quality of life criteria. However, few registration files contain these public health criteria from the beginning and the predictive value of the surrogate criteria used in the trials is not always precisely assessed. It is, thus, difficult to quantify the expected benefit on these public health criteria. Moreover, the data that enable to quantify the new medicine's effects according to the various characteristics of the target population, are rarely available. Similarly, the French population epidemiological data related to the indication of the new medicine are often not available at the time of the assessment. Therefore it is difficult to evaluate the expected number of events that could be avoided if the new medicine reached the market. The authors suggest to adapt the clinical development plan for a better documentation of the PHB. They specifically recommend to integrate to the judgment criteria (endpoints) of the trials, criteria that are relevant in terms of public health, and to check for a good heterogeneity of the trial populations. They also suggest to start early enough collecting reliable national epidemiological data and the necessary elements for the assessment of the transposability of the trial results to the French population (ability to target the patients to be treated, adaptation of the healthcare system...). About the epidemiological data, the authors consider that the needs are covered in various ways depending on the diseases. To meet the needs of evaluation of the new medicines' target populations in specific indications, they recommend to use ad hoc studies as much as needed. In addition, epidemiological studies designed for market purpose with an acceptable methodology should not be systematically rejected but deserve to be presented. To be able to assess the importance of the expected theoretical benefit of a new medicine in a population, the authors underline the necessity to have access to study results with criteria related to this objective. They suggest to first define and list the criteria by disease. Regarding the representativity of the populations, it comes out that it would be advisable, but unrealistic to include in trials a population 100% representative of the population to be treated. Therefore the effect of the new medicine must be modelised (the "effect model") to be evaluated in the general population. Yet to obtain a reliable effect model, the study population must be sufficiently heterogeneous, which legitimates the demand to ensure a good population heterogeneity at the time of decision-making about trials methodology. When the criteria assessed during the development plan does not correspond to the PHB criteria, the only way to evaluate the number of events related to the PHB criterion is, again, to use modelisation. However, modelisation is only possible when the scientific literature has established a reliable correlation between the two types of criteria. In this case, the new model should be applied to a French target population to assess the expected benefit. As a conclusion, the possibilities to estimate the expected benefit of a new medicine on the health status of a specific population are currently limited. These limitations are regrettable because such an estimate is feasible without disrupting the development plans. The authors' general recommendations to update the development plans seem especially appropriate as the additions should not only be beneficial to France but to all the health authorities who would wish to assess the expected benefit of a new medicine on their territories. Anticipating the lack of clinical and epidemiological data and the lack of data that enable to evaluate the transposability of the trials results to real clinical practice is a sine qua none condition to improve the PHB assessment. The anticipation of these needs should be planned early enough by the pharmaceutical companies which could in this purpose meet the health authorities and the heads of the French public health policy in a consultation.Finally, because of the PHB's universal dimension, it is suggested that the necessary actions and publications be initiated so that the PHB can be acknowledged at the European level.

Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study.

PubMed

Manning, J T; Peters, M

2009-09-01

The ratio of the length of the second to the fourth digit (2D:4D) may be negatively correlated with prenatal testosterone. Hand preference has been linked with prenatal testosterone and 2D:4D. Here we show that 2D:4D is associated with hand preference for writing in a large internet sample (n>170,000) in which participants self-reported their finger lengths. We replicated a significant association between right 2D:4D and writing hand preference (low right 2D:4D associated with left hand preference) as well as a significant correlation between writing hand preference and the difference between left and right 2D:4D or Dr-l (low Dr-l associated with left hand preference). A new significant correlation between left 2D:4D and writing hand preference was also shown (high left 2D:4D associated with left hand preference). There was a clear interaction between writing hand preference and 2D:4D: The left 2D:4D was significantly larger than the right 2D:4D in male and female left-handed writers, and the right hand 2D:4D was significantly larger than the left hand 2D:4D in male and female right-handed writers.

New chemical constituents from Oryza sativa straw and their algicidal activities against blue-green algae.

PubMed

Ahmad, Ateeque; Kim, Seung-Hyun; Ali, Mohd; Park, Inmyoung; Kim, Jin-Seog; Kim, Eun-Hye; Lim, Ju-Jin; Kim, Seul-Ki; Chung, Ill-Min

2013-08-28

Five new constituents, 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-β-D-xylopyranosyl-(2a→1b)-2a-O-β-D-xylopyranosyl-(2b→1c)-2b-O-β-D-xylopyranosyl-2c-octadecanoate (1), 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-2d-octadecanoate (2), kaempferol-3-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-2d-hexadecanoate (3), methyl salicylate-2-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-(2d→1e)-2d-O-α-D-xylopyranosyl-(2e→1f)-2e-O-α-D-xylopyranosyl-(2f→1g)-2f-O-α-D-xylopyranosyl-(2g→1h)-2g-O-α-D-xylopyranosyl-2h-geranilan-8',10'-dioic acid-1'-oate (4), and oleioyl-β-D-arabinoside (5), along with eight known compounds, were isolated from a methanol extract of Oryza sativa straw. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopies in combination with IR, ESI/MS, and HR-ESI/FTMS. In bioassays with blue-green algae, the efficacies of the algicidal activities of the five new compounds (1-5) were evaluated at concentrations of 1, 10, and 100 mg/L. Compound 5 had the highest growth inhibition (92.6 ± 0.3%) for Microcystis aeruginosa UTEX 2388 at a concentration of 100 ppm (mg/L). Compound 5 has high potential for the ecofriendly control of weeds and algae harmful to water-logged rice.

24,25,28-Trihydroxyvitamin D sub 2 and 24,25,26-trihydroxyvitamin D sub 2 : Novel metabolites of vitamin D sub 2

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

Reddy, G.S.; Tserng, K.

1990-01-30

Understanding of the inactivation pathways of 25-hydroxyvitamin D{sub 2} and 24-hydroxyvitamin D{sub 2}, the two physiologically significant monohydroxylated metabolites of vitamin D{sub 2}, is of importance, especially during hypervitaminosis D{sub 2}. At present, little information is available regarding the inactivation pathway of 25-hydroxyvitamin D{sub 2} except its further metabolism into 24,25-dihydroxyvitamin D{sub 2}. In our present study, the authors investigated the metabolic fate of 25-hydroxyvitamin D{sub 2} in the isolated perfused rat kidney and demonstrated its conversion not only into 24,25-dihydroxyvitamin D{sub 2} but also into two other new metabolites, namely, 24,25,28-trihydroxyvitamin D{sub 2} and 24,25,26-trihydroxyvitamin D{sub 2}. The structuremore » identification of the new metabolites was established by the techniques of ultraviolet absorption spectrophotometry and mass spectrometry and by the characteristic nature of each new metabolite's susceptibility to sodium metaperiodate oxidation. In order to demonstrate the physiological significance of the two new trihydroxy metabolites of vitamin D{sub 2}, induced hypervitaminosis D{sub 2} in a rat using (3{alpha}-{sup 3}H)vitamin D{sub 2} and analyzed its plasma for the various (3{alpha}-{sup 3}H)vitamin D{sub 2} metabolites on two different high-pressure liquid chromatography systems. The results indicate that both 24,25,26-trihydroxyvitamin D{sub 2} and 24,25,26-trihydroxyvitamin D{sub 2} circulate in the vitamin D{sub 2} intoxicated rat in significant amounts along with other previously identified monohydroxy and dihydroxy metabolites of vitamin D{sub 2}, namely, 24-hydroxyvitamin D{sub 2}, 25-hydroxyvitamin D{sub 2}, and 24,25-dihydroxyvitamin D{sub 2}.« less

WE-AB-BRA-07: Quantitative Evaluation of 2D-2D and 2D-3D Image Guided Radiation Therapy for Clinical Trial Credentialing, NRG Oncology/RTOG

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

Giaddui, T; Yu, J; Xiao, Y

Purpose: 2D-2D kV image guided radiation therapy (IGRT) credentialing evaluation for clinical trial qualification was historically qualitative through submitting screen captures of the fusion process. However, as quantitative DICOM 2D-2D and 2D-3D image registration tools are implemented in clinical practice for better precision, especially in centers that treat patients with protons, better IGRT credentialing techniques are needed. The aim of this work is to establish methodologies for quantitatively reviewing IGRT submissions based on DICOM 2D-2D and 2D-3D image registration and to test the methodologies in reviewing 2D-2D and 2D-3D IGRT submissions for RTOG/NRG Oncology clinical trials qualifications. Methods: DICOM 2D-2Dmore » and 2D-3D automated and manual image registration have been tested using the Harmony tool in MIM software. 2D kV orthogonal portal images are fused with the reference digital reconstructed radiographs (DRR) in the 2D-2D registration while the 2D portal images are fused with DICOM planning CT image in the 2D-3D registration. The Harmony tool allows alignment of the two images used in the registration process and also calculates the required shifts. Shifts calculated using MIM are compared with those submitted by institutions for IGRT credentialing. Reported shifts are considered to be acceptable if differences are less than 3mm. Results: Several tests have been performed on the 2D-2D and 2D-3D registration. The results indicated good agreement between submitted and calculated shifts. A workflow for reviewing these IGRT submissions has been developed and will eventually be used to review IGRT submissions. Conclusion: The IROC Philadelphia RTQA center has developed and tested a new workflow for reviewing DICOM 2D-2D and 2D-3D IGRT credentialing submissions made by different cancer clinical centers, especially proton centers. NRG Center for Innovation in Radiation Oncology (CIRO) and IROC RTQA center continue their collaborative efforts to enhance quality assurance services and to be consistently adaptive to the new advances in radiation therapy. This project was supported by NCI grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Coupling between d-3-phosphoglycerate dehydrogenase and d-2-hydroxyglutarate dehydrogenase drives bacterial l-serine synthesis

PubMed Central

Zhang, Wen; Zhang, Manman; Gao, Chao; Zhang, Yipeng; Ge, Yongsheng; Guo, Shiting; Guo, Xiaoting; Zhou, Zikang; Liu, Qiuyuan; Zhang, Yingxin; Ma, Cuiqing; Tao, Fei; Xu, Ping

2017-01-01

l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1. SerA catalyzes the stereospecific reduction of 2-ketoglutarate (2-KG) to d-2-HG, responsible for the major production of d-2-HG in vivo. SerA combines the energetically favorable reaction of d-2-HG production to overcome the thermodynamic barrier of d-3-PG dehydrogenation. We identified a bacterial d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent enzyme, that converts d-2-HG back to 2-KG. Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG metabolism through their capacity to transfer electrons from D2HGDH. Furthermore, while the mutant with D2HGDH deletion displayed decreased growth, the defect was rescued by adding l-serine, suggesting that the D2HGDH is functionally tied to l-serine synthesis. Substantial flux flows through d-2-HG, being produced by SerA and removed by D2HGDH, ETF, and ETFQO, maintaining d-2-HG homeostasis. Overall, our results uncover that d-2-HG–mediated coupling between SerA and D2HGDH drives bacterial l-serine synthesis. PMID:28827360

In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

PubMed Central

Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

2014-01-01

We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

Snow cover volumes dynamic monitoring during melting season using high topographic accuracy approach for a Lebanese high plateau witness sinkhole

NASA Astrophysics Data System (ADS)

Abou Chakra, Charbel; Somma, Janine; Elali, Taha; Drapeau, Laurent

2017-04-01

Climate change and its negative impact on water resource is well described. For countries like Lebanon, undergoing major population's rise and already decreasing precipitations issues, effective water resources management is crucial. Their continuous and systematic monitoring overs long period of time is therefore an important activity to investigate drought risk scenarios for the Lebanese territory. Snow cover on Lebanese mountains is the most important water resources reserve. Consequently, systematic observation of snow cover dynamic plays a major role in order to support hydrologic research with accurate data on snow cover volumes over the melting season. For the last 20 years few studies have been conducted for Lebanese snow cover. They were focusing on estimating the snow cover surface using remote sensing and terrestrial measurement without obtaining accurate maps for the sampled locations. Indeed, estimations of both snow cover area and volumes are difficult due to snow accumulation very high variability and Lebanese mountains chains slopes topographic heterogeneity. Therefore, the snow cover relief measurement in its three-dimensional aspect and its Digital Elevation Model computation is essential to estimate snow cover volume. Despite the need to cover the all lebanese territory, we favored experimental terrestrial topographic site approaches due to high resolution satellite imagery cost, its limited accessibility and its acquisition restrictions. It is also most challenging to modelise snow cover at national scale. We therefore, selected a representative witness sinkhole located at Ouyoun el Siman to undertake systematic and continuous observations based on topographic approach using a total station. After four years of continuous observations, we acknowledged the relation between snow melt rate, date of total melting and neighboring springs discharges. Consequently, we are able to forecast, early in the season, dates of total snowmelt and springs low water flows which are essentially feeded by snowmelt water. Simulations were ran, predicting the snow level between two sampled dates, they provided promising result for national scale extrapolation.

Fate of Organic Matters in a Soil Erosion Context : Qualitative and Quantitative Monitoring in a Karst Hydrosystem

NASA Astrophysics Data System (ADS)

Quiers, M.; Gateuille, D.; Perrette, Y.; Naffrechoux, E.; David, B.; Malet, E.

2017-12-01

Soils are a key compartments of hydrosystems, especially in karst aquifers which are characterized by fast hydrologic responses to rainfalls. In steady state, soils are efficient filters preventing karst water from pollutions. But agricultural or forestry land uses can alter or even reverse the role of soils. Thus , soils can act as pollution sources rather than pollution filters. In order to manage water quality together with man activities in karst environment, the development of new tools and procedures designed to monitor the fate of soil organic matter are needed. This study reports two complementary methods applied in a moutain karst system impacted by anthropic activities and environmental stresses. A continuous monitoring of water fluorescence coupled with punctual sampling was analyzed by chemiometric methods and allowed to discriminate the type of organic matter transferred through the karst system along the year (winter / summer) and hydrological stages. As a main result, the modelisation of organic carbone fluxes is dominated by a colloidal or particulate part during highwaters, and a main part dissolved in solution during low water, demonstrating the change of organic carbone source. To confirm this result, a second method was used based on the observation of Polycyclic Aromatic Hydrocarbons (PAH) profiles. Two previous studies (Perrette et al 2013, Schwarz et al 2011) led to opposite conclusions about the fate of PAH from soil to groundwaters. This opposition leads to a potential use of PAH profiles (low molecular weight less hydrophobic ones versus high molecular weight more hydrophobic ones) as an indicator of soil erosion. We validate that use by the anaylsis of these PAH profiles for low and high waters (floods). These results demonstrate if needed the high vulnerability of karst system to soil erosion, and propose a new proxy to record soils erosion in groundwaters and in natural archives as stalagmites or sediments.

Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist

PubMed Central

Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P.; Newman, Amy Hauck

2016-01-01

The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180

Photobiology of vitamin D in mushrooms and its bioavailability in humans

PubMed Central

Keegan, Raphael-John H.; Lu, Zhiren; Bogusz, Jaimee M.; Williams, Jennifer E.; Holick, Michael F.

2013-01-01

Mushrooms exposed to sunlight or UV radiation are an excellent source of dietary vitamin D2 because they contain high concentrations of the vitamin D precursor, provitamin D2. When mushrooms are exposed to UV radiation, provitamin D2 is converted to previtamin D2. Once formed, previtamin D2 rapidly isomerizes to vitamin D2 in a similar manner that previtamin D3 isomerizes to vitamin D3 in human skin. Continued exposure of mushrooms to UV radiation results in the production of lumisterol2 and tachysterol2. It was observed that the concentration of lumisterol2 remained constant in white button mushrooms for up to 24 h after being produced. However, in the same mushroom tachysterol2 concentrations rapidly declined and were undetectable after 24 h. Shiitake mushrooms not only produce vitamin D2 but also produce vitamin D3 and vitamin D4. A study of the bioavailability of vitamin D2 in mushrooms compared with the bioavailability of vitamin D2 or vitamin D3 in a supplement revealed that ingestion of 2000 IUs of vitamin D2 in mushrooms is as effective as ingesting 2000 IUs of vitamin D2 or vitamin D3 in a supplement in raising and maintaining blood levels of 25-hydroxyvitamin D which is a marker for a person's vitamin D status. Therefore, mushrooms are a rich source of vitamin D2 that when consumed can increase and maintain blood levels of 25-hydroxyvitamin D in a healthy range. Ingestion of mushrooms may also provide the consumer with a source of vitamin D3 and vitamin D4. PMID:24494050

The stay green mutations d1 and d2 increase water stress susceptibility in soybeans.

PubMed

Luquez, Virginia M; Guiamét, Juan J

2002-06-01

The stay green mutant genotype d1d1d2d2 inhibits the breakdown of chloroplast components in senescing leaves of soybean (Glycine max L. Merr.). Together with G (a gene that preserves chlorophyll in the seed coat) they may extend photosynthetic activity in some conditions. While wild-type soybeans maintain high leaf water potentials right up to abscission, leaves of (GG)d1d1d2d2 dehydrate late in senescence, which suggests that water relations may be altered in the mutant. Three-week-old plants were subjected to a moderate water deficit (soil water potential=-0.7 MPa) for 7-10 d. Leaf water potential and relative water content decreased significantly more in response to water deficit in unifoliate leaves of GGd1d1d2d2 than in a near-isogenic wild-type line. Down-regulation of stomatal conductance in response to drought was similar in mutant and wild-type leaves. Likewise, exogenously applied ABA reduced stomatal conductance to a similar extent in the mutant and the wild type, and applied ABA failed to restore water deficit tolerance in GGd1d1d2d2. Experiments with explants lacking roots indicate that the accelerated dehydration of GGd1d1d2d2 is probably not due to alterations in the roots. In a comparison of near-isogenic lines carrying different combinations of d1, d2 and G, only d1d1d2d2 and GGd1d1d2d2 (i.e. the genotypes that cause the stay green phenotype) were more susceptible to water deficit than the wild type. These data suggest that pathways involved in chloroplast disassembly and in the regulation of stress responses may be intertwined and controlled by the same factors.

Large scale CIV3 calculations of fine-structure energy levels, oscillator strengths, and lifetimes in Fe XIV and Ni XVI

NASA Astrophysics Data System (ADS)

Gupta, G. P.; Msezane, A. Z.

2005-01-01

We have performed large scale CIV3 calculations of excitation energies from ground states for 109 fine-structure levels as well as of oscillator strengths and radiative decay rates for all electric-dipole-allowed and intercombination transitions among the (1s 22s 22p 6)3s 23p( 2P 0), 3s3p 2( 2S, 2P, 2D, 4P), 3s 23d( 2D), 3p 3( 4S 0, 2P 0, 2D 0), 3s3p( 3P 0)3d( 2P 0, 2D 0, 2F 0, 4P 0, 4D 0, 4F 0), 3s3p( 1P 0)3d( 2P 0, 2D 0, 2F 0), 3p 2( 1S)3d( 2D), 3p 2( 1D)3d( 2S, 2P, 2D), 3p 2( 3P)3d( 2P, 2D, 4P), 3s3d 2( 2S, 2P, 2D, 4P), 3p3d 2( 1S)( 2P 0), 3p3d 2( 1D)( 2P 0, 2D 0, 2F 0), 3p3d 2( 1G)( 2F 0), 3p3d 2( 3P)( 2P 0, 2D 0, 4S 0, 4P 0, 4D 0), 3p3d 2( 3F)( 2D 0, 2F 0, 4D 0, 4F 0), 3s 24s( 2S), 3s 24p( 2P 0), 3s 24d( 2D), 3s 24f( 2F 0), 3s3p( 3P 0)4s( 2P 0, 4P 0), and 3s3p( 1P 0)4s( 2P 0) states of Fe XIV and Ni XVI. These states are represented by very extensive configuration-interaction (CI) wavefunctions obtained using the CIV3 computer code of Hibbert. The relativistic effects in intermediate coupling are incorporated by means of the Breit-Pauli Hamiltonian which consists of the nonrelativistic term plus the one-body mass correction, Darwin term, and spin-orbit, spin-other-orbit, and spin-spin operators. The errors which often occur with sophisticated ab initio atomic structure calculations are reduced. Our calculated excitation energies, including their ordering, are in excellent agreement with the available experimental results for both of the ions studied. From our transition probabilities, we have also calculated radiative lifetimes of the lowest 37 fine-structure levels in Fe XIV and Ni XVI and compared them with available theoretical and experimental results. The mixing among several fine-structure levels is found to be so strong that the correct identification of these levels becomes very difficult. We predict new data for several levels where no other theoretical and/or experimental results are available. We hope that our extensive calculations will be useful to experimentalists in identifying the fine-structure levels in their future work.

Index to ring digit ratio in Saudi Arabia at Almadinah Almonawarah province: a direct and indirect measurement study

PubMed Central

Almasry, Shaima M; El Domiaty, Magda A; Algaidi, Sami A; Elbastawisy, Yasser M; Safwat, Maha D

2011-01-01

The digit ratio, or the relative lengths, of the 2nd and 4th digits (2D : 4D) shows a sex difference, with males tending to have lower values in comparison with females. This sex differences arises early in the fetus and may result from the effects of prenatal testosterone and estrogen on the relative growth rate of the 2nd and 4th digits. This study aimed to estimate finger lengths and the 2D : 4D ratios for the first time in Saudi Arabian subjects using direct and indirect measurements, and to evaluate the correlations between both indirect and direct 2D : 4D with adult testosterone and various sexually dimorphic physical traits. The results revealed the following: (i) mean 2D : 4D in Saudi Arabian samples varied from 0.96 to 0.99; (ii) mean 2D : 4D was lower for indirect compared to direct 2D : 4D; (iii) sex differences in indirect 2D : 4D were higher than in direct 2D : 4D measurements; (iv) there were no significant correlations between indirect or direct 2D : 4D and testosterone level; (v) there were four significant correlations between direct 2D : 4D and body size traits but no significant correlations between indirect 2D : 4D and body size. PMID:21044064

24,25,28-trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2: novel metabolites of vitamin D2.

PubMed

Reddy, G S; Tserng, K Y

1990-01-30

Understanding of the inactivation pathways of 25-hydroxyvitamin D2 and 24-hydroxyvitamin D2, the two physiologically significant monohydroxylated metabolites of vitamin D2, is of importance, especially during hypervitaminosis D2. In a recent study, it has been demonstrated that the inactivation of 24-hydroxyvitamin D2 occurs through its conversion into 24,26-dihydroxyvitamin D2 [Koszewski, N.J., Reinhardt, T.A., Napoli, J.L., Beitz, C.D., & Horst, R.L. (1988) Biochemistry 27, 5785]. At present, little information is available regarding the inactivation pathway of 25-hydroxyvitamin D2 except its further metabolism into 24,25-dihydroxyvitamin D2 [Jones, G., Rosenthal, A., Segev, D., Mazur, Y., Frolow, F., Halfon, Y., Rabinovich, D., & Shakked, Z. (1979) Biochemistry 18, 1094]. In our present study, we investigated the metabolic fate of 25-hydroxyvitamin D2 in the isolated perfused rat kidney and demonstrated its conversion not only into 24,25-dihydroxyvitamin D2 but also into two other new metabolites, namely, 24,25,28-trihydroxyvitamin D2 and 24,25,26-trihydroxyvitamin D2. The structure identification of the new metabolites was established by the techniques of ultraviolet absorption spectrophotometry and mass spectrometry and by the characteristic nature of each new metabolite's susceptibility to sodium metaperiodate oxidation. In order to demonstrate the physiological significance of the two new trihydroxy metabolites of vitamin D2, we induced hypervitaminosis D2 in a rat using [3 alpha-3H]vitamin D2 and analyzed its plasma for the various [3 alpha-3H]vitamin D2 metabolites on two different high-pressure liquid chromatography systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Myocardial Infarct Size by Three-Dimensional and Two-Dimensional Speckle Tracking Echocardiography: A Comparative Study to Single Photon Emission Computed Tomography.

PubMed

Wang, Qiushuang; Huang, Dangsheng; Zhang, Liwei; Shen, Dong; Ouyang, Qiaohong; Duan, Zhongxiang; An, Xiuzhi; Zhang, Meiqing; Zhang, Chunhong; Yang, Feifei; Zhi, Guang

2015-10-01

To compare three-dimensional (3D) and two-dimensional (2D) speckle tracking echocardiography (STE) techniques in the assessment of left ventricular function and myocardial infarct size (MIS). Thirty-two patients diagnosed with ST elevation myocardial infarction and 18 healthy control patients underwent 2D echocardiography, 3D echocardiography, and single photon emission computed tomography (SPECT). 3D left ventricular global area strain (GAS), 2D and 3D global longitudinal strain (GLS), global radial strain (GRS) as well as global circumferential strain (GCS) were analyzed to correlate with myocardial infarct size detected by SPECT. 2D and 3D left ventricular ejection fraction (LVEF) as well as 2D and 3D wall motion score index (WMSI) also were measured using conventional echocardiography. The 2D-GLS values were significantly higher than that of 3D-GLS, while 2D-GCS and GRS were significantly lower than 3D-GCS and GRS, respectively. However, no significant differences in LVEF and WMSI could be observed between 2D and 3D echocardiography. Myocardial strain indices, LVEF, and WMSI using 2D and 3D echocardiography also had good correlations with MIS as measured by SPECT. ROC curve analysis showed that the 3D and 2D myocardial indices, LVEF, and WMSI could distinguish between small and large MIS, while 2D-GLS had the highest AUC. The 2D and 3D myocardial strain indices correlated well with MIS by SPECT. Among them, the 2D-GLS showed the highest diagnostic value, while 3D-GRS and GCS had better diagnostic value than 2D-GRS and GCS. © 2015, Wiley Periodicals, Inc.

Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors

PubMed Central

Radl, Daniela; Borrelli, Emiliana; Williams, John T; Neve, Kim A

2017-01-01

The dopamine D2 receptor has two splice variants, D2S (Short) and D2L (Long). In dopamine neurons, both variants can act as autoreceptors to regulate neuronal excitability and dopamine release, but the roles of each variant are incompletely characterized. In a previous study we used viral receptor expression in D2 receptor knockout mice to show distinct effects of calcium signaling on D2S and D2L autoreceptor function (Gantz et al., 2015). However, the cocaine-induced plasticity of D2 receptor desensitization observed in wild type mice was not recapitulated with this method of receptor expression. Here we use mice with genetic knockouts of either the D2S or D2L variant to investigate cocaine-induced plasticity in D2 receptor signaling. Following a single in vivo cocaine exposure, the desensitization of D2 receptors from neurons expressing only the D2S variant was reduced. This did not occur in D2L-expressing neurons, indicating differential drug-induced plasticity between the variants. PMID:29154756

Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors.

PubMed

Robinson, Brooks G; Condon, Alec F; Radl, Daniela; Borrelli, Emiliana; Williams, John T; Neve, Kim A

2017-11-20

The dopamine D2 receptor has two splice variants, D2S (Short) and D2L (Long). In dopamine neurons, both variants can act as autoreceptors to regulate neuronal excitability and dopamine release, but the roles of each variant are incompletely characterized. In a previous study we used viral receptor expression in D2 receptor knockout mice to show distinct effects of calcium signaling on D2S and D2L autoreceptor function (Gantz et al., 2015). However, the cocaine-induced plasticity of D2 receptor desensitization observed in wild type mice was not recapitulated with this method of receptor expression. Here we use mice with genetic knockouts of either the D2S or D2L variant to investigate cocaine-induced plasticity in D2 receptor signaling. Following a single in vivo cocaine exposure, the desensitization of D2 receptors from neurons expressing only the D2S variant was reduced. This did not occur in D2L-expressing neurons, indicating differential drug-induced plasticity between the variants.

Synthesis, molecular properties estimations, and dual dopamine D2 and D3 receptor activities of Benzthiazole-based ligands.

NASA Astrophysics Data System (ADS)

Schübler, Moritz; Sadek, Bassem; Kottke, Tim; Weizel, Lilia; Stark, Holger

2017-09-01

Neurleptic drugs, e.g. aripiprazole, targeting the dopamine D2s and D3 receptors (D2sR and D3R) in the central nervous system are widely used in the treatment of several psychotic and neurodegenerative diseases. Therefore, a new series of benz[d]thiazole-based ligands (1-18) was synthesized by applying the bioisosteric approach derived from the selective D3Rs ligand BP-897 and its structurally related benz[d]imidazole derivatives. Herein, introduction of the benz[d]thiazole moiety was well tolerated by D2sR and D3R binding sites leading to antagonist affinities in the low nanomolar concentration range at both receptor subtypes. Further exploration of different substitution patterns at the benz[d]thiazole heterocycle and the basic 4-phenylpiperazine resulted in the discovery of high dually acting D2sR and D3R ligands. Moreover, the methoxy substitution at 2-position of 4-phenylpiperazine resulted in significantly (22-fold) increased D2sR binding affinity as compared to the parent ligand BP-897, and improved physicochemical and drug-likeness properties of ligands 1-9. However, the latter structural modifications failed to improve the drug-able properties in ligands having un-substituted 4-phenylpiperazine analogues (10-18). Accordingly, compound 7 showed in addition to high dual affinity at the D2sR and D3R (Ki (hD2SR) = 2.8 ± 0.8 nM; Ki (hD3R) = 3.0 ± 1.6 nM), promising clogS, clogP, LE (hD2sR, hD3R), LipE (hD2sR, hD3R), and drug-likeness score values of -4.7, 4.2, (0.4, 0.4), (4.4, 4.3), and 0.7, respectively. Also, the deaminated analogue 8 (Ki (hD2SR) = 3.2 ± 0.4 nM; Ki (hD3R) = 8.5 ± 2.2 nM) revealed clogS, clogP, LE (hD2sR, hD3R), LipE (hD2sR, hD3R) and drug-likeness score values of -4.7, 4.2, (0.4, 0.4), (3.9, 3.5), and 0.4, respectively. The results observed for the newly developed benz[d]thiazole-based ligands 1-18 provide clues for the diversity in structure activity relationships (SARs) at the D2sR and D3R subtypes.

Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms.

PubMed

Radl, Daniela; Chiacchiaretta, Martina; Lewis, Robert G; Brami-Cherrier, Karen; Arcuri, Ludovico; Borrelli, Emiliana

2018-01-02

The dopamine D2 receptor (D2R) is a major component of the dopamine system. D2R-mediated signaling in dopamine neurons is involved in the presynaptic regulation of dopamine levels. Postsynaptically, i.e., in striatal neurons, D2R signaling controls complex functions such as motor activity through regulation of cell firing and heterologous neurotransmitter release. The presence of two isoforms, D2L and D2S, which are generated by a mechanism of alternative splicing of the Drd2 gene, raises the question of whether both isoforms may equally control presynaptic and postsynaptic events. Here, we addressed this question by comparing behavioral and cellular responses of mice with the selective ablation of either D2L or D2S isoform. We establish that the presence of either D2L or D2S can support postsynaptic functions related to the control of motor activity in basal conditions. On the contrary, absence of D2S but not D2L prevents the inhibition of tyrosine hydroxylase phosphorylation and, thereby, of dopamine synthesis, supporting a major presynaptic role for D2S. Interestingly, boosting dopamine signaling in the striatum by acute cocaine administration reveals that absence of D2L, but not of D2S, strongly impairs the motor and cellular response to the drug, in a manner similar to the ablation of both isoforms. These results suggest that when the dopamine system is challenged, D2L signaling is required for the control of striatal circuits regulating motor activity. Thus, our findings show that D2L and D2S share similar functions in basal conditions but not in response to stimulation of the dopamine system.

Potencies of vitamin D analogs, 1α-hydroxyvitamin D3 , 1α-hydroxyvitamin D2 and 25-hydroxyvitamin D3 , in lowering cholesterol in hypercholesterolemic mice in vivo.

PubMed

Quach, Holly P; Dzekic, Tamara; Bukuroshi, Paola; Pang, K Sandy

2018-04-01

Vitamin D 3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D 3 [1α(OH)D 3 ], 1α-hydroxyvitamin D 2 [1α(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D 3 and 1α(OH)D 2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and 1α,25-dihydroxyvitamin D 2 [1,25(OH) 2 D 2 ] , respectively. 1α(OH)D 2 may also be activated by CYP24A1 to 1α,24-dihydroxyvitamin D 2 [1,24(OH) 2 D 2 ], another active VDR ligand. 25(OH)D 3 , the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D 3 , is activated by CYP27B1 in the kidney to 1,25(OH) 2 D 3 . In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (Shp) inhibition and increased cholesterol 7α-hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D 3  > 1248 nmol/kg 25(OH)D 3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D 3 . Except for 1.21 nmol/kg 1α(OH)D 2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH) 2 D 3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D 3 and 25(OH)D 3 exhibit cholesterol lowering properties upon activation to 1,25(OH) 2 D 3 : 1α(OH)D 3 is rapidly activated by liver enzymes and 25(OH)D 3 is slowly activated by renal Cyp27b1 in mouse. Copyright © 2018 John Wiley & Sons, Ltd.

Tunneling chemical reactions D +H2→DH+H and D +DH→D2+H in solid D2-H2 and HD -H2 mixtures: An electron-spin-resonance study

NASA Astrophysics Data System (ADS)

Kumada, Takayuki

2006-03-01

Tunneling chemical reactions D +H2→DH+H and D +DH→D2+H in solid HD -H2 and D2-H2 mixtures were studied in the temperature range between 4 and 8K. These reactions were initiated by UV photolysis of DI molecules doped in these solids for 30s and followed by measuring the time course of electron-spin-resonance (ESR) intensities of D and H atoms. ESR intensity of D atoms produced by the photolysis decreases but that of H atoms increases with time. Time course of the D and H intensities has the fast and slow processes. The fast process, which finishes within ˜300s after the photolysis, is assigned to the reaction of D atom with one of its nearest-neighboring H2 molecules, D(H2)n(HD)12-n→H(H2)n-1(HD)13-n or D(H2)n(D2)12-n→H(HD )(H2)n-1(D2)12-n for 12⩾n⩾1. Rate constant for the D +H2 reaction between neighboring D atom-H2 molecule pair is determined to be (7.5±0.7)×10-3s-1 in solid HD -H2 and (1.3±0.3)×10-2s-1 in D2-H2 at 4.1K, which is very close to that calculated based on the theory of chemical reaction in gas phase by Hancock et al. [J. Chem. Phys. 91, 3492 (1989)] and Takayanagi and Sato [J. Chem. Phys. 92, 2862 (1990)]. This rate constant was found to be independent of temperature up to 7K within experimental error of ±30%. The slow process is assigned to the reaction of D atom produced in a cage fully surrounded by HD or D2 molecules, D(HD)12 or D(D2)12. This D atom undergoes the D +DH reaction with one of its nearest-neighboring HD molecules in solid HD -H2 or diffuses to the neighbor of H2 molecules to allow the D +H2 reaction in solid HD -H2 and D2-H2. The former is the main channel in solid HD -H2 below 6K where D atoms diffuse very slowly, whereas the latter dominates over the former above 6K. Rate for the reactions in the slow process is independent of temperature below 6K but increases with the increase in temperature above 6K. We found that the increase is due to the increase in hopping rate of D atoms to the neighbor of H2 molecules. Rate constant for the D +DH reaction was found to be independent of temperature up to 7K as well.

Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers.

PubMed

Tsuji, Hideto; Noda, Soma; Kimura, Takayuki; Sobue, Tadashi; Arakawa, Yuki

2017-03-24

D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as "a configurational or helical molecular glue" for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers

NASA Astrophysics Data System (ADS)

Tsuji, Hideto; Noda, Soma; Kimura, Takayuki; Sobue, Tadashi; Arakawa, Yuki

2017-03-01

D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as “a configurational or helical molecular glue” for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

D1((2)B2g) to D0((2)Au) Fluorescence from the Matrix-Isolated Perylene Cation Following Laser Excitation into the D5(2)B3g) and D2 ((2)B3g) Electronic States

NASA Technical Reports Server (NTRS)

Chillier, Xavier D. F.; Stone, Bradley M.; Joblin, Christine; Salama, Farid; Allamandola, Louis J.; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

Fluorescence spectra of the perylene cation, pumped by direct laser excitation via the D(sub 2)((2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) and D(sub 5)(2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) transitions, are presented. Direct excitation into the D5 or D2 states is followed by rapid non-radiative relaxation to D1 that, in turn,relaxes radiatively. Excitation spectroscopy across the D(sub 2)((2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) transition near 730 nm shows that site splitting plays little or no role in determining the spectral substructure in the ion spectra. Tentative assignments for ground state vibrational frequencies are made by comparison of spectral intervals with calculated normal mode frequencies.

Satisfactory surgical outcome of T2 gastric cancer after modified D2 lymphadenectomy.

PubMed

Zhang, Shupeng; Wu, Liangliang; Wang, Xiaona; Ding, Xuewei; Liang, Han

2017-04-01

Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), the modified D2 (D1 + 7, 8a and 9) lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy: the modified D2 group (mD2) and the standard D2 group (D2). Surgical outcome and recurrence date were compared between the two groups. The 5-year overall survival (OS) rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss (P=0.001) and shorter operation time (P<0.001) than those in the D2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

Design and Analysis of Multi-Sensor Sequential Detection System

DTIC Science & Technology

1991-07-01

7 - A7Ŗ y - 2 Y21 -~ TI 21D2 T 2 -DI T2 2 Tj I e I11 921 f e-21Y-92 T -X-iIx-Liil X f- TD T2 +D2 f e fj e-1Y-2 1 1 log T T1-D1 2 T 2 D2 2. -’! IL...T2 +D2 X2 1 e-X2(T 2 -9 21) _1 e-x 2( T2 +D2 -IL21) q2 2 2 20 T40= 2 x-L2 Y - 2 e2(T 2-D2 -1) _ 1 e-X2(T2-9 21) T2 -D 2 2 2 T2 - 2 X2 2( TD 2 IL2 ) q10...0.5 * exp((-l) * (t - u)); retumn(i); ) double P2(ujl,t,d) double u,I, td ; double i; i= I - 0.5 * exp((-I) * (u - t)) - 0.5 *exp((-l) *(t + d - u

Modelisation de materiaux composites adaptatifs munis d'actionneurs en alliage a memoire de forme

NASA Astrophysics Data System (ADS)

Simoneau, Charles

Technological development of structures having the capabilities to adapt themselves to different operating conditions is increasing in many areas of research such as aerospace. In fact, numerous works are now oriented toward the design of adaptive aircraft wings where the goal is to enhance the aerodynamic properties of the wing. Following this approach, the work realised in the framework of this master thesis presents the steps leading to the creation of a numerical model that can be used to predict the behavior of an adaptive panel, and therefore, eventually of an adaptive aircraft wing. Foremost, the adaptive panel of this project has been designed from a carbon-epoxy composite, acting as host structure, where shape memory alloy (SMA) wires, acting as actuators, have been inserted in it. SMA actuators have also been embedded asymmetrically along the direction of the panel thickness in order to generate a bending moment when the SMA wires are activated. To achieve the modeling of such structure it has been firstly shown that a numerical model composed of only solid finite elements could be used to represent the panel. However, a second numerical model composed of shell, beam and link finite elements showed that identical results can be obtained with much less nodes (the first model was composed of more than 300 000 nodes compared with 1 000 nodes for the second). The combination of shell-beam-link elements has then been chosen. Secondly, a constitutive relation had to be used for modeling the particular behavior of SMA. For the present work, a uniaxial version of the Likhachev's model is used. Due to its fairly straightforward mathematical formulation, this material law is able to model the main functional properties of SMA including the two-way shape memory effect (TWSME) at zero stress obtained after a thermomechanical education treatment. The last step was to compare the results of the numerical simulations with those obtained with a prototype where 19 actuators were embedded in a composite panel of 425 mm x 425 mm. Various load cases were performed. However, during experimental tests, it has been found that the measured actuator temperature was systematically underestimated. Therefore, by comparing the radius of curvature (rho) of the panel as a function of the activation temperature (T) of the actuators, an offset (in temperature) between the curves numerically and experimentally obtained is observable. Aside from this technological difficulty, the experimental and numerical results are very similar and therefore, this numerical model can be used for predicting the behavior of an adaptive panel. In addition, one the main advantages of this numerical model resides in its versatility where it has been shown that a "warping" of the panel could be realized by controlling independently each actuator. Future works should now obviously focus on the temperature measurement while considering the improvement of the numerical model and the possibility to model an initially curved adaptive panel whose form could resemble an aircraft wing.

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

PubMed Central

Gagnon, D.; Petryszyn, S.; Sanchez, M. G.; Bories, C.; Beaulieu, J. M.; De Koninck, Y.; Parent, A.; Parent, M.

2017-01-01

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease. PMID:28128287

Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice.

PubMed

Gagnon, D; Petryszyn, S; Sanchez, M G; Bories, C; Beaulieu, J M; De Koninck, Y; Parent, A; Parent, M

2017-01-27

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D 1 or D 2 dopamine receptor. Consequences on MSNs expressing both receptors (D 1 /D 2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D 1 /D 2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D 1 /D 2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D 1 and D 2 MSNs, D 1 /D 2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D 1 /D 2 MSNs, but also of D 1 and D 2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D 1 and D 2 MSNs, the extent of dendritic arborization of D 1 /D 2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D 1 /D 2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.

The effects of sex, ethnicity, and sexual orientation on self-measured digit ratio (2D:4D).

PubMed

Manning, John T; Churchill, Andrew J G; Peters, Michael

2007-04-01

We used self-reported direct finger measurements from 255,116 participants in a BBC Internet survey to investigate the measurement of 2D:4D ratios and their association with sex, ethnicity, and sexual orientation. We found significant sex differences such that males had lower 2D:4D than females and the effect size of the sex differences was greatest for right hand 2D:4D. Mean 2D:4D was lower for right hands than for left hands in men, but lower for left hands compared to right hands in women. The sexual dimorphism in 2D:4D was present across ethnic and country groupings, suggesting that it is universal in humans. However, there was also evidence that mean 2D:4D varied across ethnic groups with higher ratios for Whites, Non-Chinese Asians, and Mid-Easterners and lower ratios in Chinese and Black samples. There were significant differences in 2D:4D across sexual orientation groups but these were confined to men. Male homosexuals and bisexuals had higher mean 2D:4D (suggesting exposure to lower prenatal T) than heterosexuals. The effect was present in Whites, but there was no evidence for the pattern among Black and Chinese participants. In women, there were no significant effects of sexual orientation on 2D:4D. Most studies of sexual orientation effects on 2D:4D have measured finger length from photocopies of the hands. In comparison, our self-reported measures gave higher mean 2D:4D, lower effect sizes, and, in some instances, different patterns of effect size. The implications of our findings for future research into 2D:4D are discussed.

Comparison of diagnostic accuracies of 2D and 3D MR elastography of the liver

PubMed Central

Morisaka, Hiroyuki; Motosugi, Utaroh; Glaser, Kevin J.; Ichikawa, Shintaro; Ehman, Richard L.; Sano, Katsuhiro; Ichikawa, Tomoaki; Onishi, Hiroshi

2017-01-01

Purpose To evaluate the effect of imaging sequence (spin-echo echo-planar imaging [EPI] and gradient-echo [GRE]) and postprocessing method (2-dimensional [2D] and 3D inversion algorithms) on liver magnetic resonance elastography (MRE) and to validate the diagnostic performance of EPI-MRE3D versus conventional GRE-MRE2D for liver fibrosis staging. Materials and Methods Three MRE methods (EPI-MRE3D, EPI-MRE2D, and GRE-MRE2D) were performed on soft and mildly stiff phantoms and 58 patients with chronic liver disease at a 3-Tesla clinical MRI scanner, and stiffness values were compared among the 3 methods. A validation study comprised 73 patients with histological liver fibrosis (F0–4, METAVIR system). Areas under the receiver operating characteristic curves (AUCs) and accuracies for diagnosing significant fibrosis (F3–4) and cirrhosis (F4) were compared between EPI-MRE3D and GRE-MRE2D. Results Stiffness values of soft and mildly stiff phantoms were 2.4 kPa and 4.0kPa by EPI-MRE3D; 2.6 kilopascal [kPa] and 4.2kPa by EPI-MRE2D; and 2.7 kPa and 4.2kPa by GRE-MRE2D. In patients, EPI-MRE3D provided significantly lower stiffness values than other methods (p<0.001). However, there was no significant difference between GRE-MRE2D and EPI-MRE2D (p=0.12). The AUCs and accuracies of EPI-MRE3D and GRE-MRE2D were statistically equivalent in the diagnoses of significant fibrosis (F3–4) and cirrhosis (F4) (all p<0.005). Conclusion EPI-MRE3D showed lower modestly liver stiffness values than conventional GRE-MRE2D. The diagnostic performances of EPI-MRE3D and GRE-MRE2D were equivalent for liver fibrosis staging. PMID:27662640

UV-LIGA Microfabrication of 220 GHz Sheet Beam Amplifier Gratings with SU-8 Photoresists

DTIC Science & Technology

2010-01-01

4 4 4a Diethyl ether 3d, RT 0 Tetrahydrofuran (THF) 3d, RT 1 2 4 3 3 Py + pyridinium (Pym) HBr crystals 2d, RT 1 2 3 2 Py + Pym HCl crystals 2d, RT 1...1 1 Acetone + Pym HBr crystals 2d, RT 1 0 Pym dichromate in Py 2d, RT 1 2 1 Pym chlorochromate in Py 2d, RT 4 1 2 1a Propylamine (PA) 2d, RT 1 2 3 2

The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors.

PubMed

Kuzhikandathil, Eldo V; Bartoszyk, Gerd D

2006-09-01

Sarizotan (EMD 128130) is a chromane derivative that exhibits affinity at serotonin and dopamine receptors. Sarizotan effectively suppresses levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model. Results from clinical trials suggest that sarizotan significantly alleviates levodopa-induced dyskinesia. The functional effects of sarizotan on individual dopamine receptor subtypes are not known. Here we report the functional effects of sarizotan on human D2-like dopamine receptors (D2S, D2L, D3, D4.2 and D4.4) individually expressed in the AtT-20 neuroendocrine cell line. Using the coupling of D2-like dopamine receptors to G-protein coupled inward rectifier potassium channels we determined that sarizotan is a full agonist at D3 and D4.4 receptors (EC50=5.6 and 5.4 nM, respectively) but a partial agonist at D2S, D2L and D4.2 receptors (EC50=29, 23 and 4.5 nM, respectively). Consistent with its partial agonist property, sarizotan is an antagonist at D2S and D2L receptors (IC50=52 and 121 nM, respectively). Using the coupling of D2-like dopamine receptors to adenylyl cyclase we determined that sarizotan is a full agonist at D2L, D3, D4.2 and D4.4 receptors (EC50=0.51, 0.47, 0.48 and 0.23 nM, respectively) but a partial agonist at D2S receptors (EC50=0.6 nM).

A Comparison of 2,4-Dichlorophenoxyacetic Acid Metabolism in Cultured Soybean Cells and in Embryogenic Carrot Cells

PubMed Central

Montague, Michael J.; Enns, Russell K.; Siegel, Ned R.; Jaworski, Ernest G.

1981-01-01

The removal or reduction in concentration of auxin is often a successful method for obtaining morphogenesis in cell cultures of higher plants, such as carrot, but not for soybean. For this reason, the metabolism of one auxin, 2,4-dichlorophenoxyacetic acid (2,4-D), was compared in both carrot and soybean cells. Whereas soybean cells conjugated a high percentage of their 2,4-D to amino acids, carrot cells contained primarily free 2,4-D. Moreover, after long-term exposure to 2,4-D, carrot cells released much more 2,4-D upon transfer to 2,4-D-free (embryogenic) medium than did soybean cells. It appears that the retention of 2,4-D by soybean cells might interfere with subsequent morphogenesis. Because no impairment of 2,4-D efflux was found with short-term exposure to radiolabeled 2,4-D, it was concluded that 2,4-D retention in soybean cells might be due to a time-dependent, metabolic process. The conjugation of 2,4-D to amino acids was shown to be one such time-dependent process. Additionally, the release of 2,4-D from the cells was shown to be due primarily to a loss of free 2,4-D and not 2,4-D-amino acid conjugates. It seems that the greater retention of 2,4-D by soybean cells upon transfer to 2,4-D-free medium is due to greater formation of 2,4-D-amino acid conjugates. PMID:16661722

Each Individual Isoform of the Dopamine D2 Receptor Protects from Lactotroph Hyperplasia

PubMed Central

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna

2013-01-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R−/− mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states. PMID:23608643

Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia.

PubMed

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna; Borrelli, Emiliana

2013-06-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R-/- mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.

Deoxycytidine and deoxythymidine treatment for thymidine kinase 2 deficiency

PubMed Central

Lopez-Gomez, Carlos; Levy, Rebecca J; Sanchez-Quintero, Maria J; Juanola-Falgarona, Marti; Barca, Emanuele; Garcia-Diaz, Beatriz; Tadesse, Saba; Garone, Caterina; Hirano, Michio

2017-01-01

Objective Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2-/-) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy. Methods To test these hypotheses, we assessed two therapies in Tk2-/- mice: 1) dT+dC and 2) co-administration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP. Results We observed that dC+dT delayed disease onset, prolonged lifespan of Tk2-deficient mice, and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased lifespan of Tk2-/- animals compared to dCMP+dTMP. Interpretation Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. PMID:28318037

Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates: isotopic discrimination between hydrogen and deuterium.

PubMed

Malaisse, W J; Malaisse-Lagae, F; Liemans, V; Ottinger, R; Willem, R

1990-03-27

The discrimination between the isotopes of hydrogen in the reaction catalyzed by yeast phosphoglucoisomerase is examined by NMR, as well as by spectrofluorometric or radioisotopic methods. The monodirectional conversion of D-glucose 6-phosphate to D-fructose 6-phosphate displays a lower maximal velocity with D-[2-2H]glucose 6-phosphate than unlabelled D-glucose 6-phosphate, with little difference in the affinity of the enzyme for these two substrates. About 72% of the deuterium located on the C2 of D-[1-13C,2-2H]glucose 6-phosphate is transferred intramolecularly to the C1 of D-[1-13C,1-2H]fructose 6-phosphate. The velocity of the monodirectional conversion of D-[U-14C]glucose 6-phosphate (or D-[2-3H]glucose 6-phosphate) to D-fructose 6-phosphate is virtually identical in H2O and D2O, respectively, but is four times lower with the tritiated than 14C-labelled ester. In the monodirectional reaction, the intramolecular transfer from the C2 of D-[2-3H]glucose 6-phosphate is higher in the presence of D2O than H2O. Whereas prolonged exposure of D-[1-13C]glucose 6-phosphate to D2O, in the presence of phosphoglucoisomerase, leads to the formation of both D-[1-13C,2-2H]glucose 6-phosphate and D-[1-13C,1-2H]fructose 6-phosphate, no sizeable incorporation of dueterium from D2O on the C1 of D-[1-13C]fructose 1,6-bisphosphate is observed when the monodirectional conversion of D-[1-13C]glucose 6-phosphate occurs in the concomitant presence of phosphoglucoisomerase and phosphofructokinase. The latter finding contrasts with the incorporation of hydrogen from 1H2O or tritium from 3H2O in the monodirectional conversion of D-[2-3H]glucose 6-phosphate and unlabelled D-glucose 6-phosphate, respectively, to their corresponding ketohexose esters.

Synthetic mucin fragments: synthesis of O-sulfo and O-methyl derivatives of allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-alpha-D- galactopyranoside as potential compounds for sulfotransferases.

PubMed

Jain, R K; Piskorz, C F; Matta, K L

1995-10-02

Allyl 2-acetamido-4,6-O-(4-methoxybenzylidene)-2-deoxy-alpha-D-galact opy ranoside (1) was condensed with either 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (2) or 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-alpha-D-galactopyranosyl bromide (14) in the presence of mercuric cyanide. Selective substitution with methyl, sulfo or both at desired positions, followed by the removal of protecting groups, afforded allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-6-O-methyl-alpha -D- galactopyranoside (5), allyl O-(6-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy-6- O-methyl-alpha-D-galactopyranoside (10), allyl O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-6-O-sulfo-alpha- D- galactopyranoside sodium salt (13), allyl O-(6-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy- alpha-D-galactopyranoside (17) and allyl O-(3-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy- alpha-D-galactopyranoside (22). The structures of compounds 5, 10, 13, 17 and 22 were established by 13C NMR and FAB mass spectroscopy.

Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

PubMed

Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

2016-10-11

The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine

PubMed Central

Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

2016-01-01

The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos. Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R+-MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits. PMID:27671625

Effect of genetic polymorphism on the inhibition of dopamine formation from p-tyramine catalyzed by brain cytochrome P450 2D6.

PubMed

Niwa, Toshiro; Shizuku, Marina; Yamano, Kaori

2017-04-15

The inhibitory effects of steroid hormones, including glucocorticoids such as cortisol, and related compounds on dopamine formation from p-tyramine, catalyzed by cytochrome P450 (CYP) 2D6.2 (Arg296Cys, Ser486Thr) and CYP2D6.10 (Pro34Ser, Ser486Thr) were compared with the effects of those catalyzed by CYP2D6.1 (wild type), to investigate the effect of a CYP2D6 polymorphism on neuroactive amine metabolism in the brain. Inhibition constants (K i ) or 50% inhibitory concentrations of six steroid hormones (cortisol, cortisone, corticosterone, dehydroepiandrosterone, progesterone, and pregnenolone) and quinidine and quinine-typical potent inhibitors of the human CYP2D6 and rat CYP2D subfamily, respectively-toward dopamine formation catalyzed by CYP2D6.1, CYP2D6.2, and CYP2D6.10 expressed in recombinant Escherichia coli were compared. Although most steroid hormones had no or minor inhibitory effects on the dopamine formation by all CYP2D6 variants, progesterone inhibited the metabolism and K i value against CYP2D6.10 was approximately twice that for CYP2D6.1 and CYP2D6.2. Quinidine exhibited stronger inhibition than quinine; however, these two compounds inhibited the CYP2D6.10-mediated reaction more weakly than the CYP2D6.1 and CYP2D6.2 reactions. These results suggest that CYP2D6 polymorphism would affect drug interaction through dopamine formation in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking.

PubMed

Heinsbroek, Jasper A; Neuhofer, Daniela N; Griffin, William C; Siegel, Griffin S; Bobadilla, Ana-Clara; Kupchik, Yonatan M; Kalivas, Peter W

2017-01-25

Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTD GABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic plasticity was selectively lost in D2, but not D1 inputs to the ventral pallidum. The selective impairment in D2 afferents may promote the influence of D1 inputs to drive relapse to cocaine seeking. Copyright © 2017 the authors 0270-6474/17/370757-11$15.00/0.

Loss of Plasticity in the D2-Accumbens Pallidal Pathway Promotes Cocaine Seeking

PubMed Central

Neuhofer, Daniela N.; Griffin, William C.; Siegel, Griffin S.; Bobadilla, Ana-Clara; Kupchik, Yonatan M.

2017-01-01

Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTDGABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. SIGNIFICANCE STATEMENT More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic plasticity was selectively lost in D2, but not D1 inputs to the ventral pallidum. The selective impairment in D2 afferents may promote the influence of D1 inputs to drive relapse to cocaine seeking. PMID:28123013

A Context Dependent Interpretation of Inconsistencies in 2D:4D Findings: The Moderating Role of Status Relevance

PubMed Central

Millet, Kobe; Buehler, Florian

2018-01-01

Whereas direct relationships between 2D:4D and dominance related attitudes or behavior often turn out to be weak, some literature suggests that the relation between 2D:4D and dominance is context-specific. That is, especially in status-challenging situations 2D:4D may be related to dominant behavior and its correlates. Based on this perspective, we interpret inconsistencies in the literature on the relation between 2D:4D and risk taking, aggression and dominance related outcomes and investigate in our empirical study how attitudes in low 2D:4D men may change as a function of the status relevance of the context. We provide evidence for the idea that status relevance of the particular situation at hand influences the attitude towards performance-enhancing means for low 2D:4D men, but not for high 2D:4D men. We argue that 2D:4D may be related to any behavior that is functional to attain status in a specific context. Implications for (economic) decision making are discussed. PMID:29403365

Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.

PubMed

Ocampo-Pelland, Alanna S; Gastonguay, Marc R; Riggs, Matthew M

2017-08-01

Association of Vitamin D (D3 & D2) and its 25OHD metabolite (25OHD3 & 25OHD2) exposures with various diseases is an active research area. D3 and D2 dose-equivalency and each form's ability to raise 25OHD concentrations are not well-defined. The current work describes a population pharmacokinetic (PK) model for D2 and 25OHD2 and the use of a previously developed D3-25OHD3 PK model [1] for comparing D3 and D2-related exposures. Public-source D2 and 25OHD2 PK data in healthy or osteoporotic populations, including 17 studies representing 278 individuals (15 individual-level and 18 arm-level units), were selected using search criteria in PUBMED. Data included oral, single and multiple D2 doses (400-100,000 IU/d). Nonlinear mixed effects models were developed simultaneously for D2 and 25OHD2 PK (NONMEM v7.2) by considering 1- and 2-compartment models with linear or nonlinear clearance. Unit-level random effects and residual errors were weighted by arm sample size. Model simulations compared 25OHD exposures, following repeated D2 and D3 oral administration across typical dosing and baseline ranges. D2 parent and metabolite were each described by 2-compartment models with numerous parameter estimates shared with the D3-25OHD3 model [1]. Notably, parent D2 was eliminated (converted to 25OHD) through a first-order clearance whereas the previously published D3 model [1] included a saturable non-linear clearance. Similar to 25OHD3 PK model results [1], 25OHD2 was eliminated by a first-order clearance, which was almost twice as fast as the former. Simulations at lower baselines, following lower equivalent doses, indicated that D3 was more effective than D2 at raising 25OHD concentrations. Due to saturation of D3 clearance, however, at higher doses or baselines, the probability of D2 surpassing D3's ability to raise 25OHD concentrations increased substantially. Since 25OHD concentrations generally surpassed 75 nmol/L at these higher baselines by 3 months, there would be no expected clinical difference in the two forms.

The endocannabinoid 2-arachidonoylglycerol mediates D1 and D2 receptor cooperative enhancement of rat nucleus accumbens core neuron firing.

PubMed

Seif, T; Makriyannis, A; Kunos, G; Bonci, A; Hopf, F W

2011-10-13

Many motivated and addiction-related behaviors are sustained by activity of both dopamine D1- and D2-type receptors (D1Rs and D2Rs) as well as CB1 receptors (CB1Rs) in the nucleus accumbens (NAc). Here, we use in vitro whole-cell patch-clamp electrophysiology to describe an endocannabinoid (eCB)-dopamine receptor interaction in adult rat NAc core neurons. D1R and D2R agonists in combination enhanced firing, with no effect of a D1R or D2R agonist alone. This D1R+D2R-mediated firing increase required CB1Rs, since it was prevented by the CB1R antagonists AM251 and Rimonabant. The D1R+D2R firing increase also required phospholipase C (PLC), the major synthesis pathway for the eCB 2-arachidonoylglycerol (2-AG) and one of several pathways for anandamide. Further, inhibition of 2-AG hydrolysis with the monoglyceride lipase (MGL) inhibitor JZL184 allowed subthreshold levels of D1R+D2R receptor agonists to enhance firing, while inhibition of anandamide hydrolysis with the fatty acid amide hydrolase (FAAH) inhibitors URB597 or AM3506 did not. Filling the postsynaptic neuron with 2-AG enabled subthreshold D1R+D2R agonists to increase firing, and the 2AG+D1R+D2R increase in firing was prevented by a CB1R antagonist. Also, the metabotropic glutamate receptor 5 (mGluR5) blocker MPEP prevented the ability of JZL184 to promote subthreshold D1R+D2R enhancement of firing, while the 2-AG+D1R+D2R increase in firing was not prevented by the mGluR5 blocker, suggesting that mGluR5s acted upstream of 2-AG production. Thus, our results taken together are consistent with the hypothesis that NAc core eCBs mediate dopamine receptor (DAR) enhancement of firing, perhaps providing a cellular mechanism underlying the central role of NAc core D1Rs, D2Rs, CB1Rs, and mGluR5s during many drug-seeking behaviors. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

THE ENDOCANNABINOID 2-ARACHIDONOYLGLYCEROL MEDIATES D1 AND D2 RECEPTOR COOPERATIVE ENHANCEMENT OF RAT NUCLEUS ACCUMBENS CORE NEURON FIRING

PubMed Central

Seif, T.; Makriyannis, A.; Kunos, G.; Bonci, A.; Hopf, F. W.

2011-01-01

Many motivated and addiction-related behaviors are sustained by activity of both dopamine D1- and D2-type receptors (D1Rs and D2Rs) as well as CB1 receptors (CB1Rs) in the nucleus accumbens (NAc). Here, we use in vitro whole-cell patch-clamp electrophysiology to describe an endocannabinoid (eCB)–dopamine receptor interaction in adult rat NAc core neurons. D1R and D2R agonists in combination enhanced firing, with no effect of a D1R or D2R agonist alone. This D1R+D2R-mediated firing increase required CB1Rs, since it was prevented by the CB1R antagonists AM251 and Rimonabant. The D1R+D2R firing increase also required phospholipase C (PLC), the major synthesis pathway for the eCB 2-arachidonoylglycerol (2-AG) and one of several pathways for anandamide. Further, inhibition of 2-AG hydrolysis with the monoglyceride lipase (MGL) inhibitor JZL184 allowed subthreshold levels of D1R+D2R receptor agonists to enhance firing, while inhibition of anandamide hydrolysis with the fatty acid amide hydrolase (FAAH) inhibitors URB597 or AM3506 did not. Filling the postsynaptic neuron with 2-AG enabled subthreshold D1R+D2R agonists to increase firing, and the 2AG+D1R+D2R increase in firing was prevented by a CB1R antagonist. Also, the metabotropic glutamate receptor 5 (mGluR5) blocker MPEP prevented the ability of JZL184 to promote subthreshold D1R+D2R enhancement of firing, while the 2-AG+D1R+D2R increase in firing was not prevented by the mGluR5 blocker, suggesting that mGluR5s acted upstream of 2-AG production. Thus, our results taken together are consistent with the hypothesis that NAc core eCBs mediate dopamine receptor (DAR) enhancement of firing, perhaps providing a cellular mechanism underlying the central role of NAc core D1Rs, D2Rs, CB1Rs, and mGluR5s during many drug-seeking behaviors. PMID:21821098

Delineating the role of ripples on the thermal expansion of 2D honeycomb materials: graphene, 2D h-BN and monolayer (ML)-MoS2.

PubMed

Anees, P; Valsakumar, M C; Panigrahi, B K

2017-04-19

We delineated the role of thermally excited ripples on the thermal expansion properties of 2D honeycomb materials (free-standing graphene, 2D h-BN, and ML-MoS 2 ), by explicitly carrying out three-dimensional (3D) and two-dimensional (2D) molecular dynamics simulations. In 3D simulations, the in-plane lattice parameter (a-lattice) of graphene and 2D h-BN shows thermal contraction over a wide range of temperatures and exhibits a strong system size dependence. The 2D simulations of the very same system show a reverse trend, where the a-lattice expands in the whole computed temperature range. In contrast to graphene and 2D h-BN, the a-lattice of ML-MoS 2 shows thermal expansion in both 2D and 3D simulations and their system size dependence is marginal. By analyzing the phonon dispersion at 300 K, we found that the discrepancy between 2D and 3D simulations of graphene and 2D h-BN is due to the absence of out-of-plane bending modes (ZA) in 2D simulations, which is responsible for the thermal contraction of the a-lattice at low temperature. Meanwhile, all the phonon modes are present in the 2D phonon dispersion of ML-MoS 2 , which indicates that the origin of the ZA mode is not purely due to the out-of-plane movement of atoms and also its effect on thermal expansion is not significant as found in graphene and 2D h-BN.

An intracellular loop 2 amino acid residue determines differential binding of arrestin to the dopamine D2 and D3 receptors.

PubMed

Lan, Hongxiang; Teeter, Martha M; Gurevich, Vsevolod V; Neve, Kim A

2009-01-01

Dopamine D(2) and D(3) receptors are similar subtypes with distinct interactions with arrestins; the D(3) receptor mediates less agonist-induced translocation of arrestins than the D(2) receptor. The goals of this study were to compare nonphosphorylated arrestin-binding determinants in the second intracellular domain (IC2) of the D(2) and D(3) receptors to identify residues that contribute to the differential binding of arrestin to the subtypes. Arrestin 3 bound to glutathione transferase (GST) fusion proteins of the D(2) receptor IC2 more avidly than to the D(3) receptor IC2. Mutagenesis of the fusion proteins identified a residue at the C terminus of IC2, Lys149, that was important for the preferential binding of arrestin 3 to D(2)-IC2; arrestin binding to D(2)-IC2-K149C was greatly decreased compared with wild-type D(2)-IC2, whereas binding to the reciprocal mutant D(3)-IC2-C147K was enhanced compared with wild-type D(3)-IC2. Mutating this lysine in the full-length D(2) receptor to cysteine decreased the ability of the D(2) receptor to mediate agonist-induced arrestin 3 translocation to the membrane and decreased agonist-induced receptor internalization in human embryonic kidney 293 cells. The reciprocal mutation in the D(3) receptor increased receptor-mediated translocation of arrestin 3 without affecting agonist-induced receptor internalization. G protein-coupled receptor crystal structures suggest that Lys149, at the junction of IC2 and the fourth membrane-spanning helix, has intramolecular interactions that contribute to maintaining an inactive receptor state. It is suggested that the preferential agonist-induced binding of arrestin3 to the D(2) receptor over the D(3) receptor is due in part to Lys149, which could be exposed as a result of receptor activation.

Vitamin D(3) is more potent than vitamin D(2) in humans.

PubMed

Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G

2011-03-01

Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

Ultrafast Charge Transfer and Hybrid Exciton Formation in 2D/0D Heterostructures

DOE PAGES

Boulesbaa, Abdelaziz; Wang, Kai; Mahjouri-Samani, Masoud; ...

2016-10-18

We report that photoinduced interfacial charge transfer is at the heart of many applications, including photovoltaics, photocatalysis, and photodetection. With the emergence of a new class of semiconductors such as monolayer two-dimensional transition metal dichalcogenides (2D-TMDs), charge transfer at the 2D/2D heterojunctions attracted several efforts due to the remarkable optical and electrical properties of 2D-TMDs. Unfortunately, in 2D/2D heterojunctions, for a given combination of two materials, the relative energy band alignment and the charge transfer efficiency are locked. Due to their large variety and broad size tunability, semiconductor quantum dots (0D-QDs) interfaced with 2D-TMDs may become an attractive heterostructure formore » optoelectronic applications. Here, we incorporate femtosecond pump-probe spectroscopy to reveal the sub-45 fs charge transfer at a 2D/0D heterostructure composed of tungsten disulfide monolayers (2D-WS 2) and a single layer of cadmium selenide (CdSe)/zinc sulfide (ZnS) core/shell 0D-QDs. Furthermore, ultrafast dynamics and steady-state measurements suggested that following electron transfer from the 2D to the 0D, hybrid excitons (HXs), wherein the electron resides in the 0D and hole resides in the 2D-TMD monolayer, are formed with a binding energy on the order of ~140 meV, which is several times lower than that of tightly bound excitons in 2D-TMDs.« less

Ultrafast Charge Transfer and Hybrid Exciton Formation in 2D/0D Heterostructures

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

Boulesbaa, Abdelaziz; Wang, Kai; Mahjouri-Samani, Masoud

We report that photoinduced interfacial charge transfer is at the heart of many applications, including photovoltaics, photocatalysis, and photodetection. With the emergence of a new class of semiconductors such as monolayer two-dimensional transition metal dichalcogenides (2D-TMDs), charge transfer at the 2D/2D heterojunctions attracted several efforts due to the remarkable optical and electrical properties of 2D-TMDs. Unfortunately, in 2D/2D heterojunctions, for a given combination of two materials, the relative energy band alignment and the charge transfer efficiency are locked. Due to their large variety and broad size tunability, semiconductor quantum dots (0D-QDs) interfaced with 2D-TMDs may become an attractive heterostructure formore » optoelectronic applications. Here, we incorporate femtosecond pump-probe spectroscopy to reveal the sub-45 fs charge transfer at a 2D/0D heterostructure composed of tungsten disulfide monolayers (2D-WS 2) and a single layer of cadmium selenide (CdSe)/zinc sulfide (ZnS) core/shell 0D-QDs. Furthermore, ultrafast dynamics and steady-state measurements suggested that following electron transfer from the 2D to the 0D, hybrid excitons (HXs), wherein the electron resides in the 0D and hole resides in the 2D-TMD monolayer, are formed with a binding energy on the order of ~140 meV, which is several times lower than that of tightly bound excitons in 2D-TMDs.« less

New antagonists of LHRH. II. Inhibition and potentiation of LHRH by closely related analogues.

PubMed

Bajusz, S; Csernus, V J; Janaky, T; Bokser, L; Fekete, M; Schally, A V

1988-12-01

Modifications of the previously described LHRH antagonists, [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Trp3, D-Cit6, D-Ala10]LHRH and the corresponding D-Hci6 analogue, have been made to alter the hydrophobicity of the N-terminal acetyl-tripeptide portion. Substitution of D-Trp3 with the less hydrophobic D-Pal(3) had only marginal effects on the antagonistic activities and receptor binding potencies of the D-Cit/D-Hci6 analogues, but it appeared to further improve the toxicity lowering effect of D-Cit/D-Hci6 substitution. Antagonists containing D-Pal(3)3 and D-Cit/D-Hci6 residues, i.e. [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]LHRH (SB-75) and [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Hci6, D-Ala10]LHRH (SB-88), were completely free of the toxic effects, such as cyanosis and respiratory depression leading to death, which have been observed in rats with the D-Trp3, D-Arg6 antagonist and related antagonists. Replacement of the N-acetyl group with the hydrophilic carbamoyl group caused a slight decrease in antagonistic activities, particularly in vitro. Introduction of urethane type acyl group such as methoxycarbonyl (Moc) or t-butoxycarbonyl (Boc) led to analogues that showed LHRH-potentiating effect. The increase in potency induced by these analogues, e.g. [Moc-D-Nal(2)1, D-Phe(4Cl)2, D-Trp3, D-Cit6, D-Ala10]LHRH and [Boc-D-Phe1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]LHRH, was 170-260% and persisted for more than 2 h when studied in a superfused rat pituitary system.

Breast screening using 2D-mammography or integrating digital breast tomosynthesis (3D-mammography) for single-reading or double-reading--evidence to guide future screening strategies.

PubMed

Houssami, Nehmat; Macaskill, Petra; Bernardi, Daniela; Caumo, Francesca; Pellegrini, Marco; Brunelli, Silvia; Tuttobene, Paola; Bricolo, Paola; Fantò, Carmine; Valentini, Marvi; Ciatto, Stefano

2014-07-01

We compared detection measures for breast screening strategies comprising single-reading or double-reading using standard 2D-mammography or 2D/3D-mammography, based on the 'screening with tomosynthesis or standard mammography' (STORM) trial. STORM prospectively examined screen-reading in two sequential phases, 2D-mammography alone and integrated 2D/3D-mammography, in asymptomatic women participating in Trento and Verona (Northern Italy) population-based screening services. Outcomes were ascertained from assessment and/or excision histology or follow-up. For each screen-reading strategy we calculated the number of detected and non-detected (including interval) cancers, cancer detection rates (CDRs), false positive recall (FPR) measures and incremental CDR relative to a comparator strategy. We estimated the false:true positive (FP:TP) ratio and sensitivity of each mammography screening strategy. Paired binary data were compared using McNemar's test. Amongst 7292 screening participants, there were 65 (including six interval) breast cancers; estimated first-year interval cancer rate was 0.82/1000 screens (95% confidence interval (CI): 0.30-1.79/1000). For single-reading, 35 cancers were detected at both 2D and 2D/3D-mammography, 20 cancers were detected only with 2D/3D-mammography compared with none at 2D-mammography alone (p<0.001) and 10 cancers were not detected. For double-reading, 39 cancers were detected at 2D-mammography and 2D/3D-mammography, 20 were detected only with 2D/3D-mammography compared with none detected at 2D-mammography alone (p<0.001) and six cancers were not detected. The incremental CDR attributable to 2D/3D-mammography (versus 2D-mammography) of 2.7/1000 screens (95% CI: 1.6-4.2) was evident for single and for double-reading. Incremental CDR attributable to double-reading (versus single-reading) of 0.55/1000 screens (95% CI: -0.02-1.4) was evident for 2D-mammography and for 2D/3D-mammography. Estimated FP:TP ratios showed that 2D/3D-mammography screening strategies had more favourable FP to TP trade-off and higher sensitivity, applying single-reading or double-reading, relative to 2D-mammography screening. The evidence we report warrants rethinking of breast screening strategies and should be used to inform future evaluations of 2D/3D-mammography that assess whether or not the estimated incremental detection translates into improved screening outcomes such as a reduction in interval cancer rates. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Indian Ocean Validation,

DTIC Science & Technology

1987-09-01

S9 fd 30 2 D0i 0m10 20 802 AR. Oy ad n A o io in 3 0 3 7 ..n . . . w o w., , ... .. . . . . d ata m gaterng eie ws amdfe Lito sT-1 Omeg nav~igtion AE...signals propagated from each of N stations over paths of 2-10 length dl, d2, ... as shown in Figure 2.1. Station 2 Station N Station 1 D dl SUBJECT Figure...t2* = (d1* - d2*)/c + ( El - 62) t2* - t3* = (d2* - d3*)/c + ( E2 - E3) t*N 1 - t*N - ( d *N 1 - dN*)/c + ( N-1 EN) (6) 47he results obtained in

Synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 3-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

PubMed

Dubey, R; Jain, R K; Abbas, S A; Matta, K L

1987-08-01

Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha- D-mannopyranoside (4) and methyl 2-O-benzyl-3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (6) were prepared from a common intermediate, namely, methyl 2-O-benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D- mannopyranosyl)-alpha-D-mannopyranoside. On treatment with tert-butylchlorodiphenylsilane, in N,N-dimethylformamide in the presence of imidazole, 4 and 6 afforded methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (7), and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert- butyldiphenylsilyl-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (8), respectively. Compound 8 was converted into its 2,3-O-isopropylidene derivative (9), and oxidation of 7 and 9 with pyridinium chlorochromate, and reduction of the resulting carbonyl intermediates gave methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-talopyranoside and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert-butyldiphe nylsilyl- 2,3-O-isopropylidene-alpha-D-talopyranosyl)-alpha-D-talopyranoside , respectively. Removal of the protecting groups furnished the title disaccharides.

Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

PubMed Central

Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

2014-01-01

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [35S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction. PMID:24513972

Amphetamine self-administration attenuates dopamine D2 autoreceptor function.

PubMed

Calipari, Erin S; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C; Jones, Sara R; Chen, Rong

2014-07-01

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [(35)S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.

SU-E-T-202: Comparison of 4D-Measurement-Guided Dose Reconstructions (MGDR) with COMPASS and OCTAVIUS 4D System

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

Leung, R; Wong, M; Lee, V

2015-06-15

Purpose: To cross-validate the MGDR of COMPASS (IBA dosimetry, GmbH, Germany) and OCTAVIUS 4D system (PTW, Freiburg, Germany). Methods: Volumetric-modulated arc plans (5 head-and-neck and 3 prostate) collapsed to 40° gantry on the OCTAVIUS 4D phantom in QA mode on Monaco v5.0 (Elekta, CMS, Maryland Heights, MO) were delivered on a Elekta Agility linac. This study was divided into two parts: (1) error-free measurements by gantry-mounted EvolutionXX 2D array were reconstructed in COMPASS (IBA dosimetry, GmbH, Germany), and by OCTAVIUS 1500 array in Versoft v6.1 (PTW, Freiburg, Germany) to obtain the 3D doses (COM4D and OCTA4D). COM4D and OCTA4D weremore » compared to the raw measurement (OCTA3D) at the same detector plane for which OCTAVIUS 1500 was perpendicular to 0° gantry axis while the plans were delivered at gantry 40°; (2) beam steering errors of energy (Hump=-2%) and symmetry (2T=+2%) were introduced during the delivery of 5 plans to compare the MGDR doses COM4D-Hump (COM4D-2T), OCTA4D-Hump (OCTA4D-2T), with raw doses OCTA3D-Hump (OCTA3D-2T) and with OCTA3D to assess the error reconstruction and detection ability of MGDR tools. All comparisons used Υ-criteria of 2%(local dose)/2mm and 3%/3mm. Results: Averaged Υ passing rates were 85% and 96% for COM4D,and 94% and 99% for OCTA4D at 2%/2mm and 3%/3mm criteria respectively. For error reconstruction, COM4D-Hump (COM4D-2T) showed 81% (93%) at 2%/2mm and 94% (98%) at 3%/3mm, while OCTA4D-Hump (OCTA4D-2T) showed 96% (96%) at 2%/2mm and 99% (99%) at 3%/3mm. For error detection, OCTA3D doses were compared to COM4D-Hump (COM4D-2T) showing Υ passing rates of 93% (93%) at 2%/2mm and 98% (98%), and to OCTA4D-Hump (OCTA4D -2T) showing 94% (99%) at 2%/2mm and 81% (96%) at 3%/3mm, respectively. Conclusion: OCTAVIUS MGDR showed better agreement to raw measurements in both error- and error-free comparisons. COMPASS MGDR deviated from the raw measurements possibly owing to beam modeling uncertainty.« less

Digit ratio (2D:4D), aggression, and testosterone in men exposed to an aggressive video stimulus.

PubMed

Kilduff, Liam P; Hopp, Renato N; Cook, Christian J; Crewther, Blair T; Manning, John T

2013-10-10

The relative lengths of the 2(nd) and 4(th) digits (2D:4D) is a negative biomarker for prenatal testosterone, and low 2D:4D may be associated with aggression. However, the evidence for a 2D:4D-aggression association is mixed. Here we test the hypothesis that 2D:4D is robustly linked to aggression in "challenge" situations in which testosterone is increased. Participants were exposed to an aggressive video and a control video. Aggression was measured after each video and salivary free testosterone levels before and after each video. Compared to the control video, the aggressive video was associated with raised aggression responses and a marginally significant increase in testosterone. Left 2D:4D was negatively correlated with aggression after the aggressive video and the strength of the correlation was higher in those participants who showed the greatest increases in testosterone. Left 2D:4D was also negatively correlated to the difference between aggression scores in the aggressive and control conditions. The control video did not influence testosterone concentrations and there were no associations between 2D:4D and aggression. We conclude that 2D:4D moderates the impact of an aggressive stimulus on aggression, such that an increase in testosterone resulting from a "challenge" is associated with a negative correlation between 2D:4D and aggression.

Lipoprotein lipase links vitamin D, insulin resistance, and type 2 diabetes: a cross-sectional epidemiological study

PubMed Central

2013-01-01

Background Lipoprotein lipase (LPL) and serum 25-hydroxyvitamin D [25(OH)D] play important roles in the regulation of lipid metabolism. Although dyslipidemia is associated with insulin resistance (IR) and type 2 diabetes (T2D), there are limited data available regarding the relationship of LPL and 25(OH)D to IR and T2D at a population level. The objective of the present study is to investigate the associations of LPL and 25(OH)D with IR and T2D in a Chinese population. Methods The study cohort consisted of 2708 subjects (1326 males, 1382 females; mean age 48.5 ± 12.6 years) in main communities of Harbin, China. Serum 25(OH)D, LPL, free fatty acids (FFAs), fasting glucose (FG), fasting insulin, lipid profile, apoA and apoB concentrations were measured. Results Serum 25(OH)D concentration was positively associated with LPL (β = 0.168, P < 0.001). LPL was inversely associated with IR and T2D. Subjects in the lowest quartile of LPL had the highest risk of IR [odds ratio (OR) = 1.85, 95% CI = 1.22-2.68] and T2D (OR = 1.65, 95% CI = 1.14-2.38). Serum 25(OH)D was also inversely associated with IR and T2D. Vitamin D deficiency [25(OH)D < 20 ng/ml] was associated with an increasing risk of IR (OR = 1.91, 95% CI = 1.23-2.76) and T2D (OR = 2.06, 95% CI = 1.37-3.24). The associations of 25(OH)D with IR and T2D were attenuated by further adjustment for LPL. Conclusions LPL is associated with serum 25(OH)D, IR and T2D in the Chinese population. These results suggest a potential mediating role of LPL in the associations of 25(OH)D with IR and T2D. PMID:23320821

Dopamine D4 receptor, but not the ADHD-associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain

PubMed Central

González, Sergio; Rangel-Barajas, Claudia; Peper, Marcela; Lorenzo, Ramiro; Moreno, Estefanía; Ciruela, Francisco; Borycz, Janusz; Ortiz, Jordi; Lluís, Carme; Franco, Rafael; McCormick, Peter J.; Volkow, Nora D.; Rubinstein, Marcelo; Floran, Benjamin; Ferré, Sergi

2011-01-01

Polymorphic variants of the dopamine D4 receptor have been consistently associated with attention-deficit hyperactivity disorder (ADHD). However the functional significance of the risk polymorphism (variable number of tandem repeats in exon 3) is still unclear. Here we show that whereas the most frequent 4-repeat (D4.4) and the 2-repeat (D4.2) variants form functional heteromers with the short isoform of the dopamine D2 receptor (D2S), the 7-repeat risk allele (D4.7) does not. D2 receptor activation in the D2S-D4 receptor heteromer potentiates D4 receptor-mediated MAPK signaling in transfected cells and in the striatum, which did not occur in cells expressing D4.7 or in the striatum of knock-in mutant mice carrying the 7 repeats of the human D4.7 in the third intracellular loop of the D4 receptor. In the striatum D4 receptors are localized in cortico-striatal glutamatergic terminals, where they selectively modulate glutamatergic neurotransmission by interacting with D2S receptors. This interaction shows the same qualitative characteristics than the D2S-D4 receptor heteromer-mediated MAPK signaling and D2S receptor activation potentiates D4 receptor-mediated inibition of striatal glutamate release. It is therefore postulated that dysfunctional D2S-D4.7 heteromers may impair presynaptic dopaminergic control of corticostriatal glutamatergic neurotransmission and explain functional deficits associated with ADHD. PMID:21844870

Emotional response in dopamine D2L receptor-deficient mice

PubMed Central

Hranilovic, Dubravka; Bucan, Maja; Wang, Yanyan

2008-01-01

The dopamine D2 receptor (D2R) system has been implicated in emotional processing which is often impaired in neuropsychiatric disorders. The long (D2L) and the short (D2S) isoforms of D2R are generated by alternative splicing of the same gene. To study differential roles of the two D2R isoforms, D2L-deficient mice (D2L−/−) expressing functional D2S were previously generated. In this study the contribution of D2L isoform to emotional response was investigated by examining behaviors that reflect emotionality (exploratory behavior, anxiety-like behavior and learned helplessness) in D2L−/− and (wild-type) WT mice. While the thigmotactic, locomotor and general components of anxiety in zero maze did not differ among the genotypes, D2L−/− mice displayed significantly lower level of exploration in a hole board and zero maze, and significantly higher increase in latency to escape from a foot shock after the learned helplessness training, compared with WT mice. These results suggest that D2L may play a more prominent role than D2S in mediating emotional response, such as behavioral reactions to novelty and inescapable stress. Our findings contribute to a better understanding of the molecular and cellular mechanisms underlying emotional responses. PMID:18835570

Comparison of 4D flow and 2D velocity-encoded phase contrast MRI sequences for the evaluation of aortic hemodynamics

PubMed Central

Bollache, Emilie; van Ooij, Pim; Powell, Alex; Carr, James; Markl, Michael; Barker, Alex J.

2016-01-01

The purpose of this study was to compare aortic flow and velocity quantification using 4D flow MRI and 2D CINE phase-contrast (PC)-MRI with either one-directional (2D-1dir) or three-directional (2D-3dir) velocity encoding. 15 healthy volunteers (51 ± 19 years) underwent MRI including (1) breath-holding 2D-1dir and (2) free breathing 2D-3dir PC-MRI in planes orthogonal to the ascending (AA) and descending (DA) aorta, as well as (3) free breathing 4D flow MRI with full thoracic aorta coverage. Flow quantification included the co-registration of the 2D PC acquisition planes with 4D flow MRI data, AA and DA segmentation, and calculation of AA and DA peak systolic velocity, peak flow and net flow volume for all sequences. Additionally, the 2D-3dir velocity taking into account the through-plane component only was used to obtain results analogous to a free breathing 2D-1dir acquisition. Good agreement was found between 4D flow and 2D-3dir peak velocity (differences = −3 to 6 %), peak flow (−7 %) and net volume (−14 to −9 %). In contrast, breath-holding 2D-1dir measurements exhibited indices significantly lower than free breathing 2D-3dir and 2D-1dir (differences = −35 to −7 %, p < 0.05). Finally, high correlations (r ≥ 0.97) were obtained for indices estimated with or without eddy current correction, with the lowest correlation observed for net volume. 4D flow and 2D-3dir aortic hemodynamic indices were in concordance. However, differences between respiration state and 2D-1dir and 2D-3dir measurements indicate that reference values should be established according to the PC-MRI sequence, especially for the widely used net flow (e.g. stroke volume in the AA). PMID:27435230

Effect of vitamin D treatments on plasma metabolism and immune parameters of healthy dairy cows.

PubMed

Yue, Yuan; Hymøller, Lone; Jensen, Søren Krogh; Lauridsen, Charlotte

2018-06-01

The objective of this study was to investigate the possible beneficial effect of vitamin D repletion on certain immune parameters of vitamin D insufficient dairy cows. Twenty dairy cows in late lactation were treated daily with vitamin D in five different ways: sunlight exposure (SUN), D 2 supplementation combined with sunlight exposure (D2SUN), D 2 supplementation (D2), D 3 supplementation (D3), and D 2 and D 3 supplementation combined (D2D3). The cows had very low vitamin D levels at d 0 because of the vitamin D deprivation before the study. After 1 month of vitamin D repletion, all cows had plasma 25(OH)D levels within the normal range. Total 25(OH)D concentration was significantly higher in SUN, D2SUN and D2D3 than D2 or D3 at the end of the study. However, milk yield, as well as protein and fat content of the milk, was not influenced by vitamin D treatments. There was no difference obtained in the measured immune parameters: Leucocyte populations, somatic cell count, immunoglobulin concentrations in plasma and milk, and antigen-stimulated cytokine productions did not change in response to vitamin D repletion or difference in vitamin D sources, and no relations to plasma 25(OH)D levels were identified. Despite the fact that plasma 25(OH)D increased from a very low level to normal range, the present study did not show any effect of vitamin D repletion on the tested immune parameters of healthy dairy cows. Therefore, in this study, it was concluded that repletion to physiologically normal plasma 25-hydroxyvitamin D levels of vitamin D-depleted healthy dairy cows had no influence on immune parameters.

Infrared spectra and tunneling dynamics of the N2-D2O and OC-D2O complexes in the v2 bend region of D2O.

PubMed

Zhu, Yu; Zheng, Rui; Li, Song; Yang, Yu; Duan, Chuanxi

2013-12-07

The rovibrational spectra of the N2-D2O and OC-D2O complexes in the v2 bend region of D2O have been measured in a supersonic slit jet expansion using a rapid-scan tunable diode laser spectrometer. Both a-type and b-type transitions were observed for these two complexes. All transitions are doubled, due to the heavy water tunneling within the complexes. Assuming the tunneling splittings are the same in K(a) = 0 and K(a) = 1, the band origins, all three rotational and several distortion constants of each tunneling state were determined for N2-D2O in the ground and excited vibrational states, and for OC-D2O in the excited vibrational state, respectively. The averaged band origin of OC-D2O is blueshifted by 2.241 cm(-1) from that of the v2 band of the D2O monomer, compared with 1.247 cm(-1) for N2-D2O. The tunneling splitting of N2-D2O in the ground state is 0.16359(28) cm(-1), which is about five times that of OC-D2O. The tunneling splittings decrease by about 26% for N2-D2O and 23% for OC-D2O, respectively, upon excitation of the D2O bending vibration, indicating an increase of the tunneling barrier in the excited vibrational state. The tunneling splittings are found to have a strong dependence on intramolecular vibrational excitation as well as a weak dependence on quantum number K(a).

Neurochemical evidence supporting dopamine D1-D2 receptor heteromers in the striatum of the long-tailed macaque: changes following dopaminergic manipulation.

PubMed

Rico, Alberto J; Dopeso-Reyes, Iria G; Martínez-Pinilla, Eva; Sucunza, Diego; Pignataro, Diego; Roda, Elvira; Marín-Ramos, David; Labandeira-García, José L; George, Susan R; Franco, Rafael; Lanciego, José L

2017-05-01

Although it has long been widely accepted that dopamine receptor types D1 and D2 form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers has been recently challenged. In an attempt to properly characterize D1-D2 receptor heteromers, here we have used the in situ proximity ligation assay (PLA) in striatal sections comprising the caudate nucleus, the putamen and the core and shell territories of the nucleus accumbens. Experiments were carried out in control macaques as well as in MPTP-treated animals (with and without dyskinesia). Obtained data support the presence of D1-D2 receptor heteromers within all the striatal subdivisions, with the highest abundance in the accumbens shell. Dopamine depletion by MPTP resulted in an increase of D1-D2 density in caudate and putamen which was normalized by levodopa treatment. Two different sizes of heteromers were consistently found, thus suggesting that besides individual heteromers, D1-D2 receptor heteromers are sometimes organized in macromolecular complexes made of a number of D1-D2 heteromers. Furthermore, the PLA technique was combined with different neuronal markers to properly characterize the identities of striatal neurons expressing D1-D2 heteromers. We have found that striatal projection neurons giving rise to either the direct or the indirect basal ganglia pathways expressed D1-D2 heteromers. Interestingly, macromolecular complexes of D1-D2 heteromers were only found within cholinergic interneurons. In summary, here we provide overwhelming proof that D1 and D2 receptors form heteromeric complexes in the macaque striatum, thus representing a very appealing target for a number of brain diseases involving dopamine dysfunction.

Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

PubMed Central

Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

2016-01-01

Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

Tuning different kinds of entangled metal-organic frameworks by modifying the spacer group of aliphatic dicarboxylate ligands and the reactant ratio.

PubMed

Yang, Jin-Xia; Zhai, Ji-Quan; Zhang, Xin; Qin, Ye-Yan; Yao, Yuan-Gen

2016-01-14

Taking advantage of the conformational flexibility of the bpp ligand and aliphatic dicarboxylic acids, six interesting entangled coordination polymers, {[Cd(fum)(bpp)(H2O)]·(H2O)}n (), {[Cd(fum)(bpp)2]·(H2O)5}n (), {[Cd2(suc)1.5(bpp)2(NO3)(H2O)2]·6H2O}n (), {[Cd(suc)(bpp)2]·(H2O)1.5}n (), {[Cd2(glu)2(bpp)3]·10H2O}n (), and {Cd(adp)(bpp)(H2O)}n () have been prepared and structurally characterized (bpp = 1,3-bi(4-pyridyl)propane, fum = fumaric, suc = succinate, glu = glutaric, adp = adipic). Compounds and are comprised of undulated 2D 4(4)-sql networks. In the structure of compound , two identical undulated layers are parallelly interpenetrated with each other to give a 2D → 2D interpenetrating framework. For , the dangling arms projected from 2D layers are intercalated into the neighboring sheets, producing a 2D → 3D polythreading framework. Compound shows a rare example of a 2D self-penetrating framework with a (3,4)-connected (4(2)·6(3)·8)(4(2)·6) topology. Compound presents an unusual 2D self-threading network with a novel 4-connected {4(2)·6(3)·8} topology. Compound displays a 3D self-penetrating system based on a 2D → 3D parallel polycatenation array. Compound exhibits an unprecedented 3D self-penetrating structure having both 1D + 1D → 1D polycatenation and 3D + 3D → 3D interpenetration characteristics. A comparison of these six compounds demonstrates that both the different spacer lengths of the aliphatic dicarboxylates and reactant ratios appear to play a significant role in the assembly of entangled frameworks. In addition, thermal stabilities and photoluminescence properties of have been examined in the solid state at room temperature.

Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

PubMed

Jain, R K; Dubey, R; Abbas, S A; Matta, K L

1987-03-15

Treatment of methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (1) with tert-butyldiphenylsilyl chloride in N,N-dimethylformamide afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (2). Oxidation of 2 with pyridinium chlorochromate, followed by reduction of the carbonyl group, and subsequent O-deacetylation afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-alpha-D-mannopyranosyl- alpha-D- talopyranoside (5). Cleavage of the tert-butyldiphenylsilyl group of 5 with tetrabutylammonium fluoride in oxolane, followed by hydrogenolysis, gave methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside (7). O-Deacetylation of 1 gave methyl 3-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (8). Treatment of 8 with tert-butyldiphenylsilyl chloride afforded a 6,6'-disilyl derivative, which was converted into a 2',3'-O-isopropylidene derivative, and then further oxidized with pyridinium chlorochromate. The resulting diketone was reduced and removal of the protecting groups gave methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside (15). The structures of both 7 and 15 were established by 13C-n.m.r. spectroscopy.

SU-E-T-20: A Correlation Study of 2D and 3D Gamma Passing Rates for Prostate IMRT Plans

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

Zhang, D; Sun Yat-sen University Cancer Center, Guangzhou, Guangdong; Wang, B

2015-06-15

Purpose: To investigate the correlation between the two-dimensional gamma passing rate (2D %GP) and three-dimensional gamma passing rate (3D %GP) in prostate IMRT quality assurance. Methods: Eleven prostate IMRT plans were randomly selected from the clinical database and were used to obtain dose distributions in the phantom and patient. Three types of delivery errors (MLC bank sag errors, central MLC errors and monitor unit errors) were intentionally introduced to modify the clinical plans through an in-house Matlab program. This resulted in 187 modified plans. The 2D %GP and 3D %GP were analyzed using different dose-difference and distance-toagreement (1%-1mm, 2%-2mm andmore » 3%-3mm) and 20% dose threshold. The 2D %GP and 3D %GP were then compared not only for the whole region, but also for the PTVs and critical structures using the statistical Pearson’s correlation coefficient (γ). Results: For different delivery errors, the average comparison of 2D %GP and 3D %GP showed different conclusions. The statistical correlation coefficients between 2D %GP and 3D %GP for the whole dose distribution showed that except for 3%/3mm criterion, 2D %GP and 3D %GP of 1%/1mm criterion and 2%/2mm criterion had strong correlations (Pearson’s γ value >0.8). Compared with the whole region, the correlations of 2D %GP and 3D %GP for PTV were better (the γ value for 1%/1mm, 2%/2mm and 3%/3mm criterion was 0.959, 0.931 and 0.855, respectively). However for the rectum, there was no correlation between 2D %GP and 3D %GP. Conclusion: For prostate IMRT, the correlation between 2D %GP and 3D %GP for the PTV is better than that for normal structures. The lower dose-difference and DTA criterion shows less difference between 2D %GP and 3D %GP. Other factors such as the dosimeter characteristics and TPS algorithm bias may also influence the correlation between 2D %GP and 3D %GP.« less

40 CFR 52.1783 - Original identification of plan section.

Code of Federal Regulations, 2013 CFR

2013-07-01

... of Particulates from Hot Mix Asphalt Plants 2D.0507—Particulates from Chemical Fertilizer Manufacturing Plants 2D.0508—Control of Particulates from Pulp and Paper Mills 2D.0509—Particulates from Mica or... Emissions from Bulk Gasoline Terminals 2D.0918—Can Coating 2D.0919—Coil Coating 2D.0920—Paper Coating 2D...

40 CFR 52.1783 - Original identification of plan section.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of Particulates from Hot Mix Asphalt Plants 2D.0507—Particulates from Chemical Fertilizer Manufacturing Plants 2D.0508—Control of Particulates from Pulp and Paper Mills 2D.0509—Particulates from Mica or... Emissions from Bulk Gasoline Terminals 2D.0918—Can Coating 2D.0919—Coil Coating 2D.0920—Paper Coating 2D...

40 CFR 52.1783 - Original identification of plan section.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of Particulates from Hot Mix Asphalt Plants 2D.0507—Particulates from Chemical Fertilizer Manufacturing Plants 2D.0508—Control of Particulates from Pulp and Paper Mills 2D.0509—Particulates from Mica or... Emissions from Bulk Gasoline Terminals 2D.0918—Can Coating 2D.0919—Coil Coating 2D.0920—Paper Coating 2D...

Measurement of semileptonic B decays into orbitally excited charmed mesons.

PubMed

Aubert, B; Bona, M; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Cahn, R N; Jacobsen, R G; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Ulmer, K A; Wagner, S R; Ayad, R; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Karbach, M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Mader, W F; Nogowski, R; Schubert, K R; Schwierz, R; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Klose, V; Lacker, H M; Bard, D J; Dauncey, P D; Nash, J A; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Firmino da Costa, J; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; George, K A; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Schott, G; Alwyn, K E; Bailey, D; Barlow, R J; Chia, Y M; Edgar, C L; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Li, X; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Wang, W F; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Del Amo Sanchez, P; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; Hamon, O; Leruste, Ph; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Escalier, M; Esteve, L; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Gabareen, A M; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Pierini, M; Prepost, R; Vuosalo, C O; Wu, S L

2009-07-31

We present a study of B decays into semileptonic final states containing charged and neutral D1(2420) and D_{2};{*}(2460). The analysis is based on a data sample of 208 fb;{-1} collected at the Upsilon(4S) resonance with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. With a simultaneous fit to four different decay chains, the semileptonic branching fractions are extracted from measurements of the mass difference Deltam=m(D;{**})-m(D) distributions. Product branching fractions are determined to be B(B;{+}-->D_{1};{0}l;{+}nu_{l})xB(D_{1};{0}-->D;{*+}pi;{-})=(2.97+/-0.17+/-0.17)x10;{-3}, B(B;{+}-->D_{2};{*0}l;{+}nu_{l})xB(D_{2};{*0}-->D;{(*)+}pi;{-})=(2.29+/-0.23+/-0.21)x10;{-3}, B(B;{0}-->D_{1};{-}l;{+}nu_{l})xB(D_{1};{-}-->D;{*0}pi;{-})=(2.78+/-0.24+/-0.25)x10;{-3} and B(B;{0}-->D_{2};{*-}l;{+}nu_{l})xB(D_{2};{*-}-->D;{(*)0}pi;{-})=(1.77+/-0.26+/-0.11)x10;{-3}. In addition we measure the branching ratio Gamma(D_{2};{*}-->Dpi;{-})/Gamma(D_{2};{*}-->D;{(*)}pi;{-})=0.62+/-0.03+/-0.02.

Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity

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

Sarfarazi, M.; Akarsu, A.N.; Hossain, A.

1995-11-20

Primary congenital glaucoma (GLC3) is an inherited eye disorder that accounts for 0.01-0.04% of total blindness. Although a large number of chromosomal abnormalities have already been reported in patients with congenital glaucoma, the precise location and pathogenesis of this condition remain elusive. By using a group of 17 GLC3 families and a combination of both candidate regional and general positional mapping strategies, we have mapped a locus for GLC3 to the short arm of chromosome 2. Eleven families showed no recombination with 3 tightly linked markers of D2S177 (Z = 9.40), D2S1346 (Z = 8.83), and D2S1348 (Z = 8.90)more » with a combined haplotype lod score of 11.50. Haplotype and multipoint linkage analyses of 14 DNA markers from 2p indicated that the disease gene is located in the 2p21 region and is flanked by DNA markers D2S1788/D2S1325 ({theta} = 0.03; Z = 5.42) and D2S1356 ({theta} = 0.05; Z = 4.69). Inspection of haplotype and heterogeneity analysis confirmed that 6 families are not linked to the 2p21 region, thus providing the first proof of genetic heterogeneity for this phenotype. We therefore designated the locus on 2p21 GLC3A and positioned it in the overall linkage map of Tel-D2S405-D2S367-(D2S1788/D2S1325)-[(GLC 3A,D2S177)/(D2S1346/D2S1348)]-D2S1356-D2S119-D2S1761-D2S1248-D2S1352-D2S406-D2S441-Cen. Of the seven genes mapping to the 2p21 region, CAD, CALM2, and LHCGR are centromeric to D2S119 and can be excluded as a candidate for GLC3A, but mutations in PRK-R, TIK, SOS1, or SPTBN1 may still be accountable for this phenotype. As human 2p21 shows homology with mouse chromosomes 11 and 17, the homolog of GLC3A is expected to reside on one of these two chromosomes. 36 refs., 3 figs., 5 tabs.« less

Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency.

PubMed

Lopez-Gomez, Carlos; Levy, Rebecca J; Sanchez-Quintero, Maria J; Juanola-Falgarona, Martí; Barca, Emanuele; Garcia-Diaz, Beatriz; Tadesse, Saba; Garone, Caterina; Hirano, Michio

2017-05-01

Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, deoxycytidine monophosphate (dCMP) and deoxythymidine monophosphate (dTMP), prolongs the life span of Tk2-deficient (Tk2 -/- ) mice by 2- to 3-fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: (1) deoxynucleosides might be the major active agents and (2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy. To test these hypotheses, we assessed two therapies in Tk2 -/- mice: (1) dT+dC and (2) coadministration of the deaminase inhibitor, tetrahydrouridine (THU), with dTMP+dCMP. We observed that dC+dT delayed disease onset, prolonged life span of Tk2-deficient mice and restored mtDNA copy number as well as respiratory chain enzyme activities and levels. In contrast, dCMP+dTMP+THU therapy decreased life span of Tk2 -/- animals compared to dCMP+dTMP. Our studies demonstrate that deoxynucleoside substrate enhancement is a novel therapy, which may ameliorate TK2 deficiency in patients. Ann Neurol 2017;81:641-652. © 2017 American Neurological Association.

Tunneling chemical reactions D+H{sub 2}{yields}DH+H and D+DH{yields}D{sub 2}+H in solid D{sub 2}-H{sub 2} and HD-H{sub 2} mixtures: An electron-spin-resonance study

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

Kumada, Takayuki

2006-03-07

Tunneling chemical reactions D+H{sub 2}{yields}DH+H and D+DH{yields}D{sub 2}+H in solid HD-H{sub 2} and D{sub 2}-H{sub 2} mixtures were studied in the temperature range between 4 and 8 K. These reactions were initiated by UV photolysis of DI molecules doped in these solids for 30 s and followed by measuring the time course of electron-spin-resonance (ESR) intensities of D and H atoms. ESR intensity of D atoms produced by the photolysis decreases but that of H atoms increases with time. Time course of the D and H intensities has the fast and slow processes. The fast process, which finishes within {approx}300more » s after the photolysis, is assigned to the reaction of D atom with one of its nearest-neighboring H{sub 2} molecules, D(H{sub 2}){sub n}(HD){sub 12-n}{yields}H(H{sub 2}){sub n-1}(HD){sub 13-n} or D(H{sub 2}){sub n}(D{sub 2}){sub 12-n}{yields}H(HD)(H{sub 2}){sub n-1}(D{sub 2}){sub 12-n} for 12{>=}n{>=}1. Rate constant for the D+H{sub 2} reaction between neighboring D atom-H{sub 2} molecule pair is determined to be (7.5{+-}0.7)x10{sup -3} s{sup -1} in solid HD-H{sub 2} and (1.3{+-}0.3)x10{sup -2} s{sup -1} in D{sub 2}-H{sub 2} at 4.1 K, which is very close to that calculated based on the theory of chemical reaction in gas phase by Hancock et al. [J. Chem. Phys. 91, 3492 (1989)] and Takayanagi and Sato [J. Chem. Phys. 92, 2862 (1990)]. This rate constant was found to be independent of temperature up to 7 K within experimental error of {+-}30%. The slow process is assigned to the reaction of D atom produced in a cage fully surrounded by HD or D{sub 2} molecules, D(HD){sub 12} or D(D{sub 2}){sub 12}. This D atom undergoes the D+DH reaction with one of its nearest-neighboring HD molecules in solid HD-H{sub 2} or diffuses to the neighbor of H{sub 2} molecules to allow the D+H{sub 2} reaction in solid HD-H{sub 2} and D{sub 2}-H{sub 2}. The former is the main channel in solid HD-H{sub 2} below 6 K where D atoms diffuse very slowly, whereas the latter dominates over the former above 6 K. Rate for the reactions in the slow process is independent of temperature below 6 K but increases with the increase in temperature above 6 K. We found that the increase is due to the increase in hopping rate of D atoms to the neighbor of H{sub 2} molecules. Rate constant for the D+DH reaction was found to be independent of temperature up to 7 K as well.« less

ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue

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

Liu, Xiaoxi, E-mail: xiaoxi.liu@uky.edu; Liu, Jingjing, E-mail: jingjing.liu0@gmail.com; Lester, Joshua D., E-mail: joshua.lester@uky.edu

2015-01-02

Highlights: • We examined the D2 localization and the proteome of D2-containing compartment in mouse adipose tissue. • We confirmed the presence of D2 on a subcellular compartment that has typical structure as a microperoxisome. • We demonstrated the scarcity of peroxisome markers on D2-containing compartment. • The D2-containing compartment may be a subpopulation of peroxisome in mouse adipose tissue. • Proteomic data suggests potential association between D2-containing compartment and mitochondria and ER. - Abstract: ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Bothmore » D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.« less

Semiautomated thyroid volumetry using 3D CT: prospective comparison with measurements obtained using 2D ultrasound, 2D CT, and water displacement method of specimen.

PubMed

Lee, Sun Jin; Chong, Semin; Kang, Kyung Ho; Hur, Joonho; Hong, Byung-Woo; Kim, Hyun Jung; Kim, Soo Jin

2014-11-01

The objective of our study was to measure thyroid volumes using semiautomated 3D CT and to compare the 3D CT volumes with volumes measured using 2D ultrasound, 2D CT, and the water displacement method. In 47 patients, 2D ultrasound volumes and 2D CT volumes of the thyroid gland were estimated using the ellipsoid volume formula, and 3D CT volumes were calculated using semiautomated reconstructive techniques. All volume data were compared with thyroid specimen volumes obtained using the water displacement method and were statistically analyzed using the one-way ANOVA, the Pearson correlation coefficient (R), linear regression, and the concordance correlation coefficient (CCC). The processing time of semiautomated 3D CT thyroid volumetry was measured. The paired mean differences ± SD between the three imaging-determined volumes and the specimen volumes were 0.8 ± 3.1 mL for 2D ultrasound, 4.0 ± 4.7 mL for 2D CT, and 0.2 ± 2.5 mL for 3D CT. A significant difference in the mean thyroid volume was found between 2D CT and specimen volumes (p = 0.016) compared with the other pairs (p = 0.937 for 2D ultrasound mean volume vs specimen mean volume, and p = 0.999 for 3D CT mean volume vs specimen mean volume). Between specimen volume and 2D ultrasound volume, specimen volume and 2D CT volume, and specimen volume and 3D CT volume, R values were 0.885, 0.724, and 0.929, respectively, and CCC values were 0.876, 0.598, and 0.925, respectively. The mean processing time of semiautomated 3D CT thyroid volumetry was 7.0 minutes. Thyroid volumes measured using 2D ultrasound or semiautomated 3D CT are substantially close to thyroid specimen volumes measured using the water displacement method. Semiautomated 3D CT thyroid volumetry can provide a more reliable measure of thyroid volume than 2D ultrasound.

Comparison of two-dimensional fast spin echo T2 weighted sequences and three-dimensional volume isotropic T2 weighted fast spin echo (VISTA) MRI in the evaluation of triangular fibrocartilage of the wrist.

PubMed

Park, Hee Jin; Lee, So Yeon; Kang, Kyung A; Kim, Eun Young; Shin, Hun Kyu; Park, Se Jin; Park, Jai Hyung; Kim, Eugene

2018-04-01

To compare image quality of three-dimensional volume isotropic T 2 weighted fast spin echo (3D VISTA) and two-dimensional (2D) T 2 weighted images (T2WI) for evaluation of triangular fibrocartilage (TFC) and to investigate whether 3D VISTA can replace 2D T 2 WI in evaluating TFC injury. This retrospective study included 69 patients who received wrist MRIs using both 2D T 2 WI and 3D VISTA techniques for assessment of wrist pathology, including TFC injury. Two radiologists measured the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) of the two sequences. The anatomical identification score and diagnostic performance were independently assessed by two interpreters. The diagnostic abilities of 3D VISTA and 2D T 2 WI were analysed by sensitivity, specificity and accuracy for diagnosing TFC injury using surgically or clinically confirmed diagnostic reference standards. 17 cases (25%) were classified as having TFC injury. 2 cases (12%) were diagnosed surgically, and 15 cases (88%) were diagnosed by physical examination. 52 cases (75%) were diagnosed as having intact TFC. 8 of these cases (15%) were surgically confirmed, while the others were diagnosed by physical examination and clinical findings. The 3D VISTA images had significantly higher SNR and CNR values for the TFC than 2D T 2 WI images. The scores of 3D VISTA's total length, full width and sharpness were similar to those of 2D T 2 WI. We were unable to find a significant difference between 3D VISTA and 2D T 2 WI in the ability to diagnose TFC injury. 3D VISTA image quality is similar to that of 2D T 2 WI for TFC evaluation and is also excellent for tissue contrast. 3D VISTA can replace 2D images in TFC injury assessment. Advances in knowledge: 3D VISTA image quality is similar to that of 2D T 2 WI for TFC evaluation and is also excellent for tissue contrast. 3D VISTA can replace 2D images in TFC injury assessment.

Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6*1 and CYP2D6*10 using cell-based models in vitro

PubMed Central

Qu, Qiang; Qu, Jian; Han, Lu; Zhan, Min; Wu, Lan-xiang; Zhang, Yi-wen; Zhang, Wei; Zhou, Hong-hao

2014-01-01

Aim: Herbal products have been widely used, and the safety of herb-drug interactions has aroused intensive concerns. This study aimed to investigate the effects of phytochemicals on the catalytic activities of human CYP2D6*1 and CYP2D6*10 in vitro. Methods: HepG2 cells were stably transfected with CYP2D6*1 and CYP2D6*10 expression vectors. The metabolic kinetics of the enzymes was studied using HPLC and fluorimetry. Results: HepG2-CYP2D6*1 and HepG2-CYP2D6*10 cell lines were successfully constructed. Among the 63 phytochemicals screened, 6 compounds, including coptisine sulfate, bilobalide, schizandrin B, luteolin, schizandrin A and puerarin, at 100 μmol/L inhibited CYP2D6*1- and CYP2D6*10-mediated O-demethylation of a coumarin compound AMMC by more than 50%. Furthermore, the inhibition by these compounds was dose-dependent. Eadie-Hofstee plots demonstrated that these compounds competitively inhibited CYP2D6*1 and CYP2D6*10. However, their Ki values for CYP2D6*1 and CYP2D6*10 were very close, suggesting that genotype-dependent herb-drug inhibition was similar between the two variants. Conclusion: Six phytochemicals inhibit CYP2D6*1 and CYP2D6*10-mediated catalytic activities in a dose-dependent manner in vitro. Thus herbal products containing these phytochemicals may inhibit the in vivo metabolism of co-administered drugs whose primary route of elimination is CYP2D6. PMID:24786236

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

Chao, Tzu-Ling; Yang, Chen-I., E-mail: ciyang@thu.edu.tw

The preparations and properties of three new homochiral three-dimensional (3D) coordination polymers, [M(D-cam)(pyz)(H{sub 2}O){sub 2}]{sub n} (M=Co (1) and Ni (2); D-H{sub 2}cam=(+) D-camphoric acid; pyz=pyrazine) and [Mn{sub 2}(D-cam){sub 2}(H{sub 2}O){sub 2}] (3), under solvothermal conditions is described. Single-crystal X-ray diffraction analyses revealed that all of compounds are homochiral 3D structure. 1 and 2 are isostructural and crystallize in the trigonal space group P3{sub 2}21, while 3 crystallizes in monoclinic space group P2{sub 1}. The structure of 1 and 2 consists of metal-D-cam helical chains which are pillared with pyrazine ligands into a 3D framework structure and 3 features amore » 3D homochiral framework involving one-dimensional manganese-carboxylate chains that are aligned parallel to the b axis. Magnetic susceptibility data of all compounds were collected. The findings indicate that μ{sub 2}-pyrazine dominate weak antiferromagnetic coupling within 1 and 2, while 3 exhibits antiferromagnetic behavior through the carboxylate groups of D-cam ligand. -- Graphical abstract: The preparations and properties of three new homochiral three-dimensional (3D) coordination polymers, [M(D-cam)(pyz)(H{sub 2}O){sub 2}]{sub n} (M=Co (1) and Ni (2); D-H{sub 2}cam=(+) D-camphoric acid; pyz=pyrazine) and [Mn{sub 2}(D-cam){sub 2}(H{sub 2}O){sub 2}] (3), under solvothermal conditions is described. Single-crystal X-ray diffraction analyses revealed that all of compounds are homochiral 3D structure. 1 and 2 are isostructural and crystallize in the trigonal space group P3{sub 2}21, while 3 crystallizes in monoclinic space group P2{sub 1}. The structure of 1 and 2 consists of metal-D-cam helical chains which are pillared with pyrazine ligands into a 3D framework structure and 3 features a 3D homochiral framework involving one-dimensional manganese-carboxylate chains that are aligned parallel to the b axis. Magnetic susceptibility data of all compounds were collected. The findings indicate that μ{sub 2}-pyrazine dominate weak antiferromagnetic coupling within 1 and 2, while 3 exhibits antiferromagnetic behavior through the carboxylate groups of D-cam ligand. Highlights: • Three homochiral 3D coordination polymers were synthesized. • 1 and 2 are 3D structure with metal-D-cam helical chains pillared by pyrazine. • 3 shows a 3D homochiral framework involving 1D manganese-carboxylate chains. • Magnetic data analysis indicates that 1–3 exhibit weak antiferromagnetic coupling.« less

Endomorphin analogues containing D-Pro2 discriminate different μ-opioid receptor mediated antinociception in mice

PubMed Central

Sakurada, Shinobu; Watanabe, Hiroyuki; Hayashi, Takafumi; Yuhki, Masayuki; Fujimura, Tsutomu; Murayama, Kimie; Sakurada, Chikai; Sakurada, Tsukasa

2002-01-01

The antagonistic actions of D-Pro2-endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D-Pro2-endomorphin-1 and D-Pro2-endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D-Pro2-endomorphin-1 (0.05–0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D-Pro2-endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D-Pro2-endomorphin-2 (100 pmol), but not by D-Pro2-endomorphin-1. D-Pro2-endomorphin-1. D-Pro2-endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a μ-opioid receptor agonist, whereas D-Pro2-endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D-Pro2 are able to discriminate the antinociceptive actions of μ1- and μ2-opioid receptor agonists at the spinal cord level. PMID:12466222

Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor

PubMed Central

Bulwa, Zachary B.; Sharlin, Jordan A.; Clark, Peter J.; Bhattacharya, Tushar K.; Kilby, Chessa N.; Wang, Yanyan; Rhodes, Justin S.

2011-01-01

Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or over-representation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose- dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that over-representation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. PMID:21803530

Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

PubMed

Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

2011-11-01

Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. Copyright © 2011 Elsevier Inc. All rights reserved.

Synthesis of 7-(2,4-dichlorophenyl)-D-erythro-3-hydroxy-5-heptanolide, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexane-1-sulfonic acid, and 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexylphosphonic acid.

PubMed

Hodosi, G; Galambos, G; Podányi, B; Kuszmann, J

1992-03-02

6-(2,4-Dichlorophenyl)-D-erythro-1,2,4-hexanetriol, synthesised from D-glucose, was partially silylated, then reacted with 2-methoxypropene to afford 1-O-tert-butyldimethylsilyl-6-(2,4- dichlorophenyl)-2,4-O-isopropylidene-D-erythro-1,2,4-hexanetriol (17). Desilylation of 17 gave 6-(2,4-dichlorophenyl)-2,4-O-isopropylidene-D- erythro-1,2,4-hexanetriol, which was converted into the 1-tosylate 18 and the 1-bromo derivative 19. Reaction of 18 with potassium thiolbenzoate gave, after debenzoylation, oxidation, and deprotection, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexane-1-sulfonic acid (4). Reaction of 18 or 19 with triethyl phosphite gave, after deprotection, 6-(2,4-dichlorophenyl)-D-erythro-2,4-dihydroxyhexyl-phosphonic acid (5), and reaction of 19 with potassium cyanide gave, after subsequent hydrolysis and deprotection, 7-(2,4-dichlorophenyl)-D-erythro-3-hydroxy-5-heptanolide (3).

Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status

PubMed Central

Eisenstein, Sarah A.; Bogdan, Ryan; Love-Gregory, Latisha; Corral-Frías, Nadia S.; Koller, Jonathan M.; Black, Kevin J.; Moerlein, Stephen M.; Perlmutter, Joel S.; Barch, Deanna M.; Hershey, Tamara

2016-01-01

In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are non-selective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N‐[11C]methyl)benperidol ([11C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in 2 independent samples. Sample 1 (n = 39) was composed of obese and non-obese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5-12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1−), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1− was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [11C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states. GRAPHICAL ABSTRACT We investigated the difference in striatal dopamine D2 receptor binding, as measured by PET with (N-[11C]methyl)benperidol ([11C]NMB), between A1 allele carriers (A1+) and individuals homozygous for the A2 allele (A1−) of the DRD2/ANKK1 TaqIA single nucleotide polymorphism. In Study 1, A1+ had 5-12% less striatal [11C]NMB binding than A1−. PMID:27241797

A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism.

PubMed

Hasbi, Ahmed; Perreault, Melissa L; Shen, Maurice Y F; Zhang, Lucia; To, Ryan; Fan, Theresa; Nguyen, Tuan; Ji, Xiaodong; O'Dowd, Brian F; George, Susan R

2014-11-01

Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues (404)Glu and (405)Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment. © FASEB.

[Accommodation to monochromatic targets in people with different color vision statuses].

PubMed

Qian, Yishan; Huang, Jia; Chu, Renyuan

2015-01-01

To compare the accommodation response (AR) to monochromatic targets in subjects with different color vision statuses, and to investigate the role of color vision in the control of accommodation and emmetropization. It was a case-control study. Accommodation was measured with a dynamic infrared optometer while subjects [17 protans, 47 deutans, and 23 normals; mean age: (20.0 ± 4.4) years] viewed a (1) red on black or (2) green on black vertical square-wave gratings of iso-luminance (3 cycles/deg; 0.9 contrast) in a Badal optic system. The grating stepped 1.00 D towards the eye from an initial position of 0 D until 5.00 D. With red-black targets, the AR in the protans (AR = 1.98 D) was worse than that in the normals (AR = 2.55 D) when the accommodation stimulus (AS) was 4.00 D (LSD, P = 0.031). The AR in the deutans were worse than that in the normals when the AS was 3.00, 4.00, and 5.00 D (3.00 D: 1.23 D vs. 1.69 D, P = 0.002; 4.00 D: 1.89 D vs. 2.55 D, P = 0.002; 5.00 D: 2.40 D vs. 3.17 D, P = 0.003). With green-black targets, the AR in the protans were worse than that in the normals when the AS was 3.00 and 4.00 D (3.00 D: 1.13 D vs. 1.61 D, P = 0.004; 4.00 D: 1.80 D vs. 2.34 D, P = 0.021). In the deutans, the AR was worse with stimuli of 3.00, 4.00, and 5.00 D (3.00 D: 1.21 D vs. 1.61 D, P = 0.003; 4.00 D: 1.65 D vs. 2.34 D, P < 0.001; 5.00 D: 2.36 D vs. 2.93 D, P = 0.007). No significant differences between the protans and deutans were found for all the stimulus conditions. In the protans, accommodation to red-black targets was better than that to green-black targets when the stimulus was 2.00, 3.00, and 5.00 D (2.00 D: t = -2.81, P = 0.013; 3.00 D: t = -4.55, P < 0.001; 5.00 D: t = -3.15, P = 0.006). In the deutans, accommodation to red-black targets was better than that to green-black targets when the stimulus was 4.00 D (t = -2.19, P = 0.034). In the normals, accommodation to red-black targets were better than that to green-black targets when the stimulus was 2.00, 4.00, and 5.00 D (2.00 D: t = -2.57, P = 0.017; 4.00 D, t = -2.67, P = 0.014; 5.00 D: t = -2.15, P = 0.043). Individuals with a color vision deficiency tend to have a larger accommodative lag than normals. Red targets tend to induce better accommodation response than green ones. Color vision may play a role in the control of accommodation and emmetropization.

Rationale and design of the vitamin D and type 2 diabetes (D2d) study: a diabetes prevention trial

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supp...

A preliminary comparison of hydrodynamic approaches for flood inundation modeling of urban areas in Jakarta Ciliwung river basin

NASA Astrophysics Data System (ADS)

Rojali, Aditia; Budiaji, Abdul Somat; Pribadi, Yudhistira Satya; Fatria, Dita; Hadi, Tri Wahyu

2017-07-01

This paper addresses on the numerical modeling approaches for flood inundation in urban areas. Decisive strategy to choose between 1D, 2D or even a hybrid 1D-2D model is more than important to optimize flood inundation analyses. To find cost effective yet robust and accurate model has been our priority and motivation in the absence of available High Performance Computing facilities. The application of 1D, 1D/2D and full 2D modeling approach to river flood study in Jakarta Ciliwung river basin, and a comparison of approaches benchmarked for the inundation study are presented. This study demonstrate the successful use of 1D/2D and 2D system to model Jakarta Ciliwung river basin in terms of inundation results and computational aspect. The findings of the study provide an interesting comparison between modeling approaches, HEC-RAS 1D, 1D-2D, 2D, and ANUGA when benchmarked to the Manggarai water level measurement.

Digit ratio (2D:4D), dominance, reproductive success, asymmetry, and sociosexuality in the BBC Internet Study.

PubMed

Manning, John T; Fink, Bernhard

2008-01-01

Digit ratio (2D:4D) may be a correlate of prenatal sex steroids, and has been linked to traits, which are influenced by fetal testosterone and estrogen. Here we consider such links in a large Internet study of sex differences (the BBC Internet Study) in which finger lengths were self-measured. Consistent with lab-based findings the 2D:4D in this study shows sexual dimorphism, ethnic differences and higher dimorphism of right 2D:4D than left, thereby indicating that 2D:4D does measure real between-participant variation. High error in self-measurement of fingers reduces effect sizes. However, the large sample size gives assurance that significant effects are likely to be real. We controlled for ethnicity and sexual orientation by considering White heterosexuals only (153,429 participants). Sexual dimorphism was confirmed in 2D:4D and for the difference of right-left 2D:4D. After Bonferroni correction we found highly significant relationships with low effect sizes as follows. In males and females there were negative associations between 2D:4D and dominance. In males there were negative associations between 2D:4D and family size and factors associated with reproductive success. For females these associations were positive. For asymmetry we found U-shaped relationships with 2D:4D in both males and females. We found no relationship between 2D:4D and promiscuity (sociosexuality). In total, we considered 48 relationships and found 29 to be significant. We compare our findings with a similar study reported by Putz et al. (2004), which found only 2 out of 57 correlations to be significant and discuss possible reasons for the discrepancies between the studies. Copyright 2008 Wiley-Liss, Inc.

The role of dimension and shape in colloidal liquids and glasses

NASA Astrophysics Data System (ADS)

Vivek, Skanda

In two-dimensions, the laws of physics give rise to intriguing phenomena such as long-range correlations that do not decay at infinity. However, reality can only be quasi-2D at best. This thesis is an effort to bridge the gap between 2D theory and reality, by doing experiments. Here we consider two different model systems - soap films as 2D fluids, and 2D colloidal glass formers. We look at diffusion of tracer particles in soap films and test the validity of 2D theory. We find that for thin films, both 2D surface viscosity and 3D viscosity are important. To a good approximation, soap films are thin films and can be considered 2D for flow. Next, we look at glassy dynamics in 2D and 3D colloidal glass formers. We demonstrate that the differences between 2D and 3D are long-wavelength fluctuations, precisely those that distinguish 2D and 3D phase transitions. Through a novel analysis method that removes the influence of these fluctuations, we show that 2D and 3D glass transitions are otherwise similar. Finally, we look at the effect of shape anisotropy of dimers in 2D glasses, and find that glass dynamics are highly dependent on shape, both in experiments and simulations. These colloidal and simulation results are a prediction of aspect ratio dependent diffusion in real glasses.

CYP2D6 Genetic Polymorphisms and Phenotypes in Different Ethnicities of Malaysian Breast Cancer Patients.

PubMed

Chin, Fee Wai; Chan, Soon Choy; Abdul Rahman, Sabariah; Noor Akmal, Sharifah; Rosli, Rozita

2016-01-01

The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the clinical outcome of the patients. © 2015 Wiley Periodicals, Inc.

Non-analytic terms from nested divergences in maximal supergravity

NASA Astrophysics Data System (ADS)

Basu, Anirban

2016-07-01

The {D}4{{ R }}4 and {D}6{{ R }}4 coefficient functions in the effective action of type II string theory compactified on T d contain terms of the form {{ E }}1{{ln}}{g}d and {{ E }}2{({{ln}}{g}d)}2 in specific dimensions, where g d is the T-duality invariant string coupling, and {{ E }}1 and {{ E }}2 are U-duality invariant coefficient functions. We derive these non-analytic terms from nested ultraviolet divergences in two and three loop maximal supergravity. For the {D}4{{ R }}4 coupling, the contribution involves {{ E }}{{ R }4}{{ln}}{g}d, while for the {D}6{{ R }}4 coupling, it involves {{ E }}{{ R }4}{{ln}}{g}d, {{ E }}{D2{{ R }}4}{({{ln}}{g}d)}2 and {{ E }}{D4{{ R }}4}{{ln}}{g}d; where {{ E }}{{ R }4}, {{ E }}{D2{{ R }}4} and {{ E }}{D4{{ R }}4} are the {{ R }}4, {D}2{{ R }}4 and {D}4{{ R }}4 coefficient functions respectively. The contribution from {{ E }}{D2{{ R }}4}, the coefficient function of an amplitude that vanishes onshell, arises from a two loop nested subdivergence of the three loop amplitude.

Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions

PubMed Central

Espinoza, J. Luis; Takami, Akiyoshi; Yoshioka, Katsuji; Nakata, Katsuya; Sato, Tokiharu; Kasahara, Yoshihito; Nakao, Shinji

2012-01-01

Background NKG2D is an activating receptor expressed by natural killer and T cells, which have crucial functions in tumor and microbial immunosurveillance. Several cytokines have been identified as modulators of NKG2D receptor expression. However, little is known about NKG2D gene regulation. In this study, we found that microRNA 1245 attenuated the expression of NKG2D in natural killer cells. Design and Methods We investigated the potential interactions between the 3′-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells. Results Transforming growth factor-β1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity. Conclusions These results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-β1 to attenuate NKG2D expression in natural killer cells. PMID:22491735

Targeted delivery of vitamin D to the colon using β-glucuronides of vitamin D: therapeutic effects in a murine model of inflammatory bowel disease

PubMed Central

Koszewski, Nicholas J.; Haynes, Joseph S.; Horst, Ronald L.

2012-01-01

1,25-Dihydroxyvitamin D3 [1,25(OH)2D] has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether β-glucuronides of vitamin D could deliver 1,25(OH)2D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH)2D from 1,25-dihydroxyvitamin D3-25-β-glucuronide [β-gluc-1,25(OH)2D]. We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of β-gluc-1,25(OH)2D than 1,25(OH)2D, demonstrating targeted delivery of 1,25(OH)2D to the colon. We then tested β-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH)2D or β-gluc-1,25(OH)2D, severity of colitis was reduced. Combination of β-gluc-1,25(OH)2D with 25-hydroxyvitamin D3-25-β-glucuronide [β-gluc-25(OH)D] resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with β-gluc-1,25(OH)2D alone or in combination with β-gluc-25(OH)D than in mice treated with 1,25(OH)2D, which were hypercalcemic at the time of death. β-Glucuronides of vitamin D compounds can deliver 1,25(OH)2D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model. PMID:22114117

Genetic algorithm prediction of two-dimensional group-IV dioxides for dielectrics

NASA Astrophysics Data System (ADS)

Singh, Arunima K.; Revard, Benjamin C.; Ramanathan, Rohit; Ashton, Michael; Tavazza, Francesca; Hennig, Richard G.

2017-04-01

Two-dimensional (2D) materials present a new class of materials whose structures and properties can differ from their bulk counterparts. We perform a genetic algorithm structure search using density-functional theory to identify low-energy structures of 2D group-IV dioxides A O2 (A =Si , Ge, Sn, Pb). We find that 2D SiO2 is most stable in the experimentally determined bi-tetrahedral structure, while 2D SnO2 and PbO2 are most stable in the 1 T structure. For 2D GeO2, the genetic algorithm finds a new low-energy 2D structure with monoclinic symmetry. Each system exhibits 2D structures with formation energies ranging from 26 to 151 meV/atom, below those of certain already synthesized 2D materials. The phonon spectra confirm their dynamic stability. Using the HSE06 hybrid functional, we determine that the 2D dioxides are insulators or semiconductors, with a direct band gap of 7.2 eV at Γ for 2D SiO2, and indirect band gaps of 4.8-2.7 eV for the other dioxides. To guide future applications of these 2D materials in nanoelectronic devices, we determine their band-edge alignment with graphene, phosphorene, and single-layer BN and MoS2. An assessment of the dielectric properties and electrochemical stability of the 2D group-IV dioxides shows that 2D GeO2 and SnO2 are particularly promising candidates for gate oxides and 2D SnO2 also as a protective layer in heterostructure nanoelectronic devices.

Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice.

PubMed

Armando, Ines; Asico, Laureano D; Wang, Xiaoyan; Jones, John E; Serrão, Maria Paula; Cuevas, Santiago; Grandy, David K; Soares-da-Silva, Patricio; Jose, Pedro A

2018-04-13

Abnormalities of the D 2 R gene (DRD2) play a role in the pathogenesis of human essential hypertension; variants of the DRD2 have been reported to be associated with hypertension. Disruption of Drd2 (D 2 -/- ) in mice increases blood pressure. The hypertension of D 2 -/- mice has been related, in part, to increased sympathetic activity, renal oxidative stress, and renal endothelin B receptor (ETBR) expression. We tested in D 2 -/- mice the effect of etamicastat, a reversible peripheral inhibitor of dopamine-β-hydroxylase that reduces the biosynthesis of norepinephrine from dopamine and decreases sympathetic nerve activity. Blood pressure was measured in anesthetized D 2 -/- mice treated with etamicastat by gavage, (10 mg/kg), conscious D 2 -/- mice, and D 2 +/+ littermates, and mice with the D 2 R selectively silenced in the kidney, treated with etamicastat in the drinking water (10 mg/kg per day). Tissue and urinary catecholamines and renal expression of selected G protein-coupled receptors, enzymes related to the production of reactive oxygen species, and sodium transporters were also measured. Etamicastat decreased blood pressure both in anesthetized and conscious D 2 -/- mice and mice with renal-selective silencing of D 2 R to levels similar or close to those measured in D 2 +/+ littermates. Etamicastat decreased cardiac and renal norepinephrine and increased cardiac and urinary dopamine levels in D 2 -/- mice. It also normalized the increased renal protein expressions of ETBR, NADPH oxidase isoenzymes, and urinary 8-isoprostane, as well as renal NHE3 and NCC, and increased the renal expression of D 1 R but not D 5 R in D 2 -/- mice. In conclusion, etamicastat is effective in normalizing the increased blood pressure and some of the abnormal renal biochemical alterations of D 2 -/- mice.

Complementary DNA cloning, functional expression and characterization of a novel cytochrome P450, CYP2D50, from equine liver.

PubMed

DiMaio Knych, H K; Stanley, S D

2008-10-01

Members of the CYP2D family constitute only about 2-4% of total hepatic CYP450s, however, they are responsible for the metabolism of 20-25% of commonly prescribed therapeutic compounds. CYP2D enzymes have been identified in a number of different species. However, vast differences in the metabolic activity of these enzymes have been well documented. In the horse, the presence of a member of the CYP2D family has been suggested from studies with equine liver microsomes, however its presence has not been definitively proven. In this study a cDNA encoding a novel CYP2D enzyme (CYP2D50) was cloned from equine liver and expressed in a baculovirus expression system. The nucleotide sequence of CYP2D50 was highly homologous to that of human CYP2D6 and therefore the activity of the enzyme was characterized using dextromethorphan and debrisoquine, two isoform selective substrates for the human orthologue. CYP2D50 displayed optimal catalytic activity with dextromethorphan using molar ratios of CYP2D50 to NADPH CYP450 reductase of 1:15. Although CYP2D50 and CYP2D6 shared significant sequence homology, there were striking differences in the catalytic activity between the two enzymes. CYP2D50 dextromethorphan-O-demethylase activity was nearly 180-fold slower than the human counterpart, CYP2D6. Similarly, rates of formation of 4-hydroxydebrisoquine activity were 50-fold slower for CYP2D50 compared to CYP2D6. The results of this study demonstrate substantial interspecies variability in metabolism of substrates by CYP2D orthologues in the horse and human and support the need to fully characterize this enzyme system in equids.

[D2 lymph node dissection in gastric cancer surgery: long term results--analysis of an experience with 227 patients].

PubMed

Vasilescu, C; Herlea, V; Tidor, S; Ivanov, B; Stănciulea, Oana; Mănuc, M; Gheorghe, C; Ionescu, M; Diculescu, M; Popescu, I

2006-01-01

The main objective of the study was to evaluate the postoperative mortality and 5 year survival in gastric cancer patients undergoing a minimum of D2 lymphadenectomy. A retrospective study was conducted on 1170 patients operated for gastric adenocarcinoma in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute, between 1997 and April 2005. Only 443 patients underwent a curative resection, from which 216 patients had D1 resection and in 227 cases a D2 or D3/D4 lymphadenectomy was performed. Information about survival was available for 189 patients of those who had a D1 resection and for 210 of those who underwent a D2 or D3/D4 lymphadenectomy. Postoperative mortality was 6.5% in the group of curative resection, with 9.2% for D1 and 3.9% for D2/D3 D4. Five year survival according to Kaplan Meier curves was 32 % in the D1 group vs. 51,8% in D2/D3-D4 (p <0.0001). Significant differences were noted in the median survival-- D2/D3-D4 group 63 months vs. 28 months in D1 group. Our data support the gastric resection with a minimum of D2 lymphadenectomy in the radical surgery of gastric cancer. However, an accurate interpretation of the statistical interpretation between the different groups of patients is difficult, mainly because of the retrospective character of the study.

EEG-based cognitive load of processing events in 3D virtual worlds is lower than processing events in 2D displays.

PubMed

Dan, Alex; Reiner, Miriam

2017-12-01

Interacting with 2D displays, such as computer screens, smartphones, and TV, is currently a part of our daily routine; however, our visual system is built for processing 3D worlds. We examined the cognitive load associated with a simple and a complex task of learning paper-folding (origami) by observing 2D or stereoscopic 3D displays. While connected to an electroencephalogram (EEG) system, participants watched a 2D video of an instructor demonstrating the paper-folding tasks, followed by a stereoscopic 3D projection of the same instructor (a digital avatar) illustrating identical tasks. We recorded the power of alpha and theta oscillations and calculated the cognitive load index (CLI) as the ratio of the average power of frontal theta (Fz.) and parietal alpha (Pz). The results showed a significantly higher cognitive load index associated with processing the 2D projection as compared to the 3D projection; additionally, changes in the average theta Fz power were larger for the 2D conditions as compared to the 3D conditions, while alpha average Pz power values were similar for 2D and 3D conditions for the less complex task and higher in the 3D state for the more complex task. The cognitive load index was lower for the easier task and higher for the more complex task in 2D and 3D. In addition, participants with lower spatial abilities benefited more from the 3D compared to the 2D display. These findings have implications for understanding cognitive processing associated with 2D and 3D worlds and for employing stereoscopic 3D technology over 2D displays in designing emerging virtual and augmented reality applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Regulation of dopaminergic neuron firing by heterogeneous dopamine autoreceptors in the substantia nigra pars compacta.

PubMed

Jang, Jin Young; Jang, Miae; Kim, Shin Hye; Um, Ki Bum; Kang, Yun Kyung; Kim, Hyun Jin; Chung, Sungkwon; Park, Myoung Kyu

2011-03-01

Dopamine (DA) receptors generate many cellular signals and play various roles in locomotion, motivation, hormone production, and drug abuse. According to the location and expression types of the receptors in the brain, DA signals act in either stimulatory or inhibitory manners. Although DA autoreceptors in the substantia nigra pars compacta are known to regulate firing activity, the exact expression patterns and roles of DA autoreceptor types on the firing activity are highly debated. Therefore, we performed individual correlation studies between firing activity and receptor expression patterns using acutely isolated rat substantia nigra pars compacta DA neurons. When we performed single-cell RT-PCR experiments, D(1), D(2)S, D(2)L, D(3), and D(5) receptor mRNA were heterogeneously expressed in the order of D(2)L > D(2)S > D(3) > D(5) > D(1). Stimulation of D(2) receptors with quinpirole suppressed spontaneous firing similarly among all neurons expressing mRNA solely for D(2)S, D(2)L, or D(3) receptors. However, quinpirole most strongly suppressed spontaneous firing in the neurons expressing mRNA for both D(2) and D(3) receptors. These data suggest that D(2) S, D(2)L, and D(3) receptors are able to equally suppress firing activity, but that D(2) and D(3) receptors synergistically suppress firing. This diversity in DA autoreceptors could explain the various actions of DA in the brain. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Rationale and Design of the Vitamin D and Type 2 Diabetes (D2d) Study: A Diabetes Prevention Trial

PubMed Central

Pittas, Anastassios G.; Dawson-Hughes, Bess; Rosen, Clifford J.; Ware, James H.; Knowler, William C.; Staten, Myrlene A.

2014-01-01

OBJECTIVE Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes. RESEARCH DESIGN AND METHODS D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m2, increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100–125 mg/dL (5.5–6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140–199 mg/dL (7.7–11.0 mmol/L), hemoglobin A1c 5.7–6.4% (39–46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D3 (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013. CONCLUSIONS D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes. PMID:25205139

Saccharomyces cerevisiae Forms d-2-Hydroxyglutarate and Couples Its Degradation to d-Lactate Formation via a Cytosolic Transhydrogenase*♦

PubMed Central

Becker-Kettern, Julia; Paczia, Nicole; Conrotte, Jean-François; Kay, Daniel P.; Guignard, Cédric; Jung, Paul P.; Linster, Carole L.

2016-01-01

The d or l form of 2-hydroxyglutarate (2HG) accumulates in certain rare neurometabolic disorders, and high d-2-hydroxyglutarate (d-2HG) levels are also found in several types of cancer. Although 2HG has been detected in Saccharomyces cerevisiae, its metabolism in yeast has remained largely unexplored. Here, we show that S. cerevisiae actively forms the d enantiomer of 2HG. Accordingly, the S. cerevisiae genome encodes two homologs of the human d-2HG dehydrogenase: Dld2, which, as its human homolog, is a mitochondrial protein, and the cytosolic protein Dld3. Intriguingly, we found that a dld3Δ knock-out strain accumulates millimolar levels of d-2HG, whereas a dld2Δ knock-out strain displayed only very moderate increases in d-2HG. Recombinant Dld2 and Dld3, both currently annotated as d-lactate dehydrogenases, efficiently oxidized d-2HG to α-ketoglutarate. Depletion of d-lactate levels in the dld3Δ, but not in the dld2Δ mutant, led to the discovery of a new type of enzymatic activity, carried by Dld3, to convert d-2HG to α-ketoglutarate, namely an FAD-dependent transhydrogenase activity using pyruvate as a hydrogen acceptor. We also provide evidence that Ser3 and Ser33, which are primarily known for oxidizing 3-phosphoglycerate in the main serine biosynthesis pathway, in addition reduce α-ketoglutarate to d-2HG using NADH and represent major intracellular sources of d-2HG in yeast. Based on our observations, we propose that d-2HG is mainly formed and degraded in the cytosol of S. cerevisiae cells in a process that couples d-2HG metabolism to the shuttling of reducing equivalents from cytosolic NADH to the mitochondrial respiratory chain via the d-lactate dehydrogenase Dld1. PMID:26774271

Saccharomyces cerevisiae Forms D-2-Hydroxyglutarate and Couples Its Degradation to D-Lactate Formation via a Cytosolic Transhydrogenase.

PubMed

Becker-Kettern, Julia; Paczia, Nicole; Conrotte, Jean-François; Kay, Daniel P; Guignard, Cédric; Jung, Paul P; Linster, Carole L

2016-03-18

The D or L form of 2-hydroxyglutarate (2HG) accumulates in certain rare neurometabolic disorders, and high D-2-hydroxyglutarate (D-2HG) levels are also found in several types of cancer. Although 2HG has been detected in Saccharomyces cerevisiae, its metabolism in yeast has remained largely unexplored. Here, we show that S. cerevisiae actively forms the D enantiomer of 2HG. Accordingly, the S. cerevisiae genome encodes two homologs of the human D-2HG dehydrogenase: Dld2, which, as its human homolog, is a mitochondrial protein, and the cytosolic protein Dld3. Intriguingly, we found that a dld3Δ knock-out strain accumulates millimolar levels of D-2HG, whereas a dld2Δ knock-out strain displayed only very moderate increases in D-2HG. Recombinant Dld2 and Dld3, both currently annotated as D-lactate dehydrogenases, efficiently oxidized D-2HG to α-ketoglutarate. Depletion of D-lactate levels in the dld3Δ, but not in the dld2Δ mutant, led to the discovery of a new type of enzymatic activity, carried by Dld3, to convert D-2HG to α-ketoglutarate, namely an FAD-dependent transhydrogenase activity using pyruvate as a hydrogen acceptor. We also provide evidence that Ser3 and Ser33, which are primarily known for oxidizing 3-phosphoglycerate in the main serine biosynthesis pathway, in addition reduce α-ketoglutarate to D-2HG using NADH and represent major intracellular sources of D-2HG in yeast. Based on our observations, we propose that D-2HG is mainly formed and degraded in the cytosol of S. cerevisiae cells in a process that couples D-2HG metabolism to the shuttling of reducing equivalents from cytosolic NADH to the mitochondrial respiratory chain via the D-lactate dehydrogenase Dld1. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The effects of vitamin D supplementation on hepatic dysfunction, vitamin D status, and glycemic control in children and adolescents with vitamin D deficiency and either type 1 or type 2 diabetes mellitus.

PubMed

Nwosu, Benjamin Udoka; Maranda, Louise

2014-01-01

The effects of vitamin D supplementation on mild hepatic dysfunction and glycemic control are unclear in children and adolescents with either type 1 (T1D) or type 2 diabetes (T2D). Vitamin D supplementation will improve hepatic dysfunction and glycemic control. To determine the effect of vitamin D supplementation on alanine transaminase (ALT), hemoglobin A1c (HbA1c), and serum 25-hydroxyvitamin D [25(OH)D] concentration. A retrospective study of 131 subjects with either T1D (n = 88 ∶ 46 females, 42 males), or T2D (n = 43 ∶ 26 females, 17 males) of ages 3-18 years between 2007-2013. All subjects had (1) a diagnosis of diabetes for > 12 mo, (2) received vitamin D supplementation for the management of vitamin D deficiency (3) had baseline and subsequent simultaneous measurements of HbA1c, ALT, and 25(OH)D. Vitamin D deficiency was defined as 25(OH)D concentration of < 50 nmol/L (20 ng/mL). At baseline, vitamin D deficiency occurred in 72.1% of patients with T2D and in 37.5% of T1D patients (p < 0.001). Patients with T2D had significantly higher values for BMI SDS (p < 0.001), alanine transaminase (ALT) (p = 0.001), but lower 25(OH)D p < 0.001), and no difference in HbA1c (p = 0.94), and total daily dose (TDD) of insulin per kg body weight (p = 0.48) as compared to T1D patients. After 3 months of vitamin D supplementation, there was a significant increase in 25(OH)D in both T2D (p = 0.015), and T1D patients (p < 0.001); significant reduction in BMI SDS (p = 0.015) and ALT (p = 0.012) in T2D, but not in T1D. There was a clinically-significant decrease in HbA1c in T2D from 8.5 ± 2.9% at baseline to 7.7 ± 2.5 at 3 mo, but not in T1D, 8.5 ± 1.2 to 8.53 ± 1.1%. Vitamin D supplementation in subjects with T2D was associated with statistically significant decreases in BMI SDS, ALT, and a clinically-significant decrease in HbA1c.

Binding Interactions of Dopamine and Apomorphine in D2High and D2Low States of Human Dopamine D2 Receptor Using Computational and Experimental Techniques.

PubMed

Durdagi, Serdar; Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip

2016-02-17

We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model.

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

PubMed

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

From 2D to 3D: The morphology, proliferation and differentiation of MC3T3-E1 on silk fibroin/chitosan matrices.

PubMed

Li, Da-Wei; He, Feng-Li; He, Jin; Deng, Xudong; Liu, Ya-Li; Liu, Yang-Yang; Ye, Ya-Jing; Yin, Da-Chuan

2017-12-15

It has been widely accepted that cell culture in two-dimensional (2D) conditions may not be able to represent growth in three-dimensional (3D) conditions. Systematic comparisons between 2D and 3D cell cultures are needed to appropriately use the existing 2D results. In this work, we conducted a comparative study between 2D and 3D cell cultures of MC3T3-E1 using the same type of material (a mixture of silk fibroin (SF) and chitosan (CS)). Our results showed 3D SF/CS scaffold exhibited different effects on cell culture compared with the 2D cases. 1) The cells grown in 3D scaffold showed multiple morphologies. 2) The proliferation of cells in 3D scaffold was long-term and sustainable. 3) Cell differentiation occurred throughout the entire 3D scaffold. The results showed that cell culture in 3D SF/CS scaffold exhibited different features than 2D cases and 3D SF/CS scaffold could be a promising material for 3D cell culture. Copyright © 2017 Elsevier Ltd. All rights reserved.

The presence of aggression cues inverts the relation between digit ratio (2D:4D) and prosocial behaviour in a dictator game.

PubMed

Millet, Kobe; Dewitte, Siegfried

2009-02-01

Digit ratio (2D:4D) is a sexually dimorphic trait. Men have relatively shorter index (2D) compared to ring (4D) fingers than women. More masculine ratios are thought to be influenced by higher prenatal testosterone levels. In the present paper, we aim to show the context-dependency of the relation between 2D:4D and social behaviour. In two studies, we expose participants either to control or to aggression cues. Afterwards, they make a decision in a dictator game. Participants with low 2D:4D showed higher allocation levels (i.e. they were more prosocial) than participants with high 2D:4D in a neutral situation. However, this relationship inverts after exposure to an aggression cue. It turns out that in high 2D:4D people, aggression cues even increase prosocial behaviour. We call for future research which focuses on other plausible interactions between 2D:4D and context cues rather than on linear relations.

Comparison of HELIX TWT Simulation Using 2-D PIC (Magic), 2-D Modal (Gator), and 1-D Modal (Christine) Methods

DTIC Science & Technology

1998-05-01

Mission Research Corporation MRC/WDC-R-424 COMPARISON OF HELIX TWT SIMULATION USING 2-D PIC ( MAGIC ), 2-D MODAL (GATOR), AND 1-D MODAL (CHRISTINE...BRILLOUIN RUN 9 3.4 OUTLIER ELECTRON EFFECT IN GATOR 12 3.5 EMISSION CONDITION AND NONLAMINAR FLOW IN MAGIC 12 3.6 RADIAL SHEAR 13 SECTION 4. PPM B...Simulation using 2-D PIC ( MAGIC ), 2-D Modal (GATOR) and 1-D Modal (CHRISTINE) methods * D.N. Smithe(a), H. Freund(b), T. M. Antonsen Jr.,(b)’(c), E

Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol.

PubMed

Kessler, Robert M; Ansari, Mohammad Sib; Riccardi, Patrizia; Li, Rui; Jayathilake, Karuna; Dawant, Benoit; Meltzer, Herbert Y

2005-12-01

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) receptors was 85-93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.

Applications of 2D to 3D conversion for educational purposes

NASA Astrophysics Data System (ADS)

Koido, Yoshihisa; Morikawa, Hiroyuki; Shiraishi, Saki; Takeuchi, Soya; Maruyama, Wataru; Nakagori, Toshio; Hirakata, Masataka; Shinkai, Hirohisa; Kawai, Takashi

2013-03-01

There are three main approaches creating stereoscopic S3D content: stereo filming using two cameras, stereo rendering of 3D computer graphics, and 2D to S3D conversion by adding binocular information to 2D material images. Although manual "off-line" conversion can control the amount of parallax flexibly, 2D material images are converted according to monocular information in most cases, and the flexibility of 2D to S3D conversion has not been exploited. If the depth is expressed flexibly, comprehensions and interests from converted S3D contents are anticipated to be differed from those from 2D. Therefore, in this study we created new S3D content for education by applying 2D to S3D conversion. For surgical education, we created S3D surgical operation content under a surgeon using a partial 2D to S3D conversion technique which was expected to concentrate viewers' attention on significant areas. And for art education, we converted Ukiyoe prints; traditional Japanese artworks made from a woodcut. The conversion of this content, which has little depth information, into S3D, is expected to produce different cognitive processes from those evoked by 2D content, e.g., the excitation of interest, and the understanding of spatial information. In addition, the effects of the representation of these contents were investigated.

Are natural scientists more masculine than humanists? The association patterns between 2D:4D ratio and field of study.

PubMed

Kainz, Sarah; Weitzer, Jacob; Zingale, Stefania; Köllner, Johanna; Albrecht, Cornelia; Gaidora, Angelika; Rudorfer, Marie-Theres; Nürnberger, Anna; Kirchengast, Sylvia

2018-06-11

Natural sciences are still considered as typical male fields, while humanities are interpreted as typical female topics. Economic, social but also biological factors are discussed to influence the choice of study field. In the present study, the impact of prenatal sex hormone exposure - estimated by 2D:4D ratio - on the choice of study field was analyzed. Two hundred Viennese students between the ages 18 and 28 years were enrolled. Lengths of the index finger and the ring finger were measured directly from the hand of the participants. 2D:4D ratios were calculated. Male and female students differed significantly in 2D:4D ratio. As expected, female students showed significantly higher 2D:4D ratios than their male counterparts ( p < 0.001). Male scientists and male humanists differed significantly in 2D:4D ratio. The 2D:4D of male humanists was significantly higher than that of scientists ( p = 0.037). Female scientists and female humanists however, did not differ significantly in 2D:4D ratio. Both showed a typical female 2D:4D ratio. This was also true of male humanists. Consequently low prenatal androgen exposure may be associated with the choice of humanities among male students.

Energy Efficiency of D2D Multi-User Cooperation.

PubMed

Zhang, Zufan; Wang, Lu; Zhang, Jie

2017-03-28

The Device-to-Device (D2D) communication system is an important part of heterogeneous networks. It has great potential to improve spectrum efficiency, throughput and energy efficiency cooperation of multiple D2D users with the advantage of direct communication. When cooperating, D2D users expend extraordinary energy to relay data to other D2D users. Hence, the remaining energy of D2D users determines the life of the system. This paper proposes a cooperation scheme for multiple D2D users who reuse the orthogonal spectrum and are interested in the same data by aiming to solve the energy problem of D2D users. Considering both energy availability and the Signal to Noise Ratio (SNR) of each D2D user, the Kuhn-Munkres algorithm is introduced in the cooperation scheme to solve relay selection problems. Thus, the cooperation issue is transformed into a maximum weighted matching (MWM) problem. In order to enhance energy efficiency without the deterioration of Quality of Service (QoS), the link outage probability is derived according to the Shannon Equation by considering the data rate and delay. The simulation studies the relationships among the number of cooperative users, the length of shared data, the number of data packets and energy efficiency.

Two-dimensional vocal tracts with three-dimensional behavior in the numerical generation of vowels.

PubMed

Arnela, Marc; Guasch, Oriol

2014-01-01

Two-dimensional (2D) numerical simulations of vocal tract acoustics may provide a good balance between the high quality of three-dimensional (3D) finite element approaches and the low computational cost of one-dimensional (1D) techniques. However, 2D models are usually generated by considering the 2D vocal tract as a midsagittal cut of a 3D version, i.e., using the same radius function, wall impedance, glottal flow, and radiation losses as in 3D, which leads to strong discrepancies in the resulting vocal tract transfer functions. In this work, a four step methodology is proposed to match the behavior of 2D simulations with that of 3D vocal tracts with circular cross-sections. First, the 2D vocal tract profile becomes modified to tune the formant locations. Second, the 2D wall impedance is adjusted to fit the formant bandwidths. Third, the 2D glottal flow gets scaled to recover 3D pressure levels. Fourth and last, the 2D radiation model is tuned to match the 3D model following an optimization process. The procedure is tested for vowels /a/, /i/, and /u/ and the obtained results are compared with those of a full 3D simulation, a conventional 2D approach, and a 1D chain matrix model.

Factors Influencing Dislodgeable 2, 4-D Plant Residues from Hybrid Bermudagrass (Cynodon dactylon L. x C. transvaalensis) Athletic Fields.

PubMed

Jeffries, Matthew D; Gannon, Travis W; Brosnan, James T; Ahmed, Khalied A; Breeden, Gregory K

2016-01-01

Research to date has confirmed 2,4-D residues may dislodge from turfgrass; however, experiments have not been conducted on hybrid bermudagrass (Cynodon dactylon L. x C. transvaalensis), the most common athletic field turfgrass in subtropical climates. More specifically, previous research has not investigated the effect of post-application irrigation on dislodgeable 2,4-D residues from hybrid bermudagrass and across turfgrass species, research has been nondescript regarding sample time within a d (TWD) or conducted in the afternoon when the turfgrass canopy is dry, possibly underestimating potential for dislodgement. The effect of irrigation and TWD on 2,4-D dislodgeability was investigated. Dislodgeable 2,4-D amine was reduced > 300% following irrigation. From 2 to 7 d after treatment (DAT), ≤ 0.5% of applied 2,4-D was dislodged from irrigated turfgrass, while ≤ 2.3% of applied 2,4-D was dislodged when not irrigated. 2,4-D dislodgeability decreased as TWD increased. Dislodgeable 2,4-D residues declined to < 0.1% of the applied at 1 DAT- 13:00, and increased to 1 to 3% of the applied 2 DAT- 5:00, suggesting 2,4-D re-suspended on treated turfgrass vegetation overnight. In conclusion, irrigating treated turfgrass reduced dislodgeable 2,4-D. 2,4-D dislodgeability increased as TWD decreased, which was attributed to non-precipitation climatic conditions favoring turfgrass canopy wetness. This research will improve turfgrass management practices and research designed to minimize human 2,4-D exposure.

The Contribution of Common UGT2B10 and CYP2A6 Alleles to Variation in Nicotine Glucuronidation among European Americans

PubMed Central

Bloom, A. Joseph; von Weymarn, Linda B.; Martinez, Maribel; Bierut, Laura J.; Goate, Alison; Murphy, Sharon E.

2014-01-01

UDP-glucuronosytransferase-2B10 (UGT2B10) is the primary catalyst of nicotine glucuronidation. To develop a predictive genetic model of nicotine metabolism, the conversion of deuterated (D2)-nicotine to D2-nicotine-glucuronide, D2-cotinine, D2-cotinine-glucuronide, and D2-trans-3'-hydroxycotinine were quantified in 188 European Americans, and the contribution of UGT2B10 genotype to variability in first-pass nicotine glucuronidation assessed, following a procedure previously applied to nicotine C-oxidation. The proportion of total nicotine converted to nicotine-glucuronide (D2-nicotine-glucuronide/ (D2-nicotine +D2-nicotine-glucuronide +D2-cotinine +D2-cotinine-glucuronide +D2-trans-3'-hydroxycotinine)) was the primary phenotype. The variant, rs61750900T (D67Y) (minor allele frequency (MAF) = 10%), is confirmed to abolish nicotine glucuronidation activity. Another variant, rs112561475G (N397D) (MAF = 2%), is significantly associated with enhanced glucuronidation. rs112561475G is the ancestral allele of a well-conserved amino acid, indicating that the majority of human UGT2B10 alleles are derived hypomorphic alleles. CYP2A6 and UGT2B10 genotype explain 53% of the variance in oral nicotine glucuronidation in this sample. CYP2A6 and UGT2B10 genetic variants are also significantly associated with un-deuterated (D0) nicotine glucuronidation in subjects smoking ad libitum. We find no evidence for further common variation markedly influencing hepatic UGT2B10 expression in European Americans. PMID:24192532

Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

PubMed Central

Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

2011-01-01

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process. PMID:21464994

Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

PubMed

Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

2011-03-25

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

The Relationship Between Digit Ratio (2D:4D) and Sexual Orientation in Men from China.

PubMed

Xu, Yin; Zheng, Yong

2016-04-01

We examined the relationship between 2D:4D digit ratio and sexual orientation in men from China and analyzed the influences of the components used to assess sexual orientation and the criteria used to classify individuals as homosexual on this relationship. A total of 309 male and 110 female participants took part in a web-based survey. Our results showed that heterosexual men had a significantly lower 2D:4D than heterosexual women and exclusively homosexual men had a significantly higher left 2D:4D than heterosexual men whereas only exclusively homosexual men had a significantly higher right 2D:4D than heterosexual men when sexual orientation was assessed via sexual attraction. The left 2D:4D showed a significant positive correlation with sexual identity, sexual attraction, and sexual behavior, and the right 2D:4D showed a significant positive correlation with sexual attraction. The effect sizes for differences in 2D:4D between homosexual and heterosexual men varied according to criteria used to classify individuals as homosexual and sexual orientation components; the more stringent the criteria (scores closer to the homosexual category), the larger the effect sizes; further, sexual attraction yielded the largest effect size. There were no significant effects of age and latitude on Chinese 2D:4D. This study contributes to the current understanding of the relationship between 2D:4D and male sexual orientation.

D/H fractionation in the H2-H2O system at supercritical water conditions: Compositional and hydrogen bonding effects

NASA Astrophysics Data System (ADS)

Foustoukos, Dionysis I.; Mysen, Bjorn O.

2012-06-01

A series of experiments has been conducted in the H2-D2-D2O-H2O-Ti-TiO2 system at temperatures ranging from 300 to 800 °C and pressures between ∼0.3 and 1.3 GPa in a hydrothermal diamond anvil cell, utilizing Raman spectroscopy as a quantitative tool to explore the relative distribution of hydrogen and deuterium isotopologues of the H2 and H2O in supercritical fluids. In detail, H2O-D2O solutions (1:1) were reacted with Ti metal (3-9 h) in the diamond cell, leading to formation of H2, D2, HD, and HDO species through Ti oxidation and H-D isotope exchange reactions. Experimental results obtained in situ and at ambient conditions on quenched samples indicate significant differences from the theoretical estimates of the equilibrium thermodynamic properties of the H-D exchange reactions. In fact, the estimated enthalpy for the H2(aq)-D2(aq) disproportionation reaction (ΔHrxn) is about -3.4 kcal/mol, which differs greatly from the +0.16 kcal/mol predicted for the exchange reaction in the gas phase by statistical mechanics models. The exothermic behavior of the exchange reaction implies enhanced stability of H2 and D2 relative to HD. Accordingly, the significant energy difference of the internal H2(aq)-D2(aq)-HD(aq) equilibrium translates to strong differences of the fractionation effects between the H2O-H2 and D2O-D2 isotope exchange relationships. The D/H fractionation factors between H2O-H2(aq) and D2O-D2(aq) differ by 365‰ in the 600-800 °C temperature range, and are indicative of the greater effect of D2O contribution to the δD isotopic composition of supercritical fluids. The negative ΔHrxn values for the H2(aq)-D2(aq)-HD(aq) equilibrium and the apparent decrease of the equilibrium constant with increasing temperature might be because of differences of the Henry’s law constant between the H- and D-bearing species dissolved in supercritical aqueous solutions. Such effects may be attributed to the stronger hydrogen bonding in the O-H⋯O relative to the O-D⋯O environment. This difference allows enhanced gas solubility in the denser and more polar H2O clusters, and thus, affects the D/H exchange between the H2-D2 volatiles and the coexisting H2O-D2O mixtures. The proposed role of temperature in promoting differences in the density and polarity of hydrogen-bonded OHO and ODO molecules may be explained with isotope-specific molar volume effects similar to those suggested to account for the hydrogen isotope fractionation between H2O and hydroxide mineral phases (e.g. brucite) across large pressure intervals.

Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD.

PubMed

Kaufmann, Martin; Gallagher, J Christopher; Peacock, Munro; Schlingmann, Karl-Peter; Konrad, Martin; DeLuca, Hector F; Sigueiro, Rita; Lopez, Borja; Mourino, Antonio; Maestro, Miguel; St-Arnaud, René; Finkelstein, Joel S; Cooper, Donald P; Jones, Glenville

2014-07-01

The discovery of hypercalcemic diseases due to loss-of-function mutations in 25-hydroxyvitamin D-24-hydroxylase has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D [24,25-(OH)2D]. We describe a novel liquid chromatography and tandem mass spectrometry-based method involving derivatization with DMEQ-TAD {4-[2-(6,7-dimethoxy-4-methyl-3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione} to simultaneously assay multiple vitamin D metabolites including 25-hydroxyvitamin D (25-OH-D) and 24,25-(OH)2D using 100 μL of serum with a 5-minute run time. The assay uses a newly synthesized internal standard d6-24,25-(OH)2D3 enabling the quantitation of 24,25-(OH)2D3 as well as the determination of the ratio of 25-OH-D3 to 24,25-(OH)2D3, a physiologically useful parameter. We report data on more than 1000 normal and disease samples involving vitamin D deficiency or hypercalcemia in addition to studies involving knockout mouse models. The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2% to -5% bias) and exhibited low inter- and intraassay coefficients of variation (4%-7%) and lower limits of quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2) = 0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3 to 24,25-(OH)2D3, which remained less than 25 in vitamin D-sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile hypercalcemia. The new method showed good utility in clinical settings involving vitamin D deficiency; supplementation with vitamin D and idiopathic infantile hypercalcemia, as well as in animal models with ablation of selected cytochrome P450-containing enzymes involved in vitamin D metabolism.

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

PubMed

Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

2008-12-01

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence. (c) 2008 Wiley-Liss, Inc.

3D-2D registration in endovascular image-guided surgery: evaluation of state-of-the-art methods on cerebral angiograms.

PubMed

Mitrović, Uroš; Likar, Boštjan; Pernuš, Franjo; Špiclin, Žiga

2018-02-01

Image guidance for minimally invasive surgery is based on spatial co-registration and fusion of 3D pre-interventional images and treatment plans with the 2D live intra-interventional images. The spatial co-registration or 3D-2D registration is the key enabling technology; however, the performance of state-of-the-art automated methods is rather unclear as they have not been assessed under the same test conditions. Herein we perform a quantitative and comparative evaluation of ten state-of-the-art methods for 3D-2D registration on a public dataset of clinical angiograms. Image database consisted of 3D and 2D angiograms of 25 patients undergoing treatment for cerebral aneurysms or arteriovenous malformations. On each of the datasets, highly accurate "gold-standard" registrations of 3D and 2D images were established based on patient-attached fiducial markers. The database was used to rigorously evaluate ten state-of-the-art 3D-2D registration methods, namely two intensity-, two gradient-, three feature-based and three hybrid methods, both for registration of 3D pre-interventional image to monoplane or biplane 2D images. Intensity-based methods were most accurate in all tests (0.3 mm). One of the hybrid methods was most robust with 98.75% of successful registrations (SR) and capture range of 18 mm for registrations of 3D to biplane 2D angiograms. In general, registration accuracy was similar whether registration of 3D image was performed onto mono- or biplanar 2D images; however, the SR was substantially lower in case of 3D to monoplane 2D registration. Two feature-based and two hybrid methods had clinically feasible execution times in the order of a second. Performance of methods seems to fall below expectations in terms of robustness in case of registration of 3D to monoplane 2D images, while translation into clinical image guidance systems seems readily feasible for methods that perform registration of the 3D pre-interventional image onto biplanar intra-interventional 2D images.

Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase.

PubMed

Park, I S; Lin, C H; Walsh, C T

1997-09-16

The VanC phenotype for clinical resistance of enterococci to vancomycin is exhibited by Enterococcus gallinarum and Enterococcus casseliflavus. Based on the detection of the cell precursor UDP-N-acetylmuramic acid pentapeptide intermediate terminating in D-Ala-D-Ser instead of D-Ala-D-Ala, it has been predicted that the VanC ligase would be a D-Ala-D-Ser rather than a D-Ala-D-Ala ligase. Overproduction of the E. casseliflavus ATCC 25788 vanC2 gene in Escherichia coli and its purification to homogeneity allowed demonstration of ATP-dependent D-Ala-D-Ser ligase activity. The kcat/Km2 (Km2 = Km for D-Ser or C-terminal D-Ala) ratio for D-Ala-D-Ser/D-Ala-D-Ala dipeptide formation is 270/0.69 for a 400-fold selection against D-Ala in the C-terminal position. VanC2 also has substantial D-Ala-D-Asn ligase activity (kcat/Km2 = 74 mM-1min-1).

Remedial Investigation of Contaminant Mobility at Naval Weapons Station, Concord, California. Subtitle Appendix 2.5. 1986/1987.

DTIC Science & Technology

1988-06-01

sandwiched between relatively dry, clayey silt beds of low permeability. c. The aquifer is confined under a piezometric head, and water rose a few feet in...2.5-D12 Field Measurements for Kiln Site Monitoring Wells (May and August 1987 ) ............... D15 2.5-D13 Well Development and Ground- water ...Analysis .... D16 2.5-D14 Water Sample Analysis (May 1987 ) ............... D17 2.5-D15 Water Sample Quality Control Data (May 1987 )... D18 2.5-D16 Water

Link between D sub 1 and D sub 2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

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

Seeman, P.; Niznik, H.B.; Guan, H.C.

1989-12-01

Dopamine receptor types D{sub 1} and D{sub 2} can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D{sub 1}-D{sub 2} interaction in homogenized tissue as revealed by ligand binding. D{sub 2} agonists lowered the binding of ({sup 3}H)raclopride to D{sub 2} receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D{sub 1}-selective antagonist SCH 23390 prevented the agonist-induced decrease in ({sup 3}H)raclopride binding to D{sub 2} sites in the striatum but not in the anterior pituitary, which has no D{sub 1} receptors. Conversely, a dopamine-induced reduction in the binding ofmore » ({sup 3}H)SCH 23390 to D{sub 1} receptors could be prevented by the D{sub 2}-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D{sub 1}-D{sub 2} interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D{sub 2} receptors in the high-affinity state. Thus, the D{sub 1}-D{sub 2} link may be mediated by guanine nucleotide-binding protein components. The link may underlie D{sub 1}-D{sub 2} interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata.« less

Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

PubMed Central

Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

2016-01-01

The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological allosteric facilitatory 5-HT2A–D2 interaction increasing D2 protomer signaling. Neurotensin (NTS1)–D2 heterocomplexes also exist in the ventral and dorsal striatum, and likely also in midbrain DA nerve cells as NTS1-D2 autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively. PMID:27141290

The effect on surgical skills of expert surgeons using 3D/HD and 2D/4K resolution monitors in laparoscopic phantom tasks.

PubMed

Harada, Hitoshi; Kanaji, Shingo; Hasegawa, Hiroshi; Yamamoto, Masashi; Matsuda, Yoshiko; Yamashita, Kimihiro; Matsuda, Takeru; Oshikiri, Taro; Sumi, Yasuo; Nakamura, Tetsu; Suzuki, Satoshi; Kakeji, Yoshihiro

2018-03-30

Recently, several new imaging technologies, such as three-dimensional (3D)/high-definition (HD) stereovision and high-resolution two-dimensional (2D)/4K monitors, have been introduced in laparoscopic surgery. However, it is still unclear whether these technologies actually improve surgical performance. Participants were 11 expert laparoscopic surgeons. We designed three laparoscopic suturing tasks (task 1: simple suturing, task 2: knotting thread in a small box, and task 3: suturing in a narrow space) in training boxes. Performances were recorded by an optical position tracker. All participants first performed each task five times consecutively using a conventional 2D/HD monitor. Then they were randomly divided into two groups: six participants performed the tasks using 3D/HD before using 2D/4K; the other five participants performed the tasks using a 2D/4K monitor before the 3D/HD monitor. After the trials, we evaluated the performance scores (operative time, path length of forceps, and technical errors) and compared performance scores across all monitors. Surgical performances of participants were ranked in decreasing order: 3D/HD, 2D/4K, and 2D/HD using the total scores for each task. In task 1 (simple suturing), some surgical performances using 3D/HD were significantly better than those using 2D/4K (P = 0.017, P = 0.033, P = 0.492 for operative time, path length, and technical errors, respectively). On the other hand, with operation in narrow spaces such as in tasks 2 and 3, performances using 2D/4K were not inferior to 3D/HD performances. The high-resolution images from the 2D/4K monitor may enhance depth perception in narrow spaces and may complement stereoscopic vision almost as well as using 3D/HD. Compared to a 2D/HD monitor, a 3D/HD monitor improved the laparoscopic surgical technique of expert surgeons more than a 2D/4K monitor. However, the advantage of 2D/4K high-resolution images may be comparable to a 3D/HD monitor especially in narrow spaces.

Development of a Glycoprotein D-Expressing Dominant-Negative and Replication-Defective Herpes Simplex Virus 2 (HSV-2) Recombinant Viral Vaccine against HSV-2 Infection in Mice ▿

PubMed Central

Akhrameyeva, Natalie V.; Zhang, Pengwei; Sugiyama, Nao; Behar, Samuel M.; Yao, Feng

2011-01-01

Using the T-REx (Invitrogen, California) gene switch technology and a dominant-negative mutant polypeptide of herpes simplex virus 1 (HSV-1)-origin binding protein UL9, we previously constructed a glycoprotein D-expressing replication-defective and dominant-negative HSV-1 recombinant viral vaccine, CJ9-gD, for protection against HSV infection and disease. It was demonstrated that CJ9-gD is avirulent following intracerebral inoculation in mice, cannot establish detectable latent infection following different routes of infection, and offers highly effective protective immunity against primary HSV-1 and HSV-2 infection and disease in mouse and guinea pig models of HSV infections. Given these favorable safety and immunological profiles of CJ9-gD, aiming to maximize levels of HSV-2 glycoprotein D (gD2) expression, we have constructed an ICP0 null mutant-based dominant-negative and replication-defective HSV-2 recombinant, CJ2-gD2, that contains 2 copies of the gD2 gene driven by the tetracycline operator (tetO)-bearing HSV-1 major immediate-early ICP4 promoter. CJ2-gD2 expresses gD2 as efficiently as wild-type HSV-2 infection and can lead to a 150-fold reduction in wild-type HSV-2 viral replication in cells coinfected with CJ2-gD2 and wild-type HSV-2 at the same multiplicity of infection. CJ2-gD2 is avirulent following intracerebral injection and cannot establish a detectable latent infection following subcutaneous (s.c.) immunization. CJ2-gD2 is a more effective vaccine than HSV-1 CJ9-gD and a non-gD2-expressing dominant-negative and replication-defective HSV-2 recombinant in protection against wild-type HSV-2 genital disease. Using recall response, we showed that immunization with CJ2-gD2 elicited strong HSV-2-specific memory CD4+ and CD8+ T-cell responses. Collectively, given the demonstrated preclinical immunogenicity and its unique safety profiles, CJ2-gD2 represents a new class of HSV-2 replication-defective recombinant viral vaccines in protection against HSV-2 genital infection and disease. PMID:21389121

Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years.

PubMed

Puthanakit, Thanyawee; Huang, Li-Min; Chiu, Cheng-Hsun; Tang, Ren-Bin; Schwarz, Tino F; Esposito, Susanna; Frenette, Louise; Giaquinto, Carlo; McNeil, Shelly; Rheault, Paul; Durando, Paolo; Horn, Michael; Klar, Maximilian; Poncelet, Sylviane; De Simoni, Stéphanie; Friel, Damien; De Muynck, Benoit; Suryakiran, Pemmaraju V; Hezareh, Marjan; Descamps, Dominique; Thomas, Florence; Struyf, Frank

2016-08-15

This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years. Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety. Limits of noninferiority were predefined as <5% difference in seroconversion rate and <2-fold difference in geometric mean antibody titer ratio. One month after the last dose, both 2D regimens in girls aged 9-14 years were noninferior to 3D in women aged 15-25 years and 2D (M0,12) was noninferior to 2D (M0,6). Geometric mean antibody titer ratios (3D/2D) for HPV-16 and HPV-18 were 1.09 (95% confidence interval, .97-1.22) and 0.85 (.76-.95) for 2D (M0,6) versus 3D and 0.89 (.79-1.01) and 0.75 (.67-.85) for 2D (M0,12) versus 3D. The safety profile was clinically acceptable in all groups. The 2D regimens for the HPV-16/18 AS04-adjuvanted vaccine in girls aged 9-14 years (M0,6 or M0,12) elicited HPV-16/18 immune responses that were noninferior to 3D in women aged 15-25 years. NCT01381575. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.

PubMed

Xue, Liang; Xi, Hongjuan; Kumar, Sunil; Gray, David; Davis, Erik; Hamilton, Paris; Skriba, Michael; Arya, Dev P

2010-07-06

Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA).2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (T(m3-->2)) at which poly(dA).2poly(dT) dissociated into poly(dA).poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator-neomycin conjugates (1-4) even at a very low concentration (2 muM). In contrast to intercalator-neomycin conjugates, the increment of T(m3-->2) of poly(dA).2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator-neomycin conjugates (1-4) to poly(dA).2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size ( approximately 7-7.5) with poly(dA).2poly(dT) as compared to neomycin ( approximately 6.5). The thermodynamic parameters of these intercalator-neomycin conjugates with poly(dA).2poly(dT) were derived from an integrated van't Hoff equation using the T(m3-->2) values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA).2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M(-1)] of 2 with poly(dA).2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA).2poly(dT) was mostly enthalpy-driven and gave negative DeltaC(p) values. The results described here suggest that the binding affinity of intercalator-neomycin conjugates for poly(dA).2poly(dT) increases as a function of the surface area of the intercalator moiety.

Relationships between digit ratio (2D:4D) and basketball performance in Australian men.

PubMed

Frick, Nathan A; Hull, Melissa J; Manning, John T; Tomkinson, Grant R

2017-05-06

To investigate relationships between the digit ratio (2D:4D) and competitive basketball performance in Australian men. Using an observational cross-sectional design a total of 221 Australian basketball players who competed in the Olympic Games, International Basketball Federation World Championships/Cup, Australian National Basketball League, Central Australian Basketball League or socially had their 2D:4Ds measured. Analysis of variance was used to assess differences in mean 2D:4Ds between men playing at different competitive standards, with relationships between 2D:4Ds and basketball game-related statistics assessed using Pearson's product moment correlations in men playing at a single competitive standard. There were significant differences between competitive standards for the left 2D:4D following Bonferroni correction, but not for the right 2D:4D, with basketballers who achieved higher competitive standards tending to have lower left 2D:4Ds. No important correlations between 2D:4D and basketball game-related statistics were found, with correlations typically negligible. This study indicated that the 2D:4D can discriminate between basketballers competing at different standards, but not between basketballers within a single competitive standard using objective game-related statistics. © 2016 Wiley Periodicals, Inc.

Four new triterpenoid glycosides from the seed residue of Hippophae rhamnoides subsp. sinensis.

PubMed

Chen, Chao; Gao, Wen; Cheng, Liang; Shao, Yan; Kong, De-Yun

2014-01-01

Four new triterpenoid saponins (1-4) were isolated from the seed residue of Hippophae rhamnoides subsp. sinensis, named 3-O-[β-D-glucopyranosyl(1 → 2)-β-D-glucopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosyl-13-ene-19-one-28-oic acid 28-O-β-D-glucopyranosyl ester (1), 3-O-[β-D-glucopyranosyl(1 → 2)-β-D-glucopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-α-L-arabinopyranosyl-13-ene-19-one-30-hydroxyolean-28-oic acid 28-O-β-D-glucopyranosyl ester (2), 3-O-[β-D-glucopyranosyl(1 → 2)-β-D-glucopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-13-ene-19-one-28-oic acid 28-O-β-D-glucopyranosyl ester (3), and 3-O-[β-D-glucopyranosyl(1 → 2)-β-D-glucopyranosyl-(1 → 3)]-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-glucopyranosyl-13-ene-19-one-30-hydroxyolean-28-oic acid 28-O-β-D-glucopyranosyl ester (4), and their structures were elucidated on the basis of spectroscopic and chemical methods.

3D isotropic T2-weighted fast spin echo (VISTA) versus 2D T2-weighted fast spin echo in evaluation of the calcaneofibular ligament in the oblique coronal plane.

PubMed

Park, H J; Lee, S Y; Choi, Y J; Hong, H P; Park, S J; Park, J H; Kim, E

2017-02-01

To investigate whether the image quality of three-dimensional (3D) volume isotropic fast spin echo acquisition (VISTA) magnetic resonance imaging (MRI) of the calcaneofibular ligament (CFL) view is comparable to that of 2D fast spin echo T2-weighted images (2D T2 FSE) for the evaluation of the CFL, and whether 3D VISTA can replace 2D T2 FSE for the evaluation of CFL injuries. This retrospective study included 76 patients who underwent ankle MRI with CFL views of both 2D T2 FSE MRI and 3D VISTA. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of both techniques were measured. The anatomical identification score and diagnostic performances were evaluated by two readers independently. The diagnostic performances of 3D VISTA and 2D T2 FSE were analysed by sensitivity, specificity, and accuracy for diagnosing CFL injury with reference standards of surgically or clinically confirmed diagnoses. Surgical correlation was performed in 29% of the patients, and clinical examination was used in those who did not have surgery (71%). The SNRs and CNRs of 3D VISTA were significantly higher than those of 2D T2 FSE. The anatomical identification scores on 3D VISTA were inferior to those on 2D T2 FSE, and the differences were statistically significant (p<0.05). There were no significant differences in diagnostic performance between the two sequences when diagnoses were classified as normal or abnormal. Although the image quality of 3D VISTA MRI of the CFL view is not equal to that of 2D T2 FSE for the anatomical evaluation of CFL, 3D VISTA has a diagnostic performance comparable to that of 2D T2 FSE for the diagnosis of CFL injuries. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effects of dimensionality and laser polarization on kinetic simulations of laser-ion acceleration in the transparency regime

NASA Astrophysics Data System (ADS)

Stark, David; Yin, Lin; Albright, Brian; Guo, Fan

2017-10-01

The often cost-prohibitive nature of three-dimensional (3D) kinetic simulations of laser-plasma interactions has resulted in heavy use of two-dimensional (2D) simulations to extract physics. However, depending on whether the polarization is modeled as 2D-S or 2D-P (laser polarization in and out of the simulation plane, respectively), different results arise. In laser-ion acceleration in the transparency regime, VPIC particle-in-cell simulations show that 2D-S and 2D-P capture different physics that appears in 3D simulations. The electron momentum distribution is virtually two-dimensional in 2D-P, unlike the more isotropic distributions in 2D-S and 3D, leading to greater heating in the simulation plane. As a result, target expansion time scales and density thresholds for the onset of relativistic transparency differ dramatically between 2D-S and 2D-P. The artificial electron heating in 2D-P exaggerates the effectiveness of target-normal sheath acceleration (TNSA) into its dominant acceleration mechanism, whereas 2D-S and 3D both have populations accelerated preferentially during transparency to higher energies than those of TNSA. Funded by the LANL Directed Research and Development Program.

SU-D-BRA-03: Analysis of Systematic Errors with 2D/3D Image Registration for Target Localization and Treatment Delivery in Stereotactic Radiosurgery

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

Xu, H; Chetty, I; Wen, N

Purpose: Determine systematic deviations between 2D/3D and 3D/3D image registrations with six degrees of freedom (6DOF) for various imaging modalities and registration algorithms on the Varian Edge Linac. Methods: The 6DOF systematic errors were assessed by comparing automated 2D/3D (kV/MV vs. CT) with 3D/3D (CBCT vs. CT) image registrations from different imaging pairs, CT slice thicknesses, couch angles, similarity measures, etc., using a Rando head and a pelvic phantom. The 2D/3D image registration accuracy was evaluated at different treatment sites (intra-cranial and extra-cranial) by statistically analyzing 2D/3D pre-treatment verification against 3D/3D localization of 192 Stereotactic Radiosurgery/Stereotactic Body Radiation Therapy treatmentmore » fractions for 88 patients. Results: The systematic errors of 2D/3D image registration using kV-kV, MV-kV and MV-MV image pairs using 0.8 mm slice thickness CT images were within 0.3 mm and 0.3° for translations and rotations with a 95% confidence interval (CI). No significant difference between 2D/3D and 3D/3D image registrations (P>0.05) was observed for target localization at various CT slice thicknesses ranging from 0.8 to 3 mm. Couch angles (30, 45, 60 degree) did not impact the accuracy of 2D/3D image registration. Using pattern intensity with content image filtering was recommended for 2D/3D image registration to achieve the best accuracy. For the patient study, translational error was within 2 mm and rotational error was within 0.6 degrees in terms of 95% CI for 2D/3D image registration. For intra-cranial sites, means and std. deviations of translational errors were −0.2±0.7, 0.04±0.5, 0.1±0.4 mm for LNG, LAT, VRT directions, respectively. For extra-cranial sites, means and std. deviations of translational errors were - 0.04±1, 0.2±1, 0.1±1 mm for LNG, LAT, VRT directions, respectively. 2D/3D image registration uncertainties for intra-cranial and extra-cranial sites were comparable. Conclusion: The Varian Edge radiosurgery 6DOF-based system, can perform 2D/3D image registration with high accuracy for target localization in image-guided stereotactic radiosurgery. The work was supported by a Research Scholar Grant, RSG-15-137-01-CCE from the American Cancer Society.« less

Evolution of the CYP2D gene cluster in humans and four non-human primates.

PubMed

Yasukochi, Yoshiki; Satta, Yoko

2011-01-01

The human cytochrome P450 2D6 (CYP2D6) is a primary enzyme involved in the metabolism of about 25% of commonly used therapeutic drugs. CYP2D6 belongs to the CYP2D subfamily, a gene cluster located on chromosome 22, which comprises the CYP2D6 gene and pseudogenes CYP2D7P and CYP2D8P. Although the chemical and physiological properties of CYP2D6 have been extensively studied, there has been no study to date on molecular evolution of the CYP2D subfamily in the human genome. Such knowledge could greatly contribute to the understanding of drug metabolism in humans because it makes us to know when and how the current metabolic system has been constructed. The knowledge moreover can be useful to find differences in exogenous substrates in a particular metabolism between human and other animals such as experimental animals. Here, we conducted a preliminary study to investigate the evolution and gene organization of the CYP2D subfamily, focused on humans and four non-human primates (chimpanzees, orangutans, rhesus monkeys, and common marmosets). Our results indicate that CYP2D7P has been duplicated from CYP2D6 before the divergence between humans and great apes, whereas CYP2D6 and CYP2D8P have been already present in the stem lineages of New World monkeys and Catarrhini. Furthermore, the origin of the CYP2D subfamily in the human genome can be traced back to before the divergence between amniotes and amphibians. Our analyses also show that reported chimeric sequences of the CYP2D6 and CYP2D7 genes in the chimpanzee genome appear to be exchanged in its genome database.

A General Purpose Ionospheric Ray Tracing Procedure

DTIC Science & Technology

1993-08-01

hmE-bmF2) /ymF2) al(2)=chap( .5d0,2.d09 (hmPl- bmE )/ymE) a2 (2) =1. a3(2)-chap(l.dOl .4142d09 (bm~l.-hmP2) ymP2) al(3)=chap( .5d0,2.d0*(bmF2- bmE )iymE...R.H Clarke, Radiowave Propagation 1 Libraries and Information Services Australian Government Publishing Service 1 Defence Central Library - Technical

State Estimation of a Hybrid Markov Process with Application to Multitarget Tracking.

DTIC Science & Technology

1982-01-01

k (d k))T P (dk - k -1 k kP~d kzk ) IPk~k (d k) (.Zkik (d 2) - xkk dl)) + 2 2.n P~-d k 1zk n J k ( .15d2 I) Ipklk1dk)I 66 k < c k an kk k if Pkk(d I...bealat more likely at time k, i.e., P(d kzk ) < P(d2[zk). Thus, if we want to kdiscard a given sequence d0, we try to compare it only with other more k

New steroidal glycosides from Tribulus terrestris L.

PubMed

Chen, Gang; Liu, Tao; Lu, Xuan; Wang, Hai-Feng; Hua, Hui-Ming; Pei, Yue-Hu

2012-01-01

Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

Two new lignan glycosides from the seeds of Cuscuta chinensis.

PubMed

He, Xiang-Hui; Yang, Wen-Zhi; Meng, A-Hui; He, Wen-Ni; Guo, De-An; Ye, Min

2010-11-01

Two new lignan glycosides, 2'-hydroxyl asarinin 2'-O-β-D-glucopyranoside (cuscutoside C, 1) and 2'-hydroxyl asarinin 2'-O-β-D-apiofuranosyl-(1 → 2)-[β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranoside (cuscutoside D, 2), were isolated from the seeds of Cuscuta chinensis Lam., along with six known compounds, 2'-hydroxyl asarinin 2'-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (3), 2'-hydroxyl asarinin 2'-O-β-D-apiofuranosyl-(1 → 2)-β-D-glucopyranoside (cuscutoside A, 4), kaempferol 3,7-di-O-β-D-glucopyranoside (5), 5-caffeoyl quinic acid (6), 4-caffeoyl quinic acid (7), and cinnamic acid (8). Their structures were elucidated on the basis of spectroscopic analyses including HR-ESI-MS, ESI-MS/MS, (1)H and (13)C NMR, HSQC, HMBC, and TOCSY.

UV-dependent production of 25-hydroxyvitamin D{sub 2} in the recombinant yeast cells expressing human CYP2R1

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

Yasuda, Kaori; Endo, Mariko; Ikushiro, Shinichi

Highlights: •We produce 25-hydroxyvitamin D in the recombinant yeast expressing human CYP2R1. •Vitamin D2 is produced in yeast from endogenous ergosterol with UV irradiation. •We produce 25-hydroxyvitamin D2 in the recombinant yeast without added substrate. -- Abstract: CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D{sub 3} or vitamin D{sub 2} was added to the cell suspension of CYP2R1-expressing yeast cells in amore » buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D{sub 2} was produced without additional vitamin D{sub 2}. Endogenous ergosterol was likely converted into vitamin D{sub 2} by UV irradiation and thermal isomerization, and then the resulting vitamin D{sub 2} was converted to 25-hydroxyvitamin D{sub 2} by CYP2R1. This novel method for producing 25-hydroxyvitamin D{sub 2} without a substrate could be useful for practical purposes.« less

Study of Three Dimensional Transonic Flow Separations.

DTIC Science & Technology

1988-04-01

22222222222222222222222222222222222222 CD22 2 NN 22 0 2 2 C 22 .2 2 .2 .2 .2 .’ 22 . . . cD( C) DC)C DC D CC 222 2 22 2 2- C 2 22 22 22 - 22 02 N NT NL z...In1.0 INco (N -.- L’ c3 107 :-I--cnr -! - - N N 1 f;CC-7 cD c, 222 c222 cN -) H22 o cc -- -4 0,2222222" (D2 C22 22 D2 220 CD22 CD 2 CD CD N22 22D2

Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca(superscript)2+]subscript)i Imaging

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

Du, C.; Luo, Z.; Volkow, N.D.

Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca{sup 2+}]{sub i} ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum.more » Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca{sup 2+}]{sub i} in D1R-expressing neurons (10.6 {+-} 3.2%) in striatum within 8.3 {+-} 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca{sup 2+}]{sub i} increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca{sup 2+}]{sub i} in D2R-expressing neurons (10.4 {+-} 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca{sup 2+}]{sub i} decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.« less

Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats.

PubMed

Pinski, J; Yano, T; Janaky, T; Nagy, A; Juhasz, A; Bokser, L; Groot, K; Schally, A V

1993-01-01

A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-D-Nal(2), D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Car)2)6, D-Ala10]LH-RH (T-140); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(Ac)2)6, D-Ala10]LH-RH (T-148); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2pr(For)2)6, D-Ala10]LH-RH (T-151) and [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Lys(A2bu(For)2)6, D-Ala10]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 micrograms/rat and antagonist T-159 at a dose of only 0.75 micrograms/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 micrograms/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P < 0.01) decrease in LH levels for more than 6 h. Significant (P < 0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 micrograms sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 micrograms/rat sc.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of strong decays of charmed mesons D2*(2460 ) , D0(2560 ), D2(2740 ), D1(3000 ), D2*(3000 ), and their spin partners D1*(2680 ), D3*(2760 ), and D0*(3000 )

NASA Astrophysics Data System (ADS)

Gupta, Pallavi; Upadhyay, A.

2018-01-01

Using the effective Lagrangian approach, we examine the recently observed charm states DJ*(2460 ), DJ(2560 ), DJ(2740 ), DJ(3000 ), and their spin partners DJ*(2680 ), DJ*(2760 ), and DJ*(3000 ) with JP states 1 P3/22+, 2 S1/20-, 1 D5/22-, 2 P1/21+, and 2 S1/21-, 1 D5/23-, 2 P1/20+ respectively. We study their two body strong decays, coupling constants and branching ratios with the emission of light pseudo-scalar mesons (π ,η ,K ). We also analyze the newly observed charm state D2*(3000 ) and suggest it to be either 1 F (2+) or 2 P (2+) state and justify one of them to be the most favorable assignment for D2*(3000 ). We study the partial and the total decay width of unobserved states D (1 1F3) , Ds(1 1F3) and Ds(1 1F2) as the spin and the strange partners of the D2*(3000 ) charmed meson. The branching ratios and the coupling constants gT H, g˜H H, gY H, g˜S H, and gZ H calculated in this work can be confronted with the future experimental data.

Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity

PubMed Central

2016-01-01

Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy. PMID:27035329

Structure–Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

PubMed Central

Paul, Noel M.; Taylor, Michelle; Kumar, Rakesh; Deschamps, Jeffrey R.; Luedtke, Robert R.; Newman, Amy Hauck

2011-01-01

Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; Ki(D2R/D3R) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2LR- or hD3R-transfected HEK 293 cells (31, Ki(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, Ki(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes. PMID:18774793

Formation of Fused-Ring 2′-Deoxycytidine Adducts from 1-Chloro-3-buten-2-one, an in Vitro 1,3-Butadiene Metabolite, under in Vitro Physiological Conditions

PubMed Central

Sun, Liang; Pelah, Avishay; Zhang, Dong-Ping; Zhong, Yu-Fang; An, Jing; Yu, Ying-Xin; Zhang, Xin-Yu; Elfarra, Adnan A.

2013-01-01

1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic and genotoxic in human liver cells in culture with CBO being approximately 100-fold more potent than CHB. In the present study, CBO was shown to react readily with 2′-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 °C) to form four dC adducts with the CBO moieties forming fused rings with the N3 and N4 atoms of dC. The four products were structurally characterized as 2-hydroxy-2-hydroxymethyl-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahy dro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydr o-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydr o-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4). Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH 7.4, 37 °C, 6 h) and existed in equilibrium as indicated by HPLC analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 ± 0.36 and 1.7 ± 0.06 h, respectively. Decomposition of dC-4 produced both dC-1 and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 °C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H, respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the characterized CBO-dC adducts could be mutagenic and play a role in the cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC adducts may also be used as standards to characterize CBO-DNA adducts and to develop potential biomarkers for CBO formation in vivo. PMID:24020501

Nucleus accumbens dopamine D2-receptor expressing neurons control behavioral flexibility in a place discrimination task in the IntelliCage.

PubMed

Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

2016-07-01

Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1- and D2-MSNs in the acquisition and reversal learning of a place discrimination task. We demonstrated that NAc D1- and D2-MSNs do not mediate the acquisition of the task, but that suppression of activity in D2-MSNs impairs reversal learning and increased perseverative errors. Additionally, global knockout of the dopamine D2L receptor isoform produced a similar behavioral phenotype to D2-MSN-blocked mice. These results suggest that D2L receptors and NAc D2-MSNs act to suppress the influence of previously correct behavioral strategies allowing transfer of behavioral control to new strategies. © 2016 Macpherson et al.; Published by Cold Spring Harbor Laboratory Press.

MO-FG-CAMPUS-TeP1-01: An Efficient Method of 3D Patient Dose Reconstruction Based On EPID Measurements for Pre-Treatment Patient Specific QA

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

David, R; Lee, C; Calvary Mater Newcastle, Newcastle

Purpose: To demonstrate an efficient and clinically relevant patient specific QA method by reconstructing 3D patient dose from 2D EPID images for IMRT plans. Also to determine the usefulness of 2D QA metrics when assessing 3D patient dose deviations. Methods: Using the method developed by King et al (Med Phys 39(5),2839–2847), EPID images of IMRT fields were acquired in air and converted to dose at 10 cm depth (SAD setup) in a flat virtual water phantom. Each EPID measured dose map was then divided by the corresponding treatment planning system (TPS) dose map calculated with an identical setup, to derivemore » a 2D “error matrix”. For each field, the error matrix was used to adjust the doses along the respective ray lines in the original patient 3D dose. All field doses were combined to derive a reconstructed 3D patient dose for quantitative analysis. A software tool was developed to efficiently implement the entire process and was tested with a variety of IMRT plans for 2D (virtual flat phantom) and 3D (in-patient) QA analysis. Results: The method was tested on 60 IMRT plans. The mean (± standard deviation) 2D gamma (2%,2mm) pass rate (2D-GPR) was 97.4±3.0% and the mean 2D gamma index (2D-GI) was 0.35±0.06. The 3D PTV mean dose deviation was 1.8±0.8%. The analysis showed very weak correlations between both the 2D-GPR and 2D-GI when compared with PTV mean dose deviations (R2=0.3561 and 0.3632 respectively). Conclusion: Our method efficiently calculates 3D patient dose from 2D EPID images, utilising all of the advantages of an EPID-based dosimetry system. In this study, the 2D QA metrics did not predict the 3D patient dose deviation. This tool allows reporting of the 3D volumetric dose parameters thus providing more clinically relevant patient specific QA.« less

Syntheses, structural analyses and redox kinetics of four-coordinate [CuL2]2+ and five-coordinate [CuL2(solvent)]2+ complexes (L = 6,6'-dimethyl-2,2'-bipyridine or 2,9-dimethyl-1,10-phenanthroline): completely gated reduction reaction of [Cu(dmp)2]2+ in nitromethane.

PubMed

Itoh, Sumitaka; Kishikawa, Nobuyuki; Suzuki, Takayoshi; Takagi, Hideo D

2005-03-21

[Cu(2,9-dimethyl-1,10-phenanthroline)(2)](2+) and [Cu(6,6'-dimethyl-2,2'-bipyridine)(2)](2+/+) complexes with no coordinated solvent molecule were synthesized and the crystal structures were analyzed: the coordination geometry around the Cu(i) center was in the D(2d) symmetry while a D(2) structure was observed for the four-coordinate Cu(ii) complexes. Coordination of a water or an acetonitrile molecule was found in the trigonal plane of the five-coordinate Cu(ii) complex in the Tbp(trigonal bipyramidal) structure. Spectrophotometric analyses revealed that the D(2) structure of the Cu(ii) complex was retained in nitromethane, although a five-coordinate Tbp species (green in color), was readily formed upon dissolution of the solid (reddish brown) in acetonitrile. The electron self-exchange reaction between D(2d)-Cu(I) and D(2)-Cu(II), observed by the NMR method, was very rapid with k(ex)=(1.1 +/- 0.2) x 10(5) kg mol(-1) s(-1) at 25 degrees C (DeltaH*= 15.6 +/- 1.3 kJ mol(-1) and DeltaS*=-96 +/- 4 J mol(-1) K(-1)), which was more than 10 times larger than that reported for the self-exchange reaction between D(2d)-Cu(I) and Tbp-Cu(II) in acetonitrile. The cross reduction reactions of D(2)-Cu(ii) by ferrocene and decamethylferrocene in nitromethane exhibited a completely gated behavior, while the oxidation reaction of D(2d)-Cu(i) by [Ni(1,4,7-triazacyclononane)(2)](3+) in nitromethane estimated an identically large self-exchange rate constant to that directly obtained by the NMR method. The electron self-exchange rate constant estimated from the oxidation cross reaction in 50% v/v acetonitrile-nitromethane mixture was 10 times smaller than that observed in pure nitromethane. On the basis of the Principle of the Least Motion (PLM) and the Symmetry Rules, it was concluded that gated behaviors observed for the reduction reactions of the five-coordinate Cu(ii)-polypyridine complexes are related to the high-energy C(2v)--> D(2d) conformational change around Cu(ii), and that the electron self-exchange reactions of the Cu(ii)/(i) couples are always adiabatic through the C(2v) structures for both Cu(ii) and Cu(i) since the conformational changes between D(2d), D(2) and C(2v) structures for Cu(i) as well as the conformational change between Tbp and C(2v) structures for Cu(ii) are symmetry-allowed. The completely gated behavior observed for the reduction reactions of D(2)-Cu(ii) species in nitromethane was attributed to the very slow conformational change from the ground-state D(2) to the entatic D(2d) structure that is symmetry-forbidden for d(9) metal complexes: the very slow back reaction, the forbidden conformational change from entatic D(2d) to the ground-state D(2) structure, ensures that the rate of the reduction reaction is independent of the concentration of the reducing reagent.

26 CFR 1.355-6 - Recognition of gain on certain distributions of stock or securities in controlled corporation.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., unless otherwise stated, assume that P, S, T, X, Y, N, HC, D, D1, D2, D3, and C are corporations, A and B... and D2, D1 and D2 each owns 50 percent of the stock of D3, and D3 owns all of the stock of C. Within... the stock of D1, D2, D3, and C on the date A purchases the T stock under the attribution rules of...

A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism

PubMed Central

Hasbi, Ahmed; Perreault, Melissa L.; Shen, Maurice Y. F.; Zhang, Lucia; To, Ryan; Fan, Theresa; Nguyen, Tuan; Ji, Xiaodong; O'Dowd, Brian F.; George, Susan R.

2014-01-01

Although the dopamine D1-D2 receptor heteromer has emerging physiological relevance and a postulated role in different neuropsychiatric disorders, such as drug addiction, depression, and schizophrenia, there is a need for pharmacological tools that selectively target such receptor complexes in order to analyze their biological and pathophysiological functions. Since no selective antagonists for the D1-D2 heteromer are available, serial deletions and point mutations were used to precisely identify the amino acids involved in an interaction interface between the receptors, residing within the carboxyl tail of the D1 receptor that interacted with the D2 receptor to form the D1-D2 receptor heteromer. It was determined that D1 receptor carboxyl tail residues 404Glu and 405Glu were critical in mediating the interaction with the D2 receptor. Isolated mutation of these residues in the D1 receptor resulted in the loss of agonist activation of the calcium signaling pathway mediated through the D1-D2 receptor heteromer. The physical interaction between the D1 and D2 receptor could be disrupted, as shown by coimmunoprecipitation and BRET analysis, by a small peptide generated from the D1 receptor sequence that contained these amino acids, leading to a switch in G-protein affinities and loss of calcium signaling, resulting in the inhibition of D1-D2 heteromer function. The use of the D1-D2 heteromer-disrupting peptide in vivo revealed a pathophysiological role for the D1-D2 heteromer in the modulation of behavioral despair. This peptide may represent a novel pharmacological tool with potential therapeutic benefits in depression treatment.—Hasbi, A., Perreault, M. L., Shen, M. Y. F., Zhang, L., To, R., Fan, T., Nguyen, T., Ji, X., O'Dowd, B. F., George, S. R. A peptide targeting an interaction interface disrupts the dopamine D1-D2 receptor heteromer to block signaling and function in vitro and in vivo: effective selective antagonism. PMID:25063849

Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow-independent non-subtractive MRA.

PubMed

Knobloch, Gesine; Lauff, Marie-Teres; Hirsch, Sebastian; Schwenke, Carsten; Hamm, Bernd; Wagner, Moritz

2016-12-01

To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow-independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. Image quality scores of 2D-bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p < 0.0001) with lower rates of non-diagnostic vessel segments on 2D-bSSFP-MRA (reader 1: <1 % vs. 15 %; reader 2: 1 % vs. 29 %; p < 0.05). Diagnostic performance of 2D-bSSFP-MRA and 3D-FSE-MRA across readers showed sensitivities of 89 % (214/240) vs. 70 % (168/240), p = 0.0153; specificities: 91 % (840/926) vs. 63 % (585/926), p < 0.0001; and diagnostic accuracies of 90 % (1054/1166) vs. 65 % (753/1166), p < 0.0001. 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust nonenhanced MRA technique for assessment of the calf arteries at 3 Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D-FSE-MRA). • 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust NE-MRA technique at 3T • 2D-bSSFP-MRA outperforms 3D flow-dependent subtractive MRA (3D-FSE-MRA) as NE-MRA of calf arteries • 2D-bSSFP-MRA is a promising alternative to CE-MRA for calf PAOD evaluation.

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

PubMed

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-02-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models.

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

PubMed Central

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-01-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models. PMID:1310542

Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs.

PubMed

Savino, Maria; Seripa, Davide; Gallo, Antonietta P; Garrubba, Maria; D'Onofrio, Grazia; Bizzarro, Alessandra; Paroni, Giulia; Paris, Francesco; Mecocci, Patrizia; Masullo, Carlo; Pilotto, Alberto; Santini, Stefano A

2011-01-01

Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs. An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele *2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D6*2A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer. A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320). The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.

Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

PubMed

Skelton, Joshua J; Simpson, David M; Peterson, Mark A; Riechers, Dean E

2017-07-26

The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U 50 = 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M 50 = 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

Factors Influencing Dislodgeable 2, 4-D Plant Residues from Hybrid Bermudagrass (Cynodon dactylon L. x C. transvaalensis) Athletic Fields

PubMed Central

Ahmed, Khalied A.; Breeden, Gregory K.

2016-01-01

Research to date has confirmed 2,4-D residues may dislodge from turfgrass; however, experiments have not been conducted on hybrid bermudagrass (Cynodon dactylon L. x C. transvaalensis), the most common athletic field turfgrass in subtropical climates. More specifically, previous research has not investigated the effect of post-application irrigation on dislodgeable 2,4-D residues from hybrid bermudagrass and across turfgrass species, research has been nondescript regarding sample time within a d (TWD) or conducted in the afternoon when the turfgrass canopy is dry, possibly underestimating potential for dislodgement. The effect of irrigation and TWD on 2,4-D dislodgeability was investigated. Dislodgeable 2,4-D amine was reduced > 300% following irrigation. From 2 to 7 d after treatment (DAT), ≤ 0.5% of applied 2,4-D was dislodged from irrigated turfgrass, while ≤ 2.3% of applied 2,4-D was dislodged when not irrigated. 2,4-D dislodgeability decreased as TWD increased. Dislodgeable 2,4-D residues declined to < 0.1% of the applied at 1 DAT– 13:00, and increased to 1 to 3% of the applied 2 DAT– 5:00, suggesting 2,4-D re-suspended on treated turfgrass vegetation overnight. In conclusion, irrigating treated turfgrass reduced dislodgeable 2,4-D. 2,4-D dislodgeability increased as TWD decreased, which was attributed to non-precipitation climatic conditions favoring turfgrass canopy wetness. This research will improve turfgrass management practices and research designed to minimize human 2,4-D exposure. PMID:26863005

Is maternal periconceptional smoking associated with 2D:4D digit ratio in their children?

PubMed

Velez, M P; Arbuckle, T E; Monnier, P; Fraser, W D

2017-10-01

The 2nd--4th finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Maternal periconceptional smoking may alter the homeostasis of fetal androgens, which could in turn result in differential development of 2D:4Ds in utero. The aim of the present study was to assess the effect of maternal periconceptional smoking (i.e. 1 year before through the first trimester of pregnancy) on the 2D:4D of children within The Maternal-Infant Research on Environmental Chemicals (MIREC) study. Maternal smoking history was obtained through questionnaires during the first trimester of pregnancy in 2001 women from 10 cities across Canada. The periconceptional smoking prevalence was 12%. A follow-up study was conducted to measure growth and development up to 5 years of age in a subsample of some 800 MIREC children (MIREC-CD Plus), and digital pictures of the ventral surface of both hands were obtained in mothers and children (2-5 years). The 2D:4D was calculated as the ratio of the 2nd and 4th fingers of each hand. Boys had lower mean 2D:4Ds compared with girls in both hands. Age and maternal 2D:4D were strong determinants of the children's 2D:4D, however, the mean 2D:4D did not differ among children whose mothers had smoked during the periconceptional period compared with those who had not, irrespective of sex. In conclusion, we did not find an association between maternal periconceptional smoking and children's 2D:4D, although the smoking prevalence was low.

Evaluation of various modelling approaches in flood routing simulation and flood area mapping

NASA Astrophysics Data System (ADS)

Papaioannou, George; Loukas, Athanasios; Vasiliades, Lampros; Aronica, Giuseppe

2016-04-01

An essential process of flood hazard analysis and mapping is the floodplain modelling. The selection of the modelling approach, especially, in complex riverine topographies such as urban and suburban areas, and ungauged watersheds may affect the accuracy of the outcomes in terms of flood depths and flood inundation area. In this study, a sensitivity analysis implemented using several hydraulic-hydrodynamic modelling approaches (1D, 2D, 1D/2D) and the effect of modelling approach on flood modelling and flood mapping was investigated. The digital terrain model (DTMs) used in this study was generated from Terrestrial Laser Scanning (TLS) point cloud data. The modelling approaches included 1-dimensional hydraulic-hydrodynamic models (1D), 2-dimensional hydraulic-hydrodynamic models (2D) and the coupled 1D/2D. The 1D hydraulic-hydrodynamic models used were: HECRAS, MIKE11, LISFLOOD, XPSTORM. The 2D hydraulic-hydrodynamic models used were: MIKE21, MIKE21FM, HECRAS (2D), XPSTORM, LISFLOOD and FLO2d. The coupled 1D/2D models employed were: HECRAS(1D/2D), MIKE11/MIKE21(MIKE FLOOD platform), MIKE11/MIKE21 FM(MIKE FLOOD platform), XPSTORM(1D/2D). The validation process of flood extent achieved with the use of 2x2 contingency tables between simulated and observed flooded area for an extreme historical flash flood event. The skill score Critical Success Index was used in the validation process. The modelling approaches have also been evaluated for simulation time and requested computing power. The methodology has been implemented in a suburban ungauged watershed of Xerias river at Volos-Greece. The results of the analysis indicate the necessity of sensitivity analysis application with the use of different hydraulic-hydrodynamic modelling approaches especially for areas with complex terrain.

The non-modulated transfer of total effluent for serially coupled columns in gas chromatography.

PubMed

Krupcík, Ján; Mydlová-Memersheimerová, Janka; Májek, Pavel; Zapadlo, Michal; Sandra, Pat

2010-03-12

The non-modulated transfer (NMT) of the total effluent of the separation of polychlorinated biphenyls (PCBs) on two columns coupled in series has been studied. A non-polar poly(5%-phenyl-95%-methyl)siloxane column (40 m x 100 microm x 0.1 microm) and a polar 70%-cyanopropyl-polysilphenylene-siloxane column (4 m x 0.1 mm x 0.1 microm) were used as (1)D and (2)D columns, respectively. The effluents from both the (1)D column and the (1)D+(2)D column series were monitored independently by two FIDs. Data from the (1)D and (1)D+(2)D integration reports were used to evaluate the NMT experiment. (1)D retention times, t(R,i,D1), were directly accessible from (1)D integration report while (2)D retention times, t(R,i,B), were calculated for all corresponding peak pairs from (1)D and (1)D+(2)D integration reports as a difference t(R,i,D2)=t(R,i,D1+D2)-t(R,i,D1). Search for corresponding peaks of PCB congeners in the (1)D and (1)D+(2)D chromatograms is elucidated in detail on standard PCB samples and on PCB congeners present in the technical formulation Arochlor 1242. Both retention times (t(R,i,D1) and t(R,i,D2)) as well as peak widths at half height (w(h,i)) and peak heights (h(i)) obtained from integration reports were used to construct 2D and 3D images for PCB NMT separations on serially coupled columns. The performance of the NMT procedure is illustrated by the separation of (i) standard PCB solutions, (ii) a mixture of the 209 PCBs, and (iii) a mixture of Arochlor 1242 and hydrocarbons on the DB-5+BPX-70 column series. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Molecular evolution of the CYP2D subfamily in primates: purifying selection on substrate recognition sites without the frequent or long-tract gene conversion.

PubMed

Yasukochi, Yoshiki; Satta, Yoko

2015-03-25

The human cytochrome P450 (CYP) 2D6 gene is a member of the CYP2D gene subfamily, along with the CYP2D7P and CYP2D8P pseudogenes. Although the CYP2D6 enzyme has been studied extensively because of its clinical importance, the evolution of the CYP2D subfamily has not yet been fully understood. Therefore, the goal of this study was to reveal the evolutionary process of the human drug metabolic system. Here, we investigate molecular evolution of the CYP2D subfamily in primates by comparing 14 CYP2D sequences from humans to New World monkey genomes. Window analysis and statistical tests revealed that entire genomic sequences of paralogous genes were extensively homogenized by gene conversion during molecular evolution of CYP2D genes in primates. A neighbor-joining tree based on genomic sequences at the nonsubstrate recognition sites showed that CYP2D6 and CYP2D8 genes were clustered together due to gene conversion. In contrast, a phylogenetic tree using amino acid sequences at substrate recognition sites did not cluster the CYP2D6 and CYP2D8 genes, suggesting that the functional constraint on substrate specificity is one of the causes for purifying selection at the substrate recognition sites. Our results suggest that the CYP2D gene subfamily in primates has evolved to maintain the regioselectivity for a substrate hydroxylation activity between individual enzymes, even though extensive gene conversion has occurred across CYP2D coding sequences. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Molecular Evolution of the CYP2D Subfamily in Primates: Purifying Selection on Substrate Recognition Sites without the Frequent or Long-Tract Gene Conversion

PubMed Central

Yasukochi, Yoshiki; Satta, Yoko

2015-01-01

The human cytochrome P450 (CYP) 2D6 gene is a member of the CYP2D gene subfamily, along with the CYP2D7P and CYP2D8P pseudogenes. Although the CYP2D6 enzyme has been studied extensively because of its clinical importance, the evolution of the CYP2D subfamily has not yet been fully understood. Therefore, the goal of this study was to reveal the evolutionary process of the human drug metabolic system. Here, we investigate molecular evolution of the CYP2D subfamily in primates by comparing 14 CYP2D sequences from humans to New World monkey genomes. Window analysis and statistical tests revealed that entire genomic sequences of paralogous genes were extensively homogenized by gene conversion during molecular evolution of CYP2D genes in primates. A neighbor-joining tree based on genomic sequences at the nonsubstrate recognition sites showed that CYP2D6 and CYP2D8 genes were clustered together due to gene conversion. In contrast, a phylogenetic tree using amino acid sequences at substrate recognition sites did not cluster the CYP2D6 and CYP2D8 genes, suggesting that the functional constraint on substrate specificity is one of the causes for purifying selection at the substrate recognition sites. Our results suggest that the CYP2D gene subfamily in primates has evolved to maintain the regioselectivity for a substrate hydroxylation activity between individual enzymes, even though extensive gene conversion has occurred across CYP2D coding sequences. PMID:25808902

Digit Ratio (2D:4D): A Biomarker for Prenatal Sex Steroids and Adult Sex Steroids in Challenge Situations.

PubMed

Manning, John; Kilduff, Liam; Cook, Christian; Crewther, Blair; Fink, Bernhard

2014-01-01

Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. This ratio is considered to be a biomarker of the balance between fetal testosterone (T) and estrogen (E) in a narrow window of early ontogeny. Evidence for this assertion is derived from direct and indirect measures of prenatal hormonal exposure (in experimental animals, via amniotic fluid samples and in the study of sex-typical traits) in relation to 2D:4D. In contrast, the relationships between 2D:4D and levels of sex steroids in adults are less clear, as many correlational studies of 2D:4D and adult sex steroids have concluded that this association is statistically non-significant. Here, we suggest that in order to understand the link between 2D:4D and sex hormones, one must consider both fetal organizing and adult activating effects of T and E. In particular, we hypothesize that 2D:4D correlates with organizing effects on the endocrine system that moderate activating effects in adulthood. We argue that this is particularly evident in "challenging" conditions such as aggressive and sexual encounters, in which individuals show increased levels of T. We discuss this refinement of the 2D:4D paradigm in relation to the links between 2D:4D and sports performance, and aggression.

Digit Ratio (2D:4D): A Biomarker for Prenatal Sex Steroids and Adult Sex Steroids in Challenge Situations

PubMed Central

Manning, John; Kilduff, Liam; Cook, Christian; Crewther, Blair; Fink, Bernhard

2013-01-01

Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. This ratio is considered to be a biomarker of the balance between fetal testosterone (T) and estrogen (E) in a narrow window of early ontogeny. Evidence for this assertion is derived from direct and indirect measures of prenatal hormonal exposure (in experimental animals, via amniotic fluid samples and in the study of sex-typical traits) in relation to 2D:4D. In contrast, the relationships between 2D:4D and levels of sex steroids in adults are less clear, as many correlational studies of 2D:4D and adult sex steroids have concluded that this association is statistically non-significant. Here, we suggest that in order to understand the link between 2D:4D and sex hormones, one must consider both fetal organizing and adult activating effects of T and E. In particular, we hypothesize that 2D:4D correlates with organizing effects on the endocrine system that moderate activating effects in adulthood. We argue that this is particularly evident in “challenging” conditions such as aggressive and sexual encounters, in which individuals show increased levels of T. We discuss this refinement of the 2D:4D paradigm in relation to the links between 2D:4D and sports performance, and aggression. PMID:24523714

Evaluating the impact of missenses mutations in CYP2D6*7 and CYP2D6*14A: does it compromise tamoxifen metabolism?

PubMed

Borba, Maria Acsm; Melo-Neto, Renato P; Leitão, Glauber M; Castelletti, Carlos Hm; Lima-Filho, José L; Martins, Danyelly Bg

2016-04-01

CYP2D6 is a high polymorphic enzyme from P450, responsible for metabolizing almost 25% of drugs. The distribution of different mutations among CYP2D6 alleles has been associated with poor, intermediate, extensive and ultra-metabolizers. To evaluate how missenses mutations in CYP2D6*7 and CYP2D6*14A poor metabolizer alleles affect CYP2D6 stability and function. CYPalleles database was used to collect polymorphisms data present in 105 alleles. We selected only poor metabolizers alleles that presented exclusively missenses mutations. They were analyzed through seven algorithms to predict the impact on CYP2D6 structure and function. H324P, the unique mutation in CYP2D6*7, has high impact in enzyme function due to its occurrence between two alpha-helixes involved in active site dynamics. G169R, a mutation that occurs only in CYP2D6*14A, leads to the gain of solvent accessibility and severe protein destabilization. Our in silico analysis showed that missenses mutations in CYP2D6*7 and CYP2D6*14A cause CYP2D6 dysfunction.

2D or Not 2D? Testing the Utility of 2D Vs. 3D Landmark Data in Geometric Morphometrics of the Sculpin Subfamily Oligocottinae (Pisces; Cottoidea).

PubMed

Buser, Thaddaeus J; Sidlauskas, Brian L; Summers, Adam P

2018-05-01

We contrast 2D vs. 3D landmark-based geometric morphometrics in the fish subfamily Oligocottinae by using 3D landmarks from CT-generated models and comparing the morphospace of the 3D landmarks to one based on 2D landmarks from images. The 2D and 3D shape variables capture common patterns across taxa, such that the pairwise Procrustes distances among taxa correspond and the trends captured by principal component analysis are similar in the xy plane. We use the two sets of landmarks to test several ecomorphological hypotheses from the literature. Both 2D and 3D data reject the hypothesis that head shape correlates significantly with the depth at which a species is commonly found. However, in taxa where shape variation in the z-axis is high, the 2D shape variables show sufficiently strong distortion to influence the outcome of the hypothesis tests regarding the relationship between mouth size and feeding ecology. Only the 3D data support previous studies which showed that large mouth sizes correlate positively with high percentages of elusive prey in the diet. When used to test for morphological divergence, 3D data show no evidence of divergence, while 2D data show that one clade of oligocottines has diverged from all others. This clade shows the greatest degree of z-axis body depth within Oligocottinae, and we conclude that the inability of the 2D approach to capture this lateral body depth causes the incongruence between 2D and 3D analyses. Anat Rec, 301:806-818, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Comparative Analysis of 2-D Versus 3-D Ultrasound Estimation of the Fetal Adrenal Gland Volume and Prediction of Preterm Birth

PubMed Central

Turan, Ozhan M.; Turan, Sifa; Buhimschi, Irina A.; Funai, Edmund F.; Campbell, Katherine H.; Bahtiyar, Ozan M.; Harman, Chris R.; Copel, Joshua A.; Baschat, Ahmet A; Buhimschi, Catalin S.

2013-01-01

Objective We aim to test the hypothesis that 2D fetal AGV measurements offer similar volume estimates as volume calculations based on 3D technique Methods Fetal AGV was estimated by 3D ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2D measurements of the same blocks (0.523× length × width × depth). Comparisons were performed by intra-class correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The cAGV (AGV/fetal weight) was calculated for both methods and compared for prediction of PTB within 7 days. Results Among 168 volumes, there was a significant correlation between 3D and 2D methods (ICC=0.979[95%CI: 0.971-0.984]). The coefficient of repeatability for the 3D was superior to the 2D method (Intra-observer 3D: 30.8, 2D:57.6; inter-observer 3D: 12.2, 2D: 15.6). Based on 2D calculations, a cAGV≥433mm3/kg, was best for prediction of PTB (sensitivity: 75%(95%CI=59-87); specificity: 89%(95%CI=82-94). Sensitivity and specificity for the 3D cAGV (cut-off ≥420mm3/kg) was 85%(95%CI=70-94) and 95%(95%CI=90-98), respectively. In receiver-operating-curve curve analysis, 3D cAGV was superior to 2D cAGV for prediction of PTB (z=1.99, p=0.047). Conclusion 2D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3D AGV calculations for prediction of PTB. PMID:22644825

Local doping of two-dimensional materials

DOEpatents

Wong, Dillon; Velasco, Jr, Jairo; Ju, Long; Kahn, Salman; Lee, Juwon; Germany, Chad E.; Zettl, Alexander K.; Wang, Feng; Crommie, Michael F.

2016-09-20

This disclosure provides systems, methods, and apparatus related to locally doping two-dimensional (2D) materials. In one aspect, an assembly including a substrate, a first insulator disposed on the substrate, a second insulator disposed on the first insulator, and a 2D material disposed on the second insulator is formed. A first voltage is applied between the 2D material and the substrate. With the first voltage applied between the 2D material and the substrate, a second voltage is applied between the 2D material and a probe positioned proximate the 2D material. The second voltage between the 2D material and the probe is removed. The first voltage between the 2D material and the substrate is removed. A portion of the 2D material proximate the probe when the second voltage was applied has a different electron density compared to a remainder of the 2D material.

Synthesis of N1-tritylethane-1,1,2,2-d4-1,2-diamine: a novel mono-protected C-deuterated ethylenediamine synthon

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

Yang, Jun; Hong, Kunlun; Bonnesen, Peter V

2012-01-01

A convenient and high-yield synthesis for N1-tritylethane-1,1,2,2-d4-1,2-diamine, a novel mono-protected ethylenediamine-C-d4, is reported. N1-tritylethane-1,1,2,2-d4-1,2-diamine was prepared in three steps from ethylene oxide-d4 in a combined yield in the range 68-76%. Also reported is a synthesis of ethylenediamine-C-d4 in two steps from 1,2-dibromoethane-d4 in a combined yield in the range 61-65%.

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

PubMed Central

Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

2016-01-01

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

X-ray variability of Pleiades late-type stars as observed with the ROSAT-PSPC

NASA Astrophysics Data System (ADS)

Marino, A.; Micela, G.; Peres, G.; Sciortino, S.

2003-08-01

We present a comprehensive analysis of X-ray variability of the late-type (dF7-dM) Pleiades stars, detected in all ROSAT-PSPC observations; X-ray variations on short (hours) and medium (months) time scales have been explored. We have grouped the stars in two samples: 89 observations of 42 distinct dF7-dK2 stars and 108 observations of 61 dK3-dM stars. The Kolmogorov-Smirnov test applied on all X-ray photon time series show that the percentage of cases of significant variability is quite similar on both samples, suggesting that the presence of variability does not depend on mass for the time scales and mass range explored. The comparison between the Time X-ray Amplitude Distribution functions (XAD) of the set of dF7-dK2 and of the dK3-dM show that, on short time scales, dK3-dM stars show larger variations than dF7-dK2. A subsample of eleven dF7-dK2 and eleven dK3-dM Pleiades stars allows the study of variability on longer time scales: we found that variability on medium - long time scales is relatively more common among dF7-dK2 stars than among dK3-dM ones. For both dF7-dK2 Pleiades stars and dF7-dK2 field stars, the variability on short time scales depends on Lx while this dependence has not been observed among dK3-dM stars. It may be that the variability among dK3-dM stars is dominated by flares that have a similar luminosity distribution for stars of different Lx, while flaring distribution in dF7-dK2 stars may depend on X-ray luminosity. The lowest mass stars show significant rapid variability (flares?) and no evidence of rotation modulation or cycles. On the contrary, dF7-dK2 Pleiades stars show both rapid variability and variations on longer time scales, likely associated with rotational modulation or cycles.

Electron-ion recombination in low temperature hydrogen/deuterium plasma

NASA Astrophysics Data System (ADS)

Glosík, Juraj; Dohnal, Petr; Kálosi, Ábel; Augustovičová, Lucie D.; Shapko, Dmytro; Roučka, Štěpán; Plašil, Radek

2018-01-01

The stationary afterglow with cavity ring down spectrometer (SA-CRDS) was used to study the recombination of H3+, H2D+, HD2+ and D3+ ions with electrons in low temperature (77-300 K) plasmas in He/Ar/H2/D2 gas mixtures. By measuring effective recombination rate coefficients (αeff) in plasma with mixtures of ions and their dependences on temperature and partial densities of He, H2 and D2, αeff (T, [He],[H2],[D2]), we determined binary (αbinH3, αbinH2D, αbinHD2, αbinD3) and ternary (KH3, KH2D, KHD2, KD3) recombination rate coefficients for H3+, H2D+, HD2+ and D3+ ions. For all four ions we observed very efficient He assisted ternary recombination which is comparable with binary recombination already at [He] =1 × 1017 cm-3. The removal of excited particles in afterglow plasma was monitored to obtain the plasma thermalisation rate at given experimental conditions. The inferred deexcitation rates for reaction of helium metastable atoms with D2 are kD2 (300 K)=(2.1 ± 0.3) × 10-10 cm3 s-1 and kD2 (140 K)=(1.3 ± 0.3) × 10-10 cm3 s-1. Contribution to the topical issue "Plasma Sources and Plasma Processes (PSPP)", edited by Luis Lemos Alves, Thierry Belmonte and Tiberiu Minea.

Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells

PubMed Central

Coldwell, Martyn C; Boyfield, Izzy; Brown, Tony; Hagan, Jim J; Middlemiss, Derek N

1999-01-01

The aim of the present study was to characterize functional responses to ropinirole, its major metabolites in man (SKF-104557 (4-[2-(propylamino)ethyl]-2-(3H) indolone), SKF-97930 (4-carboxy-2-(3H) indolone)) and other dopamine receptor agonists at human dopamine D2(long) (hD2), D3 (hD3) and D4.4 (hD4) receptors separately expressed in Chinese hamster ovary cells using microphysiometry.All the receptor agonists tested (ropinirole, SKF-104557, SKF-97930, bromocriptine, lisuride, pergolide, pramipexole, talipexole, dopamine) increased extracellular acidification rate in Chinese hamster ovary clones expressing the human D2, D3 or D4 receptor. The pEC50s of ropinirole at hD2, hD3 and hD4 receptors were 7.4, 8.4 and 6.8, respectively. Ropinirole is therefore at least 10 fold selective for the human dopamine D3 receptor over the other D2 receptor family members.At the hD2 and hD3 dopamine receptors all the compounds tested were full agonists as compared to quinpirole. Talipexole and the ropinirole metabolite, SKF-104557, were partial agonists at the hD4 receptor.Bromocriptine and lisuride had a slow onset of agonist action which precluded determination of EC50s.The rank order of agonist potencies was dissimilar to the rank order of radioligand binding affinities at each of the dopamine receptor subtypes. Functional selectivities of the dopamine receptor agonists, as measured in the microphysiometer, were less than radioligand binding selectivities.The results show that ropinirole is a full agonist at human D2, D3 and D4 dopamine receptors. SKF-104557 the major human metabolite of ropinirole, had similar radioligand binding affinities to, but lower functional potencies than, the parent compound. PMID:10455328

Value of digit ratio 2D:4D, a biomarker of prenatal hormone exposure, is stable across the menstrual cycle.

PubMed

Klimek, Magdalena; Marcinkowska, Urszula M; Jasienska, Grazyna

2017-07-01

Digit ratio (2D:4D) is used as a marker of prenatal hormone exposure and, consequently, as a predictor of many characteristics throughout a woman's lifespan. A previous study has suggested that values of 2D:4D vary across menstrual cycles and further questioned the reliability of a single measurement of 2D:4D among cycling women, while another study failed to confirm these results. However, these studies estimated the timing of cycle phases based on a date of menstruation reported by participants and also had small sample sizes. For our study, we evaluated potential changes in 2D:4D values across a menstrual cycle in a group of women among whom the phases of the menstrual cycle were determined by hormonal (luteinizing hormone based) ovulation tests. We studied 32 naturally cycling women aged 22-37 from rural Poland. Lengths of second and fourth digits were measured based on scans of both hands taken three times (i.e. in the follicular phase, peri-ovulatory phase and luteal phase of the cycle) for each participant. No differences in 2D:4D value across the menstrual cycle were detected either when right-hand, left-hand, and mean 2D:4D for both hands were analysed, nor when difference in the 2D:4D value between hands (D left-right ) was evaluated. We documented that 2D:4D is independent of the phase of the menstrual cycle and these findings suggest that among naturally cycling women, a value of 2D:4D can be reliably obtained from measurements taken during any day of the menstrual cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

PubMed Central

Breslin, Susan; O'Driscoll, Lorraine

2016-01-01

Solid tumours naturally grow in 3D wherein the spatial arrangement of cells affects how they interact with each other. This suggests that 3D cell culture may mimic the natural in vivo setting better than traditional monolayer (2D) cell culture, where cells are grown attached to plastic. Here, using HER2-positive breast cancer cell lines as models (BT474, HCC1954, EFM192A), the effects of culturing cells in 3D using the poly-HEMA method compared to 2D cultures were assessed in terms of cellular viability, response/resistance to anti-cancer drugs, protein expression and enzyme activity. Scanning electron microscopy showed the morphology of cells in 3D to be substantially different to those cultured in 2D. Cell viability in 3D cells was substantially lower than that of cells in 2D cultures, while 3D cultures were more resistant to the effects of HER-targeted (neratinib) and classical chemotherapy (docetaxel) drugs. Expression of proteins involved in cell survival, transporters associated with drug resistance and drug targets were increased in 3D cultures. Finally, activity of drug metabolising enzyme CYP3A4 was substantially increased in 3D compared to 2D cultures. Together this data indicates that the biological information represented by 3D and 2D cell cultures is substantially different i.e. 3D cell cultures demonstrate higher innate resistance to anti-cancer drugs compared to 2D cultures, which may be facilitated by the altered receptor proteins, drug transporters and metabolising enzyme activity. This highlights the importance of considering 3D in addition to 2D culture methods in pre-clinical studies of both newer targeted and more traditional anti-cancer drugs. PMID:27304190

Age–dependent regulation of synaptic connections by dopamine D2 receptors

PubMed Central

Jia, Jie–Min; Zhao, Jun; Hu, Zhonghua; Lindberg, Daniel; Li, Zheng

2013-01-01

Dopamine D2 receptors (D2R) are G protein–coupled receptors that modulate synaptic transmission and play an important role in various brain functions including affect learning and working memory. Abnormal D2R signaling has been implicated in psychiatric disorders such as schizophrenia. Here we report a new function of D2R in dendritic spine morphogenesis. Activation of D2R reduces spine number via GluN2B– and cAMP–dependent mechanisms in mice. Notably, this regulation takes place only during adolescence. During this period, D2R overactivation caused by mutations in the schizophrenia–risk–gene dysbindin leads to spine deficiency, dysconnectivity within the entorhinal–hippocampal circuit and impairment of spatial working memory. Notably, these defects can be ameliorated by D2R blockers administered during adolescence. These findings uncover a novel age–dependent function of D2R in spine development, provide evidence that D2R dysfunction during adolescence impairs neuronal circuits and working memory, and suggest that adolescent interventions of aberrant D2R activity protect against cognitive impairment. PMID:24121738

Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel targets for antipsychotic drugs.

PubMed

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Tarakanov, Alexander O; Romero-Fernandez, Wilber; Ferraro, Luca; Tanganelli, Sergio; Perez-Alea, Mileidys; Di Palma, Michael; Agnati, Luigi F

2014-01-01

This review is focused on the D2 heteroreceptor complexes within the ventral striatum with their receptor-receptor interactions and relevance for the treatment of schizophrenia. A "guide-and-clasp" manner for receptor-receptor interactions is proposed where "adhesive guides" may be amino acid triplet homologies, which were determined for different kinds of D2 heteroreceptor complexes. The first putative D2 heteroreceptor complex to be discovered in relation to schizophrenia was the A2A-D2 heteroreceptor complex where antagonistic A2A-D2 receptor-receptor interactions were demonstrated after A2A agonist treatment in the ventral striatum. The A2A agonist CGS 21680 with atypical antipsychotic properties may at least in part act by increasing β-arrestin2 signaling over the D2 protomer in the A2A-D2 heteroreceptor complex in the ventral striatum. The antagonistic NTS1-D2 interactions in the NTS1-D2 heteroreceptor complex in the ventral striatum are proposed as one molecular mechanism for the potential antipsychotic effects of NT. Indications were obtained that the psychotic actions of the 5-HT2AR hallucinogens LSD and DOI can involve enhancement of D2R protomer signaling via a biased agonist action at the 5-HT2A protomer in the D2-5-HT2A heteroreceptor complex in the ventral striatum. Facilitatory allosteric D2likeR-OTR interactions in heteroreceptor complexes in nucleus accumbens may have a role in social and emotional behaviors. By blocking the D2 protomers of these heteroreceptor complexes, antipsychotics can fail to reduce the negative symptoms of schizophrenia. The discovery of different types of D2 heteroreceptor complexes gives an increased understanding of molecular mechanisms involved in causing schizophrenia and new strategies for its treatment and understanding the side effects of antipsychotics. © 2014 Elsevier B.V. All rights reserved.

Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

PubMed Central

Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

2015-01-01

The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

PubMed Central

Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluís, Carme; Cortés, Antoni; Volkow, Nora D.; Schiffmann, Serge N.; Ferré, Sergi; Casadó, Vicent

2015-01-01

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain. PMID:26100888

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

PubMed

Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Cortés, Antoni; Volkow, Nora D; Schiffmann, Serge N; Ferré, Sergi; Casadó, Vicent

2015-07-07

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

Clinical Utility of Simultaneous Quantitation of 25-Hydroxyvitamin D and 24,25-Dihydroxyvitamin D by LC-MS/MS Involving Derivatization With DMEQ-TAD

PubMed Central

Kaufmann, Martin; Gallagher, J. Christopher; Peacock, Munro; Schlingmann, Karl-Peter; Konrad, Martin; DeLuca, Hector F.; Sigueiro, Rita; Lopez, Borja; Mourino, Antonio; Maestro, Miguel; St-Arnaud, René; Finkelstein, Joel S.; Cooper, Donald P.

2014-01-01

Context: The discovery of hypercalcemic diseases due to loss-of-function mutations in 25-hydroxyvitamin D-24-hydroxylase has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D [24,25-(OH)2D]. Objective: We describe a novel liquid chromatography and tandem mass spectrometry-based method involving derivatization with DMEQ-TAD {4-[2-(6,7-dimethoxy-4-methyl-3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione} to simultaneously assay multiple vitamin D metabolites including 25-hydroxyvitamin D (25-OH-D) and 24,25-(OH)2D using 100 μL of serum with a 5-minute run time. Design: The assay uses a newly synthesized internal standard d6-24,25-(OH)2D3 enabling the quantitation of 24,25-(OH)2D3 as well as the determination of the ratio of 25-OH-D3 to 24,25-(OH)2D3, a physiologically useful parameter. Setting: We report data on more than 1000 normal and disease samples involving vitamin D deficiency or hypercalcemia in addition to studies involving knockout mouse models. Results: The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (−2% to −5% bias) and exhibited low inter- and intraassay coefficients of variation (4%–7%) and lower limits of quantitation of 0.25–0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r2 = 0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3 to 24,25-(OH)2D3, which remained less than 25 in vitamin D-sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80–100) in patients with idiopathic infantile hypercalcemia. Conclusions: The new method showed good utility in clinical settings involving vitamin D deficiency; supplementation with vitamin D and idiopathic infantile hypercalcemia, as well as in animal models with ablation of selected cytochrome P450-containing enzymes involved in vitamin D metabolism. PMID:24670084

Computational methods for 2D materials: discovery, property characterization, and application design.

PubMed

Paul, J T; Singh, A K; Dong, Z; Zhuang, H; Revard, B C; Rijal, B; Ashton, M; Linscheid, A; Blonsky, M; Gluhovic, D; Guo, J; Hennig, R G

2017-11-29

The discovery of two-dimensional (2D) materials comes at a time when computational methods are mature and can predict novel 2D materials, characterize their properties, and guide the design of 2D materials for applications. This article reviews the recent progress in computational approaches for 2D materials research. We discuss the computational techniques and provide an overview of the ongoing research in the field. We begin with an overview of known 2D materials, common computational methods, and available cyber infrastructures. We then move onto the discovery of novel 2D materials, discussing the stability criteria for 2D materials, computational methods for structure prediction, and interactions of monolayers with electrochemical and gaseous environments. Next, we describe the computational characterization of the 2D materials' electronic, optical, magnetic, and superconducting properties and the response of the properties under applied mechanical strain and electrical fields. From there, we move on to discuss the structure and properties of defects in 2D materials, and describe methods for 2D materials device simulations. We conclude by providing an outlook on the needs and challenges for future developments in the field of computational research for 2D materials.

Computational methods for 2D materials: discovery, property characterization, and application design

NASA Astrophysics Data System (ADS)

Paul, J. T.; Singh, A. K.; Dong, Z.; Zhuang, H.; Revard, B. C.; Rijal, B.; Ashton, M.; Linscheid, A.; Blonsky, M.; Gluhovic, D.; Guo, J.; Hennig, R. G.

2017-11-01

The discovery of two-dimensional (2D) materials comes at a time when computational methods are mature and can predict novel 2D materials, characterize their properties, and guide the design of 2D materials for applications. This article reviews the recent progress in computational approaches for 2D materials research. We discuss the computational techniques and provide an overview of the ongoing research in the field. We begin with an overview of known 2D materials, common computational methods, and available cyber infrastructures. We then move onto the discovery of novel 2D materials, discussing the stability criteria for 2D materials, computational methods for structure prediction, and interactions of monolayers with electrochemical and gaseous environments. Next, we describe the computational characterization of the 2D materials’ electronic, optical, magnetic, and superconducting properties and the response of the properties under applied mechanical strain and electrical fields. From there, we move on to discuss the structure and properties of defects in 2D materials, and describe methods for 2D materials device simulations. We conclude by providing an outlook on the needs and challenges for future developments in the field of computational research for 2D materials.

Transcriptional Regulation of CYP2D6 Expression

PubMed Central

Pan, Xian; Ning, Miaoran

2017-01-01

CYP2D6-mediated drug metabolism exhibits large interindividual variability. Although genetic variations in the CYP2D6 gene are well known contributors to the variability, the sources of CYP2D6 variability in individuals of the same genotype remain unexplained. Accumulating data indicate that transcriptional regulation of CYP2D6 may account for part of CYP2D6 variability. Yet, our understanding of factors governing transcriptional regulation of CYP2D6 is limited. Recently, mechanistic studies of increased CYP2D6-mediated drug metabolism in pregnancy revealed two transcription factors, small heterodimer partner (SHP) and Krüppel-like factor 9, as a transcriptional repressor and an activator, respectively, of CYP2D6. Chemicals that increase SHP expression (e.g., retinoids and activators of farnesoid X receptor) were shown to downregulate CYP2D6 expression in the humanized mice as well as in human hepatocytes. This review summarizes the series of studies on the transcriptional regulation of CYP2D6 expression, potentially providing a basis to better understand the large interindividual variability in CYP2D6-mediated drug metabolism. PMID:27698228

A comprehensive allometric analysis of 2nd digit length to 4th digit length in humans.

PubMed

Lolli, Lorenzo; Batterham, Alan M; Kratochvíl, Lukáš; Flegr, Jaroslav; Weston, Kathryn L; Atkinson, Greg

2017-06-28

It has been widely reported that men have a lower ratio of the 2nd and 4th human finger lengths (2D : 4D). Size-scaling ratios, however, have the seldom-appreciated potential for providing biased estimates. Using an information-theoretic approach, we compared 12 candidate models, with different assumptions and error structures, for scaling untransformed 2D to 4D lengths from 154 men and 262 women. In each hand, the two-parameter power function and the straight line with intercept models, both with normal, homoscedastic error, were superior to the other models and essentially equivalent to each other for normalizing 2D to 4D lengths. The conventional 2D : 4D ratio biased relative 2D length low for the generally bigger hands of men, and vice versa for women, thereby leading to an artefactual indication that mean relative 2D length is lower in men than women. Conversely, use of the more appropriate allometric or linear regression models revealed that mean relative 2D length was, in fact, greater in men than women. We conclude that 2D does not vary in direct proportion to 4D for both men and women, rendering the use of the simple 2D : 4D ratio inappropriate for size-scaling purposes and intergroup comparisons. © 2017 The Author(s).

Absence of rotational activity detected using 2-dimensional phase mapping in the corresponding 3-dimensional phase maps in human persistent atrial fibrillation.

PubMed

Pathik, Bhupesh; Kalman, Jonathan M; Walters, Tomos; Kuklik, Pawel; Zhao, Jichao; Madry, Andrew; Sanders, Prashanthan; Kistler, Peter M; Lee, Geoffrey

2018-02-01

Current phase mapping systems for atrial fibrillation create 2-dimensional (2D) maps. This process may affect the accurate detection of rotors. We developed a 3-dimensional (3D) phase mapping technique that uses the 3D locations of basket electrodes to project phase onto patient-specific left atrial 3D surface anatomy. We sought to determine whether rotors detected in 2D phase maps were present at the corresponding time segments and anatomical locations in 3D phase maps. One-minute left atrial atrial fibrillation recordings were obtained in 14 patients using the basket catheter and analyzed off-line. Using the same phase values, 2D and 3D phase maps were created. Analysis involved determining the dominant propagation patterns in 2D phase maps and evaluating the presence of rotors detected in 2D phase maps in the corresponding 3D phase maps. Using 2D phase mapping, the dominant propagation pattern was single wavefront (36.6%) followed by focal activation (34.0%), disorganized activity (23.7%), rotors (3.3%), and multiple wavefronts (2.4%). Ten transient rotors were observed in 9 of 14 patients (64%). The mean rotor duration was 1.1 ± 0.7 seconds. None of the 10 rotors observed in 2D phase maps were seen at the corresponding time segments and anatomical locations in 3D phase maps; 4 of 10 corresponded with single wavefronts in 3D phase maps, 2 of 10 with 2 simultaneous wavefronts, 1 of 10 with disorganized activity, and in 3 of 10 there was no coverage by the basket catheter at the corresponding 3D anatomical location. Rotors detected in 2D phase maps were not observed in the corresponding 3D phase maps. These findings may have implications for current systems that use 2D phase mapping. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a randomized controlled trial.

PubMed

Mehrotra, A; Calvo, M S; Beelman, R B; Levy, E; Siuty, J; Kalaras, M D; Uribarri, J

2014-10-01

Based on the growing evidence of risk reduction from fresh fruit and vegetable consumption and an inverse relationship between serum 25-hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit to deficient prediabetics and glucose metabolism remains untested. Forty-three prediabetic, D-deficient adults (25OHD≤20 ng/ml), BMI>25 were randomized to four groups consuming daily entrées containing 100 g fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one also received one capsule of placebo daily. Two control groups were fed untreated mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in over-the-counter supplements. After 16 weeks, both D2-UVB-mushroom entrée doses, which were significantly lower after cooking, produced modest or no increases in 25OHD2 or total 25OHD relative to the positive control subjects who actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the label). Unanticipated D2 cooking loss from fresh UVB mushrooms and probable low absorption and/or hydroxylation may explain the smaller increase in 25OHD2 in our prediabetic overweight/obese cohort compared with past findings in younger, healthy subjects. Moreover, no dose or vitamin D source was associated with modifying T2D risk factors.

Dynamic accommodative response to different visual stimuli (2D vs 3D) while watching television and while playing Nintendo 3DS console.

PubMed

Oliveira, Sílvia; Jorge, Jorge; González-Méijome, José M

2012-09-01

The aim of the present study was to compare the accommodative response to the same visual content presented in two dimensions (2D) and stereoscopically in three dimensions (3D) while participants were either watching a television (TV) or Nintendo 3DS console. Twenty-two university students, with a mean age of 20.3 ± 2.0 years (mean ± S.D.), were recruited to participate in the TV experiment and fifteen, with a mean age of 20.1 ± 1.5 years took part in the Nintendo 3DS console study. The accommodative response was measured using a Grand Seiko WAM 5500 autorefractor. In the TV experiment, three conditions were used initially: the film was viewed in 2D mode (TV2D without glasses), the same sequence was watched in 2D whilst shutter-glasses were worn (TV2D with glasses) and the sequence was viewed in 3D mode (TV3D). Measurements were taken for 5 min in each condition, and these sections were sub-divided into ten 30-s segments to examine changes within the film. In addition, the accommodative response to three points of different disparity of one 3D frame was assessed for 30 s. In the Nintendo experiment, two conditions were employed - 2D viewing and stereoscopic 3D viewing. In the TV experiment no statistically significant differences were found between the accommodative response with TV2D without glasses (-0.38 ± 0.32D, mean ± S.D.) and TV3D (-0.37 ± 0.34D). Also, no differences were found between the various segments of the film, or between the accommodative response to different points of one frame (p > 0.05). A significant difference (p = 0.015) was found, however, between the TV2D with (-0.32 ± 0.32D) and without glasses (-0.38 ± 0.32D). In the Nintendo experiment the accommodative responses obtained in modes 2D (-2.57 ± 0.30D) and 3D (-2.49 ± 0.28D) were significantly different (paired t-test p = 0.03). The need to use shutter-glasses may affect the accommodative response during the viewing of displays, and the accommodative response when playing Nintendo 3DS in 3D mode is lower than when it is viewed in 2D. © 2012 The College of Optometrists.

Objective and subjective comparison of standard 2-D and fully 3-D reconstructed data on a PET/CT system.

PubMed

Strobel, Klaus; Rüdy, Matthias; Treyer, Valerie; Veit-Haibach, Patrick; Burger, Cyrill; Hany, Thomas F

2007-07-01

The relative advantage of fully 3-D versus 2-D mode for whole-body imaging is currently the focus of considerable expert debate. The nature of 3-D PET acquisition for FDG PET/CT theoretically allows a shorter scan time and improved efficiency of FDG use than in the standard 2-D acquisition. We therefore objectively and subjectively compared standard 2-D and fully 3-D reconstructed data for FDG PET/CT on a research PET/CT system. In a total of 36 patients (mean 58.9 years, range 17.3-78.9 years; 21 male, 15 female) referred for known or suspected malignancy, FDG PET/CT was performed using a research PET/CT system with advanced detector technology with improved sensitivity and spatial resolution. After 45 min uptake, a low-dose CT (40 mAs) from head to thigh was performed followed by 2-D PET (emission 3 min per field) and 3-D PET (emission 1.5 min per field) with both seven slices overlap to cover the identical anatomical region. Acquisition time was therefore 50% less (seven fields; 21 min vs. 10.5 min). PET data was acquired in a randomized fashion, so in 50% of the cases 2-D data was acquired first. CT data was used for attenuation correction. 2-D (OSEM) and 3-D PET images were iteratively reconstructed. Subjective analysis of 2-D and 3-D images was performed by two readers in a blinded, randomized fashion evaluating the following criteria: sharpness of organs (liver, chest wall/lung), overall image quality and detectability and dignity of each identified lesion. Objective analysis of PET data was investigated measuring maximum standard uptake value with lean body mass (SUV(max,LBM)) of identified lesions. On average, per patient, the SUV(max) was 7.86 (SD 7.79) for 2-D and 6.96 (SD 5.19) for 3-D. On a lesion basis, the average SUV(max) was 7.65 (SD 7.79) for 2-D and 6.75 (SD 5.89) for 3-D. The absolute difference on a paired t-test of SUV 3-D-2-D based on each measured lesion was significant with an average of -0.956 (P=0.002) and an average of -0.884 on a patient base (P<0.05). With 3-D the SUV(max) decreased by an average of 5.2% for each lesion, and an average of 6.0% for each patient. Subjective analysis showed fair inter-observer agreement regarding detectability (kappa=0.24 for 3-D; 0.36 for 3-D) and dignity (kappa=0.44 for 3-D and 0.4 for 2-D) of the lesions. There was no significant diagnostic difference between 3-D and 2-D. Only in one patient, a satellite liver metastasis of a colon cancer was missed in 3-D and detected only in 2-D. On average, the overall image quality for 3-D images was equal (in 24%) or inferior (in 76%) compared to 2-D. A possible major advantage of 3-D data acquisition is the faster patient throughput with a 50% reduction in scan time. The fully 3-D reconstruction technique has overcome the technical drawbacks of current 3-D imaging technique. In our limited number of patients there was no significant diagnostic difference between 2-D and fully 3-D.

Automatic correspondence detection in mammogram and breast tomosynthesis images

NASA Astrophysics Data System (ADS)

Ehrhardt, Jan; Krüger, Julia; Bischof, Arpad; Barkhausen, Jörg; Handels, Heinz

2012-02-01

Two-dimensional mammography is the major imaging modality in breast cancer detection. A disadvantage of mammography is the projective nature of this imaging technique. Tomosynthesis is an attractive modality with the potential to combine the high contrast and high resolution of digital mammography with the advantages of 3D imaging. In order to facilitate diagnostics and treatment in the current clinical work-flow, correspondences between tomosynthesis images and previous mammographic exams of the same women have to be determined. In this paper, we propose a method to detect correspondences in 2D mammograms and 3D tomosynthesis images automatically. In general, this 2D/3D correspondence problem is ill-posed, because a point in the 2D mammogram corresponds to a line in the 3D tomosynthesis image. The goal of our method is to detect the "most probable" 3D position in the tomosynthesis images corresponding to a selected point in the 2D mammogram. We present two alternative approaches to solve this 2D/3D correspondence problem: a 2D/3D registration method and a 2D/2D mapping between mammogram and tomosynthesis projection images with a following back projection. The advantages and limitations of both approaches are discussed and the performance of the methods is evaluated qualitatively and quantitatively using a software phantom and clinical breast image data. Although the proposed 2D/3D registration method can compensate for moderate breast deformations caused by different breast compressions, this approach is not suitable for clinical tomosynthesis data due to the limited resolution and blurring effects perpendicular to the direction of projection. The quantitative results show that the proposed 2D/2D mapping method is capable of detecting corresponding positions in mammograms and tomosynthesis images automatically for 61 out of 65 landmarks. The proposed method can facilitate diagnosis, visual inspection and comparison of 2D mammograms and 3D tomosynthesis images for the physician.

Sex-different abnormalities in the right second to fourth digit ratio in Japanese individuals with autism spectrum disorders.

PubMed

Masuya, Yasuhiro; Okamoto, Yuko; Inohara, Keisuke; Matsumura, Yukiko; Fujioka, Toru; Wada, Yuji; Kosaka, Hirotaka

2015-01-01

The prevalence of autism spectrum disorders (ASDs) is higher in men than in women. The extreme male brain theory proposes that excessive prenatal testosterone activity could be a risk factor for ASDs. However, it is unclear whether prenatal sex hormone activity is a risk factor for women. The ratio of the length of the second to fourth digits (2D:4D) is considered to be a biomarker of the prenatal ratio of testosterone to estrogen. Therefore, this study compared the 2D:4D ratios of women with and without ASDs to determine if prenatal sex hormone activity could be a risk factor for ASDs in women. The study included 35 Japanese men with ASDs, 17 Japanese women with ASDs, 59 typically developed (TD) Japanese men, and 57 TD Japanese women. We measured digit lengths and compared the 2D:4D ratios among the four groups. We also examined the relationship between the 2D:4D ratio and the autism-spectrum quotient score of each group. In our cohort, men with ASDs tended to have lower right-hand 2D:4D ratios relative to TD men. In contrast, the right 2D:4D ratios in women with ASDs were higher compared to those of TD women. No significant correlations were found between the 2D:4D ratios and the autism-spectrum quotient scores in any group. The higher right 2D:4D ratios in women could not be explained by age or full-scale intelligent quotients. This group difference was not found for the left 2D:4D or right-left 2D:4D ratios. We found a reverse direction of abnormality in the right 2D:4D ratio for men and women with ASDs. It has been posited that high prenatal testosterone levels lead to a lower 2D:4D ratio. However, a recent animal study showed that testosterone injection to dam leads to a higher right 2D:4D ratio especially for female offspring, which might be mediated by abnormal adipose accumulation in the fingertip. Therefore, the present findings suggest that high prenatal testosterone could be a risk factor both for Japanese men and women with ASDs, elucidating one potential etiology of ASDs in women.

Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of synaptic transmission in the mouse prefrontal cortex.

PubMed

Real, Joana I; Simões, Ana Patrícia; Cunha, Rodrigo A; Ferreira, Samira G; Rial, Daniel

2018-05-01

Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D 1 - and D 2 -like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A 2 A R) also control PFC-related responses and A 2 A R antagonists are potential anti-psychotic drugs. As tight antagonistic A 2 A R-D 2 R and synergistic A 2 A R-D 1 R interactions occur in other brain regions, we now investigated the crosstalk between A 2 A R and D 1 /D 2 R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired-pulse responses. Dopamine inhibition was prevented by the D 2 R-like antagonist sulpiride but not by the D 1 R antagonist SCH23390 and was mimicked by the D 2 R agonist sumanirole, but not by the agonists of either D 4 R (A-412997) or D 3 R (PD128907). Dopamine inhibition was prevented by the A 2 A R antagonist, SCH58261, and attenuated in A 2 A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A 2 A R and D 2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A 2 A R-D 2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A 2 A R antagonists. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Influence of 2D and 3D view on performance and time estimation in minimal invasive surgery.

PubMed

Blavier, A; Nyssen, A S

2009-11-01

This study aimed to evaluate the impact of two-dimensional (2D) and three-dimensional (3D) images on time performance and time estimation during a surgical motor task. A total of 60 subjects without any surgical experience (nurses) and 20 expert surgeons performed a fine surgical task with a new laparoscopic technology (da Vinci robotic system). The 80 subjects were divided into two groups, one using 3D view option and the other using 2D view option. We measured time performance and asked subjects to verbally estimate their time performance. Our results showed faster performance in 3D than in 2D view for novice subjects while the performance in 2D and 3D was similar in the expert group. We obtained a significant interaction between time performance and time evaluation: in 2D condition, all subjects accurately estimated their time performance while they overestimated it in the 3D condition. Our results emphasise the role of 3D in improving performance and the contradictory feeling about time evaluation in 2D and 3D. This finding is discussed in regard with the retrospective paradigm and suggests that 2D and 3D images are differently processed and memorised.

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

Banerjee, Surajit; Christov, Plamen P.; Kozekova, Albena

trans-4-Hydroxynonenal (HNE) is the major peroxidation product of {omega}-6 polyunsaturated fatty acids in vivo. Michael addition of the N{sub 2}-amino group of dGuo to HNE followed by ring closure of N1 onto the aldehyde results in four diastereomeric 1,N{sub 2}-dGuo (1,N{sub 2}-HNE-dGuo) adducts. The (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct was incorporated into the 18-mer templates 5'-d(TCATXGAATCCTTCCCCC)-3' and d(TCACXGAATCCTTCCCCC)-3', where X = (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct. These differed in the identity of the template 5'-neighbor base, which was either Thy or Cyt, respectively. Each of these templates was annealed with either a 13-mer primer 5'-d(GGGGGAAGGATTC)-3' or a 14-mer primer 5'-d(GGGGGAAGGATTCC)-3'. The addition of dNTPsmore » to the 13-mer primer allowed analysis of dNTP insertion opposite to the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, whereas the 14-mer primer allowed analysis of dNTP extension past a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) belongs to the Y-family of error-prone polymerases. Replication bypass studies in vitro reveal that this polymerase inserted dNTPs opposite the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct in a sequence-specific manner. If the template 5'-neighbor base was dCyt, the polymerase inserted primarily dGTP, whereas if the template 5'-neighbor base was dThy, the polymerase inserted primarily dATP. The latter event would predict low levels of Gua {yields} Thy mutations during replication bypass when the template 5'-neighbor base is dThy. When presented with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, the polymerase conducted full-length primer extension. Structures for ternary (Dpo4-DNA-dNTP) complexes with all four template-primers were obtained. For the 18-mer:13-mer template-primers in which the polymerase was confronted with the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, the (6S,8R,11S)-1,N{sub 2}-dGuo lesion remained in the ring-closed conformation at the active site. The incoming dNTP, either dGTP or dATP, was positioned with Watson-Crick pairing opposite the template 5'-neighbor base, dCyt or dThy, respectively. In contrast, for the 18-mer:14-mer template-primers with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, ring opening of the adduct to the corresponding N{sub 2}-dGuo aldehyde species occurred. This allowed Watson-Crick base pairing at the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair.« less

Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects.

PubMed

Wager, Travis T; Chappie, Thomas; Horton, David; Chandrasekaran, Ramalakshmi Y; Samas, Brian; Dunn-Sims, Elizabeth R; Hsu, Cathleen; Nawreen, Nawshaba; Vanase-Frawley, Michelle A; O'Connor, Rebecca E; Schmidt, Christopher J; Dlugolenski, Keith; Stratman, Nancy C; Majchrzak, Mark J; Kormos, Bethany L; Nguyen, David P; Sawant-Basak, Aarti; Mead, Andy N

2017-01-18

Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K i = 3.1 nM), good subtype selectivity over D2R (D2 K i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated opioid self-administration and opioid drug-seeking behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further, traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3 has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

Low bioaccessibility of vitamin D2 from yeast-fortified bread compared to crystalline D2 bread and D3 from fluid milks.

PubMed

Lipkie, Tristan E; Ferruzzi, Mario G; Weaver, Connie M

2016-11-09

The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D 2 and vitamin D 3 . Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D 2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D 3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D 2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D 2 fortified bread (p < 0.05). Intact yeast cells were observed in the digesta of yeast fortified bread. These results indicate that the low bioavailability of yeast D 2 in comparison to other vitamin D 2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D 2 and D 3 .

Infant Imitation from Television Using Novel Touch Screen Technology

ERIC Educational Resources Information Center

Zack, Elizabeth; Barr, Rachel; Gerhardstein, Peter; Dickerson, Kelly; Meltzoff, Andrew N.

2009-01-01

Infants learn less from a televised demonstration than from a live demonstration, the "video deficit effect." The present study employs a novel approach, using touch screen technology to examine 15-month olds' transfer of learning. Infants were randomly assigned either to within-dimension (2D/2D or 3D/3D) or cross-dimension (3D/2D or 2D/3D)…

Synthesis of P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate for the investigation of biosynthesis of O-antigenic polysaccharides in Pseudomonas aeruginosa and Escherichia coli O104.

PubMed

Torgov, Vladimir; Danilov, Leonid; Utkina, Natalia; Veselovsky, Vladimir; Brockhausen, Inka

2017-12-01

Two new phenoxyundecyl diphosphate sugars were synthesized for the first time: P 1 -(11-phenoxyundecyl)-P 2 - (2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P 1 -(11-phenoxyundecyl)-P 2 -(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate to study the third step of biosynthesis of the repeating units of O-antigenic polysaccharides in Pseudomonas aeruginosa and E.coli O104 respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

From 1D Polymers to 2D Polymers: Preparation of Free-Standing Single-Monomer-Thick Two-Dimensional Conjugated Polymers in Water.

PubMed

Zhang, Na; Wang, Taisheng; Wu, Xing; Jiang, Chen; Zhang, Taiming; Jin, Bangkun; Ji, Hengxing; Bai, Wei; Bai, Ruke

2017-07-25

Recently, investigation on two-dimensional (2D) organic polymers has made great progress, and conjugated 2D polymers already play a dynamic role in both academic and practical applications. However, a convenient, noninterfacial approach to obtain single-layer 2D polymers in solution, especially in aqueous media, remains challenging. Herein, we present a facile, highly efficient, and versatile "1D to 2D" strategy for preparation of free-standing single-monomer-thick conjugated 2D polymers in water without any aid. The 2D structure was achieved by taking advantage of the side-by-side self-assembly of a rigid amphiphilic 1D polymer and following topochemical photopolymerization in water. The spontaneous formation of single-layer polymer sheets was driven by synergetic association of the hydrophobic interactions, π-π stacking interactions, and electrostatic repulsion. Both the supramolecular sheets and the covalent sheets were confirmed by spectroscopic analyses and electron microscope techniques. Moreover, in comparison of the supramolecular 2D polymer, the covalent 2D polymer sheets exhibited not only higher mechanical strength but also higher conductivity, which can be ascribed to the conjugated network within the covalent 2D polymer sheets.

Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates. Study by 13C NMR of proton and deuteron exchange.

PubMed

Malaisse, W J; Liemans, V; Malaisse-Lagae, F; Ottinger, R; Willem, R

1991-05-15

The exchange of protons and deuterons by phosphoglucoisomerase during the single passage conversion of D-[2-13C,1-2H]fructose 6-phosphate in H2O or D-[2-13C]fructose 6-phosphate in D2O to D-[2-13C]glucose 6-phosphate, as coupled with the further generation of 6-phospho-D-[2-13C]gluconate in the presence of excess glucose-6-phosphate dehydrogenase was investigated by 13C NMR spectroscopy of the latter metabolite. In H2O, the intramolecular deuteron transfer from the C1 of D-fructose 6-phosphate to the C2 of D-glucose 6-phosphate amounted to 65%, a value only slightly lower than the 72% intramolecular proton transfer in D2O. Both percentages, especially the latter one, were lower than those previously recorded during the single passage conversion of D-[1-13C,2-2H]glucose 6-phosphate in H2O or D-[1-13C]glucose 6-phosphate in D2O to D-fructose 6-phosphate and then to D-fructose 1,6-bisphosphate. These differences indicate that the sequence of interactions between the hexose esters and the binding sites of phosphoglucoisomerase is not strictly in mirror image during, respectively, the conversion of the aldose phosphate to ketose phosphate and the opposite process.

Ultrathin 2D Photocatalysts: Electronic-Structure Tailoring, Hybridization, and Applications.

PubMed

Di, Jun; Xiong, Jun; Li, Huaming; Liu, Zheng

2018-01-01

As a sustainable technology, semiconductor photocatalysis has attracted considerable interest in the past several decades owing to the potential to relieve or resolve energy and environmental-pollution issues. By virtue of their unique structural and electronic properties, emerging ultrathin 2D materials with appropriate band structure show enormous potential to achieve efficient photocatalytic performance. Here, the state-of-the-art progress on ultrathin 2D photocatalysts is reviewed and a critical appraisal of the classification, controllable synthesis, and formation mechanism of ultrathin 2D photocatalysts is presented. Then, different strategies to tailor the electronic structure of ultrathin 2D photocatalysts are summarized, including component tuning, thickness tuning, doping, and defect engineering. Hybridization with the introduction of a foreign component and maintaining the ultrathin 2D structure is presented to further boost the photocatalytic performance, such as quantum dots/2D materials, single atoms/2D materials, molecular/2D materials, and 2D-2D stacking materials. More importantly, the advancement of versatile photocatalytic applications of ultrathin 2D photocatalysts in the fields of water oxidation, hydrogen evolution, CO 2 reduction, nitrogen fixation, organic syntheses, and removal pollutants is discussed. Finally, the future opportunities and challenges regarding ultrathin 2D photocatalysts to bring about new opportunities for future research in the field of photocatalysis are also presented. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selection of High-Quality Spermatozoa May Be Promoted by Activated Vitamin D in the Woman.

PubMed

Bøllehuus Hansen, Lasse; Rehfeld, Anders; de Neergaard, Rosanna; Nielsen, John Erik; Iversen, Lea Hedegaard; Boisen, Ida Marie; Mortensen, Li Juel; Lanske, Beate; Almstrup, Kristian; Carlsen, Elisabeth; Berg, Anders Hayden; Jørgensen, Niels; Andersen, Anders Nyboe; Juul, Anders; Blomberg Jensen, Martin

2017-03-01

The vitamin D receptor (VDR) and enzymes involved in activation (CYP2R1, CYP27B1) and inactivation (CYP24A1) of vitamin D are expressed in ovary, testes, and spermatozoa. Determine responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in spermatozoa from normal and infertile men, and identify the site of exposure and how 1,25(OH)2D3 influences sperm function. Spermatozoa expressing VDR, CYP2R1, CYP27B1, and CYP24A1 were analyzed in normal and infertile men. 25-Hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D3], and 1,25(OH)2D3 were measured in serum, seminal fluid, cervical secretions, and ovarian follicular fluid. 1,25(OH)2D3 was tested on human spermatozoa. Tertiary center for fertility. Protein expression in spermatozoa and semen quality were assessed in 230 infertile and 114 healthy men. Vitamin D metabolites were measured in fluids from 245 men and 13 women, while 74 oocytes and 17 semen donors were used for sperm-function tests. VDR and CYP24A1 expressions in spermatozoa, fluid concentrations of 25-OHD, 24,25(OH)2D3, and 1,25(OH)2D3, and 1,25(OH)2D3-induced effects on intracellular calcium concentration ([Ca2+]i) and sperm-oocyte binding in vitro. VDR and CYP24A1 were expressed in a >2-fold higher fraction of spermatozoa from normal than infertile men (P < 0.01). Concentrations of 25-OHD, 24,25(OH)2D, and 1,25(OH)2D3 were undetectable in seminal fluid but high in ovarian follicular fluid. Follicular concentrations of 1,25(OH)2D3 induced a modest increase in [Ca2+]i and sperm-oocyte binding in vitro (P < 0.05). Presence of VDR and CYP24A1 mainly in spermatozoa of higher quality supports that 1,25(OH)2D3 available in the female reproductive tract may promote selection of the best gametes for fertilization. Copyright © 2017 by the Endocrine Society

3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.

PubMed

Polanec, Stephan H; Lazar, Mathias; Wengert, Georg J; Bickel, Hubert; Spick, Claudio; Susani, Martin; Shariat, Shahrokh; Clauser, Paola; Baltzer, Pascal A T

2018-04-01

To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.

dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes

PubMed Central

Korenjak, Michael; Kwon, Eunjeong; Morris, Robert T.; Anderssen, Endre; Amzallag, Arnaud; Ramaswamy, Sridhar; Dyson, Nicholas J.

2014-01-01

dREAM complexes represent the predominant form of E2F/RBF repressor complexes in Drosophila. dREAM associates with thousands of sites in the fly genome but its mechanism of action is unknown. To understand the genomic context in which dREAM acts we examined the distribution and localization of Drosophila E2F and dREAM proteins. Here we report a striking and unexpected overlap between dE2F2/dREAM sites and binding sites for the insulator-binding proteins CP190 and Beaf-32. Genetic assays show that these components functionally co-operate and chromatin immunoprecipitation experiments on mutant animals demonstrate that dE2F2 is important for association of CP190 with chromatin. dE2F2/dREAM binding sites are enriched at divergently transcribed genes, and the majority of genes upregulated by dE2F2 depletion represent the repressed half of a differentially expressed, divergently transcribed pair of genes. Analysis of mutant animals confirms that dREAM and CP190 are similarly required for transcriptional integrity at these gene pairs and suggest that dREAM functions in concert with CP190 to establish boundaries between repressed/activated genes. Consistent with the idea that dREAM co-operates with insulator-binding proteins, genomic regions bound by dREAM possess enhancer-blocking activity that depends on multiple dREAM components. These findings suggest that dREAM functions in the organization of transcriptional domains. PMID:25053843

Synthesis of methyl 2-O- and 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside.

PubMed

Rana, S S; Matta, K L

1986-09-01

Methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-alpha-D- mannopyranosyl]-alpha-D-mannopyranoside (2) was synthesized by treatment of methyl 3,4,6-tri-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside with tert-butylchlorodiphenylsilane in the presence of imidazole. Isopropylidenation, followed by oxidation with pyridinium chlorochromate, and stereoselective reduction with sodium borohydride, converted 2 into methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-2,3-O-isopro pylidene- alpha-D-talopyranosyl]-alpha-D-mannopyranoside (5). Treatment of 5 with a molar solution of tetrabutylammonium fluoride in dry oxolane produced a diol which, on O-de-isopropylidenation followed by catalytic hydrogenolysis, afforded the disaccharide glycoside methyl 2-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside. Synthesis of methyl 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside was accomplished by a similar reaction-sequence. The structures of the final disaccharides, and of various other intermediates, were established by 1H- and 13C-n.m.r. spectroscopy.

Low-resistance 2D/2D ohmic contacts: A universal approach to high-performance WSe 2, MoS 2, and MoSe 2 transistors

DOE PAGES

Chuang, Hsun -Jen; Chamlagain, Bhim; Koehler, Michael; ...

2016-02-04

Here, we report a new strategy for fabricating 2D/2D low-resistance ohmic contacts for a variety of transition metal dichalcogenides (TMDs) using van der Waals assembly of substitutionally doped TMDs as drain/source contacts and TMDs with no intentional doping as channel materials. We demonstrate that few-layer WSe 2 field-effect transistors (FETs) with 2D/2D contacts exhibit low contact resistances of ~0.3 kΩ μm, high on/off ratios up to >10 9, and high drive currents exceeding 320 μA μm –1. These favorable characteristics are combined with a two-terminal field-effect hole mobility μ FE ≈ 2 × 10 2 cm 2 V –1 smore » –1 at room temperature, which increases to >2 × 10 3 cm 2 V –1 s –1 at cryogenic temperatures. We observe a similar performance also in MoS 2 and MoSe 2 FETs with 2D/2D drain and source contacts. The 2D/2D low-resistance ohmic contacts presented here represent a new device paradigm that overcomes a significant bottleneck in the performance of TMDs and a wide variety of other 2D materials as the channel materials in postsilicon electronics.« less

Characterization of mutants expressing thermostable D1 and D2 polypeptides of photosystem II in the cyanobacterium Synechococcus elongatus PCC 7942.

PubMed

Haraguchi, Norihisa; Kaseda, Jun; Nakayama, Yasumune; Nagahama, Kazuhiro; Ogawa, Takahira; Matsuoka, Masayoshi

2018-06-08

Photosystem II complex embedded in thylakoid membrane performs oxygenic photosynthesis where the reaction center D1/D2 heterodimer accommodates all components of the electron transport chain. To express thermostable D1/D2 heterodimer in a cyanobacterium Synechococcus elongatus PCC 7942, we constructed a series of mutant strains whose psbA1 and psbD1 genes encoding, respectively, the most highly expressed D1 and D2 polypeptides were replaced with those of a thermophilic strain, Thermosynechococcus vulcanus. Because the C-terminal 16 amino acid sequences of D1 polypeptides should be processed prior to maturation but diverge from each other, we also constructed the psbA1ΔC-replaced strain expressing a thermostable D1 polypeptide devoid of the C-terminal extension. The psbA1/psbD1-replaced strain showed decreased growth rate and oxygen evolution rate, suggesting inefficient photosystem II. Immunoblot analyses for thermostable D1, D2 polypeptides revealed that the heterologous D1 protein was absent in thylakoid membrane from any mutant strains with psbA1, psbA1ΔC, and psbA1/psbD1-replacements, whereas the heterologous D2 protein was present in thylakoid membrane as well as purified photosystem II complex from the psbA1/psbD1-replaced strain. In the latter strain, the compensatory expression of psbA3 and psbD2 genes was elevated. These data suggest that heterologous D2 polypeptide could be combined with the host D1 polypeptide to form chimeric D1/D2 heterodimer, whereas heterologous D1 polypeptide even without the C-terminal extension was unable to make complex with the host D2 polypeptide. Since the heterologous D1 could not be detected even in the whole cells of psbA1/psbD1-replaced strain, the rapid degradation of unprocessed or unassembled heterologous D1 was implicated. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Electric field effect in multilayer Cr2Ge2Te6: a ferromagnetic 2D material

NASA Astrophysics Data System (ADS)

Xing, Wenyu; Chen, Yangyang; Odenthal, Patrick M.; Zhang, Xiao; Yuan, Wei; Su, Tang; Song, Qi; Wang, Tianyu; Zhong, Jiangnan; Jia, Shuang; Xie, X. C.; Li, Yan; Han, Wei

2017-06-01

The emergence of two-dimensional (2D) materials has attracted a great deal of attention due to their fascinating physical properties and potential applications for future nano-electronic devices. Since the first isolation of graphene, a Dirac material, a large family of new functional 2D materials have been discovered and characterized, including insulating 2D boron nitride, semiconducting 2D transition metal dichalcogenides and black phosphorus, and superconducting 2D bismuth strontium calcium copper oxide, molybdenum disulphide and niobium selenide, etc. Here, we report the identification of ferromagnetic thin flakes of Cr2Ge2Te6 (CGT) with thickness down to a few nanometers, which provides a very important piece to the van der Waals structures consisting of various 2D materials. We further demonstrate the giant modulation of the channel resistance of 2D CGT devices via electric field effect. Our results illustrate the gate voltage tunability of 2D CGT and the potential of CGT, a ferromagnetic 2D material, as a new functional quantum material for applications in future nanoelectronics and spintronics.

Rapid degradation of 2,4-dichlorophenoxyacetic acid facilitated by acetate under methanogenic condition.

PubMed

Yang, Zhiman; Xu, Xiaohui; Dai, Meng; Wang, Lin; Shi, Xiaoshuang; Guo, Rongbo

2017-05-01

Acetate can be used as an electron donor to stimulate 2,4-dichlorophenoxyacetic acid (2,4-D), which has not been determined under methanogenic condition. This study applied high-throughput sequencing and methanogenic inhibition approaches to investigate the 2,4-D degradation process using the enrichments obtained from paddy soil. Acetate addition significantly promoted 2,4-D degradation, which was 5-fold higher than in the acetate-unsupplemented enrichments in terms of the 2,4-D degradation rate constant. Dechloromonas and Pseudomonas were the dominant 2,4-D degraders. Methanogenic inhibition experiments indicated that the 2,4-D degradation was independent of methanogenesis. It was proposed that the accelerated 2,4-D degradation in the acetate-supplemented enrichment involved an unusual interaction, where members of the acetate oxidizers primarily oxidized acetate and produced H 2 . H 2 was utilized by the 2,4-D degraders to degrade 2,4-D, but also partially consumed by the hydrogenotrophic methanogens to produce methane. The findings presented here provide a new strategy for the remediation of 2,4-D-polluted soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes.

PubMed

Pueyo, Neus; Ortega, Francisco J; Mercader, Josep M; Moreno-Navarrete, José M; Sabater, Monica; Bonàs, Sílvia; Botas, Patricia; Delgado, Elías; Ricart, Wifredo; Martinez-Larrad, María T; Serrano-Ríos, Manuel; Torrents, David; Fernández-Real, José M

2013-01-01

Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D). We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met(31)Thr) in a sample of T2D patients and non-diabetic controls (n = 2,711). In a subset of subjects (n = 1,062), this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA) database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004), decreased fasting glucose (p = 0.0002), glycated hemoglobin (p = 0.0005), and 33% (p = 0.002) lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.

Intensity-based 2D 3D registration for lead localization in robot guided deep brain stimulation

NASA Astrophysics Data System (ADS)

Hunsche, Stefan; Sauner, Dieter; El Majdoub, Faycal; Neudorfer, Clemens; Poggenborg, Jörg; Goßmann, Axel; Maarouf, Mohammad

2017-03-01

Intraoperative assessment of lead localization has become a standard procedure during deep brain stimulation surgery in many centers, allowing immediate verification of targeting accuracy and, if necessary, adjustment of the trajectory. The most suitable imaging modality to determine lead positioning, however, remains controversially discussed. Current approaches entail the implementation of computed tomography and magnetic resonance imaging. In the present study, we adopted the technique of intensity-based 2D 3D registration that is commonly employed in stereotactic radiotherapy and spinal surgery. For this purpose, intraoperatively acquired 2D x-ray images were fused with preoperative 3D computed tomography (CT) data to verify lead placement during stereotactic robot assisted surgery. Accuracy of lead localization determined from 2D 3D registration was compared to conventional 3D 3D registration in a subsequent patient study. The mean Euclidian distance of lead coordinates estimated from intensity-based 2D 3D registration versus flat-panel detector CT 3D 3D registration was 0.7 mm  ±  0.2 mm. Maximum values of these distances amounted to 1.2 mm. To further investigate 2D 3D registration a simulation study was conducted, challenging two observers to visually assess artificially generated 2D 3D registration errors. 95% of deviation simulations, which were visually assessed as sufficient, had a registration error below 0.7 mm. In conclusion, 2D 3D intensity-based registration revealed high accuracy and reliability during robot guided stereotactic neurosurgery and holds great potential as a low dose, cost effective means for intraoperative lead localization.

The relationship between second-to-fourth digit (2D:4D) ratios and problematic and pathological Internet use among Turkish university students.

PubMed

Canan, Fatih; Karaca, Servet; Düzgün, Melike; Erdem, Ayşe Merve; Karaçaylı, Esranur; Topan, Nur Begüm; Lee, Sang-Kyu; Zhai, Zu Wei; Kuloğlu, Murat; Potenza, Marc N

2017-03-01

Background and aims The ratio of the second and fourth fingers (2D:4D ratio) is a sexually dimorphic trait, with men tending to have lower values than women. This ratio has been related to prenatal testosterone concentrations and addictive behaviors including problematic video-gaming. We aimed to investigate the possible association between 2D:4D ratios and Internet addiction and whether such a relationship would be independent of impulsivity. Methods A total of 652 university students (369 women, 283 men), aged 17-27 years, were enrolled in the study. Problematic and pathological Internet use (PPIU) was assessed using the Internet Addiction Test (IAT). The participants also completed the Barratt Impulsiveness Scale (version 11; BIS-11) and had their 2D:4D ratios measured. Results 2D:4D ratios were not significantly different in women with PPIU and in those with adaptive Internet use (AIU). Men with PPIU exhibited lower 2D:4D ratios on both hands when compared with those with AIU. Correlation analysis revealed that 2D:4D ratios on both hands were negatively correlated with IAT scores among men, but not among women. The multiple linear regression analysis revealed that age, duration of weekly Internet use, impulsiveness, and 2D:4D ratios on the right hand were independently associated with IAT scores among men, and impulsivity did not mediate the relationship between 2D:4D ratios and PPIU. Conclusions For men, 2D:4D ratios on the right hand were inversely correlated with Internet addiction severity even after controlling for individual differences in impulsivity. These findings suggest that high prenatal testosterone levels may contribute to the occurrence of PPIU among men.

The relationship between second-to-fourth digit (2D:4D) ratios and problematic and pathological Internet use among Turkish university students

PubMed Central

Canan, Fatih; Karaca, Servet; Düzgün, Melike; Erdem, Ayşe Merve; Karaçaylı, Esranur; Topan, Nur Begüm; Lee, Sang-Kyu; Zhai, Zu Wei; Kuloğlu, Murat; Potenza, Marc N.

2017-01-01

Background and aims The ratio of the second and fourth fingers (2D:4D ratio) is a sexually dimorphic trait, with men tending to have lower values than women. This ratio has been related to prenatal testosterone concentrations and addictive behaviors including problematic video-gaming. We aimed to investigate the possible association between 2D:4D ratios and Internet addiction and whether such a relationship would be independent of impulsivity. Methods A total of 652 university students (369 women, 283 men), aged 17–27 years, were enrolled in the study. Problematic and pathological Internet use (PPIU) was assessed using the Internet Addiction Test (IAT). The participants also completed the Barratt Impulsiveness Scale (version 11; BIS-11) and had their 2D:4D ratios measured. Results 2D:4D ratios were not significantly different in women with PPIU and in those with adaptive Internet use (AIU). Men with PPIU exhibited lower 2D:4D ratios on both hands when compared with those with AIU. Correlation analysis revealed that 2D:4D ratios on both hands were negatively correlated with IAT scores among men, but not among women. The multiple linear regression analysis revealed that age, duration of weekly Internet use, impulsiveness, and 2D:4D ratios on the right hand were independently associated with IAT scores among men, and impulsivity did not mediate the relationship between 2D:4D ratios and PPIU. Conclusions For men, 2D:4D ratios on the right hand were inversely correlated with Internet addiction severity even after controlling for individual differences in impulsivity. These findings suggest that high prenatal testosterone levels may contribute to the occurrence of PPIU among men. PMID:28358645

Human factors guidelines for applications of 3D perspectives: a literature review

NASA Astrophysics Data System (ADS)

Dixon, Sharon; Fitzhugh, Elisabeth; Aleva, Denise

2009-05-01

Once considered too processing-intense for general utility, application of the third dimension to convey complex information is facilitated by the recent proliferation of technological advancements in computer processing, 3D displays, and 3D perspective (2.5D) renderings within a 2D medium. The profusion of complex and rapidly-changing dynamic information being conveyed in operational environments has elevated interest in possible military applications of 3D technologies. 3D can be a powerful mechanism for clearer information portrayal, facilitating rapid and accurate identification of key elements essential to mission performance and operator safety. However, implementation of 3D within legacy systems can be costly, making integration prohibitive. Therefore, identifying which tasks may benefit from 3D or 2.5D versus simple 2D visualizations is critical. Unfortunately, there is no "bible" of human factors guidelines for usability optimization of 2D, 2.5D, or 3D visualizations nor for determining which display best serves a particular application. Establishing such guidelines would provide an invaluable tool for designers and operators. Defining issues common to each will enhance design effectiveness. This paper presents the results of an extensive review of open source literature addressing 3D information displays, with particular emphasis on comparison of true 3D with 2D and 2.5D representations and their utility for military tasks. Seventy-five papers are summarized, highlighting militarily relevant applications of 3D visualizations and 2.5D perspective renderings. Based on these findings, human factors guidelines for when and how to use these visualizations, along with recommendations for further research are discussed.

Regularity of the 3D Navier-Stokes equations with viewpoint of 2D flow

NASA Astrophysics Data System (ADS)

Bae, Hyeong-Ohk

2018-04-01

The regularity of 2D Navier-Stokes flow is well known. In this article we study the relationship of 3D and 2D flow, and the regularity of the 3D Naiver-Stokes equations with viewpoint of 2D equations. We consider the problem in the Cartesian and in the cylindrical coordinates.

Sustained Immunogenicity of 2-dose Human Papillomavirus 16/18 AS04-adjuvanted Vaccine Schedules in Girls Aged 9–14 Years: A Randomized Trial

PubMed Central

Puthanakit, Thanyawee; Cheng-Hsun, Chiu; Ren-Bin, Tang; Schwarz, Tino; Pellegrino, Angelo; Esposito, Susanna; Frenette, Louise; McNeil, Shelly; Durando, Paolo; Rheault, Paul; Giaquinto, Carlo; Horn, Michael; Petry, Karl Ulrich; Peters, Klaus; Azhar, Toma; Hillemanns, Peter; De Simoni, Stephanie; Friel, Damien; Pemmaraju, Suryakiran; Hezareh, Marjan; Thomas, Florence; Descamps, Dominique; Folschweiller, Nicolas; Struyf, Frank

2017-01-01

Abstract Background. We previously reported the noninferiority 1 month after the last dose of 2-dose human papillomavirus 16/18 AS04-adjuvanted (AS04-HPV-16/18) vaccine schedules at months 0 and 6 (2D_M0,6) and months 0 and 12 (2D_M0,12) in girls aged 9–14 years compared with a 3-dose schedule at months 0, 1, and 6 (3D_M0,1,6) in women aged 15–25 years. Here, we report the results at study end (month 36 [M36]). Methods. Girls were randomized 1:1 and received 2 vaccine doses either 6 months (2D_M0,6) or 12 months apart (2D_M0,12); women received 3 doses at months 0, 1, and 6 (3D_M0,1,6). Endpoints included noninferiority of HPV-16/18 antibodies for 2D_M0,6 versus 3D_M0,1,6; 2D_M0,12 versus 3D_M0,1,6; and 2D_M0,12 versus 2D_M0,6; and assessment of neutralizing antibodies, T cells, B cells, and safety. Results. At M36, the 2D_M0,6 and 2D_M0,12 schedules remained noninferior to the 3D_M0,1,6 schedule in terms of seroconversion rates and 3D/2D geometric mean titers for anti-HPV-16 and anti-HPV-18. All schedules elicited sustained immune responses up to M36. Conclusions. Both 2-dose schedules in young girls remained noninferior to the 3-dose schedule in women up to study conclusion at M36. The AS04-HPV-16/18 vaccine administered as a 2-dose schedule was immunogenic and well tolerated in young girls. PMID:28591778

Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

PubMed

Schepis, Tiziano; Gaemperli, Oliver; Treyer, Valerie; Valenta, Ines; Burger, Cyrill; Koepfli, Pascal; Namdar, Mehdi; Adachi, Itaru; Alkadhi, Hatem; Kaufmann, Philipp A

2007-11-01

The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.

Characterization of D150E and G196D aquaporin-2 mutations responsible for nephrogenic diabetes insipidus: importance of a mild phenotype

PubMed Central

Guyon, Cécile; Lussier, Yoann; Bissonnette, Pierre; Leduc-Nadeau, Alexandre; Lonergan, Michèle; Arthus, Marie-Françoise; Perez, Rafael Bedoya; Tiulpakov, Anatoly; Lapointe, Jean-Yves; Bichet, Daniel G.

2009-01-01

Aquaporin-2 (AQP2) is a water channel responsible for the final water reabsorption in renal collecting ducts. Alterations in AQP2 function induce nephrogenic diabetes insipidus (NDI), a condition characterized by severe polyuria and polydipsia. Three patients affected with severe NDI, who were compound heterozygous for the AQP2 mutations D150E and G196D, are presented here along with a mildly affected D150E homozygous patient from another family. Using Xenopus oocytes as an expression system, these two mutations (G196D and D150E) were compared with the wild-type protein (AQP2-wt) for functional activity (water flux analysis), protein maturation, and plasma membrane targeting. AQP2-wt induces a major increase in water permeability (Pf = 47.4 ± 12.2 × 10−4 cm/s) whereas D150E displays intermediate Pf values (Pf = 12.5 ± 3.0 × 10−4 cm/s) and G196D presents no specific water flux, similar to controls (Pf = 2.1 ± 0.8 × 10−4 cm/s and 2.2 ± 0.7 × 10−4 cm/s, respectively). Western blot and immunocytochemical evaluations show protein targeting that parallels activity levels with AQP2-wt adequately targeted to the plasma membrane, partial targeting for D150E, and complete sequestration of G196D within intracellular compartments. When coinjecting AQP2-wt with mutants, no (AQP2-wt + D150E) or partial (AQP2-wt + G196D) reduction of water flux were observed compared with AQP2-wt alone, whereas complete loss of function was found when both mutants were coinjected. These results essentially recapitulate the clinical profiles of the family members, showing a typical dominant negative effect when G196D is coinjected with either AQP2-wt or D150E but not between AQP2-wt and D150E mutant. PMID:19458121

Rebaudiosides T and U, minor C-19 xylopyranosyl and arabinopyranosyl steviol glycoside derivatives from Stevia rebaudiana (Bertoni) Bertoni.

PubMed

Perera, Wilmer H; Ghiviriga, Ion; Rodenburg, Douglas L; Alves, Kamilla; Bowling, John J; Avula, Bharathi; Khan, Ikhlas A; McChesney, James D

2017-03-01

Two diterpene glycosides were isolated from a commercial Stevia rebaudiana leaf extract. One was found to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid-(2-O-β-d-xylopyranosyl-3-O-β-d-glucopyranosyl- β-d-glucopyranosyl) ester (rebaudioside T), whereas the other was determined to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid-(6-O-α-l-arabinopyranosyl-β-d-glucopyranosyl) ester (rebaudioside U). In addition, five C-19 sugar free derivatives were prepared and identified as follows: 13-[(2-O-α-l-rhamnopyranosyl-β-d-glucopyranosyl)]oxy]kaur-16-en-19-oic acid (dulcoside A 1 ); 13-[(2-O-β-d-xylopyranosy-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]kaur-16-en-19-oic acid; 13-[(2-O-β-d-xylopyranosyl-β-d-glucopyranosyl-)oxy]kaur-16-en-19-oic acid; 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-xylopyranosyl-)oxy]kaur-16-en-19-oic acid (rebaudioside R 1 ) and 13-[(2-O-6-deoxy-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]kaur-16-en-19-oic acid, respectively. Chemical structures were determined by NMR experiments. HPLC analyses were also useful to differentiate different steviol-C13 sugar substituent patterns by elution position. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of an immunoassay for determination of 2,4-dichlorophenoxyacetic acid (2,4-D) based upon the recombinant Fab fragment of 2,4-D specific antibody

NASA Astrophysics Data System (ADS)

Nguyen, Van C.; Nguyen, Thi D. T.; Dau, Hung A.; Tham, Thu N.; Quyen, Dinh T.; Bachmman, Till; Schmid, Rolf D.

2001-09-01

To develop an immunoassay and further an immunosensor for 2,4-D based upon recombinant antibody, the Fab fragments of 2,4-D specific antibody were expressed in E. coli. Western blotting analysis of the periplasmic cell fractions shown that under the non-reducing condition only a single protein band at a molecular mass of 45-kDa, corresponding to the whole Fab fragment was detected. Antigen binding activity for 2,4-D was found only in the extract of cells bearing the 2,4-D plasmid. An immunoassay based on the competitive reaction of 2,4-D and enzyme tracer with 2,4-D Fab fragments immobilized on micro titer plates via rabbit anti-mouse IgC was developed. Using this assay, 2,4-D could be detected at concentration range of 0.5 (mu) g/1 to 10(mu) g/1. The center point of the 2,4-D test was found at a concentration of 5 (mu) g/l. The assay was applied for detection of 2,4-D in spiked orange samples, resulting in recovery rate of 90 percent. The immunoassay could be applied to monitor human exposure to 2,4-D from contamination in fruit samples.

The Validity of a New Low-Dose Stereoradiography System to Perform 2D and 3D Knee Prosthetic Alignment Measurements.

PubMed

Meijer, Marrigje F; Velleman, Ton; Boerboom, Alexander L; Bulstra, Sjoerd K; Otten, Egbert; Stevens, Martin; Reininga, Inge H F

2016-01-01

The EOS stereoradiography system has shown to provide reliable varus/valgus (VV) measurements of the lower limb in 2D (VV2D) and 3D (VV3D) after total knee arthroplasty (TKA). Validity of these measurements has not been investigated yet, therefore the purpose of this study was to determine validity of EOS VV2D and VV3D. EOS images were made of a lower limb phantom containing a knee prosthesis, while varying VV angle from 15° varus to 15° valgus and flexion angle from 0° to 20°, and changing rotation from 20° internal to 20° external rotation. Differences between the actual VV position of the lower limb phantom and its position as measured on EOS 2D and 3D images were investigated. Rotation, flexion or VV angle alone had no major impact on VV2D or VV3D. Combination of VV angle and rotation with full extension did not show major differences in VV2D measurements either. Combination of flexion and rotation with a neutral VV angle showed variation of up to 7.4° for VV2D; maximum variation for VV3D was only 1.5°. A combination of the three variables showed an even greater distortion of VV2D, while VV3D stayed relatively constant. Maximum measurement difference between preset VV angle and VV2D was 9.8°, while the difference with VV3D was only 1.9°. The largest differences between the preset VV angle and VV2D were found when installing the leg in extreme angles, for example 15° valgus, 20° flexion and 20° internal rotation. After TKA, EOS VV3D were more valid than VV2D, indicating that 3D measurements compensate for malpositioning during acquisition. Caution is warranted when measuring VV angle on a conventional radiograph of a knee with a flexion contracture, varus or valgus angle and/or rotation of the knee joint during acquisition.

Characterization of D-maltose as a T2 -exchange contrast agent for dynamic contrast-enhanced MRI.

PubMed

Goldenberg, Joshua M; Pagel, Mark D; Cárdenas-Rodríguez, Julio

2018-09-01

We sought to investigate the potential of D-maltose, D-sorbitol, and D-mannitol as T 2 exchange magnetic resonance imaging (MRI) contrast agents. We also sought to compare the in vivo pharmacokinetics of D-maltose with D-glucose with dynamic contrast enhancement (DCE) MRI. T 1 and T 2 relaxation time constants of the saccharides were measured using eight pH values and nine concentrations. The effect of echo spacing in a multiecho acquisition sequence used for the T 2 measurement was evaluated for all samples. Finally, performances of D-maltose and D-glucose during T 2 -weighted DCE-MRI were compared in vivo. Estimated T 2 relaxivities (r 2 ) of D-glucose and D-maltose were highly and nonlinearly dependent on pH and echo spacing, reaching their maximum at pH = 7.0 (∼0.08 mM -1 s -1 ). The r 2 values of D-sorbitol and D-mannitol were estimated to be ∼0.02 mM -1 s -1 and were invariant to pH and echo spacing for pH ≤7.0. The change in T 2 in tumor and muscle tissues remained constant after administration of D-maltose, whereas the change in T 2 decreased in tumor and muscle after administration of D-glucose. Therefore, D-maltose has a longer time window for T 2 -weighted DCE-MRI in tumors. We have demonstrated that D-maltose can be used as a T 2 exchange MRI contrast agent. The larger, sustained T 2 -weighted contrast from D-maltose relative to D-glucose has practical advantages for tumor diagnoses during T 2 -weighted DCE-MRI. Magn Reson Med 80:1158-1164, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

PubMed Central

Tebben, Peter J.; Singh, Ravinder J.

2016-01-01

Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment. PMID:27588937

Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

PubMed Central

Navarro, Gemma; Carriba, Paulina; Gandí, Jorge; Ciruela, Francisco; Casadó, Vicent; Cortés, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carmen; Franco, Rafael

2008-01-01

Functional interactions in signaling occur between dopamine D2 (D2R) and cannabinoid CB1 (CB1R) receptors, between CB1R and adenosine A2A (A2AR) receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells. PMID:18956124

Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes

PubMed Central

Kubota, T; Yamaura, Y; Ohkawa, N; Hara, H; Chiba, K

2000-01-01

Aims To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2,*3,*4,*5,*8,*10,*11,*12,*14,*17 and *18), and their relation to the metabolic capacity of CYP2D6 in Japanese subjects. Methods One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 subjects were phenotyped with dextromethorphan. Results The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly greater than that of heterozygotes for functional and defective alleles. Conclusions CYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6. PMID:10886115

Natural selection and type 2 diabetes-associated mortality in an isolated indigenous community in the valley of Oaxaca, southern Mexico.

PubMed

Little, Bertis B; Peña Reyes, Maria Eugenia; Malina, Robert M

2017-03-01

This study tests the hypothesis that natural selection is associated with type 2 diabetes (T2D)-associated mortality and fertility in a rural isolated Zapotec community in the Valley of Oaxaca, southern Mexico. Mortality data and related demographic and genealogic information were linked with data for fertility, prereproductive mortality and family history of mortality attributed to T2D. Physician verified T2D mortality (n = 27) between 1980 and 2009 and imputed T2D (n = 70) from cardiovascular mortality (68% random sample) and renal failure (44% random sample). Bootstrapping was used to obtain a robust variance estimate in survival analysis and multivariate analysis of variance. Estimated maximum natural selection by Crow's Index occurred circa 1930 and was relaxed after this time in the study population. Cox-regression survival analysis of T2D mortality with covariates (family history of T2D, cardiovascular disease, renal failure) indicated a significant hazard ratio (HR = 5.95, 95% CI: 1.38-25.67, p < .008) for the increase in T2D in 2000 to 2009. Survival analysis of imputed T2D resulted in a significant HR of 2.03 (95% CI: 1.08-3.85, p = .01) for the increase in T2D in the 2000 to 2009 cohort (reference group: 1980-1989). Mean number of live born offspring was lower among T2D (n = 27, 4.04 ± 3.85 SD) compared to non-T2D (n = 199, 5.30 ± 3.48) groups (p < .08). Mean number of live born offspring was lower (p = .003) among imputed T2D compared to non-T2D groups (4.10 ± 3.44 vs. 5.62 + 3.50). T2D-associated mortality increased in frequency as natural selection decreased, and favored offspring survival of non-T2D descedants. The results indicated statistically significant directional selection against T2D and imputed T2D to this population isolate. © 2016 Wiley Periodicals, Inc.

Validation of Supersonic Film Cooling Modeling for Liquid Rocket Engine Applications

NASA Technical Reports Server (NTRS)

Morris, Christopher I.; Ruf, Joseph H.

2010-01-01

Topics include: upper stage engine key requirements and design drivers; Calspan "stage 1" results, He slot injection into hypersonic flow (air); test articles for shock generator diagram, slot injector details, and instrumentation positions; test conditions; modeling approach; 2-d grid used for film cooling simulations of test article; heat flux profiles from 2-d flat plate simulations (run #4); heat flux profiles from 2-d backward facing step simulations (run #43); isometric sketch of single coolant nozzle, and x-z grid of half-nozzle domain; comparison of 2-d and 3-d simulations of coolant nozzles (run #45); flowfield properties along coolant nozzle centerline (run #45); comparison of 3-d CFD nozzle flow calculations with experimental data; nozzle exit plane reduced to linear profile for use in 2-d film-cooling simulations (run #45); synthetic Schlieren image of coolant injection region (run #45); axial velocity profiles from 2-d film-cooling simulation (run #45); coolant mass fraction profiles from 2-d film-cooling simulation (run #45); heat flux profiles from 2-d film cooling simulations (run #45); heat flux profiles from 2-d film cooling simulations (runs #47, #45, and #47); 3-d grid used for film cooling simulations of test article; heat flux contours from 3-d film-cooling simulation (run #45); and heat flux profiles from 3-d and 2-d film cooling simulations (runs #44, #46, and #47).

Inertial Navigation System Aiding Using Vision

DTIC Science & Technology

2013-03-01

abp a + Cba d dt ( pa ) + d dt ( rbba ) (2.11) vb = d dt ( rbba ) + Cba (Ω a... abp a + va) (2.12) where ddt (r b ba) accounts for the relative velocity betwwen the a-frame and b-frame, CbaΩaabp a is the instantaneous velocity of p...frame. Taking another time derivative of Eq. 2.12 results in: d dt ( vb ) , ab = d2 dt2 rbba + d dt [ Cba (Ω a abp a + va) ] (2.13) = r̈bba + dCba

Is sports choice and participation related to 2D:4D? A study among adult male students in Wrocław, Poland.

PubMed

Koziel, Slawomir; Kociuba, Marek; Ignasiak, Zofia; Chakraborty, Raja

2016-06-01

Psychology and personality of individuals may have implications for choice of, and performance in sports disciplines. Individual- and group sports differ in psychological requirements, such as, competitiveness, sensation seeking and risk taking attitude, often required in sports. There is sex difference in human in these qualities, which also show association with prenatal testosterone exposures. Second-to-fourth digit lengths ratio (2D:4D) is an indicator of prenatal testosterone exposure. Lower 2D:4D indicates higher prenatal testosteron exposure and vice versa. Males generally have lower 2D:4D than females. This study cross-sectional study investigated the relationship of 2D:4D with team based- or individual sports. The participants were 421 Polish male students with a mean (+SD) age of 19.78 (+0.79) years. Among them, 139 were engaged in sports and 282 were not. Mean 2D:4D in each hand of individual sporting group was significantly lower than the team sports- and no sports groups. Participants not involved in any sports had the highest mean 2D:4D value. However, the team sportsmen’s 2D:4D did not differ from the non sporting group. Prenatal testosterone exposure might have implication in sports choice and participation.

Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

PubMed

Arnt, J

1985-08-26

The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

PubMed Central

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

PubMed

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

PubMed Central

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-01-01

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

DOE PAGES

Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

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

Volkow, N. D.; Wang, G. -J.; Logan, J.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Prospective study aiming to compare 2D mammography and tomosynthesis + synthesized mammography in terms of cancer detection and recall. From double reading of 2D mammography to single reading of tomosynthesis.

PubMed

Romero Martín, Sara; Raya Povedano, Jose Luis; Cara García, María; Santos Romero, Ana Luz; Pedrosa Garriguet, Margarita; Álvarez Benito, Marina

2018-06-01

To evaluate tomosynthesis compared with 2D-mammography in cancer detection and recalls in a screening-programme, and assess performing synthesized instead of 2D, and compare double reading of 2D with single reading of tomosynthesis. Women (age 50-69 years) participating in the screening-programme were included. 2D-mammography and tomosynthesis were performed. There were four reading models: 2D-mammography (first); 2D-mammography (second); tomosynthesis + synthesized (third); tomosynthesis + synthesized + 2D (fourth reading). Paired double reading of 2D (first+second) and tomosynthesis (third+fourth) were analysed. In 16,067 participants, there were 98 cancers and 1,196 recalls. Comparing double reading of 2D with single reading of tomosynthesis, there was an increase of 12.6 % in cancer detection with the third reading (p= 0.043) and 6.9 % with the fourth reading (p=0.210), and a decrease in recalls of 40.5 % (p<0.001) and 44.4 % (p<0.001), respectively. With double reading of both techniques, there was an increase in cancer detection of 17.4 % (p = 0.004) and a decrease in recalls of 12.5 % (p = 0.001) with tomosynthesis. Single reading of tomosynthesis plus synthesized increased cancer detection and decreased recalls compared with double reading 2D. 2D did not improve results when added to tomosynthesis. • Tomosynthesis increases cancer detection and decreases recall rates versus 2D mammography. • Synthesized-mammography avoids performing 2D, showing higher cancer detection. • Single reading of tomosynthesis + synthesized is feasible as a new practice.

B-DNA Structure and Stability as Function of Nucleic Acid Composition: Dispersion-Corrected DFT Study of Dinucleoside Monophosphate Single and Double Strands

PubMed Central

Barone, Giampaolo; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

2013-01-01

We have computationally investigated the structure and stability of all 16 combinations of two out of the four natural DNA bases A, T, G and C in a di-2′-deoxyribonucleoside-monophosphate model DNA strand as well as in 10 double-strand model complexes thereof, using dispersion-corrected density functional theory (DFT-D). Optimized geometries with B-DNA conformation were obtained through the inclusion of implicit water solvent and, in the DNA models, of sodium counterions, to neutralize the negative charge of the phosphate groups. The results obtained allowed us to compare the relative stability of isomeric single and double strands. Moreover, the energy of the Watson–Crick pairing of complementary single strands to form double-helical structures was calculated. The latter furnished the following increasing stability trend of the double-helix formation energy: d(TpA)2

4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells.

PubMed

Kim, Young-June; Han, Myung-Kwan; Broxmeyer, Hal E

2008-02-01

Ligation of NKG2D, a potent costimulatory receptor, can be either beneficial or detrimental to CD8(+) cytotoxic T cell (CTL) responses. Factors for these diverse NKG2D effects remain elusive. In this study, we demonstrate that 4-1BB, another costimulatory receptor, is an essential regulator of NKG2D in CD8(+) T cells. Costimulation of NKG2D caused down-modulation of NKG2D, but induced 4-1BB expression on the cell surface, even in the presence of TGF-beta1, which inhibits 4-1BB expression. Resulting NKG2D(-)4-1BB(+) cells were activated but still in an immature state with low cytotoxic activity. However, subsequent 4-1BB costimulation induced cytotoxic activity and restored down-modulated NKG2D. The cytotoxic activity and NKG2D expression induced by 4-1BB on NKG2D(+)4-1BB(+) cells were refractory to TGF-beta1 down-modulation. Such 4-1BB effects were enhanced by IL-12. In contrast, in the presence of IL-4, 4-1BB effects were abolished because IL-4 down-modulated NKG2D and 4-1BB expression in cooperation with TGF-beta1, generating another CD8(+) T-cell type lacking both NKG2D and 4-1BB. These NKG2D(-)4-1BB(-) cells were inert and unable to gain cytotoxic activity. Our results suggest that 4-1BB plays a critical role in protecting NKG2D from TGF-beta1-mediated down-modulation. Co-expression of NKG2D and 4-1BB may represent an important biomarker for defining competency of tumor infiltrating CD8(+) T cells.

Nucleation and growth mechanism of 2D SnS2 by chemical vapor deposition: initial 3D growth followed by 2D lateral growth

NASA Astrophysics Data System (ADS)

Zhang, Haodong; van Pelt, Thomas; Nalin Mehta, Ankit; Bender, Hugo; Radu, Iuliana; Caymax, Matty; Vandervorst, Wilfried; Delabie, Annelies

2018-07-01

Tin disulfide (SnS2) is a n-type semiconductor with a hexagonally layered crystal structure and has promising applications in nanoelectronics, optoelectronics and sensors. Such applications require the deposition of SnS2 with controlled crystallinity and thickness control at monolayer level on large area substrate. Here, we investigate the nucleation and growth mechanism of two-dimensional (2D) SnS2 by chemical vapor deposition (CVD) using SnCl4 and H2S as precursors. We find that the growth mechanism of 2D SnS2 is different from the classical layer-by-layer growth mode, by which monolayer-thin 2D transition metal dichalcogenides can be formed. In the initial nucleation stage, isolated 2D SnS2 domains of several monolayers high are formed. Next, 2D SnS2 crystals grow laterally while keeping a nearly constant height until layer closure is achieved, due to the higher reactivity of SnS2 crystal edges than basal planes. We infer that the thickness of the 2D SnS2 crystals is determined by the height of initial SnS2 islands. After layer closure, SnS2 grows on grain boundaries and results in 3D growth mode, accompanied by spiral growth. Our findings suggest an approach to prepare 2D SnS2 with a controlled thickness of several monolayers and add more knowledge on the nucleation and growth mechanism of 2D materials.

New Constituents from Gymnocarpos decander.

PubMed

Bechlem, Houria; Mencherini, Teresa; Bouheroum, Mohamed; Benayache, Samir; Cotugno, Roberta; Braca, Alessandra; De Tommasi, Nunziatina

2017-10-01

The phytochemical investigation of Gymnocarpos decander aerial parts extract afforded two new saponins, 3- O - β -D-glucuronopyranosyl-2 β ,3 β ,16 α ,23-tetrahydroxyolean-12-en-28- O - β -D-apiofuranosyl-(1 → 3)- β -D-xylopyranosyl-(1 → 4)- α -L-rhamnopyranosyl-(1 → 2)- α -L-arabinopyranosyl ester ( 1 ), 3- O - β -D-glucuronopyranosyl-2 β ,3 β ,16 α -trihydroxyolean-12-en-28- O -α-L-rhamnopyranosyl-(1 → 3)- β -D-xylopyranosyl-(1 → 4)- α -L-rhamnopyranosyl-(1 → 2)- α -L-arabinopyranosyl ester ( 2 ), and three new flavonol glycosides, isorhamnetin 3- O -2''''- O -acetyl- β -D-xylopyranosyl-(1 → 6)-[ β -D-apiofuranosyl-(1 → 2)]- β -D-glucopyranoside ( 3 ), isorhamnetin 3- O -2‴- O -acetyl- β -D-xylopyranosyl-(1 → 6)- β -D-glucopyranoside ( 4 ), and quercetin 3- O -2‴- O -acetyl- β -D-xylopyranosyl-(1 → 6)- β -D-glucopyranoside ( 5 ), together with three known compounds. Their structures were determined by spectroscopic methods including 1D and 2D NMR analysis and high-resolution mass spectrometry. The new isolates were investigated for their potential cytotoxic activity on three cancer cell lines. Compounds 1 and 2 showed moderate antiproliferative activity. Georg Thieme Verlag KG Stuttgart · New York.

Conditional deletion of Tsc1 in the female reproductive tract impedes normal oviductal and uterine function by enhancing mTORC1 signaling in mice

PubMed Central

Daikoku, Takiko; Yoshie, Mikihiro; Xie, Huirong; Sun, Xiaofei; Cha, Jeeyeon; Ellenson, Lora Hedrick; Dey, Sudhansu K.

2013-01-01

Heightened mammalian target of rapamycin complex 1 (mTORC1) activity by genetic deletion of its direct inhibitor, Tsc1, is associated with aberrant development and dysfunction of the female reproductive tract in mice. Here, we compared the phenotypes of mice with conditional deletion of Tsc1 in the female reproductive tract by either progesterone receptor (PR)-Cre (Tsc1PR(d/d)), which inactivates Tsc1 in all major cell types in the uterus (epithelium, stroma and myometrium), or anti-Mullerian hormone type 2 receptor (Amhr2)-Cre (Tsc1Amhr2(d/d)), which inactivates stromal and myometrial Tsc1. Tsc1PR(d/d) and Tsc1Amhr2(d/d) females are infertile resulting from oviductal hyperplasia, retention of embryos in the oviduct and implantation failure. In contrast to the appropriate embryonic development after fertilization seen in Tsc1Amhr2(d/d) females, embryo development was disrupted in Tsc1PR(d/d) females. In addition, uteri in Tsc1PR(d/d) and Tsc1Amhr2(d/d) females showed epithelial hyperplasia but not endometrial cancer. In conclusion, Tsc1PR(d/d) and Tsc1Amhr2(d/d) have overlapping yet distinct phenotypes in the context of compartment-specific deletion of Tsc1. PMID:23475984

Bending Rigidity of 2D Silica

NASA Astrophysics Data System (ADS)

Büchner, C.; Eder, S. D.; Nesse, T.; Kuhness, D.; Schlexer, P.; Pacchioni, G.; Manson, J. R.; Heyde, M.; Holst, B.; Freund, H.-J.

2018-06-01

A chemically stable bilayers of SiO2 (2D silica) is a new, wide band gap 2D material. Up till now graphene has been the only 2D material where the bending rigidity has been measured. Here we present inelastic helium atom scattering data from 2D silica on Ru(0001) and extract the first bending rigidity, κ , measurements for a nonmonoatomic 2D material of definable thickness. We find a value of κ =8.8 eV ±0.5 eV which is of the same order of magnitude as theoretical values in the literature for freestanding crystalline 2D silica.

Significance of serum 24,25-dihydroxyvitamin D in the assessment of vitamin D status: a double-edged sword?

PubMed

Cashman, Kevin D; Hayes, Aoife; Galvin, Karen; Merkel, Joyce; Jones, Glenville; Kaufmann, Martin; Hoofnagle, Andrew N; Carter, Graham D; Durazo-Arvizu, Ramon A; Sempos, Christopher T

2015-04-01

24,25-Dihydroxyvitamin D [24,25(OH)2D] in serum may be both a nuisance and nutritionally valuable. We investigated the impact of 24,25(OH)2D3 on the performance of commercially available immunoassays for serum total 25-hydroxyvitamin D [25(OH)D] using (a) serum from a nationally representative sample of adults, (b) serum from a spiking experiment, and (c) data from the UK Vitamin D External Quality Assurance Scheme (DEQAS). We also investigated the utility of the serum ratio of 24,25(OH)2D3 to 25(OH)D as an index of inactivation and of response to vitamin D supplementation using randomized controlled trial (RCT) data. Measurement of 24,25(OH)2D in sera by a LC-MS/MS method allowed for an investigation of its impact on immunoassay-derived serum 25(OH)D values as well as its clinical utility. We report data from a nationally representative sample of adults, a recent vitamin D RCT in older adults, and DEQAS. 24,25(OH)2D3 contributed to the positive bias observed in some immunoassays relative to LC-MS/MS-derived estimates for total 25(OH)D. A spiking experiment showed that the degree of cross-reactivity with 24,25(OH)2D was high and may underpin this positive bias. Adjustment for 24,25(OH)2D3 concentration brought estimates closer to true values. Data from the vitamin D RCT showed that the ratio of 24,25(OH)2D3 to 25(OH)D was associated with serum 25(OH)D3 and with response of serum 25(OH)D to vitamin D supplementation. Our findings highlight that the effect of 24,25(OH)2D3 in serum is a double-edged sword-an interferent for some immunoassays, yet potentially informative of nutritional status. © 2015 American Association for Clinical Chemistry.

Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

PubMed Central

2011-01-01

Background The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot. Results The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region. Conclusions This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat. PMID:22171983

Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.

PubMed

Green, J P; Johnson, C L; Weinstein, H; Maayani, S

1977-12-01

D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide.

The stereochemical effect of SMAP-29 and SMAP-18 on bacterial selectivity, membrane interaction and anti-inflammatory activity.

PubMed

Jacob, Binu; Rajasekaran, Ganesan; Kim, Eun Young; Park, Il-Seon; Bang, Jeong-Kyu; Shin, Song Yub

2016-05-01

Sheep myeloid antimicrobial peptide-29 (SMAP-29) is a cathelicidin-related antimicrobial peptide derived from sheep myeloid cells. In order to investigate the effects of L-to-D-amino acid substitution in SMAP-29 on bacterial selectivity, membrane interaction and anti-inflammatory activity, we synthesized its two D-enantiomeric peptides (SMAP-29-E1 and SMAP-29-E2 containing D-Ile and D-allo-Ile, respectively) and two diastereomeric peptides (SMAP-29-D1 and SMAP-29-D2). Additionally, in order to address the effect of L-to-D-amino acid substitution in the N-terminal helical peptide of SMAP-29 (named SMAP-18) on antimicrobial activity, we synthesized its two D-enantiomeric peptides (SMAP-18-E1 and SMAP-18-E2), which are composed of D-amino acids entirely. L-to-D-amino acid substitution in membrane-targeting AMP, SMAP-29 did not affect its antimicrobial activity. However, D-allo-Ile containing-SMAP-29-E2 and SMAP-29-D2 exhibited less hemolytic activity compared to D-Ile containing-SMAP-29-E1 and SMAP-29-D1, respectively. L-to-D-amino acid substitution in intracellular targeting-AMPs, SMAP-18 and buforin-2 improved antimicrobial activity by 2- to eightfold. The improved antimicrobial activity of the D-isomers of SMAP-18 and buforin-2 seems to be due to the stability against proteases inside bacterial cells. Membrane depolarization and dye leakage suggested that the membrane-disruptive mode of SMAP-29-D1 and SMAP-29-D2 is different from that of SMAP-29, SMAP-29-E1, and SMAP-29-E2. L-to-D-amino acid substitution in SMAP-29 improved anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. In summary, we propose here that D-allo-Ile substitution is a more powerful strategy for increasing bacterial selectivity than D-Ile substitution in the design of D-enantiomeric and diastereomeric AMPs. SMAP-29-D1, and SMAP-29-D2 with improved bacterial selectivity and anti-inflammatory activity can serve as promising candidates for the development of anti-inflammatory and antimicrobial agents.

GRID2D/3D: A computer program for generating grid systems in complex-shaped two- and three-dimensional spatial domains. Part 2: User's manual and program listing

NASA Technical Reports Server (NTRS)

Bailey, R. T.; Shih, T. I.-P.; Nguyen, H. L.; Roelke, R. J.

1990-01-01

An efficient computer program, called GRID2D/3D, was developed to generate single and composite grid systems within geometrically complex two- and three-dimensional (2- and 3-D) spatial domains that can deform with time. GRID2D/3D generates single grid systems by using algebraic grid generation methods based on transfinite interpolation in which the distribution of grid points within the spatial domain is controlled by stretching functions. All single grid systems generated by GRID2D/3D can have grid lines that are continuous and differentiable everywhere up to the second-order. Also, grid lines can intersect boundaries of the spatial domain orthogonally. GRID2D/3D generates composite grid systems by patching together two or more single grid systems. The patching can be discontinuous or continuous. For continuous composite grid systems, the grid lines are continuous and differentiable everywhere up to the second-order except at interfaces where different single grid systems meet. At interfaces where different single grid systems meet, the grid lines are only differentiable up to the first-order. For 2-D spatial domains, the boundary curves are described by using either cubic or tension spline interpolation. For 3-D spatial domains, the boundary surfaces are described by using either linear Coon's interpolation, bi-hyperbolic spline interpolation, or a new technique referred to as 3-D bi-directional Hermite interpolation. Since grid systems generated by algebraic methods can have grid lines that overlap one another, GRID2D/3D contains a graphics package for evaluating the grid systems generated. With the graphics package, the user can generate grid systems in an interactive manner with the grid generation part of GRID2D/3D. GRID2D/3D is written in FORTRAN 77 and can be run on any IBM PC, XT, or AT compatible computer. In order to use GRID2D/3D on workstations or mainframe computers, some minor modifications must be made in the graphics part of the program; no modifications are needed in the grid generation part of the program. The theory and method used in GRID2D/3D is described.

Analysis of chronic aortic regurgitation by 2D and 3D echocardiography and cardiac MRI

PubMed Central

Stoebe, Stephan; Metze, Michael; Jurisch, Daniel; Tayal, Bhupendar; Solty, Kilian; Laufs, Ulrich; Pfeiffer, Dietrich; Hagendorff, Andreas

2018-01-01

Purpose The study compares the feasibility of the quantitative volumetric and semi-quantitative approach for quantification of chronic aortic regurgitation (AR) using different imaging modalities. Methods Left ventricular (LV) volumes, regurgitant volumes (RVol) and regurgitant fractions (RF) were assessed retrospectively by 2D, 3D echocardiography and cMRI in 55 chronic AR patients. Semi-quantitative parameters were assessed by 2D echocardiography. Results 22 (40%) patients had mild, 25 (46%) moderate and 8 (14%) severe AR. The quantitative volumetric approach was feasible using 2D, 3D echocardiography and cMRI, whereas the feasibility of semi-quantitative parameters varied considerably. LV volume (LVEDV, LVESV, SVtot) analyses showed good correlations between the different imaging modalities, although significantly increased LV volumes were assessed by cMRI. RVol was significantly different between 2D/3D echocardiography and 2D echocardiography/cMRI but was not significantly different between 3D echocardiography/cMRI. RF was not statistically different between 2D echocardiography/cMRI and 3D echocardiography/cMRI showing poor correlations (r < 0.5) between the different imaging modalities. For AR grading by RF, moderate agreement was observed between 2D/3D echocardiography and 2D echocardiography/cMRI and good agreement was observed between 3D echocardiography/cMRI. Conclusion Semi-quantitative parameters are difficult to determine by 2D echocardiography in clinical routine. The quantitative volumetric RF assessment seems to be feasible and can be discussed as an alternative approach in chronic AR. However, RVol and RF did not correlate well between the different imaging modalities. The best agreement for grading of AR severity by RF was observed between 3D echocardiography and cMRI. LV volumes can be verified by different approaches and different imaging modalities. PMID:29519957

Digit ratio (2D:4D) and male facial attractiveness: new data and a meta-analysis.

PubMed

Hönekopp, Johannes

2013-10-01

Digit ratio (2D:4D) appears to correlate negatively with prenatal testosterone (T) effects in humans. As T probably increases facial masculinity, which in turn might be positively related to male facial attractiveness, a number of studies have looked into the relationship between 2D:4D and male facial attractiveness, showing equivocal results. Here, I present the largest and third largest samples so far, which investigate the relationship between 2D:4D and male facial attractiveness in adolescents (n = 115) and young men (n = 80). I then present random-effects meta-analyses of the available data (seven to eight samples, overall n = 362 to 469). These showed small (r ≈ -.09), statistically non-significant relationships between 2D:4D measures and male facial attractiveness. Thus, 2D:4D studies offer no convincing evidence at present that prenatal T has a positive effect on male facial attractiveness. However, a consideration of confidence intervals shows that, at present, a theoretically meaningful relationship between 2D:4D and male facial attractiveness cannot be ruled out either.

Mass-Producible 2D-MoS2-Impregnated Screen-Printed Electrodes That Demonstrate Efficient Electrocatalysis toward the Oxygen Reduction Reaction.

PubMed

Rowley-Neale, Samuel J; Smith, Graham C; Banks, Craig E

2017-07-12

Two-dimensional molybdenum disulfide (2D-MoS 2 ) screen-printed electrodes (2D-MoS 2 -SPEs) have been designed, fabricated, and evaluated toward the electrochemical oxygen reduction reaction (ORR) within acidic aqueous media. A screen-printable ink has been developed that allows for the tailoring of the 2D-MoS 2 content/mass used in the fabrication of the 2D-MoS 2 -SPEs, which critically affects the observed ORR performance. In comparison to the graphite SPEs (G-SPEs), the 2D-MoS 2 -SPEs are shown to exhibit an electrocatalytic behavior toward the ORR which is found, critically, to be reliant upon the percentage mass incorporation of 2D-MoS 2 in the 2D-MoS 2 -SPEs; a greater percentage mass of 2D-MoS 2 incorporated into the 2D-MoS 2 -SPEs results in a significantly less electronegative ORR onset potential and a greater signal output (current density). Using optimally fabricated 2D-MoS 2 -SPEs, an ORR onset and a peak current of approximately +0.16 V [vs saturated calomel electrode (SCE)] and -1.62 mA cm -2 , respectively, are observed, which exceeds the -0.53 V (vs SCE) and -635 μA cm -2 performance of unmodified G-SPEs, indicating an electrocatalytic response toward the ORR utilizing the 2D-MoS 2 -SPEs. An investigation of the underlying electrochemical reaction mechanism of the ORR within acidic aqueous solutions reveals that the reaction proceeds via a direct four-electron process for all of the 2D-MoS 2 -SPE variants studied herein, where oxygen is electrochemically favorably reduced to water. The fabricated 2D-MoS 2 -SPEs are found to exhibit no degradation in the observed achievable current over the course of 1000 repeat scans. The production of such inks and the resultant mass-producible 2D-MoS 2 -SPEs mitigates the need to modify post hoc an electrode via the drop-casting technique that has been previously shown to result in a loss of achievable current over the course of 1000 repeat scans. The 2D-MoS 2 -SPEs designed, fabricated, and tested herein could have commercial viability as electrocatalytic fuel cell electrodes because of being economical as a result of their scales of economy and inherent tailorability. The technique utilized herein to produce the 2D-MoS 2 -SPEs could be adapted for the incorporation of different 2D nanomaterials, resulting in SPEs with the inherent advantages identified above.

A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

PubMed

Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

2017-01-01

Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

Development of new two-dimensional spectral/spatial code based on dynamic cyclic shift code for OCDMA system

NASA Astrophysics Data System (ADS)

Jellali, Nabiha; Najjar, Monia; Ferchichi, Moez; Rezig, Houria

2017-07-01

In this paper, a new two-dimensional spectral/spatial codes family, named two dimensional dynamic cyclic shift codes (2D-DCS) is introduced. The 2D-DCS codes are derived from the dynamic cyclic shift code for the spectral and spatial coding. The proposed system can fully eliminate the multiple access interference (MAI) by using the MAI cancellation property. The effect of shot noise, phase-induced intensity noise and thermal noise are used to analyze the code performance. In comparison with existing two dimensional (2D) codes, such as 2D perfect difference (2D-PD), 2D Extended Enhanced Double Weight (2D-Extended-EDW) and 2D hybrid (2D-FCC/MDW) codes, the numerical results show that our proposed codes have the best performance. By keeping the same code length and increasing the spatial code, the performance of our 2D-DCS system is enhanced: it provides higher data rates while using lower transmitted power and a smaller spectral width.

What is the mechanism of the OSO ring formation in sulfur tetroxide (SO4(C2v)) molecule?

NASA Astrophysics Data System (ADS)

Goodarzi, Moein; Vahedpour, Morteza; Solimannejad, Mohammad

2012-06-01

The mechanism of SO2 + O2 and O + SO3(D3h) reactions have been investigated at the MP2/6-31 + G(d) and CCSD(T)/cc-pV(Q + d)Z//MP2 levels on the triplet and singlet PESs. Although, no stable collision complexes have been found for the SO2 + O2(3∑g-), O(3P) + SO3(D3h) and O(1D) + SO3(D3h) reactions, 1IN(O2S-O2) has been considered on the singlet PES for the SO2 + O2(1Δg) reaction. The results show that there are no favorable paths for the OSO ring formation of SO4(C2v) in the atmospheric reactions of the SO2 + O2(3∑g-), SO2 + O2(1Δg) and O(3P) + SO3(D3h) while, the O(1D) + SO3(D3h) reaction can be suitable for the SO4(C2v) formation on the singlet PES.

Validation of a motion-robust 2D sequential technique for quantification of hepatic proton density fat fraction during free breathing.

PubMed

Pooler, B Dustin; Hernando, Diego; Ruby, Jeannine A; Ishii, Hiroshi; Shimakawa, Ann; Reeder, Scott B

2018-04-17

Current chemical-shift-encoded (CSE) MRI techniques for measuring hepatic proton density fat fraction (PDFF) are sensitive to motion artifacts. Initial validation of a motion-robust 2D-sequential CSE-MRI technique for quantification of hepatic PDFF. Phantom study and prospective in vivo cohort. Fifty adult patients (27 women, 23 men, mean age 57.2 years). 3D, 2D-interleaved, and 2D-sequential CSE-MRI acquisitions at 1.5T. Three CSE-MRI techniques (3D, 2D-interleaved, 2D-sequential) were performed in a PDFF phantom and in vivo. Reference standards were 3D CSE-MRI PDFF measurements for the phantom study and single-voxel MR spectroscopy hepatic PDFF measurements (MRS-PDFF) in vivo. In vivo hepatic MRI-PDFF measurements were performed during a single breath-hold (BH) and free breathing (FB), and were repeated by a second reader for the FB 2D-sequential sequence to assess interreader variability. Correlation plots to validate the 2D-sequential CSE-MRI against the phantom and in vivo reference standards. Bland-Altman analysis of FB versus BH CSE-MRI acquisitions to evaluate robustness to motion. Bland-Altman analysis to assess interreader variability. Phantom 2D-sequential CSE-MRI PDFF measurements demonstrated excellent agreement and correlation (R 2 > 0.99) with 3D CSE-MRI. In vivo, the mean (±SD) hepatic PDFF was 8.8 ± 8.7% (range 0.6-28.5%). Compared with BH acquisitions, FB hepatic PDFF measurements demonstrated bias of +0.15% for 2D-sequential compared with + 0.53% for 3D and +0.94% for 2D-interleaved. 95% limits of agreement (LOA) were narrower for 2D-sequential (±0.99%), compared with 3D (±3.72%) and 2D-interleaved (±3.10%). All CSE-MRI techniques had excellent correlation with MRS (R 2 > 0.97). The FB 2D-sequential acquisition demonstrated little interreader variability, with mean bias of +0.07% and 95% LOA of ± 1.53%. This motion-robust 2D-sequential CSE-MRI can accurately measure hepatic PDFF during free breathing in a patient population with a range of PDFF values of 0.6-28.5%, permitting accurate quantification of liver fat content without the need for suspended respiration. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Evaluation of increased vitamin D fortification in high-temperature, short-time-processed 2% milk, UHT-processed 2% fat chocolate milk, and low-fat strawberry yogurt.

PubMed

Hanson, A L; Metzger, L E

2010-02-01

The objective of this study was to determine the effect of increased vitamin D fortification (250 IU/serving) of high-temperature, short-time (HTST)-processed 2% fat milk, UHT-processed 2% fat chocolate milk, and low-fat strawberry yogurt on the sensory characteristics and stability of vitamin D during processing and storage. Three replicates of HTST pasteurized 2% fat milk, UHT pasteurized 2% fat chocolate milk, and low-fat strawberry yogurt were manufactured. Each of the 3 replicates for all products contained a control (no vitamin D fortification), a treatment group with 100 IU vitamin D/serving (current level of vitamin D fortification), and a treatment group with 250 IU vitamin D/serving. A cold-water dispersible vitamin D(3) concentrate was used for all fortifications. The HTST-processed 2% fat milk was stored for 21 d, with vitamin D analysis done before processing and on d 0, 14, and 21. Sensory analysis was conducted on d 14. The UHT-processed 2% fat chocolate milk was stored for 60 d, with vitamin D analysis done before processing and on d 0, 40, and 60. Sensory analysis was conducted on d 40. Low-fat strawberry yogurt was stored for 42 d, with vitamin D analysis done before processing, and on d 0, 28, and 42. Sensory analysis was conducted on d 28. Vitamin D levels in the fortified products were found to be similar to the target levels of fortification (100 and 250 IU vitamin D per serving) for all products, indicating no loss of vitamin D during processing. Vitamin D was also found to be stable over the shelf life of each product. Increasing the fortification of vitamin D from 100 to 250 IU/serving did not result in a change in the sensory characteristics of HTST-processed 2% fat milk, UHT-processed 2% fat chocolate milk, or low-fat strawberry yogurt. These results indicate that it is feasible to increase vitamin D fortification from 100 to 250 IU per serving in these products. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Concentrations of Trace Elements in Settling Particulate Matter and Particulate Element Fluxes in the Concepción Bay, the Gulf of California during the years 1996-1998

NASA Astrophysics Data System (ADS)

Leal Acosta, M. L.; Choumiline, E.; Silverberg, N.

2009-12-01

María Luisa Leal Acosta, Evgueni Choumiline y Norman Silverberg National Polytechnic Institute, Interdisciplinary Center of Marine Sciences Av. Instituto Politécnico Nacional s/n Col. Palo de Santa Rita Apdo. Postal 592 23096 La Paz, B.C.S., México. The Concepcion Bay on the Peninsula de Baja California outstands by its high biological productivity and shallow gas-hydrothermal discharges. During a summer season the anoxic and hypoxic conditions frequently appear in the water column. To know the biogeochemistry of elements in this bay, a preliminary study of the composition of settling particulate matter (SPM) was carried out. The samples were collected since May 22, 1996 to January 30, 1997 (first period with low fluxes) and during January 31, 1997 - March 22, 1998 (second period with high fluxes) using a trap, anchored at south of the bay. The major element (Fe and Ca) and 21 trace element contents in SPM were determined by instrumental neutron activation analysis. The average lithogenic contribution in the particulate calculated using Sc is terrigenous indicator 39% and 19% for the first and second period respectively. The As, Br, Cr, Sb, Se, Sr y U average concentrations in the SPM were higher than their average crustal abundances. The principal component analysis shows the existents of three associations of the elements in settling particles: a) lithogenic (As, Co, Cr, Fe, lantanides and Sc); b) biogenic (Sr and Ca); c) authigenic (U and Se). The average element enrichment factors were higher in the first period of SPM sampling from: Se (739)> Zn (523)> Cr(105)> Br(104)> Sb(97)> As (69). The normalization of the rare earth elements contents in SPM with North American Shale Composite allowed to establish the negative europium anomaly in 1996 samples, and second period was characterized by positive europium anomaly, also detected for the sediments beneath the trap. Average fluxes of particulate elements during this period correspond to a following sequence: Fe (8.9 mg m-2 d-1)> Ca (6.9 mg m-2 d-1)> Sb (3.2 μg m-2 d-1)>Cr (2.1 μg m-2 d-1)> Sr (0.3 μg m-2 d-1)> Br (48.2 ng m-2 d-1)> U (27.9 ng m-2 d-1)> As (21.9 ng m-2 d-1) > Co (17.9 ng m-2 d-1)> Ce (17.1 ng m-2 d-1)> Nd (9.8 ng m-2 d-1)> La (7.6 ng m-2 d-1)> Se (7.4 ng m-2 d-1)> Rb (5.7 ng m-2 d-1)> Sc (4.4 ng m-2 d-1)> Sm (3.0 ng m-2 d-1)> Th (2.9 ng m-2 d-1)> Cs (1.8 ng m-2 d-1)> Hf (1.2 ng m-2 d-1)> Tb (0.6 ng m-2 d-1)> Lu (0.4 ng m-2 d-1)> Yb (0.4 ng m-2 d-1)> Eu (0.3 ng m-2 d-1).

Dissipative Particle Dynamics at Isoenthalpic Conditions Using Shardlow-Like Splitting Algorithms

DTIC Science & Technology

2013-09-01

dd 11 d d ,...,1d 11 2 d 2 1 d dd dlnd ,...,1d1 dddd ddd ij 2 2 2...t W p t m ij i f C iji i i i i dd dlnd d1dd ddd                      pFp r p r  Ni ,...,1 , (10) while the fluctuation...pp rr v r p dd ddd             (11a) 6 j ji i i- j i- ji- j i- j mech,i j i i j mech,i j mech,i j j i 1 u 2 2m 2m u u d d d

Striatal Distribution and Cytoarchitecture of Dopamine Receptor Subtype 1 and 2: Evidence from Double-Labeling Transgenic Mice

PubMed Central

Ren, Keke; Guo, Baolin; Dai, Chunqiu; Yao, Han; Sun, Tangna; Liu, Xia; Bai, Zhantao; Wang, Wenting; Wu, Shengxi

2017-01-01

As the main input nucleus of the basal ganglion, the striatum executes different functions, including motivation, reward and attention. The functions of the striatum highly rely on its subregions that receive projections from various cortical areas and the distribution of striatonigral neurons that express D1 dopamine (DA) receptors (or D1 medium-sized spiny neurons, D1 MSNs) and striatopallidal neurons that express D2 DA receptors (or D2 MSNs). Using bacterial artificial chromosome (BAC) transgenic mice, several studies have recently been performed on the spatial distribution of D1 and D2 MSNs. However, these studies mainly focused on enumeration of either D1-enhanced fluorescent protein (eGFP) or D2-eGFP in mice. In the present work, we used Drd1a-tdTamato and Drd2-eGFP double BAC transgenic mice to evaluate the spatial pattern of D1 MSNs (red fluorescence) and D2 MSNs (green fluorescence) along the rostro-caudal axis of the dorsal striatum. The dorsal striatum was divided into three subregions: rostral caudoputamen (CPr), intermediate CP (CPi), and caudal CP (CPc) across the rostral–caudal extent of the striatum. The results demonstrate that D1 and D2 MSNs were intermingled with each other in most of these regions. The cell density of D1 MSNs was slightly higher than D2 MSNs through CPr, CPi, and CPc, though it did not reach significance. However, in CPi, the ratio of D1/D2 in the ventromedial CPi group was significantly higher than those in dorsolateral, dorsomedial, and ventrolateral CPi. There was similar proportion of cells that co-expressed D1 and D2 receptors. Moreover, we demonstrated a pathway-specific activation pattern of D1 MSNs and D2 MSNs in a manic like mouse model induced by D-Amphetamine by utilizing this double transgenic mice and c-fos immunoreactivity. Our results may provide a morphological basis for the function or pathophysiology of striatonigral and striatopallidal neurons with diverse cortical inputs to the dorsal striatum. PMID:28860974

2-D or not 2-D, that is the question: A Northern California test

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

Mayeda, K; Malagnini, L; Phillips, W S

2005-06-06

Reliable estimates of the seismic source spectrum are necessary for accurate magnitude, yield, and energy estimation. In particular, how seismic radiated energy scales with increasing earthquake size has been the focus of recent debate within the community and has direct implications on earthquake source physics studies as well as hazard mitigation. The 1-D coda methodology of Mayeda et al. has provided the lowest variance estimate of the source spectrum when compared against traditional approaches that use direct S-waves, thus making it ideal for networks that have sparse station distribution. The 1-D coda methodology has been mostly confined to regions ofmore » approximately uniform complexity. For larger, more geophysically complicated regions, 2-D path corrections may be required. The complicated tectonics of the northern California region coupled with high quality broadband seismic data provides for an ideal ''apples-to-apples'' test of 1-D and 2-D path assumptions on direct waves and their coda. Using the same station and event distribution, we compared 1-D and 2-D path corrections and observed the following results: (1) 1-D coda results reduced the amplitude variance relative to direct S-waves by roughly a factor of 8 (800%); (2) Applying a 2-D correction to the coda resulted in up to 40% variance reduction from the 1-D coda results; (3) 2-D direct S-wave results, though better than 1-D direct waves, were significantly worse than the 1-D coda. We found that coda-based moment-rate source spectra derived from the 2-D approach were essentially identical to those from the 1-D approach for frequencies less than {approx}0.7-Hz, however for the high frequencies (0.7{le} f {le} 8.0-Hz), the 2-D approach resulted in inter-station scatter that was generally 10-30% smaller. For complex regions where data are plentiful, a 2-D approach can significantly improve upon the simple 1-D assumption. In regions where only 1-D coda correction is available it is still preferable over 2-D direct wave-based measures.« less

2D-3D registration for cranial radiation therapy using a 3D kV CBCT and a single limited field-of-view 2D kV radiograph.

PubMed

Munbodh, Reshma; Knisely, Jonathan Ps; Jaffray, David A; Moseley, Douglas J

2018-05-01

We present and evaluate a fully automated 2D-3D intensity-based registration framework using a single limited field-of-view (FOV) 2D kV radiograph and a 3D kV CBCT for 3D estimation of patient setup errors during brain radiotherapy. We evaluated two similarity measures, the Pearson correlation coefficient on image intensity values (ICC) and maximum likelihood measure with Gaussian noise (MLG), derived from the statistics of transmission images. Pose determination experiments were conducted on 2D kV radiographs in the anterior-posterior (AP) and left lateral (LL) views and 3D kV CBCTs of an anthropomorphic head phantom. In order to minimize radiation exposure and exclude nonrigid structures from the registration, limited FOV 2D kV radiographs were employed. A spatial frequency band useful for the 2D-3D registration was identified from the bone-to-no-bone spectral ratio (BNBSR) of digitally reconstructed radiographs (DRRs) computed from the 3D kV planning CT of the phantom. The images being registered were filtered accordingly prior to computation of the similarity measures. We evaluated the registration accuracy achievable with a single 2D kV radiograph and with the registration results from the AP and LL views combined. We also compared the performance of the 2D-3D registration solutions proposed to that of a commercial 3D-3D registration algorithm, which used the entire skull for the registration. The ground truth was determined from markers affixed to the phantom and visible in the CBCT images. The accuracy of the 2D-3D registration solutions, as quantified by the root mean squared value of the target registration error (TRE) calculated over a radius of 3 cm for all poses tested, was ICC AP : 0.56 mm, MLG AP : 0.74 mm, ICC LL : 0.57 mm, MLG LL : 0.54 mm, ICC (AP and LL combined): 0.19 mm, and MLG (AP and LL combined): 0.21 mm. The accuracy of the 3D-3D registration algorithm was 0.27 mm. There was no significant difference in mean TRE for the 2D-3D registration algorithms using a single 2D kV radiograph with similarity measure and image view point. There was no significant difference in mean TRE between ICC LL , MLG LL , ICC (AP and LL combined), MLG (AP and LL combined), and the 3D-3D registration algorithm despite the smaller FOV used for the 2D-3D registration. While submillimeter registration accuracy was obtained with both ICC and MLG using a single 2D kV radiograph, combining the results from the two projection views resulted in a significantly smaller (P≤0.05) mean TRE. Our results indicate that it is possible to achieve submillimeter registration accuracy with both ICC and MLG using either single or dual limited FOV 2D kV radiographs of the head in the AP and LL views. The registration accuracy suggests that the 2D-3D registration solutions presented are suitable for the estimation of patient setup errors not only during conventional brain radiation therapy, but also during stereotactic procedures and proton radiation therapy where tighter setup margins are required. © 2018 American Association of Physicists in Medicine.

Tetranuclear copper(II) complexes bridged by alpha-D-glucose-1-phosphate and incorporation of sugar acids through the Cu4 core structural changes.

PubMed

Kato, Merii; Sah, Ajay Kumar; Tanase, Tomoaki; Mikuriya, Masahiro

2006-08-21

Tetranuclear copper(II) complexes containing alpha-D-glucose-1-phosphate (alpha-D-Glc-1P), [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(bpy)4(H2O)2]X3 [X = NO3 (1a), Cl (1b), Br (1c)], and [Cu4(mu-OH){mu-(alpha-D-Glc-1P)}2(phen)4(H2O)2](NO3)3 (2) were prepared by reacting the copper(II) salt with Na2[alpha-D-Glc-1P] in the presence of diimine ancillary ligands, and the structure of 2 was characterized by X-ray crystallography to comprise four {Cu(phen)}2+ fragments connected by the two sugar phosphate dianions in 1,3-O,O' and 1,1-O mu4-bridging fashion as well as a mu-hydroxo anion. The crystal structure of 2 involves two chemically independent complex cations in which the C2 enantiomeric structure for the trapezoidal tetracopper(II) framework is switched according to the orientation of the alpha-D-glucopyranosyl moieties. Temperature-dependent magnetic susceptibility data of 1a indicated that antiferromagnetic spin coupling is operative between the two metal ions joined by the hydroxo bridge (J = -52 cm(-1)) while antiferromagnetic interaction through the Cu-O-Cu sugar phosphate bridges is weak (J = -13 cm(-1)). Complex 1a readily reacted with carboxylic acids to afford the tetranuclear copper(II) complexes, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-CA)2(bpy)4](NO3)2 [CA = CH3COO (3), o-C6H4(COO)(COOH) (4)]. Reactions with m-phenylenediacetic acid [m-C6H4(CH2COOH)2] also gave the discrete tetracopper(II) cationic complex [Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)(CH2COOH))2(bpy)4](NO3)2 (5a) as well as the cluster polymer formulated as {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-m-C6H4(CH2COO)2)(bpy)4](NO3)2}n (5b). The tetracopper structure of 1a is converted into a symmetrical rectangular core in complexes 3, 4, and 5b, where the hydroxo bridge is dissociated and, instead, two carboxylate anions bridge another pair of Cu(II) ions in a 1,1-O monodentate fashion. The similar reactions were applied to incorporate sugar acids onto the tetranuclear copper(II) centers. Reactions of 1a with delta-D-gluconolactone, D-glucuronic acid, or D-glucaric acid in dimethylformamide resulted in the formation of discrete tetracopper complexes with sugar acids, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-SA)2(bpy)4](NO3)2 [SA = D-gluconate (6), D-glucuronate (7), D-glucarateH (8a)]. The structures of 6 and 7 were determined by X-ray crystallography to be almost identical with that of 3 with additional chelating coordination of the C-2 hydroxyl group of D-gluconate moieties (6) or the C-5 cyclic O atom of D-glucuronate units (7). Those with D-glucaric acid and D-lactobionic acid afforded chiral one-dimensional polymers, {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-glucarate)(bpy)4](NO3)2}n (8b) and {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-lactobionate)(bpy)4(H2O)2](NO3)3}n (9), respectively, in which the D-Glc-1P-bridged tetracopper(II) units are connected by sugar acid moieties through the C-1 and C-6 carboxylate O atoms in 8b and the C-1 carboxylate and C-6 alkoxy O atoms of the gluconate chain in 9. When complex 7 containing d-glucuronate moieties was heated in water, the mononuclear copper(II) complex with 2-dihydroxy malonate, [Cu(mu-O2CC(OH)2CO2)(bpy)] (10), and the dicopper(II) complex with oxalate, [Cu2(mu-C2O4)(bpy)2(H2O)2](NO3)2 (11), were obtained as a result of oxidative degradation of the carbohydrates through C-C bond cleavage reactions.

Structure, stability, thermodynamic properties, and infrared spectra of the protonated water octamer H(+)(H2O)8.

PubMed

Karthikeyan, S; Park, Mina; Shin, Ilgyou; Kim, Kwang S

2008-10-16

We investigated various two-dimensional (2D) and three-dimensional (3D) structures of H (+)(H 2O) 8, using density functional theory (DFT), Moller-Plesset second-order perturbation theory (MP2), and coupled cluster theory with single, double, and perturbative triple excitations (CCSD(T)). The 3D structure is more stable than the 2D structure at all levels of theory on the Born-Oppenheimer surface. With the zero-point energy (ZPE) correction, the predicted structure varies depending on the level of theory. The DFT employing Becke's three parameters with Lee-Yang-Parr functionals (B3LYP) favors the 2D structure. At the complete basis set (CBS) limit, the MP2 calculation favors the 3D structure by 0.29 kcal/mol, and the CCSD(T) calculation favors the 3D structure by 0.27 kcal/mol. It is thus expected that both 2D and 3D structures are nearly isoenergetic near 0 K. At 100 K, all the calculations show that the 2D structure is much more stable in free binding energy than the 3D structure. The DFT and MP2 vibrational spectra of the 2D structure are consistent with the experimental spectra. First-principles Car-Parrinello molecular dynamics (CPMD) simulations show that the 2D Zundel-type vibrational spectra are in good agreement with the experiment.

On operational flood forecasting system involving 1D/2D coupled hydraulic model and data assimilation

NASA Astrophysics Data System (ADS)

Barthélémy, S.; Ricci, S.; Morel, T.; Goutal, N.; Le Pape, E.; Zaoui, F.

2018-07-01

In the context of hydrodynamic modeling, the use of 2D models is adapted in areas where the flow is not mono-dimensional (confluence zones, flood plains). Nonetheless the lack of field data and the computational cost constraints limit the extensive use of 2D models for operational flood forecasting. Multi-dimensional coupling offers a solution with 1D models where the flow is mono-dimensional and with local 2D models where needed. This solution allows for the representation of complex processes in 2D models, while the simulated hydraulic state is significantly better than that of the full 1D model. In this study, coupling is implemented between three 1D sub-models and a local 2D model for a confluence on the Adour river (France). A Schwarz algorithm is implemented to guarantee the continuity of the variables at the 1D/2D interfaces while in situ observations are assimilated in the 1D sub-models to improve results and forecasts in operational mode as carried out by the French flood forecasting services. An implementation of the coupling and data assimilation (DA) solution with domain decomposition and task/data parallelism is proposed so that it is compatible with operational constraints. The coupling with the 2D model improves the simulated hydraulic state compared to a global 1D model, and DA improves results in 1D and 2D areas.

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

PubMed Central

Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio

2014-01-01

Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2−/−) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2−/− mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2−/−200dCMP/dTMP) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. Subject Categories Genetics, Gene Therapy & Genetic Disease; Metabolism PMID:24968719

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency.

PubMed

Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio

2014-08-01

Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2(-/-)) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2(-/-) mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2(-/-200dCMP/) (dTMP)) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Acute Depletion of D2 Receptors from the Rat Substantia Nigra Alters Dopamine Kinetics in the Dorsal Striatum and Drug Responsivity

PubMed Central

Budygin, Evgeny A.; Oleson, Erik B.; Lee, Yun Beom; Blume, Lawrence C.; Bruno, Michael J.; Howlett, Allyn C.; Thompson, Alexis C.; Bass, Caroline E.

2017-01-01

Recent studies have used conditional knockout mice to selectively delete the D2 autoreceptor; however, these approaches result in global deletion of D2 autoreceptors early in development. The present study takes a different approach using RNA interference (RNAi) to knockdown the expression of the D2 receptors (D2R) in the substantia nigra (SN), including dopaminergic neurons, which project primarily to the dorsal striatum (dStr) in adult rats. This approach restricts the knockdown primarily to nigrostriatal pathways, leaving mesolimbic D2 autoreceptors intact. Analyses of dopamine (DA) kinetics in the dStr reveal a decrease in DA transporter (DAT) function in the knockdown rats, an effect not observed in D2 autoreceptor knockout mouse models. SN D2 knockdown rats exhibit a behavioral phenotype characterized by persistent enhancement of locomotor activity in a familiar open field, reduced locomotor responsiveness to high doses of cocaine and the ability to overcome haloperidol-induced immobility on the bar test. Together these results demonstrate that presynaptic D2R can be depleted from specific neuronal populations and implicates nigrostriatal D2R in different behavioral responses to psychotropic drugs. PMID:28154530

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration.

PubMed

Tschen, Shuen-Ing; Zeng, Chun; Field, Loren; Dhawan, Sangeeta; Bhushan, Anil; Georgia, Senta

2017-01-01

Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2 -/- mice. Transgenic overexpression of cyclin D2 in cyclin D2 - / - β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2 -/- littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration.

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

Hefferan, T.E.; Sherman, S.S.; Sinha, R.

Eighty female Sprague-Dawley 8 week old rats were pair-fed for 2 months a semi-purified egg white diet containing 0.2% Ca and Zn at 4.5, 10, 100 or 200ppm. The vitamin D source was D/sub 3/ or 1,25(OH)/sub 2/D. Serum 1,25(OH)/sub 2/D, Ca and femur densities were determined. Femur densities were shown to regress significantly (p<0.01) with increasing dietary Zn when D/sub 3/ was in the diet. In addition, feeding D/sub 3/ resulted in a significant negative correlation of serum Ca with increased dietary Zn (p<0.05). There was a trend for 1,25(OH)/sub 2/D to increase with increasing Zn intake. However, serummore » values in rats consuming 1,25(OH)/sub 2/D were lower compared to rats consuming D/sub 3/ (25.9+/-3.6 vs 53.0+/-5.9 pg/ml). A second study was conducted to determine if non-fasted rats had elevated 1,25(OH)/sub 2/D serum levels. The rats were fed a similar semi-purified diet containing 0.2% Ca, 10ppm Zn and D/sub 3/ or 1,25(OH)/sub 2/D. No significant difference in 1,25(OH)/sub 2/D values was found between D/sub 3/ and 1,25(OH)/sub 2/D fed groups in the full fed state (80.8+/-11.4 vs 81.0+/-14.3 pg/ml). These results indicate high Zn intakes antagonize normal calcification and may interfere with normal function of the vitamin D endocrine system.« less

Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.

PubMed

van der Meijden, K; Bravenboer, N; Dirks, N F; Heijboer, A C; den Heijer, M; de Wit, G M J; Offringa, C; Lips, P; Jaspers, R T

2016-11-01

An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Paviosides A-H, eight new oleane type saponins from Aesculus pavia with cytotoxic activity.

PubMed

Lanzotti, Virginia; Termolino, Pasquale; Dolci, Marcello; Curir, Paolo

2012-05-15

A phytochemical analysis of Aesculus pavia has led to the isolation of eight novel triterpenoid saponins, based on oleane type skeleton and named paviosides A-H (1a, 1b-4a, 4b). On the basis of chemical, and 2D NMR and mass spectrometry data, the structures of the new compounds were elucidated as 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-d-glucopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (1a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-glucopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (1b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-galactopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (2a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-galactopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (2b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl barringtogenol C (3a), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-d-glucopyranosiduronic acid 21-angeloyl-22-acetyl barringtogenol C (3b), 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-tigloyl-22-acetyl protoaescigenin (4a), and 3-O-[β-D-xylopyranosyl (1 → 2)] [-β-D-xylopyranosyl (1 → 4)]-β-D-glucopyranosiduronic acid 21-angeloyl-22-acetyl protoaescigenin (4b). The compounds showed cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma, cell lines. Among them, paviosides E-H (3a, 3b and 4a, 4b) showed higher activity with values ranging from 2.1 to 3.6 μg/mL. Structure-activity relationship studies indicated the positive effect on the activity of xylose unit in the place of glucose, while a little detrimental effect is observed when glucose is substituted by galactose. The aglycone structure and the presence of a tigloyl or an angeloyl group at C-21 do not affect significantly the inhibitory activity on both tested cell lines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Potent antitrypanosomal triterpenoid saponins from Mussaenda luteola

USDA-ARS?s Scientific Manuscript database

Five new triterpenoid saponins, heinsiagenin A 3-O-[a-L-rhamnopyranosyl-(1->2)-Beta-D-glucopyranosyl-(1->2)]-B-D-glucopyranoside (1), heinsiagenin A 3-O-[a-L-rhamnopyranosyl-(1->2)-B-D-glucopyranosyl- (1->2)]-[B-D-glucopyranosyl-(1-4)]-B-D-glucopyranoside (2). 2a-hydroxyheinsiagenin A 3-o-[a-L-rhamn...

Synthesis, structures and properties of two new chiral rare earth-organic frameworks constructed by L/D-tartaric acid

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

Hu, Gonghao; Zhang, Haitao; Miao, Hao

2015-09-15

Hydrothermal reactions of rare earth cerium with L- or D- tartaric acid afford a pair of novel chiral enantiomer coordination polymers, namely, [Ce(L-tart)(CH{sub 2}OHCH{sub 2}OH)(H{sub 2}O)]Cl (L-1) and [Ce(D-tart)(CH{sub 2}OHCH{sub 2}OH)(H{sub 2}O)]Cl (D-1). Their structures were determined by single crystal X-ray diffraction analyses and further characterized by elemental analyses, XRD, IR spectra, and TG analyses. The circular dichroism (CD) spectra and second-harmonic generation (SHG) efficiency measurements proved that they are of structural chirality in the bulk samples. To the best of our knowledge, the enantiomers of L-1 and D-1 are the first 2D chiral dilayer frameworks constructed from L/D-tartrate ligands,more » ancillary ligand ethanediol and lanthanide ion Ce. - Graphical abstract: Hydrothermal reactions of rare earth cerium with L- or D- tartaric acid afford a pair of novel chiral enantiomer coordination polymers, namely, [Ce(L-tart)(CH{sub 2}OHCH{sub 2}OH)(H{sub 2}O)]Cl (L-1) and [Ce(D-tart)(CH{sub 2}OHCH{sub 2}OH)(H{sub 2}O)]Cl (D-1). Structural analysis indicates that the enantiomers of L-1 and D-1 are the first 2D chiral dilayer frameworks constructed from L/D-tartrate ligands and ancillary ligands ethanediol reacted with lanthanide ions Ce.« less

Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting.

PubMed

Heemstra, Karen A; Soeters, Maarten R; Fliers, Eric; Serlie, Mireille J; Burggraaf, Jacobus; van Doorn, Martijn B; van der Klaauw, Agatha A; Romijn, Johannes A; Smit, Johannes W; Corssmit, Eleonora P; Visser, Theo J

2009-06-01

The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T3 production. We determined D2 activity and D2 mRNA expression in human skeletal muscle biopsies under control conditions and during hypothyroidism, fasting, and hyperinsulinemia. This was a prospective study. The study was conducted at a university hospital. We studied 11 thyroidectomized patients with differentiated thyroid carcinoma (DTC) on and after 4 wk off T4( replacement and six healthy lean subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h of fasting. D2 activity and D2 mRNA levels were measured in skeletal muscle samples. No differences were observed in muscle D2 mRNA levels in DTC patients on and off T4 replacement therapy. In healthy subjects, muscle D2 mRNA levels were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 activities were very low and not influenced by hypothyroidism and fasting. Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA modulation on the observed low D2 activities questions the physiological relevance of D2 activity in human skeletal muscle.

Interpretation of the Electron Paramagnetic Resonance Spectra of Copper(II)-Tyrosine Complex

NASA Astrophysics Data System (ADS)

Xu, Xiao-Hui; Kuang, Min-Quan

2017-12-01

The electron paramagnetic resonance (EPR) spectra of [Cu(l-tyrosine)2]n (CuA) were interpreted based on the fourth-order perturbation treatments where the contributions due to the local distortion, ligand orbit and spin-orbit coupling were included. The calculated band transitions d_{x^2} - y^2 to dxy (≈16412 cm-1) and d_{z^2} (≈14845 cm-1) agree well with the band analysis results (d_{x^2} - y^2 \\to d_{xy} ≈16410 and d_{x^2} - y^2 \\to d_{z^2} ≈14850 cm-1). The unresolved separations d_{x^2} - y^2 \\to d_{xz} and d_{x^2} - y^2 \\to d_{yz} in the absorption spectra were evaluated as 26283 and 26262 cm-1, respectively. For CuA, copper chromophores in 1,3-diaminorpropane isophtalate copper(II) complex (CuB) and N-methyl-1,2-diaminoetaane-bis copper(II) polymer (CuC), the transition d_{x^2} - y^2 \\to d_{xy} (=E1≈10Dq) suffered an increase with a decrease in R̅L which was evaluated as the mean value of the copper-ligand bond lengths. The correlations between the tetragonal elongation ratio ρ (=(Rz-R̅L)/R̅L) (or the ratio G=(gz-ge)/((gx+gy)/2-ge)) and the g isotropy gav (=(gx+gy+gz)/3) (or the covalency factor N) for CuA, CuB and CuC were acquired and all the results were discussed.

Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.

PubMed

Jensen, Helle; Folkersen, Lasse; Skov, Søren

2012-01-01

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8(+) T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4(+) T-cells, however recently a subset of NKG2D(+) CD4(+) T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D(+) CD4(+) T-cells possesses effector-like functions, thus resembling the subsets of NKG2D(+) CD4(+) T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4(+) T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D(+) CD4(+) T-cells, generated from HCMV-primed CD4(+) T-cells. We show that the HCMV-primed NKG2D(+) CD4(+) T-cells possess a higher differentiated phenotype than the NKG2D(-) CD4(+) T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+) T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+) T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4(+) T-cells, whereas it is produced de novo in resting CD4(+) T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+) CD4(+) T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes.

PubMed

Chuang, Huai-Chia; Tan, Tse-Hua

2017-01-07

Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6 + Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

Characterization of the Nile Grass Rat as a Unique Model for Type 2 Diabetic Polyneuropathy.

PubMed

Singh, Jyoti; Yousuf, Muhammad Saad; Jones, Kelvin E; Shelemey, Paige T M; Joy, Twinkle; Macandili, Haecy; Kerr, Bradley J; Zochodne, Douglas W; Sauvé, Yves; Ballanyi, Klaus; Webber, Christine A

2018-06-01

Type 2 diabetes (T2D) has reached pandemic proportions worldwide. Almost half of T2D patients suffer from polyneuropathy that can present as paresthesia, hyperalgesia, allodynia, or hypoesthesia. Therapeutic treatment options are largely incomplete, suggesting new avenues of research are needed. Herein, we introduce the African Nile Grass rat (NGR), which develops T2D solely by diet manipulation, as a novel T2D polyneuropathy model. The purpose of this study was to first characterize T2D-induced polyneuropathy in the NGRs before highlighting their strength as a potential prediabetic model of T2D. NGRs with long-term T2D exhibit hallmark features of polyneuropathy such as decreased motor nerve conduction velocity, intraepidermal denervation, and hyposensitivity to noxious mechanical and thermal stimulation. At the dorsal root ganglia, T2D neurons have altered sodium channel expression, specifically increased Nav1.7 and Nav1.9, and their surrounding satellite glial cells express glial fibrillary acidic protein. Now that these T2D NGRs have been characterized and shown to have a similar presentation to human and other animal models of T2D, the strength of this diet-induced model can be exploited. The prediabetic changes can be observed over their long progression to develop T2D which may allow for a therapeutic window to prevent T2D before permanent damage occurs.

Two-dimensional hyperferroelectric metals: A different route to ferromagnetic-ferroelectric multiferroics

NASA Astrophysics Data System (ADS)

Luo, Wei; Xu, Ke; Xiang, Hongjun

2017-12-01

Recently, two-dimensional (2D) multiferroics have attracted a lot of attention due to their fascinating properties and promising applications. Although the ferroelectric (FE)-ferroelastic and ferromagnetic (FM)-ferroelastic multiferroics have been observed/predicted in 2D systems, 2D ferromagnetic-ferroelectric (FM-FE) multiferroics remain to be discovered since FM insulators are very rare. Here we proposed the concept of 2D hyperferroelectric metals, with which the insulating prerequisite for the FM-FE multiferroic is no longer required in 2D systems. We validate the concept of 2D hyperferroelectric metals and 2D metallic FM-FE multiferroics by performing first-principle calculations on 2D CrN and Cr B2 systems. The 2D buckled monolayer CrN is found to be a hyperferroelectic metal with the FM ground state, i.e., a 2D FM-FE multiferroic. With the global optimization approach, we find the 2D Cr B2 system has an antiferromagnetic (AFM)/planar ground state and a FM/FE metastable state, suggesting that it can be used to realize electric field control of magnetism. Our analysis demonstrates that the spin-phonon coupling and metal-metal interaction are two mechanisms for stabilizing the out-of-plane electric polarization in 2D systems. Our work not only extends the concept of FE to metallic systems, but also paves a way to search the long-sought high temperature FM-FE multiferroics.

Effect of inoculant strain and organic matter content on kinetics of 2,4-dichlorophenoxyacetic acid degradation in soil.

PubMed Central

Greer, L E; Shelton, D R

1992-01-01

We monitored rates of degradation of soluble and sorbed 2,4-dichlorophenoxyacetic acid (2,4-D) in low-organic-matter soil at field capacity amended with 1, 10, or 100 micrograms of 2,4-D per g of wet soil and inoculated with one of two bacterial strains (MI and 155) with similar maximum growth rates (mu max) but significantly different half-saturation growth constants (Ks). Concentrations of soluble 2,4-D were determined by analyzing samples of pore water pressed from soil, and concentrations of sorbed 2,4-D were determined by solvent extraction. Between 65 and 75% of the total 2,4-D was present in the soluble phase at equilibrium, resulting in soil solution concentrations of ca. 8, 60, and 600 micrograms of 2,4-D per ml, respectively. Soluble 2,4-D was metabolized preferentially; this was followed by degradation of both sorbed (after desorption) and soluble 2,4-D. Rates of degradation were comparable for the two strains at soil concentrations of 10 and 100 micrograms of 2,4-D per g; however, at 1 microgram/g of soil, 2,4-D was metabolized more rapidly by the strain with the lower Ks value (strain MI). We also monitored rates of biodegradation of soluble and sorbed 2,4-D in high-organic-matter soil at field capacity amended with 100 micrograms of 2,4-D per g of wet soil and inoculated with the low-Ks strain (strain MI). Ten percent of total 2,4-D was present in the soluble phase, resulting in a soil solution concentration of ca. 30 micrograms of 2,4-D per ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1622212

Effect of inoculant strain and organic matter content on kinetics of 2,4-dichlorophenoxyacetic acid degradation in soil.

PubMed

Greer, L E; Shelton, D R

1992-05-01

We monitored rates of degradation of soluble and sorbed 2,4-dichlorophenoxyacetic acid (2,4-D) in low-organic-matter soil at field capacity amended with 1, 10, or 100 micrograms of 2,4-D per g of wet soil and inoculated with one of two bacterial strains (MI and 155) with similar maximum growth rates (mu max) but significantly different half-saturation growth constants (Ks). Concentrations of soluble 2,4-D were determined by analyzing samples of pore water pressed from soil, and concentrations of sorbed 2,4-D were determined by solvent extraction. Between 65 and 75% of the total 2,4-D was present in the soluble phase at equilibrium, resulting in soil solution concentrations of ca. 8, 60, and 600 micrograms of 2,4-D per ml, respectively. Soluble 2,4-D was metabolized preferentially; this was followed by degradation of both sorbed (after desorption) and soluble 2,4-D. Rates of degradation were comparable for the two strains at soil concentrations of 10 and 100 micrograms of 2,4-D per g; however, at 1 microgram/g of soil, 2,4-D was metabolized more rapidly by the strain with the lower Ks value (strain MI). We also monitored rates of biodegradation of soluble and sorbed 2,4-D in high-organic-matter soil at field capacity amended with 100 micrograms of 2,4-D per g of wet soil and inoculated with the low-Ks strain (strain MI). Ten percent of total 2,4-D was present in the soluble phase, resulting in a soil solution concentration of ca. 30 micrograms of 2,4-D per ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol catalytic optical driven deposition for 1D and 2D materials with ultra-low power threshold of 0 dBm

NASA Astrophysics Data System (ADS)

Wang, Hao; Chen, Bohua; Xiao, Xu; Guo, Chaoshi; Zhang, Xiaoyan; Wang, Jun; Jiang, Meng; Wu, Kan; Chen, Jianping

2018-01-01

We have demonstrated a generalized optical driven deposition method, ethanol catalytic deposition (ECD) method, which is widely applicable to the deposition of a broad range of one-dimensional (1D) and two-dimensional (2D) materials with common deposition parameters. Using ECD method, deposition of 1D material carbon nanotubes and 2D materials MoS2, MoSe2, WS2 and WSe2 on tapered fiber has been demonstrated with the threshold power as low as 0 dBm. To our knowledge, this is the lowest threshold power ever reported in optical driven deposition, noting that the conventional optical driven deposition has a threshold typically near 15 dBm. It means ECD method can significantly reduce the power requirement and simplify the setup of the optical driven deposition as well as its wide applicability to different materials, which benefits the research on optical nonlinearity and ultrafast photonics of 1D and 2D materials.

Direct and indirect health economic impact of hypoglycaemia in a global population of patients with insulin-treated diabetes.

PubMed

Aronson, Ronnie; Galstyan, Gagik; Goldfracht, Margalit; Al Sifri, Saud; Elliott, Lisa; Khunti, Kamlesh

2018-04-01

The Hypoglycaemia Assessment Tool (HAT) study investigated the health economic impact of hypoglycaemic events in 24 countries, including countries without previously published data on hypoglycaemia. Self-assessment questionnaires and patient diaries (4-week prospective period) were completed by adults with type 1 (T1D) or type 2 diabetes (T2D) treated with insulin for more than 12 months (N = 27,585). Direct economic impacts of hypoglycaemia during the 4-week prospective period, included increased blood glucose monitoring (reported by 69.7% [T1D] and 60.9% [T2D] of patients), hospitalisation (T1D 2.1%; T2D 3.4% of patients) and medical contact (clinic or telephone; T1D 3.8%; T2D 6.8% of patients). Regional variation in medical contact and hospitalisation was found, with the highest usage in Russia (T1D 17.1%; T2D 17.3%), and Latin America (T1D 5.2%; T2D 6.8%) respectively. Indirect economic impacts following hypoglycaemia included loss of productivity due to absence from work or study; 3.9% (T1D) and 6.2% (T2D) of patients. Regional differences in work productivity were noted among patients with T2D, with a low prevalence in Northern Europe and Canada (0.9%) and high in Southeast Asia (14.6%). This study shows that hypoglycaemia has a significant but variable impact on the economics of diabetes healthcare globally. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

[Preliminary linkage analysis of a Chinese family with benign familial infantile convulsion].

PubMed

Xiong, Ge; Deng, Fei-yan; Xiao, Bo; Yang, Xiao-su; Ning, Jing-chun; Wu, Zhi-guo; Wang, Kang; Deng, Hong-wen

2004-06-01

Benign familial infantile convulsions (BFIC) is a recently recognized autosomal dominant inherited disorder. This epileptic syndrome typically begins between 3 and 12 months of age with clusters of partial seizures in most cases and carries a good prognosis. So far, three loci have been linked to chromosome 19q12.1-13.1, chromosome 2q24 and chromosome 16p12-q12. The authors performed linkage analysis on this pedigree. A four-generation Chinese family was investigated. The total number of members was 32 in this family and two neurologists in Xiangya Hospital gave systemic physical examinations and interictal neurological examinations to nineteen members of this family. Venous blood samples were taken for genetic analysis. DNA was extracted from peripheral blood leukocytes using phenol-chloroform method. Seventeen microsatellite markers spanning the critical regions on chromosomes 19q12-13.1, 2q24, and 16p12-q12 were genotyped. These markers included D19S49, D19S250, D19S414, D19S416 and D19S245 for the 19q region, D2S2380, D2S399, D2S111, D2S2195, D2S2330 and D2S2345 for the 2q region, D16S401, D16S3131, D16S3093, D16S517, D16S3120 and D16S415 for the 16p-q region. The DNA from each sample was amplified for the 17 markers. After polymerase chain reactions (PCR), PCR products of chromosome 19 with markers D19S49, D19S250, D19S414, D19S416 and D19S245 were subjected to electrophoresis on 8% denatured polyacrylamide gel for at least 2 hours and 20 minutes. Then the length of the PCR products was judged in the Strategene Eagle Eye II automated gel image analyzer. For the markers from chromosome 2 and 16, PCR products were scanned at ABI 377 autosequencer. The data of PCR products were analyzed using the software Genescan v3.1, Genetyper v2.1 (Applied Biosystem, CA. USA) and GenoDB v1.0. After Mendelian checking, the eligible genotyping data were used for linkage analysis. LOD scores were calculated by using MLINK program of LINKAGE v5.1, under an assumption of autosomal dominant inheritance and the estimated penetrance was 0.9. The allele frequencies of each marker were assumed to be equal and the disease-allele frequencies were designated to be 1/10,000. The LOD scores were calculated at combination rate (theta) 0.0, 0.1, 0.2, 0.3, and 0.4. Among the 17 selected microsatellite markers, which cover the previously reported regions, seven markers' data (D16S3131, D16S517, D16S3120, D16S3093, D2S2380, D19S250 and D19S414) were omitted due to failed genotyping, low genetic heterogeneity, or failure to pass Mendelian checking. Omission of these markers was to ensure the reliability of our raw data. The two-point LOD scores were below zero for all the markers and the maximum LOD scores at theta = 0.0 were less than -2 for markers D19S49, D19S416, D19S245, D16S401, D16S415, D2S399, D2S111, D2S2195, D2S2330 and D2S2345. Thus, the linkage result showed no evidence that the disease locus is linked to any of these selected markers, which excludes the previously reported candidate regions found in other ethnic families. There is no evidence that this Chinese family was linked to one of the following loci: 19q12.1-13.1, 16p12-q12 and 2q24. The results indicated that BFIC showed genetic heterogeneity and the Chinese BFIC families might be mapped on another new locus.

Design, Construction and Testing of a Pulsed High Energy Inductive Superconducting Energy Storage System

DTIC Science & Technology

1975-09-01

unit volume of conductor is: k2 2 dB 2 W" - 1 -PV : •iw2 1d11TII-3- 2 wihen the superconductor is in the normal state and: k - 2 dB I j P/ dB...C 2 -Bc ha 2 + 2 2 ’ -.4) ic ic B ~ h 2 .2t J P(-a~d) - (-• + 2_-- + 1 ) Jc Jc In the region d<x<a Jc =ici and the local power dissipation per unit ... unit length ever the whole of the circu- lar cross section is: ( 1 2 = x dh I4 :ross section

1D helix, 2D brick-wall and herringbone, and 3D interpenetration d10 metal-organic framework structures assembled from pyridine-2,6-dicarboxylic acid N-oxide.

PubMed

Wen, Li-Li; Dang, Dong-Bin; Duan, Chun-Ying; Li, Yi-Zhi; Tian, Zheng-Fang; Meng, Qing-Jin

2005-10-03

Five novel interesting d(10) metal coordination polymers, [Zn(PDCO)(H2O)2]n (PDCO = pyridine-2,6-dicarboxylic acid N-oxide) (1), [Zn2(PDCO)2(4,4'-bpy)2(H2O)2.3H2O]n (bpy = bipyridine) (2), [Zn(PDCO)(bix)]n (bix = 1,4-bis(imidazol-1-ylmethyl)benzene) (3), [Zn(PDCO)(bbi).0.5H2O]n (bbi = 1,1'-(1,4-butanediyl)bis(imidazole)) (4), and [Cd(PDCO)(bix)(1.5).1.5H2O]n (5), have been synthesized under hydrothermal conditions and structurally characterized. Polymer 1 possesses a one-dimensional (1D) helical chainlike structure with 4(1) helices running along the c-axis with a pitch of 10.090 Angstroms. Polymer 2 has an infinite chiral two-dimensional (2D) brick-wall-like layer structure in the ac plane built from achiral components, while both 3 and 4 exhibit an infinite 2D herringbone architecture, respectively extended in the ac and ab plane. Polymer 5 features a most remarkable and unique three-dimensional (3D) porous framework with 2-fold interpenetration related by symmetry, which contains channels in the b and c directions, both distributed in a rectangular grid fashion. Compounds 1-5, with systematic variation in dimensionality from 1D to 2D to 3D, are the first examples of d(10) metal coordination polymers into which pyridinedicarboxylic acid N-oxide has been introduced. In addition, polymers 1, 4, and 5 display strong blue fluorescent emissions in the solid state. Polymer 3 exhibits a strong SHG response, estimated to be approximately 0.9 times that of urea.

The modular approach enables a fully ab initio simulation of the contacts between 3D and 2D materials.

PubMed

Fediai, Artem; Ryndyk, Dmitry A; Cuniberti, Gianaurelio

2016-10-05

Up to now, the electrical properties of the contacts between 3D metals and 2D materials have never been computed at a fully ab initio level due to the huge number of atomic orbitals involved in a current path from an electrode to a pristine 2D material. As a result, there are still numerous open questions and controversial theories on the electrical properties of systems with 3D/2D interfaces-for example, the current path and the contact length scalability. Our work provides a first-principles solution to this long-standing problem with the use of the modular approach, a method which rigorously combines a Green function formalism with the density functional theory (DFT) for this particular contact type. The modular approach is a general approach valid for any 3D/2D contact. As an example, we apply it to the most investigated among 3D/2D contacts-metal/graphene contacts-and show its abilities and consistency by comparison with existing experimental data. As it is applicable to any 3D/2D interface, the modular approach allows the engineering of 3D/2D contacts with the pre-defined electrical properties.

Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity

PubMed Central

Wang, Danxin; Poi, Ming J.; Sun, Xiaochun; Gaedigk, Andrea; Leeder, J. Steven; Sadee, Wolfgang

2014-01-01

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 25% of clinically used drugs. Genetic polymorphisms cause substantial variation in CYP2D6 activity and serve as biomarkers guiding drug therapy. However, genotype–phenotype relationships remain ambiguous except for poor metabolizers carrying null alleles, suggesting the presence of yet unknown genetic variants. Searching for regulatory CYP2D6 polymorphisms, we find that a SNP defining the CYP2D6*2 allele, rs16947 [R296C, 17–60% minor allele frequency (MAF)], previously thought to convey normal activity, alters exon 6 splicing, thereby reducing CYP2D6 expression at least 2-fold. In addition, two completely linked SNPs (rs5758550/rs133333, MAF 13–42%) increase CYP2D6 transcription more than 2-fold, located in a distant downstream enhancer region (>100 kb) that interacts with the CYP2D6 promoter. In high linkage disequilibrium (LD) with each other, rs16947 and the enhancer SNPs form haplotypes that affect CYP2D6 enzyme activity in vivo. In a pediatric cohort of 164 individuals, rs16947 alone (minor haplotype frequency 28%) was associated with reduced CYP2D6 metabolic activity (measured as dextromethorphan/metabolite ratios), whereas rs5758550/rs133333 alone (frequency 3%) resulted in increased CYP2D6 activity, while haplotypes containing both rs16947 and rs5758550/rs133333 were similar to the wild-type. Other alleles used in biomarker panels carrying these variants such as CYP2D6*41 require re-evaluation of independent effects on CYP2D6 activity. The occurrence of two regulatory variants of high frequency and in high LD, residing on a long haplotype, highlights the importance of gene architecture, likely shaped by evolutionary selection pressures, in determining activity of encoded proteins. PMID:23985325

Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity.

PubMed

Natsubori, Akiyo; Tsutsui-Kimura, Iku; Nishida, Hiroshi; Bouchekioua, Youcef; Sekiya, Hiroshi; Uchigashima, Motokazu; Watanabe, Masahiko; de Kerchove d'Exaerde, Alban; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F

2017-03-08

The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca 2+ indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca 2+ elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior. SIGNIFICANCE STATEMENT An opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has been questioned by recent reports. In the present study, we measured concurrent Ca 2+ activity patterns of D1- and D2-MSNs in the ventrolateral striatum during food-incentive, goal-directed behavior in mice. According to Ca 2+ activity patterns, we conducted timing-specific optogenetic inhibition of each type of MSN. We demonstrated that both D1- and D2-MSNs in the ventrolateral striatum commonly and positively encoded action initiation, whereas only D1-MSNs positively encoded sustained motivated behavior. These findings led us to reconsider the prevailing notion of a functional segregation of MSN activity in the ventral striatum. Copyright © 2017 the authors 0270-6474/17/372724-11$15.00/0.

Four new triterpene saponins from the seeds of Aesculus chinensis.

PubMed

Zhao, Jing; Yang, Xiu-Wei

2003-09-01

Two pairs of new geometrically isomeric triterpenoid saponins were isolated from the seeds of Aesculus chinensis and characterized as 28-acetyl-21-tigloylprotoaescigenin 3-O-[beta-D-xylopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] [beta-D-glucopyranosiduronic acid (isoescin IIa, 1) and 28-acetyl-21-angeloylprotoaescigenin 3-O-[-beta-D-xylopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIb, 2); 28-acetyl-21-tigloylbarringtogenol C 3-O-[beta-D-galactopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIIa, 3) and 28-acetyl-21-angeloylbarringtogenol C 3-O-[beta-D-galactopyranosyl (1 --> 2)] [beta-D-glucopyranosyl (1 --> 4)] beta-D-glucopyranosiduronic acid (isoescin IIIb, 4). Their structures were established on the basis of spectroscopic and chemical evidence.

I2-induced SC-SC transformation within two-dimensional Zn(ii)-triazole framework: an ideal detector of cyano-containing molecules.

PubMed

Wang, Ying; Yi, Jin-Min; Zhang, Meng-Yuan; Xu, Ping; Zhao, Xiao-Jun

2016-02-21

A novel interpenetrated 2D + 2D → 2D architechture {[Zn(BTPS)(TPA)]·1.5DMF·H2O}n () has been constructed under solvothermal conditions. Interestingly, I2-induced single-crystal-to-single-crystal transformation to {[Zn(BTPS)(I)(TPA)1.5]·1.5H2O}n () showed a 2D + 1D → 2D array. Luminescent properties indicated that represents the first example of selective recognition toward cyano-containing molecules.

Drug & Gene Interaction Risk Analysis With & Without Genetic Testing Among Patients Undergoing MTM

ClinicalTrials.gov

2017-02-22

Cytochrome P450 CYP2D6 Enzyme Deficiency; Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Extensive Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Cytochrome P450 CYP2C9 Enzyme Deficiency; Cytochrome P450 CYP2C19 Enzyme Deficiency; Drug Metabolism, Poor, CYP2D6-RELATED; Drug Metabolism, Poor, CYP2C19-RELATED; CYP2D6 Polymorphism

Guanfu base A, an antiarrhythmic alkaloid of Aconitum coreanum, Is a CYP2D6 inhibitor of human, monkey, and dog isoforms.

PubMed

Sun, Jianguo; Peng, Ying; Wu, Hui; Zhang, Xueyuan; Zhong, Yunxi; Xiao, Yanan; Zhang, Fengyi; Qi, Huanhuan; Shang, Lili; Zhu, Jianping; Sun, Yue; Liu, Ke; Liu, Jinghan; A, Jiye; Ho, Rodney J Y; Wang, Guangji

2015-05-01

Guanfu base A (GFA) is a novel heterocyclic antiarrhythmic drug isolated from Aconitum coreanum (Lèvl.) rapaics and is currently in a phase IV clinical trial in China. However, no study has investigated the influence of GFA on cytochrome P450 (P450) drug metabolism. We characterized the potency and specificity of GFA CYP2D inhibition based on dextromethorphan O-demethylation, a CYP2D6 probe substrate of activity in human, mouse, rat, dog, and monkey liver microsomes. In addition, (+)-bufuralol 1'-hydroxylation was used as a CYP2D6 probe for the recombinant form (rCYP2D6), 2D1 (rCYP2D1), and 2D2 (rCYP2D2) activities. Results show that GFA is a potent noncompetitive inhibitor of CYP2D6, with inhibition constant Ki = 1.20 ± 0.33 μM in human liver microsomes (HLMs) and Ki = 0.37 ± 0.16 μM for the human recombinant form (rCYP2D6). GFA is also a potent competitive inhibitor of CYP2D in monkey (Ki = 0.38 ± 0.12 μM) and dog (Ki = 2.4 ± 1.3 μM) microsomes. However, GFA has no inhibitory activity on mouse or rat CYP2Ds. GFA did not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but showed slight inhibition of 2B6 and 2E1. Preincubation of HLMs and rCYP2D6 resulted in the inactivation of the enzyme, which was attenuated by GFA or quinidine. Beagle dogs treated intravenously with dextromethorphan (2 mg/ml) after pretreatment with GFA injection showed reduced CYP2D metabolic activity, with the Cmax of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration-time curve half that of the saline-treated group. This study suggests that GFA is a specific CYP2D6 inhibitor that might play a role in CYP2D6 medicated drug-drug interaction. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Triterpene glycosides from the tubers of Anemone coronaria.

PubMed

Mimaki, Yoshihiro; Watanabe, Kazuki; Matsuo, Yukiko; Sakagami, Hiroshi

2009-07-01

Six new triterpene glycosides (1-6), together with 11 known ones (7-17), have been isolated from a glycoside-enriched fraction prepared from the tubers of Anemone coronaria L. (Ranunculaceae). On the basis of extensive spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage, the structures of 1-6 were determined to be 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta,23-dihydroxyolean-12-en-28-oic acid (1), 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (2), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta,23-dihydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (4), 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-2beta-hydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (5), and 3beta-[(O-beta-D-glucopyranosyl-(1-->4)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-18-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (6), respectively. Furthermore, the isolated compounds were evaluated for their cytotoxic activity against HSC-2 cells.

Synthesis, metabolism, and biological activity of 2-[3-(tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3.

PubMed

Takano, Masashi; Yasuda, Kaori; Higuchi, Erika; Tohyama, Eri; Takeuchi, Akiko; Sakaki, Toshiyuki; Kittaka, Atsushi

2016-11-01

Recently, we found that 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D 3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats in vivo than those of active vitamin D 3 , 1α,25(OH) 2 D 3 . We were interested in introducing a heterocyclic ring to the C2 position of the seco-steroidal structure via an alkyl linker, and four novel C2-(3-tetrazolylpropyl) substituted 1α,25-dihydroxy-19-norvitamin D 3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH) 2 D 3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-19-nor-1α,25(OH) 2 D 3 showed weak binding affinity for human vitamin D receptor (hVDR) (2.6% of 1α,25(OH) 2 D 3 and ca. 15% of 19-nor-1α,25(OH) 2 D 3 ) and weak VDR transactivation activity in HOS cells (EC 50 7.3nM, when 1α,25(OH) 2 D 3 0.23nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH) 2 D 3 showed weak transactivation activity (EC 50 12.5nM). Metabolic stability of the 2α-substituted compounds 2α-[3-(tetrazol-1-yl)propyl]- and 2α-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH) 2 D 3 was higher than that of the 2β-substituted counterparts 2β-[3-(tetrazol-1-yl)propyl]- and 2β-[3-(tetrazol-2-yl)propyl]-19-nor-1α,25(OH) 2 D 3 against human CYP24A1. Introduction of a tetrazole ring to the C2-position of the 19-norvitamin D 3 skeleton with the propyl linker led to weak VDR agonistic activity with stability against CYP24A1 metabolism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Depressive Symptoms in Youth With Type 1 or Type 2 Diabetes: Results of the Pediatric Diabetes Consortium Screening Assessment of Depression in Diabetes Study.

PubMed

Silverstein, Janet; Cheng, Peiyao; Ruedy, Katrina J; Kollman, Craig; Beck, Roy W; Klingensmith, Georgeanna J; Wood, Jamie R; Willi, Steven; Bacha, Fida; Lee, Joyce; Cengiz, Eda; Redondo, Maria J; Tamborlane, William V

2015-12-01

To evaluate the frequency of depressive symptoms and the diagnosis and management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium T1D and T2D registries. The Children's Depression Inventory (CDI) 2 Self-Report (Short) version was completed by 261 T1D and 339 T2D youth aged 10-17 years. Symptoms of depression were identified in 13% of T1D and 22% of T2D (P = 0.007) participants; of these, only 4% of T1D and 9% of T2D youth were treated by a therapist within the prior 12 months. Depressive symptoms were associated with lower family income (P = 0.006) and obesity (P = 0.002) in T1D but not T2D youth. Depressive symptoms are more frequent than diagnosed depression in youth with T1D or T2D. These results underscore the need for regular depression screening and appropriate referral for youth with diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

PubMed

Czoty, P W; Gould, R W; Gage, H D; Nader, M A

2017-09-01

Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Digit ratio (2D:4D), testosterone, cortisol, aggression, personality and hand-grip strength: Evidence for prenatal effects on strength.

PubMed

Ribeiro, Evaldo; Neave, Nick; Morais, Rosana Nogueiro; Kilduff, Liam; Taylor, Suzan R; Butovskaya, Marina; Fink, Bernhard; Manning, John T

2016-09-01

Digit ratio (2D:4D) is a putative marker for prenatal testosterone and is correlated with performance in many sports. Low 2D:4D has been linked to strength but the evidence is mixed and strength is also influenced by mass, testosterone, and behavioural factors. It has been hypothesised that the 2D:4D-strength correlation may be strongest in challenge conditions when short-term changes occur in steroid hormones. We tested this suggestion in men. We used a cross-over study design with a challenge (an aggressive video of rugby tackles) and control (a blank screen) condition. 89 healthy men. Finger lengths (2nd and 4th for both hands), hand-grip strength (HGS), testosterone (T), cortisol (C), aggression (Buss-Perry Aggression Questionnaire) and personality type (Ten Item Personality Measure). In both conditions participants provided saliva samples (for hormone assays). In the challenge condition there was a highly significant increase in HGS, and modest changes in T, physical aggression and emotional stability. HGS correlated negatively with left hand 2D:4D. In a multiple regression, left hand 2D:4D was negatively related to HGS and emotional stability was positively related to HGS. In the control condition HGS was not correlated with 2D:4D. In a multiple regression, BMI, physical aggression, and emotional stability were significantly related to HGS. 2D:4D is a negative correlate of strength in challenge situations. This finding may in part explain associations between 2D:4D and sports performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Live-Attenuated HSV-2 ICP0 − Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

PubMed Central

Halford, William P.; Püschel, Ringo; Gershburg, Edward; Wilber, Andrew; Gershburg, Svetlana; Rakowski, Brandon

2011-01-01

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0 − virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0 − virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein. PMID:21412438

Isotopic separation of D.sub.2 O from H.sub.2 O using ruthenium adsorbent

DOEpatents

Thiel, Patricia A.

1990-04-10

A method of enrichment of D.sub.2 O in solutions of D.sub.2 O in H.sub.2 O by contacting said solutions in the steam phase with hexagonal crystalline to produce enriched D.sub.2 O. The passages may be repeated to achieve a desired amount of D.sub.2 O.

Epi-Two-Dimensional Fluid Flow: A New Topological Paradigm for Dimensionality

NASA Astrophysics Data System (ADS)

Yoshida, Z.; Morrison, P. J.

2017-12-01

While a variety of fundamental differences are known to separate two-dimensional (2D) and three-dimensional (3D) fluid flows, it is not well understood how they are related. Conventionally, dimensional reduction is justified by an a priori geometrical framework; i.e., 2D flows occur under some geometrical constraint such as shallowness. However, deeper inquiry into 3D flow often finds the presence of local 2D-like structures without such a constraint, where 2D-like behavior may be identified by the integrability of vortex lines or vanishing local helicity. Here we propose a new paradigm of flow structure by introducing an intermediate class, termed epi-two-dimensional flow, and thereby build a topological bridge between 2D and 3D flows. The epi-2D property is local and is preserved in fluid elements obeying ideal (inviscid and barotropic) mechanics; a local epi-2D flow may be regarded as a "particle" carrying a generalized enstrophy as its charge. A finite viscosity may cause "fusion" of two epi-2D particles, generating helicity from their charges giving rise to 3D flow.

PET imaging predicts future body weight and cocaine preference

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

Michaelides M.; Wang G.; Michaelides M.

Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET imaging have been reported in obese humans and rodents. Similar deficits have been reported in cocaine-addicts and cocaine-exposed primates. We found that D2R/D3R binding availability negatively correlated with measures of body weight at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months (dorsal and ventral striatum) post scan in rats. Cocaine preference was negatively correlated with D2R/D3R binding availability 2 months (ventral striatum) post scan. Our findings suggest that inherent deficits in striatal D2R/D3R signaling are related to obesity and drug addiction susceptibility and that ventralmore » and dorsal striatum serve dissociable roles in maintaining weight gain and cocaine preference. Measuring D2R/D3R binding availability provides a way for assessing susceptibility to weight gain and cocaine abuse in rodents and given the translational nature of PET imaging, potentially primates and humans.« less

Synthesis and properties of ApU analogues containing 2'-halo-2'-deoxyadenosines. Effects of 2' substituents on oligonucleotide conformation.

PubMed

Uesugi, S; Kaneyasu, T; Ikehara, M

1982-11-09

Five A-U analogues containing deoxyadenosine or 2'-halo-2'-deoxyadenosines, which are known to have widely different C3'-endo conformer populations according to their electronegativities of the halogen substituents, dAfl-U, dAcl-U, dAbr-U, dAio-U, and dA-U, were synthesized chemically. Characterization of these dimers has been performed by UV absorption, circular dichroism, and proton nuclear magnetic resonance spectroscopy. The results show that the dimers containing 2'-halo-2'-deoxyadenosines have stacked conformations with a geometry similar to that of A-U and the degree of stacking decreases in the order dAfl-U greater than dAcl-U greater than dAbr-U greater than dAio-U. dAcl-U is assumed to have the same degree of stacking as A-U. dA-U takes a more stacked conformation than does dAio-U, but the mode of stacking is different from those of the other dimers. The effects of the 2' substituents on dimer conformation are discussed in terms of electronegativity, molecular size, and hydrophobicity.

A novel 2.5D finite difference scheme for simulations of resistivity logging in anisotropic media

NASA Astrophysics Data System (ADS)

Zeng, Shubin; Chen, Fangzhou; Li, Dawei; Chen, Ji; Chen, Jiefu

2018-03-01

The objective of this study is to develop a method to model 3D resistivity well logging problems in 2D formation with anisotropy, known as 2.5D modeling. The traditional 1D forward modeling extensively used in practice lacks the capability of modeling 2D formation. A 2.5D finite difference method (FDM) solving all the electric and magnetic field components simultaneously is proposed. Compared to other previous 2.5D FDM schemes, this method is more straightforward in modeling fully anisotropic media and easy to be implemented. Fourier transform is essential to this FDM scheme, and by employing Gauss-Legendre (GL) quadrature rule the computational time of this step can be greatly reduced. In the numerical examples, we first demonstrate the validity of the FDM scheme with GL rule by comparing with 1D forward modeling for layered anisotropic problems, and then we model a complicated 2D formation case and find that the proposed 2.5D FD scheme is much more efficient than 3D numerical methods.

A survey among Brazilian thoracic surgeons about the use of preoperative 2D and 3D images

PubMed Central

Cipriano, Federico Enrique Garcia; Arcêncio, Livia; Dessotte, Lycio Umeda; Rodrigues, Alfredo José; Vicente, Walter Villela de Andrade

2016-01-01

Background Describe the characteristics of how the thoracic surgeon uses the 2D/3D medical imaging to perform surgical planning, clinical practice and teaching in thoracic surgery and check the initial choice and the final choice of the Brazilian Thoracic surgeon as the 2D and 3D models pictures before and after acquiring theoretical knowledge on the generation, manipulation and interactive 3D views. Methods A descriptive research type Survey cross to data provided by the Brazilian Thoracic Surgeons (members of the Brazilian Society of Thoracic Surgery) who responded to the online questionnaire via the internet on their computers or personal devices. Results Of the 395 invitations visualized distributed by email, 107 surgeons completed the survey. There was no statically difference when comparing the 2D vs. 3D models pictures for the following purposes: diagnosis, assessment of the extent of disease, preoperative surgical planning, and communication among physicians, resident training, and undergraduate medical education. Regarding the type of tomographic image display routinely used in clinical practice (2D or 3D or 2D–3D model image) and the one preferred by the surgeon at the end of the questionnaire. Answers surgeons for exclusive use of 2D images: initial choice =50.47% and preferably end =14.02%. Responses surgeons to use 3D models in combination with 2D images: initial choice =48.60% and preferably end =85.05%. There was a significant change in the final selection of 3D models used together with the 2D images (P<0.0001). Conclusions There is a lack of knowledge of the 3D imaging, as well as the use and interactive manipulation in dedicated 3D applications, with consequent lack of uniformity in the surgical planning based on CT images. These findings certainly confirm in changing the preference of thoracic surgeons of 2D views of technologies for 3D images. PMID:27621874

Master Lovas-Andai and equivalent formulas verifying the 8/33 two-qubit Hilbert-Schmidt separability probability and companion rational-valued conjectures

NASA Astrophysics Data System (ADS)

Slater, Paul B.

2018-04-01

We begin by investigating relationships between two forms of Hilbert-Schmidt two-rebit and two-qubit "separability functions"—those recently advanced by Lovas and Andai (J Phys A Math Theor 50(29):295303, 2017), and those earlier presented by Slater (J Phys A 40(47):14279, 2007). In the Lovas-Andai framework, the independent variable ɛ \\in [0,1] is the ratio σ (V) of the singular values of the 2 × 2 matrix V=D_2^{1/2} D_1^{-1/2} formed from the two 2 × 2 diagonal blocks (D_1, D_2) of a 4 × 4 density matrix D= ||ρ _{ij}||. In the Slater setting, the independent variable μ is the diagonal-entry ratio √{ρ _{11} ρ _ {44}/ρ _ {22 ρ _ {33}}}—with, of central importance, μ =ɛ or μ =1/ɛ when both D_1 and D_2 are themselves diagonal. Lovas and Andai established that their two-rebit "separability function" \\tilde{χ }_1 (ɛ ) (≈ ɛ ) yields the previously conjectured Hilbert-Schmidt separability probability of 29/64. We are able, in the Slater framework (using cylindrical algebraic decompositions [CAD] to enforce positivity constraints), to reproduce this result. Further, we newly find its two-qubit, two-quater[nionic]-bit and "two-octo[nionic]-bit" counterparts, \\tilde{χ _2}(ɛ ) =1/3 ɛ ^2 ( 4-ɛ ^2) , \\tilde{χ _4}(ɛ ) =1/35 ɛ ^4 ( 15 ɛ ^4-64 ɛ ^2+84) and \\tilde{χ _8} (ɛ )= 1/1287ɛ ^8 ( 1155 ɛ ^8-7680 ɛ ^6+20160 ɛ ^4-25088 ɛ ^2+12740) . These immediately lead to predictions of Hilbert-Schmidt separability/PPT-probabilities of 8/33, 26/323 and 44482/4091349, in full agreement with those of the "concise formula" (Slater in J Phys A 46:445302, 2013), and, additionally, of a "specialized induced measure" formula. Then, we find a Lovas-Andai "master formula," \\tilde{χ _d}(ɛ )= ɛ ^d Γ (d+1)^3 _3\\tilde{F}_2( -{d/2,d/2,d;d/2+1,3 d/2+1;ɛ ^2) }/{Γ ( d/2+1) ^2}, encompassing both even and odd values of d. Remarkably, we are able to obtain the \\tilde{χ _d}(ɛ ) formulas, d=1,2,4, applicable to full (9-, 15-, 27-) dimensional sets of density matrices, by analyzing (6-, 9, 15-) dimensional sets, with not only diagonal D_1 and D_2, but also an additional pair of nullified entries. Nullification of a further pair still leads to X-matrices, for which a distinctly different, simple Dyson-index phenomenon is noted. C. Koutschan, then, using his HolonomicFunctions program, develops an order-4 recurrence satisfied by the predictions of the several formulas, establishing their equivalence. A two-qubit separability probability of 1-256/27 π ^2 is obtained based on the operator monotone function √{x}, with the use of \\tilde{χ _2}(ɛ ).

GRID2D/3D: A computer program for generating grid systems in complex-shaped two- and three-dimensional spatial domains. Part 1: Theory and method

NASA Technical Reports Server (NTRS)

Shih, T. I.-P.; Bailey, R. T.; Nguyen, H. L.; Roelke, R. J.

1990-01-01

An efficient computer program, called GRID2D/3D was developed to generate single and composite grid systems within geometrically complex two- and three-dimensional (2- and 3-D) spatial domains that can deform with time. GRID2D/3D generates single grid systems by using algebraic grid generation methods based on transfinite interpolation in which the distribution of grid points within the spatial domain is controlled by stretching functions. All single grid systems generated by GRID2D/3D can have grid lines that are continuous and differentiable everywhere up to the second-order. Also, grid lines can intersect boundaries of the spatial domain orthogonally. GRID2D/3D generates composite grid systems by patching together two or more single grid systems. The patching can be discontinuous or continuous. For continuous composite grid systems, the grid lines are continuous and differentiable everywhere up to the second-order except at interfaces where different single grid systems meet. At interfaces where different single grid systems meet, the grid lines are only differentiable up to the first-order. For 2-D spatial domains, the boundary curves are described by using either cubic or tension spline interpolation. For 3-D spatial domains, the boundary surfaces are described by using either linear Coon's interpolation, bi-hyperbolic spline interpolation, or a new technique referred to as 3-D bi-directional Hermite interpolation. Since grid systems generated by algebraic methods can have grid lines that overlap one another, GRID2D/3D contains a graphics package for evaluating the grid systems generated. With the graphics package, the user can generate grid systems in an interactive manner with the grid generation part of GRID2D/3D. GRID2D/3D is written in FORTRAN 77 and can be run on any IBM PC, XT, or AT compatible computer. In order to use GRID2D/3D on workstations or mainframe computers, some minor modifications must be made in the graphics part of the program; no modifications are needed in the grid generation part of the program. This technical memorandum describes the theory and method used in GRID2D/3D.

Adding a dimension to the infrared spectra of interfaces: 2D SFG spectroscopy via mid-IR pulse shaping

NASA Astrophysics Data System (ADS)

Zanni, Martin

2012-02-01

Sum-frequency generation spectroscopy provides an infrared spectrum of interfaces and thus has widespread use in the materials and chemical sciences. In this presentation, I will present our recent work in developing a 2D pulse sequence to generate 2D SFG spectra of interfaces, in analogy to 2D infrared spectra used to measure bulk species. To develop this spectroscopy, we have utilized many of the tricks-of-the-trade developed in the 2D IR and 2D Vis communities in the last decade, including mid-IR pulse shaping. With mid-IR pulse shaping, the 2D pulse sequence is manipulated by computer programming in the desired frequency resolution, rotating frame, and signal pathway. We believe that 2D SFG will become an important tool in the interfacial sciences in an analogous way that 2D IR is now being used in many disciplines.

Doping-stabilized two-dimensional black phosphorus.

PubMed

Xuan, Xiaoyu; Zhang, Zhuhua; Guo, Wanlin

2018-05-03

Two-dimensional (2D) black phosphorus (BP) has attracted broad interests but remains to be synthesized. One of the issues lies in its large number of 2D allotropes with highly degenerate energies, especially 2D blue phosphorus. Here, we show that both nitrogen and hole-carrier doping can lift the energy degeneracy and locate 2D BP in a deep global energy minimum, while arsenic doping favours the formation of 2D blue phosphorus, attributed to a delicate interplay between s-p overlapping and repulsion of lone pairs. Chemically inert substrates, e.g. graphene and hexagonal boron nitride, can be synergic with carrier doping to stabilize the BP further over other 2D allotropes, while frequently used metal substrates severely reduce the stability of 2D BP. These results not only offer new insight into the structural stability of 2D phosphorus but also suggest a promising pathway towards the chemical synthesis of 2D BP.

Architectural Effects on Impact Resistance of Uncoated MI SiC/SiC Composites

NASA Technical Reports Server (NTRS)

Bhatt, R. T.; Cosgriff, L. M.; Fox, D. S.

2009-01-01

Impact tests were conducted on uncoated 2D and 2.5D MI SiC/SiC composite specimens at room temperature and 1316 C in air. The specimens were analyzed before and after impact using optical microscopy, pulsed thermography (PT) and computed tomography (CT). Preliminary results indicate the following. Both 2-D and 2.5D composites show increase in surface and volumetric damages with increasing impact velocity. However, 2-D composites are prone to delamination cracks. In both 2D and 2.5D composites, the magnitude of impact damage at a fixed impact velocity is slightly greater at room temperature than at 1315 C. At a fixed projectile velocity and test temperature, the depth of penetration of the projectile into the substrate is significantly lower in 2.5D composites than in 2D composites. Fiber architecture plays a significant role controlling impact damage in MI SiC/SiC composites.

Regulating the electrical behaviors of 2D inorganic nanomaterials for energy applications.

PubMed

Feng, Feng; Wu, Junchi; Wu, Changzheng; Xie, Yi

2015-02-11

Recent years have witnessed great developments in inorganic 2D nanomaterials for their unique dimensional confinement and diverse electronic energy bands. Precisely regulating their intrinsic electrical behaviors would bring superior electrical conductivity, rendering 2D nanomaterials ideal candidates for active materials in electrochemical applications when combined with the excellent reaction activity from the inorganic lattice. This Concept focuses on highly conducting inorganic 2D nanomaterials, including intrinsic metallic 2D nanomaterials and artificial highly conductive 2D nanomaterials. The intrinsic metallicity of 2D nanomaterials is derived from their closely packed atomic structures that ensure maximum overlapping of electron orbitals, while artificial highly conductive 2D nanomaterials could be achieved by designed methodologies of surface modification, intralayer ion doping, and lattice strain, in which atomic-scale structural modulation plays a vital role in realizing conducting behaviors. Benefiting from fast electron transfer, high reaction activity, as well as large surface areas arising from the 2D inorganic lattice, highly conducting 2D nanomaterials open up prospects for enhancing performance in electrochemical catalysis and electrochemical capacitors. Conductive 2D inorganic nanomaterials promise higher efficiency for electrochemical applications of energy conversion and storage. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Consequences of daily corticosteroid dosing with or without pre-treatment with quinidine on the in vivo cytochrome P450 2D (CYP2D) enzyme in rats: effect on O-demethylation activity of dextromethorphan and expression levels of CYP2D1 mRNA.

PubMed

Giri, Poonam; Delvadia, Prashant; Gupta, Laxmikant; Patel, Nirmal; Trivedi, Priyal; Lad, Krishna; Patel, Hiren M; Srinivas, Nuggehally R

2018-01-01

1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate. 2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days. 3. Five days repeat dosing of dexamethasone or prednisolone decreased the activity of the rat liver CYP2D by 37% and 34%, at 30 min incubation and decreased CYP2D1 mRNA levels by 62% and 61%, respectively. 4. Pre-treatment of quinidine decreased the enzymatic activity of rat CYP2D by 58% and did not potentiate CYP2D inhibition by corticosteroids. This observation was further complemented by qRT-PCR data. 5. Corticosteroids caused CYP2D inhibition in rats vs. literature evidence of CYP2D induction in human hepatocytes/pregnant humans demonstrating lack of concordance. In vivo inhibition should be factored for interpretation of pharmacokinetic data of CYP2D substrates when treated with corticosteroids in rats.

Crustal shortening and thickening in Neoarchean granite-greenstone belts: A case study from the link between the ∼2.7 Ga Elu and Hope Bay belts, northeast Slave craton, Canada

NASA Astrophysics Data System (ADS)

Mvondo, Hubert; Lentz, Dave; Bardoux, Marc

2017-11-01

The Elu Link between the ∼2.7 Ga Hope Bay and Elu belts in the northeast Bathurst Block of the Slave craton comprises supracrustal and intrusive rocks variably deformed by three tectono-metamorphic events (D1-D3). The geometry of D1 structures formed during prograde metamorphism is uncertain, because of subsequent overprint. D2 occurred in two stages predating (D2a) and postdating (D2b) peak metamorphism. D1 and D2a were thrusting events inferred from peak metamorphic pressures of ∼6.7 kbar (670 MPa) retained by a garnet orthogneiss. The latter is diagnostic of thrust tectonism in Archean granite-greenstone belts with no characteristic thrust faults. Unlike D2a, D2b was a vertical general flattening event prevailing during the formation of magmatic domes and interdomal folds that form the main strain patterns of the belts. This was followed by the formation of buckled F3 folds associated with D3 vertical constriction. The switch from thrust to vertical tectonics during peak metamorphism and subsequent deformation resulted in intense recrystallization that explains the poor preservation and scarcity of early-formed shears, including thrust zones. A tectonic process, combining D1+D2a thrust stacking, sagduction, and vertical stretching during D2b and D3, is suggested to explain crustal thickening in the Elu Link and terrains of similar ages.

Long-range magnetic order in the Heisenberg pyrochlore antiferromagnets G d2G e2O7 and G d2P t2O7 synthesized under high pressure

NASA Astrophysics Data System (ADS)

Li, X.; Cai, Y. Q.; Cui, Q.; Lin, C. J.; Dun, Z. L.; Matsubayashi, K.; Uwatoko, Y.; Sato, Y.; Kawae, T.; Lv, S. J.; Jin, C. Q.; Zhou, J.-S.; Goodenough, J. B.; Zhou, H. D.; Cheng, J.-G.

2016-12-01

G d2S n2O7 and G d2T i2O7 have been regarded as good experimental realizations of the classical Heisenberg pyrochlore antiferromagnet with dipolar interaction. The former was found to adopt the Palmer-Chalker state via a single, first-order transition at TN≈1 K , while the latter enters a distinct, partially ordered state through two successive transitions at TN 1≈1 K and TN 2= 0.75 K . To shed more light on their distinct magnetic ground states, we have synthesized two more gadolinium-based pyrochlore oxides, G d2G e2O7 and G d2P t2O7 , under high-pressure conditions and performed detailed characterizations via x-ray powder diffraction, dc and ac magnetic susceptibility, and specific heat measurements down to 100 mK. We found that both compounds enter a long-range antiferromagnetically ordered state through a single, first-order transition at TN= 1.4 K for G d2G e2O7 and TN= 1.56 K for G d2P t2O7 , with the specific heat anomaly similar to that of G d2S n2O7 rather than G d2T i2O7 . Interestingly, the low-temperature magnetic specific heat values of both G d2G e2O7 and G d2P t2O7 were found to follow nicely the T3 dependence as expected for a three-dimensional antiferromagnet with gapless spin-wave excitations. We have rationalized the enhancement of TN in terms of the reduced Gd-Gd distances for the chemically pressurized G d2G e2O7 and the addition of extra superexchange pathways through the empty Pt -eg orbitals for G d2P t2O7 . Our current study has expanded the family of gadolinium-based pyrochlores and permits us to achieve a better understanding of their distinct magnetic properties in a more comprehensive perspective.

SU-F-T-571: Objective Assessment of 3D Dosimetry for Flattened and Flattened Filter Free Stereotactic Rotational Delivery Using 729-Array Detector with Octavius 4D Phantom

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

Vikraman, S; Arun, C; Jain, K Sandeep

2016-06-15

Purpose: The purpose of this study was to assess the potential of 3D dosimetry for flattened and flattened filter free stereotactic rotational delivery in high definition MLC using 729-detector array with Octavius 4D phantom Methods: Twenty rapid arc plans were assessed for this study. For each patient two plans for 6X and 6FFF photon beams were generated with same prescription and critical organ constraints in Eclipse TPS version 13.0 using high definition MLC. Verification plans were generated in scanned Octavius 4D phantom in TPS. 3D dose measurements were collected from 729-ion chamber detector array in Octavius 4D phantom using verisoftmore » software v 6.0. TPS calculated dose was compared with measured 3D dose in verisoft using the following gamma analysis parameters such as 3D volumetric, 3D planar and 2D global gamma in transverse, sagittal and coronal planes for 3mm/3% and 2mm/2% distance to agreement criteria.Passing rate and arithmetic mean of global gamma were analysed for 2D and 3D global gamma in all planes. Results: The average number of dose points passing rate for 2D global gamma with 3mm/3% criteria in transverse, sagittal and coronal planes was 99.06%±2.89%, 98.8%±0.88% and 99.06%±91%, respectively. For 2mm/2% criteria 97.86%±2.26%, 94.49± 2.64% and 94.34%±2.9% was observed. In 3D planar global gamma with 3mm/3% was 99.53%±0.49%, 98.93%±1.03% and 99.29%±1.29%, for 2mm 2% criteria was 97.50%±2.24%, 94.5%±2.5% and 95.38%±4.5%. The maximum arithmetic mean gamma deviation of 0.505%±0.13% was observed in coronal plane for 2D global gamma with 2mm/2% criteria. The 3D volumetric gamma passing rate was observed as 99.61%±0.433% for 3mm /3% and 95.91%±2.51% for 2mm/2%. Conclusion: The objective assessment of 3D dosimetry have demonstrated that the rotational delivery accuracy for flattened and flattened filter free stereotactic plans can be verified by using Octavius system comprising with 729 ion chamber array and Octavius 4D phantom.« less

Aerial image based die-to-model inspections of advanced technology masks

NASA Astrophysics Data System (ADS)

Kim, Jun; Lei, Wei-Guo; McCall, Joan; Zaatri, Suheil; Penn, Michael; Nagpal, Rajesh; Faivishevsky, Lev; Ben-Yishai, Michael; Danino, Udy; Tam, Aviram; Dassa, Oded; Balasubramanian, Vivek; Shah, Tejas H.; Wagner, Mark; Mangan, Shmoolik

2009-10-01

Die-to-Model (D2M) inspection is an innovative approach to running inspection based on a mask design layout data. The D2M concept takes inspection from the traditional domain of mask pattern to the preferred domain of the wafer aerial image. To achieve this, D2M transforms the mask layout database into a resist plane aerial image, which in turn is compared to the aerial image of the mask, captured by the inspection optics. D2M detection algorithms work similarly to an Aerial D2D (die-to-die) inspection, but instead of comparing a die to another die it is compared to the aerial image model. D2M is used whenever D2D inspection is not practical (e.g., single die) or when a validation of mask conformity to design is needed, i.e., for printed pattern fidelity. D2M is of particular importance for inspection of logic single die masks, where no simplifying assumption of pattern periodicity may be done. The application can tailor the sensitivity to meet the needs at different locations, such as device area, scribe lines and periphery. In this paper we present first test results of the D2M mask inspection application at a mask shop. We describe the methodology of using D2M, and review the practical aspects of the D2M mask inspection.

The Φ43 and Φ63 matricial QFT models have reflection positive two-point function

NASA Astrophysics Data System (ADS)

Grosse, Harald; Sako, Akifumi; Wulkenhaar, Raimar

2018-01-01

We extend our previous work (on D = 2) to give an exact solution of the ΦD3 large- N matrix model (or renormalised Kontsevich model) in D = 4 and D = 6 dimensions. Induction proofs and the difficult combinatorics are unchanged compared with D = 2, but the renormalisation - performed according to Zimmermann - is much more involved. As main result we prove that the Schwinger 2-point function resulting from the ΦD3 -QFT model on Moyal space satisfies, for real coupling constant, reflection positivity in D = 4 and D = 6 dimensions. The Källén-Lehmann mass spectrum of the associated Wightman 2-point function describes a scattering part | p|2 ≥ 2μ2 and an isolated broadened mass shell around | p|2 =μ2.

Comparison Between Digital and Synthetic 2D Mammograms in Breast Density Interpretation.

PubMed

Alshafeiy, Taghreed I; Wadih, Antoine; Nicholson, Brandi T; Rochman, Carrie M; Peppard, Heather R; Patrie, James T; Harvey, Jennifer A

2017-07-01

The purpose of this study was to compare assessments of breast density on synthetic 2D images as compared with digital 2D mammograms. This retrospective study included consecutive women undergoing screening with digital 2D mammography and tomosynthesis during May 2015 with a negative or benign outcome. In separate reading sessions, three radiologists with 5-25 years of clinical experience and 1 year of experience with synthetic 2D mammography read digital 2D and synthetic 2D images and assigned breast density categories according to the 5th edition of BI-RADS. Inter- and intrareader agreement was assessed for each BI-RADS density assessment and combined dense and nondense categories using percent agreement and Cohen kappa coefficient for consensus and all reads. A total of 309 patients met study inclusion criteria. Agreement between consensus BI-RADS density categories assigned for digital and synthetic 2D mammography was 80.3% (95% CI, 75.4-84.5%) with κ = 0.73 (95% CI, 0.66-0.79). For combined dense and nondense categories, agreement reached 91.9% (95% CI, 88.2-94.7%). For consensus readings, similar numbers of patients were shifted between nondense and dense categories (11 and 14, respectively) with the synthetic 2D compared with digital 2D mammography. Interreader differences were apparent; assignment to dense categories was greater with digital 2D mammography for reader 1 (odds ratio [OR], 1.26; p = 0.002), the same for reader 2 (OR, 0.91; p = 0.262), and greater with synthetic 2D mammography for reader 3 (OR, 0.86; p = 0.033). Overall, synthetic 2D mammography is comparable with digital 2D mammography in assessment of breast density, though there is some variability by reader. Practices can readily adopt synthetic 2D mammography without concern that it will affect density assessment and subsequent recommendations for supplemental screening.

Plasmid-mediated bioaugmentation of sequencing batch reactors for enhancement of 2,4-dichlorophenoxyacetic acid removal in wastewater using plasmid pJP4.

PubMed

Tsutsui, Hirofumi; Anami, Yasutaka; Matsuda, Masami; Hashimoto, Kurumi; Inoue, Daisuke; Sei, Kazunari; Soda, Satoshi; Ike, Michihiko

2013-06-01

Plasmid-mediated bioaugmentation was demonstrated using sequencing batch reactors (SBRs) for enhancing 2,4-dichlorophenoxyacetic acid (2,4-D) removal by introducing Cupriavidus necator JMP134 and Escherichia coli HB101 harboring 2,4-D-degrading plasmid pJP4. C. necator JMP134(pJP4) can mineralize and grow on 2,4-D, while E. coli HB101(pJP4) cannot assimilate 2,4-D because it lacks the chromosomal genes to degrade the intermediates. The SBR with C. necator JMP134(pJP4) showed 100 % removal against 200 mg/l of 2,4-D just after its introduction, after which 2,4-D removal dropped to 0 % on day 7 with the decline in viability of the introduced strain. The SBR with E. coli HB101(pJP4) showed low 2,4-D removal, i.e., below 10 %, until day 7. Transconjugant strains of Pseudomonas and Achromobacter isolated on day 7 could not grow on 2,4-D. Both SBRs started removing 2,4-D at 100 % after day 16 with the appearance of 2,4-D-degrading transconjugants belonging to Achromobacter, Burkholderia, Cupriavidus, and Pandoraea. After the influent 2,4-D concentration was increased to 500 mg/l on day 65, the SBR with E. coli HB101(pJP4) maintained stable 2,4-D removal of more than 95 %. Although the SBR with C. necator JMP134(pJP4) showed a temporal depression of 2,4-D removal of 65 % on day 76, almost 100 % removal was achieved thereafter. During this period, transconjugants isolated from both SBRs were mainly Achromobacter with high 2,4-D-degrading capability. In conclusion, plasmid-mediated bioaugmentation can enhance the degradation capability of activated sludge regardless of the survival of introduced strains and their 2,4-D degradation capacity.

Bending Rigidity of 2D Silica.

PubMed

Büchner, C; Eder, S D; Nesse, T; Kuhness, D; Schlexer, P; Pacchioni, G; Manson, J R; Heyde, M; Holst, B; Freund, H-J

2018-06-01

A chemically stable bilayers of SiO_{2} (2D silica) is a new, wide band gap 2D material. Up till now graphene has been the only 2D material where the bending rigidity has been measured. Here we present inelastic helium atom scattering data from 2D silica on Ru(0001) and extract the first bending rigidity, κ, measurements for a nonmonoatomic 2D material of definable thickness. We find a value of κ=8.8  eV±0.5  eV which is of the same order of magnitude as theoretical values in the literature for freestanding crystalline 2D silica.

Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2

PubMed Central

Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; Leavy, O; McNeela, E; Mills, K H G; O'Hagan, D T

2002-01-01

The mucosal adjuvant properties of the three type 2 ribosome-inactivating proteins (RIPs) from the European mistletoe, Viscum album L., were investigated. Mistletoe lectins were compared with cholera toxin (CT) as adjuvants when delivered nasotracheally together with herpes simplex virus glycoprotein D2 (gD2). All three mistletoe lectins (MLI, MLII, MLIII) were potent mucosal adjuvants. Co-administration of MLI, MLII or MLIII with gD2 led to significantly higher levels of gD2-specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) antibody than when the antigen was delivered alone. The levels of antibodies induced were similar to those generated in mice immunized with gD2 and the potent mucosal adjuvant CT. Administration of ML1 with gD2 enhanced the antigen-specific splenic T-cell proliferative response. Interleukin-5 (IL-5), but not interferon-γ (IFN-γ), was detected in supernatants from splenocytes stimulated in vitro with gD2. This indicates that MLI enhanced type 2 T-helper cell (Th2) responses to the bystander antigen, gD2. Analysis of the gD2- and lectin-specific IgG subclass titres in mice immunized with gD2 and MLI, MLII or MLIII revealed a high ratio of IgG1 : IgG2a, which is compatible with the selective induction of Th2-type immune responses. PMID:12383207

Multifunctional Cellular Materials Based on 2D Nanomaterials: Prospects and Challenges.

PubMed

Qiu, Ling; He, Zijun; Li, Dan

2018-01-01

Recent advances in emerging 2D nanomaterial-based cellular materials (2D-CMs) open up new opportunities for the development of next generation cellular solids with exceptional properties. Herein, an overview of the current research status of 2D-CMs is provided and their future opportunities are highlighted. First, the unique features of 2D nanomaterials are introduced to illustrate why these nanoscale building blocks are promising for the development of novel cellular materials and what the new features of 2D nanoscale building blocks can offer when compared to their 0D and 1D counterparts. An in-depth discussion on the structure-property relationships of 2D-CMs is then provided, and the remarkable functions that can be achieved by engineering their cellular architecture are highlighted. Additionally, the use of 2D-CMs to tackle key challenges in different practical applications is demonstrated. In conclusion, a personal perspective on the challenges and future research directions of 2D-CMs is given. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Relationship of Digit Ratio (2D:4D) with Cerebral Lateralization and Grip Strength in Elite Swimmers

ERIC Educational Resources Information Center

Acar, Hakan; Eler, Nebahat

2018-01-01

The index finger and the 4th finger ratio (2D:4D) is the indicator of the prenatal testosterone. The aim of this study is to investigate the relationship between 2D:4D, hand preference and hand grip strength in swimmers. A total of 80 elite swimmers, participated in the study. Height, body weight, body mass index (BMI), hand 2D:4D finger…

Lebbeckoside C, a new triterpenoid saponin from the stem barks of Albizia lebbeck inhibits the growth of human glioblastoma cells.

PubMed

Noté, Olivier Placide; Ngo Mbing, Joséphine; Kilhoffer, Marie-Claude; Pegnyemb, Dieudonné Emmanuel; Lobstein, Annelise

2018-02-19

One new acacic acid-type saponin, named lebbeckoside C (1), was isolated from the stem barks of Albizia lebbeck. Its structure was established on the basis of extensive analysis of 1D and 2D NMR ( 1 H, 13 C NMR, DEPT, COSY, TOCSY, ROESY, HSQC and HMBC) experiments, HRESIMS studies, and by chemical evidence as 3-O-[β-d-xylopyranosyl-(l→2)-β-d-fucopyranosyl-(1→6)-[β-d-glucopyranosyl(1→2)]-β-d-glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(β-d-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(β-d-quinovopyranosyl)octa-2,7-dienoyl]-β-d-quinovopyranosyl}-2,6-dimethylocta-2,7-dienoyl}acacic acid 28 O-[β-d-quinovopyranosyl-(l→3)-[α-l-arabinofuranosyl-(l→4)]-α-l-rhamnopyranosyl-(l→2)-β-d-glucopyranosyl] ester. The isolated saponin (1) displayed significant cytotoxic activity against the human glioblastoma cell line U-87 MG and TG1 stem-like glioma cells isolated from a patient tumor with IC 50 values of 1.69 and 1.44 μM, respectively.

Effects of the Chinese herbal formula "Zuojin Pill" on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.

PubMed

Qiu, Furong; Liu, Songcan; Miao, Ping; Zeng, Jin; Zhu, Leilei; Zhao, TongFang; Ye, Yujie; Jiang, Jian

2016-06-01

Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype. A pharmacokinetics interaction study was carried out in three groups with CYP2D6*1/*1 (n = 6), CYP2D6*1/*10 (n = 6), and CYP2D6*10/*10 (n = 6) genotypes. Each participant received a single oral dose of dextromethorphan (15 mg) followed by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15 mg dextromethorphan in the last day. Blood samples (0-24 h) and urine samples (0-12 h) were collected at baseline and after the administration of Zuojin Pill, and the samples' concentration of dextromethorphan and its main metabolite dextrorphan was determined. Compared to baseline values, co-administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC0-24 of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49∼3.61) and 1.71-fold (1.42∼2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57-fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes, respectively. In contrast, no significant change was observed in these pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype. These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.

SutraPlot, a graphical post-processor for SUTRA, a model for ground-water flow with solute or energy transport

USGS Publications Warehouse

Souza, W.R.

1999-01-01

This report documents a graphical display post-processor (SutraPlot) for the U.S. Geological Survey Saturated-Unsaturated flow and solute or energy TRAnsport simulation model SUTRA, Version 2D3D.1. This version of SutraPlot is an upgrade to SutraPlot for the 2D-only SUTRA model (Souza, 1987). It has been modified to add 3D functionality, a graphical user interface (GUI), and enhanced graphic output options. Graphical options for 2D SUTRA (2-dimension) simulations include: drawing the 2D finite-element mesh, mesh boundary, and velocity vectors; plots of contours for pressure, saturation, concentration, and temperature within the model region; 2D finite-element based gridding and interpolation; and 2D gridded data export files. Graphical options for 3D SUTRA (3-dimension) simulations include: drawing the 3D finite-element mesh; plots of contours for pressure, saturation, concentration, and temperature in 2D sections of the 3D model region; 3D finite-element based gridding and interpolation; drawing selected regions of velocity vectors (projected on principal coordinate planes); and 3D gridded data export files. Installation instructions and a description of all graphic options are presented. A sample SUTRA problem is described and three step-by-step SutraPlot applications are provided. In addition, the methodology and numerical algorithms for the 2D and 3D finite-element based gridding and interpolation, developed for SutraPlot, are described. 1

Correlation analysis between 2D and quasi-3D gamma evaluations for both intensity-modulated radiation therapy and volumetric modulated arc therapy

PubMed Central

Kim, Jung-in; Choi, Chang Heon; Wu, Hong-Gyun; Kim, Jin Ho; Kim, Kyubo; Park, Jong Min

2017-01-01

The aim of this work was to investigate correlations between 2D and quasi-3D gamma passing rates. A total of 20 patients (10 prostate cases and 10 head and neck cases, H&N) were retrospectively selected. For each patient, both intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. For each plan, 2D gamma evaluation with radiochromic films and quasi-3D gamma evaluation with fluence measurements were performed with both 2%/2 mm and 3%/3 mm criteria. Gamma passing rates were grouped together according to delivery techniques and treatment sites. Statistical analyses were performed to examine the correlation between 2D and quasi-3D gamma evaluations. Statistically significant difference was observed between delivery techniques only in the quasi-3D gamma passing rates with 2%/2 mm. Statistically significant differences were observed between treatment sites in the 2D gamma passing rates (differences of less than 8%). No statistically significant correlations were observed between 2D and quasi-3D gamma passing rates except the VMAT group and the group including both IMRT and VMAT with 3%/3 mm (r = 0.564 with p = 0.012 for theVMAT group and r = 0.372 with p = 0.020 for the group including both IMRT and VMAT), however, those were not strong. No strong correlations were observed between 2D and quasi-3D gamma evaluations. PMID:27690300

Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation.

PubMed

Soares-Cunha, Carina; Coimbra, Bárbara; Domingues, Ana Verónica; Vasconcelos, Nivaldo; Sousa, Nuno; Rodrigues, Ana João

2018-01-01

The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement. To answer this question, in this work we combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, we showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. We demonstrated that this behavioral effect relies on cholinergic-dependent modulation of dopaminergic signalling of ventral tegmental area (VTA) terminals, which requires D1R and D2R signalling in the NAc. D2-MSN optogenetic activation decreased ventral pallidum (VP) activity, reducing the inhibitory tone to VTA, leading to increased dopaminergic activity. Importantly, optogenetic activation of D2-MSN terminals in the VP was sufficient to recapitulate the motivation enhancement. In summary, our data suggests that optogenetic stimulation of NAc D2-MSNs indirectly modulates VTA dopaminergic activity, contributing for increased motivation. Moreover, both types of dopamine receptors signalling in the NAc are required in order to produce the positive behavioral effects.

Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation

PubMed Central

Soares-Cunha, Carina; Coimbra, Bárbara; Domingues, Ana Verónica; Vasconcelos, Nivaldo; Sousa, Nuno

2018-01-01

Abstract The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement. To answer this question, in this work we combined optogenetic modulation of D2-MSNs with in loco pharmacological delivery of specific neurotransmitter antagonists in rats. First, we showed that optogenetic activation of D2-MSNs increases motivation in a progressive ratio (PR) task. We demonstrated that this behavioral effect relies on cholinergic-dependent modulation of dopaminergic signalling of ventral tegmental area (VTA) terminals, which requires D1R and D2R signalling in the NAc. D2-MSN optogenetic activation decreased ventral pallidum (VP) activity, reducing the inhibitory tone to VTA, leading to increased dopaminergic activity. Importantly, optogenetic activation of D2-MSN terminals in the VP was sufficient to recapitulate the motivation enhancement. In summary, our data suggests that optogenetic stimulation of NAc D2-MSNs indirectly modulates VTA dopaminergic activity, contributing for increased motivation. Moreover, both types of dopamine receptors signalling in the NAc are required in order to produce the positive behavioral effects. PMID:29780881

Functional Fast Scan Cyclic Voltammetry Assay to Characterize Dopamine D2 and D3 Autoreceptors in the Mouse Striatum

PubMed Central

2010-01-01

Dopamine D2 and D3 autoreceptors are located on presynaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate putamen and nucleus accumbens core and shell. The dopamine D2 agonists (−)-quinpirole hydrochloride and 5,6,7,8-tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate putamen and nucleus accumbens (core and shell) on the basis of their EC50 values and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (±)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in the caudate putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.1 μM lowered the uptake rate in caudate putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the preagonist dopamine release concentration. Finally, these results demonstrate a functional voltammetric assay that characterizes dopamine D2-like agonists as either D2- or D3-preferring agonists by taking advantage of the unique receptor density within the striatum. PMID:20567609

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

PubMed Central

Zhao, Wei; Rasheed, Asif; Tikkanen, Emmi; Lee, Jung-Jin; Butterworth, Adam S; Howson, Joanna MM; Assimes, Themistocles L; Chowdhury, Rajiv; Orho-Melander, Marju; Damrauer, Scott; Small, Aeron; Asma, Senay; Imamura, Minako; Yamauch, Toshimasa; Chambers, John C; Chen, Peng; Sapkota, Bishwa R; Shah, Nabi; Jabeen, Sehrish; Surendran, Praveen; Lu, Yingchang; Zhang, Weihua; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Trindade, Kevin; Qamar, Nadeem; Mallick, Nadeem Hayyat; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Rasheed, Syed Zahed; Memon, Fazal-ur-Rehman; Mehmood, Khalid; Ahmed, Naveeduddin; Qureshi, Irshad Hussain; Tanveer-us-Salam; Iqbal, Wasim; Malik, Uzma; Mehra, Narinder; Kuo, Jane Z; Sheu, Wayne H-H; Guo, Xiuqing; Hsiung, Chao A; Juang, Jyh-Ming J; Taylor, Kent D; Hung, Yi-Jen; Lee, Wen-Jane; Quertermous, Thomas; Lee, I-Te; Hsu, Chih-Cheng; Bottinger, Erwin P.; Ralhan, Sarju; Teo, Yik Ying; Wang, Tzung-Dau; Alam, Dewan S; Di Angelantonio, Emanuele; Epstein, Steve; Nielsen, Sune F; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne; Young, Robin; Benn, Marianne; Frikke-Schmidt, Ruth; Kamstrup, Pia R; Biobank, Michigan; Jukema, J Wouter; Sattar, Naveed; Smit, Roelof; Chung, Ren-Hua; Liang, Kae-Woei; Anand, Sonia; Sanghera, Dharambir K; Ripatti, Samuli; Loos, Ruth J.F.; Kooner, Jaspal S; Tai, E Shyong; Rotter, Jerome I; Chen, Yii-Der Ida; Frossard, Philippe; Maeda, Shiro; Kadowaki, Takashi; Reilly, Muredach; Pare, Guillaume; Melander, Olle; Salomaa, Veikko; Rader, Daniel J; Danesh, John; Voight, Benjamin F; Saleheen, Danish

2018-01-01

To evaluate the shared genetic etiology of type-2 diabetes (T2D) and coronary heart disease (CHD), we conducted a multi-ethnic study of genetic variation genome-wide for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and one for CHD, including a novel T2D association at a missense variant in HLA-DRB5 (OR=1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint analysis of T2D loci demonstrated that 24% are associated with CHD, highlighting eight variants - two of which are coding - where T2D and CHD associations appear to co-localize, and a novel joint T2D/CHD association which also replicated for T2D. Variants associated with both outcomes implicate several novel pathways including cellular proliferation and cardiovascular development. PMID:28869590

Enhanced Diagnostic Capability for Glaucoma of 3-Dimensional versus 2-Dimensional Neuroretinal Rim Parameters Using Spectral Domain Optical Coherence Tomography

PubMed Central

Fan, Kenneth Chen; Tsikata, Edem; Khoueir, Ziad; Simavli, Huseyin; Guo, Rong; DeLuna, Regina; Pandit, Sumir; Que, Christian John; de Boer, Johannes F.; Chen, Teresa C.

2017-01-01

Purpose To compare the diagnostic capability of 3-dimensional (3D) neuroretinal rim parameters with existing 2-dimensional (2D) neuroretinal and retinal nerve fiber layer (RNFL) thickness rim parameters using spectral domain optical coherence tomography (SD-OCT) volume scans Materials and Methods Design Institutional prospective pilot study. Study population 65 subjects (35 open angle glaucoma patients, 30 normal patients). Observation procedures One eye of each subject was included. SD-OCT was used to obtain 2D retinal nerve fiber layer (RNFL) thickness values and five neuroretinal rim parameters [i.e. 3D minimum distance band (MDB) thickness, 3D Bruch’s membrane opening-minimum rim width (BMO-MRW), 3D rim volume, 2D rim area, and 2D rim thickness]. Main outcome measures Area under the receiver operating characteristic (AUROC) curve values, sensitivity, specificity. Results Comparing all 3D with all 2D parameters, 3D rim parameters (MDB, BMO-MRW, rim volume) generally had higher AUROC curve values (range 0.770–0.946) compared to 2D parameters (RNFL thickness, rim area, rim thickness; range 0.678–0.911). For global region analyses, all 3D rim parameters (BMO-MRW, rim volume, MDB) were equal to or better than 2D parameters (RNFL thickness, rim area, rim thickness; p-values from 0.023–1.0). Among the three 3D rim parameters (MDB, BMO-MRW, and rim volume), there were no significant differences in diagnostic capability (false discovery rate > 0.05 at 95% specificity). Conclusion 3D neuroretinal rim parameters (MDB, BMO-MRW, and rim volume) demonstrated better diagnostic capability for primary and secondary open angle glaucomas compared to 2D neuroretinal parameters (rim area, rim thickness). Compared to 2D RNFL thickness, 3D neuroretinal rim parameters have the same or better diagnostic capability. PMID:28234677

Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO.

PubMed

Girgis, Ragy R; Slifstein, Mark; D'Souza, Deepak; Lee, Yih; Periclou, Antonia; Ghahramani, Parviz; Laszlovszky, István; Durgam, Suresh; Adham, Nika; Nabulsi, Nabeel; Huang, Yiyun; Carson, Richard E; Kiss, Béla; Kapás, Margit; Abi-Dargham, Anissa; Rakhit, Ashok

2016-10-01

Second-generation antipsychotics occupy dopamine D2 receptors and act as antagonists or partial agonists at these receptors. While these drugs alleviate positive symptoms in patients with schizophrenia, they are less effective for treating cognitive deficits and negative symptoms. Dopamine D3 receptors are highly expressed in areas of the brain thought to play a role in the regulation of motivation and reward-related behavior. Consequently, the dopamine D3 receptor has become a target for treating negative symptoms in combination with D2 antagonism to treat positive symptoms in patients with schizophrenia. The purpose of this study was to determine the cariprazine receptor occupancies in brain for D2 and D3 receptors in patients with schizophrenia. Using [(11)C]-(+)-PHNO as a radioligand, positron emission tomography (PET) scans were performed in eight patients at baseline and postdose on days 1, 4, and 15. Plasma and cerebrospinal fluid (CSF) samples were analyzed for cariprazine concentrations. A monotonic dose-occupancy relationship was observed for both receptor types. After 2 weeks of treatment, near complete (∼100 %) occupancies were observed for both receptors at a dose of 12 mg/day. At the lowest cariprazine dose (1 mg/day), mean D3 and D2 receptor occupancies were 76 and 45 %, respectively, suggesting selectivity for D3 over D2 receptors at low doses. An exposure-response analysis found a ∼3-fold difference in EC50 (D3 = 3.84 nM and D2 = 13.03 nM) in plasma after 2 weeks of dosing. This PET imaging study in patients with schizophrenia demonstrated that cariprazine is a D3-preferring dual D3/D2 receptor partial agonist.

Factors that control catalytic two- versus four-electron reduction of dioxygen by copper complexes.

PubMed

Fukuzumi, Shunichi; Tahsini, Laleh; Lee, Yong-Min; Ohkubo, Kei; Nam, Wonwoo; Karlin, Kenneth D

2012-04-25

The selective two-electron reduction of O(2) by one-electron reductants such as decamethylferrocene (Fc*) and octamethylferrocene (Me(8)Fc) is efficiently catalyzed by a binuclear Cu(II) complex [Cu(II)(2)(LO)(OH)](2+) (D1) {LO is a binucleating ligand with copper-bridging phenolate moiety} in the presence of trifluoroacetic acid (HOTF) in acetone. The protonation of the hydroxide group of [Cu(II)(2)(LO)(OH)](2+) with HOTF to produce [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF) makes it possible for this to be reduced by 2 equiv of Fc* via a two-step electron-transfer sequence. Reactions of the fully reduced complex [Cu(I)(2)(LO)](+) (D3) with O(2) in the presence of HOTF led to the low-temperature detection of the absorption spectra due to the peroxo complex [Cu(II)(2)(LO)(OO)] (D) and the protonated hydroperoxo complex [Cu(II)(2)(LO)(OOH)](2+) (D4). No further Fc* reduction of D4 occurs, and it is instead further protonated by HOTF to yield H(2)O(2) accompanied by regeneration of [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF), thus completing the catalytic cycle for the two-electron reduction of O(2) by Fc*. Kinetic studies on the formation of Fc*(+) under catalytic conditions as well as for separate examination of the electron transfer from Fc* to D1-OTF reveal there are two important reaction pathways operating. One is a rate-determining second reduction of D1-OTF, thus electron transfer from Fc* to a mixed-valent intermediate [Cu(II)Cu(I)(LO)](2+) (D2), which leads to [Cu(I)(2)(LO)](+) that is coupled with O(2) binding to produce [Cu(II)(2)(LO)(OO)](+) (D). The other involves direct reaction of O(2) with the mixed-valent compound D2 followed by rapid Fc* reduction of a putative superoxo-dicopper(II) species thus formed, producing D.

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites.

PubMed

Byeon, Ji-Yeong; Kim, Young-Hoon; Na, Han-Sung; Jang, Jong-Hwa; Kim, Se-Hyung; Lee, Yun-Jeong; Bae, Jung-Woo; Kim, In Su; Jang, Choon-Gon; Chung, Myeon-Woo; Lee, Seok-Yong

2015-11-01

To investigate the effect of the variant CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites, 4-hydroxyatomoxetine (4-HAT) and N-desmethylatomoxetine (NAT), in healthy subjects, a single oral dose of atomoxetine was administered to 62 subjects with a CYP2D6*wt/*wt (*wt = *1 or *2, n = 22), CYP2D6*wt/*10 (n = 22) or CYP2D6*10/*10 (n = 18) genotype. Plasma samples were then collected for 24 h after atomoxetine administration. The concentrations of atomoxetine and its metabolites were assayed using LC-MS/MS. For atomoxetine, the Cmax, AUC0-∞, t1/2 and CL/F showed genotype-dependent differences. The CYP2D6*10/*10 and CYP2D6*wt/*10 groups showed 1.74- and 1.15-fold higher Cmax, 3.40- and 1.33-fold higher AUC0-∞, and 69.7 and 24.6 % lower CL/F, compared to those of the CYP2D6*wt/*wt group, respectively. The Cmax and t1/2 for 4-HAT were lower and longer in the CYP2D6*10/*10 group than those in the CYP2D6*wt/*wt group, but the AUC0-∞ was not different between these groups. The Cmax, AUC0-∞ and t1/2 for NAT were profoundly greater in the CYP2D6*10/*10 group than they were in the CYP2D6*wt/*wt group. The concentration of active moieties of atomoxetine (atomoxetine + 4-HAT) in the CYP2D6*10/*10 group was 3.32-fold higher than that in the CYP2D6*wt/*wt group. The mean exposure to active moieties of atomoxetine was markedly higher in subjects with the CYP2D6*10/*10 genotype compared to that in those with the CYP2D6*wt/*wt genotype. The higher systemic exposure of the active atomoxetine moieties in CYP2D6*10/*10 individuals may increase the risk of concentration-related adverse events of atomoxetine, although this has not yet been clinically confirmed.

Overexpression of IL-10 in C2D macrophages promotes a macrophage phenotypic switch in adipose tissue environments.

PubMed

Xie, Linglin; Fu, Qiang; Ortega, Teresa M; Zhou, Lun; Rasmussen, Dane; O'Keefe, Jacy; Zhang, Ke K; Chapes, Stephen K

2014-01-01

Adipose tissue macrophages are a heterogeneous collection of classically activated (M1) and alternatively activated (M2) macrophages. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, secreted by a variety of cell types including M2 macrophages. We generated a macrophage cell line stably overexpressing IL-10 (C2D-IL10) and analyzed the C2D-IL10 cells for several macrophage markers after exposure to adipocytes compared to C2D cells transfected with an empty vector (C2D-vector). C2D-IL10 macrophage cells expressed more CD206 when co-cultured with adipocytes than C2D-vector cells; while the co-cultured cell mixture also expressed higher levels of Il4, Il10, Il1β and Tnf. Since regular C2D cells traffic to adipose tissue after adoptive transfer, we explored the impact of constitutive IL-10 expression on C2D-IL10 macrophages in adipose tissue in vivo. Adipose tissue-isolated C2D-IL10 cells increased the percentage of CD206(+), CD301(+), CD11c(-)CD206(+) (M2) and CD11c(+)CD206(+) (M1b) on their cell surface, compared to isolated C2D-vector cells. These data suggest that the expression of IL-10 remains stable, alters the C2D-IL10 macrophage cell surface phenotype and may play a role in regulating macrophage interactions with the adipose tissue.

76 FR 70046 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

... Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and AS355E, F, F1, F2, N... France (Eurocopter) Model AS350B, B1, B2, B3, BA, C, D, and D1 helicopters; and Model AS355E, F, F1, F2... (AD 2003- 22-06), for Eurocopter Model AS350B, B1, B2, B3, BA, C, D, and D1; and Model AS355E, F, F1...

Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity.

PubMed

Farber, Nuri B; Nemmers, Brian; Noguchi, Kevin K

2006-09-15

Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor, most likely by producing disinhibtion in complex circuits, acutely produce psychosis and cognitive disturbances in humans, and neurotoxicity in rodents. Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals, therefore, may provide insights into the pathophysiology of psychotic disorders. Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks, suggesting involvement of these transmitter system(s). We studied the ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both after a one-time acute exposure and after chronic daily exposure. Here we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo neurotoxicity when given acutely. The protective effect with D2/D3 agonists is not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However, after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo neurotoxicity with longer durations producing greater protection. Understanding the changes that occur in the NRHypo circuit after chronic exposure to dopaminergic agents could provide important clues into the pathophysiology of psychotic disorders.

Insilico study of the A(2A)R-D (2)R kinetics and interfacial contact surface for heteromerization.

PubMed

Prakash, Amresh; Luthra, Pratibha Mehta

2012-10-01

G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor-receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A(2A)R-D(2)R interactions was carried to acquire the understanding of the A(2A)R-D(2)R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson's disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K (off), K (on), and K (d)) of A(2A)R-D(2)R interactions. The results demonstrated the correlation coefficient 0.294 for K (d) and K (on) and the correlation coefficient 0.635 for K (d) and K (off), and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A(2A)R and intracellular loops (ICLs) of D(2)R led to the formation of interfacial contacts between A(2A)R-D(2)R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A(2A)R-D(2)R contact interfaces as dimer. The propensity of amino acid residues involved in A(2A)R-D(2)R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A(2A)R and D(2)R at interface of dimer contact. Essentially, in silico structural and dynamic study of A(2A)R-D(2)R interactions will provide the basic understanding of the A(2A)R-D(2)R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein-protein interactions in receptor assimilations.

Simultaneous quantitative analysis of eight vitamin D analogues in milk using liquid chromatography-tandem mass spectrometry.

PubMed

Gomes, Fabio P; Shaw, P Nicholas; Whitfield, Karen; Hewavitharana, Amitha K

2015-09-03

Milk is an important source of nutrients for various risk populations, including infants. The accurate measurement of vitamin D in milk is necessary to provide adequate supplementation advice for risk groups and to monitor regulatory compliance. Currently used liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods are capable of measuring only four analogues of vitamin D in unfortified milk. We report here an accurate quantitative analytical method for eight analogues of vitamin D: Vitamin D2 and D3 (D2 and D3), 25-hydroxy D2 and D3, 24,25-dihydroxy D2 and D3, and 1,25-dihydroxyD2 and D3. In this study, we compared saponification and protein precipitation for the extraction of vitamin D from milk and found the latter to be more effective. We also optimised the pre-column derivatisation using 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD), to achieve the highest sensitivity and accuracy for all major vitamin D forms in milk. Chromatography was optimised to reduce matrix effects such as ion-suppression, and the matrix effects were eliminated using co-eluting stable isotope labelled internal standards for the calibration of each analogue. The analogues, 25-hydroxyD3 (25(OH)D3) and its epimer (3-epi-25(OH)D3) were chromatographically resolved, to prevent over-estimation of 25(OH)D3. The method was validated and subsequently applied for the measurement of total vitamin D levels in human, cow, mare, goat and sheep milk samples. The detection limits, repeatability standard deviations, and recovery ranges were from 0.2 to 0.4 femtomols, 6.30-13.5%, and 88.2-105%, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Shinde, Subhash L.; Teifel, John; Flores, Richard S.

A 3D stacked sASIC is provided that includes a plurality of 2D reconfigurable structured structured ASIC (sASIC) levels interconnected through hard-wired arrays of 3D vias. The 2D sASIC levels may contain logic, memory, analog functions, and device input/output pad circuitry. During fabrication, these 2D sASIC levels are stacked on top of each other and fused together with 3D metal vias. Such 3D vias may be fabricated as through-silicon vias (TSVs). They may connect to the back-side of the 2D sASIC level, or they may be connected to top metal pads on the front-side of the 2D sASIC level.

Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis.

PubMed

Graeff-Armas, Laura A; Kaufmann, Martin; Lyden, Elizabeth; Jones, Glenville

2018-06-01

While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D 2 and Vitamin D 3 is becoming increasingly common in these patients, little is known about 24,25(OH) 2 D 3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH) 2 D 3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH) 2 D 3 levels from three controlled trials of Vitamin D 2 and Vitamin D 3 supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis. 680 samples from three controlled trials of Vitamin D 2 or Vitamin D 3 supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D 3 , or 50,000 IU Vitamin D 2 , or weekly doses of 10,000 IU or 20,000 IU Vitamin D 3 . Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH) 2 D 3 levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time. The subjects given Vitamin D 3 had significant increases in 25(OH)D levels. Serum 24,25(OH) 2 D 3 levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH) 2 D 3 in healthy populations. We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Condition Based Maintenance Technology Impacts Study for the Military Land Environment

DTIC Science & Technology

2014-08-01

3a, 2g 3b,3m,3j,3e,3d,3f,3a,3c,3i 3c,3d,3h,3n 3d,3h 3e,3k,3i 3f,3h UNCLASSIFIED DSTO-RR-0404 UNCLASSIFIED 158 3g ,3c 3h,4b 3i,3m,3j,CBM...3e -> 3k 3i Egress of 2: 3n -> 3h 4b Egress of 2: 3k -> 3j 5c Egress of 2: 4d -> 3g 3c Egress of 1: 3a -> 2g Egress of 1: 1b -> 2g Egress...Ingress+Egress of 8: 2d 3b 3g 4d 4f -> 3c -> 3d 3h 3n Ingress+Egress of 7: 1b 2e 3a -> 2g -> 3b 2e 2c 2f Ingress+Egress of 7: 2a 2d 6b 6c -> 2b -> 3a

In vitro pharmacology of aripiprazole, its metabolite and experimental dopamine partial agonists at human dopamine D2 and D3 receptors.

PubMed

Tadori, Yoshihiro; Forbes, Robert A; McQuade, Robert D; Kikuchi, Tetsuro

2011-10-15

Aripiprazole is the first dopamine D(2)/D(3) receptor partial agonist successfully developed and ultimately approved for treatment of a broad spectrum of psychiatric and neurological disorders. Aripiprazole's dopamine D(2) and serotonin 5-HT(1A) receptor partial agonist activities have been postulated to confer clinical efficacy without marked sedation, and a relatively favorable overall side-effect profile. Using aripiprazole's unique profile as a benchmark for new dopamine partial agonist development may facilitate discovery of new antipsychotics. We conducted an in vitro comparative analysis between aripiprazole, and its human metabolite OPC-14857 (7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl)butoxy)-2(1H)-quinolinone)); RGH-188 (trans-1-[4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl]-3,3-dimethylurea), and its metabolite didesmethyl-RGH-188 (DDM-RGH-188); as well as bifeprunox, sarizotan, N-desmethylclozapine (NDMC; clozapine metabolite), and SDZ 208-912 (N-[(8α)-2-chloro-6-methylergolin-8-yl]-2,2-dimethylpropanamide). In vitro pharmacological assessment included inhibition of forskolin-stimulated cAMP accumulation and the reversal of dopamine-induced inhibition in clonal Chinese hamster ovary cell lines expressing D(2S), D(2L), D(3) Ser-9 and D(3) Gly-9 for human dopamine receptors. All test compounds behaved as dopamine D(2)/D(3) receptor partial agonists. Aripiprazole's intrinsic activity at dopamine D(2S) and D(2L) receptors was similar to that of OPC-14857 and RGH-188; lower than that of dopamine and bifeprunox; and higher than that of DDM-RGH-188, SDZ 208-912, sarizotan, and NDMC. Aripiprazole's intrinsic activity at dopamine D(3) Ser-9 and D(3) Gly-9 receptors was similar to that of OPC-14857 and sarizotan; lower than that of dopamine, bifeprunox, RGH-188 and DDM-RGH-188; and higher than that of SDZ 208-912 and NDMC. A consolidated assessment of these findings may help defining the most appropriate magnitude of intrinsic activity at dopamine D(2)/D(3) receptors for clinical efficacy and safety. Copyright © 2011 Elsevier B.V. All rights reserved.

Discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers.

PubMed

Kemnitzer, William; Sirisoma, Nilantha; May, Chris; Tseng, Ben; Drewe, John; Cai, Sui Xiong

2009-07-01

We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylthieno[2,3-d]pyrimidines as potent apoptosis inducers. Compounds 5d and 5e were the most potent with EC(50) values of 0.008 and 0.004microM in T47D human breast cancer cells, respectively. Compound 5d was found to be highly active in the MX-1 breast cancer model. Functionally, compounds 5d and 5e both induced apoptosis through inhibition of tubulin polymerization.

Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

PubMed Central

Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

2016-01-01

Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

Effects of D-glucose upon D-fructose metabolism in rat hepatocytes: A 13C NMR study.

PubMed

Malaisse, W J; Ladrière, L; Verbruggen, I; Willem, R

2002-12-01

Isolated hepatocytes from fed rats were exposed for 120 min to D-glucose (10 mM) and either D-[1-13C]fructose, D-[2-13C]fructose or D-[6-13C]fructose (also 10 mM) in the presence of D2O. The identification and quantification of 13C-enriched D-fructose and its metabolites (D-glucose, L-lactate, L-alanine) in the incubation medium and the measurement of their deuterated isotopomers indicated, by comparison with a prior study conducted in the absence of exogenous D-glucose, that the major effects of the aldohexose were to increase the recovery of 13C-enriched D-fructose, decrease the production of 13C-enriched D-glucose, restrict the deuteration of the 13C-enriched isotopomers of D-glucose to those generated by cells exposed to D-[2-13C]fructose, and to accentuate the lesser deuteration of the C, (as compared to C5) of 13C-enriched D-glucose derived from D-[2-13C]fructose. The ratio between C2-deuterated and C2-hydrogenated L-lactate, as well as the relative amounts of the CH3-, CH2D-, CHD, and CD3- isotopomers of 13C-enriched L-lactate were not significantly different, however, in the absence or presence of exogenous D-glucose. These findings indicate that exogenous D-glucose suppressed the deuteration of the C1 of D-[I-13C]glucose generated by hepatocytes exposed to D-[1-13C]fructose or D-[6-13C]fructose, as otherwise attributable, in part at least, to gluconeogenesis from fructose-derived [3-13C]pyruvate, and apparently favoured the phosphorylation of D-fructose by hexokinase isoenzymes, probably through stimulation of D-fructose phosphorylation by glucokinase.

2-D Path Corrections for Local and Regional Coda Waves: A Test of Transportability

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

Mayeda, K M; Malagnini, L; Phillips, W S

2005-07-13

Reliable estimates of the seismic source spectrum are necessary for accurate magnitude, yield, and energy estimation. In particular, how seismic radiated energy scales with increasing earthquake size has been the focus of recent debate within the community and has direct implications on earthquake source physics studies as well as hazard mitigation. The 1-D coda methodology of Mayeda et al. [2003] has provided the lowest variance estimate of the source spectrum when compared against traditional approaches that use direct S-waves, thus making it ideal for networks that have sparse station distribution. The 1-D coda methodology has been mostly confined to regionsmore » of approximately uniform complexity. For larger, more geophysically complicated regions, 2-D path corrections may be required. We will compare performance of 1-D versus 2-D path corrections in a variety of regions. First, the complicated tectonics of the northern California region coupled with high quality broadband seismic data provides for an ideal ''apples-to-apples'' test of 1-D and 2-D path assumptions on direct waves and their coda. Next, we will compare results for the Italian Alps using high frequency data from the University of Genoa. For Northern California, we used the same station and event distribution and compared 1-D and 2-D path corrections and observed the following results: (1) 1-D coda results reduced the amplitude variance relative to direct S-waves by roughly a factor of 8 (800%); (2) Applying a 2-D correction to the coda resulted in up to 40% variance reduction from the 1-D coda results; (3) 2-D direct S-wave results, though better than 1-D direct waves, were significantly worse than the 1-D coda. We found that coda-based moment-rate source spectra derived from the 2-D approach were essentially identical to those from the 1-D approach for frequencies less than {approx}0.7-Hz, however for the high frequencies (0.7 {le} f {le} 8.0-Hz), the 2-D approach resulted in inter-station scatter that was generally 10-30% smaller. For complex regions where data are plentiful, a 2-D approach can significantly improve upon the simple 1-D assumption. In regions where only 1-D coda correction is available it is still preferable over 2-D direct wave-based measures.« less

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

2D Ruddlesden-Popper Perovskites for Optoelectronics.

PubMed

Chen, Yani; Sun, Yong; Peng, Jiajun; Tang, Junhui; Zheng, Kaibo; Liang, Ziqi

2018-01-01

Conventional 3D organic-inorganic halide perovskites have recently undergone unprecedented rapid development. Yet, their inherent instabilities over moisture, light, and heat remain a crucial challenge prior to the realization of commercialization. By contrast, the emerging 2D Ruddlesden-Popper-type perovskites have recently attracted increasing attention owing to their great environmental stability. However, the research of 2D perovskites is just in their infancy. In comparison to 3D analogues, they are natural quantum wells with a much larger exciton binding energy. Moreover, their inner structural, dielectric, optical, and excitonic properties remain to be largely explored, limiting further applications. This review begins with an introduction to 2D perovskites, along with a detailed comparison to 3D counterparts. Then, a discussion of the organic spacer cation engineering of 2D perovskites is presented. Next, quasi-2D perovskites that fall between 3D and 2D perovskites are reviewed and compared. The unique excitonic properties, electron-phonon coupling, and polarons of 2D perovskites are then be revealed. A range of their (opto)electronic applications is highlighted in each section. Finally, a summary is given, and the strategies toward structural design, growth control, and photophysics studies of 2D perovskites for high-performance electronic devices are rationalized. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physical Fitness And Digit Ratio (2D:4D) In Male Students From Wrocław, Poland.

PubMed

Koziel, Slawomir; Kociuba Mail, Marek; Chakraborty, Raja; Ignasiak, Zofia

2017-03-01

There is sex-difference in humans as regards aerobic efficiency, physical strength and endurance and the sex difference is greatly dependent upon differential concentration of testosterone during different phases of growth and development including the intrauterine phase or prenatal growth. Second-to-fourth digit lengths ratio (2D:4D) is an putative indicator of prenatal testosterone exposure. Lower 2D:4D indicates higher prenatal testosterone exposure and vice versa. Males generally have lower 2D:4D than females. This cross-sectional study investigated the relationship between the fitness measures and 2D:4D in young adult Polish males. The study included 118 Polish male students first course in General Kościuszko Military Academy of Land Forces in Wroclaw. Their mean (+SD) age was 20.4 (+1.60) years. Eurofit test set was employed to assess physical fitness. Apart from height, weight, second and fourth digit lengths, hand grip strength was also measured by a standard isometric dynamometer. The study showed a weak relationship between 2D:4D of right hand and results of physical fitness tests. The smaller was the 2D:4D, the better was the result of endurance and strength tests. This finding was in accord with reports by other studies, indicating that individuals with smaller 2D:4D tend to perform better in these aspects of physical ability. However, we also found an opposite relationship with the results to agility tests. Male students with higher 2D:4D scored better in 5x10 meters shuttle run. This finding did not match with results reported by other studies. This study indicated towards possibility that an association between low 2D:4D and sport and athletic achievement and also physical performances were due to, at least in part, the action of prenatal testosterone. Further studies are required to investigate the relationship of fitness parameters with digit ratio and ultimately with prenatal testosterone exposure.

Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells

PubMed Central

Jensen, Helle; Folkersen, Lasse; Skov, Søren

2012-01-01

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression. PMID:22870231

Expression levels of UL16 binding protein 1 and natural killer group 2 member D affect overall survival in patients with gastric cancer following gastrectomy

PubMed Central

Kamei, Ryoji; Yoshimura, Kiyoshi; Yoshino, Shigefumi; Inoue, Moeko; Asao, Tetsuhiko; Fuse, Masanori; Wada, Satoshi; Kuramasu, Atsuo; Furuya-Kondo, Tomoko; Oga, Atsunori; Iizuka, Norio; Suzuki, Nobuaki; Maeda, Noriko; Watanabe, Yusaku; Matsukuma, Satoshi; Iida, Michihisa; Takeda, Shigeru; Ueno, Tomio; Yamamoto, Noboru; Fukagawa, Takeo; Katai, Hitoshi; Sasaki, Hiroki; Hazama, Shoichi; Oka, Masaaki; Nagano, Hiroaki

2018-01-01

UL16 binding protein 1 (ULBP1) expressed on the tumor cell surface binds to the natural killer group 2 member D (NKG2D) receptor presenting on natural killer (NK), cluster of differentiation (CD)8+ T, and γ δ T cells. However, the roles of ULBP1 and NKG2D expression and associated immune responses in gastric cancer are unclear. The present study investigated the associations between ULBP1 and NKG2D expression and clinical outcomes in patients with gastric cancer. The levels of ULBP1 and NKG2D expression were examined in human gastric cancer cell lines and gastric cancer tissues from 98 patients who underwent surgery from 2004 to 2008. MKN-74 cells expressed ULBP1 with ULBP2, −5, or −6. NKG2D was expressed at a higher level following activation of T cells and NK cells. Among the tissue sections positive for NKG2D expression, 6 patients were positive for CD8 and CD56. In all tissues, NKG2D-expressing cells were typically aCD8+ T cells. Patients with NKG2D expression in tumors exhibited significantly longer overall survival (OS) compared with patients without NKG2D expression in tumors (P=0.0217). The longest OS was observed in patients positive for ULBP1 and NKG2D, whereas the shortest OS was observed in patients negative for ULBP1 and NKG2D. The interaction between ULBP1 and NKG2D may improve OS in patients with gastric cancer, and may have applications in immunotherapy for the induction of adaptive immunity in patients with cancer. Additionally, ULBP1 and NKG2D may be useful as prognostic biomarkers in gastric cancer. PMID:29391893

Calcium metabolism in cows receiving an intramuscular injection of 1,25-dihydroxyvitamin D3 combined with prostaglandin F(2alpha) closely before parturition.

PubMed

Yamagishi, Norio; Ayukawa, Yu; Lee, Inhyung; Oboshi, Kenji; Naito, Yoshihisa

2005-06-01

To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F(2alpha) (PGF(2alpha)) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF(2alpha)) and control group (five treated with PGF(2alpha)). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during -0.5 to 3 days after parturition.

2D Echocardiographic Evaluation of Right Ventricular Function Correlates With 3D Volumetric Models in Cardiac Surgery Patients.

PubMed

Magunia, Harry; Schmid, Eckhard; Hilberath, Jan N; Häberle, Leo; Grasshoff, Christian; Schlensak, Christian; Rosenberger, Peter; Nowak-Machen, Martina

2017-04-01

The early diagnosis and treatment of right ventricular (RV) dysfunction are of critical importance in cardiac surgery patients and impact clinical outcome. Two-dimensional (2D) transesophageal echocardiography (TEE) can be used to evaluate RV function using surrogate parameters due to complex RV geometry. The aim of this study was to evaluate whether the commonly used visual evaluation of RV function and size using 2D TEE correlated with the calculated three-dimensional (3D) volumetric models of RV function. Retrospective study, single center, University Hospital. Seventy complete datasets were studied consisting of 2D 4-chamber view loops (2-3 beats) and the corresponding 4-chamber view 3D full-volume loop of the right ventricle. RV function and RV size of the 2D loops then were assessed retrospectively purely qualitatively individually by 4 clinician echocardiographers certified in perioperative TEE. Corresponding 3D volumetric models calculating RV ejection fraction and RV end-diastolic volumes then were established and compared with the 2D assessments. 2D assessment of RV function correlated with 3D volumetric calculations (Spearman's rho -0.5; p<0.0001). No correlation could be established between 2D estimates of RV size and actual 3D volumetric end-diastolic volumes (Spearman's rho 0.15; p = 0.25). The 2D assessment of right ventricular function based on visual estimation as frequently used in clinical practice appeared to be a reliable method of RV functional evaluation. However, 2D assessment of RV size seemed unreliable and should be used with caution. Copyright © 2017 Elsevier Inc. All rights reserved.

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration

PubMed Central

2017-01-01

ABSTRACT Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2−/− mice. Transgenic overexpression of cyclin D2 in cyclin D2−/− β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2−/− littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration. PMID:28763258

The Involvement of PPARs in the Selective Regulation of Brain CYP2D by Growth Hormone.

PubMed

Zhang, Furong; Li, Jie; Na, Shufang; Wu, Juan; Yang, Zheqiong; Xie, Xianfei; Wan, Yu; Li, Ke; Yue, Jiang

2018-05-21

Brain CYP2D is responsible for the synthesis of endogenous neurotransmitters such as dopamine and serotonin. This study is to investigate the effects of cerebral CYP2D on mouse behavior and the mechanism whereby growth hormone regulates brain CYP2D. The inhibition of cerebellar CYP2D significantly affected the spatial learning and exploratory behavior of mice. CYP2D expression was lower in the brain in GHR-/- mice than that in WT mice; however, hepatic CYP2D levels were similar. Brain PPARα expression in male GHR-/- mice were markedly higher than those in WT mice, while brain PPARγ levels were decreased or unchanged in different regions. However, both hepatic PPARα and PPARγ in male GHR-/- mice were markedly higher than those in WT mice. Pulsatile GH decreased the PPARα mRNA level and increased the mRNA levels of CYP2D6 and PPARγ in SH-SY5Y cells. A luciferase assay showed that PPARγ activated the CYP2D6 gene promoter while PPARα inhibited its function. Pulsatile GH decreased the binding of PPARα to the CYP2D6 promoter by 40% and promoted the binding of PPARγ to the CYP2D6 promoter by approximately 60%. The male GH secretory pattern altered PPAR expression and the binding of PPARs to the CYP2D promoter, leading to the elevation of brain CYP2D in a tissue-specific manner. Growth hormone may alter the learning and memory functions in patients receiving GH replacement therapy via brain CYP2D. Copyright © 2018. Published by Elsevier Ltd.

Detection of Interstellar Ortho-D2H+ with SOFIA

NASA Astrophysics Data System (ADS)

Harju, Jorma; Sipilä, Olli; Brünken, Sandra; Schlemmer, Stephan; Caselli, Paola; Juvela, Mika; Menten, Karl M.; Stutzki, Jürgen; Asvany, Oskar; Kamiński, Tomasz; Okada, Yoko; Higgins, Ronan

2017-05-01

We report on the detection of the ground-state rotational line of ortho-D2H+ at 1.477 THz (203 μm) using the German REceiver for Astronomy at Terahertz frequencies (GREAT) on board the Stratospheric Observatory For Infrared Astronomy (SOFIA). The line is seen in absorption against far-infrared continuum from the protostellar binary IRAS 16293-2422 in Ophiuchus. The para-D2H+ line at 691.7 GHz was not detected with the APEX telescope toward this position. These D2H+ observations complement our previous detections of para-H2D+ and ortho-H2D+ using SOFIA and APEX. By modeling chemistry and radiative transfer in the dense core surrounding the protostars, we find that the ortho-D2H+ and para-H2D+ absorption features mainly originate in the cool (T < 18 K) outer envelope of the core. In contrast, the ortho-H2D+ emission from the core is significantly absorbed by the ambient molecular cloud. Analyses of the combined D2H+ and H2D+ data result in an age estimate of ˜5 × 105 yr for the core, with an uncertainty of ˜2 × 105 yr. The core material has probably been pre-processed for another 5 × 105 years in conditions corresponding to those in the ambient molecular cloud. The inferred timescale is more than 10 times the age of the embedded protobinary. The D2H+ and H2D+ ions have large and nearly equal total (ortho+para) fractional abundances of ˜10-9 in the outer envelope. This confirms the central role of {{{H}}}3+ in the deuterium chemistry in cool, dense gas, and adds support to the prediction of chemistry models that also {{{D}}}3+ should be abundant in these conditions.

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells.

PubMed

Lencesova, L; Szadvari, I; Babula, P; Kubickova, J; Chovancova, B; Lopusna, K; Rezuchova, I; Novakova, Z; Krizanova, O; Novakova, M

2017-12-15

Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP 3 receptors (IP 3 R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP 3 R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP 3 R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP 3 R1 activity, which in turn may account for the increase expression of IP 3 R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

All-cause mortality in adults with and without type 2 diabetes: findings from the national health monitoring in Germany

PubMed Central

Brinks, Ralph; Baumert, Jens; Paprott, Rebecca; Du, Yong; Heidemann, Christin; Scheidt-Nave, Christa

2017-01-01

Objective To estimate age-specific and sex-specific all-cause mortality among adults with and without type 2 diabetes (T2D) in Germany. Research design and methods The German National Health Interview and Examination Survey 1998 (GNHIES98) included a mortality follow-up (median follow-up time 12.0 years) of its nationwide sample representative of the population aged 18–79 years. After exclusion of participants with type 1 diabetes, age- and sex-stratified mortality rates (MR) were calculated for 330 GNHIES98 participants with diagnosed T2D (self-reported diagnosis or antidiabetic medication), 245 with undiagnosed T2D (no diagnosed T2D, glycated hemoglobin A1c ≥6.5% (≥48 mmol/mol)), and 5975 without T2D. Mortality rate ratios (MRR) comparing MR of persons with and without T2D were estimated. Age-/sex-standardized MR and MRR were calculated including persons aged 45 years or older. MRR were used to estimate the number of years of life lost (YLL) due to diagnosed diabetes in 2010. Results Over 75 994 person-years, 73 persons with undiagnosed T2D, 103 with diagnosed T2D, and 425 persons without T2D died. MRR were significantly higher in younger age groups, except for analyses limited to women or diagnosed T2D. Age- and sex-standardized MRR (95% CI) among persons aged 45 years or older were 1.96 (1.41 to 2.71) for undiagnosed, 1.68 (1.26 to 2.23) for diagnosed, and 1.82 (1.45 to 2.28) for total (undiagnosed or diagnosed) T2D. Sex-stratified analysis revealed similar age-standardized MRR for undiagnosed (1.56 (0.79 to 3.06)) and diagnosed T2D (1.56 (1.03 to 2.37)) among women, and a higher age-standardized MRR for undiagnosed (2.06 (1.43 to 2.97)) than diagnosed T2D (1.70 (1.10 to 2.63)) among men. YLL due to diagnosed diabetes in Germany in 2010 were 164 600 (35 000 to 279 300) among women and 169 900 (28 300 to 328 300) among men. Conclusions In Germany, age- and sex-standardized all-cause mortality is almost twice as high for adults with T2D as for adults without T2D. The T2D-associated excess risk of mortality appears to be most pronounced in younger adults and among men unaware of their T2D. PMID:29435349

Two-dimensional planning can result in internal rotation of the femoral component in total knee arthroplasty.

PubMed

Okamoto, Shigetoshi; Mizu-uchi, Hideki; Okazaki, Ken; Hamai, Satoshi; Tashiro, Yasutaka; Nakahara, Hiroyuki; Iwamoto, Yukihide

2016-01-01

The first purpose of this study was to compare the reproducibility of two-dimensional (2D) and three-dimensional (3D) measurements for preoperative planning of the femoral side in total knee arthroplasty (TKA). The second purpose was to evaluate the factors affecting the differences between the 2D and 3D measurements. Two-dimensional and 3D measurements for preoperative planning of the femoral side in TKA were evaluated in 75 varus knees with osteoarthritis. The femoral valgus angle, defined as the angle between the mechanical and anatomical axes of the femur, and the clinical rotation angle and surgical rotation angle, defined by the angles between the posterior condylar line and the clinical or surgical transepicondylar axes, respectively, were analysed using 2D (radiographs and axial CT slices) and 3D (3D bone models reconstructed from CT images) measurements. For all variables, 3D measurements were more reliable and reproducible than 2D measurements. The medians and ranges of the clinical rotation angle and surgical rotation angle were 6.6° (-1.7° to 12.1°) and 2.3° (-2.5° to 8.6°) in 2D, and 7.1° (2.7° to 11.4°) and 3.0° (-2.0° to 7.5°) in 3D. Varus/valgus alteration of the CT scanning direction relative to the mechanical axis affected the difference in clinical rotation angles between 2D and 3D measurements. Significantly, smaller values of the clinical rotation angle and surgical rotation angle were obtained by 2D compared to 3D measurements, which could result in internal rotation of the femoral component even if the surgeon performs the bone cutting precisely. Regarding clinical relevance, first, this study confirmed the reliability of 3D measurements. Second, it underscored the risk of internal rotation of the femoral component when using 2D measurement, even with precise bone cutting technique. These results will help surgeons avoid malpositioning of the femoral component if 2D measurements are used for preoperative planning in TKA. Prospective comparative study, Level Ш.

Associations between the 2D:4D Proxy Biomarker for Prenatal Hormone Exposures and Symptoms of Developmental Language Disorder

ERIC Educational Resources Information Center

Redmond, Sean M.; Ash, Andrea C.

2017-01-01

Purpose: Relative lengths of the index (2D) and ring (4D) fingers in humans represent a retrospective biomarker of prenatal hormonal exposures. For this reason, the 2D:4D digit ratio can be used to investigate potential hormonal contributions to the etiology of neurodevelopmental disorders. This study tested potential group differences in 2D:4D…

Distortions in 2p4d Partial Fluorescence yield for 4d elements

NASA Astrophysics Data System (ADS)

Price, Alexander; de Groot, Frank; Datta, Trinanjan

2014-03-01

X-ray absorption spectroscopy (XAS) is a standard tool to determine the electronic structure of molecules and materials. CTM4XAS and CTM4RIXS are semi-empirical programs to analyze transition metal L - and M - edge transitions by evaluating the effects of crystal field and charge transfer parameters on the atomic multiplets. We compute and compare the XAS and the fluorescence yield (FY) XAS, of the 3d and 4d transition metal ions. In the case of 2p edges of 3d elements Auger decay dominates and sets the time scale. The 2p3d X -ray emission spectra (XES) accounts for approximately 80% of the radiative decay. The 2p3d partial FY is distorted and because it dominates the FY, the total FY is also distorted. For the 4d elements the 2p4d XES decay is approximately 10% of 2p3d XES decay, implying that (the energy-constant) core-core XES and Auger channels dominate the decay. The computed 2p4d partial FY -XAS spectra are different from the 2p XAS. Although 2p4d partial FY is distorted, the total FY is not because it is dominated by 2p3d XES. We also find that the 2p3s and 2p4s XES channels contribute less than 1% and can be neglected. Cottrell Research Corporation.

Eating patterns and type 2 diabetes risk in men: breakfast omission, eating frequency, and snacking1234

PubMed Central

Mekary, Rania A; Giovannucci, Edward; Willett, Walter C; van Dam, Rob M

2012-01-01

Background: Little is known about the association between eating patterns and type 2 diabetes (T2D) risk. Objective: The objective of this study was to prospectively examine associations between breakfast omission, eating frequency, snacking, and T2D risk in men. Design: Eating patterns were assessed in 1992 in a cohort of 29,206 US men in the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, and cancer and were followed for 16 y. We used Cox proportional hazards analysis to evaluate associations with incident T2D. Results: We documented 1944 T2D cases during follow-up. After adjustment for known risk factors for T2D, including BMI, men who skipped breakfast had 21% higher risk of T2D than did men who consumed breakfast (RR: 1.21; 95% CI: 1.07, 1.35). Compared with men who ate 3 times/d, men who ate 1–2 times/d had a higher risk of T2D (RR: 1.25; 95% CI: 1.08, 1.45). These findings persisted after stratification by BMI or diet quality. Additional snacks beyond the 3 main meals (breakfast, lunch, and dinner) were associated with increased T2D risk, but these associations were attenuated after adjustment for BMI. Conclusions: Breakfast omission was associated with an increased risk of T2D in men even after adjustment for BMI. A direct association between snacking between meals and T2D risk was mediated by BMI. PMID:22456660

Functions of NKG2D in CD8+ T cells: an opportunity for immunotherapy.

PubMed

Prajapati, Kushal; Perez, Cynthia; Rojas, Lourdes Beatriz Plaza; Burke, Brianna; Guevara-Patino, Jose A

2018-02-05

Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8 + T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8 + T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling. CD28 has been established as an archetype provider of costimulation during T-cell priming. It has become apparent, however, that signals from other costimulatory receptors, such as NKG2D, are required for optimal T-cell function outside the priming phase. This review will focus on the similarities and differences between NKG2D and CD28; less well-described characteristics of NKG2D, such as the potential role of NKG2D in CD8 + T-cell memory formation, cancer immunity and autoimmunity; and the opportunities for targeting NKG2D in immunotherapy.Cellular and Molecular Immunology advance online publication, 5 February 2018; doi:10.1038/cmi.2017.161.

Three new triterpenoid saponins from the seeds of Aesculus turbinata.

PubMed

Yang, Xiu-Wei; Zhao, Jing; Hattori, Masao

2008-01-01

Three new triterpenoid saponins, named isoescins VIIa (1), VIa (2), and VIIIa (3), were isolated from the seeds of Aesculus turbinata and identified by spectroscopic analysis and chemical hydrolysis. Their structures were established as 21beta-O-tigloyl-28-O-acetylprotoaescigenin 3beta-O-[beta-d-galactopyranosyl(1 --> 2)][beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIIa, 1), 21beta-O-(2-methylbutyryl)-28-O-acetylprotoaescigenin 3beta-O-[beta-d-glucopyranosyl(1 --> 2)] [beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIa, 2), and 21beta-O-angeloyl-28-O-acetylbarringtogenol C 3beta-O-[beta-d-glucopyranosyl(1 --> 2)] [beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIIIa, 3).

Recent software developments for biomechanical assessment

NASA Astrophysics Data System (ADS)

Greaves, John O. B.

1990-08-01

While much of the software developed in research laboratories is narrow in focus and suited for a specific experiment, some of it is broad enough and of high enough quality to be useful to others in solving similar problems. Several biomechanical assessment packages are now beginning to emerge, including: * 3D research biomechanics (5- and 6-DOF) with kinematics, kinetics, 32-channel analog data subsystem, and project management. * 3D full-body gait analysis with kinematics, kinetics, EMG charts, and force plate charts. * 2D dynamic rear-foot assessment. * 2D occupational biomechanics lifting task and personnel assessments. * 2D dynamic gait analysis. * Multiple 2D dynamic spine assessments. * 2D sport and biomechanics assessments with kinematics and kinetics. * 2D and 3D equine gait assessments.

Monomorphism of cytidine (Cyd) vs. polymorphism of 2'deoxycytidine (dCyd). Structural and functional consequences

NASA Astrophysics Data System (ADS)

Wiewiórowski, M.; Alejska, M.; Malinowska, N.; Bratek-Wiewiórowska, M. D.

1997-12-01

It has been found that 2'deoxycytidine (dCyd) crystallizes in different forms, denoted dCyd A, dCyd B and dCyd C·H 2O. In the crystal lattice of the newly discovered form dCydC·H 2O there is a crystalline water molecule present. The monohydrate of dCydC, under suitable conditions (RT, over P 2O 5, 48h), undergoes transformation into the fully dehydrated form—dCydC anhydro. The whole process of de- and re-hydratation has been observed by FTIR-PAS spectroscopy. The nature of the differences and similarities between structural and functional properties of crystalline forms of 2'dCyd and Cyd molecules has been discussed.

Impact of 2D and 3D vision on performance of novice subjects using da Vinci robotic system.

PubMed

Blavier, A; Gaudissart, Q; Cadière, G B; Nyssen, A S

2006-01-01

The aim of this study was to evaluate the impact of 3D and 2D vision on performance of novice subjects using da Vinci robotic system. 224 nurses without any surgical experience were divided into two groups and executed a motor task with the robotic system in 2D for one group and with the robotic system in 3D for the other group. Time to perform the task was recorded. Our data showed significant better time performance in 3D view (24.67 +/- 11.2) than in 2D view (40.26 +/- 17.49, P < 0.001). Our findings emphasized the advantage of 3D vision over 2D view in performing surgical task, encouraging the development of efficient and less expensive 3D systems in order to improve the accuracy of surgical gesture, the resident training and the operating time.

Synthesis of orthogonally protected bacterial, rare-sugar and D-glycosamine building blocks.

PubMed

Emmadi, Madhu; Kulkarni, Suvarn S

2013-10-01

Bacterial glycoconjugates comprise atypical deoxy amino sugars that are not present on the human cell surface, making them good targets for drug discovery and carbohydrate-based vaccine development. Unfortunately, they cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products. Here we describe a detailed protocol for the synthesis of orthogonally protected bacterial deoxy amino hexopyranoside (2,4-diacetamido-2,4,6-trideoxyhexose (DATDH), D-bacillosamine, D-fucosamine, and 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT)), D-glucosamine and D-galactosamine building blocks starting from β-D-thiophenylmannoside. Readily available β-D-thiophenylmannoside was first converted into the corresponding 2,4-diols via deoxygenation or silylation at C6, followed by O3 acylation. The 2,4-diols were converted into 2,4-bis-trifluoromethanesulfonates, which underwent highly regioselective, one-pot, double-serial and double-parallel displacements by azide, phthalimide, acetate and nitrite ions as nucleophiles. Thus, D-rhamnosyl- and D-mannosyl 2,4-diols can be efficiently transformed into various rare sugars and D-galactosamine, respectively, as orthogonally protected thioglycoside building blocks on a gram scale in 1-2 d, in 54-85% overall yields, after a single chromatographic purification. This would otherwise take 1-2 weeks. D-Glucosamine building blocks can be prepared from β-D-thiophenylmannoside in four steps via C2 displacement of triflates by azide in 2 d and in 66-70% overall yields. These procedures have been applied to the synthesis of L-serine-linked trisaccharide of Neisseria meningitidis and a rare disaccharide fragment of the zwitterionic polysaccharide (ZPS) A1 (ZPS A1) of Bacteroides fragilis.

Soft 2D nanoarchitectonics

NASA Astrophysics Data System (ADS)

Ariga, Katsuhiko; Watanabe, Shun; Mori, Taizo; Takeya, Jun

2018-04-01

Nanoarchitectonics is a new paradigm to combine and unify nanotechnology with other sciences and technologies, such as supramolecular chemistry, self-assembly, self-organization, materials technology for manipulation of the size of material objects, and even biotechnology for hybridization with bio-components. The nanoarchitectonic concept leads to the synergistic combination of various methodologies in materials production, including atomic/molecular-level control, self-organization, and field-controlled organization. The focus of this review is on soft 2D nanoarchitectonics. Scientific views on soft 2D nanomaterials are not fully established compared with those on rigid 2D materials. Here, we collect recent examples of 2D nanoarchitectonic constructions of functional materials and systems with soft components. These examples are selected according to the following three categories on the basis of 2D spatial density and motional freedom: (i) well-packed and oriented organic 2D materials with rational design of component molecules and device applications, (ii) well-defined assemblies with 2D porous structures as 2D network materials, and (iii) 2D control of molecular machines and receptors on the basis of certain motional freedom confined in two dimensions.

Interaction of Thioamides, Selenoamides, and Amides With Diiodine

PubMed Central

Hadjikakou, Sotiris K.; Hadjiliadis, Nick

2006-01-01

We review the results of our work on the iodine interaction with thioamides, selenoamides, and amides. Complexes with (i) “spoke” or “extended spoke” structures, D · I2 and D · I2 · I2, respectively, (D is the ligand donor) (ii) iodonium salts of {[D2 − I]+[In]−} (n = 3, 7) and {[D2 − I]+[FeCl4]−} formulae and (iii) disulfides of the categories (a) [D − D], (b) {[D − DH]+[I3]−} have been isolated and characterized. A compound of formula {[D2 − I]+[I3]−[D · I2]} containing both types of complexes (i) and (ii) was also isolated. The interaction of diiodine with selenium analogs of the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU (6-alkyl-2-Selenouracil) results in the formation of complexes with formulae [(RSeU)I2]. All these results are correlated with the mechanism of action of antithyroid drugs. Finally, we review here our work on the diiodine interaction with the amides (LO). PMID:17497011

Hierarchical porous carbons with layer-by-layer motif architectures from confined soft-template self-assembly in layered materials

NASA Astrophysics Data System (ADS)

Wang, Jie; Tang, Jing; Ding, Bing; Malgras, Victor; Chang, Zhi; Hao, Xiaodong; Wang, Ya; Dou, Hui; Zhang, Xiaogang; Yamauchi, Yusuke

2017-06-01

Although various two-dimensional (2D) nanomaterials have been explored as promising capacitive materials due to their unique layered structure, their natural restacking tendency impedes electrolyte transport and significantly restricts their practical applications. Herein, we synthesize all-carbon layer-by-layer motif architectures by introducing 2D ordered mesoporous carbons (OMC) within the interlayer space of 2D nanomaterials. As a proof of concept, MXenes are selected as 2D hosts to design 2D-2D heterostructures. Further removing the metal elements from MXenes leads to the formation of all-carbon 2D-2D heterostructures consisting of alternating layers of MXene-derived carbon (MDC) and OMC. The OMC layers intercalated with the MDC layers not only prevent restacking but also facilitate ion diffusion and electron transfer. The performance of the obtained hybrid carbons as supercapacitor electrodes demonstrates their potential for upcoming electronic devices. This method allows to overcome the restacking and blocking of 2D nanomaterials by constructing ion-accessible OMC within the 2D host material.

Inconsistency in the Crown-to-Root Ratios of Single-Rooted Premolars Measured by 2D and 3D Examinations.

PubMed

Hong, Hsiang-Hsi; Liu, Heng-Liang; Hong, Adrienne; Chao, Pu

2017-11-28

Micro-computed tomography (micro-CT) was applied to elucidate the relationship between the three-dimensional (3D) root surface area (RSA) and two-dimensional (2D) crown-to-root ratio (CRR) of extracted teeth to classify the periodontitis and assign a periodontal/prosthetic prognosis. A total of 31 maxillary and 35 mandibular single-rooted human premolars were examined. The amount of periodontal support on the basis of 3D RSA and 2D root length (RL) at CRRs of 1:1, 5:4, 3:2, and 2:1 were analyzed. Both maxillary and mandibular premolars demonstrated a nonsignificant RSA percentage at the evaluated CRRs. The coronal 21%-22% 2D RL and the 26%-28% 3D RSA bone loss apical to the cemento-enamel junction corresponded to a CRR of 1:1, relating to mild-moderate periodontitis. The coronal 30%-31% 2D RL and the 41%-42% 3D RSA bone loss corresponded to a CRR of 5:4, correlating to severe periodontitis. More severe clinical attachment loss (CAL) was observed in the 3D RSA measurement than in the 2D RL measurement at the evaluated CRRs. The amount of CAL at the CRR of 1:1 was inadequate to assess the severity of periodontitis on the basis of the 2D RL and 3D RSA measurements.

Screening and transport in 2D semiconductor systems at low temperatures

PubMed Central

Das Sarma, S.; Hwang, E. H.

2015-01-01

Low temperature carrier transport properties in 2D semiconductor systems can be theoretically well-understood within RPA-Boltzmann theory as being limited by scattering from screened Coulomb disorder arising from random quenched charged impurities in the environment. In this work, we derive a number of analytical formula, supported by realistic numerical calculations, for the relevant density, mobility, and temperature range where 2D transport should manifest strong intrinsic (i.e., arising purely from electronic effects) metallic temperature dependence in different semiconductor materials arising entirely from the 2D screening properties, thus providing an explanation for why the strong temperature dependence of the 2D resistivity can only be observed in high-quality and low-disorder 2D samples and also why some high-quality 2D materials manifest much weaker metallicity than other materials. We also discuss effects of interaction and disorder on the 2D screening properties in this context as well as compare 2D and 3D screening functions to comment why such a strong intrinsic temperature dependence arising from screening cannot occur in 3D metallic carrier transport. Experimentally verifiable predictions are made about the quantitative magnitude of the maximum possible low-temperature metallicity in 2D systems and the scaling behavior of the temperature scale controlling the quantum to classical crossover. PMID:26572738

Stability of vitamin D3 and vitamin D2 in oil, fish and mushrooms after household cooking.

PubMed

Ložnjak, Petra; Jakobsen, Jette

2018-07-15

Information on the retention of vitamin D in food following household cooking is scarce. So far the retention of its metabolites vitamin D 3 , vitamin D 2 , and 25-hydroxyvitamin D 3 has shown that the type of food and the cooking method are the essential determinants, and there is no significant difference between the metabolites. We investigated the retention of vitamin D 3 and vitamin D 2 in sunflower oil, vitamin D 3 in rainbow trout, and vitamin D 2 in button mushrooms. The investigated cooking methods were boiling at different pH, steam cooking, microwave cooking, pan-frying, and oven baking. There was no difference between the retention of vitamin D 3 and vitamin D 2 added to sunflower oil, which ranged from 70 to 99%. In rainbow trout, the retention of vitamin D 3 at 85-114% was not significantly different from 100%, except for panfrying at 85%. However, the retention of vitamin D 2 in mushrooms at 62-88% was significantly different from 100% (p ≤ 0.05). Copyright © 2018 Elsevier Ltd. All rights reserved.