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Sample records for par emission acoustique

  1. Detection de l'initiation de la delamination des materiaux composites par suivi de l'emission acoustique

    NASA Astrophysics Data System (ADS)

    Silversides, Ian

    Cette étude, basée sur la surveillance des ondes d'émission acoustique (E.A.), présente le développement d'une approche de prédiction de l'initiation de la délamination de pièces composites soumises à des chargements statiques et en fatigue. La surveillance des ondes d'E.A. fait parti d'un nombre restreint de méthodes pouvant détecter, en continu, l'apparition et la croissance de dommages dans les matériaux composites. L'approche est comparée à des méthodes conventionnelles ainsi qu'à une modélisation numérique pour des composites à fibre de carbone unidirectionnels et tissés, sur une gamme de rapports de mode mixte. Le présent mémoire met en lumière les différentes étapes abordées durant l'étude. L'utilisation des matériaux composites est mise en contexte au premier chapitre. La complexité des matériaux composites ainsi que la nécessité de modèles de prédiction fiables sont soulignées. Le deuxième chapitre contient une revue de la littérature et présente les outils disponibles pour analyser le délaminage et bâtir un modèle prédictif de sa propagation. Les sujets traités sont la délamination dans un contexte de mécanique de la rupture, la modélisation numérique d'une propagation de fissure, l'approche du monitorage par émission acoustique puis l'analyse fractographiques des surfaces de rupture. Les résultats des essais mécaniques et de la modélisation sont présentés sous forme d'article dans le troisième chapitre. Des essais statiques et en fatigue ont permis de calculer le taux de restitution d'énergie de déformation à l'initiation de la délamination selon des méthodes classiques pour ensuite les comparer à une méthode développée, basée sur le suivi des ondes d'émission acoustique. Une série d'essais de propagation de la délamination en fatigue ont permis d'observer des corrélations entre les émissions acoustiques, la longueur de la délamination, la vitesse de croissance des fissures et la s

  2. Mesure de profils sans contact mécanique par interférométrie acoustique

    NASA Astrophysics Data System (ADS)

    Olive, F.; Waintal, A.; Buévoz, J. L.; Reynaud, J. C.

    1992-10-01

    The analysis of the Acoustical Material Signature is mandatory in order to explain the image formation in an acoustical microscope. We have developed and experimental setup including a dedicated electronic system which allows for the measurement of the phase of the reflected acoustical signal, with respect to a fixed reference. As a consequence, the acoustical microscope can be operated as an interferometer allowing the characterization of micron size mechanical profiles without contact other than the water droplet which permits the acoustical coupling between the lens and the sample. The method has been evaluated on numerous patterns etched on different materials. In all the measurement accuracy was at least similar to results obtained by means of the best mechanical profilometers. L'analyse de la signature acoustique des matériaux est indispensable à la compréhension des images de microscopie acoustique. Nous avons développé un dispositif expérimental dont l'électronique originale permet la mesure de la phase du signal acoustique réfléchi, par rapport à uen référence fixe. Le microscope acoustique peut ainsi être utilisé comme un interféromètre, dont la principale application est la mesure de profils mécaniques, de dimensions microniques, sans contact si ce n'est avec la goutte d'eau qui assure le couplage de l'onde acoustique entre la lentille et l'échantillon. Les performances de la méthode ont été évaluées sur plusieurs motifs gravés sur différents matériaux. Dans tous les cas, la précision des mesures est au moins égale à celle obtenue par les meilleurs profilomètres mécaniques.

  3. Étude par microscopie acoustique de couches minces de Ag2S déposées par spray

    NASA Astrophysics Data System (ADS)

    Amlouk, M.; Brunet, N.; Cros, B.; Belgacem, S.; Barjon, D.

    1997-09-01

    Silver sulfide Ag2S thin films have been prepared on pyrex glass substrates by the spray pyrolysis technique at 250 °C. We have analyzed by acoustic microscopy and particularly by acoustic signature V(z) these films with various thickness (0.4 2 μm). The acoustic signature, performed at 50, 130 and 570 MHz allow us to reach elastic properties of Ag2S material and specially Young modulus. Its value, of the order of 180 GPa, is consistent with the relative low linkage of Ag^+ in the structure and the character of fast-ion conductor of Ag2S. Besides elastic properties and using MEB and AFM investigations, we have shown that the V(z) signature gives valuable information about the bulk defects in the material. Finally, the experimental results have been discussed related to the dispersion curves of velocity of the first mode of Ag2S/pyrex system. Des couches minces de sulfure d'argent Ag2S sont préparées sur substrat de pyrex, à la température de 250 °C, par la technique de pulvérisation chimique réactive en phase liquide ou “spray". Ces dépôts, d'épaisseur variable (0,4 2 μm), sont analysés par microscopie acoustique et, plus particulièrement, par la méthode de relevé de la signature acoustique V(z). Cette signature, effectuée à différentes fréquences (50, 130, 570 MHz), a permis de caractériser les propriétés élastiques du matériau Ag2S. La valeur du module d'Young, de l'ordre de 180 GPa, est en accord avec la faible cohésion de la liaison Ag-S et le caractère de conducteur ionique rapide de Ag2S. Les observations par MEB et AFM permettent d'expliquer l'allure des courbes V(z) par les défauts de compacité liés à la méthode de préparation. Les résultats expérimentaux sont discutés en liaison avec la courbe de dispersion de vitesses du premier mode du système Ag2S/pyrex.

  4. Etude par émission acoustique de la dynamique des dislocations pendant la déformation cyclique de polycristaux d'aluminium

    NASA Astrophysics Data System (ADS)

    Slimani, A.; Fleischmann, P.; Fougères, R.

    1992-06-01

    The cyclic plasticity of 5N polycrystalline aluminium have been studied at room temperature by measuring the continuous acoustic emission (A.E.) due to dislocations movements in the metal. In this study, original data have been obtained in the understanding of continuous A.E. sources. In comparison with classical interpretation given in the literature, the fact that dislocations are arranged according to a dislocation cell structure from the first cycle has been included in the analysis of the results. From this, it has been shown that the amplitude of the A.E. signal is not directly connected with the plastic strain rate prescribed to the fatigue sample and that the probability density function of dislocation loops created during the cycling can be determined. La plasticité cyclique de l'AI 5N polycristallin a été étudiée à la température ambiante à partir de mesures d'émission acoustique continue (E.A.). L'application de la technique de l'E.A. nous a permis d'obtenir des données originales quant aux mécanismes sources d'E.A. Par rapport aux interprétations classiques de la littérature, nous avons fait intervenir le fait que, dès les premiers cycles, une structure cellulaire de dislocations est établie. Nous montrons que l'amplitude du signal d'E.A. n'est plus liée directement à la vitesse de déformation plastique macroscopique. A partir de cette donnée, l'analyse des résultats d'E.A. permet d'obtenir des informations sur la fonction distribution des boucles de dislocations créées au cours de la déformation cyclique.

  5. Étude de l'efficacité des modes de Lamb dans la signature acoustique V(z) d'une couche mince par la théorie de la résonance

    NASA Astrophysics Data System (ADS)

    Ramdani, Abderrafi; Augereau, Franck; Despaux, Gilles

    1996-05-01

    Experimental acoustic signatures measured on thin films are perturbated by an interference process between the different Lamb waves generated at various incident angular values. This disables the correct determination of the layer's acoustic parameters and for this reason, it is helpful to develop a powerful method to study the influence of each layer parameter on these modes. For this purpose, a technique based on the calculation of the half-height width on resonance peaks of the reflectance power has been elaborated. From these simulations, we may determine which modes will be more efficiently extracted from acoustic signatures for steel and glass films. This result has been confirmed experimentally using ultrasonic frequencies optimized versus the sample thicknesses for glass and steel plates. Indeed, from experimental acoustic signatures, we have next been able to retrieve the acoustic parameters of these samples. Les relevés expérimentaux des signatures acoustiques sur des couches minces sont difficiles à interpréter car tous les modes de Lamb générés à differents angles d'incidence vont interférer, ce qui rend impossible toute détermination des paramètres acoustiques de la couche. Il est alors nécessaire de mettre en oeuvre une méthode d'analyse rapide afin d'étudier l'influence de chacun des paramètres de la couche sur ces modes afin de déterminer les conditions optimales de mesure. La méthode d'analyse basée sur la détermination de la largeur à mi-hauteur des pics de résonance du pouvoir réflecteur est un moyen original de résolution du problème direct, qui permet de montrer que certains modes sont plus efficaces que d'autres, et donc plus faciles à détecter sur les signatures expérimentales. Grâce aux résulats théoriques obtenus, les fréquences d'observation ont pu être optimisées pour des épaisseurs de plaques d'acier et de verre utilisées dans la partie expérimentale de ce travail. De ces mesures et en utilisant notre

  6. Developpement d'un vibrateur acoustique pour precipiter les defauts latents de circuits electroniques

    NASA Astrophysics Data System (ADS)

    Lafleur, Francois

    2003-08-01

    Le procede de deverminage, ou Environmental Stress Screening (ESS), est employe principalement dans le domaine de l'electronique pour reduire les mortalites infantiles des produits avant leur livraison. Il utilise usuellement des stimulations environnementales telles que les vibrations ou la temperature produites a l'aide d'equipements conventionnels d'essais qui sont tres couteux et difficiles a implanter. Le but de cette recherche est le developpement d'une nouvelle methode d'excitation vibratoire des plaques de circuits electroniques a moindre cout par l'emploi de l'excitation acoustique. Le projet a mene au developpement d'un vibrateur acoustique pouvant etre utilise lors d'implantations du procede ESS en milieu industriel. L'utilisation de cette nouvelle technologie et des methodes novatrices de personnalisation des spectres ESS proposees dans cette these permettent la precipitation de defaillances latentes presentes dans les produits electroniques de facon efficace et securitaire et ce, a moindre cout par rapport aux technologies concurrentes. La methodologie des travaux presentes dans cette these inclus: (1) La generation acoustique des vibrations sur les circuits; (2) L'analyse modale acoustique des circuits par des methodes a reference unique et a references multiples; (3) La precipitation de defauts latents typiques des circuits electroniques; (4) Une methode d'individualisation des spectres vibratoires tenant compte des caracteristiques structurelles des circuits; (5) La presentation de la configuration de l'equipement acoustique et les resultats d'implantation du procede. Nonobstant la fabrication, l'installation et la mise en service d'un equipement en milieu industriel (depuis le mois de mai 2002), ces travaux ont permis l'obtention de trois familles de brevets et la publication de six articles de conference: trois portant sur l'analyse modale a reference unique, un portant sur l'analyse modale a references multiples, un autre portant sur la

  7. Caracterisation des proprietes acoustiques des materiaux poreux a cellules ouvertes et a matrice rigide ou souple

    NASA Astrophysics Data System (ADS)

    Salissou, Yacoubou

    L'objectif global vise par les travaux de cette these est d'ameliorer la caracterisation des proprietes macroscopiques des materiaux poreux a structure rigide ou souple par des approches inverses et indirectes basees sur des mesures acoustiques faites en tube d'impedance. La precision des approches inverses et indirectes utilisees aujourd'hui est principalement limitee par la qualite des mesures acoustiques obtenues en tube d'impedance. En consequence, cette these se penche sur quatre problemes qui aideront a l'atteinte de l'objectif global precite. Le premier probleme porte sur une caracterisation precise de la porosite ouverte des materiaux poreux. Cette propriete en est une de passage permettant de lier la mesure des proprietes dynamiques acoustiques d'un materiau poreux aux proprietes effectives de sa phase fluide decrite par les modeles semi-phenomenologiques. Le deuxieme probleme traite de l'hypothese de symetrie des materiaux poreux selon leur epaisseur ou un index et un critere sont proposes pour quantifier l'asymetrie d'un materiau. Cette hypothese est souvent source d'imprecision des methodes de caracterisation inverses et indirectes en tube d'impedance. Le critere d'asymetrie propose permet ainsi de s'assurer de l'applicabilite et de la precision de ces methodes pour un materiau donne. Le troisieme probleme vise a mieux comprendre le probleme de transmission sonore en tube d'impedance en presentant pour la premiere fois un developpement exact du probleme par decomposition d'ondes. Ce developpement permet d'etablir clairement les limites des nombreuses methodes existantes basees sur des tubes de transmission a 2, 3 ou 4 microphones. La meilleure comprehension de ce probleme de transmission est importante puisque c'est par ce type de mesures que des methodes permettent d'extraire successivement la matrice de transfert d'un materiau poreux et ses proprietes dynamiques intrinseques comme son impedance caracteristique et son nombre d'onde complexe. Enfin, le

  8. Caracterisation experimentale de la transmission acoustique de structures aeronautiques

    NASA Astrophysics Data System (ADS)

    Pointel, Vincent

    Le confort des passagers à l'intérieur des avions pendant le vol est un axe en voie d'amélioration constante. L'augmentation de la proportion des matériaux composites dans la fabrication des structures aéronautiques amène de nouvelles problématiques à résoudre. Le faible amortissement de ces structures, en contre partie de leur poids/raideur faible, est non favorable sur le plan acoustique, ce qui oblige les concepteurs à devoir trouver des moyens d'amélioration. De plus, les mécanismes de transmission du son au travers d'un système double paroi de type aéronautique ne sont pas complètement compris, c'est la raison qui motive cette étude. L'objectif principal de ce projet est de constituer une base de données pour le partenaire industriel de ce projet : Bombardier Aéronautique. En effet, les données expérimentales de performance d'isolation acoustique, de systèmes complets représentatifs d'un fuselage d'avion sont très rares dans la littérature scientifique. C'est pourquoi une méthodologie expérimentale est utilisée dans ce projet. Deux conceptions différentes de fuselage sont comparées. La première possède une peau (partie extérieure du fuselage) métallique raidie, alors que la deuxième est constituée d'un panneau sandwich composite. Dans les deux cas, un panneau de finition de fabrication sandwich est utilisé. Un traitement acoustique en laine de verre est placé à l'intérieur de chacun des fuselages. Des isolateurs vibratoires sont utilisés pour connecter les deux panneaux du fuselage. La simulation en laboratoire de la couche limite turbulente, qui est la source d'excitation prépondérante pendant la phase de vol, n'est pas encore possible hormis en soufflerie. C'est pourquoi deux cas d'excitation sont considérés pour essayer d'approcher cette sollicitation : une excitation mécanique (pot vibrant) et une acoustique (champ diffus). La validation et l'analyse des résultats sont effectuées par le biais des logiciels

  9. Etude numerique et experimentale de la reponse vibro-acoustique des structures raidies a des excitations aeriennes et solidiennes

    NASA Astrophysics Data System (ADS)

    Mejdi, Abderrazak

    Les fuselages des avions sont generalement en aluminium ou en composite renforces par des raidisseurs longitudinaux (lisses) et transversaux (cadres). Les raidisseurs peuvent etre metalliques ou en composite. Durant leurs differentes phases de vol, les structures d'avions sont soumises a des excitations aeriennes (couche limite turbulente : TBL, champs diffus : DAF) sur la peau exterieure dont l'energie acoustique produite se transmet a l'interieur de la cabine. Les moteurs, montes sur la structure, produisent une excitation solidienne significative. Ce projet a pour objectifs de developper et de mettre en place des strategies de modelisations des fuselages d'avions soumises a des excitations aeriennes et solidiennes. Tous d'abord, une mise a jour des modeles existants de la TBL apparait dans le deuxieme chapitre afin de mieux les classer. Les proprietes de la reponse vibro-acoustique des structures planes finies et infinies sont analysees. Dans le troisieme chapitre, les hypotheses sur lesquelles sont bases les modeles existants concernant les structures metalliques orthogonalement raidies soumises a des excitations mecaniques, DAF et TBL sont reexamines en premier lieu. Ensuite, une modelisation fine et fiable de ces structures est developpee. Le modele est valide numeriquement a l'aide des methodes des elements finis (FEM) et de frontiere (BEM). Des tests de validations experimentales sont realises sur des panneaux d'avions fournis par des societes aeronautiques. Au quatrieme chapitre, une extension vers les structures composites renforcees par des raidisseurs aussi en composites et de formes complexes est etablie. Un modele analytique simple est egalement implemente et valide numeriquement. Au cinquieme chapitre, la modelisation des structures raidies periodiques en composites est beaucoup plus raffinee par la prise en compte des effets de couplage des deplacements planes et transversaux. L'effet de taille des structures finies periodiques est egalement pris en

  10. Mesure du parametre acoustique non lineaire dans les solvants et dans les polymeres

    NASA Astrophysics Data System (ADS)

    Banchet, Julien

    Dans cette étude, une technique d'amplitude finie visant la mesure du paramètre non linéaire B/A fut mise au point puis appliquée à trois familles de solvants à savoir les 1- alkanols, les cétones et les esters, ainsi qu'à deux polymères. Par l'intermédiaire d'une lentille acoustique, un signal fut focalisé dans le milieu à caractériser et l'amplitude du second harmonique généré, mesurée. Le paramètre non linéaire put alors être calculé pour chacun des liquides et solides testés. Les résultats obtenus concernant les liquides permirent de démontrer la variation de B/A avec la longueur de chaîne et la dépendance de ce paramètre avec la vitesse du son. Un modèle fut par la suite établi puis appliqué aux 1-alkanols, obtenant une description de la variation de B/A à la vitesse du son conforme à nos résultats expérimentaux. Le même principe de mesure fut appliqué à deux polymères, montrant le potentiel de cette technique pour déterminer la valeur du paramètre non linéaire dans les solides.

  11. Developpement et validation d'un outil base sur l'acoustique geometrique pour le diagnostic du bruit de nacelle

    NASA Astrophysics Data System (ADS)

    Minard, Benoit

    De nos jours, la problématique du bruit généré par les avions est devenue un point de développement important dans le domaine de l'aéronautique. C'est ainsi que de nombreuses études sont faites dans le domaine et une première approche consiste à modéliser de façon numérique ce bruit de manière à réduire de façon conséquente les coûts lors de la conception. C'est dans ce contexte qu'un motoriste a demandé à l'université de Sherbrooke, et plus particulièrement au groupe d'acoustique de l'Université de Sherbrooke (GAUS), de développer un outil de calcul de la propagation des ondes acoustiques dans les nacelles mais aussi pour l'étude des effets d'installation. Cet outil de prédiction leur permet de réaliser des études afin d'optimiser les traitements acoustiques (« liners »), la géométrie de ces nacelles pour des études portant sur l'intérieur de la nacelle et des études de positionnement des moteurs et de design pour les effets d'installation. L'objectif de ce projet de maîtrise était donc de poursuivre le travail réalisé par [gousset, 2011] sur l'utilisation d'une méthode de lancer de rayons pour l'étude des effets d'installation des moteurs d'avion. L'amélioration du code, sa rapidité, sa fiabilité et sa généralité étaient les objectifs principaux. Le code peut être utilisé avec des traitements acoustiques de surfaces («liners») et peut prendre en compte le phénomène de la diffraction par les arêtes et enfin peut être utilisé pour réaliser des études dans des environnements complexes tels que les nacelles d'avion. Le code développé fonctionne en 3D et procéde en 3 étapes : (1) Calcul des faisceaux initiaux (division d'une sphère, demi-sphère, maillage des surfaces de la géométrie) (2) Propagation des faisceaux dans l'environnement d'étude : calcul de toutes les caractéristiques des rayons convergents (amplitude, phase, nombre de réflexions, ...) (3) Reconstruction du champ de pression en un ou

  12. D'une ouverture de la voyelle /epsilon/ en finale absolue en francais quebecois : analyse acoustique et perceptive

    NASA Astrophysics Data System (ADS)

    Riverin-Coutlee, Josiane

    Cette contribution est consacree a l'ouverture du /epsilon/ en finale absolue, un phenomene phonetique repute etre en declin en francais quebecois et caracteristique de locuteurs âges, peu scolarises, issus de milieux populaires et s'exprimant en situation de communication informelle. Une analyse acoustique de 480 voyelles /epsilon/ issues de la parole formelle de 40 jeunes etudiants universitaires originaires des centres urbains de Saguenay et de Quebec revele toutefois que le phenomene est encore bien vivant en francais quebecois et qu'il est plus frequent chez les locuteurs de Saguenay, une tendance validee auditivement par accord inter-juges. Les resultats d'un test de discrimination et d'identification mene aupres de 26 etudiants universitaires originaires de ces deux memes villes indiquent que les auditeurs naifs de Saguenay semblent moins sensibles a la variation et moins enclins a juger de l'origine geographique d'un locuteur a partir de sa prononciation de la voyelle /epsilon/ en fin de mot.

  13. Imagerie par modulation acoustique de conductivite electrique destinee au diagnostic du cancer du sein

    NASA Astrophysics Data System (ADS)

    Gendron, Mathieu

    This thesis describes a new medical imaging technique for determining the electrical conductivity distribution of tissues in a body region with a resolution comparable to that of current ultrasound techniques. The new technique, henceforth referred to as "Acousto-Electric Conductivity Modulation" (AECM) imaging, is based on the interaction of a sound wave with an electrical field. In its simplest form, four electrodes located near the region to be imaged apply a low-amplitude electrical current and measure the potential difference arising from current flow in the tissues. A focused ultrasound transducer directs a pressure wave to a voxel of the region of interest, modifying its conductivity distribution and, as a result, the amplitude of the potential measured by the electrodes. An image of the conductivity distribution can thus be constructed point-by-point by moving the electrodes and transducer to scan the object. In this context, the acoustic wave acts as the localization agent while the electrical potential provides a measure of the local conductivity change that occurs in the voxel. The first model presented in the thesis is based on the use of bipolar acoustic waves for excitation. This waveform is generally used with narrow band transducers. Acoustic waves generated by an ultrasound transducer driven with a burst of sine waves consists of alternating compression and rarefaction phases which tend to cancel each other in terms of the conductivity changes they produce. However when the thickness of the target object is small compared to the wavelength of the acoustic wave, this cancelling effect will not occur and the AECM signals will have sufficiently high amplitude to achieve image reconstruction using successive transducer positions to scan the region of interest. By extracting from the spectra of the AECM signals the amplitude of the peak at the excitation frequency, a map of the acousto-electric sensitivity of the system can be obtained. This map is then used to reconstruct the electrical conductivity distribution. The second model presented in the thesis uses a unipolar acoustic wave to generate AECM signals of relatively large amplitude. There are two aspects related to this type of wave. The first aspect is that the acoustic modulation is unidirectional if the applied pressure is unidirectional. As a result, a positive pressure only produces an increase in electrical conductivity and this will result in a large AECM signal even when the thickness of the object is large. The second aspect concerns the shape of the acoustic field. Since the unipolar acoustic wave is not focused, it modulates the conductivity over a large area, and thus the associated AECM signals needs to be processed through a reconstruction algorithm so as to recover local conductivity. In this model, the data required for image reconstruction are acquired by rotating the transducer around the target object. An experimental setup has been developed during our project to get values of certain parameter that are required to define the numerical models. The setup comprises a large tank which is filled with water and in which are immersed the ultrasound transducer, a hydrophone and a measurement cell. The acousto-electric interaction takes place within this cell. A computer controlled positioning system allows precise displacements of the transducer relative to the hydrophone and the measurement cell. This cell comprises a cavity in which the object to be analyzed is placed and that is then filled with an electrolytic solution. The cavity is closed on two sides by an acoustic window to allow propagation of the ultrasound wave and on another side by six Ag/AgCl electrodes that are used to apply current and to measure the resulting electrical potential. Mammography is presently the most widely used medical imaging procedure for breast cancer screening. The average sensitivity of this technique is 80 % but it is less for younger women. According to recent studies, MRI offers a higher sensitivity and the possibility of detecting very small tumors, thus allowing earlier treatment. The operating costs of MRI systems are at the moment too high to consider using the modality for breast cancer screening on a large scale. AECM imaging could eventually provide an interesting compromise between operating costs and the sensitivity required for screening patients of all ages. (Abstract shortened by UMI.).

  14. Étude de l'efficacité des modes de Lamb dans la signature acoustique en fonction du liquide de couplage

    NASA Astrophysics Data System (ADS)

    Brunet, N.; Cros, B.; Despaux, G.; Saurel, J.-M.

    1998-06-01

    The acoustic signature allows to measure the velocity of the longitudinal and transverse acoustic waves in bulk materials. From the velocities and density values the elastic properties can be calculated. For thin layer materials, these velocities are not directly measured but computed from the experimentally available velocities: the generalized Lamb waves velocities. These waves velocities are dispersive and their measurement depends on the liquid acting as a coupling fluid. In this study, the two faces of the layer are in contact with the liquid (methanol, water or aqueous solutions of potassium iodide KI_aq. 6 M and potassium hydroxyde KOH_aq. 12 M) chosen according to its acoustic parameters. The acoustic signature modeling allows to know their respective influence, the possible detection of the fast modes and, in general, the velocity measurement accuracy increase for all available modes. The experimental studies bear out that each mode characterization may be optimized by the appropriate choice of the frequency and of the coupling liquid according to its velocity, density and attenuation. L'étude de la signature acoustique permet de mesurer les vitesses de propagation des ondes acoustiques longitudinale et transverse dans les matériaux massifs, vitesses à partir desquelles on détermine leurs propriétés mécaniques. Pour des matériaux en couche mince, ces vitesses ne sont plus mesurées directement mais calculées à partir des vitesses accessibles expérimentalement : celles des modes de Lamb généralisés. Ces modes ont des vitesses dispersives et leur mesure dépend du liquide servant de couplant, dans lequel la couche est immergée. Dans cette étude, les liquides de couplage (méthanol, eau et solutions aqueuses de iodure de potassium KI_aq. 6 M et d'hydroxyde de potassium KOH_aq. 12 M) sont choisis en fonction de leurs paramètres acoustiques. La modélisation de la signature acoustique permet de prévoir leur influence respective, comment ils

  15. Modelisation de photodetecteurs a base de matrices de diodes avalanche monophotoniques pour tomographie d'emission par positrons

    NASA Astrophysics Data System (ADS)

    Corbeil Therrien, Audrey

    La tomographie d'emission par positrons (TEP) est un outil precieux en recherche preclinique et pour le diagnostic medical. Cette technique permet d'obtenir une image quantitative de fonctions metaboliques specifiques par la detection de photons d'annihilation. La detection des ces photons se fait a l'aide de deux composantes. D'abord, un scintillateur convertit l'energie du photon 511 keV en photons du spectre visible. Ensuite, un photodetecteur convertit l'energie lumineuse en signal electrique. Recemment, les photodiodes avalanche monophotoniques (PAMP) disposees en matrice suscitent beaucoup d'interet pour la TEP. Ces matrices forment des detecteurs sensibles, robustes, compacts et avec une resolution en temps hors pair. Ces qualites en font un photodetecteur prometteur pour la TEP, mais il faut optimiser les parametres de la matrice et de l'electronique de lecture afin d'atteindre les performances optimales pour la TEP. L'optimisation de la matrice devient rapidement une operation difficile, car les differents parametres interagissent de maniere complexe avec les processus d'avalanche et de generation de bruit. Enfin, l'electronique de lecture pour les matrices de PAMP demeure encore rudimentaire et il serait profitable d'analyser differentes strategies de lecture. Pour repondre a cette question, la solution la plus economique est d'utiliser un simulateur pour converger vers la configuration donnant les meilleures performances. Les travaux de ce memoire presentent le developpement d'un tel simulateur. Celui-ci modelise le comportement d'une matrice de PAMP en se basant sur les equations de physique des semiconducteurs et des modeles probabilistes. Il inclut les trois principales sources de bruit, soit le bruit thermique, les declenchements intempestifs correles et la diaphonie optique. Le simulateur permet aussi de tester et de comparer de nouvelles approches pour l'electronique de lecture plus adaptees a ce type de detecteur. Au final, le simulateur vise a

  16. Diurnal and seasonal variation of monoterpene emission rates for two typical Mediterranean species ( Pinus pinea and Quercus ilex) from field measurements—relationship with temperature and PAR

    NASA Astrophysics Data System (ADS)

    Sabillón, Danelia; Cremades, Lázaro V.

    Two of the most typical Mediterranean tree species ( Pinus pinea [ Pp] and Quercus ilex [ Qi]) were screened for emissions of monoterpenes during the period of June 1997-July 1998 in the field at a semi-rural location near Terrassa (Barcelona, Spain) using a bag-enclosure sampling method followed by gas chromatography analysis with mass selective detection (GC/MSD). A mean of about eight samples per day were measured. A periodical sampling throughout 1 yr allowed to examine data for long-term influences. The main compounds emitted from Pp were linalool, limonene, trans-ocimene and 1,8-cineole (80% on average). Eighty percent of total emissions in Qi were β-pinene, α-pinene, myrcene and sabinene, followed by limonene, β-phellandrene, γ-terpinene and trans-ocimene (20%). On average, the standard monoterpene emission rate from Qi was approximately three times higher than from Pp. Diurnal and seasonal emission variations were characterized with regard to temperature and PAR. For both species a statistically significant variation in monoterpene emissions was observed between seasons for 1 yr period. For Pp, the seasonal variability not accounted for by PAR and temperature is also estimated and compared with existing models in the literature.

  17. Détermination des temps d'arrivée de fronts d'onde acoustiques divergents dans une lame anisotrope

    NASA Astrophysics Data System (ADS)

    Mourad, André; Castagnède, Bemard

    1993-10-01

    The present work is an attempt to extend to the acoustics of anisotropic media the basic principles of optics (i.e. Fermat, and Huyghens principles). The acoustical case is much more intricate because of the possibility of existence of the cuspidal caustics. Firstly, one discusses the mathematical transformation between phase and group wavespeeds. Then, the problem of the reflection of a divergent acoustical ray onto an interface is studied with the help of Huyghens construction. A generalization of the classical refraction law is obtained. Such a result can also be derived from Fermat principle. It is possible to numerically verify the absence of precursor on the converted mode, due to the non-existence of caustics after reflection. A discussion on the so-called Cagniard-de-Hoop contours is introduced, as well as a numerical procedure to compute the direction of the reflected ray. Different cases, depending on the source dimension (point-like or line) and on the orientation cut of the anisotropic solid, are discussed. The extension of the study to several reflections is proposed. Special attention is also devoted to the analysis of the head wavefront reflection. Last, some experimental results dealing with the measurements of group wavespeeds in a transversely isotropic composite material are described. The present study will be followed by the computation of the Green functions and the comparison with experimental displacement fields for various anisotropic solids. Ce travail cherche à étendre les principes de base de l'optique (principe de Fermat et principe d'Huyghens) à l'acoustique cristalline, cas plus complexe par nature, notamment du fait de la possibilité de présence des caustiques en forme de “corne de croissant”. Après une discussion sur la transformation mathématique entre vitesses de phase et vitesses de groupe, l'étude de la réflexion d'un rayon acoustique divergent sur un interface est abordée à l'aide de la construction d

  18. Cristallisation par onde acoustique : le cas de l'héliumCrystallization by acoustic waves: the case of helium

    NASA Astrophysics Data System (ADS)

    Ben Amar, Martine; Brenner, Michael P.; Rice, James R.

    2003-09-01

    We establish a theoretical model to explain the nucleation of a crystal of helium by an acoustic over-pressure. We explain the interfacial laws for this ultra-fast cristallization, close to the sound speed. Assuming spherical symmetry and taking into account the experimental data, we recover the dynamics of the growth and melting during an over-pressure impulse. To cite this article: M. Ben Amar et al., C. R. Mecanique 331 (2003).

  19. Suivi in situ de cultures tridimensionnelles en bioreacteur a perfusion grace a la tomographie d'emission par positrons

    NASA Astrophysics Data System (ADS)

    Chouinard, Julie

    The continuous assessment of developing tissue substitutes is crucial to understand their evolution over time. However, this represents quite a challenge when thick samples must be evaluated with standard microscopy techniques. Common characterization methods are time consuming and usually result in the destruction of the culture. Real-time, in situ, non-invasive and non-destructives methods are needed to monitor the growth of large non-transparent constructs in tissue engineering. Medical imaging modalities, which can provide information on the structure and function of internal organs and tissues in living organisms, have the potential of allowing repetitive monitoring of these 3D cultures in vitro. The working hypothesis of this thesis was to establish standard noninvasive and nondestructive real-time bioreactor imaging protocols for in situ monitoring of the viability and metabolism of endothelial cells when grown in perfused 3D fibrin gel scaffolds. To achieve this goal, a culture chamber with hollow fibers was designed and a pulsatile perfusion bioreactor system, able to promote cell survival and proliferation, was constructed and validated. Standard imaging protocols in Positron Emission Tomography (PET) are not adapted to image bioreactor systems. A suitable method had to be devised using the well-known radiotracer 18F-fluorodeoxyglucose ( 18FDG), a marker of glucose metabolism. Optimal uptake conditions were determined using cell monolayers and the best parameters were then applied on perfused 3D cultures to evaluate perfusion, cell viability and emerging cell structures. After only 12 hours of culture, the cell density could be estimated and cell structures were localized within the fibrin gels after 1-2 weeks of culture. PET is a promising tool for tissue engineering with many specific tracers available that might eventually be able to reveal new information on tissue development. Key words: Endothelial cells, Perfusion bioreactor, Positron Emission

  20. 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

  1. Land use change emissions from oil palm expansion in Pará, Brazil depend on proper policy enforcement on deforested lands

    NASA Astrophysics Data System (ADS)

    Yui, Sahoko; Yeh, Sonia

    2013-12-01

    Brazil aims to increase palm oil production to meet the growing national and global demand for edible oil and biodiesel while preserving environmentally and culturally significant areas. As land use change (LUC) is the result of complex interactions between socio-economic and biophysical drivers operating at multiple temporal and spatial scales, the type and location of LUC depend on drivers such as neighboring land use, conversion elasticity, access to infrastructure, distance to markets, and land suitability. The purpose of this study is to develop scenarios to measure the impact of land conversion under three different enforcement scenarios (none, some, and strict enforcement). We found that converting 22.5 million hectares of land can produce approximately 29 billion gallons (110 billion liters) of biodiesel a year. Of that, 22-71% of the area can come from forest land, conservation units, wetland and indigenous areas, emitting 14-84 gCO2e MJ-1. This direct land use emission alone can be higher than the carbon intensity of diesel that it intends to displace for lowering greenhouse gas emissions. This letter focuses narrowly on GHG emissions and does not address socio-economic-ecological prospects for these degraded lands for palm oil or for other purposes. Future studies should carefully evaluate these tradeoffs.

  2. Etude par Imagerie à faible Niveau dans le proche Infrarouge d'une Emission de la haute Atmosphère

    NASA Astrophysics Data System (ADS)

    Pautet, Pierre-Dominique

    2000-12-01

    requises pour de bonnes observations dans le domaine du proche infrarouge ont aussi été étudiées. Ensuite, la construction d'une station mobile de prise de vues est détaillée. Celle-ci doit permettre d'observer l'émission et d'obtenir des résultats exploitables par la suite. Trois méthodes d'observation ont été décrites: visuelle, photographique et à l'aide d'un détecteur CCD. La troisième, qui a été retenue, a été vue plus en détail. Le matériel utilisé, de la caméra à la plate-forme de prise de vues en passant par les objectifs et les filtres optiques, est ensuite décrit. Lorsque le matériel a été choisi, un protocole d'observation a été défini et mis au point. Le choix du site d'observation a été crucial. Plusieurs lieux géographiques ont été retenus et sont présentés dans le mémoire. Le déroulement d'une séance de prise de vue a été décrit afin de faciliter un futur programme d'observation. Deux séquences types d'observations ont été plus particulièrement détaillées: -la réalisation de panoramas permettant une étude des structures que fait apparaître l'émission, -la réalisation de séquences vidéos afin d'étudier la dynamique du phénomène. Dans une quatrième partie, je décris les méthodes de traitement des images qui ont été développées. Tout d'abord, des prétraitements sont appliqués aux images pour corriger les défauts (champ plat, offset,?). Ensuite, une méthode de restitution géographique permet d'obtenir une image plus exploitable de la couche émissive ; elle n'est alors plus observée à partir d'une station au sol, mais en employant une caméra virtuelle située à la verticale du site d'observation. Différents problèmes liés à cette méthode ont aussi été traités: réfraction atmosphérique proche de l'horizon, passage d'une surface atmosphérique à la surface du pixel correspondant, et effet de Van Rhijn. Plusieurs traitements ont été appliqués aux images pour faciliter leur

  3. THE MEASURES PAR PROJECT

    NASA Astrophysics Data System (ADS)

    Frouin, R. J.; Franz, B.

    2009-12-01

    The solar energy available for photosynthesis, known as PAR, controls the growth of phytoplankton and, therefore, regulates the composition and evolution of marine ecosystems. Knowing the spatial and temporal distribution of PAR over the oceans is critical to understanding biogeochemical cycles of carbon, nutrients, and oxygen, and to address important climate and global change issues such as the fate of anthropogenic atmospheric carbon dioxide. In view of this, a 12-year time series of PAR at the ocean surface, starting in September 1997, is being produced by the NASA Ocean Biology Processing Group from SeaWiFS, MODIS-Terra, and MODIS-Aqua data. The product covers the global oceans, with a spatial resolution of about 9.3x9.3 km (equal area grid) and a temporal resolution of one day. PAR is computed as the difference between the 400-700 nm solar flux incident on the top of the atmosphere (known) and reflected back to space by the atmosphere and surface (derived from satellite radiance), taking into account atmospheric absorption (modeled). Knowledge of pixel composition is not required, eliminating the need for cloud screening and arbitrary assumptions about sub-pixel cloudiness. Combining data from satellite sensors with different equatorial crossing times accounts for the diurnal variability of clouds and, therefore, increases accuracy on a daily time scale. The processing system, including routine check of accuracy and control of quality, is designed to operate during the entire lifetime of SeaWiFS and MODIS, and to accommodate future sensors with ocean-color capabilities. Maps of daily, weekly, and monthly PAR obtained from individual sensors are presented, as well as merged products. Accuracy is quantified in comparisons with other satellite estimates, the National Centers for Environmental Prediction reanalysis product, and in-situ measurements from fixed buoys and platforms. The good statistical performance makes the satellite PAR product suitable for large

  4. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

  5. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre les schémas thérapeutiques et les résultats des traitements pour la pelade par plaques, de même que les aider à identifier les patients pour qui une demande de consultation en dermatologie pourrait s’imposer. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant le traitement de la pelade par plaques. Message principal La pelade par plaques est une forme auto-immune de perte pileuse qui touche à la fois les enfants et les adultes. Même s’il n’y a pas de mortalité associée à la maladie, la morbidité découlant des effets psychologiques de la perte des cheveux peut être dévastatrice. Lorsque la pelade par plaques et le sous-type de la maladie sont identifiés, un schéma thérapeutique approprié peut être amorcé pour aider à arrêter la chute des cheveux et possiblement faire commencer la repousse. Les traitements de première intention sont la triamcinolone intralésionnelle avec des corticostéroïdes topiques ou du minoxidil ou les 2. Les médecins de famille peuvent prescrire ces traitements en toute sécurité et amorcer ces thérapies. Les cas plus avancés ou réfractaires pourraient avoir besoin de diphénylcyclopropénone topique ou d’anthraline topique. On peut traiter la perte de cils avec des analogues de la prostaglandine. Les personnes ayant subi une perte de cheveux abondante peuvent recourir à des options de camouflage ou à des prothèses capillaires. Il est important de surveiller les troubles psychiatriques en raison des effets psychologiques profonds de la perte de cheveux. Conclusion Les médecins de famille verront de nombreux patients qui perdent leurs cheveux. La reconnaissance de la pelade par plaques et la compréhension du processus pathologique sous-jacent permettent d’amorcer un schéma thérapeutique approprié. Les cas plus graves ou r

  6. Improved Satellite-based Photosysnthetically Active Radiation (PAR) for Air Quality Studies

    NASA Astrophysics Data System (ADS)

    Pour Biazar, A.; McNider, R. T.; Cohan, D. S.; White, A.; Zhang, R.; Dornblaser, B.; Doty, K.; Wu, Y.; Estes, M. J.

    2015-12-01

    One of the challenges in understanding the air quality over forested regions has been the uncertainties in estimating the biogenic hydrocarbon emissions. Biogenic volatile organic compounds, BVOCs, play a critical role in atmospheric chemistry, particularly in ozone and particulate matter (PM) formation. In southeastern United States, BVOCs (mostly as isoprene) are the dominant summertime source of reactive hydrocarbon. Despite significant efforts in improving BVOC estimates, the errors in emission inventories remain a concern. Since BVOC emissions are particularly sensitive to the available photosynthetically active radiation (PAR), model errors in PAR result in large errors in emission estimates. Thus, utilization of satellite observations to estimate PAR can help in reducing emission uncertainties. Satellite-based PAR estimates rely on the technique used to derive insolation from satellite visible brightness measurements. In this study we evaluate several insolation products against surface pyranometer observations and offer a bias correction to generate a more accurate PAR product. The improved PAR product is then used in biogenic emission estimates. The improved biogenic emission estimates are compared to the emission inventories over Texas and used in air quality simulation over the period of August-September 2013 (NASA's Discover-AQ field campaign). A series of sensitivity simulations will be performed and evaluated against Discover-AQ observations to test the impact of satellite-derived PAR on air quality simulations.

  7. Brulures par Diluant

    PubMed Central

    Benbrahim, A.; Jerrah, H.; Diouri, M.; Bahechar, N.; Boukind, E.H.

    2009-01-01

    Summary La flamme de diluant est une cause non rare de brûlure dans le contexte marocain. Nous avons jugé intéressant de faire une étude épidémiologique sur la brûlure par flamme de diluant (BFD) au centre national des brûlés (CNB) du CHU Ibn-Rochd de Casablanca. Ce travail a été réalisé sur une période de 10 mois (septembre 2007/juin 2008). Le but du travail est de montrer les caractéristiques de ce type de brûlures pour les prévenir et ce par l'information sur le diluant, produit causant ces brûlures, et ses différents dangers, la brûlure notamment. Durant cette période, nous avons colligé 17 cas de BFD sur un total de 356 patients admis au CNB pour brûlures aiguës toute étiologie confondue. La moyenne d'age des patients concernés est de 32 ans. Ils sont presque tous de sexe masculin (16 hommes/1 femme) et ont des antécédents de toxicomanie et/ou de délinquance. Tous nos patients sont de bas niveau socio-économique et habitent dans des bidonvilles pour la plupart. La brûlure est souvent secondaire à une agression dans la rue (92% des cas). Concernant les caractéristiques de la brûlure, la surface cutanée brûlée moyenne est de 23%; elle est souvent profonde et siège surtout au niveau des membres supérieurs et du tronc. PMID:21991179

  8. Contribution au contrôle de la fluidisation des sédiments marins par ultrasons

    NASA Astrophysics Data System (ADS)

    Bresson, J.; Daïf, A.; Longuemard, J. P.; Mevel, Y.

    1994-08-01

    The authors present an original method based on acoustic propagation of longitudinal waves to determine the state of fluidisation in marine sediments as a function of wave characteristics. Indeed, the pressure variations due to the wave in permeable marine sediments contributes to the desegregation of the inter granular structure. This approach have been tested in wave's channel before being experiment in sea environment. Après avoir présenté le phénomène de fluidisation des sédiments marins et sa modélisation simple, les auteurs étudient dans un canal à houle et expérimentent en mer une méthode, basée sur la propagation d'ondes ultrasonores longitudinales, permettant de détecter l'état de fluidisation du sédiment marin en fonction des caractéristiques de la houle. En effet, les variations de pression engendrées par la houle, dans les sédiments marins perméables, détruisent la liaison du "squelette" inter granulaire existant dans celui-ci quand il est consolidé. Il n'y a plus de contact grain à grain, mais un mince film d'eau sépare complètement ces derniers. On assiste alors à la fluidisation des sédiments près du fond. Cet état est détecté par moyens acoustiques.

  9. Par Pond vegetation status 1996

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-12-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned.

  10. The pars interarticularis stress reaction, spondylolysis, and spondylolisthesis progression.

    PubMed

    Motley, G; Nyland, J; Jacobs, J; Caborn, D N

    1998-10-01

    To review the classification, etiology, clinical and radiologic evaluation, and management of the pars interarticularis stress reaction, spondylolysis, and spondylolisthesis progression. Grateful Med was searched from 1980 to 1998 using the terms "spondylolysis," "spondylolisthesis," "female athlete" "spondylogenic," and "pars interarticularis." The progression from pars interarticularis stress reaction through spondylolysis to spondylolisthesis is common in adolescent athletes, and, because of hormonal influences and cheerleading and gymnastic maneuvers, females are particularly at risk. Proper diagnosis and management include a thorough evaluation, radiographs (possibly with technetium bone scan or single-photon emission computed tomography), activity modification, dietary counseling, a therapeutic exercise program focusing on proper trunk and hip muscle strength and extensibility balances, and education regarding proper back postures, positioning, lifting mechanics, and jump landings. The athletic trainer plays an integral part in managing this injury progression, particularly with identifying at-risk individuals and intervening appropriately.

  11. Exploration of locomotion in the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Jindal, Lavisha; Emberly, Eldon

    2015-03-01

    In many bacteria the ParA/ParB system is responsible for actively segregating DNA during replication. ParB precessively moves by hydrolyzing DNA bound ParA-ATP forming a depleted ParA region in its wake. Recent in-vitro experiments have shown that a ParB covered bead can traverse a ParA bound DNA substrate. It has been suggested that the formation of a gradient in ParA leads to diffusion-ratchet like motion of the ParB bead but its origin and potential consequences requires investigation. We have developed a deterministic model for the in-vitro ParA/ParB system and show that any amount of spatial noise in ParA can lead to the spontaneous formation of its gradient. The velocity of the bead is independent of this noise but depends on the scale over which ParA exerts a force on the bead and the scale over which ParB hydrolyzes ParA from the substrate. There is a particular ratio of these scales at which the velocity is a maximum. We also explore the effects of cooperative vs independent rebinding of ParA to the substrate. Our model shows how the driving force for ParB originates and highlights necessary conditions for directed motion in the in-vitro system that may provide insight into the in-vivo behaviour of the ParA/ParB system.

  12. Developpement de mesures non destructives, par ondes ultrasonores, d'epaisseurs de fronts de solidification dans les reacteurs metallurgiques

    NASA Astrophysics Data System (ADS)

    Floquet, Jimmy

    Dans les cuves d'electrolyse d'aluminium, le milieu de reaction tres corrosif attaque les parois de la cuve, ce qui diminue leur duree de vie et augmente les couts de production. Le talus, qui se forme sous l'effet des pertes de chaleur qui maintiennent un equilibre thermique dans la cuve, sert de protection naturelle a la cuve. Son epaisseur doit etre controlee pour maximiser cet effet. Advenant la resorption non voulue de ce talus, les degats generes peuvent s'evaluer a plusieurs centaines de milliers de dollars par cuve. Aussi, l'objectif est de developper une mesure ultrasonore de l'epaisseur du talus, car elle serait non intrusive et non destructive. La precision attendue est de l'ordre du centimetre pour des mesures d'epaisseurs comprenant 2 materiaux, allant de 5 a 20 cm. Cette precision est le facteur cle permettant aux industriels de controler l'epaisseur du talus de maniere efficace (maximiser la protection des parois tout en maximisant l'efficacite energetique du procede), par l'ajout d'un flux thermique. Cependant, l'efficacite d'une mesure ultrasonore dans cet environnement hostile reste a demontrer. Les travaux preliminaires ont permis de selectionner un transducteur ultrasonore a contact ayant la capacite a resister aux conditions de mesure (hautes temperatures, materiaux non caracterises...). Differentes mesures a froid (traite par analyse temps-frequence) ont permis d'evaluer la vitesse de propagation des ondes dans le materiau de la cuve en graphite et de la cryolite, demontrant la possibilite d'extraire l'information pertinente d'epaisseur du talus in fine. Fort de cette phase de caracterisation des materiaux sur la reponse acoustique des materiaux, les travaux a venir ont ete realises sur un modele reduit de la cuve. Le montage experimental, un four evoluant a 1050 °C, instrumente d'une multitude de capteurs thermique, permettra une comparaison de la mesure intrusive LVDT a celle du transducteur, dans des conditions proches de la mesure

  13. Les Traits acoustiques (Acoustic Features)

    ERIC Educational Resources Information Center

    Rossi, Mario

    1977-01-01

    An analysis of the theory of distinctive features advanced by Roman Jakobson, Gunnar Fant and Morris Halle in "Preliminaries to Speech Analysis." The notion of binarism, the criterion of distinctiveness and the definition of features are discussed. Questions leading to further research are raised. (Text is in French.) (AMH)

  14. Les Traits acoustiques (Acoustic Features)

    ERIC Educational Resources Information Center

    Rossi, Mario

    1977-01-01

    An analysis of the theory of distinctive features advanced by Roman Jakobson, Gunnar Fant and Morris Halle in "Preliminaries to Speech Analysis." The notion of binarism, the criterion of distinctiveness and the definition of features are discussed. Questions leading to further research are raised. (Text is in French.) (AMH)

  15. Par Pond Fish, Water, and Sediment Chemistry

    SciTech Connect

    Paller, M.H.; Wike, L.D.

    1996-06-01

    The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

  16. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

    NASA Astrophysics Data System (ADS)

    Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

    The segregation of DNA prior to cell division is essential for faithful genetic inheritance. In many bacteria, segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and its stimulator protein ParB. Recent experiments suggest that ParA/ParB system motility is driven by a diffusion-ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. We develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB bound cargo. Paradoxically, the resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work sheds light on a new emergent phenomenon in which non-motor proteins work collectively via mechanochemical coupling to propel cargos -- an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

  17. Parallel Climate Analysis Toolkit (ParCAT)

    SciTech Connect

    Smith, Brian Edward

    2013-06-30

    The parallel analysis toolkit (ParCAT) provides parallel statistical processing of large climate model simulation datasets. ParCAT provides parallel point-wise average calculations, frequency distributions, sum/differences of two datasets, and difference-of-average and average-of-difference for two datasets for arbitrary subsets of simulation time. ParCAT is a command-line utility that can be easily integrated in scripts or embedded in other application. ParCAT supports CMIP5 post-processed datasets as well as non-CMIP5 post-processed datasets. ParCAT reads and writes standard netCDF files.

  18. Overproduction and localization of Mycobacterium tuberculosis ParA and ParB proteins

    PubMed Central

    Maloney, Erin; Madiraju, Murty; Rajagopalan, Malini

    2011-01-01

    SUMMARY The ParA and ParB family proteins are required for accurate partitioning of replicated chromosomes. The Mycobacterium tuberculosis genome contains parB, parA and two parA homologs, Rv1708 and Rv3213c. It is unknown if parA and its homologs are functionally related. To understand the roles of ParA and ParB proteins in M. tuberculosis cell cycle, we have evaluated the consequences of their overproduction and visualized their localization patterns in M. smegmatis. We show that cells overproducing of ParA, Rv1708 and Rv3213c and ParB are filamentous and multinucleoidal indicating defects in cell cycle progression. Visualization of green-fluorescent protein fusions of ParA and its homologues showed similar localization patterns with foci at poles, quarter-cell, midcell positions and spiral-like structures indicating that they are functionally related. On the other hand, the ParBGFP fusion protein localized only to the cell poles. The cyan and yellow fluorescent fusion proteins of ParA and ParB, respectively, colocalized at the cell poles indicating that these proteins interact and possibly associate with the chromosomal origin of replication. Collectively our results suggest that the M. tuberculosis Par proteins play important roles in cell cycle progression. PMID:20006309

  19. suPAR: The Molecular Crystal Ball

    PubMed Central

    Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper

    2009-01-01

    soluble urokinase Plasminogen Activator Receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. suPAR exists in three forms; suPARI-III, suPARII-III and suPARI which show different properties due to structural differences. Studies suggest that full-length suPAR is a regulator of uPAR/uPA by acting as uPA-scavenger, whereas the cleaved suPARII-III act as a chemotactic agent promoting the immune response via the SRSRY sequence in the linker-region. This review focus on the various suPAR fragments and their involvement in inflammation and pathogenic processes. We focus on the molecular mechanisms of the suPAR fragments and the link to the inflammatory process, as this could lead to medical applications in infectious and pathological conditions. PMID:19893210

  20. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

    PubMed Central

    Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

    2015-01-01

    The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA–nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos—an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria. PMID:26647183

  1. [Ambroise Paré, landlord].

    PubMed

    Pion-Graff, Joëlle; Bonnichon, Philippe

    2010-01-01

    Paré is well-known through many papers. His incomes allowed him to have a middle-class Parisian living. It is impossible to have an accurate knowledge of his fortune before his death but we have a good idea of his landed property. In fact as a Parishioner of Saint-Andre-des-Arts Church he probably was a landlord only in Paris and its vicinity with a building (rue de l'Hirondelle), two houses (rue Garancière), Meudon, Cormeille-en-Parisis and La-Ville-Du-Bois which the authors describe the present state of.

  2. Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer.

    PubMed

    LeBeau, Aaron M; Duriseti, Sai; Murphy, Stephanie T; Pepin, Francois; Hann, Byron; Gray, Joe W; VanBrocklin, Henry F; Craik, Charles S

    2013-04-01

    Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and (111)In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard (18)F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope (177)Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology.

  3. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target: potential clinical applications

    PubMed Central

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) has been shown to be of special importance during cancer invasion and metastasis. However, currently, tissue samples are needed for measurement of uPAR expression limiting the potential as a clinical routine. Therefore, non-invasive methods are needed. In line with this, uPAR has recently been identified as a very promising imaging target candidate. uPAR consists of three domains attached to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor and binds it natural ligand uPA with high affinity to localize plasminogen activation at the cell surface. Due to the importance of uPAR in cancer invasion and metastasis, a number of high-affinity ligands have been identified during the last decades. These ligands have recently been used as starting point for the development of a number of ligands for imaging of uPAR using various imaging modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker. PMID:23701192

  4. PAR for the Course: A Congruent Pedagogical Approach for a PAR Methods Class

    ERIC Educational Resources Information Center

    Hammond, Joyce D.; Hicks, Maria; Kalman, Rowenn; Miller, Jason

    2005-01-01

    In the past two years, three graduate students and a senior faculty member have co-taught a participatory action research (PAR) course to undergraduate and graduate students. In this article the co-teachers advocate a set of pedagogical principles and practices in a PAR-oriented classroom that establishes congruency with community PAR projects in…

  5. The Pars Interarticularis Stress Reaction, Spondylolysis, and Spondylolisthesis Progression

    PubMed Central

    Motley, Gina; Nyland, John; Jacobs, Jake; Caborn, David N. M.

    1998-01-01

    Objective: To review the classification, etiology, clinical and radiologic evaluation, and management of the pars interarticularis stress reaction, spondylolysis, and spondylolisthesis progression. Data Sources: Grateful Med was searched from 1980 to 1998 using the terms “spondylolysis,” “spondylolisthesis,” “female athlete” “spondylogenic,” and “pars interarticularis.” Data Synthesis: The progression from pars interarticularis stress reaction through spondylolysis to spondylolisthesis is common in adolescent athletes, and, because of hormonal influences and cheerleading and gymnastic maneuvers, females are particularly at risk. Proper diagnosis and management include a thorough evaluation, radiographs (possibly with technetium bone scan or single-photon emission computed tomography), activity modification, dietary counseling, a therapeutic exercise program focusing on proper trunk and hip muscle strength and extensibility balances, and education regarding proper back postures, positioning, lifting mechanics, and jump landings. Conclusions/Recommendations: The athletic trainer plays an integral part in managing this injury progression, particularly with identifying at-risk individuals and intervening appropriately. ImagesFigure 4. PMID:16558534

  6. Par Pond vegetation status Summer 1995 -- Summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1996-01-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  7. Comparative cactus architecture and par interception

    SciTech Connect

    Geller, G.N.; Nobel, P.S. )

    1987-07-01

    Because CO{sup 2} uptake by cacti can be limited by low levels of photosynthetically active radiation (PAR) and because plant form affects PAR interception, various cactus forms were studied using a computer model, field measurements, and laboratory phototropic studies. Model predictions indicated that CO{sub 2} uptake by individual stems at an equinox was greatest when the stem were vertical, but at the summer and the winter solstice CO{sub 2} uptake was greatest for stems titled 30{degree} away from the equator. Stem tilting depended on form and taxonomic group. Not only can the shape of cacti be affected by PAR, but also shape influences PAR interception and hence CO{sub 2} uptake.

  8. Techniques for measuring intercepted and absorbed PAR in corn canopies

    NASA Technical Reports Server (NTRS)

    Gallo, K. P.; Daughtry, C. S. T.

    1984-01-01

    The quantity of radiation potentially available for photosynthesis that is captured by the crop is best described as absorbed photosynthetically active radiation (PAR). Absorbed PAR (APAR) is the difference between descending and ascending fluxes. The four components of APAR were measured above and within two planting densities of corn (Zea mays L.) and several methods of measuring and estimating APAR were examined. A line quantum sensor that spatially averages the photosynthetic photon flux density provided a rapid and portable method of measuring APAR. PAR reflectance from the soil (Typic Argiaquoll) surface decreased from 10% to less than 1% of the incoming PAR as the canopy cover increased. PAR reflectance from the canopy decreased to less than 3% at maximum vegetative cover. Intercepted PAR (1 - transmitted PAR) generally overestimated absorbed PAR by less than 4% throughout most of the growing season. Thus intercepted PAR appears to be a reasonable estimate of absorbed PAR.

  9. Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.

    PubMed

    Duvernay, Matthew; Young, Summer; Gailani, David; Schoenecker, Jonathan; Hamm, Heidi E; Hamm, Heidi

    2013-04-01

    With the recent interest of protease-activated receptors (PAR) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease-activated receptor (PAR)1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes. PAR4-activating peptide (AP)-stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1-AP-stimulated platelets. PAR4-AP-mediated factor V (FV) association with the platelet surface was 1.6-fold greater than for PAR1-AP. Moreover, PAR4 stimulation resulted in a 3-fold greater release of microparticles, compared with PAR1 stimulation. More robust FV secretion and microparticle generation with PAR4-AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18. Inhibition of Rho-kinase reduced PAR4-AP-mediated FV secretion and microparticle generation to PAR1-AP-mediated levels. Thrombin generation assays measuring prothrombinase complex activity demonstrated 1.5-fold higher peak thrombin levels on PAR4-AP-stimulated platelets, compared with PAR1-AP-stimulated platelets. Rho-kinase inhibition reduced PAR4-AP-mediated peak thrombin generation by 25% but had no significant effect on PAR1-AP-mediated thrombin generation. In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation. The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation. These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.

  10. ParCAT: Parallel Climate Analysis Toolkit

    SciTech Connect

    Smith, Brian E.; Steed, Chad A.; Shipman, Galen M.; Ricciuto, Daniel M.; Thornton, Peter E.; Wehner, Michael; Williams, Dean N.

    2013-01-01

    Climate science is employing increasingly complex models and simulations to analyze the past and predict the future of Earth s climate. This growth in complexity is creating a widening gap between the data being produced and the ability to analyze the datasets. Parallel computing tools are necessary to analyze, compare, and interpret the simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools to efficiently use parallel computing techniques to make analysis of these datasets manageable. The toolkit provides the ability to compute spatio-temporal means, differences between runs or differences between averages of runs, and histograms of the values in a data set. ParCAT is implemented as a command-line utility written in C. This allows for easy integration in other tools and allows for use in scripts. This also makes it possible to run ParCAT on many platforms from laptops to supercomputers. ParCAT outputs NetCDF files so it is compatible with existing utilities such as Panoply and UV-CDAT. This paper describes ParCAT and presents results from some example runs on the Titan system at ORNL.

  11. PAR2 regulates regeneration, transdifferentiation, and death

    PubMed Central

    Piran, Ron; Lee, Seung-Hee; Kuss, Pia; Hao, Ergeng; Newlin, Robbin; Millán, José Luis; Levine, Fred

    2016-01-01

    Understanding the mechanisms by which cells sense and respond to injury is central to developing therapies to enhance tissue regeneration. Previously, we showed that pancreatic injury consisting of acinar cell damage+β-cell ablation led to islet cell transdifferentiation. Here, we report that the molecular mechanism for this requires activating protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2 modulation was sufficient to induce islet cell transdifferentiation in the absence of β-cells. Its expression was modulated in an islet cell type-specific manner in murine and human type 1 diabetes (T1D). In addition to transdifferentiation, PAR2 regulated β-cell apoptosis in pancreatitis. PAR2's role in regeneration is broad, as mice lacking PAR2 had marked phenotypes in response to injury in the liver and in digit regeneration following amputation. These studies provide a pharmacologically relevant target to induce tissue regeneration in a number of diseases, including T1D. PMID:27809303

  12. ATP-regulated interactions between P1 ParA, ParB and non-specific DNA that are stabilized by the plasmid partition site, parS

    PubMed Central

    Havey, James C.; Vecchiarelli, Anthony G.; Funnell, Barbara E.

    2012-01-01

    Localization of the P1 plasmid requires two proteins, ParA and ParB, which act on the plasmid partition site, parS. ParB is a site-specific DNA-binding protein and ParA is a Walker-type ATPase with non-specific DNA-binding activity. In vivo ParA binds the bacterial nucleoid and forms dynamic patterns that are governed by the ParB–parS partition complex on the plasmid. How these interactions drive plasmid movement and localization is not well understood. Here we have identified a large protein–DNA complex in vitro that requires ParA, ParB and ATP, and have characterized its assembly by sucrose gradient sedimentation and light scattering assays. ATP binding and hydrolysis mediated the assembly and disassembly of this complex, while ADP antagonized complex formation. The complex was not dependent on, but was stabilized by, parS. The properties indicate that ParA and ParB are binding and bridging multiple DNA molecules to create a large meshwork of protein–DNA molecules that involves both specific and non-specific DNA. We propose that this complex represents a dynamic adaptor complex between the plasmid and nucleoid, and further, that this interaction drives the redistribution of partition proteins and the plasmid over the nucleoid during partition. PMID:21965538

  13. Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions.

    PubMed

    Hosokawa, Kazuya; Ohnishi, Tomoko; Miura, Naoki; Sameshima, Hisayo; Koide, Takehiko; Tanaka, Kenichi A; Maruyama, Ikuro

    2014-01-01

    Thrombin-mediated activation of human platelets involves the G-protein-coupled protease-activated receptors PAR1 and PAR4. Inhibition of PAR1 and/or PAR4 is thought to modulate platelet activation and subsequent procoagulant reactions. However, the antithrombotic effects of PAR1 and PAR4 antagonism have not been fully elucidated, particularly under flow conditions. A microchip-based flow chamber system was used to evaluate the influence of SCH79797 (PAR1 antagonist) and YD-3 (PAR4 antagonist) on thrombus formation mediated by collagen and tissue thromboplastin at shear rates simulating those experienced in small- to medium-sized arteries (600s(-1)) and large arteries and small veins (240s(-1)). At a shear rate of 600s(-1), SCH79797 (10μM) efficiently reduced fibrin-rich platelet thrombi and significantly delayed occlusion of the flow chamber capillary (1.44 fold of control; P<0.001). The inhibitory activity of SCH79797 was diminished at 240s(-1). YD-3 (20μM) had no significant effect at either shear rate. The antithrombotic effects of SCH79797 were significantly augmented when combined with aspirin and AR-C66096 (P2Y12 antagonist), but not with YD-3. In contrast, no significant inhibition of tissue factor-induced clot formation under static conditions was observed in blood treated with SCH79797 and YD-3, although thrombin generation in platelet-rich plasma was weakly delayed by these antagonists. Our results suggest that the antithrombotic activities of PAR1 and/or PAR4 antagonism is influenced by shear conditions as well as by combined platelet inhibition with aspirin and a P2Y12-antagonist. © 2013.

  14. Humanizing the Protease-Activated Receptor (PAR) Expression Profile in Mouse Platelets by Knocking PAR1 into the Par3 Locus Reveals PAR1 Expression Is Not Tolerated in Mouse Platelets

    PubMed Central

    French, Shauna L.; Paramitha, Antonia C.; Moon, Mitchell J.; Dickins, Ross A.; Hamilton, Justin R.

    2016-01-01

    Anti-platelet drugs are the mainstay of pharmacotherapy for heart attack and stroke prevention, yet improvements are continually sought. Thrombin is the most potent activator of platelets and targeting platelet thrombin receptors (protease-activated receptors; PARs) is an emerging anti-thrombotic approach. Humans express two PARs on their platelets–PAR1 and PAR4. The first PAR1 antagonist was recently approved for clinical use and PAR4 antagonists are in early clinical development. However, pre-clinical studies examining platelet PAR function are challenging because the platelets of non-primates do not accurately reflect the PAR expression profile of human platelets. Mice, for example, express Par3 and Par4. To address this limitation, we aimed to develop a genetically modified mouse that would express the same repertoire of platelet PARs as humans. Here, human PAR1 preceded by a lox-stop-lox was knocked into the mouse Par3 locus, and then expressed in a platelet-specific manner (hPAR1-KI mice). Despite correct targeting and the predicted loss of Par3 expression and function in platelets from hPAR1-KI mice, no PAR1 expression or function was detected. Specifically, PAR1 was not detected on the platelet surface nor internally by flow cytometry nor in whole cell lysates by Western blot, while a PAR1-activating peptide failed to induce platelet activation assessed by either aggregation or surface P-selectin expression. Platelets from hPAR1-KI mice did display significantly diminished responsiveness to thrombin stimulation in both assays, consistent with a Par3-/- phenotype. In contrast to the observations in hPAR1-KI mouse platelets, the PAR1 construct used here was successfully expressed in HEK293T cells. Together, these data suggest ectopic PAR1 expression is not tolerated in mouse platelets and indicate a different approach is required to develop a small animal model for the purpose of any future preclinical testing of PAR antagonists as anti-platelet drugs. PMID

  15. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

    PubMed

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer (64)Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

  16. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation.

    PubMed

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2016-04-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins.

  17. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

    PubMed Central

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

    2016-01-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

  18. suPAR and Team Nephrology

    PubMed Central

    2014-01-01

    Primary focal segmental glomerulosclerosis (FSGS) accounts for nearly 10 % of patients who require renal replacement therapy. Elevated circulating levels of soluble urokinase receptor (suPAR) have been identified as a biomarker to discriminate primary FSGS from other glomerulopathies. Subsequent reports have questioned the diagnostic utility of this test. In a study in BMC Medicine, Huang et al. demonstrate that urinary soluble urokinase receptor (suPAR) excretion assists in distinguishing primary FSGS from other glomerular diseases, and that high plasma suPAR concentrations are not directly linked to a decline in glomerular filtration rate (GFR). This observation suggests that further investigation of suPAR is warranted in patients with FSGS. It should be interpreted in light of a recent report that B7-1 is expressed in the podocytes of a subset of patients with FSGS, and that blocking this molecule may represent the first successful targeted intervention for this disease. These advances highlight the rapid pace of scientific progress in the field of nephrology. Nephrologists should work together, share resources, and expedite the design of protocols to evaluate these novel biomarkers in a comprehensive and scientifically valid manner. Please see related article http://www.biomedcentral.com/1741-7015/12/81. PMID:24885021

  19. PAR Corneal Topography System (PAR CTS): the clinical application of close-range photogrammetry.

    PubMed

    Belin, M W; Cambier, J L; Nabors, J R; Ratliff, C D

    1995-11-01

    The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system which uses close-range photogrammetry (rasterphotogrammetry) to measure and produce a topographic map of the corneal surface. The PAR CTS makes direct point-by-point measurements of surface elevation using a stereo-triangulation technique. The CTS uses a grid pattern composed of horizontal and vertical lines spaced about 0.2 mm (200 microns) apart. Each grid intersection comprises a surface feature which can be located in multiple images and used to generate an (x,y,z) coordinate. Unlike placido disc-based videokeratoscopes, the PAR CTS requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. In addition to surface elevation, the PAR CTS computes axial and tangential curvatures and refractive power. Difference maps are available in all curvatures, refractive power, and in absolute elevation.

  20. First-in-human uPAR PET: Imaging of Cancer Aggressiveness

    PubMed Central

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene; Christensen, Camilla; Madsen, Jacob; Nielsen, Carsten H.; Thurison, Tine; Klausen, Thomas Levin; Holm, Søren; Loft, Annika; Berthelsen, Anne Kiil; Ploug, Michael; Pappot, Helle; Brasso, Klaus; Kroman, Niels; Højgaard, Liselotte; Kjaer, Andreas

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with 64Cu for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of 64Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment with laboratory blood screening tests was performed before and after PET ligand injection. In a subgroup of the patients, the in vivo stability of our targeted PET ligand was determined in collected blood and urine. No adverse or clinically detectable side effects in any of the 10 patients were found. The ligand exhibited good in vivo stability and fast clearance from plasma and tissue compartments by renal excretion. In addition, high uptake in both primary tumor lesions and lymph node metastases was seen and paralleled high uPAR expression in excised tumor tissue. Overall, this first-in-human study therefore provides promising evidence for safe use of 64Cu-DOTA-AE105 for uPAR PET imaging in cancer patients. PMID:26516369

  1. View from west to east of PAR site resident engineer's ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from west to east of PAR site resident engineer's office building (REOB) - Stanley R. Mickelsen Safeguard Complex, Resident Engineers Office Building, Southeast of intersection of PAR Access Road & Fourth Avenue, Nekoma, Cavalier County, ND

  2. Élaboration de films de molécules organiques par ablation par laser UV

    NASA Astrophysics Data System (ADS)

    Hernandez-Perez, M. A.; Garapon, C.; Champeaux, C.; Coleman, A. W.

    2006-12-01

    Les potentialités des méthodes de dépôt par ablation laser (PLD) pour la préparation de films minces de matériaux organiques sont illustrées par un bref rappel bibliographique et par des résultats expérimentaux concernant des molécules d'intérêt biologique (acides aminés, calix-arènes, protéines). Les films sont préparés par PLD avec un laser KrF sans dégradation de la structure chimique des molécules dans une gamme de fluences de quelques dizaines à quelques centaines de mJ/cm2. Les propriétés structurales et optiques des films sont étudiées en fonction de la fluence du laser et mettent en évidence des arrangements moléculaires particuliers induits par cette méthode de dépôt. Le guidage optique a été obtenu pour des films de toutes ces molécules.

  3. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition Assembly

    SciTech Connect

    B Chaudhuri; S Gupta; V Urban; M Chance; R DMello; L Smith; K Lyons; J Gee

    2011-12-31

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  4. Kallikrein 6 Signals through PAR1 and PAR2 to Promote Neuron Injury and Exacerbate Glutamate Neurotoxicity

    PubMed Central

    Yoon, Hyesook; Radulovic, Maja; Wu, Jianmin; Blaber, Sachiko I.; Blaber, Michael; Fehlings, Michael G.; Scarisbrick, Isobel A.

    2014-01-01

    CNS trauma generates a proteolytic imbalance contributing to secondary injury, including axonopathy and neuron degeneration. Kallikrein 6 (Klk6) is a serine protease implicated in neurodegeneration and here we investigate the role of protease activated receptors 1 (PAR1) and PAR2 in mediating these effects. First we demonstrate Klk6 and the prototypical activator of PAR1, thrombin, as well as PAR1 and PAR2, are each elevated in murine experimental traumatic spinal cord injury (SCI) at acute or subacute time points. Recombinant Klk6 triggered ERK1/2 signaling in cerebellar granule neurons and in the NSC34 spinal cord motoneuron cell line, in a PI3K and MEK-dependent fashion. Importantly, lipopeptide inhibitors of PAR1 or PAR2, and PAR1 genetic deletion, each reduced Klk6-ERK1/2 activation. In addition, Klk6 and thrombin promoted degeneration of cerebellar neurons and exacerbated glutamate neurotoxicity. Moreover, genetic deletion of PAR1 blocked thrombin-mediated cerebellar neurotoxicity and reduced the neurotoxic effects of Klk6. Klk6 also increased glutamate-mediated Bim signaling, PARP cleavage and lactate dehydrogenase (LDH) release in NSC34 motoneurons and these effects were blocked by PAR1 and PAR2 lipopeptide inhibitors. Taken together these data point to a novel Klk6-signaling axis in CNS neurons that is mediated by PAR1 and PAR2 and is positioned to contribute to neurodegeneration. PMID:23647384

  5. A Combined Global and Local Approach to Elucidate Spatial Organization of the Mycobacterial ParB-parS Partition

    SciTech Connect

    Chaudhuri, Barnali; Gupta, Sayan; Urban, Volker S; Chance, Mark; D'Mello, Rhijuta; Smith, Lauren; Lyons, Kelly; Gee, Jessica

    2010-01-01

    Combining diverse sets of data at global (size, shape) and local (residue) scales is an emerging trend for elucidating the organization and function of the cellular assemblies. We used such a strategy, combining data from X-ray and neutron scattering with H/D-contrast variation and X-ray footprinting with mass spectrometry, to elucidate the spatial organization of the ParB-parS assembly from Mycobacterium tuberculosis. The ParB-parS participates in plasmid and chromosome segregation and condensation in predivisional bacterial cells. ParB polymerizes around the parS centromere(s) to form a higher-order assembly that serves to recruit cyto-skeletal ParA ATPases and SMC proteins for chromosome segregation. A hybrid model of the ParB-parS was built by combining and correlating computational models with experiment-derived information about size, shape, position of the symmetry axis within the shape, internal topology, DNA-protein interface, exposed surface patches, and prior knowledge. This first view of the ParB-parS leads us to propose how ParB spread on the chromosome to form a larger assembly.

  6. Host response biomarker in sepsis: suPAR detection.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna

    2015-01-01

    Recent studies of our group have shown that suPAR may complement APACHE II score for risk assessment in sepsis. suPAR may be measured in serum of patients by an enzyme immunosorbent assay developed by Virogates (suPARnostic™). Production of suPAR from circulating neutrophils and monocytes may be assessed after isolation of neutrophils and monocytes and ex vivo culture. This is followed by measurement of suPAR in culture supernatants.

  7. Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation.

    PubMed

    Benton, Richard; Palacios, Isabel M; St Johnston, Daniel

    2002-11-01

    PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries.

  8. [Ambroise Paré in French literature].

    PubMed

    Dumaitre, P

    1995-01-01

    The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

  9. [Ambroise Paré and Latin].

    PubMed

    Drouin, Emmanuel

    2010-06-01

    We report a study of a medical book written by Antoine Mizaud (Memorabilium utilium, in ac iucundorum aphorismos Arcanorum omnis generis locupletes, perpulchre digestae), which was written in Latin, but has been extensively annotated in French.The book is from the personal collection of one of the physicians of Napoleon III. There is an oral tradition within his family that one of the works in the book had been annotated by Ambroise Paré. We know very little, apart from a few receipts and his signature, about the writing of the master of French surgery. Did he understand the language of Galen? There are many annotated passages in the works of Pare which are in the book. We examine whether these annotations were actually made by Ambroise Paré or whether they were done for him.

  10. Les Brulures Chimiques Par Le Laurier Rose

    PubMed Central

    Bakkali, H.; Ababou, M.; Nassim Sabah, T.; Moussaoui, A.; Ennouhi, A.; Fouadi, F.Z.; Siah, S.; Ihrai, H.

    2010-01-01

    Summary Le laurier rose ou Nerium oleander est un arbuste qui pousse naturellement dans les régions méditerranéennes. Au Maroc on le trouve dans les lieux humides. Il est réputé par ses risques de toxicité systémique en cas d'empoisonnement à cause de la présence de deux alcaloïdes, surtout l'oléandrine. La littérature illustre des cas d'utilisation locale des feuilles de cette plante contre la gale, les hémorroïdes et les furoncles. Nous rapportons deux cas de brûlures chimiques par le laurier rose de gravité différente. Cela doit aboutir à une information élargie de la population, ainsi qu'une réglementation stricte de sa commercialisation. PMID:21991211

  11. Combined DSEK and Transconjunctival Pars Plana Vitrectomy

    PubMed Central

    Sane, Mona; Shaikh, Naazli

    2016-01-01

    We report here three patients who underwent combined Descemet's stripping with endothelial keratoplasty and transconjunctival pars plana vitrectomy for bullous keratopathy and posterior segment pathology. A surgical technique and case histories are described. Anatomic and visual outcomes of combined Descemet's stripping with endothelial keratoplasty and vitrectomy were excellent. Our experience provides technical guidelines and limitations. The combined minimally invasive techniques allow for rapid anatomical recovery and return of function and visual acuity in a single sitting. PMID:27413563

  12. Par Pond refill water quality sampling

    SciTech Connect

    Koch, J.W. II; Martin, F.D.; Westbury, H.M.

    1996-08-01

    This study was designed to document anoxia and its cause in the event that the anoxia caused a fish kill. However, no fish kill was observed during this study, and dissolved oxygen and nutrient concentrations generally remained within the range expected for southeastern reservoirs. Par Pond water quality monitoring will continue during the second summer after refill as the aquatic macrophytes become reestablished and nutrients in the sediments are released to the water column.

  13. Critical Role for PAR1 in Kallikrein 6-Mediated Oligodendrogliopathy

    PubMed Central

    Burda, Joshua E.; Radulovic, Maja; Yoon, Hyesook; Scarisbrick, Isobel A.

    2014-01-01

    Kallikrein 6 (Klk6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of Klk6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke and glioblastoma. Taken with recent evidence establishing Klk6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that Klk6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR+/+ but not PAR−/− mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1+ oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that PAR1 or PAR1-agonists may represent new targets to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease. PMID:23832758

  14. TEMPORAL VARIABILITY IN BASAL ISOPRENE EMISSION FACTOR

    EPA Science Inventory

    Seasonal variability in basal isoprene emission factor (micrograms C /g hr or nmol/ m2 sec, leaf temperature at 30 degrees C and photosynthetically active radiation (PAR) at 1000 micromol/ m2 sec) was studied during the 1998 growing season at Duke Forest in the North Carolina Pie...

  15. TEMPORAL VARIABILITY IN BASAL ISOPRENE EMISSION FACTOR

    EPA Science Inventory

    Seasonal variability in basal isoprene emission factor (micrograms C /g hr or nmol/ m2 sec, leaf temperature at 30 degrees C and photosynthetically active radiation (PAR) at 1000 micromol/ m2 sec) was studied during the 1998 growing season at Duke Forest in the North Carolina Pie...

  16. Conception et calibration d'un sonoreacteur pour l'oxydation de la cellulose par le systeme TEMPO/NaOCl/NaBr

    NASA Astrophysics Data System (ADS)

    Paquin, Michel

    grande consommation d'energie et de reactif qui rend le procede difficilement accessible au milieu industriel. L'utilisation des ultrasons lors de la reaction d'oxydation permet de reduire de 50% le temps de reaction et d'autant la consommation de produits chimiques. Actuellement le processus d'oxydation s'effectue en mode discontinu pour une quantite de 20 grammes de pate dans un reacteur en verre dans un bain a ultrason. L'objectif principal de ce travail est d'elaborer un sonoreacteur en mode semi-continu afin d'etre en mesure de transferer une reaction d'oxydation du mode discontinu en mode semi-continu. Le transfert de reaction sera effectue en realisant la calibration de l'activite acoustique des deux differents reacteurs, discontinu et semi-continu, par la methode de Weissler. La methode de Weissler quantifie le taux de production radicalaire en mesurant la formation d'iode moleculaire d'une solution aqueuse d'iodure de potassium sous ultrason. Suite a sa calibration, le sonoreacteur pilote (mode semi-continu) a demontre une augmentation de la production radicalaire de 683 % a 170 kHz en comparaison avec l'utilisation d'un bain a ultrason a la meme frequence. Lors de la reaction d'oxydation, la puissance optimale utilisee dans le bain a ultrason a 170 kHz est de 1000 W. La puissance utilisee selon les resultats de calibration obtenue dans le sonoreacteur pilote est de 125 W soit une diminution de l'energie appliquee de 87,5 %. Lors de la reaction d'oxydation, le taux de production des groupements carboxylates est de 2,6 mmol COOH kg/min dans le bain a ultrason et de 6,87 mmol COOH kg/min dans le sonoreacteur pilote soit une augmentation de 164% du taux de formation. Selon les resultats obtenus, l'utilisation d'un sonoreacteur en mode continu peut etre envisageable pour la reaction d'oxydation de la cellulose par le systeme TEMPO-NaOCl-NaBr en industrie au niveau industriel.

  17. The novel PAR2 ligand C391 blocks multiple PAR2 signalling pathways in vitro and in vivo

    PubMed Central

    Boitano, Scott; Hoffman, Justin; Flynn, Andrea N; Asiedu, Marina N; Tillu, Dipti V; Zhang, Zhenyu; Sherwood, Cara L; Rivas, Candy M; DeFea, Kathryn A; Vagner, Josef; Price, Theodore J

    2015-01-01

    Background and Purpose Proteinase-activated receptor-2 (PAR2) is a GPCR linked to diverse pathologies, including acute and chronic pain. PAR2 is one of the four PARs that are activated by proteolytic cleavage of the extracellular amino terminus, resulting in an exposed, tethered peptide agonist. Several peptide and peptidomimetic agonists, with high potency and efficacy, have been developed to probe the functions of PAR2, in vitro and in vivo. However, few similarly potent and effective antagonists have been described. Experimental Approach We modified the peptidomimetic PAR2 agonist, 2-furoyl-LIGRLO-NH2, to create a novel PAR2 peptidomimetic ligand, C391. C391 was evaluated for PAR2 agonist/antagonist activity to PAR2 across Gq signalling pathways using the naturally expressing PAR2 cell line 16HBE14o-. For antagonist studies, a highly potent and specific peptidomimetic agonist (2-aminothiazo-4-yl-LIGRL-NH2) and proteinase agonist (trypsin) were used to activate PAR2. C391 was also evaluated in vivo for reduction of thermal hyperalgesia, mediated by mast cell degranulation, in mice. Key Results C391 is a potent and specific peptidomimetic antagonist, blocking multiple signalling pathways (Gq-dependent Ca2+, MAPK) induced following peptidomimetic or proteinase activation of human PAR2. In a PAR2-dependent behavioural assay in mice, C391 dose-dependently (75 μg maximum effect) blocked the thermal hyperalgesia, mediated by mast cell degranulation. Conclusions and Implications C391 is the first low MW antagonist to block both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation. C391 represents a new molecular structure for PAR2 antagonism and can serve as a basis for further development for this important therapeutic target. PMID:26140338

  18. Review of PAR parameterizations in ocean ecosystem models

    NASA Astrophysics Data System (ADS)

    Byun, Do-Seong; Wang, Xiao Hua; Hart, Deirdre E.; Zavatarelli, Marco

    2014-12-01

    Commonly-used empirical equations for calculating downward 'photosynthetically available radiation' or PAR were reviewed in order to identify a more theoretically-sound parameterization for application to ocean biogeochemical models. Three different forms of broadband PAR parameterization are currently employed in biogeochemical models, each of them originating from the downward irradiance formulations normally applied to ocean circulation models, which produce poor attenuation estimates for PAR. Two of the PAR formulations, a single-exponential function and a double-exponential function, are parameterized by multiplying surface irradiance by a coefficient determining the portion of underwater PAR. The third formulation uses the second term of the double-exponential function. After elucidating the theoretical problems of modeling PAR using these parameterizations, we suggest an improved, R-modified double-exponential PAR formulation, including Paulson and Simpson's (1977) parameter values. We also newly estimate PAR penetration via least-squares fitting of values digitized from Jerlov's (1976) observations in different oceanic water types, and compare this PAR-observation derived parameterization with our new, theoretical, R-modified parameterization. Finally, we discuss a universal limitation inherent in current theoretical approaches to PAR parameterization.

  19. Modelisation par elements finis du muscle strie

    NASA Astrophysics Data System (ADS)

    Leonard, Mathieu

    Ce present projet de recherche a permis. de creer un modele par elements finis du muscle strie humain dans le but d'etudier les mecanismes engendrant les lesions musculaires traumatiques. Ce modele constitue une plate-forme numerique capable de discerner l'influence des proprietes mecaniques des fascias et de la cellule musculaire sur le comportement dynamique du muscle lors d'une contraction excentrique, notamment le module de Young et le module de cisaillement de la couche de tissu conjonctif, l'orientation des fibres de collagene de cette membrane et le coefficient de poisson du muscle. La caracterisation experimentale in vitro de ces parametres pour des vitesses de deformation elevees a partir de muscles stries humains actifs est essentielle pour l'etude de lesions musculaires traumatiques. Le modele numerique developpe est capable de modeliser la contraction musculaire comme une transition de phase de la cellule musculaire par un changement de raideur et de volume a l'aide des lois de comportement de materiau predefinies dans le logiciel LS-DYNA (v971, Livermore Software Technology Corporation, Livermore, CA, USA). Le present projet de recherche introduit donc un phenomene physiologique qui pourrait expliquer des blessures musculaires courantes (crampes, courbatures, claquages, etc.), mais aussi des maladies ou desordres touchant le tissu conjonctif comme les collagenoses et la dystrophie musculaire. La predominance de blessures musculaires lors de contractions excentriques est egalement exposee. Le modele developpe dans ce projet de recherche met ainsi a l'avant-scene le concept de transition de phase ouvrant la porte au developpement de nouvelles technologies pour l'activation musculaire chez les personnes atteintes de paraplegie ou de muscles artificiels compacts pour l'elaboration de protheses ou d'exosquelettes. Mots-cles Muscle strie, lesion musculaire, fascia, contraction excentrique, modele par elements finis, transition de phase

  20. Developpement d'algorithmes de reconstruction statistique appliques en tomographie rayons-X assistee par ordinateur

    NASA Astrophysics Data System (ADS)

    Thibaudeau, Christian

    La tomodensitometrie (TDM) permet d'obtenir, et ce de facon non invasive, une image tridimensionnelle de l'anatomie interne d'un sujet. Elle constitue l'evolution logique de la radiographie et permet l'observation d'un volume sous differents plans (sagittal, coronal, axial ou n'importe quel autre plan). La TDM peut avantageusement completer la tomographie d'emission par positrons (TEP), un outil de predilection utilise en recherche biomedicale et pour le diagnostic du cancer. La TEP fournit une information fonctionnelle, physiologique et metabolique, permettant la localisation et la quantification de radiotraceurs a l'interieur du corps humain. Cette derniere possede une sensibilite inegalee, mais peut neanmoins souffrir d'une faible resolution spatiale et d'un manque de repere anatomique selon le radiotraceur utilise. La combinaison, ou fusion, des images TEP et TDM permet d'obtenir cette localisation anatomique de la distribution du radiotraceur. L'image TDM represente une carte de l'attenuation subie par les rayons-X lors de leur passage a travers les tissus. Elle permet donc aussi d'ameliorer la quantification de l'image TEP en offrant la possibilite de corriger pour l'attenuation. L'image TDM s'obtient par la transformation de profils d'attenuation en une image cartesienne pouvant etre interpretee par l'humain. Si la qualite de cette image est fortement influencee par les performances de l'appareil, elle depend aussi grandement de la capacite de l'algorithme de reconstruction a obtenir une representation fidele du milieu image. Les techniques de reconstruction standards, basees sur la retroprojection filtree (FBP, filtered back-projection), reposent sur un modele mathematiquement parfait de la geometrie d'acquisition. Une alternative a cette methode etalon est appelee reconstruction statistique, ou iterative. Elle permet d'obtenir de meilleurs resultats en presence de bruit ou d'une quantite limitee d'information et peut virtuellement s'adapter a toutes formes

  1. A Conserved Mode of Protein Recognition and Binding in a ParD−ParE Toxin−Antitoxin Complex

    SciTech Connect

    Dalton, Kevin M.; Crosson, Sean

    2010-05-06

    Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and binding groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.

  2. A new model for estimating boreal forest fPAR

    NASA Astrophysics Data System (ADS)

    Majasalmi, Titta; Rautiainen, Miina; Stenberg, Pauline

    2014-05-01

    Life on Earth is continuously sustained by the extraterrestrial flux of photosynthetically active radiation (PAR, 400-700 nm) from the sun. This flux is converted to biomass by chloroplasts in green vegetation. Thus, the fraction of absorbed PAR (fPAR) is a key parameter used in carbon balance studies, and is listed as one of the Essential Climate Variables (ECV). Temporal courses of fPAR for boreal forests are difficult to measure, because of the complex 3D structures. Thus, they are most often estimated based on models which quantify the dependency of absorbed radiation on canopy structure. In this study, we adapted a physically-based canopy radiation model into a fPAR model, and compared modeled and measured fPAR in structurally different boreal forest stands. The model is based on the spectral invariants theory, and uses leaf area index (LAI), canopy gap fractions and spectra of foliage and understory as input data. The model differs from previously developed more detailed fPAR models in that the complex 3D structure of coniferous forests is described using an aggregated canopy parameter - photon recollision probability p. The strength of the model is that all model inputs are measurable or available through other simple models. First, the model was validated with measurements of instantaneous fPAR obtained with the TRAC instrument in nine Scots pine, Norway spruce and Silver birch stands in a boreal forest in southern Finland. Good agreement was found between modeled and measured fPAR. Next, we applied the model to predict temporal courses of fPAR using data on incoming radiation from a nearby flux tower and sky irradiance models. Application of the model to simulate diurnal and seasonal values of fPAR indicated that the ratio of direct-to-total incident radiation and leaf area index are the key factors behind the magnitude and variation of stand-level fPAR values.

  3. Emissions Inventory

    EPA Pesticide Factsheets

    This page describes the role of emission inventories in the air quality management process, a description of how emission inventories are developed, and where U.S. emission inventory information can be found.

  4. 2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) BARRACKS WITH RADAR ATTACHED. - Nike Hercules Missile Battery Summit Site, Battery Control Administration & Barracks Building, Anchorage, Anchorage, AK

  5. First 18F-labeled ligand for PET imaging of uPAR: In vivo studies in human prostate cancer xenografts☆

    PubMed Central

    Persson, Morten; Liu, Hongguang; Madsen, Jacob; Cheng, Zhen; Kjaer, Andreas

    2014-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA-conjugated version (NOTA-AE105) for development of the first 18F-labeled uPAR positron-emission-tomography PET ligand using the Al18F radiolabeling method. In this study, the potential of 18F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated. Methods NOTA-conjugated AE105 was synthesized and radiolabeled with 18F-AlF according to a recently published optimized protocol. The labeled product was purified by reverse phase high performance liquid chromatography RP-HPLC. The tumor targeting properties were evaluated in mice with subcutaneously inoculated PC-3 xenografts using small animal PET and ex vivo biodistribution studies. uPAR-binding specificity was studied by coinjection of an excess of a uPAR antagonist peptide AE105 analogue (AE152). Results NOTA-AE105 was labeled with 18F-AlF in high radiochemical purity (> 92%) and yield (92.7%) and resulted in a specific activity of greater than 20 GBq/μmol. A high and specific tumor uptake was found. At 1 h post injection, the uptake of 18F-AlF-NOTA-AE105 in PC-3 tumors was 4.22 ± 0.13%ID/g. uPAR-binding specificity was demonstrated by a reduced uptake of 18F-AlF-NOTA-AE105 after coinjection of a blocking dose of uPAR antagonist at all three time points investigated. Good tumor-to-background ratio was observed with small animal PET and confirmed in the biodistribution analysis. Ex vivo uPAR expression analysis on extracted tumors confirmed human uPAR expression that correlated close with tumor uptake of 18F-AlF-NOTA-AE105. Conclusion The first 18F-labeled uPAR PET ligand, 18F-AlF-NOTA-AE105, has successfully been prepared and effectively visualized noninvasively uPAR positive prostate cancer. The favorable in

  6. Taare Zameen Par and dyslexic savants

    PubMed Central

    Chakravarty, Ambar

    2009-01-01

    The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at school and at home of a child with dyslexia and his eventual success after his artistic talents are discovered by his art teacher at the boarding school. The film hints at a curious neurocognitive phenomenon of creativity in the midst of language disability, as exemplified in the lives of people like Leonardo da Vinci and Albert Einstein, both of whom demonstrated extraordinary creativity even though they were probably affected with developmental learning disorders. It has been hypothesized that a developmental delay in the dominant hemisphere most likely ‘disinhibits’ the nondominant parietal lobe, unmasking talents—artistic or otherwise—in some such individuals. It has been suggested that, in remedial training, children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to the usual overemphasis on the correction of the disturbed coded symbol operations. PMID:20142854

  7. Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa

    PubMed Central

    2013-01-01

    Background The ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa. It was demonstrated that in the presence of antimicrobials, ParR enhances bacterial survival by distinct mechanisms including activation of the mexXY efflux genes, enhancement of lipopolysaccharide modification through the arn operon, and reduction of the expression of oprD porin. Results In this study, we report on transcriptomic analyses of P. aeruginosa PAO1 wild type and parS and parR mutants growing in a defined minimal medium. Our transcriptomic analysis provides the first estimates of transcript abundance for the 5570 coding genes in P. aeruginosa PAO1. Comparative transcriptomics of P. aeruginosa PAO1 and par mutants identified a total of 464 genes regulated by ParS and ParR. Results also showed that mutations in the parS/parR system abolished expression of the mexEF-oprN operon by down-regulating the regulatory gene mexS. In addition to the known effects on drug resistance genes, transcript abundances of the quorum sensing genes (rhlIR and pqsABCDE-phnAB) were higher in both parS and parR mutants. In accordance with these results, a significant portion of the ParS/ParR regulated genes belonged to the MexEF-OprN and quorum sensing regulons. Deletion of the par genes also led to increased phenazine production and swarming motility, consistent with the up-regulation of the phenazine and rhamnolipid biosynthetic genes, respectively. Conclusion Our results link the ParS/ParR two component signal transduction system to MexEF-OprN and quorum sensing systems in P. aeruginosa. These results expand our understanding of the roles of the ParS/ParR system in the regulation of gene expression in P. aeruginosa, especially in the absence of antimicrobials. PMID:24034668

  8. TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

    PubMed Central

    Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

    2011-01-01

    This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

  9. Tumour-suppression activity of the proapoptotic regulator Par4.

    PubMed

    García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J; Martín-Caballero, Juan; Flores, Juana M; Diaz-Meco, Maria T; Moscat, Jorge; Serrano, Manuel

    2005-06-01

    The proapoptotic protein encoded by Par4 (prostate apoptosis response 4) has been implicated in tumour suppression, particularly in the prostate. We report here that Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4-null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. Finally, the uterus and prostate of young Par4-null mice have increased levels of the apoptosis inhibitor XIAP (X-chromosome-linked inhibitor of apoptosis), supporting the previously proposed function of Par4 as an inhibitor of the (zeta)PKC (atypical protein kinase)-NF-(kappa)B (nuclear factor-(kappa)B)-XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate.

  10. Tumour-suppression activity of the proapoptotic regulator Par4

    PubMed Central

    García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J.; Martín-Caballero, Juan; Flores, Juana M.; Diaz-Meco, Maria T.; Moscat, Jorge; Serrano, Manuel

    2005-01-01

    The proapoptotic protein encoded by Par4 (prostate apoptosis response 4) has been implicated in tumour suppression, particularly in the prostate. We report here that Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4-null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. Finally, the uterus and prostate of young Par4-null mice have increased levels of the apoptosis inhibitor XIAP (X-chromosome-linked inhibitor of apoptosis), supporting the previously proposed function of Par4 as an inhibitor of the ζPKC (atypical protein kinase)–NF-κB (nuclear factor-κB)–XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate. PMID:15877079

  11. [Around Ambroise Paré: his pupils and friends].

    PubMed

    Dumaître, P

    1996-01-01

    The most important pupil of Paré was Jacques Guillemeau (1550-1613), a famous surgeon from Montpellier. He lived at Paré's during eight years and wrote there his first work "Traité des maladies des yeux" (1585) and was really his "spiritual son". The barber-surgeon Martin Boursier, husband of the famous midwife Louise Bourgeois stayed twenty years with Paré and she learned her practice in his works. Attracted by Paré's fame, Melchior Sebiz (1539-1625) who shall become a famous professor of medicine in Strasbourg attended Paré's lessons and "was with him in great friendship". Among his friends, Thierry de Héry (ca. 1505-ca. 1560), companion of his youth as a barber-surgeon and author of the first French book on syphilis seems to have been the dearest and the nearest to his heart.

  12. Structures of partition protein ParA with nonspecific DNA and ParB effector reveal molecular insights into principles governing Walker-box DNA segregation.

    PubMed

    Zhang, Hengshan; Schumacher, Maria A

    2017-03-01

    Walker-box partition systems are ubiquitous in nature and mediate the segregation of bacterial and archaeal DNA. Well-studied plasmid Walker-box partition modules require ParA, centromere-DNA, and a centromere-binding protein, ParB. In these systems, ParA-ATP binds nucleoid DNA and uses it as a substratum to deliver ParB-attached cargo DNA, and ParB drives ParA dynamics, allowing ParA progression along the nucleoid. How ParA-ATP binds nonspecific DNA and is regulated by ParB is unclear. Also under debate is whether ParA polymerizes on DNA to mediate segregation. Here we describe structures of key ParA segregation complexes. The ParA-β,γ-imidoadenosine 5'-triphosphate (AMPPNP)-DNA structure revealed no polymers. Instead, ParA-AMPPNP dimerization creates a multifaceted DNA-binding surface, allowing it to preferentially bind high-density DNA regions (HDRs). DNA-bound ParA-AMPPNP adopts a dimer conformation distinct from the ATP sandwich dimer, optimized for DNA association. Our ParA-AMPPNP-ParB structure reveals that ParB binds at the ParA dimer interface, stabilizing the ATPase-competent ATP sandwich dimer, ultimately driving ParA DNA dissociation. Thus, the data indicate how harnessing a conformationally adaptive dimer can drive large-scale cargo movement without the requirement for polymers and suggest a segregation mechanism by which ParA-ATP dimers equilibrate to HDRs shown to be localized near cell poles of dividing chromosomes, thus mediating equipartition of attached ParB-DNA substrates. © 2017 Zhang and Schumacher; Published by Cold Spring Harbor Laboratory Press.

  13. Recombination in the Human Pseudoautosomal Region PAR1

    PubMed Central

    Hinch, Anjali G.; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R.

    2014-01-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome. PMID:25033397

  14. Recombination in the human Pseudoautosomal region PAR1.

    PubMed

    Hinch, Anjali G; Altemose, Nicolas; Noor, Nudrat; Donnelly, Peter; Myers, Simon R

    2014-07-01

    The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  15. Megestrol acetate NCD oral suspension -- Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  16. Megestrol acetate NCD oral suspension--Par Pharmaceutical: megestrol acetate nanocrystal dispersion oral suspension, PAR 100.2, PAR-100.2.

    PubMed

    2007-01-01

    Par Pharmaceutical has developed megestrol acetate (Megace ES) oral suspension for the treatment of anorexia, cachexia and a significant weight loss associated with AIDS. Par Pharmaceutical used Elan Corporation's NanoCrystal Dispersion (NCD) technology to develop an advanced, concentrated formulation of megestrol acetate with improved bioavailability, more rapid onset of action, more convenient dosing and a lower dosing regimen compared with the original marketed formulation of megestrol acetate oral suspension. Patients are administered a teaspoon (5mL) of the new NCD formulation once daily, compared with a daily 20mL dosage cup of the original formulation. The new megestrol acetate NCD formulation represents a line-extension of Par's megestrol acetate oral suspension (800mg/20mL, Megace O/S) that has been marketed for anorexia, cachexia and AIDS-related weight loss since July 2001. Par's megestrol acetate is the generic version of Bristol-Myers Squibb's Megace Oral Suspension. NanoCrystal Dispersion (NCD) is a trademark of Elan Corporation. Par Pharmaceutical will market megestol acetate NCD oral suspension under the Megace brand name. The company licensed the Megace name from Bristol-Myers Squib in August 2003. The US FDA approved megestrol acetate oral suspension (625 mg/mL) in July 2005 for the treatment of anorexia, cachexia or a significant, unexplained weight loss in patients with AIDS. The NDA for the product was accepted for review by the agency in September 2004, following its submission in June of that year.Par Pharmaceutical commenced the first of two phase III clinical trials of megestrol acetate oral suspension (PAR 100.2) in cancer-induced anorexia in the first quarter of 2006. However, this trial was discontinued in September 2006 because of slow patient enrolment. The company intends to discuss future development options in this indication with the FDA.New formulations or dosage forms of megestrol acetate concentrated suspension are also in

  17. Condensation and localization of the partitioning protein ParB on the bacterial chromosome.

    PubMed

    Broedersz, Chase P; Wang, Xindan; Meir, Yigal; Loparo, Joseph J; Rudner, David Z; Wingreen, Ned S

    2014-06-17

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB-DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB-DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB-DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes.

  18. Condensation and localization of the partitioning protein ParB on the bacterial chromosome

    PubMed Central

    Broedersz, Chase P.; Wang, Xindan; Meir, Yigal; Loparo, Joseph J.; Rudner, David Z.; Wingreen, Ned S.

    2014-01-01

    The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB–DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein–DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB–DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB–DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB–DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes. PMID:24927534

  19. Control of cleavage spindle orientation in Caenorhabditis elegans: The role of the genes par-2 and par-3

    SciTech Connect

    Cheng, N.N.; Kirby, C.M.; Kemphues, K.J.

    1995-02-01

    Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these divisions. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2 (it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage. 44 refs., 5 figs., 5 tabs.

  20. Scleral Buckling for Rhegmatogenous Retinal Detachment Associated with Pars Planitis

    PubMed Central

    Ahn, Jae Kyoun

    2016-01-01

    Purpose. To evaluate the surgical outcome of scleral buckling (SB) in rhegmatogenous retinal detachment (RRD) patients associated with pars planitis. Methods. Retrospective review of RRD patients (32 eyes of pars planitis RRD and 180 eyes of primary RRD) who underwent SB. We compared primary and final anatomical success rates and visual outcomes between two groups. Results. Primary and final anatomical success were achieved in 25 (78.1%) and 31 (96.8%) eyes in the pars planitis RRD group and in 167 eyes (92.7%) and 176 eyes (97.7%) in primary RRD group, respectively. Both groups showed significant visual improvement (p < 0.001) and there were no significant differences in final visual acuity. Pars planitis RRD group was associated with higher rate of postoperative proliferative vitreoretinopathy (PVR) development (12.5% versus 2.8%, p = 0.031). Pars planitis and high myopia were significant preoperative risk factors and pseudophakia was borderline risk for primary anatomical failure after adjusting for various clinical factors. Conclusions. Pars planitis associated RRD showed inferior primary anatomical outcome after SB due to postoperative PVR development. However, final anatomical and visual outcomes were favorable. RRD cases associated with pars planitis, high myopia, and pseudophakia might benefit from different surgical approaches, such as combined vitrectomy and SB. PMID:27688907

  1. The Pars Triangularis in Dyslexia and ADHD

    PubMed Central

    Kibby, Michelle Y.; Kroese, Judith M.; Krebbs, Hillery; Hill, Crystal E.; Hynd, George W.

    2009-01-01

    Limited research has been conducted on the structure of the pars triangularis (PT) in dyslexia despite functional neuroimaging research finding it may play a role in phonological processing. Furthermore, research to date has not examined PT size in ADHD even though the right inferior frontal region has been implicated in the disorder. Hence, one of the purposes of this study was to examine the structure of the PT in dyslexia and ADHD. The other purposes included examining the PT in relation to overall expressive language ability and in relation to several specific linguistic functions given language functioning often is affected in both dyslexia and ADHD. Participants included 50 children: 10 with dyslexia, 15 with comorbid dyslexia/ADHD, 15 with ADHD, and 10 controls. Using a 2 (dyslexia or not) X 2 (ADHD or not) MANCOVA, findings revealed PT length and shape were comparable between those with and without dyslexia. However, children with ADHD had smaller right PT lengths than those without ADHD, and right anterior ascending ramus length was related to attention problems in the total sample. In terms of linguistic functioning, presence of an extra sulcus in the left PT was related to poor expressive language ability. In those with adequate expressive language functioning, left PT length was related to phonological awareness, phonological short-term memory and rapid automatic naming (RAN). Right PT length was related to RAN and semantic processing. Further work on PT morphology in relation to ADHD and linguistic functioning is warranted. PMID:19356794

  2. Multi-scale photoacoustic remote sensing (PARS) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Haji Reza, Parsin; Bell, Kevan; Shi, W.; Zemp, Roger J.

    2016-03-01

    We introduce a novel multi-scale photoacoustic remote sensing (PARS) imaging system. Our system can provide optical resolution details for superficial structures as well as acoustic resolution for deep-tissue imaging down to 5 cm, in a non-contact setting. PARS system does not require any contact with the sample or ultrasound coupling medium. The optical resolution PARS (OR-OARS) system uses optically focused pulsed excitation with optical detection of photoacoustic signatures using a long-coherence interrogation beam co-focused and co-scanned with the excitation spot. In the OR-PARS initial pressures are sampled right at their subsurface origin where acoustic pressures are largest. The Acoustic resolution PARS (AR-PARS) picks up the surface oscillation of the tissue caused by generated photoacoustic signal using a modified version of Michelson interferometry. By taking advantage of 4-meters polarization maintaining single-mode fiber and a green fiber laser we have generated a multi-wavelength source using stimulated Raman scattering. Remote functional imaging using this multi-wavelength excitation source and PARS detection mechanism has been demonstrated. The oxygen saturation estimations are shown for both phantom and in vivo studies. Images of blood vessel structures for an In vivo chicken embryo model is demonstrated. The Phantom studies indicates ~3µm and ~300µm lateral resolution for OR-PARS and AR-PARS respectively. To the best of our knowledge this is the first dual modality non-contact optical and acoustic resolution system used for in vivo imaging.

  3. Predicted PAR1 inhibitors from multiple computational methods

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Liu, Jinfeng; Zhu, Tong; Zhang, Lujia; He, Xiao; Zhang, John Z. H.

    2016-08-01

    Multiple computational approaches are employed in order to find potentially strong binders of PAR1 from the two molecular databases: the Specs database containing more than 200,000 commercially available molecules and the traditional Chinese medicine (TCM) database. By combining the use of popular docking scoring functions together with detailed molecular dynamics simulation and protein-ligand free energy calculations, a total of fourteen molecules are found to be potentially strong binders of PAR1. The atomic details in protein-ligand interactions of these molecules with PAR1 are analyzed to help understand the binding mechanism which should be very useful in design of new drugs.

  4. Limnological database for Par Pond: 1959 to 1980

    SciTech Connect

    Tilly, L.J.

    1981-03-01

    A limnological database for Par Pond, a cooling reservoir for hot reactor effluent water at the Savannah River Plant, is described. The data are derived from a combination of research and monitoring efforts on Par Pond since 1959. The approximately 24,000-byte database provides water quality, primary productivity, and flow data from a number of different stations, depths, and times during the 22-year history of the Par Pond impoundment. The data have been organized to permit an interpretation of the effects of twenty years of cooling system operations on the structure and function of an aquatic ecosystem.

  5. Positron Accumulator Ring (PAR) power supply

    SciTech Connect

    Fathizadeh, M.

    1995-08-01

    The Positron Accumulator Ring (PAR) consists of 8 dipole magnets connected in series. These magnets are energized via one 12-pulse dc power supply. The power supply consists of four phase controlled half-wave wye group converters. Each of the two half-wave converters are connected through an interphase transformer to obtain a full-wave converter with 120{degrees} conduction. The input voltage for these two half-wave converters are 180{degrees} apart. The two full-wave converters are connected in parallel through a third interphase transformer. This type of connection of the converters not only provides the required output current, it also improves the input power factor of the power supply. The output of the wye group converters is filtered through a passive L-R-C filter to reduce the ripple content of the output current. At low current values of the power supply the current ripple is high, thus a large filter is needed, which adds to the cost of the power supply, however at high output current levels, the current ripple is less severe. The large size of the filter can be reduced by adding an anti-parallel rectifier diode(D1) to the output of the power supply. A freewheeling diode(D2) is connected before the choke to circulate the current once the power supply is turned off. In order to measure the current in the magnet a high precision, low drift, zero flux current transductor is used. This transductor senses the magnet current which provides a feedback signal to control the gating of the converter`s thyristors. A true 14 bit Digital to Analog Converter (DAC) is programmed by the control computer for the required current value, providing a reference for the current regulator. Fast correction of the line transients is provided by a relatively fast voltage loop controlled by a high gain slow response current loop.

  6. The Study of Biogenetic Organic Compound Emissions and Ozone in a Subtropical Bamboo Forest

    NASA Astrophysics Data System (ADS)

    Bai, Jianhui; Guenther, Alex; Turnipseed, Andrew; Duhl, Tiffany; Duhl, Nanhao; van der A, Ronald; Yu, Shuquan; Wang, Bin

    2016-08-01

    Emissions of Biogenic Volatile Organic compounds (BVOCs), Photosynthetically Active Radiation (PAR), and meteorological parameters were measured in some ecosystems in China. A Relaxed Eddy Accumulation system and an enclosure technique were used to measure BVOC emissions. Obvious diurnal and seasonal variations of BVOC emissions were found. Empirical models of BVOC emissions were developed, the estimated BVOC emissions were in agreement with observations. BVOC emissions in growing seasons in the Inner Mongolia grassland, Chnagbai Mountain temperate forest, LinAn subtropical bamboo forest were estimated. The emission factors of these ecosystems were calculated.

  7. PARS: Programs for Analysis and Resizing of Structures, user manual

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Prasad, B.; Tsach, U.

    1979-01-01

    PARS processors and their use, flutter analysis, sensitivity analysis for stresses, and resizing are presented. Design variable definition and interface with finite element model, static constraints and their derivatives, flutter derivatives, and optimization are discussed.

  8. View from southwest to northeast of PAR site fresh water ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from southwest to northeast of PAR site fresh water pump house - Stanley R. Mickelsen Safeguard Complex, Fresh Water Pump House, In Limited Access Area, on Patrol Road next to Open Storage Reservoir No. 736, Nekoma, Cavalier County, ND

  9. The use of statistical techniques in par-level management.

    PubMed

    Klee, W B

    1994-02-01

    The total quality management movement has allowed the reintroduction of statistics in the materials management workplace. Statistical methods can be applied to the par level management process with significant results.

  10. View from northeast to southwest of PAR site sentry station; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from northeast to southwest of PAR site sentry station; formerly the bachelor's enlisted men's quarter (BEQ) - Stanley R. Mickelsen Safeguard Complex, Sentry Station, North of Second Avenue & West of Electrical Switch Station No. 2, Nekoma, Cavalier County, ND

  11. Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

    NASA Astrophysics Data System (ADS)

    Belanger, Simon

    La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

  12. Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer

    DTIC Science & Technology

    2007-05-01

    Sambrook J, Fritsch EF, Maniatis T. (1989). Molecular Cloning : A Laboratory Manual (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory...AD_________________ Award Number: W81XWH-05-1-0622 TITLE: Molecular Mechanisms of Par-4-Induced...SUBTITLE 5a. CONTRACT NUMBER Molecular Mechanisms of Par-4-Induced Apoptosis in Prostate Cancer 5b. GRANT NUMBER W81XWH-05-1-0622 5c. PROGRAM

  13. StePar: an automatic code for stellar parameter determination

    NASA Astrophysics Data System (ADS)

    Tabernero, H. M.; González Hernández, J. I.; Montes, D.

    2013-05-01

    We introduce a new automatic code (StePar) for determinig stellar atmospheric parameters (T_{eff}, log{g}, ξ and [Fe/H]) in an automated way. StePar employs the 2002 version of the MOOG code (Sneden 1973) and a grid of Kurucz ATLAS9 plane-paralell model atmospheres (Kurucz 1993). The atmospheric parameters are obtained from the EWs of 263 Fe I and 36 Fe II lines (obtained from Sousa et al. 2008, A&A, 487, 373) iterating until the excitation and ionization equilibrium are fullfilled. StePar uses a Downhill Simplex method that minimizes a quadratic form composed by the excitation and ionization equilibrium conditions. Atmospheric parameters determined by StePar are independent of the stellar parameters initial-guess for the problem star, therefore we employ the canonical solar values as initial input. StePar can only deal with FGK stars from F6 to K4, also it can not work with fast rotators, veiled spectra, very metal poor stars or Signal to noise ratio below 30. Optionally StePar can operate with MARCS models (Gustafson et al. 2008, A&A, 486, 951) instead of Kurucz ATLAS9 models, additionally Turbospectrum (Alvarez & Plez 1998, A&A, 330, 1109) can replace the MOOG code and play its role during the parameter determination. StePar has been used to determine stellar parameters for some studies (Tabernero et al. 2012, A&A, 547, A13; Wisniewski et al. 2012, AJ, 143, 107). In addition StePar is being used to obtain parameters for FGK stars from the GAIA-ESO Survey.

  14. The signaling adaptor GAB1 regulates cell polarity by acting as a PAR protein scaffold.

    PubMed

    Yang, Ziqiang; Xue, Bin; Umitsu, Masataka; Ikura, Mitsuhiko; Muthuswamy, Senthil K; Neel, Benjamin G

    2012-08-10

    Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypophosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased transepithelial resistance, and lateral domain shortening. Conversely, GAB1 overexpression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multilumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Par Pond vegetation status Summer 1995 -- June survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-06-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments have been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned.

  16. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis

    PubMed Central

    Ozdal, Pinar Cakar; Berker, Nilufer; Tugal-Tutkun, Ilknur

    2015-01-01

    Pars planitis is an idiopathic chronic intermediate uveitis which predominantly affects children and adolescents, and accounts for 5-26.7% of pediatric uveitis. Although an autoimmune process with a genetic predisposition has been suggested, its etiology still remains unknown. The most common presenting symptoms are floaters and blurred vision. Diffuse vitreous cells, haze, snowballs and snowbanks are typical findings of pars planitis. Peripheral retinal vasculitis, optic disc edema and anterior segment inflammation are other well-known findings. Although pars planitis is known to be a benign form of uveitis in most cases, it may become a potentially blinding disease due to complications including cataract, cystoid macular edema, vitreous opacities and optic disc edema. Cystoid macular edema is the most common cause of visual morbidity. Band keratopathy, epiretinal membrane formation, vitreous condensation, neovascularizations, vitreous hemorrhage, retinal detachment, cyclitic membranes, glaucoma and amblyopia may develop as a consequence of the chronic course of the disease. Exclusion of infectious and non-infectious causes which may present with intermediate uveitis is of utmost importance before starting treatment. Treatment of pars planitis has been a controversial issue. There is no consensus specifically for treatment of cases with minimal inflammation and relatively good visual acuity. However, current experience shows that pars planitis may cause severe inflammation and needs an aggressive treatment. A stepladder approach including corticosteroids, immunosupressive agents, anti-tumor necrosis factor-alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. Adequate control of inflammation and prompt detection of associated complications are crucial in order to improve the overall prognosis of the disease. PMID:27051493

  17. Par Pond vegetation status Summer 1995 -- October survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-11-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  18. Par Pond vegetation status Summer 1995 -- September survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-09-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.

  19. Protease-activated receptor-2 (PAR2) in cardiovascular system.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cirino, Giuseppe

    2005-10-01

    Vascular system is constituted by a complex and articulate network, e.g. arteries, arterioles, venules and veins, that requires a high degree of coordination between different elemental cell types. Proteinase-activated receptors (PARs) constitute a recent described family of 7-transmembrane G protein-coupled receptors that are activated by proteolysis. In recent years several evidence have been accumulated for an involvement of this receptor in the response to endothelial injury in vitro and in vivo experimental settings suggesting a role for PAR2 in the pathophysiology of cardiovascular system. This review will deal with the role of PAR2 receptor in the cardiovascular system analyzing both in vivo and in vitro published data. In particular this review will deal with the role of this receptor in vascular reactivity, ischemia/reperfusion injury, coronary atherosclerotic lesions and angiogenesis.

  20. Couches Minces de Titanate de Baryum Par Depot Organometallique

    NASA Astrophysics Data System (ADS)

    Ousi Benomar, Wahib

    1993-01-01

    Nous avons demontre la possibilite de realiser des couches minces de titanate de baryum par depot organometallique. Les films sont obtenus apres dissolution d'organometalliques choisis dans un solvant et une cuisson a une temperature determinee par thermogravimetrie. Apres un second traitement thermique a des temperatures plus elevees, les echantillons presentent une structure polycristalline tetragonale; les cristallites sont observes par microscopie electronique a balayage. La mesure de la constante dielectrique a permis de mettre en evidence une transition de phase de la structure tetragonale a la structure cubique a une temperature d'environ 125^circC. Les mesures d'indice ont ete effectuees. On note une augmentation de l'indice de refraction des films avec la temperature indiquant une meilleure densification des films. Nous avons aussi montre qu'il etait possible d'utiliser ce materiau en tant que guide d'onde optique pour pouvoir exploiter ses proprietes electrooptiques dans l'avenir.

  1. Keratometric alterations following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy.

    PubMed

    Citirik, Mehmet; Batman, Cosar; Bicer, Tolga; Zilelioglu, Orhan

    2009-09-01

    To assess the alterations in keratometric astigmatism following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy. Sixteen consecutive patients were enrolled into the study. Conventional vitrectomy was applied to eight of the cases and 25-gauge transconjunctival sutureless vitrectomy was performed in eight patients. Keratometry was performed before and after the surgery. In the 25-gauge transconjunctival sutureless pars plana vitrectomy group, statistically significant changes were not observed in the corneal curvature in any post-operative follow-up measurement (p > 0.05); whereas in the conventional pars plana vitrectomy group, statistically significant changes were observed in the first postoperative day (p = 0.01) and first postoperative month (p = 0.03). We noted that these changes returned to baseline in three months (p = 0.26). Both 25-gauge transconjunctival sutureless and conventional pars plana vitrectomy are effective surgical modalities for selected diseases of the posterior segment. Surgical procedures are critical for the visual rehabilitation of the patients. The post-operative corneal astigmatism of the vitrectomised eyes can be accurately determined at least two months post-operatively.

  2. Both PHYTOCHROME RAPIDLY REGULATED1 (PAR1) and PAR2 Promote Seedling Photomorphogenesis in Multiple Light Signaling Pathways1[C][W][OPEN

    PubMed Central

    Zhou, Peng; Song, Meifang; Yang, Qinghua; Su, Liang; Hou, Pei; Guo, Lin; Zheng, Xu; Xi, Yulin; Meng, Fanhua; Xiao, Yang; Yang, Li; Yang, Jianping

    2014-01-01

    Arabidopsis (Arabidopsis thaliana) seedlings undergo photomorphogenesis in the light and etiolation in the dark. Light-activated photoreceptors transduce the light signals through a series of photomorphogenesis promoting or repressing factors to modulate many developmental processes in plants, such as photomorphogenesis and shade avoidance. CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is a conserved RING finger E3 ubiquitin ligase, which mediates degradation of several photomorphogenesis promoting factors, including ELONGATED HYPOCOTYL5 (HY5) and LONG HYPOCOTYL IN FAR-RED1 (HFR1), through a 26S proteasome-dependent pathway. PHYTOCHROME RAPIDLY REGULATED1 (PAR1) was first detected as an early repressed gene in both phytochrome A (phyA)-mediated far-red and phyB-mediated red signaling pathways, and subsequent studies showed that both PAR1 and PAR2 are negative factors of shade avoidance in Arabidopsis. However, the role of PAR1 and PAR2 in seedling deetiolation, and their relationships with other photomorphogenesis promoting and repressing factors are largely unknown. Here, we confirmed that both PAR1 and PAR2 redundantly enhance seedling deetiolation in multiple photoreceptor signaling pathways. Their transcript abundances are repressed by phyA, phyB, and cryptochrome1 under far-red, red, and blue light conditions, respectively. Both PAR1 and PAR2 act downstream of COP1, and COP1 mediates the degradation of PAR1 and PAR2 through the 26S proteasome pathway. Both PAR1 and PAR2 act in a separate pathway from HY5 and HFR1 under different light conditions, except for sharing in the same pathway with HFR1 under far-red light. Together, our results substantiate that PAR1 and PAR2 are positive factors functioning in multiple photoreceptor signaling pathways during seedling deetiolation. PMID:24335334

  3. Seasonal and interannual variations in whole-ecosystem BVOC emissions from a subtropical plantation in China

    NASA Astrophysics Data System (ADS)

    Bai, Jianhui; Guenther, Alex; Turnipseed, Andrew; Duhl, Tiffany; Greenberg, James

    2017-07-01

    Measurements of BVOC emissions, ozone concentration and environmental parameters were carried out from May 2013 to January 2016 in a subtropical Pinus plantation in China. Isoprene and monoterpene emissions were measured using a relaxed eddy accumulation (REA) system and a gradient technique on an above-canopy tower. In 2013, isoprene comprised 21.2% of total terpenoid emissions, while α-pinene, camphene, β-pinene and limonene constituting 51.5%, 2.4%, 9.1%, and 13.0% of total emissions, respectively. Monoterpenes together were the dominant VOCs measured contributing 71.6%. α-pinene, camphene, β-pinene and limonene constituted 67.7%, 3.2%, 11.9%, 17.2% of total monoterpene emissions. Isoprene and monoterpene emissions displayed strong diurnal variations, with lower emissions in the morning and late evening, and the highest emissions around noon. BVOC peak emissions typically occurred a few hours after the noon PAR peak. Isoprene and monoterpene emissions varied with season and were the highest in summer, contributing more than half of the total annual emission, and the lowest emissions were in winter. Evident interannual variations of isoprene, monoterpenes and total BVOCs were observed. Compared to 2013, annual BVOC emissions decreased in 2015, associated with decreases of PAR, Temperature, water vapor, and an increase of all substances in gas, liquid and solid phases in the atmospheric column (e.g., S/Q, the ratio of solar scattered radiation to global radiation). Ozone concentration showed clear diurnal variation with PAR, higher around noon and lower in the early morning and late evening. Generally, there were no evident correlations between ozone concentrations and BVOC emissions, or the vertical gradients of ozone concentrations and BVOC concentrations. Under all sky conditions (including cloudy skies), no strong correlations at a high confidence level or very similar variation patterns were observed between any two following parameters, BVOC emissions

  4. Traumatisme de la main par injection a haute pression

    PubMed Central

    Mabchoure, K.; Diouri, M.; Bahechar, N.; Chlihi, A.

    2016-01-01

    Summary Les traumatismes de la main par injection à haute pression sont des accidents relativement rares et souvent mal connus par le praticien. Les lésions qui dépendent du produit injecté et du site d’injection sont pourvoyeuses de séquelles esthétiques et fonctionnelles lourdes. Le traitement repose sur la chirurgie, l’antibiothérapie et la rééducation précoce et spécifique. Nous rapportons notre expérience ainsi qu’une revue de la littérature. PMID:27857654

  5. PAR-3 oligomerization may provide an actin-independent mechanism to maintain distinct par protein domains in the early Caenorhabditis elegans embryo.

    PubMed

    Dawes, Adriana T; Munro, Edwin M

    2011-09-21

    Par proteins establish discrete intracellular spatial domains to polarize many different cell types. In the single-cell embryo of the nematode worm Caenorhabditis elegans, the segregation of Par proteins is crucial for proper division and cell fate specification. Actomyosin-based cortical flows drive the initial formation of anterior and posterior Par domains, but cortical actin is not required for the maintenance of these domains. Here we develop a model of interactions between the Par proteins that includes both mutual inhibition and PAR-3 oligomerization. We show that this model gives rise to a bistable switch mechanism, allowing the Par proteins to occupy distinct anterior and posterior domains seen in the early C. elegans embryo, independent of dynamics or asymmetries in the actin cortex. The model predicts a sharp loss of cortical Par protein asymmetries during gradual depletion of the Par protein PAR-6, and we confirm this prediction experimentally. Together, these results suggest both mutual inhibition and PAR-3 oligomerization are sufficient to maintain distinct Par protein domains in the early C. elegans embryo.

  6. Emissions Inventories

    EPA Pesticide Factsheets

    This document provides the details of emissions data processing done in support of the Environmental Protection Agency’s rulemaking effort for the Federal Transport Rule proposal (now known as the Cross-State Air Pollution Rule).

  7. Isoprene emission from Indian trees

    NASA Astrophysics Data System (ADS)

    Varshney, C. K.; Singh, Abhai Pratap

    2003-12-01

    Isoprene is the most dominant non-methane volatile organic compound (NMVOC) emitted by plants. NMVOCs play an important role in regulating the composition of atmospheric trace gases including global concentration of tropospheric ozone. Our present knowledge about NMVOCs emission is mainly from studies on temperate tree species. So far information on biogenic NMVOCs emission from tropical tree species is limited. In this study, isoprene emission rates from 40 tropical Indian tree species belonging to 33 genera and 17 families were measured for the first time using a dynamic flow through enclosure chamber technique. The isoprene emission rate from plants (30°C and PAR 1000 μmolm-2s-1) ranged from undetectable to 81.5 μg g-1 h-1 and values were found to be comparable with other studies on tropical tree species. Tree species screened for isoprene emission in the present study may be grouped into the four categories, proposed by [2001], namely, 18 species were negligible or BDL isoprene emitting (<1 μg g-1 h-1), 6 species were low emitting (1 ≤ to <10 μg g-1 h-1), 5 species were moderate emitting (10≤ to <25 μg g-1 h-1), and 11 species were high isoprene emitting (≥25 μg g-1 h-1). Maximum isoprene emission rate (81.5 μg g-1 h-1) was observed in the case of Dalbergia sissoo Linn. It was interesting to find that Citrus limon Linn., Citrus reticulata Linn., Citrus sinensis Linn., Grevillea robusta A. Cunn., and Morus alba Linn., which were earlier reported as BDL or non isoprene emitters in US [, 1998; , 2001] were found to be appreciably high isoprene emitters (0.61-21.60 μg g-1 h-1) in the present study.

  8. Are You Up to PAR? (Program Administrative Review).

    ERIC Educational Resources Information Center

    Southwest Regional Resource Center, Salt Lake City, UT.

    The document focuses on the workings of PAR (Program Administrative Review), a method by which local education agencies (LEAs) and state operated programs (SOPs) in Utah can conduct ongoing self-evaluation and identify areas where additional efforts are needed to improve the quality of programs and services for handicapped children. It is…

  9. Par Pond vegetation status summer 1995 - July survey descriptive summary

    SciTech Connect

    Mackey, H.E. Jr.; Riley, R.S.

    1995-07-01

    A survey of the emergent shoreline aquatic plant, communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet (61 meters) above mean sea level, and continued with this July survey. Aquatic plant communities, similar to the pre-drawdown Par Pond communities, are becoming reestablished. Beds of maidencane (Panicum hemitomon), lotus (Nelumbo lutea), water lily (Nymphaea odorata), and watershield (Brasenia schreberi) are now extensive and well established. In addition, within isolated coves, extensive beds of water lilies and spike-rush (Eleocharis sp.) are common. Cattail occurrence has increased since refill, but large beds common to Par Pond prior to the drawdown have not formed. Invasion of willow (Salix sp.) and red maple (Acer rubrum) occurred along the lake shoreline during drawdown. The red maples along the present shoreline are beginning to show evidence of stress and mortality from flooding over the past four months. Some of the willows appear to be stressed as well. The loblolly pines (Pinus taeda), which were flooded in all but the shallow shoreline areas, are now dead. Future surveys are planned for the growing seasons of 1995, 1996, and 1997, along with the evaluation of satellite data for mapping the areal extent of the macrophyte beds of Par Pond.

  10. BOREAS RSS-10 TOMS Circumpolar One-Degree PAR Images

    NASA Technical Reports Server (NTRS)

    Dye, Dennis G.; Holben, Brent; Nickeson, Jaime (Editor); Hall, Forrest G. (Editor); Smith, David E. (Technical Monitor)

    2000-01-01

    The Boreal Ecosystem-Atmosphere Study (BOREAS) Remote Sensing Science (RSS)-10 team investigated the magnitude of daily, seasonal, and yearly variations of Photosynthetically Active Radiation (PAR) from ground and satellite observations. This data set contains satellite estimates of surface-incident PAR (400-700 nm, MJ/sq m) at one-degree spatial resolution. The spatial coverage is circumpolar from latitudes of 41 to 66 degrees north. The temporal coverage is from May through September for years 1979 through 1989. Eleven-year statistics are also provided: (1) mean, (2) standard deviation, and (3) coefficient of variation for 1979-89. The PAR estimates were derived from the global gridded ultraviolet reflectivity data product (average of 360, 380 nm) from the Nimbus-7 Total Ozone Mapping Spectrometer (TOMS). Image mask data are provided for identifying the boreal forest zone, and ocean/land and snow/ice-covered areas. The data are available as binary image format data files. The PAR data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). The data files are available on a CD-ROM (see document number 20010000884).

  11. Radiological impact of Par Pond drawdown from liquid effluent pathways

    SciTech Connect

    Carlton, W.H.; Hamby, D.M.

    1991-10-25

    The water level of Par Pond has been lowered over the past several months to reduce the effects in the event of catastrophic dam failure while assessing the condition of the dam and determining if repairs are necessary. In lowering the level of Par Pond, 60 billion liters of water containing low levels of tritium and cesium-137 were discharged to several onsite streams. SRS surface streams flow to the Savannah River. An assessment made to determine the total amount of tritium and Cs-137 discharged and to estimate the consequences to downstream Savannah River users. It is estimated that a total of 160 curies of tritium were displaced from Par Pond to the Savannah River between June 28, 1991 and September 19, 1991. This release could hypothetically result in a maximum individual dose of 3. 2{times}10{sup {minus}4} mrem and a total (80-km and drinking water populations) population dose of 1.4{times}10{sup {minus}2} person-rem. Likewise, a maximum individual dose of 5.0{times}10{sup {minus}2} mrem and a total population dose of 1.7{times}10{sup {minus}1} person- rem are predicted as a result of an estimated 0.21 curies of Cs-137 being discharged from Par Pond to the Savannah River.

  12. PAR-5 is a PARty hub in the germline

    PubMed Central

    Aristizábal-Corrales, David; Schwartz Jr, Simo; Cerón, Julián

    2013-01-01

    As our understanding of how molecular machineries work expands, an increasing number of proteins that appear as regulators of different processes have been identified. These proteins are hubs within and among functional networks. The 14-3-3 protein family is involved in multiple cellular pathways and, therefore, influences signaling in several disease processes, from neurobiological disorders to cancer. As a consequence, 14-3-3 proteins are currently being investigated as therapeutic targets. Moreover, 14-3-3 protein levels have been associated with resistance to chemotherapies. There are seven 14-3-3 genes in humans, while Caenorhabditis elegans only possesses two, namely par-5 and ftt-2. Among the C. elegans scientific community, par-5 is mainly recognized as one of the par genes that is essential for the asymmetric first cell division in the embryo. However, a recent study from our laboratory describes roles of par-5 in germ cell proliferation and in the cellular response to DNA damage induced by genotoxic agents. In this review, we explore the broad functionality of 14-3-3 proteins in C. elegans and comment on the potential use of worms for launching a drugs/modifiers discovery platform for the therapeutic regulation of 14-3-3 function in cancer. PMID:24058859

  13. Emission inventory of evaporative emissions of VOCs in four metro cities in India.

    PubMed

    Srivastava, Anjali; née Som Majumdar, Dipanjali

    2010-01-01

    High concentrations of volatile organic compounds (VOCs) in ambient air of urban areas stress the need for the control of VOC emissions due to the toxic and carcinogenic nature of many VOCs commonly encountered in urban air. Emission inventories are an essential tool in the management of local air quality, which provide a listing of sources of air pollutant emissions within a specific area over a specified period of time. This study intended to provide a level IV emission inventory as par the United States Environmental Protection Agency (USEPA) definition for evaporative VOC emissions in the metro cities of India namely Delhi, Mumbai, Chennai, and Kolkata. The vehicular evaporative emissions are found to be the largest contributor to the total evaporative emissions of hydrocarbons followed by evaporative losses related to petrol loading and unloading activities. Besides vehicle-related activities, other major sources contributing to evaporative emissions of hydrocarbons are surface coating, dry cleaning, graphical art applications, printing (newspaper and computer), and the use of consumer products. Various specific preventive measures are also recommended for reducing the emissions.

  14. Promiscuous stimulation of ParF protein polymerization by heterogeneous centromere binding factors.

    PubMed

    Machón, Cristina; Fothergill, Timothy J G; Barillà, Daniela; Hayes, Finbarr

    2007-11-16

    The segrosome is the nucleoprotein complex that mediates accurate segregation of bacterial plasmids. The segrosome of plasmid TP228 comprises ParF and ParG proteins that assemble on the parH centromere. ParF, which exemplifies one clade of the ubiquitous ParA superfamily of segregation proteins, polymerizes extensively in response to ATP binding. Polymerization is modulated by the ParG centromere binding factor (CBF). The segrosomes of plasmids pTAR, pVT745 and pB171 include ParA homologues of the ParF subgroup, as well as diverse homodimeric CBFs with no primary sequence similarity to ParG, or each other. Centromere binding by these analogues is largely specific. Here, we establish that the ParF homologues of pTAR and pB171 filament modestly with ATP, and that nucleotide hydrolysis is not required for this polymerization, which is more prodigious when the cognate CBF is also present. By contrast, the ParF homologue of plasmid pVT745 did not respond appreciably to ATP alone, but polymerized extensively in the presence of both its cognate CBF and ATP. The co-factors also stimulated nucleotide-independent polymerization of cognate ParF proteins. Moreover, apart from the CBF of pTAR, the disparate ParG analogues promoted polymerization of non-cognate ParF proteins suggesting that filamentation of the ParF proteins is enhanced by a common mechanism. Like ParG, the co-factors may be modular, possessing a centromere-specific interaction domain linked to a flexible region containing determinants that promiscuously stimulate ParF polymerization. The CBFs appear to function as bacterial analogues of formins, microtubule-associated proteins or related ancillary factors that regulate eucaryotic cytoskeletal dynamics.

  15. Uncertainties of isoprene emissions in the MEGAN model estimated for a coniferous and broad-leaved mixed forest in Southern China

    NASA Astrophysics Data System (ADS)

    Situ, Shuping; Wang, Xuemei; Guenther, Alex; Zhang, Yanli; Wang, Xinming; Huang, Minjuan; Fan, Qi; Xiong, Zhe

    2014-12-01

    With local observed emission factor and meteorological data, this study constrained the Model of Emissions of Gases and Aerosols from Nature (MEGAN) v2.1 to estimate isoprene emission from the Dinghushan forest during fall 2008 and quantify the uncertainties associated with MEGAN parameters using Monte Carlo approach. Compared with observation-based isoprene emission data originated from a campaign during this period at this site, the local constrained MEGAN tends to reproduce the diurnal variations and magnitude of isoprene emission reasonably well, with correlation coefficient of 0.7 and mean bias of 47.5%. The results also indicate high uncertainties in isoprene emission estimated, with the relative error varied from -89.0-111.0% at the 95% confidence interval. The key uncertainty sources include emission factors, γTLD, photosynthetically active radiation (PAR) and temperature. This implies that accurate input of emission factor, PAR and temperature is a key approach to reduce uncertainties in isoprene emission estimation.

  16. Re-Signifying Participatory Action Research (PAR) in Higher Education: What Does "P" Stand for in PAR?

    ERIC Educational Resources Information Center

    Santos, Doris

    2016-01-01

    While carrying out a study aimed at understanding the contribution of participatory action research (PAR) to the political realm in contemporary higher education, a problematic situation was found when doing a literature review in the field of action research. This problem concerns the intermittent appearance of the "participatory"…

  17. Re-Signifying Participatory Action Research (PAR) in Higher Education: What Does "P" Stand for in PAR?

    ERIC Educational Resources Information Center

    Santos, Doris

    2016-01-01

    While carrying out a study aimed at understanding the contribution of participatory action research (PAR) to the political realm in contemporary higher education, a problematic situation was found when doing a literature review in the field of action research. This problem concerns the intermittent appearance of the "participatory"…

  18. Targeting a Proteinase-Activated Receptor 4 (PAR4) Carboxyl Terminal Motif to Regulate Platelet Function.

    PubMed

    Ramachandran, Rithwik; Mihara, Koichiro; Thibeault, Pierre; Vanderboor, Christina M; Petri, Björn; Saifeddine, Mahmoud; Bouvier, Michel; Hollenberg, Morley D

    2017-04-01

    Thrombin initiates human platelet aggregation by coordinately activating proteinase-activated receptors (PARs) 1 and 4. However, targeting PAR1 with an orthosteric-tethered ligand binding-site antagonist results in bleeding, possibly owing to the important role of PAR1 activation on cells other than platelets. Because of its more restricted tissue expression profile, we have therefore turned to PAR4 as an antiplatelet target. We have identified an intracellular PAR4 C-terminal motif that regulates calcium signaling and β-arrestin interactions. By disrupting this PAR4 calcium/β-arrestin signaling process with a novel cell-penetrating peptide, we were able to inhibit both thrombin-triggered platelet aggregation in vitro and clot consolidation in vivo. We suggest that targeting PAR4 represents an attractive alternative to blocking PAR1 for antiplatelet therapy in humans.

  19. Urokinase Plasminogen Activator Receptor (uPAR) Targeted Nuclear Imaging and Radionuclide Therapy

    PubMed Central

    Li, Dan; Liu, Shuanglong; Shan, Hong; Conti, Peter; Li, Zibo

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein. Besides regulating proteolysis, uPAR could also activate many intracellular signaling pathways that promote cell motility, invasion, proliferation, and survival through cooperating with transmembrane receptors. uPAR is overexpressed across a variety of tumors and is associated with cancer invasion and metastasis. In order to meet the demand for a rapid development and potential clinical application of anti-cancer therapy based on uPA/uPAR system, it is desirable to develop non-invasive imaging methods to visualize and quantify uPAR expression in vivo. In this review, we will discuss recent advances in the development of uPAR-targeted nuclear imaging and radionuclide therapy agents. The successful development of molecular imaging probes to visualize uPAR expression in vivo would not only assist preclinical researches on uPAR function, but also eventually impact patient management. PMID:23843898

  20. Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.

    PubMed

    Alvarez, James V; Pan, Tien-Chi; Ruth, Jason; Feng, Yi; Zhou, Alice; Pant, Dhruv; Grimley, Joshua S; Wandless, Thomas J; Demichele, Angela; Chodosh, Lewis A

    2013-07-08

    Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in patients with breast cancer, and Par-4 is downregulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Attic cholesteatoma with tiny retraction of pars flaccida.

    PubMed

    Lee, Jun Ho; Hong, Seok Min; Kim, Chang Woo; Park, Yeo Hoon; Baek, So-Hye

    2015-04-01

    This clinical study was performed to analyze the characteristics of attic cholesteatoma occurring behind a tiny retraction of the pars flaccida, which was classified as Tos type I or II and had an intact pars tensa of the tympanic membrane. The clinical records of patients who underwent tympanomastoidectomy for attic cholesteatoma at a tertiary care referral center (Kangdong Sacred Heart Hospital of Seoul, Korea) between March 2004 and December 2012 were retrospectively reviewed. Eleven patients (five men and six women) who underwent tympanomastoidectomy between March 2004 and December 2012 for attic cholesteatoma occurring behind a tiny attic retraction were included. The mean age of patients was 41.1 years (range 20-58 years) and the mean duration of follow-up was 29.5 months (range 13-52 months). Every patient had a unilateral cholesteatoma, and the opposite side was normal except in one patient. Hearing loss was the most common symptom, followed by earfullness and otalgia. Five patients had type I attic retraction, and six patients had type II attic retraction. No patient had definite scutum erosion. Interestingly, during regular postoperative checkup, one patient was found incidentally for the opposite ear. Six patients had a cholesteatoma sac that was separated from the pars flaccida, whereas in five patients it was in contact with the pars flaccida but was easily separated. Six patients had a limited cholesteatoma within the epitympanum, and five patients had extension beyond the epitympanum. The average air-bone gap was 24.3±10.1dB before the operation and 14.2±6.6dB after the operation. Every patient had an intact tympanic membrane without retraction pocket postoperatively. There was no recurrence of cholesteatoma during follow-up. The rate of attic cholesteatomas occurring behind a tiny retraction of the pars flaccida was 7.7% (11 of 142 patients with attic cholesteatoma). Attic retractions must be followed closely using endoscopy, microscopy, and

  2. ParCAT: A Parallel Climate Analysis Toolkit

    NASA Astrophysics Data System (ADS)

    Haugen, B.; Smith, B.; Steed, C.; Ricciuto, D. M.; Thornton, P. E.; Shipman, G.

    2012-12-01

    Climate science has employed increasingly complex models and simulations to analyze the past and predict the future of our climate. The size and dimensionality of climate simulation data has been growing with the complexity of the models. This growth in data is creating a widening gap between the data being produced and the tools necessary to analyze large, high dimensional data sets. With single run data sets increasing into 10's, 100's and even 1000's of gigabytes, parallel computing tools are becoming a necessity in order to analyze and compare climate simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools that efficiently use parallel computing techniques to narrow the gap between data set size and analysis tools. ParCAT was created as a collaborative effort between climate scientists and computer scientists in order to provide efficient parallel implementations of the computing tools that are of use to climate scientists. Some of the basic functionalities included in the toolkit are the ability to compute spatio-temporal means and variances, differences between two runs and histograms of the values in a data set. ParCAT is designed to facilitate the "heavy lifting" that is required for large, multidimensional data sets. The toolkit does not focus on performing the final visualizations and presentation of results but rather, reducing large data sets to smaller, more manageable summaries. The output from ParCAT is provided in commonly used file formats (NetCDF, CSV, ASCII) to allow for simple integration with other tools. The toolkit is currently implemented as a command line utility, but will likely also provide a C library for developers interested in tighter software integration. Elements of the toolkit are already being incorporated into projects such as UV-CDAT and CMDX. There is also an effort underway to implement portions of the CCSM Land Model Diagnostics package using ParCAT in conjunction with Python and gnuplot. Par

  3. Is There an "F" in Your PAR? Understanding, Teaching and Doing Action Research

    ERIC Educational Resources Information Center

    Lorenzetti, Liza; Walsh, Christine Ann

    2014-01-01

    Participatory Action Research (PAR) is increasingly recognized within academic research and pedagogy. What are the benefits of including feminism within participatory action research and teaching? In responding to this question, we discuss the similarities and salient differences between PAR and feminist informed PAR (FPAR). There are eight themes…

  4. Emission Spectrometry.

    ERIC Educational Resources Information Center

    Keliher, Peter N.; And Others

    1984-01-01

    Presented is a review of selected literature on emission spectrometry published during 1982 and 1983. The review is organized under these headings: books and reviews; spectral descriptions and classifications; instrumentation; standards, samples, nomenclature, calibration, calculations; excitation sources; selected applications; and meetings. (JN)

  5. Emissions Overview

    NASA Technical Reports Server (NTRS)

    Rohde, John

    2001-01-01

    The Emissions Reduction Project is working in close partnership with the U.S. aircraft engine manufacturers and academia to develop technologies to reduce NO, emissions by 70 percent over the LTO cycle from 1996 ICAO standards with no increase in other emission constituents (carbon monoxide, smoke, and unburned hydrocarbons) and with comparable NO, reduction during cruise operations. These technologies cannot impact the overall combustor and fuel delivery system operability, affordability or maintainability. These new combustion concepts and technologies will include lean burning combustors with higher operating gas temperatures and pressures, fuel staging, ceramic matrix composite material liners with reduced cooling air and possibly advanced controls. Improved physics-based analysis tool will be developed and validated and some longer term technologies that are more revolutionary will be assessed. These improved computational codes will provide improved design tools to increase design confidence and cut the development time to achieve major reductions in NO, emissions. Longer term, revolutionary technologies like active combustion controls, combustion from a large array of micro-injectors, electrostatic fuel injectors, fuel additives and others will be investigated and assessed through proof-of-concept testing.

  6. Endophthalmitis following 27-Gauge Pars Plana Vitrectomy for Vitreous Floaters

    PubMed Central

    Lin, Zhong; Wu, Rong Han; Moonasar, Nived

    2016-01-01

    Purpose To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. Methods The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. Results The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6. Conclusion Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters. PMID:28101041

  7. Intraoperative raster photogrammetry--the PAR Corneal Topography System.

    PubMed

    Belin, M W

    1993-01-01

    The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system that uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. The CTS determines distortion in a projected two-dimensional grid. Unlike Placido-disc-based videokeratoscopes, the PAR CTS produces a true topographic map (elevation map) and requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. Because the system uses two noncoaxial optical paths, it can be integrated into other optical devices. A modified CTS was integrated into an experimental erbium: YAG photoablative laser. The CTS successfully imaged corneas before, after, and during laser photoablation. Its ability to image nonreflective surfaces and to be integrated into other optical systems may make it suitable for intraoperative refractive monitoring.

  8. Exploration of a new series of PAR1 antagonists.

    PubMed

    Planty, Bruno; Pujol, Chantal; Lamothe, Marie; Maraval, Catherine; Horn, Clemens; Le Grand, Bruno; Perez, Michel

    2010-03-01

    Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.

  9. Developmental patterns of emission of scent compounds and related gene expression in roses of the cultivar Rosa x hybrida cv. 'Yves Piaget'.

    PubMed

    Chen, Xiaomin; Baldermann, Susanne; Cao, Shuyan; Lu, Yao; Liu, Caixia; Hirata, Hiroshi; Watanabe, Naoharu

    2015-02-01

    2-Phenylethanol (2PE) and 3,5-dimethoxytoluene (DMT) are characteristic scent compounds in specific roses such as Rosa x hybrida cv. 'Yves Piaget'. We analyzed the endogenous concentrations and emission of 2PE and DMT during the unfurling process in different floral organs, as well as changes in transcript levels of the two key genes, PAR and OOMT2. The emission of both 2PE and DMT increased during floral development to reach peaks at the fully unfurled stage. The relative transcripts of PAR and OOMT2 also increased during floral development. Whereas the maximum for OOMT2 was found at the fully unfurled stage (stage 4), similar expression levels of PAR were detected at stage 4 and the senescence stage (stage 6). The results demonstrate a positive correlation between the expression levels of PAR and OOMT2 and the emission of 2PE and DMT. In addition, endogenous volatiles and relative transcripts showed tissue- and development-specific patterns.

  10. La modélisation par Reverse Monte Carlo (RMC)

    NASA Astrophysics Data System (ADS)

    McGreevy, R. L.

    2003-09-01

    La technique de modélisation par Reverse Monte Carlo (RMC) est une méthode générale de modélisation structurale à partir d'un ensemble de données expérimentales. Cette méthode étant très souple, elle peut s'appliquer à de nombreux types de données. Jusqu'à présent ces applications comprennent : la diffraction des neutrons (y compris la substitution isotopique), la diffraction des rayons X (y compris la diffusion anomale), la diffraction des électrons, la RMN (les techniques d'angle magique et de 2ème moment) et l'EXAFS. Les systèmes étudiés sont également d'une grande variété : liquides, verres, polymères, cristaux et matériaux magnétiques, par exemple. Ce cours présente les bases de la méthode RMC en signalant certaines des idées fausses répandues. L'accent sera mis sur le fait que les modèles structuraux obtenus par RMC ne sont ni'uniques' ni 'exacts' ; cependant ils sont souvent utiles à la compréhension soit de la structure du système, soit des relations entre structure et autres propriétés physiques.

  11. Accuracy of the PAR corneal topography system with spatial misalignment.

    PubMed

    Belin, M W; Zloty, P

    1993-01-01

    The PAR Corneal Topography System is a computerized corneal imaging system which uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. Raster photogrammetry is a standard method of extracting object information by projecting a known pattern onto an object and recording the distortion when viewed from an oblique angle. Unlike placido disc based videokeratoscopes, the PAR system requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. We studied both the accuracy of the system with purposeful misalignment (defocusing) of the test object and determined the ability to image freshly deepithelialized, keratectomized, and photoablated corneas. The PAR system was both accurate and reproducible in imaging calibrated spheres within a defined zone in space. Whole cadaver eyes were imaged both before and immediately after removal of the epithelium, lamellar keratectomy, and laser photoablation. The system demonstrated the ability to image irregular, deepithelialized, and keratectomized corneas. The ability to maintain accuracy without precise alignment and the facility to image freshly deepithelialized and keratectomized corneas may make the system suitable for intraoperative refractive monitoring.

  12. Two cases of malignant glaucoma unresolved by pars plana vitrectomy

    PubMed Central

    Hosoda, Yoshikatsu; Akagi, Tadamichi; Yoshimura, Nagahisa

    2014-01-01

    Malignant glaucoma, which is characterized by a shallow or flat anterior chamber with high intraocular pressure, can usually be resolved by pars plana vitrectomy with anterior hyaloidectomy. We describe two cases in which malignant glaucoma was refractory to conventional treatment and complete vitrectomy. Case one an 88-year-old woman with pseudoexfoliation glaucoma underwent trabeculotomy and subsequently developed malignant glaucoma. Four months after transient recovery by pars plana vitrectomy, the malignant glaucoma recurred. She underwent peripheral iridectomy and local zonulectomy with successful control of her intraocular pressure. In case two, an 85-year-old man had a history of pseudoexfoliation glaucoma. Seven months after phacoemulsification and intraocular lens implantation, he developed malignant glaucoma that was refractory to pars plana vitrectomy. He underwent peripheral iridectomy, goniosynechialysis and trabectome surgery resulting in the successful control of his intraocular pressure. In rare cases of malignant glaucoma refractive to vitrectomy, peripheral iridectomy with or without local zonulectomy is a reasonable and minimally invasive surgical procedure. PMID:24729683

  13. Isoprene emissions from a tundra ecosystem

    NASA Astrophysics Data System (ADS)

    Potosnak, M. J.; Baker, B. M.; LeStourgeon, L.; Disher, S. M.; Griffin, K. L.; Bret-Harte, M. S.

    2012-10-01

    Whole-system fluxes of isoprene from a~moist acidic tundra ecosystem and leaf-level emission rates of isoprene from a common species (Salix pulchra) in that same ecosystem were measured during three separate field campaigns. The field campaigns were conducted during the summers of 2005, 2010 and 2011 and took place at the Toolik Field Station (68.6° N, 149.6° W) on the north slope of the Brooks Range in Alaska, USA. The maximum rate of whole-system isoprene flux measured was over 1.2 mg C m-2 h-1 with an air temperature of 22 ° C and a PAR level over 1500 μmol m-2 s-1. Leaf-level isoprene emission rates for S. pulchra averaged 12.4 nmol m-2 s-1 (27.4 μg C gdw-1 h-1) extrapolated to standard conditions (PAR = 1000 μmol m-2 s-1 and leaf temperature = 30° C). Leaf-level isoprene emission rates were well characterized by the Guenther algorithm for temperature, but less so for light. Chamber measurements from a nearby moist acidic tundra ecosystem with less S. pulchra emitted significant amounts of isoprene, but at lower rates (0.45 mg C m-2 h-1). Comparison of our results to predictions from a global model found broad agreement, but a detailed analysis revealed some significant discrepancies. An atmospheric chemistry box model predicts that the observed isoprene emissions have a significant impact on Arctic atmospheric chemistry, including the hydroxyl radical (OH). Our results support the prediction that isoprene emissions from Arctic ecosystems will increase with global climate change.

  14. Isoprene emissions from a tundra ecosystem

    NASA Astrophysics Data System (ADS)

    Potosnak, M. J.; Baker, B. M.; LeStourgeon, L.; Disher, S. M.; Griffin, K. L.; Bret-Harte, M. S.; Starr, G.

    2013-02-01

    Whole-system fluxes of isoprene from a moist acidic tundra ecosystem and leaf-level emission rates of isoprene from a common species (Salix pulchra) in that same ecosystem were measured during three separate field campaigns. The field campaigns were conducted during the summers of 2005, 2010 and 2011 and took place at the Toolik Field Station (68.6° N, 149.6° W) on the north slope of the Brooks Range in Alaska, USA. The maximum rate of whole-system isoprene flux measured was over 1.2 mg C m-2 h-1 with an air temperature of 22 °C and a PAR level over 1500 μmol m-2 s-1. Leaf-level isoprene emission rates for S. pulchra averaged 12.4 nmol m-2 s-1 (27.4 μg C gdw-1 h-1) extrapolated to standard conditions (PAR = 1000 μmol m-2 s-1 and leaf temperature = 30 °C). Leaf-level isoprene emission rates were well characterized by the Guenther algorithm for temperature with published coefficients, but less so for light. Chamber measurements from a nearby moist acidic tundra ecosystem with little S. pulchra emitted significant amounts of isoprene, but at lower rates (0.45 mg C m-2 h-1) suggesting other significant isoprene emitters. Comparison of our results to predictions from a global model found broad agreement, but a detailed analysis revealed some significant discrepancies. An atmospheric chemistry box model predicts that the observed isoprene emissions have a significant impact on Arctic atmospheric chemistry, including a reduction of hydroxyl radical (OH) concentrations. Our results support the prediction that isoprene emissions from Arctic ecosystems will increase with global climate change.

  15. The Role of Neurosecretory Neurons in the Pars Intercerebralis and Pars Lateralis in Reproductive Diapause of the Blowfly, Protophormia terraenovae

    NASA Astrophysics Data System (ADS)

    Shiga, S.; Numata, H.

    Microlesions of the brain were made to examine the role of neurosecretory neurons in the pars intercerebralis (PI) and pars lateralis (PL) in the induction of reproductive diapause of the female blowfly Protophormia terraenovae. Under both diapause-inducing (LD 12 : 12, 20° C) and diapause-averting conditions (LD 18 : 6, 25° C), the ovaries invariably failed to develop when the PI was removed. When the PL was removed bilaterally, the ovaries developed in most of the females, irrespective of the rearing conditions. Removal of the PL prevented females from entering reproductive diapause. These results show that certain neurosecretory neurons in the PI are necessary for vitellogenesis, and that the PL contains inhibitory neurons which suppress vitellogenesis during reproductive diapause.

  16. Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein

    PubMed Central

    Brzoska, Anthony J.; Jensen, Slade O.; Barton, Deborah A.; Davies, Danielle S.; Overall, Robyn L.; Skurray, Ronald A.; Firth, Neville

    2016-01-01

    Actin-like proteins (Alps) are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments. PMID:27310470

  17. ParB Partition Proteins: Complex Formation and Spreading at Bacterial and Plasmid Centromeres

    PubMed Central

    Funnell, Barbara E.

    2016-01-01

    In bacteria, active partition systems contribute to the faithful segregation of both chromosomes and low-copy-number plasmids. Each system depends on a site-specific DNA binding protein to recognize and assemble a partition complex at a centromere-like site, commonly called parS. Many plasmid, and all chromosomal centromere-binding proteins are dimeric helix-turn-helix DNA binding proteins, which are commonly named ParB. Although the overall sequence conservation among ParBs is not high, the proteins share similar domain and functional organization, and they assemble into similar higher-order complexes. In vivo, ParBs “spread,” that is, DNA binding extends away from the parS site into the surrounding non-specific DNA, a feature that reflects higher-order complex assembly. ParBs bridge and pair DNA at parS and non-specific DNA sites. ParB dimers interact with each other via flexible conformations of an N-terminal region. This review will focus on the properties of the HTH centromere-binding protein, in light of recent experimental evidence and models that are adding to our understanding of how these proteins assemble into large and dynamic partition complexes at and around their specific DNA sites. PMID:27622187

  18. Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation

    PubMed Central

    Taylor, James A.; Pastrana, Cesar L.; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J.; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S.

    2015-01-01

    The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed. PMID:25572315

  19. Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2

    PubMed Central

    Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

    2010-01-01

    Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex. PMID:20392744

  20. Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2.

    PubMed

    Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

    2010-05-01

    Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

  1. Characterization of a Par j 1/Par j 2 mutant hybrid with reduced allergenicity for immunotherapy of Parietaria allergy.

    PubMed

    Bonura, A; Passantino, R; Costa, M A; Montana, G; Melis, M; Bondì, M Luisa; Butteroni, C; Barletta, B; Corinti, S; Di Felice, G; Colombo, P

    2012-03-01

    Parietaria pollen is one of the major cause of pollinosis in the southern Europe. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease restoring a normal immunity against allergens. We designed a recombinant molecule (PjEDloop1) comprised of genetic-engineered variants of the major allergens of the Parietaria pollen (Par j 2/Par j 1). Purity and chemical-physical properties of the derivative were analysed by RP-HPLC chromatography and Photon Correlation Spectroscopy. Immunological activity was evaluated by means of Western blotting, ELISA inhibition and PBMC proliferation assay in 10 Parietaria allergic patients. Basophil activation was studied in six subjects. The immunogenicity of the hybrid was studied looking at the immune responses induced in a mouse model of sensitization. The PjEDloop1 hybrid was produced as a purified recombinant protein with high stability in solution. Western blot, ELISA inhibition and basophil activation test showed that the PjEDloop1 displays a remarkable reduced IgE binding and anaphylactic activity. CD3 reactivity was conserved in all patients. Mice immunization with the rPjEDloop1 induced antibodies and T cell responses comparable to that obtained by the wild type allergens. Such antibodies shared the specificities to rPar j 1 and rPar j 2 with human IgE antibodies. Our results demonstrated that a mutant hybrid expressing genetically engineered forms of the major P. judaica allergens displayed reduced allergenicity and retained T cell reactivity for the induction of protective antibodies in vaccination approaches for the treatment of Parietaria pollinosis. © 2011 Blackwell Publishing Ltd.

  2. Developmental Control of a parAB Promoter Leads to Formation of Sporulation-Associated ParB Complexes in Streptomyces coelicolor

    PubMed Central

    Jakimowicz, Dagmara; Mouz, Sebastien; Zakrzewska-Czerwińska, Jolanta; Chater, Keith F.

    2006-01-01

    The Streptomyces coelicolor partitioning protein ParB binds to numerous parS sites in the oriC-proximal part of the linear chromosome. ParB binding results in the formation of large complexes, which behave differentially during the complex life cycle (D. Jakimowicz, B. Gust, J. Zakrzewska-Czerwinska, and K. F. Chater, J. Bacteriol. 187:3572-3580, 2005). Here we have analyzed the transcriptional regulation that underpins this developmentally specific behavior. Analysis of promoter mutations showed that the irregularly spaced complexes present in vegetative hyphae are dependent on the constitutive parABp1 promoter, while sporulation-specific induction of the promoter parABp2 is required for the assembly of arrays of ParB complexes in aerial hyphae and thus is necessary for efficient chromosome segregation. Expression from parABp2 depended absolutely on two sporulation regulatory genes, whiA and whiB, and partially on two others, whiH and whiI, all four of which are needed for sporulation septation. Because of this pattern of dependence, we investigated the transcription of these four whi genes in whiA and whiB mutants, revealing significant regulatory interplay between whiA and whiB. A strain in which sporulation septation (but not vegetative septation) was blocked by mutation of a sporulation-specific promoter of ftsZ showed close to wild-type induction of parABp2 and formed fairly regular ParB-enhanced green fluorescent protein foci in aerial hyphae, ruling out strong morphological coupling or checkpoint regulation between septation and DNA partitioning during sporulation. A model for developmental regulation of parABp2 expression is presented. PMID:16484182

  3. Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.

    PubMed

    Hidalgo-Carcedo, Cristina; Hooper, Steven; Chaudhry, Shahid I; Williamson, Peter; Harrington, Kevin; Leitinger, Birgit; Sahai, Erik

    2011-01-01

    Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell-cell contact. When actomyosin is not downregulated at cell-cell contacts, migrating cells lose cohesion. We provide a molecular mechanism for this downregulation. Depletion of discoidin domain receptor 1 (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional, three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion.

  4. Caracterisation et transformation par hydroviscoreduction du brut lourd de Doba/Tchad: Strategie de pompage par pipeline

    NASA Astrophysics Data System (ADS)

    Dehkissia, Soumaine

    Le projet de la these est defini par rapport a la recente exploitation commerciale du brut lourd de Doba, une region du Tchad, pays enclave d'ou le brut ainsi produit doit etre achemine par pipeline. Le but dans ce travail est de caracteriser ce brut et de determiner une strategie thermique de transformation en vue de reduire de la facon la plus economique, la viscosite du brut pour permettre son transport par pipeline. Concernant la partie caracterisation, nous avons utilise entre autres, un rheometre rotatif et des analyseurs (LECO CHN-2000 & LECO S-144DR Elemental Analyzers) pour evaluer respectivement la viscosite et les elements tels que C, H, N, O, S. Sur la base des methodes de transformation disponibles, nous avons determine une strategie simple de transformation thermique par hydroviscoreduction , strategie dans laquelle, la fraction legere du brut comme le naphta (80--180°C), pourrait constituer la source d'hydrogene a utiliser. Le brut de Doba, a une faible teneur en soufre (0.14%) et sa densite specifique de 0.940 a 15.6°C, soit 18.8° API, le classe parmi les bruts lourds. Outre le point initial se situant a 85°C, la distillation du brut a revele que la fraction distillant avant 250°C ne represente que 10% (v/v) et que le craquage thermique du substrat debute a 300°C. Par ailleurs, outre son caractere Newtonien, les densites specifiques de la fraction lourde de l'essence (100--200°C) et de la fraction distillant au-dessus 350°C, etant respectivement de 0.813 (0.813 > 0.800) et de 0.951 (0.930 < 0.951 < 0.975), le brut de Doba est donc de type aromatique. Les viscosites du brut et du brut desasphalte, sont respectivement de 184.4 cSt et 152.4 cSt a 50°C, suggerant que le desasphaltage ne constitue pas une methode efficace pouvant aider au pompage du brut par pipeline, d'ou la necessite de transformation. Les resultats des travaux en autoclave montrent que, si le brut doit etre traite entierement, la viscosite de 25cSt 50°C, recommandee pour le

  5. ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

    PubMed Central

    Dubarry, Nelly; Pasta, Franck; Lane, David

    2006-01-01

    Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

  6. Is PAR a Good Investment? Understanding the Costs and Benefits of Teacher Peer Assistance and Review Programs

    ERIC Educational Resources Information Center

    Papay, John P.; Johnson, Susan Moore

    2012-01-01

    Peer Assistance and Review (PAR) is a local labor-management initiative designed to improve teacher quality. In PAR, expert "consulting teachers" mentor, support, and evaluate novice and underperforming veteran teachers. Evaluations under PAR can lead to dismissals. The authors examine the costs and benefits of PAR, both financial and…

  7. Anterior PAR Proteins Function During Cytokinesis and Maintain DYN-1 at the Cleavage Furrow in Caenorhabditis elegans

    PubMed Central

    Pittman, Kelly J.; Skop, Ahna R.

    2013-01-01

    PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time. PMID:22887994

  8. Anterior PAR proteins function during cytokinesis and maintain DYN-1 at the cleavage furrow in Caenorhabditis elegans.

    PubMed

    Pittman, Kelly J; Skop, Ahna R

    2012-10-01

    PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR-6 and posterior PAR-2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR-6 and PAR-2 localize to the furrow membrane during ingression but PAR-2-GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR-2-GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR-3 and PAR-6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR-3 and PAR-6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN-1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time. Copyright © 2012 Wiley Periodicals, Inc.

  9. A model for the condensation of the bacterial chromosome by the partitioning protein ParB

    NASA Astrophysics Data System (ADS)

    Broedersz, Chase; Wingreen, Ned

    2013-03-01

    The molecular machinery responsible for faithful segregation of the chromosome in bacteria such as Caulobacter crescentus and Bacillus subtilis includes the ParABS a.k.a. Spo0J/Soj partitioning system. In Caulobacter, prior to division, hundreds of ParB proteins bind to the DNA near the origin of replication, and localize to one pole of the cell. Subsequently, the ParB-DNA complex is translocated to the far pole by the binding and retraction of the ParA spindle-like apparatus. Remarkably, the localization of ParB proteins to specific regions of the chromosome appears to be controlled by only a few centromeric parS binding sites. Although lateral interactions between DNA-bound ParB are likely to be important for their localization, the long-range order of ParB domains on the chromosome appears to be inconsistent with a picture in which protein-protein interactions are limited to neighboring DNA-bound proteins. We developed a coarse-grained Brownian dynamics model that allows for lateral and 3D protein-protein interactions among bound ParB proteins. Our model shows how such interactions can condense and organize the DNA spatially, and can control the localization and the long-range order of the DNA-bound proteins.

  10. A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation

    PubMed Central

    McLeod, Brett N.; Allison-Gamble, Gina E.; Barge, Madhuri T.; Tonthat, Nam K.; Schumacher, Maria A.; Hayes, Finbarr

    2017-01-01

    Abstract Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis. Mutants in which this ParG temporal regulation is ablated show partition deficient phenotypes as a result of either altered ParF structure or dynamics and indicate that ParF nucleoid localization and dynamic relocation, although necessary, are not sufficient per se to ensure plasmid segregation. We propose a Venus flytrap model that merges the concepts of ParA polymerization and gradient formation and speculate that a transient, dynamic network of intersecting polymers that branches into the nucleoid interior is a widespread mechanism to distribute sizeable cargos within prokaryotic cells. PMID:28034957

  11. PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

    PubMed

    Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

    2017-01-26

    Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05) PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

  12. Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1.

    PubMed

    Guo, Xingjun; Wang, Min; Zhao, Yan; Wang, Xin; Shen, Ming; Zhu, Feng; Shi, Chengjian; Xu, Meng; Li, Xu; Peng, Feng; Zhang, Hang; Feng, Yechen; Xie, Yu; Xu, Xiaodong; Jia, Wei; He, Ruizhi; Jiang, Jianxin; Hu, Jun; Tian, Rui; Qin, Renyi

    2016-08-01

    The conserved polarity complex, which comprises partitioning-defective proteins Par3, Par6, and the atypical protein kinase C, affects various cell-polarization events, including assembly of tight junctions. Control of tight junction assembly is closely related to invasion and migration potential. However, as the importance of conserved polarity complexes in regulating pancreatic cancer invasion and metastasis is unclear, we investigated their role and mechanism in pancreatic cancers. We first detect that the key protein of the conserved polarity complex finds that only Par3 is down-regulated in pancreatic cancer tissues while Par6 and aPKC show no difference. What is more, Par3 tissues level was significantly and positively associated with patient overall survival. Knocking-down Par3 promotes pancreatic cancer cells invasion and migration. And Par3 requires interaction with Tiam1 to affect tight junction assembly, and then affect invasion and migration of pancreatic cancer cells. Then, we find that tight junction marker protein ZO-1 and claudin-1 are down-regulated in pancreatic cancer tissues. And the relationship of the expression of Par3 and ZO-1 in pancreatic cancer tissue is linear correlation. We establish liver metastasis model of human pancreatic cancer cells in Balb/c nude mice and find that knocking down Par3 promotes invasion and metastasis and disturbs tight junction assembly in vivo. Taken together, these results suggest that the Par3 regulates invasion and metastasis in pancreatic cancers by controlling tight junction assembly.

  13. MAP kinase signaling antagonizes PAR-1 function during polarization of the early Caenorhabditis elegans embryo.

    PubMed

    Spilker, Annina C; Rabilotta, Alexia; Zbinden, Caroline; Labbé, Jean-Claude; Gotta, Monica

    2009-11-01

    PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell divisions, the asymmetric distribution of cell fate specification markers, and the distribution of PAR-1 protein in par-1 mutant embryos, indicating that this genetic interaction is functionally relevant for embryonic development. Furthermore, disrupting the function of other components of the MAPK signaling pathway resulted in suppression of par-1 embryonic lethality. Our data therefore indicates that MAP kinase signaling antagonizes PAR-1 signaling during early C. elegans embryonic polarization.

  14. Function, expression, specificity, diversity and incompatibility of actinobacteriophage parABS systems.

    PubMed

    Dedrick, Rebekah M; Mavrich, Travis N; Ng, Wei L; Cervantes Reyes, Juan C; Olm, Matthew R; Rush, Rachael E; Jacobs-Sera, Deborah; Russell, Daniel A; Hatfull, Graham F

    2016-08-01

    More than 180 individual phages infecting hosts in the phylum Actinobacteria have been sequenced and grouped into Cluster A because of their similar overall nucleotide sequences and genome architectures. These Cluster A phages are either temperate or derivatives of temperate parents, and most have an integration cassette near the centre of the genome containing an integrase gene and attP. However, about 20% of the phages lack an integration cassette, which is replaced by a 1.4 kbp segment with predicted partitioning functions, including plasmid-like parA and parB genes. Phage RedRock forms stable lysogens in Mycobacterium smegmatis in which the prophage replicates at 2.4 copies/chromosome and the partitioning system confers prophage maintenance. The parAB genes are expressed upon RedRock infection of M. smegmatis, but are downregulated once lysogeny is established by binding of RedRock ParB to parS-L, one of two centromere-like sites flanking the parAB genes. The RedRock parS-L and parS-R sites are composed of eight directly repeated copies of an 8 bp motif that is recognized by ParB. The actinobacteriophage parABS cassettes span considerable sequence diversity and specificity, providing a suite of tools for use in mycobacterial genetics. © 2016 John Wiley & Sons Ltd.

  15. Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

    PubMed

    Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

    2015-07-02

    Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

  16. Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer

    PubMed Central

    Montuori, Nunzia; Pesapane, Ada; Rossi, Francesca W; Giudice, Valentina; De Paulis, Amato; Selleri, Carmine; Ragno, Pia

    2016-01-01

    The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials. PMID:27896223

  17. PAR-1 contributes to the innate immune response during viral infection

    PubMed Central

    Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

    2013-01-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

  18. Microscopie en champ proche par réflexion

    NASA Astrophysics Data System (ADS)

    Spajer, M.; Courjon, D.; Sarayeddine, K.; Jalocha, A.; Vigoureux, J.-M.

    1991-01-01

    This communication presents two techniques for high resolution surface analysis. In the first one, the illumination beam is totally reflected under the object surface, which must be transparent. The evanescent wave confined on the surface is frustrated locally by a dielectric probe of nanometric dimension which scans the objetc. A horizontal resolution of 10 nm and a vertical one of 1 nm have been obtained. In the second one, more adapted to metallic objects, the surface is illuminated by the near-field of the stylus, in which the reflected beam is Partially launched. First results dealing with the characterization of the dielectric stylus are presented. Cette communication présente deux techniques permettant l'analyse de surface haute résolution. Dans la première, le faisceau d'éclairage est réfléchi totalement sous la surface de l'objet, nécessairement transparent. L'onde évanescente qui l'accompagne est frustrée localement par une pointe diélectrique de dimension nanométrique balayant la surface. Une résolution de 10 nm horizontalement et de 1nm verticalement a été obtenue. Dans la seconde, qui permet d'étudier un objet opaque, celui-ci est éclairé par le champ proche émis par la pointe, dans laquelle le faisceau réfléchi est partiellement réinjecté. Les premiers résultats concernant la caractérisation de la pointe sont présentés.

  19. Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.

    PubMed

    Nakamura, Hiroe; Nagasaka, Kazunori; Kawana, Kei; Taguchi, Ayumi; Uehara, Yuriko; Yoshida, Mitsuyo; Sato, Masakazu; Nishida, Haruka; Fujimoto, Asaha; Inoue, Tomoko; Adachi, Katsuyuki; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-11-17

    Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer. First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays. Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity. Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.

  20. PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

    PubMed Central

    Hernández, Norma A; Correa, Elma; Avila, Esther P; Vela, Teresa A; Pérez, Víctor M

    2009-01-01

    Background The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality. Methods In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor. Results Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009). Conclusion Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients. PMID:19538737

  1. uPAR regulates bronchial epithelial repair in vitro and is elevated in asthmatic epithelium

    PubMed Central

    Nijmeh, Hala S; Brightling, Christopher E; Sayers, Ian

    2011-01-01

    Background The asthma-associated gene urokinase plasminogen activator receptor (uPAR) may be involved in epithelial repair and airway remodelling. These processes are not adequately targeted by existing asthma therapies. A fuller understanding of the pathways involved in remodelling may lead to development of new therapeutic opportunities. uPAR expression in the lung epithelium of normal subjects and patients with asthma was investigated and the contribution of uPAR to epithelial wound repair in vitro was studied using primary bronchial epithelial cells (NHBECs). Methods Bronchial biopsy sections from normal subjects and patients with asthma were immunostained for uPAR. NHBECs were used in a scratch wound model to investigate the contribution of the plasminogen pathway to repair. The pathway was targeted via blocking of the interaction between urokinase plasminogen activator (uPA) and uPAR and overexpression of uPAR. The rate of wound closure and activation of intracellular signalling pathways and matrix metalloproteinases (MMPs) were measured. Results uPAR expression was significantly increased in the bronchial epithelium of patients with asthma compared with controls. uPAR expression was increased during wound repair in monolayer and air-liquid interface-differentiated NHBEC models. Blocking the uPA–uPAR interaction led to attenuated wound repair via changes in Erk1/2, Akt and p38MAPK signalling. Cells engineered to have raised levels of uPAR showed attenuated repair via sequestration of uPA by soluble uPAR. Conclusions The uPAR pathway is required for efficient epithelial wound repair. Increased uPAR expression, as seen in the bronchial epithelium of patients with asthma, leads to attenuated wound repair which may contribute to the development and progression of airway remodelling in asthma. This pathway may therefore represent a potential novel therapeutic target for the treatment of asthma. PMID:22139533

  2. [Relationships of rice canopy PAR interception and light use efficiency to grain yield].

    PubMed

    Tang, Liang; Zhu, Xiang-Cheng; Cao, Meng-Ying; Cao, Wei-Xing; Zhu, Yan

    2012-05-01

    Taking two rice cultivars (Liangyoupeijiu and Wuxiangjing 14) with different plant types as test materials, a 2-year field experiment was conducted to study the relationships of rice canopy photosynthetically active radiation (PAR) interception and light use efficiency to grain yield under three planting densities and five nitrogen (N) application rates. From tillering to maturing stage, the average PAR reflectance in all treatments was 3.45%. The ratio of reflected PAR to the total loss of PAR from tillering to heading stage was 10.90%, which was significantly lower than that (22.06%) from heading to maturiting stage. The PAR conversion efficiency from tillering to maturing stage decreased with increasing planting density but increased with increasing nitrogen rate, and the conversion efficiency was significantly higher from tillering to heading than from heading to maturing stage. The PAR use efficiency from tillering to maturing stage increased with the increase of planting density and nitrogen application rate, and the average PAR use efficiency of Liangyoupeijiu (1.83 g x MJ(-1)) was significantly higher than that of Wuxiangjing 14 (1.42 g x MJ(-1)). Due to the longer growth period of Wuxiangjing 14, its incident PAR and intercepted PAR under midium and high planting densities were higher, as compared with Liangyoupeijiu. The grain yield was significantly positively correlated with the canopy PAR interceptance and use efficiency at different growth stages, but less correlated with the PAR conversion efficiency. To increase the canopy PAR use efficiency and conversion efficiency on the basis of maintaining higher PAR interception rate could be an effective way to increase rice yield.

  3. Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis

    SciTech Connect

    Boosen, Meike; Vetterkind, Susanne; Koplin, Ansgar; Illenberger, Susanne; Preuss, Ute . E-mail: u.preuss@uni-bonn.de

    2005-12-10

    Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm and is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis.

  4. A systematic computation scheme of PAR-WIG cruising performance

    NASA Astrophysics Data System (ADS)

    Ando, Shigenori

    1993-08-01

    A systematic computation scheme is presented for PAR-WIG cruising performance, on a FORTRAN program. It is suitable for implementation on PCs. Effects of many parameters on the transportation efficiency are explored. Two concepts are presented in three views and artist impressions. One is a smallest single-crewman vehicle for experiment, sports, or pleasure. The other is a large vehicle for civil transportation. Both have twin hulls, which are quite suitable for installing a 'SMALL-TAIL-WIG' or 'WIG-let' to establish longitudinal attitude stability.

  5. BOREAS TE-12 Incoming PAR Through the Forest Canopy Data

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Papagno, Andrea (Editor); Walter-Shea, Elizabeth A.; Mesarch, Mark A.

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-12 (Terrestrial Ecology) team collected photosynthetically active radiation (PAR) data sets in support of its efforts to characterize and interpret information on shoot geometry, leaf optical properties, leaf water potential, and leaf gas exchange. The data were collected at the Southern Study Area-Old Black Spruce (SSA-OBS) site from 04-Jul-1996 to 25-Jul-1996. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  6. Recalculation of shielding for the addition of a PAR

    SciTech Connect

    Moe, H.J.

    1988-08-01

    The shielding estimates for the Electron and Positron Linacs and the Booster Synchrotron, contained in the 1987 Conceptual Design Report (CDR) of the APS (ANL-87-15), have been reviewed and recalculated, along with newly initiated calculations of the required shielding for the addition of a Positron Accumulator Ring (PAR). Several new assumptions with respect to beam intensity, projected losses in the system, and assumed operational time have been incorporated into the calculations. Details of the previous calculations, which describe the methodology used, may be found in APS Light Source Note LS-90.

  7. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  8. Simulated effects of changes in direct and diffuse radiation on canopy scale isoprene emissions from vegetation following volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Wilton, D. J.; Hewitt, C. N.; Beerling, D. J.

    2011-03-01

    Volcanic eruptions can alter the quality of incoming solar irradiance reaching the Earth's surface thereby influencing the interactions between vegetation and the Earth system. Isoprene (C5H8) is a biogenic volatile organic compound emitted from leaves at a rate strongly dependent on the received flux of photosynthetically radiation radiation (PAR). We investigated the potential for volcanic eruptions to change the isoprene flux from terrestrial vegetation using canopy-scale isoprene emission simulations that vary either the relative or absolute amount of diffuse (Idiff) and direct (Idir) PAR. According to our simulations, if the total amount of PAR remains constant while the proportion of Idiff increases, canopy-scale isoprene emissions increase. This effect increases as leaf area index increases. Simulating a~decrease in the total amount of PAR, and a corresponding increase in Idiff fraction, as measured during the 1992 Pinatubo eruption, decreases daily total canopy-scale isoprene emissions from terrestrial vegetation by 17-19% (for leaf area indices of 6 and 2, respectively). These effects have not previously been realized or quantified. Better capturing the effects of volcanic eruptions (and other major perturbations to the atmospheric aerosol content) on isoprene emissions from the terrestrial biosphere, and hence on the chemistry of the atmosphere, therefore requires inclusion of the effects of aerosols they produce on climate and total PAR and the Idiff/Idir ratio.

  9. Simulated effects of changes in direct and diffuse radiation on canopy scale isoprene emissions from vegetation following volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Wilton, D. J.; Hewitt, C. N.; Beerling, D. J.

    2011-11-01

    Volcanic eruptions can alter the quality of incoming solar irradiance reaching the Earth's surface thereby influencing the interactions between vegetation and the Earth system. Isoprene (C5H8) is a biogenic volatile organic compound emitted from leaves at a rate that is strongly dependent on the received flux of photosynthetically active radiation (PAR). We used a theoretical approach to investigate the potential for volcanic eruptions to change the isoprene flux from terrestrial forests using canopy-scale isoprene emission simulations that vary either the relative or absolute amount of diffuse (Idiff) and direct (Idir) PAR. According to our simulations for a northern hardwood deciduous forest, if the total amount of PAR during summer remains constant while the proportion of Idiff increases, canopy-scale isoprene emissions increase. This effect increases as leaf area index (LAI) increases. Simulating a decrease in the total amount of PAR, and a corresponding increase in Idiff fraction, as measured during the 1992 Pinatubo eruption, changes daily total canopy-scale isoprene emissions from terrestrial vegetation in summertime by +2.8% and -1.4% for LAI of 6 and 2, respectively. These effects have not previously been realized or quantified. Better capturing the effects of volcanic eruptions (and other major perturbations to the atmospheric aerosol content) on isoprene emissions from the terrestrial biosphere, and hence on the chemistry of the atmosphere, therefore may require inclusion of the effects of aerosols they produce on climate and the quality of PAR.

  10. Antibody-based PET of uPA/uPAR signaling with broad applicability for cancer imaging

    PubMed Central

    Dougherty, Casey A.; Lombardi, Rachel; Chen, Daiqin; Van Dort, Marcian E.; Barnhart, Todd E.; Ross, Brian D.; Mazar, Andrew P.; Hong, Hao

    2016-01-01

    Mounting evidence suggests that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a central role in tumor progression. The goal of this study was to develop an 89Zr-labeled, antibody-based positron emission tomography (PET) tracer for quantitative imaging of the uPA/uPAR system. An anti-uPA monoclonal antibody (ATN-291) was conjugated with a deferoxamine (Df) derivative and subsequently labeled with 89Zr. Flow cytometry, microscopy studies, and competitive binding assays were conducted to validate the binding specificity of Df-ATN-291 against uPA. PET imaging with 89Zr-Df-ATN-291 was carried out in different tumors with distinct expression levels of uPA. Biodistribution, histology examination, and Western blotting were performed to correlate tumor uptake with uPA or uPAR expression. ATN-291 retained uPA binding affinity and specificity after Df conjugation. 89Zr-labeling of ATN-291 was achieved in good radiochemical yield and high specific activity. Serial PET imaging demonstrated that, in most tumors studied (except uPA- LNCaP), the uptake of 89Zr-Df-ATN-291 was higher compared to major organs at 120 h post-injection, providing excellent tumor contrast. The tumor-to-muscle ratio of 89Zr-Df-ATN-291 in U87MG was as high as 45.2 ± 9.0 at 120 h p.i. In vivo uPA specificity of 89Zr-Df-ATN-291 was confirmed by successful pharmacological blocking of tumor uptake with ATN-291 in U87MG tumors. Although the detailed mechanisms behind in vivo 89Zr-Df-ATN-291 tumor uptake remained to be further elucidated, quantitative PET imaging with 89Zr-Df-ATN-291 in tumors can facilitate oncologists to adopt more relevant cancer treatment planning. PMID:27729618

  11. Mutations in the gyrB, parC, and parE genes of quinolone-resistant isolates and mutants of Edwardsiella tarda.

    PubMed

    Kim, Myoung Sug; Jun, Lyu Jin; Shin, Soon Bum; Park, Myoung Ae; Jung, Sung Hee; Kim, Kwangil; Moon, Kyung Ho; Jeong, Hyun Do

    2010-12-01

    The full length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in Edwardsiella tarda were cloned by PCR with degenerate primers based on the sequence of the respective quinolone resistance-determining region (QRDR), followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved gyrase/topoisomerase features and motifs important for enzymatic function. The ORFs were preceded by putative promoters, ribosome binding sites, and inverted repeats with the potential to form cruciform structures for binding of DNA-binding proteins. When comparing the deduced amino acid sequences of E. tarda GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria, they were found to be most closely related to Escherichia coli GyrB (87.6% identity), Klebsiella pneumoniae ParC (78.8% identity) and Salmonella typhimurium ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE, were found to be contiguous on the E. tarda chromosome. All 18 quinoloneresistant isolates obtained from Korea thus far did not contain subunit alternations apart from a substitution in GyrA (Ser83→Arg). However, an alteration in the QRDR of ParC (Ser84→Ile) following an amino acid substitution in GyrA (Asp87→Gly) was detected in E. tarda mutants selected in vitro at 8 microng/ml ciprofloxacin (CIP). A mutant with a GyrB (Ser464→Leu) and GyrA (Asp87→Gly) substitution did not show a significant increase in the minimum inhibitory concentration (MIC) of CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and parC should be considered to be the primary and secondary targets, respectively, of quinolones in E. tarda.

  12. The Par3 polarity protein is an exocyst receptor essential for mammary cell survival

    PubMed Central

    Ahmed, Syed Mukhtar; Macara, Ian G.

    2017-01-01

    The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 polarity protein associates with TJs but has no known function in membrane traffic. We now show that, unexpectedly, Par3 is essential for mammary cell survival. Par3 silencing causes apoptosis, triggered by phosphoinositide trisphosphate depletion and decreased Akt phosphorylation, resulting from failure of the exocyst to deliver basolateral proteins to the cortex. A small region of PAR3 binds directly to Exo70 and is sufficient for exocyst docking, membrane-protein delivery and cell survival. PAR3 lacking this domain can associate with the cortex but cannot support exocyst function. We conclude that Par3 is the long-sought exocyst receptor required for targeted membrane-protein delivery. PMID:28358000

  13. The Scribble and Par complexes in polarity and migration: friends or foes?

    PubMed

    Humbert, Patrick O; Dow, Lukas E; Russell, Sarah M

    2006-12-01

    The Par complex [consisting of Bazooka (also called Par3), Par6 and aPKC] is a well-described regulator of cell polarity whose role in many aspects of cell morphogenesis is under intense investigation. Recently, another set of proteins known as the Scribble complex (consisting of Scribble, Discs large and Lethal giant larvae) has also been shown to be important in polarity regulation in several settings. Here, we describe the current status of Scribble in polarity and review evidence from various model systems that indicates an essential but context-dependent role for the Scribble and Par complexes in directed cell migration. Based on the known interactions of Scribble and Par complexes with each other and with other signalling pathways, we propose models by which Par and Scribble might interact to regulate cell migration.

  14. Estimating Photosynthetically Available Radiation (PAR) at the Earth's surface from satellite observations

    NASA Technical Reports Server (NTRS)

    Frouin, Robert

    1993-01-01

    Current satellite algorithms to estimate photosynthetically available radiation (PAR) at the earth' s surface are reviewed. PAR is deduced either from an insolation estimate or obtained directly from top-of-atmosphere solar radiances. The characteristics of both approaches are contrasted and typical results are presented. The inaccuracies reported, about 10 percent and 6 percent on daily and monthly time scales, respectively, are useful to model oceanic and terrestrial primary productivity. At those time scales variability due to clouds in the ratio of PAR and insolation is reduced, making it possible to deduce PAR directly from insolation climatologies (satellite or other) that are currently available or being produced. Improvements, however, are needed in conditions of broken cloudiness and over ice/snow. If not addressed properly, calibration/validation issues may prevent quantitative use of the PAR estimates in studies of climatic change. The prospects are good for an accurate, long-term climatology of PAR over the globe.

  15. Brulure par Foudre. A Propos d’une Observation

    PubMed Central

    Mradmi, W.; Fassi-Fihri, J.; Mehaji, G.; Ezzoubi, M.; Diouri, M.; Bahechar, N.; Boukind, E.H.

    2005-01-01

    Summary Aussi loin que l’on remonte dans la littérature, on retrouve des récits relatant des accidents consécutifs à la fulguration chez l’homme. La foudre était alors associée à la colère des dieux ou à la notion de châtiment. La fulguration correspond à un transfert d’énergie entre un cumulonimbus de charge négative et un objet de charge positive se trouvant au niveau du sol. Les lésions déterminées sont à la fois thermiques et électrothermiques. Bien que l’arrêt cardiorespiratoire soit une cause bien documentée de décès, la plupart des cas rapportés dans la littérature décrivent un éventail très disparate des séquelles qui surviennent suite à cet accident. Les Auteurs rapportent le cas d’un patient atteint par la foudre en insistant particulièrement sur les complications neurologiques qui sont survenues en cours d’évolution. Se basant sur cette observation et sur une revue de la littérature, les Auteurs soulignent que le pronostic des patients atteints par la foudre est plus favorable que généralement rapporté. PMID:21990993

  16. Fluoroquinolone Resistance Mutations in the parC, parE, and gyrA Genes of Clinical Isolates of Viridans Group Streptococci

    PubMed Central

    González, Irene; Georgiou, Marios; Alcaide, Fernando; Balas, Delia; Liñares, Josefina; de la Campa, Adela G.

    1998-01-01

    The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cpr) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrB genes from the five low-level Cpr S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cpr S. oralis isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transform Streptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniae only when mutations in parC were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target. PMID:9797205

  17. Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci.

    PubMed

    González, I; Georgiou, M; Alcaide, F; Balas, D; Liñares, J; de la Campa, A G

    1998-11-01

    The nucleotide sequences of the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes from seven ciprofloxacin-resistant (Cpr) isolates of viridans group streptococci (two high-level Cpr Streptococcus oralis and five low-level Cpr Streptococcus mitis isolates) were determined and compared with those obtained from susceptible isolates. The nucleotide sequences of the QRDRs of the parE and gyrB genes from the five low-level Cpr S. mitis isolates and from the NCTC 12261 type strain were also analyzed. Four of these low-level Cpr isolates had changes affecting the subunits of DNA topoisomerase IV: three in Ser-79 (to Phe or Ile) of ParC and one in ParE at a position not previously described to be involved in quinolone resistance (Pro-424). One isolate did not show any mutation. The two high-level Cpr S. oralis isolates showed mutations affecting equivalent residue positions of ParC and GyrA, namely, Ser-79 to Phe and Ser-81 to Phe or Tyr, respectively. The parC mutations were able to transform Streptococcus pneumoniae to ciprofloxacin resistance, while the gyrA mutations transformed S. pneumoniae only when mutations in parC were present. These results suggest that DNA topoisomerase IV is a primary target of ciprofloxacin in viridans group streptococci, DNA gyrase being a secondary target.

  18. Cathepsin S Causes Inflammatory Pain via Biased Agonism of PAR2 and TRPV4*

    PubMed Central

    Zhao, Peishen; Lieu, TinaMarie; Barlow, Nicholas; Metcalf, Matthew; Veldhuis, Nicholas A.; Jensen, Dane D.; Kocan, Martina; Sostegni, Silvia; Haerteis, Silke; Baraznenok, Vera; Henderson, Ian; Lindström, Erik; Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E.; Liedtke, Wolfgang; McIntyre, Peter; Vanner, Stephen J.; Korbmacher, Christoph; Bunnett, Nigel W.

    2014-01-01

    Serine proteases such as trypsin and mast cell tryptase cleave protease-activated receptor-2 (PAR2) at R36↓S37 and reveal a tethered ligand that excites nociceptors, causing neurogenic inflammation and pain. Whether proteases that cleave PAR2 at distinct sites are biased agonists that also induce inflammation and pain is unexplored. Cathepsin S (Cat-S) is a lysosomal cysteine protease of antigen-presenting cells that is secreted during inflammation and which retains activity at extracellular pH. We observed that Cat-S cleaved PAR2 at E56↓T57, which removed the canonical tethered ligand and prevented trypsin activation. In HEK and KNRK cell lines and in nociceptive neurons of mouse dorsal root ganglia, Cat-S and a decapeptide mimicking the Cat-S-revealed tethered ligand-stimulated PAR2 coupling to Gαs and formation of cAMP. In contrast to trypsin, Cat-S did not mobilize intracellular Ca2+, activate ERK1/2, recruit β-arrestins, or induce PAR2 endocytosis. Cat-S caused PAR2-dependent activation of transient receptor potential vanilloid 4 (TRPV4) in Xenopus laevis oocytes, HEK cells and nociceptive neurons, and stimulated neuronal hyperexcitability by adenylyl cyclase and protein kinase A-dependent mechanisms. Intraplantar injection of Cat-S caused inflammation and hyperalgesia in mice that was attenuated by PAR2 or TRPV4 deletion and adenylyl cyclase inhibition. Cat-S and PAR2 antagonists suppressed formalin-induced inflammation and pain, which implicates endogenous Cat-S and PAR2 in inflammatory pain. Our results identify Cat-S as a biased agonist of PAR2 that causes PAR2- and TRPV4-dependent inflammation and pain. They expand the role of PAR2 as a mediator of protease-driven inflammatory pain. PMID:25118282

  19. Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4.

    PubMed

    Zhao, Peishen; Lieu, TinaMarie; Barlow, Nicholas; Metcalf, Matthew; Veldhuis, Nicholas A; Jensen, Dane D; Kocan, Martina; Sostegni, Silvia; Haerteis, Silke; Baraznenok, Vera; Henderson, Ian; Lindström, Erik; Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Liedtke, Wolfgang; McIntyre, Peter; Vanner, Stephen J; Korbmacher, Christoph; Bunnett, Nigel W

    2014-09-26

    Serine proteases such as trypsin and mast cell tryptase cleave protease-activated receptor-2 (PAR2) at R(36)↓S(37) and reveal a tethered ligand that excites nociceptors, causing neurogenic inflammation and pain. Whether proteases that cleave PAR2 at distinct sites are biased agonists that also induce inflammation and pain is unexplored. Cathepsin S (Cat-S) is a lysosomal cysteine protease of antigen-presenting cells that is secreted during inflammation and which retains activity at extracellular pH. We observed that Cat-S cleaved PAR2 at E(56)↓T(57), which removed the canonical tethered ligand and prevented trypsin activation. In HEK and KNRK cell lines and in nociceptive neurons of mouse dorsal root ganglia, Cat-S and a decapeptide mimicking the Cat-S-revealed tethered ligand-stimulated PAR2 coupling to Gαs and formation of cAMP. In contrast to trypsin, Cat-S did not mobilize intracellular Ca(2+), activate ERK1/2, recruit β-arrestins, or induce PAR2 endocytosis. Cat-S caused PAR2-dependent activation of transient receptor potential vanilloid 4 (TRPV4) in Xenopus laevis oocytes, HEK cells and nociceptive neurons, and stimulated neuronal hyperexcitability by adenylyl cyclase and protein kinase A-dependent mechanisms. Intraplantar injection of Cat-S caused inflammation and hyperalgesia in mice that was attenuated by PAR2 or TRPV4 deletion and adenylyl cyclase inhibition. Cat-S and PAR2 antagonists suppressed formalin-induced inflammation and pain, which implicates endogenous Cat-S and PAR2 in inflammatory pain. Our results identify Cat-S as a biased agonist of PAR2 that causes PAR2- and TRPV4-dependent inflammation and pain. They expand the role of PAR2 as a mediator of protease-driven inflammatory pain. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. The PARA-suite: PAR-CLIP specific sequence read simulation and processing

    PubMed Central

    Kloetgen, Andreas; Borkhardt, Arndt; Hoell, Jessica I.

    2016-01-01

    Background Next-generation sequencing technologies have profoundly impacted biology over recent years. Experimental protocols, such as photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP), which identifies protein–RNA interactions on a genome-wide scale, commonly employ deep sequencing. With PAR-CLIP, the incorporation of photoactivatable nucleosides into nascent transcripts leads to high rates of specific nucleotide conversions during reverse transcription. So far, the specific properties of PAR-CLIP-derived sequencing reads have not been assessed in depth. Methods We here compared PAR-CLIP sequencing reads to regular transcriptome sequencing reads (RNA-Seq) to identify distinctive properties that are relevant for reference-based read alignment of PAR-CLIP datasets. We developed a set of freely available tools for PAR-CLIP data analysis, called the PAR-CLIP analyzer suite (PARA-suite). The PARA-suite includes error model inference, PAR-CLIP read simulation based on PAR-CLIP specific properties, a full read alignment pipeline with a modified Burrows–Wheeler Aligner algorithm and CLIP read clustering for binding site detection. Results We show that differences in the error profiles of PAR-CLIP reads relative to regular transcriptome sequencing reads (RNA-Seq) make a distinct processing advantageous. We examine the alignment accuracy of commonly applied read aligners on 10 simulated PAR-CLIP datasets using different parameter settings and identified the most accurate setup among those read aligners. We demonstrate the performance of the PARA-suite in conjunction with different binding site detection algorithms on several real PAR-CLIP and HITS-CLIP datasets. Our processing pipeline allowed the improvement of both alignment and binding site detection accuracy. Availability The PARA-suite toolkit and the PARA-suite aligner are available at https://github.com/akloetgen/PARA-suite and https

  1. Participation of the urokinase-type plasminogen activator receptor (uPAR) in neutrophil transendothelial migration.

    PubMed

    Pliyev, Boris K; Antonova, Olga A; Menshikov, Mikhail

    2011-05-01

    The mechanisms underlying migration of neutrophils across endothelium are not completely understood. The urokinase-type plasminogen activator receptor (uPAR) plays a key role in neutrophil adhesion and migration. In the present study, we addressed whether uPAR regulates neutrophil transendothelial migration. We first showed that siRNA-mediated knockdown of uPAR in human umbilical vein endothelial cells (HUVECs) did not affect neutrophil migration across HUVEC monolayers indicating that endothelial uPAR does not regulate neutrophil transmigration. In contrast, the transmigration was significantly inhibited by Fab' fragment of anti-uPAR monoclonal antibody and proteolytically inactive urokinase (uPA), whereas inhibition of proteolytical activity of endogenous uPA (with amiloride or plasminogen activator inhibitor-1) did not affect the transmigration. Both the anti-uPAR Fab' fragment and proteolytically inactive uPA did not exert significant effects upon the transmigration conducted in the presence of F(ab')(2) fragment of blocking antibody to integrin Mac-1 indicating that uPAR regulates Mac-1-dependent transmigration. Mac-1-dependent, but not Mac-1-independent, transmigration was significantly reduced in the presence of N-acetyl-d-glucosamine and d-mannose, the saccharides that disrupt uPAR/Mac-1 association, but was unaffected in the presence of control saccharides (d-sorbitol and sucrose). We conclude that physical association of uPAR with Mac-1 mediates the regulatory effect of uPAR over the transmigration. Finally, we provide evidence that the functional cooperation between uPAR and Mac-1 is essential at both adhesion and diapedesis steps of neutrophil migration across endothelium. Thus, uPAR expressed on neutrophil plasma membrane regulates transendothelial migration independently of uPA proteolytical activity and acting as a cofactor for integrin Mac-1.

  2. The two Cis-acting sites, parS1 and oriC1, contribute to the longitudinal organisation of Vibrio cholerae chromosome I.

    PubMed

    David, Ariane; Demarre, Gaëlle; Muresan, Leila; Paly, Evelyne; Barre, François-Xavier; Possoz, Christophe

    2014-07-01

    The segregation of bacterial chromosomes follows a precise choreography of spatial organisation. It is initiated by the bipolar migration of the sister copies of the replication origin (ori). Most bacterial chromosomes contain a partition system (Par) with parS sites in close proximity to ori that contribute to the active mobilisation of the ori region towards the old pole. This is thought to result in a longitudinal chromosomal arrangement within the cell. In this study, we followed the duplication frequency and the cellular position of 19 Vibrio cholerae genome loci as a function of cell length. The genome of V. cholerae is divided between two chromosomes, chromosome I and II, which both contain a Par system. The ori region of chromosome I (oriI) is tethered to the old pole, whereas the ori region of chromosome II is found at midcell. Nevertheless, we found that both chromosomes adopted a longitudinal organisation. Chromosome I extended over the entire cell while chromosome II extended over the younger cell half. We further demonstrate that displacing parS sites away from the oriI region rotates the bulk of chromosome I. The only exception was the region where replication terminates, which still localised to the septum. However, the longitudinal arrangement of chromosome I persisted in Par mutants and, as was reported earlier, the ori region still localised towards the old pole. Finally, we show that the Par-independent longitudinal organisation and oriI polarity were perturbed by the introduction of a second origin. Taken together, these results suggest that the Par system is the major contributor to the longitudinal organisation of chromosome I but that the replication program also influences the arrangement of bacterial chromosomes.

  3. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

    PubMed

    Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

    2016-09-01

    The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb

    PubMed Central

    Sun, Miao; Asghar, Suwaiba Z.; Zhang, Huaye

    2016-01-01

    The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer’s disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. PMID:27072891

  5. A Desired PAR-Achieving Precoder Design for Multiuser MIMO OFDM Based on Concentration of Measure

    NASA Astrophysics Data System (ADS)

    Cha, Hyun-Su; Kim, Dong Ku

    2017-03-01

    For multi-user multiple-input and multiple-output (MIMO) wireless communications in orthogonal frequency di- vision multiplexing systems, we propose a MIMO precoding scheme providing a desired peak-to-average power ratio (PAR) at the minimum cost that is defined as received SNR degradation. By taking advantage of the concentration of measure, we formulate a convex problem with constraint on the desired PAR. Consequently, the proposed scheme almost exactly achieves the desired PAR on average, and asymptotically attains the desired PAR at the 0.001 point of its complementary cumulative distribution function, as the number of subcarriers increases.

  6. Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.

    PubMed

    Roman, Kenny; Done, Joseph D; Schaeffer, Anthony J; Murphy, Stephen F; Thumbikat, Praveen

    2014-07-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.

  7. Cancer-Selective Apoptotic Effects of Extracellular and Intracellular Par-4

    PubMed Central

    Bhattarai, Tripti Shrestha; Rangnekar, Vivek M.

    2010-01-01

    Selectivity toward cancer cells is the most desirable element in cancer therapeutics. Par-4 is a cancer cell-selective pro-apoptotic protein that functions intracellularly in the cytoplasmic and nuclear compartments, as a tumor suppressor. Moreover, recent findings indicate that the Par-4 protein is secreted by cells, and extracellular Par-4 induces cancer cell-specific apoptosis by interaction with the cell-surface receptor GRP78. This review describes the mechanisms underlying the apoptotic effects of both extracellular and intracellular Par-4 acting via its effector domain SAC. PMID:20440265

  8. TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells

    PubMed Central

    Nguyen, Jeffrey Q.; Irby, Rosalyn B.

    2017-01-01

    ABSTRACT The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain. Additional studies show that TRIM21 downregulates Par-4 levels in response to cisplatin, and that TRIM21 can increase the resistance of colon cancer cells to cisplatin. Furthermore, forced Par-4 expression can sensitize pancreatic cancer cells to cisplatin. Finally, we demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. Our work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer. PMID:27830973

  9. Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

    PubMed Central

    Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

    2014-01-01

    Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

  10. Biomass Burning Emissions and Deforestation in The Legal Amazon

    NASA Astrophysics Data System (ADS)

    Ellicott, E. A.; Vermote, E. F.

    2010-12-01

    Biomass burning, often concomitant with deforestation, is recognized as a significant source of atmospheric trace gases and aerosols and has received attention from the scientific community as an important agent in climate change. Earth observing satellites have made significant contributions to fire and deforestation detection, monitoring, and characterization for nearly three decades. In this work, we demonstrate the application of our approach to estimate fire radiative energy (FRE) released from biomass burning to infer CO2 and organic and black carbon aerosol (OCBC) emissions from biomass burning in the Legal Amazon. We then compared emission estimates with deforestation rates produced by the Brazilian National Institute for Space Research (INPE). Our research offers a new approach and insights to the dynamics of fire, deforestation, emissions. The annual mean CO2 and OCBC emitted for the study period (2001-2009) from the Legal Amazon biomass burning was estimated to be 253 Tg and 2.3 Tg, respectively. This represents 9% and 14% of the global CO2 and OCBC, respectively, emitted from fires. In general, the trend in emission estimates mirrored deforestation rates. However, 2007 was an anomalous year in Brazil as it was one of the highest years in emissions from fire, but a relatively low year for deforestation (Fig. 1). This discrepancy is a result of an abnormally dry year which resulted in a greater frequency of fires not directly associated with deforestation, but which may be tied to agricultural and pasture maintenance fires. A similar discrepancy was observed when comparing deforestation and emission rates from Mato Grosso and Pará; the two states responsible for most of the deforestation (71%) and emissions (~65%) from the Legal Amazon during the study period. Although as of 2006 Pará had annually surpassed Mato Grosso in annual forest loss it wasn’t until 2009 that emissions from Pará were greater. Thus, suggesting the importance of non

  11. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race

    PubMed Central

    Edelstein, Leonard C.; Simon, Lukas M.; Lindsay, Cory R.; Kong, Xianguo; Teruel-Montoya, Raúl; Tourdot, Benjamin E.; Chen, Edward S.; Ma, Lin; Coughlin, Shaun; Nieman, Marvin; Holinstat, Michael; Shaw, Chad A.

    2014-01-01

    Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n = 70) express 14% more PAR4 protein than those from whites (n = 84), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca2+ flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists. PMID:25293779

  12. Mapping transmembrane residues of proteinase activated receptor 2 (PAR2) that influence ligand-modulated calcium signaling.

    PubMed

    Suen, J Y; Adams, M N; Lim, J; Madala, P K; Xu, W; Cotterell, A J; He, Y; Yau, M K; Hooper, J D; Fairlie, D P

    2017-03-01

    Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor involved in metabolism, inflammation, and cancers. It is activated by proteolysis, which exposes a nascent N-terminal sequence that becomes a tethered agonist. Short synthetic peptides corresponding to this sequence also activate PAR2, while small organic molecules show promising PAR2 antagonism. Developing PAR2 ligands into pharmaceuticals is hindered by a lack of knowledge of how synthetic ligands interact with and differentially modulate PAR2. Guided by PAR2 homology modeling and ligand docking based on bovine rhodopsin, followed by cross-checking with newer PAR2 models based on ORL-1 and PAR1, site-directed mutagenesis of PAR2 was used to investigate the pharmacology of three agonists (two synthetic agonists and trypsin-exposed tethered ligand) and one antagonist for modulation of PAR2 signaling. Effects of 28 PAR2 mutations were examined for PAR2-mediated calcium mobilization and key mutants were selected for measuring ligand binding. Nineteen of twenty-eight PAR2 mutations reduced the potency of at least one ligand by >10-fold. Key residues mapped predominantly to a cluster in the transmembrane (TM) domains of PAR2, differentially influence intracellular Ca(2+) induced by synthetic agonists versus a native agonist, and highlight subtly different TM residues involved in receptor activation. This is the first evidence highlighting the importance of the PAR2 TM regions for receptor activation by synthetic PAR2 agonists and antagonists. The trypsin-cleaved N-terminus that activates PAR2 was unaffected by residues that affected synthetic peptides, challenging the widespread practice of substituting peptides for proteases to characterize PAR2 physiology.

  13. Painful spondylolysis or spondylolisthesis studied by radiography and single-photon emission computed tomography

    SciTech Connect

    Collier, B.D.; Johnson, R.P.; Carrera, G.F.; Meyer, G.A.; Schwab, J.P.; Flatley, T.J.; Isitman, A.T.; Hellman, R.S.; Zielonka, J.S.; Knobel, J.

    1985-01-01

    Planar bone scintigraphy (PBS) and single-photon emission computed tomography (SPECT) were compared in 19 adults with radiographic evidence of spondylolysis and/or spondylolisthesis. SPECT was more sensitive than PBS when used to identify symptomatic patients and sites of painful defects in the pars interarticularis. In addition, SPECT allowed more accurate localization than PBS. In 6 patients, spondylolysis or spondylolisthesis was unrealted to low back pain, and SPECT images of the posterior neural arch were normal. The authors conclude that when spondylolysis or spondylolisthesis is the cause of low back pain, pars defects are frequently heralded by increased scintigraphic activity which is best detected and localized by SPECT.

  14. Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

    PubMed Central

    Gur-Cohen, Shiri; Kollet, Orit; Graf, Claudine; Esmon, Charles T.; Ruf, Wolfram; Lapidot, Tsvee

    2016-01-01

    The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/PAR1 signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR+ LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NOlow LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling which overcomes BM EPCR+ LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production. PMID:26928241

  15. Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF

    PubMed Central

    Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

    2005-01-01

    Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins. PMID:15775965

  16. Inactivation of the candidate tumor suppressor par-4 in endometrial cancer.

    PubMed

    Moreno-Bueno, Gema; Fernandez-Marcos, Pablo J; Collado, Manuel; Tendero, Mercedes J; Rodriguez-Pinilla, Socorro M; Garcia-Cao, Isabel; Hardisson, David; Diaz-Meco, Maria T; Moscat, Jorge; Serrano, Manuel; Palacios, Jose

    2007-03-01

    Recently, it has been shown that mice deficient in the proapoptotic protein prostate apoptosis response 4 (Par-4) are specifically prone to develop endometrial carcinomas. Based on this, we have examined here the possible role of Par-4 as a tumor suppressor gene in human endometrial cancer. Using cDNA arrays, quantitative reverse transcription-PCR, and immunohistochemistry, we detected Par-4 down-regulation in approximately 40% of endometrial carcinomas. This alteration was not associated with phosphatase and tensin homologue (PTEN), K-RAS, or beta-catenin mutations, but was more frequent among tumors showing microsatellite instability (MSI) or among tumors that were estrogen receptor positive. Mutational analysis of the complete coding sequence of Par-4 in endometrial cancer cell lines (n = 6) and carcinomas (n = 69) detected a mutation in a single carcinoma, which was localized in exon 3 [Arg (CGA) 189 (TGA) Stop]. Interestingly, Par-4 promoter hypermethylation was detected in 32% of the tumors in association with low levels of Par-4 protein and was more common in MSI-positive carcinomas. Par-4 promoter hypermethylation and silencing was also detected in endometrial cancer cell lines SKUT1B and AN3CA, and reexpression was achieved by treatment with the demethylating agent 5'-aza-2'-deoxycytidine. Together, these data show that Par-4 is a relevant tumor suppressor gene in human endometrial carcinogenesis.

  17. Participatory Action Research (PAR) cum Action Research (AR) in Teacher Professional Development: A Literature Review

    ERIC Educational Resources Information Center

    Morales, Marie Paz E.

    2016-01-01

    This paper reviews Participatory Action Research as an approach to teacher professional development. It maps the origins of Participatory Action Research (PAR) and discusses the benefits and challenges that have been identified by other researchers in utilizing PAR approaches in conducting research. It draws ideas of combining the features of…

  18. Questioning Our Questions: Assessing Question Asking Practices to Evaluate a yPAR Program

    ERIC Educational Resources Information Center

    Grace, Sarah; Langhout, Regina Day

    2014-01-01

    The purpose of this research was to examine question asking practices in a youth participatory action research (yPAR) after school program housed at an elementary school. The research question was: In which ways did the adult question asking practices in a yPAR setting challenge and/or reproduce conventional models of power in educational…

  19. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein

    PubMed Central

    Tong, Song; Xia, Tian; Fan, Kai; Jiang, Ke; Zhai, Wei; Li, Jing-Song; Wang, Si-Hua; Wang, Jian-Jun

    2016-01-01

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein. PMID:27588399

  20. Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.

    PubMed

    Ubl, Joachim J; Grishina, Zoryana V; Sukhomlin, Tatiana K; Welte, Tobias; Sedehizade, Fariba; Reiser, Georg

    2002-06-01

    Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin.

  1. Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion

    PubMed Central

    Moore, Rachel; Theveneau, Eric; Pozzi, Sara; Alexandre, Paula; Richardson, Joanna; Merks, Anne; Parsons, Maddy; Kashef, Jubin; Linker, Claudia; Mayor, Roberto

    2013-01-01

    There is growing evidence that contact inhibition of locomotion (CIL) is essential for morphogenesis and its failure is thought to be responsible for cancer invasion; however, the molecular bases of this phenomenon are poorly understood. Here we investigate the role of the polarity protein Par3 in CIL during migration of the neural crest, a highly migratory mesenchymal cell type. In epithelial cells, Par3 is localised to the cell-cell adhesion complex and is important in the definition of apicobasal polarity, but the localisation and function of Par3 in mesenchymal cells are not well characterised. We show in Xenopus and zebrafish that Par3 is localised to the cell-cell contact in neural crest cells and is essential for CIL. We demonstrate that the dynamics of microtubules are different in different parts of the cell, with an increase in microtubule catastrophe at the collision site during CIL. Par3 loss-of-function affects neural crest migration by reducing microtubule catastrophe at the site of cell-cell contact and abrogating CIL. Furthermore, Par3 promotes microtubule catastrophe by inhibiting the Rac-GEF Trio, as double inhibition of Par3 and Trio restores microtubule catastrophe at the cell contact and rescues CIL and neural crest migration. Our results demonstrate a novel role of Par3 during neural crest migration, which is likely to be conserved in other processes that involve CIL such as cancer invasion or cell dispersion. PMID:24173803

  2. Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion.

    PubMed

    Moore, Rachel; Theveneau, Eric; Pozzi, Sara; Alexandre, Paula; Richardson, Joanna; Merks, Anne; Parsons, Maddy; Kashef, Jubin; Linker, Claudia; Mayor, Roberto

    2013-12-01

    There is growing evidence that contact inhibition of locomotion (CIL) is essential for morphogenesis and its failure is thought to be responsible for cancer invasion; however, the molecular bases of this phenomenon are poorly understood. Here we investigate the role of the polarity protein Par3 in CIL during migration of the neural crest, a highly migratory mesenchymal cell type. In epithelial cells, Par3 is localised to the cell-cell adhesion complex and is important in the definition of apicobasal polarity, but the localisation and function of Par3 in mesenchymal cells are not well characterised. We show in Xenopus and zebrafish that Par3 is localised to the cell-cell contact in neural crest cells and is essential for CIL. We demonstrate that the dynamics of microtubules are different in different parts of the cell, with an increase in microtubule catastrophe at the collision site during CIL. Par3 loss-of-function affects neural crest migration by reducing microtubule catastrophe at the site of cell-cell contact and abrogating CIL. Furthermore, Par3 promotes microtubule catastrophe by inhibiting the Rac-GEF Trio, as double inhibition of Par3 and Trio restores microtubule catastrophe at the cell contact and rescues CIL and neural crest migration. Our results demonstrate a novel role of Par3 during neural crest migration, which is likely to be conserved in other processes that involve CIL such as cancer invasion or cell dispersion.

  3. 12 CFR 925.19 - Par value and price of stock.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Par value and price of stock. 925.19 Section 925.19 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK MEMBERS AND HOUSING ASSOCIATES MEMBERS OF THE BANKS Stock Requirements § 925.19 Par value and price of stock. The capital...

  4. Slmb antagonises the aPKC/Par-6 complex to control oocyte and epithelial polarity.

    PubMed

    Morais-de-Sá, Eurico; Mukherjee, Avik; Lowe, Nick; St Johnston, Daniel

    2014-08-01

    The Drosophila anterior-posterior axis is specified when the posterior follicle cells signal to polarise the oocyte, leading to the anterior/lateral localisation of the Par-6/aPKC complex and the posterior recruitment of Par-1, which induces a microtubule reorganisation that localises bicoid and oskar mRNAs. Here we show that oocyte polarity requires Slmb, the substrate specificity subunit of the SCF E3 ubiquitin ligase that targets proteins for degradation. The Par-6/aPKC complex is ectopically localised to the posterior of slmb mutant oocytes, and Par-1 and oskar mRNA are mislocalised. Slmb appears to play a related role in epithelial follicle cells, as large slmb mutant clones disrupt epithelial organisation, whereas small clones show an expansion of the apical domain, with increased accumulation of apical polarity factors at the apical cortex. The levels of aPKC and Par-6 are significantly increased in slmb mutants, whereas Baz is slightly reduced. Thus, Slmb may induce the polarisation of the anterior-posterior axis of the oocyte by targeting the Par-6/aPKC complex for degradation at the oocyte posterior. Consistent with this, overexpression of the aPKC antagonist Lgl strongly rescues the polarity defects of slmb mutant germline clones. The role of Slmb in oocyte polarity raises an intriguing parallel with C. elegans axis formation, in which PAR-2 excludes the anterior PAR complex from the posterior cortex to induce polarity, but its function can be substituted by overexpressing Lgl.

  5. Bacterial actin homolog ParM: arguments for an apolar, antiparallel double helix.

    PubMed

    Erickson, Harold P

    2012-09-28

    The bacterial actin homolog ParM has always been modeled as a polar filament, comprising two parallel helical strands, like actin itself. I present arguments here that ParM may be an apolar filament, in which the two helical strands are antiparallel. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Questioning Our Questions: Assessing Question Asking Practices to Evaluate a yPAR Program

    ERIC Educational Resources Information Center

    Grace, Sarah; Langhout, Regina Day

    2014-01-01

    The purpose of this research was to examine question asking practices in a youth participatory action research (yPAR) after school program housed at an elementary school. The research question was: In which ways did the adult question asking practices in a yPAR setting challenge and/or reproduce conventional models of power in educational…

  7. The parA resolvase performs site-specific genomic excision in Arabidopsis

    USDA-ARS?s Scientific Manuscript database

    We have designed a site-specific excision detection system in Arabidopsis to study the in planta activity of the small serine recombinase ParA. Using a transient expression assay as well as stable transgenic plant lines, we show that the ParA recombinase is catalytically active and capable of perfo...

  8. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein.

    PubMed

    Song, Tong; Tian, Xia; Kai, Fan; Ke, Jiang; Wei, Zhai; Jing-Song, Li; Si-Hua, Wang; Jian-Jun, Wang

    2016-09-27

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein.

  9. Solar PAR and UVR modify the community composition and photosynthetic activity of sea ice algae.

    PubMed

    Enberg, Sara; Piiparinen, Jonna; Majaneva, Markus; Vähätalo, Anssi V; Autio, Riitta; Rintala, Janne-Markus

    2015-10-01

    The effects of increased photosynthetically active radiation (PAR) and ultraviolet radiation (UVR) on species diversity, biomass and photosynthetic activity were studied in fast ice algal communities. The experimental set-up consisted of nine 1.44 m(2) squares with three treatments: untreated with natural snow cover (UNT), snow-free (PAR + UVR) and snow-free ice covered with a UV screen (PAR). The total algal biomass, dominated by diatoms and dinoflagellates, increased in all treatments during the experiment. However, the smaller biomass growth in the top 10-cm layer of the PAR + UVR treatment compared with the PAR treatment indicated the negative effect of UVR. Scrippsiella complex (mainly Scrippsiella hangoei, Biecheleria baltica and Gymnodinium corollarium) showed UV sensitivity in the top 5-cm layer, whereas Heterocapsa arctica ssp. frigida and green algae showed sensitivity to both PAR and UVR. The photosynthetic activity was highest in the top 5-cm layer of the PAR treatment, where the biomass of the pennate diatom Nitzschia frigida increased, indicating the UV sensitivity of this species. This study shows that UVR is one of the controlling factors of algal communities in Baltic Sea ice, and that increased availability of PAR together with UVR exclusion can cause changes in algal biomass, photosynthetic activity and community composition. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Design and synthesis of peptides from bacterial ParE toxin as inhibitors of topoisomerases.

    PubMed

    Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Garcia, Anderson; Delfino, Davi Barbosa; Santos, Laura do Nascimento; Marchetto, Reinaldo

    2012-08-01

    Toxin-antitoxin (TA) proteic systems encode a toxin and an antitoxin that regulate the growth and death of bacterial cells under various stress conditions. The ParE protein is a toxin that inhibits DNA gyrase activity and thereby blocks DNA replication. Based on the Escherichia coli ParE structure, a series of linear peptides were designed and synthesized by solid-phase methodology. The ability of the peptides to inhibit the activity of bacterial topoisomerases was investigated. Four peptides (ParELC3, ParELC8, ParELC10 and ParELC12), showed complete inhibition of DNA gyrase supercoiling activity with an IC(100) between 20 and 40 μmol L(-1). In contrast to wild-type ParE, the peptide analogues were able to inhibit the DNA relaxation of topoisomerase IV, another type IIA bacterial topoisomerase, with lower IC(100) values. Interestingly only ParELC12 displayed inhibition of the relaxation activity of human topoisomerase II. Our findings reveal new inhibitors of bacterial topoisomerases and are a good starting point for the development of a new class of antibacterial agents that targets the DNA topoisomerases.

  11. Field studies of isoprene emissions from vegetation in the Northwest Mediterranean region

    NASA Astrophysics Data System (ADS)

    Owen, Susan M.; Boissard, C.; Hagenlocher, B.; Hewitt, C. Nicholas

    1998-10-01

    During the Biogenic Emissions in the Mediterranean Area (BEMA) project field campaigns (1993-1997), 40 native Mediterranean plant species were screened for emissions of isoprene and monoterpenes using a branch enclosure sampling method with subsequent gas chromatographic-flame ionization detector (GC-FID) and GC-mass selective detector (MS) analysis. Thirteen species emitted more than 0.5 μg (C) g-1 dw h-1 isoprene at 30°C and 1000 μmol m-2 s-1 photosynthetically active radiation (PAR), of which nine species emitted more than 20 μg (C) g-1 dw h-1. Emissions of isoprene were strongly correlated with temperature and PAR, and were reasonably well predicted by existing algorithms. There was little intraspecies and day to day variation in base emission rates. In general, median base emission rates were higher in summer compared to autumn for most species. Significant difference in aggregated habitat base emission rates was found between dunes, garrigue, woodland, and riverside sample sites. Although considerable unexplained variability in base emission rates remains to be explored, first estimates of base emission rates for Mediterranean shrublands are presented here.

  12. Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis

    PubMed Central

    Joshi, Jayashree; Fernandez-Marcos, Pablo J; Galvez, Anita; Amanchy, Ramars; Linares, Juan F; Duran, Angeles; Pathrose, Peterson; Leitges, Michael; Cañamero, Marta; Collado, Manuel; Salas, Clara; Serrano, Manuel; Moscat, Jorge; Diaz-Meco, Maria T

    2008-01-01

    The atypical PKC-interacting protein, Par-4, inhibits cell survival and tumorigenesis in vitro, and its genetic inactivation in mice leads to reduced lifespan, enhanced benign tumour development and low-frequency carcinogenesis. Here, we demonstrate that Par-4 is highly expressed in normal lung but reduced in human lung cancer samples. We show, in a mouse model of lung tumours, that the lack of Par-4 dramatically enhances Ras-induced lung carcinoma formation in vivo, acting as a negative regulator of Akt activation. We also demonstrate in cell culture, in vivo, and in biochemical experiments that Akt regulation by Par-4 is mediated by PKCζ, establishing a new paradigm for Akt regulation and, likely, for Ras-induced lung carcinogenesis, wherein Par-4 is a novel tumour suppressor. PMID:18650932

  13. ParA-like protein uses nonspecific chromosomal DNA binding to partition protein complexes.

    PubMed

    Roberts, Mark A J; Wadhams, George H; Hadfield, Katie A; Tickner, Susan; Armitage, Judith P

    2012-04-24

    Recent data have shown that plasmid partitioning Par-like systems are used by some bacterial cells to control localization of protein complexes. Here we demonstrate that one of these homologs, PpfA, uses nonspecific chromosome binding to separate cytoplasmic clusters of chemotaxis proteins upon division. Using fluorescent microscopy and point mutations, we show dynamic chromosome binding and Walker-type ATPase activity are essential for cluster segregation. The N-terminal domain of a cytoplasmic chemoreceptor encoded next to ppfA is also required for segregation, probably functioning as a ParB analog to control PpfA ATPase activity. An orphan ParA involved in segregating protein clusters therefore uses a similar mechanism to plasmid-segregating ParA/B systems and requires a partner protein for function. Given the large number of genomes that encode orphan ParAs, this may be a common mechanism regulating segregation of proteins and protein complexes.

  14. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.

    PubMed

    McCaffrey, Luke Martin; Montalbano, JoAnne; Mihai, Constantina; Macara, Ian G

    2012-11-13

    Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. To address this issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras(61L) expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models and produced invasive and metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer.

  15. Compression Myelopathy due to Proliferative Changes around C2 Pars Defects without Instability

    PubMed Central

    Kimura, Tetsuya; Tezuka, Fumitake; Abe, Mitsunobu; Yamashita, Kazuta; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

    2016-01-01

    We report a case with compression myelopathy due to proliferative changes around the C2 pars defects without instability. A 69-year-old man presented with progressive clumsy hands and spastic gait. Plain radiographs showed bilateral spondylolysis (pars defects) at C2 and fusion between C2 and C3 spinous processes. Dynamic views revealed mobility through the pars defects, but there was no apparent instability. Computed tomography showed proliferative changes at the pars defects, which protruded into spinal canal. On magnetic resonance imaging, the spinal cord was compressed and intramedullary high signal change was found. A diagnosis of compression myelopathy due to proliferative changes around the C2 pars defects was made. We performed posterior decompression. Postoperatively, symptoms have been alleviated and images revealed sufficient decompression and no apparent instability. In patients with the cervical spondylolysis, myelopathy caused by instability or slippage have been periodically reported. The present case involving C2 spondylolysis is extremely rare. PMID:27340539

  16. Inhibition of uPAR-TGFβ crosstalk blocks MSC-dependent EMT in melanoma cells.

    PubMed

    Laurenzana, Anna; Biagioni, Alessio; Bianchini, Francesca; Peppicelli, Silvia; Chillà, Anastasia; Margheri, Francesca; Luciani, Cristina; Pimpinelli, Nicola; Del Rosso, Mario; Calorini, Lido; Fibbi, Gabriella

    2015-07-01

    The capacity of cancer cells to undergo epithelial-to-mesenchymal transition (EMT) is now considered a hallmark of tumor progression, and it is known that interactions between cancer cells and mesenchymal stem cells (MSCs) of tumor microenvironment may promote this program. Herein, we demonstrate that MSC-conditioned medium (MSC-CM) is a potent inducer of EMT in melanoma cells. The EMT profile acquired by MSC-CM-exposed melanoma cells is characterized by an enhanced level of mesenchymal markers, including TGFβ/TGFβ-receptors system upregulation, by increased invasiveness and uPAR expression, and in vivo tumor growth. Silencing TGFβ in MSC is found to abrogate ability of MSC to promote EMT characteristics in melanoma cells, together with uPAR expression, and this finding is strengthened using an antagonist peptide of TGFβRIII, the so-called P17. Finally, we demonstrate that the uPAR antisense oligonucleotide (uPAR aODN) may inhibit EMT of melanoma cells either stimulated by exogenous TGFβ or MSC-CM. Thus, uPAR upregulation in melanoma cells exposed to MSC-medium drives TGFβ-mediated EMT. On the whole, TGFβ/uPAR dangerous liaison in cancer cell/MSC interactions may disclose a new strategy to abrogate melanoma progression. Mesenchymal stem cell (MSC)-conditioned medium induces EMT-like profile in melanoma. MSC-derived TGFβ promotes uPAR and TGFβ/TGFβ-receptor upregulation in melanoma. TGFβ gene silencing in MSCs downregulates uPAR expression and EMT in melanoma. uPAR downregulation prevents MSC-induced EMT-like profile in melanoma cells. Inhibition of the dangerous TGFβ/uPAR relationship might abrogate melanoma progression.

  17. PAR Interception and Utilization in Different Maize and Soybean Intercropping Patterns

    PubMed Central

    Liu, Xin; Rahman, Tanzeelur; Yang, Feng; Song, Chun; Yong, Taiwen; Liu, Jiang; Zhang, Cuiying; Yang, Wenyu

    2017-01-01

    The crop intercepted photosynthetically active radiation (PAR) and radiation use efficiency (RUE) vary markedly in different intercropping systems. The HHLA (horizontally homogeneous leaf area) and ERCRT (extended row crop radiation transmission) models have been established to calculate the intercepted PAR for intercrops. However, there is still a lack of study on the intercepted PAR and RUE under different intercropping configurations using different models. To evaluate the intercepted PAR and RUE in maize and soybean under different intercropping systems, we tested different strip intercropping configurations (SI1, SI2, and SI3 based on ERCRT model) and a row intercropping configurations (RI based on HHLA model) in comparison to monoculture. Our results showed that the intercepted PAR and RUE of intercropping systems were all higher than those of monoculture. The soybean intercepted PAR in strip intercropping was 1.35 times greater than that in row intercropping. In row intercropping (RI), the lack of soybean intercepted PAR resulted in a significant reduction of soybean dry matter. Therefore, it is not the recommended configuration for soybean. In strip intercropping patterns, with the distance between maize strip increased by 0.2 m, the intercepted PAR of soybean increased by 20%. The SI2 (maize row spacing at 0.4 m and the distance between maize strip at 1.6 m) was the recommended configuration to achieve the highest value of intercepted PAR and RUE among tested strip intercropping configurations. The method of dry matter estimation using intercepted PAR and RUE is useful in simulated experiments. The simulated value was verified in comparison with experimental data, which confirmed the credibility of the simulation model. Moreover, it also provides help in the development of functional-structural plant model (FSPM). PMID:28056056

  18. Circulating suPAR as a biomarker of disease severity in children with proteinuric glomerulonephritis.

    PubMed

    Soltysiak, Jolanta; Zachwieja, Jacek; Benedyk, Anna; Lewandowska-Stachowiak, Maria; Nowicki, Michal; Ostalska-Nowicka, Danuta

    2016-04-12

    The increase of circulating urokinase plasminogen activator receptor (suPAR) was demonstrated in various diseases showing its prognostic value as well as the link to the inflammatory reaction. In glomerular diseases suPAR was consider to be a causative factor of proteinuria. In present study we aimed to evaluate serum concentration of suPAR in children with primary and secondary glomerulonephritis (GN) and its association with disease severity. The study involved 22 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), 7 with Henoch-Schönlein nephritis (HSN), 7 with lupus nephritis (LN) and 16 controls. Serum suPAR was significantly higher in children with FSGS and LN than controls (respectively: 4.47±1.39 ng/mL vs. 3.23±0.76 ng/mL; p=0.011 and 6.17±1.12 ng/mL vs. 3.23±0.76 ng/mL; p<0.0001). Further, suPAR was increased in LN when compared to FSGS (p=0.031). In the total group suPAR showed negative correlation with eGFR, serum complement C3 and positive with left ventricular mass index. In children with MCD and FSGS the inverse association of suPAR with eGFR was also shown. In children with primary and secondary glomerulonphritis suPAR levels is not associated with proteinuria. In primary GN elevated suPAR levels may result from reduced eGFR reflecting renal damage. In LN, circulating suPAR can be increased further indicating both multi-organ involvement and systemic inflammation reflecting disease severity.

  19. uPAR and cathepsin B inhibition enhanced radiation-induced apoptosis in gliomainitiating cells

    PubMed Central

    Malla, Rama Rao; Gopinath, Sreelatha; Alapati, Kiranmai; Gorantla, Bharathi; Gondi, Christopher S.; Rao, Jasti S.

    2012-01-01

    Glioblastomas present as diffuse tumors with invasion into normal brain tissue and frequently recur or progress after radiation as focal masses because of glioma-initiating cells. The role of the urokinase-type plasminogen activator receptor (uPAR) and cathepsin B in stem-like phenotype has been extensively studied in several solid tumors. In the present study, we demonstrated that selection of glioma-initiating cells using CD133 expression leads to a specific enrichment of CD133+ cells in both U87 and 4910 cells. In addition, CD133+ cells exhibited a considerable amount of other stem cell markers, such as Nestin and Sox-2. Radiation treatment significantly enhanced uPAR and cathepsin B levels in glioma-initiating cells. To downregulate radiation-induced uPAR and cathepsin B expression, we used a bicistronic shRNA construct that simultaneously targets both uPAR and cathepsin B (pCU). Downregulation of uPAR and cathepsin B using pCU decreased radiation-enhanced uPAR and cathepsin B levels and caused DNA damage-induced apoptosis in glioma cell lines and glioma-initiating cells. The most striking finding of this study is that knockdown of uPAR and cathepsin B inhibited ongoing transcription by suppressing BrUTP incorporation at γH2AX foci. In addition, uPAR and cathepsin B gene silencing inversely regulated survivin and H2AX expression in both glioma cells and glioma-initiating cells. Pretreatment with pCU reduced radiation-enhanced expression of uPAR, cathepsin B, and survivin and enhanced DNA damage in pre-established glioma in nude mice. Taken together, our in vitro and in vivo findings suggest that uPAR and cathepsin B inhibition might serve as an adjunct to radiation therapy to target glioma-initiating cells and, therefore, for the treatment of glioma. PMID:22573309

  20. ESO-Hα 574 and Par-Lup 3-4 jets: Exploring the spectral, kinematical, and physical properties

    NASA Astrophysics Data System (ADS)

    Whelan, E. T.; Bonito, R.; Antoniucci, S.; Alcalá, J. M.; Giannini, T.; Nisini, B.; Bacciotti, F.; Podio, L.; Stelzer, B.; Comerón, F.

    2014-05-01

    In this paper a comprehensive analysis of VLT/X-Shooter observations of two jet systems, namely ESO-Hα 574 a K8 classical T Tauri star and Par-Lup 3-4 a very low mass (0.13 M⊙) M5 star, is presented. Both stars are known to have near-edge on accretion disks. A summary of these first X-shooter observations of jets was given in a 2011 letter. The new results outlined here include flux tables of identified emission lines, information on the morphology, kinematics and physical conditions of both jets and, updated estimates of Ṁout/Ṁacc. Asymmetries in the ESO-Hα 574 flow are investigated while the Par-Lup 3-4 jet is much more symmetric. The density, temperature, and therefore origin of the gas traced by the Balmer lines are investigated from the Balmer decrements and results suggest an origin in a jet for ESO-Hα 574 while for Par-Lup 3-4 the temperature and density are consistent with an accretion flow. Ṁacc is estimated from the luminosity of various accretion tracers. For both targets, new luminosity relationships and a re-evaluation of the effect of reddening and grey extinction (due to the edge-on disks) allows for substantial improvements on previous estimates of Ṁacc. It is found that log(Ṁacc) = -9.15 ± 0.45M⊙ yr-1 and -9.30 ± 0.27M⊙ yr-1 for ESO-Hα 574 and Par-Lup 3-4 respectively. Additionally, the physical conditions in the jets (electron density, electron temperature, and ionisation) are probed using various line ratios and compared with previous determinations from iron lines. The results are combined with the luminosity of the [SII]λ6731 line to derive Ṁout through a calculation of the gas emissivity based on a 5-level atom model. As this method for deriving Ṁout comes from an exact calculation based on the jet parameters (measured directly from the spectra) rather than as was done previously from an approximate formula based on the value of the critical density at an assumed unknown temperature, values of Ṁout are far more

  1. Seasonal variations in whole-ecosystem BVOC emissions from a subtropical bamboo plantation in China

    NASA Astrophysics Data System (ADS)

    Bai, Jianhui; Guenther, Alex; Turnipseed, Andrew; Duhl, Tiffany; Yu, Shuquan; Wang, Bin

    2016-01-01

    Isoprene and monoterpene emissions and environmental conditions were measured over a six month period in a Lei bamboo (Phyllostachys violascens) forest in a subtropical region in China. Isoprene and monoterpene emissions were measured using a relaxed eddy accumulation (REA) system on an above-canopy tower. From July to November of 2012, isoprene contributed 99.1% of terpenoid emissions. α-pinene, constituting 0.8% of total observed terpenoid emissions, was the only monoterpene for which a significant flux was detected. Emissions of the sesquiterpenes longifolene and α-cedrene were observed at very low rates. Isoprene and α-pinene emissions exhibited strong diurnal variations, with lower emissions in the morning and late evening, and the highest emissions around noon. BVOC peak emissions typically occurred a few hours after the noon PAR peak and coincided with the daily temperature peak. This behavior can be described reasonably well by the MEGANv2.1 biogenic emission model. During the campaign (i.e., from 7 July, 2012 to 19 Jan., 2013), the mean (and maximum) emission fluxes (mg m-2 h-1) were 0.95 (10.32) for isoprene, 0.010 (0.176) for α pinene, 0.001 (0.063) for longifolene, and 2.6 × 10-4 (0.009) for α-cedrene, respectively. During the winter season, when the ground was covered by organic mulch to increase soil temperature and to increase the yield of bamboo shoot, there was no evident impact on BVOC emissions. The observed seasonal variation followed the general behavior predicted by the MEGANv2.1 model, with lower emissions associated with cooler conditions, but the magnitude of the emission decrease was greater than expected indicating driving variables are missing from the model. Emission factors, representing the emission expected for a Leaf Area Index of 5 at a temperature of 30 °C and PAR of 1500 μmol m-2 s-1, during the peak growing season for this site were 0.008 mg m-2 h-1 for α-pinene and 3.3 mg m-2 h-1 for isoprene. The isoprene emission

  2. Facteurs de risque de mortalité par tuberculose pulmonaire

    PubMed Central

    Janah, Hicham; Souhi, Hicham; Kouismi, Hatim; Mark, Karima; Zahraoui, Rachida; Benamor, Jouda; Soualhi, Mona; Bourkadi, Jamal Eddine

    2014-01-01

    La tuberculose est une maladie infectieuse transmissible provoquée par myco-bacterium tuberculosis (bacille de Koch ou BK). Elle représente, selon les estimations del'Organisation Mondiale de la Santé (OMS), l'une des pathologies infectieuses causant le plus de décès au niveau mondial avec plus de 1 million de décès par an. Pour déterminer les facteurs de risque de mortalité au cours de la tuberculose pulmonaire à microscopie positive nous avons mené une étude rétrospective portant sur tous les cas de tuberculose pulmonaire à microscopie positive et qui étaient décédés au cours de leur hospitalisation. Cette étude a colligé 1803 cas de tuberculose sur une période de 2 ans et demi dont 46 sont décédés. La prévalence de décès est de 2,55%. La population se répartit en 32 hommes et 14 femmes. L’âge moyen était de 53ans ± 17 ans. Le tabagisme était retrouvé chez la moitié des cas. Une comorbidité était retrouvée dans 43%, avec 17% de diabète. Le délai de diagnostic avait une médiane de 60 jours avec percentile (30j; 105j). La symptomatologie clinique était dominée par la toux, la dyspnée et les expectorations soit respectivement: 97,8%, 69,6% et 67,4% des cas. Sur le plan radiologique les lésions étaient diffuses et bilatérales dans 76,1% des cas. Tous les patients étaient mis sous SRHZ. 11% avaient présenté une toxicité aux antibacillaires (de type hépatiques dans 3 cas et neurologiques dans 2 cas). Le délai médian de décès était de 8,5 jours (5j; 17j). Les causes de décès retrouvées étaient: Une hépatite fulminante (3 cas), une décompensation acido-cétosique (3 cas), un SDRA (2 cas), des hémoptysies foudroyantes (2 cas), et respectivement un cas secondaire à une décompensation de BPCO, une décompensation cardiaque, une hypoglycémie et un tableau d'anasarque. Cette étude suggère que le terrain, le retard diagnostique et les effets secondaires du traitement sont les principaux facteurs de risque de

  3. Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

    PubMed Central

    Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

    2013-01-01

    Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

  4. Proteinase-activated receptor-1 and immunomodulatory effects of a PAR1-activating peptide in a mouse model of prostatitis.

    PubMed

    Stanton, M Mark; Nelson, Lisa K; Benediktsson, Hallgrimur; Hollenberg, Morley D; Buret, Andre G; Ceri, Howard

    2013-01-01

    Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor.

  5. Light dependency of VOC emissions from selected Mediterranean plant species

    NASA Astrophysics Data System (ADS)

    Owen, S. M.; Harley, P.; Guenther, A.; Hewitt, C. N.

    The light, temperature and stomatal conductance dependencies of volatile organic compound (VOC) emissions from ten plant species commonly found in the Mediterranean region were studied using a fully controlled leaf cuvette in the laboratory. At standard conditions of temperature and light (30°C and 1000 μmol m -2 s -1 PAR), low emitting species ( Arbutus unedo, Pinus halepensis, Cistus incanus, Cistus salvifolius, Rosmarinus officinalis and Thymus vulgaris) emitted between 0.1 and 5.0 μg (C) (total VOCs) g -1 dw h -1, a medium emitter ( Pinus pinea) emitted between 5 and 10 μg (C) g -1 dw h -1 and high emitters ( Cistus monspeliensis, Lavendula stoechas and Quercus sp.) emitted more than 10 μg (C) g -1 dw h -1. VOC emissions from all of the plant species investigated showed some degree of light dependency, which was distinguishable from temperature dependency. Emissions of all compounds from Quercus sp. were light dependent. Ocimene was one of several monoterpene compounds emitted by P. pinea and was strongly correlated to light. Only a fraction of monoterpene emissions from C. incanus exhibited apparent weak light dependency but emissions from this plant species were strongly correlated to temperature. Data presented here are consistent with past studies, which show that emissions are independent of stomatal conductance. These results may allow more accurate predictions of monoterpene emission fluxes from the Mediterranean region to be made.

  6. Life cycle environmental impacts of a prospective palm-based biorefinery in Pará State-Brazil.

    PubMed

    Delivand, Mitra Kami; Gnansounou, Edgard

    2013-12-01

    The availability of about 18 million hectares of grassland in Pará State, Brazil, and the possibility of increasing the livestock density display a good perspective for the oil palm expansion in pasture land. A life cycle assessment is performed for a prospective palm-based biorefinery to view two regional and one global environmental impact and the consequences of the land-use change in terms of GHG emissions. Oil palm cultivation in an area of ∼110,000 hectares of land can annually produce ∼39,000 tons of bioethanol, ∼340,000 tons of biodiesel, ∼268 GW h net electricity and other co-products. The life cycle GHG emissions reduction for biodiesel and bioethanol as compared to fossil diesel and gasoline would be 76.9-79.3% and 83.7-88.6%. The advantage of grassland rehabilitation by oil palm plantation is the removal of ∼188 t CO2/ha from the atmosphere during the plant lifetime. The entire inflows and outflows for the conversion processes are schemed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

    PubMed Central

    Sweeney, Amanda M.; Fleming, Kelsey E.; McCauley, John P.; Rodriguez, Marvin F.; Martin, Elliot T.; Sousa, Alioscka A.; Leapman, Richard D.; Scimemi, Annalisa

    2017-01-01

    The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke. PMID:28256580

  8. Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation.

    PubMed

    Lim, Hoong Chuin; Surovtsev, Ivan Vladimirovich; Beltran, Bruno Gabriel; Huang, Fang; Bewersdorf, Jörg; Jacobs-Wagner, Christine

    2014-05-23

    The widely conserved ParABS system plays a major role in bacterial chromosome segregation. How the components of this system work together to generate translocation force and directional motion remains uncertain. Here, we combine biochemical approaches, quantitative imaging and mathematical modeling to examine the mechanism by which ParA drives the translocation of the ParB/parS partition complex in Caulobacter crescentus. Our experiments, together with simulations grounded on experimentally-determined biochemical and cellular parameters, suggest a novel 'DNA-relay' mechanism in which the chromosome plays a mechanical function. In this model, DNA-bound ParA-ATP dimers serve as transient tethers that harness the elastic dynamics of the chromosome to relay the partition complex from one DNA region to another across a ParA-ATP dimer gradient. Since ParA-like proteins are implicated in the partitioning of various cytoplasmic cargos, the conservation of their DNA-binding activity suggests that the DNA-relay mechanism may be a general form of intracellular transport in bacteria.DOI: http://dx.doi.org/10.7554/eLife.02758.001.

  9. Par-4/NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity

    PubMed Central

    QiNan, Wu; XiaGuang, Gan; XiaoTian, Lei; WuQuan, Deng; Ling, Zhang; Bing, Chen

    2016-01-01

    Apoptosis of islet β cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process. Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction. However, the mechanism by which Par-4/NF-κB induces islet β cell apoptosis remains unknown. We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro. We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4. It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction. Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them. Inhibition of NF-κB inhibited the Par-4-induced apoptosis. Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis. Our findings reveal a novel role for Par-4/NF-κB in islet β cell apoptosis and type 2 diabetes. PMID:27340675

  10. Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.

    PubMed

    Wojtukiewicz, Marek Z; Hempel, Dominika; Sierko, Ewa; Tucker, Stephanie C; Honn, Kenneth V

    2015-12-01

    Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs-mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.

  11. Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal.

    PubMed

    Chen, Daihui; Liu, Nian; Li, Mao; Liang, Simin

    2016-01-01

    Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

  12. Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal

    PubMed Central

    Chen, Daihui; Liu, Nian; Li, Mao

    2016-01-01

    Abstract Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. PMID:28123833

  13. PAR-2 receptor-induced effects on human eccrine sweat gland cells.

    PubMed

    L Bovell, Douglas; Kofler, Barbara; Lang, Roland

    2009-01-01

    Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

  14. CERCLA interim action at the Par Pond unit: A case study

    SciTech Connect

    Hickey, H.M.; Matthews, S.S.; Neal, L.W.; Weiss, W.R.

    1993-11-01

    The Par Pond unit designated under CERCLA consists of sediments within a Savannah River Site (SRS) cooling water reservoir. The sediments are contaminated with radionuclides and nonradioactive constituents from nuclear production reactor operations. The mercury in Par Pond is believed to have originated from the Savannah River. Because of Par Pond Dam safety Issues, the water level of the reservoir was drawn down, exposing more than 1300 acres of contaminated sediments and triggering the need for CERCLA interim remedial action. This paper presents the interim action approach taken with Par Pond as a case study. The approach considered the complexity of the Par Pond ecosystem, the large size of Par Pond, the volume of contaminated sediments, and the institutional controls existing at SRS. The Environmental Protection Agency (EPA) considers units with large volumes of low-concentration wastes, as is the case with Par Pond, to be {open_quotes}special sites.{close_quotes} Accordingly, EPA guidance establishes that the range of alternatives developed focus primarily on containment options and other remedial approaches that mitigate potential risks associated with the {open_quotes}special site.{close_quotes} The remedial alternatives, according to EPA, are not to be prohibitively expensive or difficult to implement. This case study also is representative of the types of issues that will need to be addressed within the Department of Energy (DOE) complex as nuclear facilities are transitioned to inactive status and corrective/remedial actions are warranted.

  15. Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

    PubMed Central

    2013-01-01

    Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

  16. [Development of agonists/antagonists for protease-activated receptors (PARs) and the possible therapeutic application to gastrointestinal diseases].

    PubMed

    Sekiguchi, Fumiko

    2005-06-01

    Protease-activated receptors (PARs), a family of G-protein-coupled seven-transmembrane-domain receptors, are activated by proteolytic unmasking of the N-terminal cryptic tethered ligand by certain serine proteases. Among four PAR family members cloned to date, PAR-1, PAR-2, and PAR-4 can also be activated through a non-enzymatic mechanism, which is achieved by direct binding of exogenously applied synthetic peptides based on the tethered ligand sequence, known as PARs-activating peptides, to the body of the receptor. Various peptide mimetics have been synthesized as agonists for PARs with improved potency, selectivity, and stability. Some peptide mimetics and/or nonpeptide compounds have also been developed as antagonists for PAR-1 and PAR-4. PARs are widely distributed in the mammalian body, especially throughout the alimentary systems, and play various roles in physiological/pathophysiological conditions, i.e., modulation of salivary, gastric, or pancreatic glandular exocrine secretion, gastrointestinal smooth muscle motility, gastric mucosal cytoprotection, suppression/facilitation of visceral pain and inflammation, etc. Thus PARs are now considered novel therapeutic targets, and development of selective agonists and/or antagonists for PARs might provide a novel strategy for the treatment of various diseases that are resistant to current therapeutics.

  17. Design of 118 MHz twelfth harmonic cavity of APS PAR

    SciTech Connect

    Kang, Y.W.; Kustom, R.L.; Bridges, J.F.

    1992-10-22

    Two radio frequency (RF) cavities are needed in the Positron Accumulator Ring (PAR) of the Advanced Photon Source. One is for the first harmonic frequency at 9.8 MHz, and the other is for the twelfth harmonic frequency at 118 MHz. This note reports on the design of the 118 MHz RF cavity. Computer models are used to find the mode frequencies, impedances, Q-factors, and field distributions in the cavity. The computer codes MAFIA, URMEL, and URMEL-T are useful tools which model and simulate the resonance characteristics of a cavity. These codes employ the finite difference method to solve Maxwell`s equations. MAFIA is a three-dimensional problem solver and uses square patches to approximate the inner surface of a cavity. URMEL and URMEL-T are two-dimensional problem solvers and use rectangular and triangular meshes, respectively. URMEL-T and MAFIA can handle problems with arbitrary dielectric materials located inside the boundary. The cavity employs a circularly cylindrical ceramic window to limit the vacuum to the beam pipe. The ceramic window used in the modeling will have a wall thickness of 0.9 cm. This wall thickness is not negligible in determining the resonant frequencies of the cavity. In the following, results of two- and three-dimensional modeling of the cavities using the URMEL-T and MAFIA codes are reported.

  18. [Association of epiretinal membranes with macular edema in pars planitis].

    PubMed

    Salcedo-Villanueva, G; Arellanes-García, L; Fromow-Guerra, J; Hernández-Quintela, E

    2014-01-01

    Pars planitis (PP) is a form of intermediate uveitis that manifests with several posterior segment complications, including cystoid macular edema (CME) and epiretinal membrane formation (ERM). On the presence of CME the patient is usually treated with anti-inflammatory and/or immunosuppressive drugs. However the presence of CME may coexist with ERM formation, and therefore the treatment could be different. To determine the association between ERM and CME in PP. Case control series. The charts of patients diagnosed with PP were retrospectively reviewed. All patients had fluorescein angiogram (FA) and spectral domain optical coherence tomography (SD-OCT). Presence of ERM was determined by SD-OCT, while CME was determined by FA. Contingency tables were used to determine the risk of developing CME with ERM. 31 eyes presented ERM. 16 eyes presented CME. Relative risk to have CME and ERM was 0.971, with a P value of 0.77 (χ(2)). There is no association between ERM formation and the development of CME. There is no evidence to suggest a surgical approach as first line of treatment with the presence of ERM in PP. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  19. Plaies des membres par agression: analyse de 245 dossiers

    PubMed Central

    Boufettal, Monsef; Mahfoud, Mustapha; Ismael, Farid; Kharmaz, Mohamed; Bardouni, Ahmed El; Berrada, Mohamed Saleh; Yaacoubi, Moradh El

    2015-01-01

    Il s'agit d'une étuderétrospective, analytique, monocentrique rentrant dans le cadre d'une étude épidémiologique s’étalant sur une période de trois années (de 2010 à 2012) durant laquelle nous avons revu les dossiers de 245 patients victimes de violence et d'agression. Nous avons exclu les lésions simples traitées en ambulatoire. Par conséquent, nous nous sommes limités aux cas de blessures ayant nécessité une prise en charge spécialisée au bloc opératoire. Les objectifs de notre travail étaient de connaitre la fréquence des agressions au service de traumatologie du CHU de Rabat, classer les différents types de lésions, évaluer leur gravité, mettre la lumière sur les populations les plus touchées et enfin montrer les différentes modalités de prise en charge thérapeutiques. PMID:26918078

  20. Photometric monitoring of the young star Par 1724 in Orion

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Koeltzsch, A.; Raetz, St.; Schmidt, T. O. B.; Mugrauer, M.; Young, N.; Bertoldi, F.; Roell, T.; Eisenbeiss, T.; Hohle, M. M.; Vaňko, M.; Ginski, C.; Rammo, W.; Moualla, M.; Broeg, C.

    2009-05-01

    We report new photometric observations of the ˜ 200 000 year old naked weak-line run-away T Tauri star Par 1724, located north of the Trapezium cluster in Orion. We observed in the broad band filters B, V, R, and I using the 90 cm Dutch telescope on La Silla, the 80 cm Wendelstein telescope, and a 25 cm telescope of the University Observatory Jena in Großschwabhausen near Jena. The photometric data in V and R are consistent with a ˜ 5.7 day rotation period due to spots, as observed before between 1960ies and 2000. Also, for the first time, we present evidence for a long-term 9 or 17.5 year cycle in photometric data (V band) of such a young star, a cycle similar to that to of the Sun and other active stars. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University; a telescope of the University Observatory Munich on Mount Wendelstein, the 0.9m ESO-Dutch telescope on La Silla, Chile, and with the All Sky Automated Survey (ASAS) project (www.astrouw.edu.pl/asas).

  1. Caractérisation par ellipsométrie spectroscopique de films minces de tellurure de bismuth obtenus par voie électrochimique

    NASA Astrophysics Data System (ADS)

    Zimmer, A.; Stein, N.; Boulanger, C.; Johann, L.

    2004-12-01

    Des films de tellurure de bismuth (Bi2Te3) d’épaisseur proche de 1 mm ont été développés par voie électrochimique. Leurs indices optiques ont été déterminés par ellipsométrie spectroscopique (SE). Le domaine spectral des indices optiques s’étend de 400 nm à 1300 nm. L’ellipsométrie spectroscopique à angle d’incidence variable (VASE) a été utilisée pour corréler les données SE. Cette partie a été complétée par des analyses par microscopie à force atomique (AFM) qui ont permis de déterminer la rugosité des films. A partir de ces résultats et en associant l’absorption fondamentale des films de Bi2Te3 à une transition indirecte, l’énergie de bande interdite a été évaluée à 0,3 eV. Par ailleurs des mesures associant ellipsométrie spectroscopique à temps réel et électrochimie ont pu être réalisées. Ainsi les premiers instants de croissance ont été observés.

  2. Small caliber arterial endothelial cells calcium signals elicited by PAR2 are preserved from endothelial dysfunction

    PubMed Central

    Hennessey, John C; Stuyvers, Bruno D; McGuire, John J

    2015-01-01

    Endothelial cell (EC)-dependent vasodilation by proteinase-activated receptor 2 (PAR2) is preserved in small caliber arteries in disease states where vasodilation by muscarinic receptors is decreased. In this study, we identified and characterized the PAR2-mediated intracellular calcium (Ca2+)-release mechanisms in EC from small caliber arteries in healthy and diseased states. Mesenteric arterial EC were isolated from PAR2 wild-type (WT) and null mice, after saline (controls) or angiotensin II (AngII) infusion, for imaging intracellular calcium and characterizing the calcium-release system by immunofluorescence. EC Ca2+ signals comprised two forms of Ca2+-release events that had distinct spatial-temporal properties and occurred near either the plasmalemma (peripheral) or center of EC. In healthy EC, PAR2-dependent increases in the densities and firing rates of both forms of Ca2+-release were abolished by inositol 1,4,5- trisphosphate receptor (IP3R) inhibitor, but partially reduced by transient potential vanilloid channels inhibitor ruthenium red (RR). Acetylcholine (ACh)-induced less overall Ca2+-release than PAR2 activation, but enhanced selectively the incidence of central events. PAR2-dependent Ca2+-activity, inhibitors sensitivities, IP3R, small- and intermediate-conductance Ca2+-activated potassium channels expressions were unchanged in EC from AngII WT. However, the same cells exhibited decreases in ACh-induced Ca2+-release, RR sensitivity, and endothelial nitric oxide synthase expression, indicating AngII-induced dysfunction was differentiated by receptor, Ca2+-release, and downstream targets of EC activation. We conclude that PAR2 and muscarinic receptors selectively elicit two elementary Ca2+ signals in single EC. PAR2-selective IP3R-dependent peripheral Ca2+-release mechanisms are identical between healthy and diseased states. Further study of PAR2-selective Ca2+-release for eliciting pathological and/or normal EC functions is warranted. PMID:25729579

  3. Evaluation of orthodontists' perception of treatment need and the peer assessment rating (PAR) index.

    PubMed

    McGorray, S P; Wheeler, T T; Keeling, S D; Yurkiewicz, L; Taylor, M G; King, G J

    1999-08-01

    This paper examines the relationship between orthodontists' subjective assessment of treatment need and objective measurements obtained during standardized intra- and extraoral examinations. Logistic regression modeling was used to develop predictive models of treatment need. Data were obtained from 1155 eighth-grade students by four orthodontists who used standardized examination forms to assess demographics, trauma, skeletal relationships, morphologic malocclusion traits, and mandibular function. At the conclusion of the examination, the orthodontist rated the subjective treatment need as none, elective, recommended, soon, or immediate. For some analyses, the categories were collapsed to represent no need and need. The peer assessment rating (PAR) index (American validated version) was computed from the clinical exam findings and scoring of dental models; PAR scores were used to document malocclusion severity and treatment difficulty. Spearman rank correlation coefficients quantified the relationship between PAR scores and need categories. Logistic regression analysis modeled treatment need using components of the PAR index as well as other variables. The components of these models, as well as sensitivity and specificity, were compared with malocclusion severity/treatment difficulty scores obtained from malocclusion assessments using the PAR index. The five subjective treatment need categories and the PAR index scores were significantly correlated (rho = 0.62, p<0.001). Significant differences were detected between the need and no need groups for all PAR components (p<0.001). PAR index scores and predicted probabilities from logistic regression models performed equally well for classification purposes (no need, need). The data suggest that the PAR index is highly correlated with orthodontists' subjective assessment of treatment need when that assessment is made in the absence of financial considerations and patient desires.

  4. Expression of prostate apoptosis response (Par-4) is associated with progesterone receptor in breast cancer.

    PubMed

    Zapata-Benavides, Pablo; Méndez-Vázquez, José L; González-Rocha, Talina R; Zamora-Avila, Diana E; Franco-Molina, Moises A; Garza-Garza, Raúl; Rodriguez-Padilla, Cristina

    2009-10-01

    The prostate apoptosis response (Par-4) gene encodes a proapoptotic protein that selectively induces apoptosis in cancer cells after diverse apoptotic stimuli. Par-4 expression and its association with other biomarkers have not been reported in breast cancer. The purpose of this study was to determine Par-4 expression in breast cancer samples and its association with other biomarkers and clinical factors (T-stage, age, nodal status). Paraffin-embedded section samples of breast cancer were evaluated by immunohistochemical analysis to determine Par-4, estrogen receptor (ER), progesterone receptor (PgR), c-erbB2, Ki67, p53 and bcl-2 expression. The correlation between Par-4 and the other biomarkers and clinical factors was determined by multivariate analysis. Thirty five percent (n=21) of samples were PAR-4 positive and 64.4% (n=38) were negative. The hormonal status was 64% ER positive (n=38), 35% ER-negative (n=21) and 40.7% PgR positive (n=24), 59.3% PgR negative (n=35). The majority (90%) of the samples presented clear cytoplasmic localization and a small portion (10%) was cytoplasmic and nuclear. Univariate analysis indicates that the Par-4 expression has a significant inverse association (p=0.04) only with expression of PgR and not with the other variables analyzed. Normal breast tissue analyzed was negative for Par-4 immunostaining. Our results suggest that, in breast cancer, Par-4 plays a similar tumor suppressor gene role as reported in endometrial carcinoma. 2009. Published by Elsevier Inc.

  5. KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation

    PubMed Central

    Jha, Hem C.; Sun, Zhiguo; Upadhyay, Santosh K.; El-Naccache, Darine W.; Singh, Rajnish K.; Sahu, Sushil K.; Robertson, Erle S.

    2016-01-01

    Studies have suggested that Epithelial–Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas. PMID:27463802

  6. Biogenic Volatile Organic Compound Emissions in a Temperature Forest and a Bamboo Forest in China

    NASA Astrophysics Data System (ADS)

    Bai, Jianhui; Guenther, Alex; Turnipseed, Andrew; Duhl, Tiffany; Duhl, Nanhao; Van der A, Ronald; Yu, Shuquan; Wang, Bin

    2014-11-01

    Emission fluxes of Biogenic V olatile Organic compounds (BVOC), solar radiation (including global radiation, Photosynthetically Active Radiation (PAR), etc.), meteorological parameters were carried out in Changbai temperature forest during growing seasons of 2010 and 2011 and Linan subtropical bamboo forest from July 2012 to Jan. 2013 in China. A REA (Relaxed Eddy Accumulation) system was used to measure BVOC emissions on an above-canopy tower. Isoprene and monoterpenes showed obvious diurnal and seasonal variations in these two forests, their daily maxima occurred around noon. The average emission fluxes (mg m-2 h-1) were 0.889 for isoprene and 0.143 for monoterpene in Changbai temperate forest in 2011 growing season, 0.95 for isopreneor and 0.012 for monoterpene in Linan bamboo forest during the whole campaign. Based on PAR energy balance, empirical models of BVOC emissions in these temperate and subtropical forests were developed, the estimated emissions of isoprene and monoterpenes were in agreement with observations. Applying these empirical models, BVOC emissions in Changbai temperate forest during growing seasons and in Linan subtropical bamboo forest from July 2012 to Jan. 2013 werecalculated. The relationships between surface measurements of BVOC emissions and HCHO vertical column densities retrieved from the satellite were found in these two forests.

  7. Biogenic Volatile Organic Compound Emissions in a Temperature Forest and a Bamboo Forest in China

    NASA Astrophysics Data System (ADS)

    Bai, Jianhui; Guenther, Alex; Turnipseed, Andrew; Duhl, Tiffany; Hao, Nan; van der A, Ronald; Yu, Shuquan; Wang, Bin

    2014-11-01

    Emission fluxes of Biogenic Volatile Organic compounds (BVOC), solar radiation (including global radiation, Photosynthetically Active Radiation (PAR), etc.), meteorological parameters were carried out in Changbai temperature forest during growing seasons of 2010 and 2011 and Linan subtropical bamboo forest from July 2012 to Jan. 2013 in China. A REA (Relaxed Eddy Accumulation) system was used to measure BVOC emissions on an above-canopy tower. Isoprene and monoterpenes showed obvious diurnal and seasonal variations in these two forests, their daily maxima occurred around noon. The average emission fluxes (mg m-2 h-1) were 0.889 for isoprene and 0.143 for monoterpene in Changbai temperate forest in 2011 growing season, 0.95 for isopreneor and 0.012 for monoterpene in Linan bamboo forest during the whole campaign. Based on PAR energy balance, empirical models of BVOC emissions in these temperate and subtropical forests were developed, the estimated emissions of isoprene and monoterpenes were in agreement with observations. Applying these empirical models, BVOC emissions in Changbai temperate forest during growing seasons and in Linan subtropical bamboo forest from July 2012 to Jan. 2013 were calculated. The relationships between surface measurements of BVOC emissions and HCHO vertical column densities retrieved from the satellite were found in these two forests.

  8. Provenance of the oil in par-fried French fries after finish frying.

    PubMed

    Al-Khusaibi, Mohammed; Gordon, Michael H; Lovegrove, Julie A; Niranjan, Keshavan

    2012-01-01

    Frozen par-fried French fries are finish-fried either by using the same type of oil used for par frying, or a different type. The nutritive quality of the final oil contained in the product depends on the relative amounts and the fatty acid (FA) composition of the oils used for par frying and finish frying. With the aim of understanding the provenance of the oil in the final product, par-fried French fries-either purchased ready or prepared in the laboratory-were finish fried in oils different from the ones used for par frying. The moisture content, oil content, and FA compositions of the par-fried and finish-fried products were experimentally determined, and the relative amounts of each of the oils present in the final product were calculated using the FAs as markers and undertaking a mass balance on each component FA. The results demonstrate that 89% to 93% of the total oil in the final product originates from the finish-frying step. The study also shows that a significant proportion of the oil absorbed during par frying is expelled from the product during finish frying. Further, the expulsion of par-frying oil was found to occur in the early stages of the finish-frying step. Experiments involving different combinations of par-frying and finish-frying oils showed that the relative proportions of the 2 oils did not depend on the individual fatty acid profiles. This study concludes that any positive health benefits of using an oil having a favorable FA profile for par frying, can potentially be lost, if the oil used for finish frying has a less favorable composition. This paper estimates the relative amounts of oil in French fries that have been fried in 2 stages-a par-frying step and a finish-frying step-which is commonly practiced in food service establishments as well as homes. The 2 key conclusions are: (1) nearly 90% of the oil content of the final product is the one used for finish frying; that is, a processor may use very good oil for par frying but if the

  9. Drug efflux and parC mutations are involved in fluoroquinolone resistance in viridans group streptococci.

    PubMed

    Ferrándiz, M J; Oteo, J; Aracil, B; Gómez-Garcés, J L; De La Campa, A G

    1999-10-01

    Nine ciprofloxacin-resistant viridans group streptococci isolated from asymptomatic carriers were analyzed. Identification to the species level by using three different commercial systems and a PCR-based approach was inconsistent. The nucleotide sequences of fragments of the parC, parE, gyrA, and gyrB genes showed considerable intra- and interspecies variations, and these variations mainly involved silent mutations. Three isolates had changes in Ser-79 of ParC (to Phe or Tyr). Phenotypic characterization indicated that eight of the nine isolates had a putative efflux mechanism that would confer low-level resistance to ciprofloxacin.

  10. Drug Efflux and parC Mutations Are Involved in Fluoroquinolone Resistance in Viridans Group Streptococci

    PubMed Central

    Ferrándiz, María José; Oteo, Jesús; Aracil, Belén; Gómez-Garcés, Jose Luis; De La Campa, Adela G.

    1999-01-01

    Nine ciprofloxacin-resistant viridans group streptococci isolated from asymptomatic carriers were analyzed. Identification to the species level by using three different commercial systems and a PCR-based approach was inconsistent. The nucleotide sequences of fragments of the parC, parE, gyrA, and gyrB genes showed considerable intra- and interspecies variations, and these variations mainly involved silent mutations. Three isolates had changes in Ser-79 of ParC (to Phe or Tyr). Phenotypic characterization indicated that eight of the nine isolates had a putative efflux mechanism that would confer low-level resistance to ciprofloxacin. PMID:10508036

  11. 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.

  12. Prostate apoptosis response 4 (PAR4) expression modulates WNT signaling pathways in MCF7 breast cancer cells: A possible mechanism underlying PAR4-mediated docetaxel chemosensitivity

    PubMed Central

    De Bessa Garcia, Simone Aparecida; Pavanelli, Ana Carolina; Melo, Natália Cruz E; Nagai, Maria Aparecida

    2017-01-01

    Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment. Some of the top gene networks generated from the differentially expressed genes were related to the wingless-type MMTV integration 1 (WNT) canonical (WNT/β-catenin) and non-canonical (β-catenin-independent) pathways. The Human WNT signaling pathway RT2 profiler™ PCR array was used to validate the effects of PAR4 on the expression pattern of genes involved in the WNT pathway. CACNAD2A3, GDF5 and IL6 were upregulated and NANOG was downregulated in the MCF7 breast cancer cells expressing increased levels of PAR4 after treatment with docetaxel, likely indicating inactivation of the WNT/β-catenin pathway. Upregulation of FGF7, LEF1 and TWIST1 indicated activation of the WNT/β-catenin pathway. Although preliminary, our findings could be of particular interest for understanding the action of PAR4 in chemosensitivity, particularly to increase the specificity and effectiveness of drug treatment and overcome resistance to chemotherapy. Further studies are needed to better understand the biological roles of PAR4 in the regulation of WNT pathways in breast cancer cells in response to docetaxel and other chemotherapeutic agents. PMID:28259909

  13. The Geoland2 BioPar burned area product

    NASA Astrophysics Data System (ADS)

    Tansey, K.; Bradley, A.; Smets, B.; van Best, C.; Lacaze, R.

    2012-04-01

    The European Commission Geoland2 project intends to constitute a major step forward to the implementation of the GMES Land Monitoring Core Service (LMCS). The Bio-geophysical Parameters (BioPar) Core Monitoring Service aims at setting-up pre-operational infrastructures for providing regional, European, and global bio-geophysical variables, both in near real time and off-line mode, for describing the vegetation state, the radiation budget at the surface, and the water cycle. The burned area product is part of the BioPar portfolio. The burned area product further builds on the experience of the Global Burned Area (GBA2000) and L3JRC projects. In the GBA2000 project, several algorithms were developed for different geographical regions of the world, and applied to a 1-year time series (the year 2000) of SPOT-VEGETATION data. In the L3JRC project, a single algorithm was improved and applied to a 7-year global dataset of SPOT-VEGETATION data. Since the conception of the Geoland2 project, work has been undertaken to improve the L3JRC algorithm, mainly based on user comments and feedback. Furthermore, the Geoland2 burned area product specification has been developed to meet the requirements of the Core Information Service, specifically LandCarbon and Natural Resource Monitoring in Africa (Narma). The Geoland2 burned area product has the following improvements over the L3JRC product: • It resolves issues with users extracting statistics and burned area estimates for time periods considered to be outside the main seasons for burning. Specifically, this deals with issues in northern latitude winters. • The number of pre-processing steps has been shortened, reducing processing time. • An improved land-water mask has been used. This resolves a problem around the coastlines of land masses which were frequently being detected as being burned. • A season metric calculation is performed over a 1x1 degree grid. For each grid cell, a date is logged against the start of the

  14. Tropospheric Emission Spectrometer and Airborne Emission Spectrometer

    NASA Technical Reports Server (NTRS)

    Glavich, T.; Beer, R.

    1996-01-01

    The Tropospheric Emission Spectrometer (TES) is an instrument being developed for the NASA Earth Observing System Chemistry Platform. TES will measure the distribution of ozone and its precursors in the lower atmosphere. The Airborne Emission Spectrometer (AES) is an aircraft precursor to TES. Applicable descriptions are given of instrument design, technology challenges, implementation and operations for both.

  15. Intrinsic and integrative properties of substantia nigra pars reticulata neurons

    PubMed Central

    Zhou, Fu-Ming; Lee, Christian R.

    2011-01-01

    The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators

  16. Unitary synaptic connections among substantia nigra pars reticulata neurons

    PubMed Central

    Wilson, Charles J.

    2016-01-01

    Neurons in substantia nigra pars reticulata (SNr) are synaptically coupled by local axon collaterals, providing a potential mechanism for local signal processing. Because SNr neurons fire spontaneously, these synapses are constantly active. To investigate their properties, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) from SNr neurons in brain slices, in which afferents from upstream nuclei are severed, and the cells fire rhythmically. The sIPSC trains contained a mixture of periodic and aperiodic events. Autocorrelation analysis of sIPSC trains showed that a majority of cells had one to four active unitary inputs. The properties of the unitary IPSCs (uIPSCs) were analyzed for cells with one unitary input, using a model of periodic presynaptic firing and stochastic synaptic transmission. The inferred presynaptic firing rates and coefficient of variation of interspike intervals (ISIs) corresponded well with direct measurements of spiking in SNr neurons. Methods were developed to estimate the success probability, amplitude distributions, and kinetics of the uIPSCs, while removing the contribution from aperiodic sIPSCs. The sIPSC amplitudes were not increased upon release from halorhodopsin silencing, suggesting that most synapses were not depressed at the spontaneous firing rate. Gramicidin perforated-patch recordings indicated that the average reversal potential of spontaneous inhibitory postsynaptic potentials was −64 mV. Because of the change in driving force across the ISI, the unitary inputs are predicted to have a larger postsynaptic impact when they arrive late in the ISI. Simulations of network activity suggest that this very sparse inhibitory coupling may act to desynchronize the activity of SNr neurons while having only a small effect on firing rate. PMID:26961101

  17. Developpement de techniques de diagnostic non intrusif par tomographie optique

    NASA Astrophysics Data System (ADS)

    Dubot, Fabien

    Que ce soit dans les domaines des procedes industriels ou de l'imagerie medicale, on a assiste ces deux dernieres decennies a un developpement croissant des techniques optiques de diagnostic. L'engouement pour ces methodes repose principalement sur le fait qu'elles sont totalement non invasives, qu'elle utilisent des sources de rayonnement non nocives pour l'homme et l'environnement et qu'elles sont relativement peu couteuses et faciles a mettre en oeuvre comparees aux autres techniques d'imagerie. Une de ces techniques est la Tomographie Optique Diffuse (TOD). Cette methode d'imagerie tridimensionnelle consiste a caracteriser les proprietes radiatives d'un Milieu Semi-Transparent (MST) a partir de mesures optiques dans le proche infrarouge obtenues a l'aide d'un ensemble de sources et detecteurs situes sur la frontiere du domaine sonde. Elle repose notamment sur un modele direct de propagation de la lumiere dans le MST, fournissant les predictions, et un algorithme de minimisation d'une fonction de cout integrant les predictions et les mesures, permettant la reconstruction des parametres d'interet. Dans ce travail, le modele direct est l'approximation diffuse de l'equation de transfert radiatif dans le regime frequentiel tandis que les parametres d'interet sont les distributions spatiales des coefficients d'absorption et de diffusion reduit. Cette these est consacree au developpement d'une methode inverse robuste pour la resolution du probleme de TOD dans le domaine frequentiel. Pour repondre a cet objectif, ce travail est structure en trois parties qui constituent les principaux axes de la these. Premierement, une comparaison des algorithmes de Gauss-Newton amorti et de Broyden- Fletcher-Goldfarb-Shanno (BFGS) est proposee dans le cas bidimensionnel. Deux methodes de regularisation sont combinees pour chacun des deux algorithmes, a savoir la reduction de la dimension de l'espace de controle basee sur le maillage et la regularisation par penalisation de Tikhonov

  18. Urokinase receptor (uPAR) ligand based recombinant toxins for human cancer therapy.

    PubMed

    de Virgilio, Maddalena; Silvestris, Franco

    2011-01-01

    The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoural cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.

  19. Detection of pars plana rupture by ultrasound biomicroscopy after cannula dislodgement during cataract wound hydration.

    PubMed

    Yonekawa, Yoshihiro; Thomas, Benjamin J; Lau-Sickon, Laurie K; Anderson, Bradley J; Ruby, Alan J

    2017-01-01

    Ultrasound biomicroscopy (UBM) is a valuable diagnostic modality for imaging anterior ocular structures. Its utility has been well studied in anterior segment, lenticular, and pars plicata pathologies. However, imaging of the pars plana has been seldom described. We present the case of a 66-year-old woman referred for vitreous hemorrhage after expulsive cannula dislodgement into the posterior segment during wound hydration at the end of cataract surgery. B-scan ultrasonography initially detected a very anterior abnormality, but the resolution was insufficient for accurate diagnosis. Subsequent UBM clearly showed rupture of the pars plana and a mild cyclodialysis cleft. To our knowledge, this is the first report of a pars plana rupture detected by ultrasound, which expands the diagnostic capacities and indications for UBM.

  20. ParTIES: a toolbox for Paramecium interspersed DNA elimination studies.

    PubMed

    Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda

    2016-02-15

    Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner.

    PubMed

    de Oliveira, Priscila; Juliano, Maria Aparecida; Tanaka, Aparecida Sadae; Carmona, Adriana Karaoglanovic; Dos Santos, Saara Maria Batista; de Barros, Bianca Carla Silva Campitelli; Maza, Paloma Korehisa; Puccia, Rosana; Suzuki, Erika

    2017-04-01

    Paracoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549. Cytokine secretion was reduced by antagonistic peptides for PAR-1 and PAR-2, but not for PAR-4. P. brasiliensis proteases were isolated from fungal culture supernatants in a p-aminomethylbenzamidine-Sepharose column. The obtained fractions were tested for enzymatic activity against fluorescence resonance energy transfer (FRET) peptides derived from sequences that spanned the activation sites of human PARs. The eluted fraction, termed PbP, contained protease activities that were able to hydrolyze the FRET peptides. PbP also induced IL-6 and IL-8 secretion in A549 epithelial cells, which was reduced upon heat inactivation of PbP, incubation with antagonistic peptides for PAR-1 and PAR-2, and the protease inhibitors aprotinin, leupeptin, and E-64. Together, these results show for the first time that P. brasiliensis yeasts secrete proteases that activate PARs in lung epithelial cells, leading to cytokine secretion.

  2. PAR2 expression in peripheral blood monocytes of patients with rheumatoid arthritis

    PubMed Central

    Crilly, A; Burns, E; Nickdel, M B; Lockhart, J C; Perry, M E; Ferrell, P W; Baxter, D; Dale, J; Dunning, L; Wilson, H; Nijjar, J S; Gracie, J A; Ferrell, W R; McInnes, I B

    2012-01-01

    Objectives Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR2 expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Methods Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR2 on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Results Patients with RA had elevated but variable surface expression of PAR2 on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86–4.10%) vs 0.06% (0.03–0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR2 expression in patients with RA compared with controls (3.05% (0.36–11.82%) vs 0.08% (0.02–0.28%), p<0.0001). For both subsets, PAR2 expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR2 expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR2 expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR2 expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR2 agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). Conclusions These findings are consistent with a pathogenic role for PAR2 in RA. PMID:22294633

  3. Systemic sclerosis-like histopathological features in the myocardium of uPAR-deficient mice.

    PubMed

    Manetti, Mirko; Rosa, Irene; Fazi, Marilena; Guiducci, Serena; Carmeliet, Peter; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

    2016-02-01

    Cardiomyopathy is among the leading causes of death from systemic sclerosis (SSc). Urokinase-type plasminogen activator receptor (uPAR)-deficient mice have been recently reported to display important histopathological hallmarks of SSc, including dermal fibrosis, reduced dermal capillary density, and pulmonary fibrosis. Here, we investigated whether uPAR-deficient mice could display the histopathological features of SSc-related cardiomyopathy. Ventricular myocardial specimens from uPAR-deficient and wild-type mice at 12 and 24 weeks of age were analysed by both light microscopy and transmission electron microscopy. Picrosirius red staining and hydroxyproline content of myocardial specimens were quantified. Myofibroblast and microvessel counts were determined by immunofluorescence for α-smooth muscle actin and CD31, respectively. Endothelial cell apoptosis was assessed by a combined TUNEL/CD31 immunofluorescence assay. Expression of uPAR in human SSc and control ventricular myocardial autopsy specimens was determined by immunohistochemistry. The myocardium of 24-week-old uPAR-deficient mice displayed focal ischaemic lesions with cardiomyocyte hypertrophy, myofibril rarefaction and contraction band necrosis. At 24 weeks of age, interstitial and perivascular collagen deposition and myofibroblast counts were significantly greater in myocardial tissue of uPAR-deficient mice than in wild-type mice. In uPAR-deficient mice, myocardial fibrosis was paralleled by microvascular endothelial cell apoptosis and reduced capillary density. uPAR expression was significantly downregulated in the myocardium of patients with SSc. Typical histopathological features of SSc-related cardiomyopathy are mimicked by uPAR-deficient mice. The downregulation of uPAR in the myocardium of patients with SSc may suggest similar underlying pathogenetic mechanisms. uPAR-deficient mice could be used as a preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement

  4. ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data.

    PubMed

    Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S; Windus, Theresa L; Dick-Perez, Marilu

    2017-03-27

    A newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides, important for metal extraction chemistry, are parametrized using ParFit. ParFit is in an open source program available for free on GitHub ( https://github.com/fzahari/ParFit ).

  5. Ambroise Paré IV: The early history of artificial limbs (from robotic to prostheses).

    PubMed

    Hernigou, Philippe

    2013-06-01

    One of the earliest written references to prosthetics is found in a book published in France in 1579. That year, French surgeon Ambroise Paré (1510-1590) published his complete works, part of which described some of the artificial limbs he fitted on his amputees. As a military surgeon, Paré had removed many a soldier's shattered arm or leg, and he eventually began designing and building artificial limbs to help the men who had been maimed.

  6. Molecular mechanism of bundle formation by the bacterial actin ParM

    SciTech Connect

    Popp, David; Narita, Akihiro; Iwasa, Mitsusada; Robinson, Robert C.

    2010-01-22

    The actin homolog ParM plays a microtubule-like role in segregating DNA prior to bacterial cell division. Fluorescence and cryo-electron microscopy have shown that ParM forms filament bundles between separating DNA plasmids in vivo. Given the lack of ParM bundling proteins it remains unknown how ParM bundles form at the molecular level. Here we show using time-lapse TIRF microscopy, under in vitro molecular crowding conditions, that ParM-bundle formation consists of two distinct phases. At the onset of polymerization bundle thickness and shape are determined in the form of nuclei of short helically disordered filaments arranged in a liquid-like lattice. These nuclei then undergo an elongation phase whereby they rapidly increase in length. At steady state, ParM bundles fuse into one single large aggregate. This behavior had been predicted by theory but has not been observed for any other cytomotive biopolymer, including F-actin. We employed electron micrographs of ParM rafts, which are 2-D analogs of 3-D bundles, to identify the main molecular interfilament contacts within these suprastructures. The interface between filaments is similar for both parallel and anti-parallel orientations and the distribution of filament polarity is random within a bundle. We suggest that the interfilament interactions are not due to the interactions of specific residues but rather to long-range, counter ion mediated, electrostatic attractive forces. A randomly oriented bundle ensures that the assembly is rigid and that DNA may be captured with equal efficiency at both ends of the bundle via the ParR binding protein.

  7. The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells

    PubMed Central

    2004-01-01

    TMPRSS2 is a type II transmembrane-bound serine protease that has gained interest owing to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. PAR (protease-activated receptor)-2 belongs to a family of G-protein-coupled receptors (PAR-1–4) that are activated by specific serine proteases, which are expressed in many normal and malignant cell types. Previous in vitro studies on prostate cancer cells suggest a role for PAR-2 in prostate cancer metastasis. A polyclonal anti-human TMPRSS2 antibody was generated against the TMPRSS2 serine protease domain. The antibody showed specific reactivity with recombinant expressed TMPRSS2, and so was used to extract and purify the cleaved active TMPRSS2 protease from prostate cancer cells. Reverse transcriptase PCR and Western blot analysis were used to show the expression of both TMPRSS2 and PAR-2 in the androgen-dependent LNCaP prostate cancer cell line. Treatment of LNCaP cells with the cellular immunopurified TMPRSS2 protease induced a transient increase in intracellular calcium, which is indicative of G-protein-coupled-receptor activation. This calcium mobilization was inhibited by cellular pre-treatment with a specific PAR-2 antagonist, but not with a PAR-1 antagonist; inhibition of the protease activity also failed to mobilize calcium, suggesting that TMPRSS2 is capable of cleaving and thereby activating the PAR-2 receptor. The calcium mobilization was also inhibited by cellular pre-treatment with suramin or 2-APB (2-aminoethoxydiphenyl borate), indicating that a G-protein pathway is involved and that subsequent calcium release is mainly from intracellular stores. The present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2. PMID:15537383

  8. The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells.

    PubMed

    Wilson, Susan; Greer, Brett; Hooper, John; Zijlstra, Andries; Walker, Brian; Quigley, James; Hawthorne, Susan

    2005-06-15

    TMPRSS2 is a type II transmembrane-bound serine protease that has gained interest owing to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. PAR (protease-activated receptor)-2 belongs to a family of G-protein-coupled receptors (PAR-1-4) that are activated by specific serine proteases, which are expressed in many normal and malignant cell types. Previous in vitro studies on prostate cancer cells suggest a role for PAR-2 in prostate cancer metastasis. A polyclonal anti-human TMPRSS2 antibody was generated against the TMPRSS2 serine protease domain. The antibody showed specific reactivity with recombinant expressed TMPRSS2, and so was used to extract and purify the cleaved active TMPRSS2 protease from prostate cancer cells. Reverse transcriptase PCR and Western blot analysis were used to show the expression of both TMPRSS2 and PAR-2 in the androgen-dependent LNCaP prostate cancer cell line. Treatment of LNCaP cells with the cellular immunopurified TMPRSS2 protease induced a transient increase in intracellular calcium, which is indicative of G-protein-coupled-receptor activation. This calcium mobilization was inhibited by cellular pre-treatment with a specific PAR-2 antagonist, but not with a PAR-1 antagonist; inhibition of the protease activity also failed to mobilize calcium, suggesting that TMPRSS2 is capable of cleaving and thereby activating the PAR-2 receptor. The calcium mobilization was also inhibited by cellular pre-treatment with suramin or 2-APB (2-aminoethoxydiphenyl borate), indicating that a G-protein pathway is involved and that subsequent calcium release is mainly from intracellular stores. The present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2.

  9. Emissions & Measurements - Black Carbon

    EPA Science Inventory

    Emissions and Measurement (EM) research activities performed within the National Risk Management Research Lab NRMRL) of EPA's Office of Research and Development (ORD) support measurement and laboratory analysis approaches to accurately characterize source emissions, and near sour...

  10. Emissions & Measurements - Black Carbon

    EPA Science Inventory

    Emissions and Measurement (EM) research activities performed within the National Risk Management Research Lab NRMRL) of EPA's Office of Research and Development (ORD) support measurement and laboratory analysis approaches to accurately characterize source emissions, and near sour...

  11. Biodiesel Emissions Analysis Program

    EPA Pesticide Factsheets

    Using existing data, the EPA's biodiesel emissions analysis program sought to quantify the air pollution emission effects of biodiesel for diesel engines that have not been specifically modified to operate on biodiesel.

  12. NARSTO EMISSION INVENTORY ASSESSMENT

    EPA Science Inventory

    The NARSTO Ozone and Particulate Matter Assessments emphasized that emission inventories are critical to the success of air quality management programs and that emissions inventories in Canada, Mexico, and the United States need improvement to meet expectations for quality, timel...

  13. What Is Emissions Trading?

    EPA Pesticide Factsheets

    Learn the basics about how emissions trading uses a market-based policy tool used to control large amounts of pollution emissions from a group of sources in order to protect human health and the environment.

  14. Control of Emissions

    NASA Technical Reports Server (NTRS)

    Parrish, Clyde F. (Inventor); Chung, Landy (Inventor)

    2013-01-01

    Methods and apparatus utilizing chlorine dioxide and hydrogen peroxide are useful to reduce NOx emissions, as well as SOx and mercury (or other heavy metal) emissions, from combustion flue gas streams.

  15. NARSTO EMISSION INVENTORY ASSESSMENT

    EPA Science Inventory

    The NARSTO Ozone and Particulate Matter Assessments emphasized that emission inventories are critical to the success of air quality management programs and that emissions inventories in Canada, Mexico, and the United States need improvement to meet expectations for quality, timel...

  16. Emissions Trading Resources

    EPA Pesticide Factsheets

    Learn about emissions trading programs, also known as cap and trade programs, which are market-based policy tools for protecting human health and the environment by controlling emissions from a group of sources.

  17. Emission scenarios: Explaining differences

    NASA Astrophysics Data System (ADS)

    Iyer, Gokul; Edmonds, James

    2017-01-01

    Carbon dioxide emission scenarios rely on a number of assumptions about how societies will develop in the future, creating uncertainty in projections. Now, research reveals the sensitivity of emission estimates to some of these assumptions.

  18. Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race.

    PubMed

    Edelstein, Leonard C; Simon, Lukas M; Lindsay, Cory R; Kong, Xianguo; Teruel-Montoya, Raúl; Tourdot, Benjamin E; Chen, Edward S; Ma, Lin; Coughlin, Shaun; Nieman, Marvin; Holinstat, Michael; Shaw, Chad A; Bray, Paul F

    2014-11-27

    Human platelets express 2 thrombin receptors: protease-activated receptor (PAR)-1 and PAR4. Recently, we reported 3.7-fold increased PAR4-mediated aggregation kinetics in platelets from black subjects compared with white subjects. We now show that platelets from blacks (n = 70) express 14% more PAR4 protein than those from whites (n = 84), but this difference is not associated with platelet PAR4 function. Quantitative trait locus analysis identified 3 common single nucleotide polymorphisms in the PAR4 gene (F2RL3) associated with PAR4-induced platelet aggregation. Among these single nucleotide polymorphisms, rs773902 determines whether residue 120 in transmembrane domain 2 is an alanine (Ala) or threonine (Thr). Compared with the Ala120 variant, Thr120 was more common in black subjects than in white subjects (63% vs 19%), was associated with higher PAR4-induced human platelet aggregation and Ca2+ flux, and generated greater inositol 1,4,5-triphosphate in transfected cells. A second, less frequent F2RL3 variant, Phe296Val, was only observed in blacks and abolished the enhanced PAR4-induced platelet aggregation and 1,4,5-triphosphate generation associated with PAR4-Thr120. PAR4 genotype did not affect vorapaxar inhibition of platelet PAR1 function, but a strong pharmacogenetic effect was observed with the PAR4-specific antagonist YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole]. These findings may have an important pharmacogenetic effect on the development of new PAR antagonists. © 2014 by The American Society of Hematology.

  19. Clinical relevance and cellular source of elevated soluble urokinase plasminogen activator receptor (suPAR) in acute liver failure.

    PubMed

    Koch, Alexander; Zimmermann, Henning W; Gassler, Nikolaus; Jochum, Christoph; Weiskirchen, Ralf; Bruensing, Jan; Buendgens, Lukas; Dückers, Hanna; Bruns, Tony; Gerken, Guido; Neumann, Ulf P; Adams, David H; Trautwein, Christian; Canbay, Ali; Tacke, Frank

    2014-10-01

    Acute liver failure (ALF) is a life-threatening condition with a high mortality rate. The expression of urokinase plasminogen activator receptor (uPAR, CD87) and release of its shedded receptor into serum as soluble uPAR (suPAR) have been closely related to immune activation and prognosis in systemic inflammation and cirrhosis. We now aimed at investigating the clinical relevance and cellular source of uPAR and circulating suPAR in ALF. Serum suPAR concentrations were measured in 48 ALF patients and 62 healthy controls from a German liver transplantation centre. Hepatic immune cell subsets and uPAR expression were studied by FACS, qPCR and immunohistochemistry. Circulating suPAR levels were significantly increased in ALF patients, independent from the underlying aetiology, in comparison to controls. Serum suPAR concentrations were closely correlated with parameters reflecting liver cell injury, decreased liver function and the model of end-stage liver disease (MELD) score in ALF patients. By immunohistochemistry from explanted livers, ALF was associated with distinct immune cell accumulation and strong up-regulation of intrahepatic uPAR mRNA expression. CD87 (uPAR) expression was specifically detected on intrahepatic 'non-classical' monocytes (CD14(+) CD16(+) ), NKT and CD56(dim) NK cells isolated from human liver, but not on parenchymal or other non-parenchymal hepatic cell types. Membrane-bound uPAR was rapidly cleaved from monocytes upon inflammatory stimulation by lipopolysaccharide (LPS) and partially by co-cultured lymphocytes. Similar to its prognostic properties in patients with sepsis or cirrhosis, intrahepatic uPAR activation and serum suPAR concentrations might serve as an interesting biomarker in ALF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Brief communication: Population variation in human maxillary premolar accessory ridges (MxPAR).

    PubMed

    Burnett, Scott E; Hawkey, Diane E; Turner, Christy G

    2010-02-01

    The purpose of this brief communication is to report the results of an analysis of maxillary premolar accessory ridges (MxPAR), a common but understudied accessory ridge that may occur both mesial and distal to the central ridge of the buccal cusp of upper premolars. We developed a new five-grade scoring plaque to better categorize MxPAR variation. Subsequently, we conducted a population analysis of MxPAR frequency in 749 dental casts of South African Indian, American Chinese, Alaskan Eskimo, Tohono O'odham (Papago), Akimel O'odham (Pima), Solomon Islander, South African Bantu, and both American and South African Whites. Northeast Asian and Asian-derived populations exhibited the highest MxPAR frequencies while Indo-European samples (South African Indians, American and South African Whites) exhibited relatively low frequencies. The Solomon Islanders and South African Bantu samples exhibited intermediate frequencies. Our analysis indicates that statistically significant differences in MxPAR frequency exist between major geographic populations. As a result, the MxPAR plaque has now been added to the Arizona State University Dental Anthropology System, an important contribution as maxillary premolar traits are underrepresented in analyses of dental morphology. 2009 Wiley-Liss, Inc.

  1. The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

    PubMed Central

    Gnazzo, Megan M.; Uhlemann, Eva-Maria E.; Villarreal, Alex R.; Shirayama, Masaki; Dominguez, Eddie G.; Skop, Ahna R.

    2016-01-01

    The spindle midzone harbors both microtubules and proteins necessary for furrow formation and the completion of cytokinesis. However, the mechanisms that mediate the temporal and spatial recruitment of cell division factors to the spindle midzone and midbody remain unclear. Here we describe a mechanism governed by the conserved RNA-binding protein ATX-2/Ataxin-2, which targets and maintains ZEN-4 at the spindle midzone. ATX-2 does this by regulating the amount of PAR-5 at mitotic structures, particularly the spindle, centrosomes, and midbody. Preventing ATX-2 function leads to elevated levels of PAR-5, enhanced chromatin and centrosome localization of PAR-5–GFP, and ultimately a reduction of ZEN-4–GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescued the localization of ZEN-4 at the spindle midzone, indicating that ATX-2 mediates the localization of ZEN-4 upstream of PAR-5. We provide the first direct evidence that ATX-2 is necessary for cytokinesis and suggest a model in which ATX-2 facilitates the targeting of ZEN-4 to the spindle midzone by mediating the posttranscriptional regulation of PAR-5. PMID:27559134

  2. Examining relational empowerment for elementary school students in a yPAR program.

    PubMed

    Langhout, Regina Day; Collins, Charles; Ellison, Erin Rose

    2014-06-01

    This paper joins relational empowerment, youth empowerment, and Bridging Multiple Worlds frameworks to examine forms of relational empowerment for children in two intermediary institutions-school and a youth participatory action research after-school program (yPAR ASP). Participants were twelve children, most of whom were Latina/o and from im/migrant families, enrolled in a yPAR ASP for 2 years. A mixed-method approach was utilized; we analyzed children's interviews, self-defined goals, and their social networks to examine their experiences of relational empowerment. We conclude that children experienced each of the five relational empowerment factors-collaborative competence, bridging social divisions, facilitating others' empowerment, mobilizing networks, and passing on a legacy-in the yPAR ASP setting, and some factors in school. These experiences, however, were more pronounced in the yPAR ASP setting. Additionally, social network analyses revealed that a small but meaningful percentage of actors bridged worlds, especially home and family, but by year 2, also school and the yPAR ASP. Finally, most helpers for school-based goals came from school, but a sizable number came from family, friends, and home worlds, and by year 2, also came from the yPAR ASP. Implications range from theoretical to methodological development, including the use of social network analysis as a tool to descriptively examine relational power in context.

  3. Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma.

    PubMed

    Hanif, Razia; Mansoor, Samina

    2014-03-01

    To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Comparative cross-sectional study. Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver.

  4. Spatial Estimates of GPP Using LiDAR- and Quickbird-Derived fPAR

    NASA Astrophysics Data System (ADS)

    Cook, B. D.; Bolstad, P. V.; Naesset, E.; Heinsch, F. A.; Anderson, R. S.; Garrigues, S.; Morisette, J. T.; Nickeson, J. E.; Hilton, T. W.; Davis, K. J.; Roman, M. O.

    2007-12-01

    Regional- to global-scale gross primary production (GPP) is commonly estimated with light-use efficiency models, which are largely dependent on remotely sensed estimates of the fraction of photosynthetically active radiation absorbed by vegetation (fPAR). Methodologies to quantify spatial variability of fPAR and improve GPP estimates have not been established for mixed forests and heterogeneous landscapes in the Great Lakes Region, and are needed to estimate photosynthetic sinks for the Mid-Continent Regional Intensive Campaign. In this study, hemispheric photos were collected during the 2006 growing season to estimate fPAR, plant area index (PAI), leaf inclination angle, and clumping factors in >130 lowland and upland stands within the footprint of a 400 m eddy covariance flux tower near Park Falls, Wisconsin, USA. Airborne LiDAR and Quickbird imagery were acquired during leaf-on and leaf-off periods to make predictions of canopy structure, and resulting PAI/fPAR estimates were compared with litterfall measurements and products derived from the Moderate Resolution Spectroradiometer (MODIS). GPP was modeled with the MODIS MOD17A2 algorithm, using fine-resolution land cover and fPAR inputs that were spatially aggregated into units ranging from 30 m to 1 km square. Uncertainties and errors associated with fPAR methods and spatial resolutions are discussed based on agreement with flux tower observations.

  5. PAR3-aPKC regulates Tiam1 by modulating suppressive internal interactions.

    PubMed

    Matsuzawa, Kenji; Akita, Hiroki; Watanabe, Takashi; Kakeno, Mai; Matsui, Toshinori; Wang, Shujie; Kaibuchi, Kozo

    2016-05-01

    Tiam1 is one of the most extensively analyzed activators of the small GTPase Rac. However, fundamental aspects of its regulation are poorly understood. Here we demonstrate that Tiam1 is functionally suppressed by internal interactions and that the PAR complex participates in its full activation. The N-terminal region of Tiam1 binds to the protein-binding and catalytic domains to inhibit its localization and activation. Atypical PKCs phosphorylate Tiam1 to relieve its intramolecular interactions, and the subsequent stabilization of its interaction with PAR3 allows it to exert localized activity. By analyzing Tiam1 regulation by PAR3-aPKC within the context of PDGF signaling, we also show that PAR3 directly binds PDGF receptor β. Thus we provide the first evidence for the negative regulation of Tiam1 by internal interactions, elucidate the nature of Tiam1 regulation by the PAR complex, and reveal a novel role for the PAR complex in PDGF signaling. © 2016 Matsuzawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. PAR3-aPKC regulates Tiam1 by modulating suppressive internal interactions

    PubMed Central

    Matsuzawa, Kenji; Akita, Hiroki; Watanabe, Takashi; Kakeno, Mai; Matsui, Toshinori; Wang, Shujie; Kaibuchi, Kozo

    2016-01-01

    Tiam1 is one of the most extensively analyzed activators of the small GTPase Rac. However, fundamental aspects of its regulation are poorly understood. Here we demonstrate that Tiam1 is functionally suppressed by internal interactions and that the PAR complex participates in its full activation. The N-terminal region of Tiam1 binds to the protein-binding and catalytic domains to inhibit its localization and activation. Atypical PKCs phosphorylate Tiam1 to relieve its intramolecular interactions, and the subsequent stabilization of its interaction with PAR3 allows it to exert localized activity. By analyzing Tiam1 regulation by PAR3-aPKC within the context of PDGF signaling, we also show that PAR3 directly binds PDGF receptor β. Thus we provide the first evidence for the negative regulation of Tiam1 by internal interactions, elucidate the nature of Tiam1 regulation by the PAR complex, and reveal a novel role for the PAR complex in PDGF signaling. PMID:26941335

  7. Role of protease-activated receptors 2 (PAR2) in ocular infections and inflammation

    PubMed Central

    Tripathi, Trivendra; Alizadeh, Hassan

    2015-01-01

    Protease-activated receptors (PARs) belong to a unique family of G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by a variety of proteinases, essentially of the serine (Ser) proteinase family. After cleavage, the new N-terminal sequence functions as a tethered ligand, which binds intramolecularly to activate the receptor and initiate signaling. Cell signals induced through the activation of PARs appear to play a significant role in innate and adoptive immune responses of the cornea, which is constantly exposed to proteinases under physiological or pathophysiological conditions. Activation of PARs interferes with all aspects of the corneal physiology such as barrier function, transports, innate and adoptive immune responses, and functions of corneal nerves. It is not known whether the proteinase released from the microorganism can activate PARs and triggers the inflammatory responses. The role of PAR2 expressed by the corneal epithelial cells and activation by serine protease released from microorganism is discussed here. Recent evidences suggest that activation of PAR2, by the serine proteinases, play an important role in innate and inflammatory responses of the corneal infection. PMID:26078987

  8. Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4

    PubMed Central

    Partanen, Johanna I.; Tervonen, Topi A.; Klefström, Juha

    2013-01-01

    The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo. Today, investigations in worms, flies and mammals have established PAR proteins as conserved and fundamental regulators of animal cell polarization in a broad range of biological phenomena requiring cellular asymmetries. The human homologue of invertebrate PAR-4, a serine–threonine kinase LKB1/STK11, has caught attention as a gene behind Peutz–Jeghers polyposis syndrome and as a bona fide tumour suppressor gene commonly mutated in sporadic cancer. LKB1 functions as a master regulator of AMP-activated protein kinase (AMPK) and 12 other kinases referred to as the AMPK-related kinases, including four human homologues of PAR-1. The role of LKB1 as part of the energy sensing LKB1-AMPK module has been intensively studied, whereas the polarity function of LKB1, in the context of homoeostasis or cancer, has gained less attention. Here, we focus on the PAR-4 identity of LKB1, discussing the weight of evidence indicating a role for LKB1 in regulation of cell polarity and epithelial integrity across species and highlight recent investigations providing new insight into the old question: does the PAR-4 identity of LKB1 matter in cancer? PMID:24062587

  9. Methanol and isoprene emissions from the fast growing tropical pioneer species Vismia guianensis (Aubl.) Pers. (Hypericaceae) in the central Amazon forest

    NASA Astrophysics Data System (ADS)

    Jardine, Kolby J.; Jardine, Angela B.; Souza, Vinicius F.; Carneiro, Vilany; Ceron, Joao V.; Gimenez, Bruno O.; Soares, Cilene P.; Durgante, Flavia M.; Higuchi, Niro; Manzi, Antonio O.; Gonçalves, José F. C.; Garcia, Sabrina; Martin, Scot T.; Zorzanelli, Raquel F.; Piva, Luani R.; Chambers, Jeff Q.

    2016-05-01

    Isoprene (Is) emissions by plants represent a loss of carbon and energy resources leading to the initial hypothesis that fast growing pioneer species in secondary tropical forests allocate carbon primarily to growth at the expense of isoprenoid defenses. In this study, we quantified leaf isoprene and methanol emissions from the abundant pantropical pioneer tree species Vismia guianensis and ambient isoprene concentrations above a diverse secondary forest in the central Amazon. As photosynthetically active radiation (PAR) was varied (0 to 3000 µmol m-2 s-1) under standard leaf temperature (30 °C), isoprene emissions from V. guianensis increased without saturation up to 80 nmol m-2 s-1. A nonlinear increase in isoprene emissions with respect to net photosynthesis (Pn) resulted in the fraction of Pn dedicated to isoprene emissions increasing with light intensity (up to 2 % of Pn). Emission responses to temperature under standard light conditions (PAR of 1000 µmol m-2 s-1) resulted in the classic uncoupling of isoprene emissions (Topt, iso > 40 °C) from net photosynthesis (Topt, Pn = 30.0-32.5 °C) with up to 7 % of Pn emitted as isoprene at 40 °C. Under standard environmental conditions of PAR and leaf temperature, young V. guianensis leaves showed high methanol emissions, low Pn, and low isoprene emissions. In contrast, mature leaves showed high Pn, high isoprene emissions, and low methanol emissions, highlighting the differential control of leaf phenology over methanol and isoprene emissions. High daytime ambient isoprene concentrations (11 ppbv) were observed above a secondary Amazon rainforest, suggesting that isoprene emissions are common among neotropical pioneer species. The results are not consistent with the initial hypothesis and support a functional role of methanol during leaf expansion and the establishment of photosynthetic machinery and a protective role of isoprene for photosynthesis during high temperature extremes regularly experienced in

  10. Acoustic emission frequency discrimination

    NASA Technical Reports Server (NTRS)

    Sugg, Frank E. (Inventor); Graham, Lloyd J. (Inventor)

    1988-01-01

    In acoustic emission nondestructive testing, broadband frequency noise is distinguished from narrow banded acoustic emission signals, since the latter are valid events indicative of structural flaws in the material being examined. This is accomplished by separating out those signals which contain frequency components both within and beyond (either above or below) the range of valid acoustic emission events. Application to acoustic emission monitoring during nondestructive bond verification and proof loading of undensified tiles on the Space Shuttle Orbiter is considered.

  11. Ocular trauma treated with pars plana vitrectomy: early outcome report

    PubMed Central

    Mansouri, Mohammad Reza; Tabatabaei, Seyed Ali; Soleimani, Mohammad; Kiarudi, Mohammad Yaser; Molaei, Saber; Rouzbahani, Mehdi; Mireshghi, Meysam; Zaeferani, Mohsen; Ghasempour, Mehrbod

    2016-01-01

    AIM To evaluate demographic variables and visual outcomes, among patients with ocular injuries involving the posterior segment, managed with pars plana vitrectomy. METHODS The records of patients were studied retrospectively from March to September 2010, to determine the age, gender, place of occurrence of trauma, visual acuity, anatomical site, nature of injury, wound length, the presence of an afferent pupillary defect, and the timing of vitrectomy. The Ocular Trauma Score was measured. The minimum follow-up from presentation was 6mo. RESULTS Ninety patients (77 males, 13 females), with a mean age of 32.7±15.8y were included over the 6-month period. The majority of cases occurred in the workplace (47 patients), followed by home (14 patients). The mean visual acuity (logMAR) of patients significantly improved from 2.36±0.72 preoperatively to 1.50±1.14 postoperatively. Twenty-three patients had preoperative vision better than 2.0 logMAR, the postoperative visual acuity was significantly better among these patients than patients with worse than 2.0 logMAR (P<0.001). Visual improvement between groups with early vitrectomy (<7d) and delayed vitrectomy (>7d) was not significantly different (P=0.66). Postoperative visual acuity was not significantly different between patients with injury in Zone I and II (P=0.64), but patients with injury in Zone III had significantly poorer visual acuity (P=0.02). Patients with relative afferent pupillary defect had significantly poorer postoperative visual acuity (P=0.02). Preoperative visual acuity, the difference of preoperative and postoperative visual acuity, and postoperative visual acuity were significantly different between groups with different ocular trauma scores (P<0.001). CONCLUSION Trauma is more likely to occur in men under 40y of age and in the workplace. The favorable final visual outcome is associated with the absence of afferent pupillary defect, ocular trauma score and presenting visual acuity as well as the zone

  12. PERSISTENT CORNEAL EPITHELIAL DEFECT AFTER PARS PLANA VITRECTOMY.

    PubMed

    Chen, Hsi-Fu; Yeung, Ling; Yang, Ko-Jen; Sun, Chi-Chin

    2016-01-01

    To investigate the incidence, risk factors, and clinical course of persistent corneal epithelial defects (PCED) after pars plana vitrectomy (PPV). The charts of 426 consecutive patients (511 eyes) who received PPV from January 2008 to December 2011 were reviewed. Corneal complications were defined as the presence of corneal epithelial defects, corneal edema, or superficial punctate keratopathy at least 1 week after vitrectomy. The PCED was defined as corneal epithelial defects lasting longer than 2 weeks after vitrectomy despite conventional treatment. The demographic, preoperative, intraoperative, and postoperative data were compared between PCED and non-PCED corneal complication groups to evaluate the risk factors and clinical outcomes. Postoperative corneal complications developed in 103 of 460 (22.4%) eyes. Diabetes was associated with postoperative corneal epithelial defects (P = 0.021) and superficial punctate keratopathy (P = 0.022) but not corneal edema (P = 0.925). Among 103 eyes with corneal complications, 21 eyes developed PCED. The eyes with PCED had poor final visual acuity, with 23.8% (5/21) of the eyes in the PCED group having visual acuity of 20/200 or better compared with 51.2% (42/82) of the eyes in the non-PCED group (P = 0.024). Logistic regression analysis demonstrated that diabetes mellitus (P = 0.025), use of perfluoropropane (P = 0.001), and assistance of a first-year resident (P = 0.029) were statistically significant risk factors for PCED after PPV. There was also a high incidence of geographic herpes simplex virus epithelial keratitis among recalcitrant PCEDs lasting longer than 4 weeks (36%, 4/11 eyes). The overall incidence of PCED after PPV was 4.8%. Diabetes mellitus, intravitreal tamponade with perfluoropropane, and assistance of a first-year resident were risk factors for PCED after PPV. Persistent corneal epithelial defects after PPV were correlated with poor postoperative visual outcomes. Early and aggressive management is

  13. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    NASA Astrophysics Data System (ADS)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  14. Role of the parCBA Operon of the Broad-Host-Range Plasmid RK2 in Stable Plasmid Maintenance

    PubMed Central

    Easter, Carla L.; Schwab, Helmut; Helinski, Donald R.

    1998-01-01

    The par region of the stably maintained broad-host-range plasmid RK2 is organized as two divergent operons, parCBA and parDE, and a cis-acting site. parDE encodes a postsegregational killing system, and parCBA encodes a resolvase (ParA), a nuclease (ParB), and a protein of unknown function (ParC). The present study was undertaken to further delineate the role of the parCBA region in the stable maintenance of RK2 by first introducing precise deletions in the three genes and then assessing the abilities of the different constructs to stabilize RK2 in three strains of Escherichia coli and two strains of Pseudomonas aeruginosa. The intact parCBA operon was effective in stabilizing a conjugation-defective RK2 derivative in E. coli MC1061K and RR1 but was relatively ineffective in E. coli MV10Δlac. In the two strains in which the parCBA operon was effective, deletions in parB, parC, or both parB and parC caused an approximately twofold reduction in the stabilizing ability of the operon, while a deletion in the parA gene resulted in a much greater loss of parCBA activity. For P. aeruginosa PAO1161Rifr, the parCBA operon provided little if any plasmid stability, but for P. aeruginosa PAC452Rifr, the RK2 plasmid was stabilized to a substantial extent by parCBA. With this latter strain, parA and res alone were sufficient for stabilization. The cer resolvase system of plasmid ColE1 and the loxP/Cre system of plasmid P1 were tested in comparison with the parCBA operon. We found that, not unlike what was previously observed with MC1061K, cer failed to stabilize the RK2 plasmid with par deletions in strain MV10Δlac, but this multimer resolution system was effective in stabilizing the plasmid in strain RR1. The loxP/Cre system, on the other hand, was very effective in stabilizing the plasmid in all three E. coli strains. These observations indicate that the parA gene, along with its res site, exhibits a significant level of plasmid stabilization in the absence of the parC and

  15. Heat stress-induced disruption of endothelial barrier function is via PAR1 signaling and suppressed by Xuebijing injection.

    PubMed

    Xu, Qiulin; Liu, Jingxian; Wang, Zhenglian; Guo, Xiaohua; Zhou, Gengbiao; Liu, Yanan; Huang, Qiaobing; Su, Lei

    2015-01-01

    Increased vascular permeability leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is central to the pathogenesis of heatstroke. Protease-activated receptor 1 (PAR1), the receptor for thrombin, plays a key role in disruption of endothelial barrier function in response to extracellular stimuli. However, the role of PAR1 in heat stress-induced endothelial hyper-permeability is unknown. In this study, we measured PAR1 protein expression in heat-stressed human umbilical venous endothelial cells (HUVECs), investigated the influences of PAR1 on endothelial permeability, F-actin rearrangement, and moesin phosphorylation by inhibiting PAR1 with its siRNA, neutralizing antibody (anti-PAR1), specific inhibitor(RWJ56110), and Xuebijing injection (XBJ), a traditional Chinese medicine used for sepsis treatment, and evaluated the role of PAR1 in heatstroke-related ALI/ARDS in mice by suppressing PAR1 with RWJ56110, anti-PAR1and XBJ. We found that heat stress induced PAR1 protein expression 2h after heat stress in endothelial cells, caused the release of endothelial matrix metalloprotease 1, an activator of PAR1, after 60 or 120 min of heat stimulation, as well as promoted endothelial hyper-permeability and F-actin rearrangement, which were inhibited by suppressing PAR1 with RWJ56110, anti-PAR1 and siRNA. PAR1 mediated moesin phosphorylation, which caused F-actin rearrangement and disruption of endothelial barrier function. To corroborate findings from in vitro experiments, we found that RWJ56110 and the anti-PAR1 significantly decreased lung edema, pulmonary microvascular permeability, protein exudation, and leukocytes infiltrations in heatstroke mice. Additionally, XBJ was found to suppress PAR1-moesin signal pathway and confer protective effects on maintaining endothelial barrier function both in vitro and in vivo heat-stressed model, similar to those observed above with the inhibition of PAR1. These results suggest that PAR1 is a potential

  16. Combination with CK19 Might Increase the Prognostic Power of Hep Par 1 in Hepatocellular Carcinoma after Curative Resection.

    PubMed

    Jin, Ye; Liang, Zhi-Yong; Zhou, Wei-Xun; Zhou, Li

    2017-07-31

    Hepatocyte Paraffin 1 (Hep Par 1) and cytokeratin 19 (CK19) were shown to be associated with post-surgical prognosis of hepatocellular carcinoma (HCC). However, further validation might be needed. Besides, their combined evaluation has not been reported. The present study was designed to address the issues. Expressions of Hep Par 1 and CK19 were detected using tissue microarray-based immunohistochemical staining in 79 patients with HCC underwent curative hepatectomy. Their associations with cliniopathologic variables, overall and recurrence-free survival were analyzed. Hep Par 1 was highly expressed in 61 patients (77.2%), whereas CK19 was positive in 8 patients (10.1%). Moreover, expressions of these two proteins were all associated with tumor-node-metastasis (TNM) stage and vascular invasion. It was found that high Hep Par 1 expression was univariately associated with good overall and recurrence-free survival, while CK19 was marginally prognostic. Also in univariate analyses, combination of the two markers more effectively predicted for long-term prognosis in HCC than Hep Par 1 did. However, neither Hep Par 1 nor Hep Par 1/CK19 was multivariately significant. Finally, Hep Par 1/CK19 combined with TNM stage might obtain more satisfactory outcome prediction, especially for overall survival. Combination of CK19 with Hep Par 1 might have higher prognostic power, which might be further improved by adding TNM stage, than Hep Par 1 alone, in resected HCC. Of course, subsequent confirmation is necessary.

  17. Estimation of photosynthetically available radiation (PAR) from OCEANSAT-I OCM using a simple atmospheric radiative transfer model

    NASA Astrophysics Data System (ADS)

    Tripathy, Madhumita; Raman, Mini; Chauhan, Prakash

    2015-10-01

    Photosynthetically available radiation (PAR) is an important variable for radiation budget, marine and terrestrial ecosystem models. OCEANSAT-1 Ocean Color Monitor (OCM) PAR was estimated using two different methods under both clear and cloudy sky conditions. In the first approach, aerosol optical depth (AOD) and cloud optical depth (COD) were estimated from OCEANSAT-1 OCM TOA (top-of-atmosphere) radiance data on a pixel by pixel basis and PAR was estimated from extraterrestrial solar flux for fifteen spectral bands using a radiative transfer model. The second approach used TOA radiances measured by OCM in the PAR spectral range to compute PAR. This approach also included surface albedo and cloud albedo as inputs. Comparison between OCEANSAT-1 OCM PAR at noon with in situ measured PAR shows that root mean square difference was 5.82% for the method I and 7.24% for the method II in daily time scales. Results indicate that methodology adopted to estimate PAR from OCEANSAT-1 OCM can produce reasonably accurate PAR estimates over the tropical Indian Ocean region. This approach can be extended to OCEANSAT-2 OCM and future OCEANSAT-3 OCM data for operational estimation of PAR for regional marine ecosystem applications.

  18. Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells

    PubMed Central

    Brasseur, Kevin; Fabi, François; Adam, Pascal; Parent, Sophie; Lessard, Laurent; Asselin, Eric

    2016-01-01

    We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines. Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data. These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells. PMID:27175591

  19. Galactic Diffuse Emissions

    SciTech Connect

    Digel, Seth W.; /SLAC

    2007-10-25

    Interactions of cosmic rays with interstellar nucleons and photons make the Milky Way a bright, diffuse source of high-energy {gamma}-rays. Observationally, the results from EGRET, COMPTEL, and OSSE have now been extended to higher energies by ground-based experiments, with detections of diffuse emission in the Galactic center reported by H.E.S.S. in the range above 100 GeV and of diffuse emission in Cygnus by MILAGRO in the TeV range. In the range above 100 keV, INTEGRAL SPI has found that diffuse emission remains after point sources are accounted for. I will summarize current knowledge of diffuse {gamma}-ray emission from the Milky Way and review some open issues related to the diffuse emission -- some old, like the distribution of cosmic-ray sources and the origin of the 'excess' of GeV emission observed by EGRET, and some recently recognized, like the amount and distribution of molecular hydrogen not traced by CO emission -- and anticipate some of the advances that will be possible with the Large Area Telescope on GLAST. We plan to develop an accurate physical model for the diffuse emission, which will be useful for detecting and accurately characterizing emission from Galactic point sources as well as any Galactic diffuse emission from exotic processes, and for studying the unresolved extragalactic emission.

  20. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage

    PubMed Central

    Kang, Ho Chul; Lee, Yun-Il; Shin, Joo-Ho; Andrabi, Shaida A.; Chi, Zhikai; Gagné, Jean-Philippe; Lee, Yunjong; Ko, Han Seok; Lee, Byoung Dae; Poirier, Guy G.; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase. Iduna’s E3 ligase activity requires PAR binding because point mutations at Y156A and R157A eliminate Iduna’s PAR binding and Iduna’s E3 ligase activity. Iduna’s E3 ligase activity also requires an intact really interesting new gene (RING) domain because Iduna possessing point mutations at either H54A or C60A is devoid of ubiquitination activity. Tandem affinity purification reveals that Iduna binds to a number of proteins that are either PARsylated or bind PAR including PAR polymerase-1, 2 (PARP1, 2), nucleolin, DNA ligase III, KU70, KU86, XRCC1, and histones. PAR binding to Iduna activates its E3 ligase function, and PAR binding is required for Iduna ubiquitination of PARP1, XRCC1, DNA ligase III, and KU70. Iduna’s PAR-dependent ubiquitination of PARP1 targets it for proteasomal degradation. Via PAR binding and ubiquitin E3 ligase activity, Iduna protects against cell death induced by the DNA damaging agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest and promotes cell survival after γ-irradiation. Moreover, Iduna facilitates DNA repair by reducing apurinic/apyrimidinic (AP) sites after MNNG exposure and facilitates DNA repair following γ-irradiation as assessed by the comet assay. These results define Iduna as a PAR-dependent E3 ligase that regulates cell survival and DNA repair. PMID:21825151

  1. Air Emissions Factors and Quantification

    EPA Pesticide Factsheets

    Emissions factors are used in developing air emissions inventories for air quality management decisions and in developing emissions control strategies. This area provides technical information on and support for the use of emissions factors.

  2. Exacerbation of Apoptosis of Cortical Neurons Following Traumatic Brain Injury in Par-4 Transgenic Mice

    PubMed Central

    Payette, Daniel J; Xie, Jun; Shirwany, Najeeb; Guo, Qing

    2008-01-01

    Traumatic brain injury (TBI) is a significant clinical problem, yet few effective strategies for treating it have emerged. People that sustain and survive a TBI are left with significant cognitive, behavioral, and communicative disabilities. Apoptotic neuronal death occurs following TBI. Prostate apoptosis response-4 (Par-4) is a death domain-containing protein initially characterized as a critical regulator of apoptosis in prostate cancer cells. We have recently generated and characterized Par-4 transgenic mice in which the expression of the par-4 transgene was limited to cells of neuronal lineage. We now provide evidence that, in cortical neurons from these mice, Par-4 drastically increases apoptotic neuronal death in both in vitro and in vivo models of TBI. In vitro experiments were performed in 7-day-old primary cultures of cortical neurons using a previously published, scratch-induced mechanical trauma model. Neurons that overexpress Par-4 showed not only a significant decrease in overall neuron survival after TBI compared to wild-type cells, but also exhibited a sharper decrease in mitochondrial transmembrane potential, a higher degree of free radical accumulation, and earlier activation of caspase-3 than wild-type cells did. In vivo experiments were performed utilizing a weight drop TBI model. A significantly increased volume of cortical injury and exacerbated activation of caspase-3 were observed in Par-4 transgenic mice when compared to those in wild-type mice. These data suggests that aberrant Par-4 expression exacerbates neuronal cell death following TBI by altering mitochondrial function, enhancing oxidative damage, and execution of apoptosis via caspase activation. PMID:18784822

  3. Evaluation of treatment and posttreatment changes of protraction facemask treatment using the PAR index.

    PubMed

    Ngan, P; Yiu, C

    2000-10-01

    The purpose of this study was to use the Peer Assesment Rating (PAR) index score to evaluate the treatment and posttreatment changes of Class III patients treated by protraction facemask. The sample consisted of 20 Chinese children, 6 to 11 years old, with Class III skeletal malocclusion who had been treated with maxillary expansion and a protraction facemask. The average treatment time was 8.2 months, followed by 1 year of retention with a Class III functional appliance. Study casts were taken pretreatment (T1), posttreatment (T2), 1 year follow-up (T3), and 2 years follow-up (T4). After treatment, PAR scores were calculated for each time period. Differences among the 4 time periods were analyzed with the Wilcoxin matched-pairs test. Significant reductions in PAR scores were found at T2 (56%), T3 (70%), and T4 (63%) compared with T1. Immediately posttreatment (T2), 17 (85%) of 20 patients had improved PAR scores by a reduction of at least 30%. Reductions were caused primarily by correction of the anterior crossbite. One year after treatment (T3), further reductions in PAR score were noted (P <.01) as a result of better alignment of the anterior segment, improvement of the buccal occlusion, and overbite and midline corrections. Two years after treatment (T4), PAR scores were higher than at the previous time period. The increases were due to relapses in overjet (4 of 20 patients), overbite, and centerline corrections. These results indicate that significant reductions in the severity of Class III malocclusion can be achieved with early orthopedic facemask treatment. In most cases, further improvement in the PAR score can be expected 1 and 2 years after treatment. In a few patients, the benefits of early treatment are negated by relapses in overjet, overbite, and centerline corrections during the follow-up period.

  4. A method for estimating the diffuse attenuation coefficient (KdPAR)from paired temperature sensors

    USGS Publications Warehouse

    Read, Jordan S.; Rose, Kevin C.; Winslow, Luke A.; Read, Emily K.

    2015-01-01

    A new method for estimating the diffuse attenuation coefficient for photosynthetically active radiation (KdPAR) from paired temperature sensors was derived. We show that during cases where the attenuation of penetrating shortwave solar radiation is the dominant source of temperature changes, time series measurements of water temperatures at multiple depths (z1 and z2) are related to one another by a linear scaling factor (a). KdPAR can then be estimated by the simple equation KdPAR ln(a)/(z2/z1). A suggested workflow is presented that outlines procedures for calculating KdPAR according to this paired temperature sensor (PTS) method. This method is best suited for conditions when radiative temperature gains are large relative to physical noise. These conditions occur frequently on water bodies with low wind and/or high KdPARs but can be used for other types of lakes during time periods of low wind and/or where spatially redundant measurements of temperatures are available. The optimal vertical placement of temperature sensors according to a priori knowledge of KdPAR is also described. This information can be used to inform the design of future sensor deployments using the PTS method or for campaigns where characterizing sub-daily changes in temperatures is important. The PTS method provides a novel method to characterize light attenuation in aquatic ecosystems without expensive radiometric equipment or the user subjectivity inherent in Secchi depth measurements. This method also can enable the estimation of KdPAR at higher frequencies than many manual monitoring programs allow.

  5. ParsEval: parallel comparison and analysis of gene structure annotations

    PubMed Central

    2012-01-01

    Background Accurate gene structure annotation is a fundamental but somewhat elusive goal of genome projects, as witnessed by the fact that (model) genomes typically undergo several cycles of re-annotation. In many cases, it is not only different versions of annotations that need to be compared but also different sources of annotation of the same genome, derived from distinct gene prediction workflows. Such comparisons are of interest to annotation providers, prediction software developers, and end-users, who all need to assess what is common and what is different among distinct annotation sources. We developed ParsEval, a software application for pairwise comparison of sets of gene structure annotations. ParsEval calculates several statistics that highlight the similarities and differences between the two sets of annotations provided. These statistics are presented in an aggregate summary report, with additional details provided as individual reports specific to non-overlapping, gene-model-centric genomic loci. Genome browser styled graphics embedded in these reports help visualize the genomic context of the annotations. Output from ParsEval is both easily read and parsed, enabling systematic identification of problematic gene models for subsequent focused analysis. Results ParsEval is capable of analyzing annotations for large eukaryotic genomes on typical desktop or laptop hardware. In comparison to existing methods, ParsEval exhibits a considerable performance improvement, both in terms of runtime and memory consumption. Reports from ParsEval can provide relevant biological insights into the gene structure annotations being compared. Conclusions Implemented in C, ParsEval provides the quickest and most feature-rich solution for genome annotation comparison to date. The source code is freely available (under an ISC license) at http://parseval.sourceforge.net/. PMID:22852583

  6. Detecting Plant Photoprotective Response to Water Stress Through Variation In PAR Reflectance

    NASA Astrophysics Data System (ADS)

    Zygielbaum, A. I.; Arkebauer, T. J.; Walter-Shea, E.

    2012-12-01

    Published papers over several decades have shown increasing leaf-level optical reflectance with decreasing leaf water content. Our experimental results using maize and sorghum showed this increase consistently, caused by variation in optical absorption, in the visible (photosynthetically active radiation - PAR) and middle infrared (MIR) spectral regions. Relatively smaller response, driven by variation in optical scatter, was observed in near infrared (NIR). The concomitant increasing reflectance in the PAR and MIR regions is perplexing. PAR reflectance is dominated by chlorophyll absorption while MIR reflectance is dominated by water molecule absorption. However, changes in chlorophyll concentration, determined by chemical extraction, were too small to account for the variation in PAR reflectance. PAR and MIR reflectances were also influenced by the strength of incident light. Hence PAR reflectance appears to be modulated not only by pigment concentration, the classical description, but also by the strength of incident light and the severity of water deficit. We previously reported that these findings were consistent with chloroplast avoidance movement, a plant photoprotective response, which limits light absorption by pigments. We report here our continuing investigation of this phenomenon. In addition to reflectance measurements, time-lapse microscope images of leaves under increasing water deficit conditions were obtained. These show a brightening between veins which strongly supports our assertion that changes in PAR reflectance accompanying water deficit are caused primarily by chloroplast avoidance movement. Our results suggest that leaf, and possibly canopy, reflectance can therefore be used to detect and measure plant stress. These results also indicate that chloroplast avoidance movement may cause poor estimates of leaf chlorophyll content using techniques based on fluoresced, reflected or transmitted light.

  7. Lumbar lordosis and pars interarticularis fractures: a case-control study.

    PubMed

    Bugg, William G; Lewis, Mark; Juette, Arne; Cahir, John G; Toms, Andoni P

    2012-07-01

    The aim of this study is to examine the relationship between lumbar lordosis and pars interarticularis fractures. In this retrospective case-control study we compare the angle of lumbar lordosis and the angle of the S1 vertebral endplate (as a measure of pelvic tilt) in patients with bilateral L5 pars interarticularis fractures with age- and sex-matched control cases with normal MRI examinations of the lumbar spine. Twenty-nine cases of bilateral L5 pars interarticularis fractures with matched control-cases were identified on MRI (16 male, 13 female, age 9-63 years). The angle of lordosis was measured between the inferior L4 and superior S1 vertebral endplates on a standing lateral lumbar spine radiograph for both groups. The mean angle of lordosis about the L5 vertebra was 36.9° (SD = 6.5°) in the pars interarticularis fracture group, and 30.1° (SD = 6.4°) in the control group. The difference between the two groups was significant (mean difference 6.8°, Student's t test: P < 0.001). The mean angle of sacral tilt measured was 122.2° (SD = 10.16°) for controls and 136.4° (SD = 10.86°) for patients with pars defects. The difference in the means of 14.2° was statistically significantly different (P < 0.0001). Sacral tilt represented by a steeply angled superior endplate of S1 is associated with a significantly increased angle of lordosis, between L4 and S1, and pars fractures at L5. Steep angulation of the first sacral vertebral segment maybe the predisposing biomechanical factor that leads to pincer-like impingement of the pars interarticularis and then spondylolysis.

  8. uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells.

    PubMed

    Laurenzana, Anna; Chillà, Anastasia; Luciani, Cristina; Peppicelli, Silvia; Biagioni, Alessio; Bianchini, Francesca; Tenedini, Elena; Torre, Eugenio; Mocali, Alessandra; Calorini, Lido; Margheri, Francesca; Fibbi, Gabriella; Del Rosso, Mario

    2017-09-15

    In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells. Further, binding of uPA to uPAR regulates expression of molecules that govern cell invasion, including extracellular matrix metallo-proteinases inducer (EMPPRIN) and enolase, a glycolytyc enzyme that also serves as a plasminogen receptor, thus providing a common denominator between tumor metabolism and phenotypic invasive features. Such effects depend on the α5β1-integrin-mediated uPAR connection with EGFR in melanoma cells with engagement of the PI3K-mTOR-HIFα pathway. HIF-1α trans-activates genes whose products mediate tumor invasion and glycolysis, thus providing the common denominator between melanoma metabolism and its invasive features. These findings unveil a unrecognized interaction between the invasion-related uPAR and IL-TKRs in the control of glycolysis and disclose a new pharmacological target (i.e., uPAR/IL-TKRs axis) for the therapy of melanoma. © 2017 UICC.

  9. Low Emissions Aftertreatment and Diesel Emissions Reduction

    SciTech Connect

    2005-05-27

    Detroit Diesel Corporation (DDC) has successfully completed a five-year Low Emissions Aftertreatment and Diesel Emissions Reduction (LEADER) program under a DOE project entitled: ''Research and Development for Compression-Ignition Direct-Injection Engines (CIDI) and Aftertreatment Sub-Systems''. The objectives of the LEADER Program were to: Demonstrate technologies that will achieve future federal Tier 2 emissions targets; and Demonstrate production-viable technical targets for engine out emissions, efficiency, power density, noise, durability, production cost, aftertreatment volume and weight. These objectives were successfully met during the course of the LEADER program The most noteworthy achievements in this program are listed below: (1) Demonstrated Tier 2 Bin 3 emissions target over the FTP75 cycle on a PNGV-mule Neon passenger car, utilizing a CSF + SCR system These aggressive emissions were obtained with no ammonia (NH{sub 3}) slip and a combined fuel economy of 63 miles per gallon, integrating FTP75 and highway fuel economy transient cycle test results. Demonstrated feasibility to achieve Tier 2 Bin 8 emissions levels without active NOx aftertreatment. (2) Demonstrated Tier 2 Bin 3 emissions target over the FTP75 cycle on a light-duty truck utilizing a CSF + SCR system, synergizing efforts with the DOE-DDC DELTA program. This aggressive reduction in tailpipe out emissions was achieved with no ammonia slip and a 41% fuel economy improvement, compared to the equivalent gasoline engine-equipped vehicle. (3) Demonstrated Tier 2 near-Bin 9 emissions compliance on a light-duty truck, without active NOx aftertreatment devices, in synergy with the DOE-DDC DELTA program. (4) Developed and applied advanced combustion technologies such as ''CLEAN Combustion{copyright}'', which yields simultaneous reduction in engine out NOx and PM emissions while also improving engine and aftertreatment integration by providing favorable exhaust species and temperature

  10. Early intraplatelet signaling enhances the release of human platelet PAR-1 and -4 amino-terminal peptides in response to thrombin.

    PubMed

    Ofosu, Frederick A; Dewar, Lori; Song, Yingqi; Cedrone, Aisha C; Hortelano, Gonzalo; Craven, Sharon J

    2009-02-24

    Activation of washed human platelets initiated with alpha-thrombin, SFLLRN, or AYPGKF invariably results in the generation of PAR-1-(1-41) and PAR-4-(1-47). PAR-1-(1-41) and PAR-4-(1-47) are amino-terminal peptides generated when PAR-1 and -4 are cleaved in their first extracellular domains after R(41) and R(47), respectively, to expose the tethered ligand domains of PAR-1 and -4. Since soybean trypsin inhibitor decreases generation of PAR-1-(1-41) and PAR-4-(1-47) and other platelet aggregation-related responses to these three agonists, but does not inactivate alpha-thrombin, a platelet trypsin-like proteinase apparently activates PAR-1 and -4 to propagate PAR-dependent platelet responses. This study identified the signaling pathways implicated in the generation of the platelet proteinase that in turn produces PAR-1-(1-41) and PAR-4-(1-47), to thereby drive the subsequent PAR-dependent platelet aggregation-related responses to alpha-thrombin, SFLLRN, or AYPGKF. Only inhibitors of signaling enzymes that prevented ATP release (forskolin, PGE(1), or BIMI-1) prevented or delayed the generation of PAR-1-(1-41) and PAR-4-(1-47) in response to all three agonists. SBTI prevented platelet aggregation initiated by alpha-thrombin, SFLLRN, or AYPGKF but did so less effectively when it was added 10 s after each agonist. Thus, the platelet-derived proteinase acts within 10 s of each agonist addition to generate PAR-1-(1-41) and PAR-4-(1-47). Furthermore, alpha-thrombin may not effectively catalyze PAR-1-(1-41) and PAR-4-(1-47) generation. We propose that unidentified ATP-dependent phosphorylation reactions catalyzed by PKC help to generate the platelet-derived proteinase that propagates human platelet PAR-1 and -4 activation by the three agonists.

  11. Protease-activated receptor-2 (PAR-2): structure-function study of receptor activation by diverse peptides related to tethered-ligand epitopes.

    PubMed

    Maryanoff, B E; Santulli, R J; McComsey, D F; Hoekstra, W J; Hoey, K; Smith, C E; Addo, M; Darrow, A L; Andrade-Gordon, P

    2001-02-15

    Protease-activated receptor-2 (PAR-2) is a tethered-ligand, G-protein-coupled receptor that is activated by proteolytic cleavage or by small peptides derived from its cleaved N-terminal sequence, such as SLIGRL-NH2. To assess specific PAR activity, we developed an immortalized murine PAR-1 (-/-) cell line transfected with either human PAR-2 or PAR-1. A "directed" library of more than 100 PAR agonist peptide analogues was synthesized and evaluated for PAR-2 and PAR-1 activity to establish an in-depth structure-function profile for specific action on PAR-2. The most potent agonist peptides (EC50 = 2-4 microM) had Lys at position 6, Ala at position 4, and pFPhe at position 2; however, these also exhibited potent PAR-1 activity (EC50 = 0.05-0.35 microM). We identified SLIARK-NH2 and SL-Cha-ARL-NH2 as relatively potent, highly selective PAR-2 agonists with EC50 values of 4 microM. Position 1 did not tolerate basic, acidic, or large hydrophobic amino acids. N-Terminal capping by acetyl eliminated PAR-2 activity, although removal of the amino group reduced potency by just 4-fold. At position 2, substitution of Leu by Cha or Phe gave equivalent PAR-2 potency, but this modification also activated PAR-1, whereas Ala, Asp, Lys, or Gln abolished PAR-2 activity; at position 3, Ile and Cha were optimal, although various amino acids were tolerated; at position 4, Ala or Cha increased PAR-2 potency 2-fold, although Cha introduced PAR-1 activity; at position 5, Arg or Lys could be replaced successfully by large hydrophobic amino acids. These results with hexapeptide C-terminal amides that mimic the native PAR-2 ligand indicate structural modes for obtaining optimal PAR-2 activity, which could be useful for the design of PAR-2 antagonists.

  12. Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (αM)

    PubMed Central

    Wei, Ying; Donate, Fernando; Juarez, Jose; Parry, Graham; Chen, Liqing; Meehan, Edward J.; Ahn, Richard W.; Ugolkov, Andrey; Dubrovskyi, Oleksii; O'Halloran, Thomas V.; Huang, Mingdong; Mazar, Andrew P.

    2014-01-01

    The urokinase plasminogen activator receptor (uPAR) plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin) to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268–275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR) regions of ATN-658 closely mimic the binding regions of the integrin CD11b (αM), a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR. PMID:24465541

  13. Analogy electromagnetism-acoustics: Validation and application to local impedance active control for sound absorption

    NASA Astrophysics Data System (ADS)

    Nicolas, L.; Furstoss, M.; Galland, M. A.

    1998-10-01

    An analogy between electromagnetism and acoustics is presented in 2D. The propagation of sound in presence of absorbing material is modeled using an open boundary microwave package. Validation is performed through analytical and experimental results. Application to local impedance active control for free field sound absorption is finally described. Une analogie entre acoustique et électromagnétisme est présentée en 2D, afin de modéliser la propagation d'ondes acoustiques, en présence de matériau absorbant et à l'aide d'un logiciel de micro-ondes en domaine ouvert. Cette analogie est validée par des résultats analytiques et expérimentaux. Une application au contrôle actif de l'impédance acoustique de surface de matériaux poreux est finalement décrite.

  14. Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

    PubMed

    Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

    2016-08-23

    Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion.

  15. EBV LMP-1 negatively regulates expression and pro-apoptotic activity of Par-4 in nasopharyngeal carcinoma cells.

    PubMed

    Lee, Jeng-Woei; Liu, Po-Fan; Hsu, Lee-Ping; Chen, Peir-Rong; Chang, Chung-Hsing; Shih, Wen-Ling

    2009-07-08

    Latent membrane protein-1 (LMP-1) of the Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), and in this study we sought to determine whether the pro-apoptotic activity of prostate apoptosis response-4 (Par-4) is modulated by LMP-1 in NPC cells. We found that LMP-1 diminished the pro-apoptotic activity of Par-4 and negatively regulated Par-4 protein by de novo synthesis; moreover, although LMP-1 accelerated a Par-4 activator, PKA, we demonstrated that LMP-1 also activated the PI3K/Akt pathway and increased Bcl-2 expression to suppress the activity of Par-4. Consequently, our results revealed a novel negative action of LMP-1 on the pro-apoptosis protein Par-4 by the coordination of multiple signaling pathways.

  16. Spatiotemporal Variability of Global and Diffuse PAR in the Amazon Region and its Significance for Tropical Forest Photosynthesis

    NASA Astrophysics Data System (ADS)

    Dye, D. G.

    2003-12-01

    This study examines seasonal and inter-annual variation in surface fluxes of global and diffuse photosynthetically active radiation (PAR, 400-700 nm) in the tropical forest of the Amazon region. Spatial and temporal patterns of global and diffuse PAR are determined from reanalysis data from the National Center for Environmental Prediction (NCEP), and from the SeaWIFS Solar Surface Irradiance (SSI) data set. The PAR data and satellite-derived estimates of leaf area index (LAI) are applied to an existing sun-shade model of forest canopy photosynthesis. The seasonality of atmospheric scattering (quantified as the diffuse fraction of global PAR) as a determining factor for the relative influence of variation and trends in incident PAR on tropical forest photosynthesis is quantitatively evaluated. The results provide insight into the role of the surface PAR regime in the dynamics of ecosystem-atmosphere carbon exchange in the Amazon and other tropical forest regions.

  17. Towards an Improved LAI Collection Protocol via Simulated and Field-Based PAR Sensing.

    PubMed

    Yao, Wei; Kelbe, David; Leeuwen, Martin van; Romanczyk, Paul; Aardt, Jan van

    2016-07-14

    In support of NASA's next-generation spectrometer-the Hyperspectral Infrared Imager (HyspIRI)-we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. These collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the "classic" Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data ( R 2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3-5 ( m 2 / m 2 )).

  18. PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.

    PubMed

    Ray, Tanusree; Pal, Amit

    2016-05-01

    Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

  19. Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase

    PubMed Central

    Barber, Kara R.; Sherman, Michael

    2017-01-01

    Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated. PMID:28222093

  20. Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.

    PubMed

    Yang, Rui; Kong, Eryan; Jin, Jing; Hergovich, Alexander; Püschel, Andreas W

    2014-08-15

    The morphology and polarized growth of cells depend on pathways that control the asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr kinases play important roles in cell polarity and morphogenesis in yeast and invertebrates but it is unclear whether they perform a similar function in mammalian cells. Here, we analyze the function of mammalian Ndr1 and Ndr2 (also known as STK38 or STK38L, respectively) in the establishment of polarity in neurons. We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3 (also known as PARD3). Rassf5 and Ndr1 or Ndr2 are required during the polarization of hippocampal neurons to prevent the formation of supernumerary axons. Mechanistically, the Ndr kinases act by phosphorylating Par3 at Ser383 to inhibit its interaction with dynein, thereby polarizing the distribution of Par3 and reinforcing axon specification. Our results identify a novel Rassf5-Ndr-Par3 signaling cascade that regulates the transport of Par3 during the establishment of neuronal polarity. Their role in neuronal polarity suggests that Ndr kinases perform a conserved function as regulators of cell polarity.

  1. Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage

    PubMed Central

    Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

    2011-01-01

    Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures. PMID:22262963

  2. uPAR induces epithelial–mesenchymal transition in hypoxic breast cancer cells

    PubMed Central

    Lester, Robin D.; Jo, Minji; Montel, Valérie; Takimoto, Shinako; Gonias, Steven L.

    2007-01-01

    Hypoxia activates genetic programs that facilitate cell survival; however, in cancer, it may promote invasion and metastasis. In this study, we show that breast cancer cells cultured in 1.0% O2 demonstrate changes consistent with epithelial–mesenchymal transition (EMT). Snail translocates to the nucleus, and E-cadherin is lost from plasma membranes. Vimentin expression, cell migration, Matrigel invasion, and collagen remodeling are increased. Hypoxia-induced EMT is accompanied by increased expression of the urokinase-type plasminogen activator receptor (uPAR) and activation of cell signaling factors downstream of uPAR, including Akt and Rac1. Glycogen synthase kinase-3β is phosphorylated, and Snail expression is increased. Hypoxia-induced EMT is blocked by uPAR gene silencing and mimicked by uPAR overexpression in normoxia. Antagonizing Rac1 or phosphatidylinositol 3-kinase also inhibits development of cellular properties associated with EMT in hypoxia. Breast cancer cells implanted on chick chorioallantoic membranes and treated with CoCl2, to model hypoxia, demonstrate increased dissemination. We conclude that in hypoxia, uPAR activates diverse cell signaling pathways that cooperatively induce EMT and may promote cancer metastasis. PMID:17664334

  3. Participatory action research (PAR) in middle school: opportunities, constraints, and key processes.

    PubMed

    Ozer, Emily J; Ritterman, Miranda L; Wanis, Maggie G

    2010-09-01

    Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth's sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools.

  4. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology

    NASA Astrophysics Data System (ADS)

    Bache, Michael; Bosco, Filippo G.; Brøgger, Anna L.; Frøhling, Kasper B.; Sonne Alstrøm, Tommy; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

    2013-11-01

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

  5. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology.

    PubMed

    Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

    2013-11-08

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

  6. The PAR index for evaluation of treatment outcomes in orthodontics: a clinical audit of 50 cases.

    PubMed

    Fadiga, Mohamed Siddick; Diouf, Joseph Samba; Diop Ba, Khady; Gueye, Idrissa; Ngom, Papa Ibrahima; Diagne, Falou

    2014-03-01

    In the context of this study, a clinical audit of cases treated by a single orthodontist was carried out to illustrate one practical application of the PAR index. Fifty pairs of dental casts taken from the patient group before and at the end of orthodontic treatment were evaluated by an orthodontist trained in the use of the PAR index. This evaluation shows that the average overall PAR score for the subjects included in the study fell from an initial value of 25.64 ± 11.73 points to 1.78 ± 2.79 points at the end of orthodontic treatment. The average reduction attributable to orthodontic treatment was 23.86 ± 0.95 points, for an average percentage reduction of 93.36 ± 9.02%. When cases were classified according to the degree of improvement suggested by the nomogram of the PAR index, 23 (46%) were in the "Improved" category after treatment, and 27 cases (54%) in the "Greatly improved" category. This adds up to a total of 100% in these two categories, with none in the "No better" or "Worse" categories. It should be recalled that a high standard of orthodontic treatment is considered to be reached when the average percentage reduction of the PAR score exceeds 70% and when the number of cases in the "Worse or no better" category is below 5%. Copyright © 2014. Published by Elsevier Masson SAS.

  7. Towards an Improved LAI Collection Protocol via Simulated and Field-Based PAR Sensing

    PubMed Central

    Yao, Wei; Kelbe, David; van Leeuwen, Martin; Romanczyk, Paul; van Aardt, Jan

    2016-01-01

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. These collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 (m2/m2)). PMID:27428969

  8. Role of PAR2 in regulating oxaliplatin-induced neuropathic pain via TRPA1.

    PubMed

    Tian, Liujun; Fan, Tianren; Zhou, Nan; Guo, Hui; Zhang, Weijie

    2015-01-01

    Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, one of the main limiting complications of OXL is neuropathic pain. In this study, the underlying mechanisms responsible for OXL evoked-neuropathic pain were examined. Using a rat model, the results demonstrated that intraperitoneal (i.p.) injection of OXL significantly increased mechanical pain and cold sensitivity as compared with control animals (P < 0.05 vs. control rats). Blocking proteinase-activated receptor 2 (PAR2) significantly attenuated mechanical pain and cold sensitivity observed in control rats and OXL rats (P < 0.05 vs. vehicle control). The attenuating effect of PAR2 on mechanical pain and cold sensitivity were significantly smaller in OXL-rats than in control rats. The role played by PAR2 downstream signaling pathways [namely, transient receptor potential ankyrin 1 (TRPA1)] in regulating OXL evoked-neuropathic pain was also examined. The data shows that TRPA1 expression was upregulated in the lumbar dorsal root ganglion (DRG) of OXL rats and blocking TRPA1 inhibited mechanical pain and heightened cold sensitivity (P < 0.05 vs. control rats). Blocking PAR2 also significantly decreased TRPA1 expression in the DRG. Findings in this study show that OXL intervention amplifies mechanical hyperalgesia and cold hypersensitivity and PAR2 plays an important role in regulating OXL-induced neuropathic pain via TRPA1 pathways.

  9. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain.

    PubMed

    Dai, Yi; Wang, Shenglan; Tominaga, Makoto; Yamamoto, Satoshi; Fukuoka, Tetsuo; Higashi, Tomohiro; Kobayashi, Kimiko; Obata, Koichi; Yamanaka, Hiroki; Noguchi, Koichi

    2007-07-01

    Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation. Transient receptor potential A1 (TRPA1) is an excitatory ion channel on primary sensory nerves of pain pathway. Here, we show that a functional interaction of PAR2 and TRPA1 in dorsal root ganglion (DRG) neurons could contribute to the sensation of inflammatory pain. Frequent colocalization of TRPA1 with PAR2 was found in rat DRG neurons. PAR2 activation increased the TRPA1 currents evoked by its agonists in HEK293 cells transfected with TRPA1, as well as DRG neurons. Application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppressed this potentiation. Decrease of plasma membrane PIP(2) levels through antibody sequestration or PLC-mediated hydrolysis mimicked the potentiating effects of PAR2 activation at the cellular level. Thus, the increased TRPA1 sensitivity may have been due to activation of PLC, which releases the inhibition of TRPA1 from plasma membrane PIP(2). These results identify for the first time to our knowledge a sensitization mechanism of TRPA1 and a novel mechanism through which trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation.

  10. Participatory Action Research (PAR) in Middle School: Opportunities, Constraints, and Key Processes

    PubMed Central

    Ritterman, Miranda L.; Wanis, Maggie G.

    2010-01-01

    Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth’s sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools. PMID:20676754

  11. "It was like reading a detective novel": Using PAR to work together for culture change.

    PubMed

    Fortune, Darla; McKeown, Janet; Dupuis, Sherry; de Witt, Lorna

    2015-08-01

    Participatory action research (PAR), with its focus on engagement and collaboration, is uniquely suited to enhancing culture change initiatives in dementia care. Yet, there is limited literature of its application to culture change approaches in care settings, and even less in dementia specific care contexts. To address these gaps in the literature, the purpose of this paper is to examine the complexities of a PAR project aimed at changing the culture of dementia care in two diverse dementia care settings, including a long term care (LTC) and community care setting. Drawing from data gathered throughout the PAR process, we unpack the challenges experienced by participants working together to guide culture change within their respective care settings. These challenges include: overextending selves through culture change participation; fluctuating group membership; feeling uncertainty, confusion and apprehension about the process; frustratingly slow process; and seeking diverse group representation in decision making. We also highlight the potential for appreciative inquiry (AI) to be integrated with PAR to guide a process whereby participants involved in culture change initiatives can develop strategies to mitigate challenges they experience. We view the challenges and strategies shared here as being constructive to would-be culture change agents and hope this paper will move others to consider the use of PAR when engaging in culture change initiatives. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. CD80, suPAR and nephrotic syndrome in a case of NPHS2 mutation.

    PubMed

    Cara-Fuentes, Gabriel; Araya, Carlos; Wei, Changli; Rivard, Christopher; Ishimoto, Takuji; Reiser, Jochen; Johnson, Richard J; Garin, Eduardo H

    2013-01-01

    Podocin mutations are characterized by progression to end stage renal disease and histologic findings of Focal Segmental Glomerulosclerosis (FSGS). CD80 is a podocytes protein that may play a role in proteinuria, particularly in Minimal Change Disease whereas the soluble urokinase receptor (suPAR) is characteristically elevated in the serum of FSGS patients. In a patient with nephrotic syndrome and podocin mutation, urinary and serum CD80 as well as suPAR were measured using commercially available kits. Urinary CD80 molecular size was determined by western blot analysis. Glomerular staining for CD80 and podocin was performed. Patient displayed marked elevated CD80 and mildly increased suPAR urinary levels compared to controls. Serum CD80 level was within the range observed in normal controls. Serum suPAR level was elevated, albeit in the lower range reported for patients with primary FSGS. Immunofluorescence examination of kidney biopsy revealed glomerular CD80 expression. The combination of serum and urinary biomarkers can help differentiate various forms of FSGS. High urinary CD80 and elevated serum and urinary suPAR might represent a profile to differentiate this genetic form of FSGS from primary FSGS.

  13. Towards an improved LAI collection protocol via simulated field-based PAR sensing

    SciTech Connect

    Yao, Wei; Van Leeuwen, Martin; Romanczyk, Paul; van Aardt, Jan; Kelbe, David

    2016-07-14

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopy gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. Furthermore, these collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 ( m2/m2)).

  14. Towards an improved LAI collection protocol via simulated field-based PAR sensing

    DOE PAGES

    Yao, Wei; Van Leeuwen, Martin; Romanczyk, Paul; ...

    2016-07-14

    In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopymore » gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. Furthermore, these collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 ( m2/m2)).« less

  15. The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

    PubMed Central

    Kessler, Daniel; Papatheodorou, Panagiotis; Stratmann, Tina; Dian, Elke Andrea; Hartmann-Fatu, Cristina; Rassow, Joachim; Bayer, Peter; Mueller, Jonathan Wolf

    2007-01-01

    Background The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study. Results Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions. Conclusion Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae. PMID:17875217

  16. The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae.

    PubMed

    Kessler, Daniel; Papatheodorou, Panagiotis; Stratmann, Tina; Dian, Elke Andrea; Hartmann-Fatu, Cristina; Rassow, Joachim; Bayer, Peter; Mueller, Jonathan Wolf

    2007-09-17

    The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study. Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions. Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae.

  17. Par-4 is a novel mediator of renal tubule cell death in models of ischemia-reperfusion injury.

    PubMed

    Xie, Jun; Guo, Qing

    2007-01-01

    Prostate apoptosis response-4 (Par-4) is a leucine zipper protein linked to apoptotic cell death in prostate cancer and neuronal tissues. The leucine zipper domain of Par-4 (Leu.zip) mediates protein-protein interactions that are essential for sensitization of cells to apoptosis, and overexpression of Leu.zip blocks Par-4 activity in a dominant negative fashion. Ischemia-reperfusion-induced renal injury (IRI) is clinically important because it typically damages renal tubular epithelial cells and glomerular cells, and it is the most common cause of acute renal failure (ARF). We now report that Par-4 is expressed in renal tubule cells and that aberrant expression of Par-4 activity plays a crucial role in activating apoptotic pathways in well-characterized models of renal IRI. Increased levels of Par-4 were observed following chemical ischemia-reperfusion in HK-2 cells in vitro and in mouse renal tubular cells following bilateral clamping of renal pedicles in vivo. Inhibition of Par-4 expression by specific par-4 antisense oligonucleotides largely prevented HK-2 cell apoptosis induced by IRI. Overexpression of Par-4 in these cells exacerbated mitochondrial dysfunction and caspase activation and conferred increased sensitivity to IRI-induced apoptosis. Expression of Leu.zip, a dominant negative regulator of Par-4, largely prevented mitochondrial dysfunction and caspase activation and significantly inhibited IRI-induced apoptosis in HK-2 cells. In addition, transfection of Par-4 increased while transfection of Leu.zip decreased necrosis in HK-2 cells following prolonged IRI. These results identify Par-4 as a novel and early mediator of renal tubule cell injury following IRI and provide a potential target for developing new therapeutic strategies for renal IRI and ARF.

  18. First record of the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Scolytidae), in Pará nut, Bertholletia excelsa (Lecythidaceae).

    PubMed

    Gumier-Costa, Fabiano

    2009-01-01

    We report the occurrence of Hypothenemus hampei (Ferrari) attacking Pará nuts stored in the southeast of Para state. The coffee berry borer successfully colonized and reproduced using Pará nuts as a food source. Based on this observation, the Pará nuts can be used as an alternative food source in rearing the coffee berry borer. Also, attention should be brought to need of proper storage of these nuts to avoid infestation by this pest.

  19. National Emission Inventory

    EPA Pesticide Factsheets

    The National Emission Inventory contains measured, modeled, and estimated data for emissions of all known source categories in the US (stationary sources, fires, light duty vehicles and trucks, Heavy duty engines, Motorcycles, ATVs, non-road engines and equipment, locomotives, aircraft, and marine vessels). The statutory authority leading to the collection of this information comes from Title II, Part A of the Clean Air Act.Substance classes include CAPs, HAPs, and some GHG data.Data included in the National Emission Inventory is collected annually, Air Pollutant Trends Data is made available annually, and an National Emissions Inventory of air emissions of both Criteria and Hazardous air pollutants from all air emissions sources is prepared every three years.

  20. High Altitude Emissions

    NASA Technical Reports Server (NTRS)

    Bulzan, Dan

    2007-01-01

    An overview of emissions related research being conducted as part of the Fundamental Aeronautics Supersonics Project is presented. The overview includes project objectives, milestones, and descriptions of major research areas. The overview also includes information on the emissions research being conducted under NASA Research Announcements. Technical challenges include: 1) Environmental impact of supersonic cruise emissions is greater due to higher flight altitudes which makes emissions reduction increasingly important. 2) Accurate prediction tools to enable combustor designs that reduce emissions at supersonic cruise are needed as well as intelligent systems to minimize emissions. 3) Combustor operating conditions at supersonic cruise are different than at subsonic cruise since inlet fuel and air temperatures are considerably increased.

  1. Global Seabird Ammonia Emissions

    NASA Astrophysics Data System (ADS)

    Riddick, S. N.; Blackall, T. D.; Dragosits, U.; Daunt, F. H.; Braban, C. F.; Tang, Y. S.; Trathan, P.; Wanless, S.; Sutton, M. A.

    2010-12-01

    Seabird colonies represent a major source of atmospheric ammonia (NH3) in remote coastal and marine systems in temperate, tropical and polar regions. Previous studies have shown that NH3 emissions from Scottish seabird colonies were substantial - of similar magnitude to the most intensive agricultural point source emissions. The UK data were used to model global seabird NH3 emissions and suggested that penguins are a major source of emissions on and around the Antarctic continent. The largest seabird colonies are in the order of millions of seabirds. Due to the isolation of these colonies from anthropogenic nitrogen sources, they may play a major role in the nitrogen cycle within these ecosystems. A global seabird database was constructed and used in conjunction with a species-specific seabird bioenergetics model to map the locations of NH3 emissions from seabird colonies. The accuracy of the modelled emissions was validated with field data of NH3 emissions measured at key seabird colonies in different climatic regions of the world: temperate (Isle of May, Scotland), tropical (Ascension Island) and polar (Signy Island, South Georgia). The field data indicated good agreement between modelled and measured NH3 emissions. The measured NH3 emissions also showed the variability of emission with climate. Climate dependence of seabird NH3 emissions may have further implications under a changing global climate. Seabird colonies represent NH3 emission ‘hotspots’, often far from anthropogenic sources, and are likely to be the major source of nitrogen input to these remote coastal ecosystems. The direct manuring by seabirds at colony locations may strongly influence species richness and biodiversity. The subsequent volatilisation and deposition of NH3 increases the spatial extent of seabird influence on nitrogen cycling in their local ecosystem. As many seabird populations are fluctuating due to changing food supply, climate change or anthropogenic pressures, these factors

  2. Spontaneous lung and lymph node metastasis in transgenic breast cancer is independent of the urokinase receptor uPAR.

    PubMed

    Almholt, Kasper; Lærum, Ole Didrik; Nielsen, Boye Schnack; Lund, Ida Katrine; Lund, Leif Røge; Rømer, John; Jögi, Annika

    2015-08-01

    Urokinase-type plasminogen activator (uPA) is an extracellular protease that plays a pivotal role in tumor progression. uPA activity is spatially restricted by its anchorage to high-affinity uPA receptors (uPAR) at the cell surface. High tumor tissue expression of uPA and uPAR is associated with poor prognosis in lung, breast, and colon cancer patients in clinical studies. Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination. To investigate the role of uPAR in cancer progression, we analyze the effect of uPAR deficiency in the same cancer model. uPAR is predominantly expressed in stromal cells in the mouse primary tumors, similar to human breast cancer. In a cohort of MMTV-PyMT mice [uPAR-deficient (n = 31) or wild type controls (n = 33)], tumorigenesis, tumor growth, and tumor histopathology were not significantly affected by uPAR deficiency. Lung and lymph node metastases were also not significantly affected by uPAR deficiency, in contrast to the significant reduction seen in uPA-deficient mice. Taken together, our data show that the genetic absence of uPAR does not influence the outcome of the MMTV-PyMT cancer model.

  3. Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae.

    PubMed

    Margheri, Francesca; Chillà, Anastasia; Laurenzana, Anna; Serratì, Simona; Mazzanti, Benedetta; Saccardi, Riccardo; Santosuosso, Michela; Danza, Giovanna; Sturli, Niccolò; Rosati, Fabiana; Magnelli, Lucia; Papucci, Laura; Calorini, Lido; Bianchini, Francesca; Del Rosso, Mario; Fibbi, Gabriella

    2011-09-29

    Endothelial urokinase-type plasminogen activator receptor (uPAR) is thought to provide a regulatory mechanism in angiogenesis. Here we studied the proangiogenic role of uPAR in endothelial colony-forming cells (ECFCs), a cell population identified in human umbilical blood that embodies all of the properties of an endothelial progenitor cell matched with a high proliferative rate. By using caveolae-disrupting agents and by caveolin-1 silencing, we have shown that the angiogenic properties of ECFCs depend on caveolae integrity and on the presence of full-length uPAR in such specialized membrane invaginations. Inhibition of uPAR expression by antisense oligonucleotides promoted caveolae disruption, suggesting that uPAR is an inducer of caveolae organization. Vascular endothelial growth factor (VEGF) promoted accumulation of uPAR in ECFC caveolae in its undegraded form. We also demonstrated that VEGF-dependent ERK phosphorylation required integrity of caveolae as well as caveolar uPAR expression. VEGF activity depends on inhibition of ECFC MMP12 production, which results in impairment of MMP12-dependent uPAR truncation. Further, MMP12 overexpression in ECFC inhibited vascularization in vitro and in vivo. Our data suggest that intratumor homing of ECFCs suitably engineered to overexpress MMP12 could have the chance to control uPAR-dependent activities required for tumor angiogenesis and malignant cells spreading.

  4. Comparison of the activation peptide regions of protease-activated receptors (PAR) in members of the Family Felidae.

    PubMed

    Boudreaux, Mary K; Barnes, Sara Madison

    2016-09-01

    There is limited information regarding the nucleotides encoding or the predicted amino acid composition of protease-activated receptors (PAR) in cats. The purpose of the study was to determine the nucleotide sequence and predicted amino acid composition of the activation peptide regions of protease-activated receptors PAR1, PAR3, and PAR4 in Felidae family members. Genomic DNA isolated from whole blood samples collected from 10 domestic cats and 45 big cats representing 11 species was subjected to PCR using primers flanking the coding regions for the activation peptides of PAR1, PAR3, and PAR4. PCR products were isolated from agarose gels and submitted for sequencing. Nucleotide sequence data was used to predict the amino acid composition of the activation peptide and flanking regions of the 3 receptors. Predicted amino acid sequences were compared between Felidae members and to human beings. Variations in the predicted amino acid composition of the activation peptides and flanking regions of the various PAR were observed when comparing Felidae family members to each other and to human beings. While the activation peptide regions of the various PAR tend to be conserved, there are differences that may impact the ability of some agonists to mediate biased signaling events documented to occur in human platelets. © 2016 American Society for Veterinary Clinical Pathology.

  5. PAR3 and aPKC regulate Golgi organization through CLASP2 phosphorylation to generate cell polarity

    PubMed Central

    Matsui, Toshinori; Watanabe, Takashi; Matsuzawa, Kenji; Kakeno, Mai; Okumura, Nobumasa; Sugiyama, Ikuko; Itoh, Norimichi; Kaibuchi, Kozo

    2015-01-01

    The organization of the Golgi apparatus is essential for cell polarization and its maintenance. The polarity regulator PAR complex (PAR3, PAR6, and aPKC) plays critical roles in several processes of cell polarization. However, how the PAR complex participates in regulating the organization of the Golgi remains largely unknown. Here we demonstrate the functional cross-talk of the PAR complex with CLASP2, which is a microtubule plus-end–tracking protein and is involved in organizing the Golgi ribbon. CLASP2 directly interacted with PAR3 and was phosphorylated by aPKC. In epithelial cells, knockdown of either PAR3 or aPKC induced the aberrant accumulation of CLASP2 at the trans-Golgi network (TGN) concomitantly with disruption of the Golgi ribbon organization. The expression of a CLASP2 mutant that inhibited the PAR3-CLASP2 interaction disrupted the organization of the Golgi ribbon. CLASP2 is known to localize to the TGN through its interaction with the TGN protein GCC185. This interaction was inhibited by the aPKC-mediated phosphorylation of CLASP2. Furthermore, the nonphosphorylatable mutant enhanced the colocalization of CLASP2 with GCC185, thereby perturbing the Golgi organization. On the basis of these observations, we propose that PAR3 and aPKC control the organization of the Golgi through CLASP2 phosphorylation. PMID:25518939

  6. Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes

    PubMed Central

    Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

    2014-01-01

    Background The urokinase plasminogen activator receptor (uPAR) is associated with poor prognosis in oral squamous cell carcinoma (OSCC), and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells’ expression level of uPAR affected the activity of gelatinolytic enzymes. Methods The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM) proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography. Results We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes. Conclusions Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the

  7. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    PubMed

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  8. Toluene emissions from plants

    NASA Astrophysics Data System (ADS)

    Heiden, A. C.; Kobel, K.; Komenda, M.; Koppmann, R.; Shao, M.; Wildt, J.

    The emission of toluene from different plants was observed in continuously stirred tank reactors and in field measurements. For plants growing without stress, emission rates were low and ranged from the detection limit up to 2·10-16 mol·cm-2·s-1. Under conditions of stress, the emission rates exceeded 10-14 mol·cm-2·s-1. Exposure of sunflower (Helianthus annuus L. cv. Gigantheus) to 13CO2 resulted in 13C-labeling of the emitted toluene on a time scale of hours. Although no biochemical pathway for the production of toluene is known, these results indicate that toluene is synthesized by the plants. The emission rates of toluene from sunflower are dependent on nutrient supply and wounding. Since α-pinene emission rates are also influenced by these factors, toluene and α-pinene emissions show a high correlation. During pathogen attack on Scots pines (Pinus sylvestris L.) significant toluene emissions were observed. In this case emissions of toluene and α-pinene also show a good correlation. Toluene emissions were also found in field experiments with pines using branch enclosures.

  9. Managing Refrigerant Emissions

    EPA Pesticide Factsheets

    Access information on EPA's efforts to address ozone layer depletion by reducing emissions of refrigerants from stationary refrigeration and air conditioning systems and motor vehicle air conditioning systems.

  10. Field emission chemical sensor

    DOEpatents

    Panitz, J.A.

    1983-11-22

    A field emission chemical sensor for specific detection of a chemical entity in a sample includes a closed chamber enclosing two field emission electrode sets, each field emission electrode set comprising (a) an electron emitter electrode from which field emission electrons can be emitted when an effective voltage is connected to the electrode set; and (b) a collector electrode which will capture said electrons emitted from said emitter electrode. One of the electrode sets is passive to the chemical entity and the other is active thereto and has an active emitter electrode which will bind the chemical entity when contacted therewith.

  11. An emissions mission

    SciTech Connect

    Van Slyke, S. ); Card, T. ); Rumpf, M. ); Ellington, L. )

    1993-10-01

    Air quality permit requirements for a Seattle, Washington waste water treatment plant were reviewed for both existing and future plant emissions when the plant was modified to include secondary treatment. While criteria pollutant emissions were an important consideration, volatile organic compound emissions were a crucial factor in the permit approval process. The difference between potential and existing emissions is presented, and specific alternatives for any increases are required. Chloroform control measures were required by the regulators, and a list of additional issues which were reconciled is presented. 1 tab.

  12. The 1943-1952 Eruption of Parícutin Volcano - the Pyroclastic Record

    NASA Astrophysics Data System (ADS)

    Cashman, K.; Pioli, L.; Rosi, M.; Erlund, E.; Delgado Granados, H.; Wallace, P.

    2007-05-01

    The 1943-1952 eruption of Parícutin volcano, Michoacan, is famous for the compositional evolution preserved in successive lava flows. The physical nature of the eruption is less well known, despite the remarkable observational record that was obtained during its nine years of activity. We have revisited both the tephra deposits and the observational accounts with the goal of reconstructing, from a modern perspective, the nature of the `cineritic' activity that serves as Walker's (1973) type example of a violent strombolian eruptive style. We have described sixteen tephra sections around the volcano. Only very proximal sections preserve the late (post-1946) andesitic tephra sequence and associated breadcrust bombs. The tephra sequence preserved in medial to distal sites varies more with direction than with distance, not surprising given the strong variations in prevailing wind directions in this region. (1) Southern sections preserve a complex basal lapilli sequence comprising thin alternating black (enriched in lithics and scoria) and tan (enriched in vesicular tephra) layers; analysis of the vesicular tephra shows it to have a more primitive composition than the earliest erupted lava. These basal layers are overlain by a coarse ash layer, consistent with observations of a persistent weak plume to the SW that accompanied early lava effusion and cone growth. The ash is overlain by a thick sequence of intercalated lapilli and ash. To the north, an ash bed forms the deposit base and is again overlain by alternating lapilli and ash; to the east, alternating beds of lapilli and ash mark the base of the section. We interpret this widespread lapilli and ash sequence to have been deposited during the `heavy cineritic phase' of activity that extended from mid-March through the summer of 1943. Lapilli are homogeneous basaltic andesite with the same bulk composition as lava erupted during this time period. Unique to eastern sections is a pronounced tan vesicular tephra in

  13. Peptidomics of the pars intercerebralis-corpus cardiacum complex of the migratory locust, Locusta migratoria.

    PubMed

    Clynen, E; Baggerman, G; Veelaert, D; Cerstiaens, A; Van der Horst, D; Harthoorn, L; Derua, R; Waelkens, E; De Loof, A; Schoofs, L

    2001-04-01

    The pars intercerebralis-corpora cardiaca system (PI-CC) of insects is the endocrinological equivalent of the hypothalamus-pituitary system of vertebrates. Peptide profiles of the pars intercerebralis and the corpora cardiaca were characterized using simple sampling protocols in combination with MALDI-TOF and electrospray ionization double quadrupole time of flight (ESI-Qq-TOF) mass spectrometric technologies. The results were compared with earlier results of conventional sequencing methods and immunocytochemical methods. In addition to many known peptides, several m/z signals corresponding to putative novel peptides were observed in the corpora cardiaca and/or pars intercerebralis. Furthermore, for a number of peptides evidence was provided about their localization and MALDI-TOF analysis of the released material from the corpora cardiaca yielded information on the hormonal status of particular brain peptides.

  14. PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo

    PubMed Central

    Descoteaux, Catherine; Chartier, Nicolas T.; Pintard, Lionel; Labbé, Jean-Claude

    2014-01-01

    Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division. PMID:24841566

  15. The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells.

    PubMed

    Goulas, Spyros; Conder, Ryan; Knoblich, Juergen A

    2012-10-05

    The adult Drosophila midgut is maintained by intestinal stem cells (ISCs) that generate both self-renewing and differentiating daughter cells. How this asymmetry is generated is currently unclear. Here, we demonstrate that asymmetric ISC division is established by a unique combination of extracellular and intracellular polarity mechanisms. We show that Integrin-dependent adhesion to the basement membrane induces cell-intrinsic polarity and results in the asymmetric segregation of the Par proteins Par-3, Par-6, and aPKC into the apical daughter cell. Cell-specific knockdown and overexpression experiments suggest that increased activity of aPKC enhances Delta/Notch signaling in one of the two daughter cells to induce terminal differentiation. Perturbing this mechanism or altering the orientation of ISC division results in the formation of intestinal tumors. Our data indicate that mechanisms for intrinsically asymmetric cell division can be adapted to allow for the flexibility in lineage decisions that is required in adult stem cells.

  16. Participatory action research (PAR): an approach for improving black women's health in rural and remote communities.

    PubMed

    Etowa, Josephine B; Bernard, Wanda Thomas; Oyinsan, Bunmi; Clow, Barbara

    2007-10-01

    Women are among the most disadvantaged members of any community, and they tend to be at greatest risk of illness. Black women are particularly vulnerable and more prone than White women to illnesses associated with social and economic deprivation, including heart disease and diabetes. They utilize preventive health services less often, and when they fall ill, the health of their families and communities typically suffers as well. This article discusses the process of doing innovative participatory action research (PAR) in southwest Nova Scotia Black communities. The effort resulted in the generation of a database, community action, and interdisciplinary analysis of the intersecting inequities that compromise the health and health care of African Canadian women, their families, and their communities. This particular research effort serves as a case study for explicating the key tenets of PAR and the barriers to and contradictions in implementing PAR in a community-academic collaborative research project.

  17. Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli.

    PubMed Central

    Vila, J; Ruiz, J; Goñi, P; De Anta, M T

    1996-01-01

    The gene parC encodes the A subunit of topoisomerase IV of Escherichia coli. Mutations in the parC region analogous to those in the quinolone resistance-determining region of gyrA were investigated in 27 clinical isolates of E. coli for which ciprofloxacin MICs were 0.0007 to 128 micrograms/ml. Of 15 isolates for which ciprofloxacin MICs were > or = 1 microgram/ml, 8 showed a change in the serine residue at position 80 (Ser-80), 4 showed a change in Glu-84, and 3 showed changes in both amino acids. No mutations were detected in 12 clinical isolates for which ciprofloxacin MICs were < or = 0.25 micrograms/ml. These findings suggest that ParC from E. coli may be another target for quinolones and that mutations at residues Ser-80 and Glu-84 may contribute to decreased fluoroquinolone susceptibility. PMID:8834907

  18. Potential Ecological Effects of Contaminants in the Exposed Par Pond Sediments

    SciTech Connect

    Paller, M.H.; Wike, L.D.

    1996-08-01

    Sediment and small mammal samples were collected from the exposed sediments of Par Pond in early 1995, shortly before the reservoir was refilled after a 4-year drawdown. Sampling was confined to elevations between 58 and 61 meters (190 and 200 feet) above mean sea level, which includes the sediments likely to be exposed if the Par Pond water level is permitted to fluctuate naturally. Both soil and small mammal samples were analyzed for a number of radionuclides and metals. Some of the soil samples were also analyzed for organic contaminants. The objective of the study was to determine if contaminant levels in the Par Pond sediments were high enough to cause deleterious ecological effects.

  19. Parádsasvárite, a new member of the malachite-rosasite group from Parádsasvár, Mátra Mountains, Hungary

    NASA Astrophysics Data System (ADS)

    Fehér, Béla; Szakáll, Sándor; Zajzon, Norbert; Mihály, Judith

    2015-08-01

    Parádsasvárite (IMA No. 2012-077) was found in the Nagy-Lápafő area, Parádsasvár, Mátra Mountains, Hungary. It forms pale beige, globular aggregates up to 0.2 mm in diameter on calcite. Associated secondary minerals are smithsonite, hemimorphite, hydrozincite, aurichalcite and rosasite. The mineral was formed as an alteration product of sphalerite and chalcopyrite in a carbonate-rich environment. Parádsasvárite is translucent with a weakly vitreous, dull or silky lustre and white streak. Its Mohs hardness is about 2-3, cleavage and parting were not observed. It is brittle; the fracture is finely fibrous. Average of nine electron-microprobe analyses gave ZnO 58.08, CuO 12.60, PbO 1.27, CO2 (calc.) 19.50, H2O (calc.) 7.94, total 99.39 wt.%, corresponding to the empirical formula (Zn0.62Cu0.36Pb0.01)Σ0.99Zn1.00(CO3)(OH)2. The seven strongest lines in the X-ray powder diffraction pattern are [dhkl in Å (Iobs %, hkl)] 6.054 (67, 200), 5.085 (100, 210), 3.703 (87, 310 and 220), 3.021 (25, 400 and 130), 2.971 (25, -211 and 001), 2.603 (62, -221) and 2.539 (36, 420). According to its X-ray powder diffraction data and chemical formula, parádsasvárite belongs to the malachite-rosasite group and it is isostructural with rosasite. It is monoclinic, space group P21/ a, a = 12.92(1), b = 9.372(7), c = 3.159(4) Å, β = 110.4(1)°, V = 358.5(5) Å3, Z = 4.

  20. Linking the fPAR, forest albedo and biomass in the northern biomes of Europe

    NASA Astrophysics Data System (ADS)

    Lukeš, Petr; Stenberg, Pauline; Manninen, Terhikki; Rautiainen, Miina; Mõttus, Matti

    2014-05-01

    Land surface albedo and the fraction of photosynthetically active radiation (fPAR) absorbed by plant canopies are two of the essential climate variables controlling the planetary radiative energy budget. Albedo is directly related to the energy exchange between land and the atmosphere as it is the reflectivity of the surface - the higher the albedo, the more incoming solar radiation is reflected and the less absorbed by the surface. The fPAR is related to plant productivity, quantifying the amount of absorbed light available for photosynthesis. It is a key parameter in the modelling of net primary production (NPP) of terrestrial ecosystems. Global climate scenarios are very sensitive to albedo and fPAR estimates, and thus, the effect of changes in canopy structure and density (biomass) on these two variables needs to be quantified reliably. Both parameters are routinely retrieved from current Earth Observation sensors using specialized algorithms. To date, these satellite products have not been linked to extensive forest inventory data sets due to the lack of ground reference data. Data availability for Finland has significantly improved in December 2012, when National Forest Inventory (NFI) data became freely available to the public. The dataset covers the geographical area of Finland (26.1 million hectares) at a spatial resolution of 20 meters including several forest structural variables. In this study, we use the NFI data to study the links between forest albedo, fPAR and forest structure and density during the green vegetation season. More specifically, we investigated the seasonal trends in fPAR and albedo of different spectral regions of northern forests. Empirical relationships between forest albedo, fPAR and total aboveground biomass were established for selected days within the vegetation growing period and across a latitudinal transect of Finland.

  1. Comparing the 7-Day PAR with a Triaxial Accelerometer for Measuring Time in Exercise

    PubMed Central

    Sloane, Richard; Snyder, Denise Clutter; Demark-Wahnefried, Wendy; Lobach, David; Kraus, William E.

    2009-01-01

    Purpose The primary study aim was to evaluate associations of estimated weekly minutes of moderate-to-vigorous intensity exercise from self-reports of the telephone-administered 7-Day Physical Activity Recall (PAR) with data captured by the RT3 triaxial accelerometer. Methods This investigation was undertaken as part of the FRESH START study, a randomized clinical trial that tested an iteratively-tailored diet and exercise mailed print intervention among newly diagnosed breast and prostate cancer survivors. A convenience sample of 139 medically-eligible subjects living within a 60-mile radius of the study center provided both 7-Day PAR and accelerometer data at enrollment. Ultimately n=115 substudy subjects were found eligible for the FRESH START study and randomized to one of two study treatment arms. Follow-up assessments at Year 1 (n=103) and Year 2 (n=99) provided both the 7-Day PAR and accelerometer data. Results There was moderate agreement between the 7-Day PAR and the accelerometer with longitudinal serial correlation coefficients of .54 (baseline), .24 (Year 1) and .53 (Year 2), all P-values < .01, though the accelerometer estimates for weekly time in moderate-to-vigorous physical activity were much higher than those of the 7-Day PAR at all time points. The two methods were poorly correlated in assessing sensitivity to change from baseline to Year 1 (rho=.11, P=.30). Using mixed models repeated measures analysis, both methods exhibited similar non-significant treatment arm X time interaction P-values (7-Day PAR=.22, accelerometer=.23). Conclusions The correlations for three serial time points were in agreement with findings of other studies that compared self-reported time in exercise with physical activity captured by accelerometry. However, these methods capture somewhat different dimensions of physical activity and provide differing estimates of change over time. PMID:19461530

  2. Function inferences from a molecular structural model of bacterial ParE toxin.

    PubMed

    Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Garcia, Anderson; Delfino, Davi Barbosa; Marchetto, Reinaldo

    2010-04-30

    Toxin-antitoxin (TA) systems contribute to plasmid stability by a mechanism that relies on the differential stabilities of the toxin and antitoxin proteins and leads to the killing of daughter bacteria that did not receive a plasmid copy at the cell division. ParE is the toxic component of a TA system that constitutes along with RelE an important class of bacterial toxin called RelE/ParE superfamily. For ParE toxin, no crystallographic structure is available so far and rare in vitro studies demonstrated that the target of toxin activity is E. coli DNA gyrase. Here, a 3D Model for E. coli ParE toxin by molecular homology modeling was built using MODELLER, a program for comparative modeling. The Model was energy minimized by CHARMM and validated using PROCHECK and VERIFY3D programs. Resulting Ramachandran plot analysis it was found that the portion residues failing into the most favored and allowed regions was 96.8%. Structural similarity search employing DALI server showed as the best matches RelE and YoeB families. The Model also showed similarities with other microbial ribonucleases but in a small score. A possible homologous deep cleft active site was identified in the Model using CASTp program. Additional studies to investigate the nuclease activity in members of ParE family as well as to confirm the inhibitory replication activity are needed. The predicted Model allows initial inferences about the unexplored 3D structure of the ParE toxin and may be further used in rational design of molecules for structure-function studies.

  3. Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR{sub 1} activation

    SciTech Connect

    Blanc-Brude, Olivier P. . E-mail: olivier.blanc-brude@larib.inserm.fr; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

    2005-03-10

    Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR{sub 1}). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR{sub 1}-deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR{sub 1}-specific agonists and inhibitors were used to demonstrate that PAR{sub 1} mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR{sub 1} and not PAR{sub 2}. These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis.

  4. Function inferences from a molecular structural model of bacterial ParE toxin

    PubMed Central

    Barbosa, Luiz Carlos Bertucci; Garrido, Saulo Santesso; Garcia, Anderson; Delfino, Davi Barbosa; Marchetto, Reinaldo

    2010-01-01

    Toxin-antitoxin (TA) systems contribute to plasmid stability by a mechanism that relies on the differential stabilities of the toxin and antitoxin proteins and leads to the killing of daughter bacteria that did not receive a plasmid copy at the cell division. ParE is the toxic component of a TA system that constitutes along with RelE an important class of bacterial toxin called RelE/ParE superfamily. For ParE toxin, no crystallographic structure is available so far and rare in vitro studies demonstrated that the target of toxin activity is E. coli DNA gyrase. Here, a 3D Model for E. coli ParE toxin by molecular homology modeling was built using MODELLER, a program for comparative modeling. The Model was energy minimized by CHARMM and validated using PROCHECK and VERIFY3D programs. Resulting Ramachandran plot analysis it was found that the portion residues failing into the most favored and allowed regions was 96.8%. Structural similarity search employing DALI server showed as the best matches RelE and YoeB families. The Model also showed similarities with other microbial ribonucleases but in a small score. A possible homologous deep cleft active site was identified in the Model using CASTp program. Additional studies to investigate the nuclease activity in members of ParE family as well as to confirm the inhibitory replication activity are needed. The predicted Model allows initial inferences about the unexplored 3D structure of the ParE toxin and may be further used in rational design of molecules for structure­function studies. PMID:20975905

  5. The ratio of transmitted near-infrared radiation to photosynthetically active radiation (PAR) increases in proportion to the adsorbed PAR in the canopy.

    PubMed

    Kume, Atsushi; Nasahara, Kenlo N; Nagai, Shin; Muraoka, Hiroyuki

    2011-01-01

    The daily total photosynthetically active radiation (400-700 nm, PAR) and near-infrared radiation (700-1000 nm, NIR) were measured in the understory beneath the canopy (PARt and NIRt) and above the canopy (PARi and NIRi) of a Japanese cool-temperate deciduous broad-leaved forest during the snow-free period (May to November). The integration of spectral radiation for NIR and that for PAR, and the daily integrations of instantaneous NIR and PAR, reduced the noises from the optical difference in spectrum and from canopy structure heterogeneity, sky condition and solar elevation. PARi/PARt was linearly related to NIRt/PARt (R² = 0.96). The effect of cloudiness was negligible, because the fluctuation of NIRi/PARi was quite small regardless of season and weather conditions compared with the range of NIRt/PARt in the forest. The ratio of NIRt/PARt beneath the canopy was log-linearly related to the in situ leaf area index (LAI) with a wide range from 0 to 5.25 (R² = 0.97). We conclude that seasonal changes in fAPAR (= 1 - PARt/PARi) and LAI of a canopy can be estimated with high accuracy by transmitted NIRt and PARt beneath the canopy.

  6. Outsourcing CO2 Emissions

    NASA Astrophysics Data System (ADS)

    Davis, S. J.; Caldeira, K. G.

    2009-12-01

    CO2 emissions from the burning of fossil fuels are the primary cause of global warming. Much attention has been focused on the CO2 directly emitted by each country, but relatively little attention has been paid to the amount of emissions associated with consumption of goods and services in each country. This consumption-based emissions inventory differs from the production-based inventory because of imports and exports of goods and services that, either directly or indirectly, involved CO2 emissions. Using the latest available data and reasonable assumptions regarding trans-shipment of embodied carbon through third-party countries, we developed a global consumption-based CO2 emissions inventory and have calculated associated consumption-based energy and carbon intensities. We find that, in 2004, 24% of CO2 emissions are effectively outsourced to other countries, with much of the developed world outsourcing CO2 emissions to emerging markets, principally China. Some wealthy countries, including Switzerland and Sweden, outsource over half of their consumption-based emissions, with many northern Europeans outsourcing more than three tons of emissions per person per year. The United States is both a big importer and exporter of emissions embodied in trade, outsourcing >2.6 tons of CO2 per person and at the same time as >2.0 tons of CO2 per person are outsourced to the United States. These large flows indicate that CO2 emissions embodied in trade must be taken into consideration when considering responsibility for increasing atmospheric greenhouse gas concentrations.

  7. K-Area and Par Pond Sewage Sludge Application Sites groundwater monitoring reports, second quarter 1992

    SciTech Connect

    Not Available

    1992-10-01

    During second quarter 1992, the three wells at the K-Area Sewage Sludge Application Site (KSS wells) and the three wells at the Par Pond Sewage Sludge Application Site (PSS wells) were sampled for analyses required each quarter or annually by South Carolina Department of Health and Environmental Control Construction Permit 13, 173. This report includes the results of those analyses. None of the analyzed constituents exceeded the Primary Drinking Water Standard or the Savannah River Site Flag 2 criteria at either the K-Area Sewage Sludge Application Site or the Par Pond Sewage Sludge Application Site.

  8. Air Emission Inventory for the INEEL -- 1999 Emission Report

    SciTech Connect

    Zohner, Steven K

    2000-05-01

    This report presents the 1999 calendar year update of the Air Emission Inventory for the Idaho National Engineering and Environmental Laboratory (INEEL). The INEEL Air Emission Inventory documents sources and emissions of nonradionuclide pollutants from operations at the INEEL. The report describes the emission inventory process and all of the sources at the INEEL, and provides nonradionuclide emissions estimates for stationary sources.

  9. Emission properties of explosive field emission cathodes

    SciTech Connect

    Roy, Amitava; Patel, Ankur; Menon, Rakhee; Sharma, Archana; Chakravarthy, D. P.; Patil, D. S.

    2011-10-15

    The research results of the explosive field emission cathode plasma expansion velocity and the initial emission area in the planar diode configuration with cathodes made of graphite, stainless steel, polymer velvet, carbon coated, and carbon fiber (needle type) cathodes are presented. The experiments have been performed at the electron accelerator LIA-200 (200 kV, 100 ns, and 4 kA). The diode voltage has been varied from 28-225 kV, whereas the current density has been varied from 86-928 A/cm{sup 2} with 100 ns pulse duration. The experimentally obtained electron beam diode perveance has been compared with the 1 dimensional Child-Langmuir- law. It was found that initially only a part of the cathode take part in the emission process. The plasma expands at 1.7-5.2 cm/{mu}s for 4 mm anode-cathode gap for various cathode materials. It was found that the plasma expansion velocity increases with the decrease in the cathode diameter. At the beginning of the accelerating pulse, the entire cathode area participates in the electron emission process only for the multiple needle type carbon fiber cathode.

  10. Emission Standards for Particulates

    ERIC Educational Resources Information Center

    Walsh, George W.

    1974-01-01

    Promulgation of standards of performance under Section 111 and national emission standards for hazardous pollutants under Section 112 of the Clean Air Act is the responsibility of the Emission Standards and Engineering Division of the Environmental Protection Agency. The problems encountered and the bases used are examined. (Author/BT)

  11. Database of emission lines

    NASA Astrophysics Data System (ADS)

    Binette, L.; Ortiz, P.; Joguet, B.; Rola, C.

    1998-11-01

    A widely accessible data bank (available through Netscape) and consiting of all (or most) of the emission lines reported in the litterature is being built. It will comprise objects as diverse as HII regions, PN, AGN, HHO. One of its use will be to define/refine existing diagnostic emission line diagrams.

  12. Emission Standards for Particulates

    ERIC Educational Resources Information Center

    Walsh, George W.

    1974-01-01

    Promulgation of standards of performance under Section 111 and national emission standards for hazardous pollutants under Section 112 of the Clean Air Act is the responsibility of the Emission Standards and Engineering Division of the Environmental Protection Agency. The problems encountered and the bases used are examined. (Author/BT)

  13. Diesel Emissions Quantifier (DEQ)

    EPA Pesticide Factsheets

    .The Diesel Emissions Quantifier (Quantifier) is an interactive tool to estimate emission reductions and cost effectiveness. Publications EPA-420-F-13-008a (420f13008a), EPA-420-B-10-035 (420b10023), EPA-420-B-10-034 (420b10034)

  14. Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

    PubMed

    Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

    2015-04-20

    During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs.

  15. Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.

    PubMed

    Roll, Patrice; Vernes, Sonja C; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E; Szepetowski, Pierre

    2010-12-15

    It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders.

  16. The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity.

    PubMed

    Pegtel, D Michiel; Ellenbroek, Saskia I J; Mertens, Alexander E E; van der Kammen, Rob A; de Rooij, Johan; Collard, John G

    2007-10-09

    The establishment and maintenance of cell polarity is crucial for many biological functions and is regulated by conserved protein complexes. The Par polarity complex consisting of Par3, Par6, and PKCzeta, in conjunction with Tiam1-mediated Rac signaling, controls apical-basal cell polarity in contacting epithelial cells. Here we tested the hypothesis that the Par complex, in conjunction with Tiam1, controls "front-rear" polarity during the persistent migration of freely migrating keratinocytes. Wild-type (WT) epidermal keratinocytes lacking cell-cell contacts are stably front-rear polarized and migrate persistently. In contrast, Tiam1-deficient (Tiam1 KO) and (si)Par3-depleted keratinocytes are generally unpolarized and migrate randomly because front-rear polarity is short lived. Immunoprecipitation experiments show that in migrating keratinocytes, Tiam1 associates with Par3 and PKCzeta. Moreover, Par3, PKCzeta, and Tiam1 proteins are enriched at the leading edges of polarized keratinocytes. Tiam1 KO keratinocytes are impaired in chemotactic migration toward growth factors, whereaes haptotactic migration is similar to WT. Par3 depletion or the blocking of PKCzeta signaling in WT keratinocytes impairs chemotaxis but has no additional effect on Tiam1 KO cells. The migratory and morphological defects in keratinocytes with impaired Par-Tiam1 function closely resemble cells with pharmacologically destabilized microtubules (MTs). Indeed, MTs in Tiam1 KO keratinocytes and WT cells treated with a PKCzeta inhibitor are unstable, thereby negatively influencing directional but not random migration. We conclude that the Par-Tiam1 complex stabilizes front-rear polarization of noncontacting migratory cells, thereby stimulating persistent and chemotactic migration, whereas in contacting keratinocytes, the same complex controls the establishment of long-lasting apical-basal polarity. These findings underscore a remarkable flexibility of the Par polarity complex that, depending on

  17. Vibrio cholerae ParE2 Poisons DNA Gyrase via a Mechanism Distinct from Other Gyrase Inhibitors*

    PubMed Central

    Yuan, Jie; Sterckx, Yann; Mitchenall, Lesley A.; Maxwell, Anthony; Loris, Remy; Waldor, Matthew K.

    2010-01-01

    DNA gyrase is an essential bacterial enzyme required for the maintenance of chromosomal DNA topology. This enzyme is the target of several protein toxins encoded in toxin-antitoxin (TA) loci as well as of man-made antibiotics such as quinolones. The genome of Vibrio cholerae, the cause of cholera, contains three putative TA loci that exhibit modest similarity to the RK2 plasmid-borne parDE TA locus, which is thought to target gyrase although its mechanism of action is uncharacterized. Here we investigated the V. cholerae parDE2 locus. We found that this locus encodes a functional proteic TA pair that is active in Escherichia coli as well as V. cholerae. ParD2 co-purified with ParE2 and interacted with it directly. Unlike many other antitoxins, ParD2 could prevent but not reverse ParE2 toxicity. ParE2, like the unrelated F-encoded toxin CcdB and quinolones, targeted the GyrA subunit and stalled the DNA-gyrase cleavage complex. However, in contrast to other gyrase poisons, ParE2 toxicity required ATP, and it interfered with gyrase-dependent DNA supercoiling but not DNA relaxation. ParE2 did not bind GyrA fragments bound by CcdB and quinolones, and a set of strains resistant to a variety of known gyrase inhibitors all exhibited sensitivity to ParE2. Together, our findings suggest that ParE2 and presumably its many plasmid- and chromosome-encoded homologues inhibit gyrase in a different manner than previously described agents. PMID:20952390

  18. 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers.

    PubMed

    Persson, Morten; Madsen, Jacob; Østergaard, Søren; Ploug, Michael; Kjaer, Andreas

    2012-05-01

    The urokinase-type plasminogen activator receptor (uPAR) is a well-established biomarker for tumor aggressiveness and metastatic potential. DOTA-AE105 and DOTA-AE105-NH(2) labeled with (64)Cu have previously been demonstrated to be able to noninvasively monitor uPAR expression using positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce (68)Ga-DOTA-AE105-NH(2) and (68)Ga-NODAGA-AE105-NH(2) and evaluate their imaging properties using small-animal PET. Synthesis of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) was based on solid-phase peptide synthesis protocols using the Fmoc strategy. (68)GaCl(3) was eluted from a (68)Ge/(68)Ga generator. The eluate was either concentrated on a cation-exchange column or fractionated and used directly for labeling. For in vitro characterization of both tracers, partition coefficient, buffer and plasma stability, uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft. In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated peptides and identical to AE105. Labeling of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) with (68)Ga was done at 95°C and room temperature, respectively. The highest radiochemical yield and purity were obtained using fractionated elution, whereas a negative effect of acetone on labeling efficiency for NODAGA-AE105-NH(2) was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min postinjection and 2.0% ID/g and 1.1% ID/g 60 min postinjection for (68)Ga-NODAGA-AE105-NH(2) and (68)Ga-DOTA-AE105-NH(2), respectively. A significantly higher tumor-to-muscle ratio (P<.05) was found for (68)Ga

  19. Observed Barium Emission Rates

    NASA Technical Reports Server (NTRS)

    Stenbaek-Nielsen, H. C.; Wescott, E. M.; Hallinan, T. J.

    1993-01-01

    The barium releases from the CRRES satellite have provided an opportunity for verifying theoretically calculated barium ion and neutral emission rates. Spectra of the five Caribbean releases in the summer of 1991 were taken with a spectrograph on board a U.S. Air Force jet aircraft. Because the line of sight release densities are not known, only relative rates could be obtained. The observed relative rates agree well with the theoretically calculated rates and, together with other observations, confirm the earlier detailed theoretical emission rates. The calculated emission rates can thus with good accuracy be used with photometric observations. It has been postulated that charge exchange between neutral barium and oxygen ions represents a significant source for ionization. If so. it should be associated with emissions at 4957.15 A and 5013.00 A, but these emissions were not detected.

  20. Graphene field emission devices

    SciTech Connect

    Kumar, S. Raghavan, S.; Duesberg, G. S.; Pratap, R.

    2014-09-08

    Graphene field emission devices are fabricated using a scalable process. The field enhancement factors, determined from the Fowler-Nordheim plots, are within few hundreds and match the theoretical predictions. The devices show high emission current density of ∼10 nA μm{sup −1} at modest voltages of tens of volts. The emission is stable with time and repeatable over long term, whereas the noise in the emission current is comparable to that from individual carbon nanotubes emitting under similar conditions. We demonstrate a power law dependence of emission current on pressure which can be utilized for sensing. The excellent characteristics and relative ease of making the devices promise their great potential for sensing and electronic applications.

  1. Auto Emission Testing

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The photos show automobile engines being tested for nitrous oxide emissions, as required by the Environmental Protection Agency (EPA), at the Research and Engineering Division of Ford Motor Company, Dearborn. Michigan. NASA technical information helped the company develop a means of calculating emissions test results. Nitrous oxide emission readings vary with relative humidity in the test facility. EPA uses a standard humidity measurement, but the agency allows manufacturers to test under different humidity conditions, then apply a correction factor to adjust the results to the EPA standard. NASA's Dryden Flight Research Center developed analytic equations which provide a simple, computer-programmable method of correcting for humidity variations. A Ford engineer read a NASA Tech Brief describing the Dryden development and requested more detailed information in the form of a technical support package, which NASA routinely supplies to industry on request. Ford's Emissions Test Laboratory now uses the Dryden equations for humidity-adjusted emissions data reported to EPA.

  2. Synchrotron emission in air

    NASA Astrophysics Data System (ADS)

    Rafat, M. Z.; Melrose, D. B.

    2015-05-01

    A conventional astrophysical treatment of synchrotron emission is modified to include the refractive index of air, written as n = 1 + 1/(2γ 02), with γ0 ≫ 1. The angular distribution of emission by an electron with Lorentz factor γ is broadened, from a range of |θ - α| ≈ 1/γ in vacuo (θ = emission angle, α = pitch angle) to |θ - α| ≈ max{1/γ, 1/γ0} in air. The emission spectrum in air is almost unchanged from that in vacuo at sufficiently low frequencies and it is modified by extending to higher frequencies with increasing γ/γ0 < 1, and to arbitrarily high frequencies for γ/γ0 ≥ 1. We estimate the frequency at which this enhancement starts, and show that it decreases with increasing γ/γ0 > 1. We interpret the enhanced high-frequency emission as Cerenkov-like, and attribute it to the formation of caustic surfaces that sweep across the observer; we use a geometric model based on Huygens construction to support this interpretation. The geometric model predicts that the so-called Cerenkov ring present at high frequencies may be circular, elliptical, or crescent shaped. In the astrophysical treatment of synchrotron emission, the dependence on azimuthal angle is lost in the expression for emissivity. A motivation for this investigation is the application to extensive air showers, and for this purpose the loss of azimuthal dependence is a limitation. We comment on methods to overcome this limitation. We show that when an observer can see emission from inside the Cerenkov cone, emission from outside the Cerenkov cone, on either side of it, arrives simultaneously; there are three emission times for a given observation time.

  3. India Co2 Emissions

    NASA Astrophysics Data System (ADS)

    Sharan, S.; Diffenbaugh, N. S.

    2010-12-01

    Is there a way to find a balance between improving living conditions for the people on the margins and also reducing emissions while limiting our negative impacts on the climate? This is a critical question today because there are many arguments between developed and developing countries about who is responsible for global warming. Developed countries believe that it is the poor countries because they are not educated enough to know about how they are affecting the climate. While the developing countries hold wealthy nations responsible because they are using the most resources. However it is important to acknowledge the fact that if there was no gap in between the developed and developing countries our emissions total would be much higher. This “gap” has been a natural controlling factor in climate change. This is why I wanted to see if I could plot what it would look like if a developing country such as India were to produce emissions that the US or Switzerland or Norway are producing as developed countries. India has a population total of 1.1 billion compared to the US with only 298 million, Switzerland with 7.5 million, and Norway with 4.6 million people. When the population is compared to the emissions output in metric tons, per capita, India produced the least emissions out of these countries, 1.4 tons per person while having the second largest population in the world, while the US produced 19 tons per capita, Switzerland produced 5.6 and Norway produced 8.7 tons per capita in 2006. The emissions rate is growing every year and increases widely and globally. If India was producing emissions that equal Norway, Switzerland and the US the total emissions it would be producing annually would be 9 billion for Norway, 6 billion for Switzerland and 20 billion emissions for the US, all in the year 2006 alone. This shows how the balance between countries with huge populations and very little emission output and average population and high emission out put has

  4. Biogenic voc emissions development and its impacts on regional o3 in PRD, china

    NASA Astrophysics Data System (ADS)

    Wang, Xuemei; Shuping, Situ; Guenther, Alex; Chen, Fei; Wu, Zhiyong

    2010-05-01

    The new Model of Emissions of Gases and Aerosols from Nature (MEGAN) has been coupled with WRF-Chem to investigate the influence of biogenic violate organic carbon (BVOC ) emissions on the regional distribution of O3 and SOA concentration in the Pearl River Delta (PRD), China. MEGAN first estimate an emission factor which represents the net above-canopy emission rate expected at optimal conditions, and use a number of environmental correction factor based on photosynthetically activated radiation (PAR) and leaf temperature to adjust the emission rate due to deviations from optimal conditions. Total emissions are the sum of emissions estimated for each plant functional type (PFT) in a given grid cell. Our model simulations estimated showed: (1) Total annual BVOCs emissions were 339.01× 106 kg, which is 40.68% of annual AVOCs emissions and 28.91% of total VOCs emission in PRD in 2006. Isoprene, monoterpene, sesquiterpene and OVOCs contributed about 31.94%, 39.23%, 3.27% and 25.56% of the estimated total annual emissions respectively. α- pinene and β- pinene were the major components in monoterpene, which contributed 28.09% and 26.98% to the total annual monoterpene emissions respectively;β-caryophyllene andα-farnesene were two important sesquiterpene, and they contributed to 22.31% and 18.76% of the annual sesquiterpene emissions.(2) BVOCs emissions have large variations in their spatial distributions, which were mainly resulted from the differences in the geographical distribution of vegetation. Their emission amounts were larger in the places where urbanization were relative lower and plants distributions were higher.(3) Emissions of terpenoids had significant annual and diurnal variations and the largest emission rate occurred at 13:00 local time while the amount of emission in summer is the largest.(4) There were significant terpenoids emission rate (≥1.21.2 kg km-2h-1) in the remote areas in PRD region where the emissions of AVOCs were low, and

  5. A Type Ib ParB Protein Involved in Plasmid Partitioning in a Gram-Positive Bacterium▿

    PubMed Central

    Yin, Ping; Li, Tai-Yuan; Xie, Mao-Hua; Jiang, Lina; Zhang, Yi

    2006-01-01

    Our current understanding of segregation of prokaryotic plasmids has been derived mainly from the study of the gram-negative bacterial plasmids. We previously reported a replicon of the cryptic plasmid from a gram-positive bacterium, Leifsonia xyli subsp. cynodontis. The replicon contains a putative plasmid partition cassette including a Walker-type ATPase followed by open reading frame 4 without sequence homologue. Here we reported that the orf4 gene was essential for maintaining the plasmid stability in L. xyli subsp. cynodontis. Furthermore, the purified orf4 protein specifically and cooperatively bound to direct repeat sequences located upstream of the parA gene in vitro, indicating that orf4 is a parB gene and that the direct repeat DNA sequences constitute a partition site, parS. The location of parS and the features of ParA and ParB proteins suggest that this plasmid partition cassette belongs to type Ib, representing the first type Ib cassette identified from a gram-positive bacterial plasmid. PMID:16997970

  6. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus.

    PubMed

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-16

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1-25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria.

  7. Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency.

    PubMed

    Yamaguchi, Maki; Kataoka, Tatsuki R; Shibayama, Takahiro; Fukuda, Akinari; Nakazawa, Atsuko; Minamiguchi, Sachiko; Sakurai, Takaki; Miyagawa-Hayashino, Aya; Yorifuji, Toru; Kasahara, Mureo; Uemoto, Shinji; Haga, Hironori

    2016-06-01

    The hepatocyte paraffin 1 (Hep Par 1) antibody is widely used as a hepatocyte marker, recognizing carbamoyl phosphate synthetase 1 (CPS1), an essential component of the urea cycle. Various missense, nonsense, and frameshift mutations occur in the CPS1 gene. In neonatal patients with homozygous CPS1 deficiency (CPS1D), urea cycle defects with resulting severe hyperammonemia can be fatal, though liver transplantation provides a complete cure for CPS1D. We performed Hep Par 1 immunostaining in the explanted livers of 10 liver transplant patients with CPS1D. Seven were negative for Hep Par 1 in the hepatocytes and the other three showed normal diffuse granular cytoplasmic staining. As expected, all three Hep Par 1-positive patients had at least one missense mutation, and all four patients who had only nonsense or frameshift mutations were Hep Par 1-negative. The other three patients were unexpectedly negative for Hep Par 1, even though each had one missense mutation. These results suggest that CPS1D can be related to the loss of Hep Par 1 reactivity due to the loss of protein production, a one amino acid substitution resulting in an abortive protein product, or both. Hep Par 1 immunohistochemistry can be used as a simple method to confirm CPS1D. © 2016 The Authors Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  8. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus

    PubMed Central

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-01

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1–25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria. PMID:28091558

  9. Crystal structure and centromere binding of the plasmid segregation protein ParB from pCXC100

    PubMed Central

    Huang, Lin; Yin, Ping; Zhu, Xing; Zhang, Yi; Ye, Keqiong

    2011-01-01

    Plasmid pCXC100 from the Gram-positive bacterium Leifsonia xyli subsp. cynodontis uses a type Ib partition system that includes a centromere region, a Walker-type ATPase ParA and a centromere-binding protein ParB for stable segregation. However, ParB shows no detectable sequence homology to any DNA-binding motif. Here, we study the ParB centromere interaction by structural and biochemical approaches. The crystal structure of the C-terminal DNA-binding domain of ParB at 1.4 Å resolution reveals a dimeric ribbon–helix–helix (RHH) motif, supporting the prevalence of RHH motif in centromere binding. Using hydroxyl radical footprinting and quantitative binding assays, we show that the centromere core comprises nine uninterrupted 9-nt direct repeats that can be successively bound by ParB dimers in a cooperative manner. However, the interaction of ParB with a single subsite requires 18 base pairs covering one immediate repeat as well as two halves of flanking repeats. Through mutagenesis, sequence specificity was determined for each position of an 18-bp subsite. These data suggest an unique centromere recognition mechanism by which the repeat sequence is jointly specified by adjacent ParB dimers bound to an overlapped region. PMID:21123191

  10. The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity

    PubMed Central

    Narayanan, Anjana S.; Reyes, Steve B.; Um, Kyongmi; McCarty, Joseph H.; Tolias, Kimberley F.

    2013-01-01

    Cell polarization is essential for many biological processes, including directed cell migration, and loss of polarity contributes to pathological conditions such as cancer. The Par complex (Par3, Par6, and PKCζ) controls cell polarity in part by recruiting the Rac-specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling. However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain cell polarity during migration remain unclear. We identify the Rac-specific GTPase-activating protein (GAP) breakpoint cluster region protein (Bcr) as a novel regulator of the Par-Tiam1 complex. We show that Bcr interacts with members of the Par complex and inhibits both Rac1 and PKCζ signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKCζ activity or by expressing full-length Bcr, but not an N-terminal deletion mutant or the homologous Rac-GAP, Abr, both of which fail to associate with the Par complex. These results demonstrate that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by locally restricting both Rac1 and PKCζ function. PMID:24152735

  11. AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway

    PubMed Central

    Dores, Michael R.; Paing, May M.; Lin, Huilan; Montagne, William A.; Marchese, Adriano; Trejo, JoAnn

    2012-01-01

    The sorting of signaling receptors within the endocytic system is important for appropriate cellular responses. After activation, receptors are trafficked to early endosomes and either recycled or sorted to lysosomes and degraded. Most receptors trafficked to lysosomes are modified with ubiquitin and recruited into an endosomal subdomain enriched in hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a ubiquitin-binding component of the endosomal-sorting complex required for transport (ESCRT) machinery, and then sorted into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)/lysosomes. However, not all receptors use ubiquitin or the canonical ESCRT machinery to sort to MVBs/lysosomes. This is exemplified by protease-activated receptor-1 (PAR1), a G protein–coupled receptor for thrombin, which sorts to lysosomes independent of ubiquitination and HRS. We recently showed that the adaptor protein ALIX binds to PAR1, recruits ESCRT-III, and mediates receptor sorting to ILVs of MVBs. However, the mechanism that initiates PAR1 sorting at the early endosome is not known. We now report that the adaptor protein complex-3 (AP-3) regulates PAR1 ubiquitin-independent sorting to MVBs through an ALIX-dependent pathway. AP-3 binds to a PAR1 cytoplasmic tail–localized tyrosine-based motif and mediates PAR1 lysosomal degradation independent of ubiquitination. Moreover, AP-3 facilitates PAR1 interaction with ALIX, suggesting that AP-3 functions before PAR1 engagement of ALIX and MVB/lysosomal sorting. PMID:22833563

  12. Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules.

    PubMed

    López-Villarejo, Juan; Diago-Navarro, Elizabeth; Hernández-Arriaga, Ana María; Díaz-Orejas, Ramón

    2012-03-01

    The coupling between the replication and parD (kis, kid) maintenance modules of R1 has been revisited here by the isolation of a significant collection of conditional replication mutants in the pKN1562 mini-R1 plasmid, and in its derivative, pJLV01, specifically affected in the RNase activity of the Kid toxin. This new analysis aims to identify key factors in this coupling. For this purpose we have quantified and characterized the restriction introduced by parD to isolate conditional replication mutants of this plasmid, a signature of the modular coupling. This restriction depends on the RNase activity of the Kid toxin and it is relieved by either over-expression of the Kis antitoxin or by preventing its degradation by Lon and ClpAP proteases. Based on these data and on the correlation between copy numbers and parD transcriptional levels obtained in the different mutants, it is proposed that a reduction of Kis antitoxin levels in response to inefficient plasmid replication is the key factor for coupling plasmid replication and parD modules.

  13. Tuberculosis prevalence and risk factors for water buffalo in Pará, Brazil.

    PubMed

    Barbosa, José D; da Silva, Jenevaldo B; Rangel, Charles P; da Fonseca, Adivaldo H; Silva, Natália S; Bomjardim, Henrique A; Freitas, Nayra F Q R

    2014-03-01

    The prevalence of and possible risk factors for tuberculosis were studied in water buffalo from Pará, Brazil. In this study, 3,917 pregnant and nonpregnant female Murrah and Mediterranean buffaloes were studied; 2,089 originated from Marajó Island, and 1,108 were from the mainland. The comparative cervical tuberculin test was used as a diagnostic test for tuberculosis in these animals. The prevalence of positive buffaloes was 3.5 % (100/2,809) on Marajó Island and 7.2 % (80/1,108) on the mainland. The municipalities with the highest tuberculosis prevalence rates in animals were Ipixuna do Pará (10.1 %), Marapanim (9.8 %), Chaves (9.4 %), Paragominas (8.6 %), and Cachoeira do Arari (6.7 %). The tuberculosis prevalence was not significantly different between the Murrah (4.3 %) and Mediterranean (4.8 %) breeds or between pregnant (5 %) and nonpregnant (4.3 %) buffaloes. Tuberculosis was detected in water buffaloes from Pará, Brazil; the mainland buffalo exhibited the highest tuberculosis prevalence. These results indicate that this disease is dangerous to public health and buffalo farming in Pará.

  14. Bilateral pars fractures complicating long fusion to L5 in a patient with rheumatoid arthritis.

    PubMed

    Mesfin, Addisu; Lemma, Mesfin A

    2011-06-01

    Case report. To report bilateral pars fractures at L5 complicating a long fusion for adult idiopathic scoliosis in a patient with rheumatoid arthritis. To our knowledge, there are no reports in the literature regarding bilateral pars fractures at the end instrumented vertebrae of a long fusion at the lumbosacral junction, nor reports that have evaluated long spinal deformity corrections in patients with rheumatoid arthritis. The question of ending a long fusion at L5 or S1 is controversial, and a review is presented. We present the patient's history, physical examination, and radiographic findings; describe the surgical treatment and long-term follow-up; and provide a literature review. Bilateral pars fractures at the end instrumented vertebrae of a long construct (T4-L5) that we discovered were subsequently revised by extension of the fusion to the sacrum. Anterior structural support at L5-S1 was also provided. At the latest follow-up (46 months), the patient has had no recurrence of her symptoms. Her radiographs showed a stable construct without loss of alignment in the sagittal or coronal planes. Her rheumatoid arthritis continues to be treated with biologic, disease-modifying antirheumatic drugs. To our knowledge, this is the first report of the treatment and long-term outcome of a patient with rheumatoid arthritis and bilateral pars fractures at the end instrumented vertebrae (L5) of a long deformity correction construct.

  15. Participation and Participatory Action Research (PAR) in Environmental Education Processes: For What Are People Empowered?

    ERIC Educational Resources Information Center

    Le Grange, Lesley

    2009-01-01

    Participatory action research (PAR) derived from anti-colonial struggles in the third world in the 1960s. Traditionally it has been a method of the margins because of its commitment to linking social justice to research. Because of its counter-hegemonic tendency it has had great appeal among environmental educators advocating a socially critical…

  16. The loss of circadian PAR bZip transcription factors results in epilepsy

    PubMed Central

    Gachon, Frédéric; Fonjallaz, Philippe; Damiola, Francesca; Gos, Pascal; Kodama, Tohru; Zakany, Jozsef; Duboule, Denis; Petit, Brice; Tafti, Mehdi; Schibler, Ueli

    2004-01-01

    DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian rhythms in tissues with high amplitudes of clock gene expression, such as the suprachiasmatic nucleus (SCN) and the liver. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. Here we show that mice deficient for all three PAR bZip proteins are highly susceptible to generalized spontaneous and audiogenic epilepsies that frequently are lethal. Transcriptome profiling revealed pyridoxal kinase (Pdxk) as a target gene of PAR bZip proteins in both liver and brain. Pyridoxal kinase converts vitamin B6 derivatives into pyridoxal phosphate (PLP), the coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism. PAR bZip-deficient mice show decreased brain levels of PLP, serotonin, and dopamine, and such changes have previously been reported to cause epilepsies in other systems. Hence, the expression of some clock-controlled genes, such as Pdxk, may have to remain within narrow limits in the brain. This could explain why the circadian oscillator has evolved to generate only low-amplitude cycles in most brain regions. PMID:15175240

  17. Participatory Action Research: Reflections on Critical Incidents in a PAR Project.

    ERIC Educational Resources Information Center

    Santelli, Betsy; Singer, George H. S.; DiVenere, Nancy; Ginsberg, Connie; Powers, Laurie E.

    1998-01-01

    This article describes a participatory action research (PAR) project designed to evaluate Parent to Parent programs in five states. The process of developing a shared understanding of the program and of the purpose for evaluating them, along with an on-going willingness of parents and researchers to compromise, led to creative solutions to…

  18. UTILITY OF A WIDE SPECTRUM LIGHT METER AS AN UNDERWATER SENSOR OF PHOTOSYNTHETICALLY ACTIVE RADIATION (PAR)

    EPA Science Inventory

    The strong attenuation of infra red wavelengths (>700 nm) in coastal waters is suggestive that some instruments with broad spectral responses might be useful, inexpensive substitutes for PAR sensors in studies of estuarine plant dynamics. Wide spectrum (350-1100 nm) light intensi...

  19. CALiPER Report 20.3: Robustness of LED PAR38 Lamps

    SciTech Connect

    none,

    2014-12-30

    A small sample of each of the CALiPER Application Summary Report 20 PAR38 lamp types underwent stress testing that included substantial temperature and humidity changes, electrical variation, and vibration. The results do not directly address expected lifetime, but can be compared with one another, as well as with benchmark conventional products, to assess the relative robustness of the product designs.

  20. The Utility of Clinicians Ratings of Anxiety Using the Pediatric Anxiety Rating Scale (PARS)

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Keeton, Courtney P.; Drazdowski, Tess K.; Riddle, Mark A.

    2011-01-01

    Clinician ratings of anxiety hold the promise of clarifying discrepancies often found between child and parent reports of anxiety. The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered instrument that assesses the frequency, severity, and impairment of common pediatric anxiety disorders and has been used as a primary outcome…

  1. The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins.

    PubMed

    Ferraris, Gian Maria Sarra; Schulte, Carsten; Buttiglione, Valentina; De Lorenzi, Valentina; Piontini, Andrea; Galluzzi, Massimiliano; Podestà, Alessandro; Madsen, Chris D; Sidenius, Nicolai

    2014-11-03

    The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure-function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin-matrix engagement. The signalling is fully active on VN mutants deficient in integrin binding site and is also efficiently transduced by integrins deficient in ligand binding. Although integrin ligation is dispensable, signalling is crucially dependent upon an active conformation of the integrin and its association with intracellular adaptors such as talin. This non-canonical integrin signalling is not restricted to uPAR as it poses no structural constraints to the receptor mediating cell attachment. In contrast to canonical integrin signalling, where integrins form direct mechanical links between the ECM and the cytoskeleton, the molecular mechanism enabling the crosstalk between non-integrin adhesion receptors and integrins is dependent upon membrane tension. This suggests that for this type of signalling, the membrane represents a critical component of the molecular clutch. © 2014 The Authors.

  2. Crystal Structure of Thrombin Bound to the Uncleaved Extracellular Fragment of PAR1

    SciTech Connect

    Gandhi, Prafull S.; Chen, Zhiwei; Di Cera, Enrico

    2010-05-11

    Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 {angstrom} resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the active site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp{sup 39}, does not hinder binding to the active site and actually makes favorable interactions with Gly{sup 219} of thrombin. The tethered ligand domain shows a considerable degree of disorder even when bound to thrombin. The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates.

  3. An Overview of the Peer Assessment Rating (par) Index for Primary Dental Care Practitioners.

    PubMed

    Green, James Ij

    2016-11-01

    The Peer Assessment Rating (PAR) index is a valid and reliable measure of orthodontic treatment outcome and is the most widely accepted such index. Assessing outcomes with the PAR index requires the examination of pre-treatment and post-treatment orthodontic study models. Beginning with the pre-treatment models, a score is given to each feature that deviates from an ideal occlusion (all anatomical contact points adjacent, good interdigitation between posterior teeth and non-excessive overjet/overbite), the scores are then added together to give a total that represents the severity of the malocclusion. The process is then repeated with the post-treatment models. The difference between the pre-treatment and the post-treatment scores reflects the improvement that has taken place during treatment. A score of zero represents an ideal occlusion and in general the higher the score, the more extensive the malocclusion. It is currently a condition of the NHS orthodontic contract for providers to monitor a proportion of their cases using the PAR index. This paper aims to provide primary dental care practitioners with an overview of the PAR index and should provide a useful guide for those wishing to seek calibration in the use of the index.

  4. Practical field methods of estimating canopy cover, PAR, and LAI in Michigan Oak and pine stands

    Treesearch

    David S. Buckley; J.G. Isebrands; Terry L. Sharik

    1999-01-01

    With the increased use of variables such as canopy cover photosynthetically active radiation (PAR) and overstory leaf area index (LAI) in forestry research, relationships between these variables and traditional forestry variables must be defined before recommended levels of these research variables can be achieved by forestry practitioners on the ground. We measured...

  5. UTILITY OF A WIDE SPECTRUM LIGHT METER AS AN UNDERWATER SENSOR OF PHOTOSYNTHETICALLY ACTIVE RADIATION (PAR)

    EPA Science Inventory

    The strong attenuation of infra red wavelengths (>700 nm) in coastal waters is suggestive that some instruments with broad spectral responses might be useful, inexpensive substitutes for PAR sensors in studies of estuarine plant dynamics. Wide spectrum (350-1100 nm) light intensi...

  6. The interaction between uPAR and vitronectin triggers ligand-independent adhesion signalling by integrins

    PubMed Central

    Ferraris, Gian Maria Sarra; Schulte, Carsten; Buttiglione, Valentina; De Lorenzi, Valentina; Piontini, Andrea; Galluzzi, Massimiliano; Podestà, Alessandro; Madsen, Chris D; Sidenius, Nicolai

    2014-01-01

    The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure–function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin–matrix engagement. The signalling is fully active on VN mutants deficient in integrin binding site and is also efficiently transduced by integrins deficient in ligand binding. Although integrin ligation is dispensable, signalling is crucially dependent upon an active conformation of the integrin and its association with intracellular adaptors such as talin. This non-canonical integrin signalling is not restricted to uPAR as it poses no structural constraints to the receptor mediating cell attachment. In contrast to canonical integrin signalling, where integrins form direct mechanical links between the ECM and the cytoskeleton, the molecular mechanism enabling the crosstalk between non-integrin adhesion receptors and integrins is dependent upon membrane tension. This suggests that for this type of signalling, the membrane represents a critical component of the molecular clutch. PMID:25168639

  7. TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells

    PubMed Central

    Smoktunowicz, Natalia; Platé, Manuela; Stern, Alejandro Ortiz; D'Antongiovanni, Vanessa; Robinson, Eifion; Chudasama, Vijay; Caddick, Stephen; Scotton, Chris J.; Jarai, Gabor; Chambers, Rachel C.

    2016-01-01

    The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an αvβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2- and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin αv and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer. PMID:27566553

  8. Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles

    ERIC Educational Resources Information Center

    Johnson, Craig W.; Johnson, Ronald; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.

    2016-01-01

    Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt,…

  9. Highest integration in microelectronics: Development of digital ASICs for PARS3-LR

    NASA Astrophysics Data System (ADS)

    Scholler, Peter; Vonlutz, Rainer

    Essential electronic system components by PARS3-LR, show high requirements in calculation power, power consumption and reliability, by immediately increasing integration thicknesses. These problems are solved by using integrated circuits, developed by LSI LOGIC, that uses the technical and economic advantages of this leading edge technology.

  10. Measurement of the topography of human cadaver lenses using the PAR corneal topography system

    NASA Astrophysics Data System (ADS)

    Fernandez, Viviana; Manns, Fabrice; Zipper, Stanley; Sandadi, Samith; Hamaoui, Marie; Tahi, Hassan; Ho, Arthur; Parel, Jean-Marie A.

    2001-06-01

    To measure the radius of curvature and asphericity of the anterior and posterior surfaces of crystalline lenses of human Eye-Bank eyes using the PAR Corneal Topography System. The measured values will be used in an optical model of the eye for lens refilling procedures.

  11. Participation and Participatory Action Research (PAR) in Environmental Education Processes: For What Are People Empowered?

    ERIC Educational Resources Information Center

    Le Grange, Lesley

    2009-01-01

    Participatory action research (PAR) derived from anti-colonial struggles in the third world in the 1960s. Traditionally it has been a method of the margins because of its commitment to linking social justice to research. Because of its counter-hegemonic tendency it has had great appeal among environmental educators advocating a socially critical…

  12. The Utility of Clinicians Ratings of Anxiety Using the Pediatric Anxiety Rating Scale (PARS)

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Keeton, Courtney P.; Drazdowski, Tess K.; Riddle, Mark A.

    2011-01-01

    Clinician ratings of anxiety hold the promise of clarifying discrepancies often found between child and parent reports of anxiety. The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered instrument that assesses the frequency, severity, and impairment of common pediatric anxiety disorders and has been used as a primary outcome…

  13. Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division

    PubMed Central

    Jordan, Shawn N.; Davies, Tim; Zhuravlev, Yelena; Dumont, Julien; Shirasu-Hiza, Mimi

    2016-01-01

    Cytokinesis, the physical division of one cell into two, is thought to be fundamentally similar in most animal cell divisions and driven by the constriction of a contractile ring positioned and controlled solely by the mitotic spindle. During asymmetric cell divisions, the core polarity machinery (partitioning defective [PAR] proteins) controls the unequal inheritance of key cell fate determinants. Here, we show that in asymmetrically dividing Caenorhabditis elegans embryos, the cortical PAR proteins (including the small guanosine triphosphatase CDC-42) have an active role in regulating recruitment of a critical component of the contractile ring, filamentous actin (F-actin). We found that the cortical PAR proteins are required for the retention of anillin and septin in the anterior pole, which are cytokinesis proteins that our genetic data suggest act as inhibitors of F-actin at the contractile ring. Collectively, our results suggest that the cortical PAR proteins coordinate the establishment of cell polarity with the physical process of cytokinesis during asymmetric cell division to ensure the fidelity of daughter cell formation. PMID:26728855

  14. Dengue epidemic in Belém, Pará, Brazil, 1996-97.

    PubMed Central

    Trravassos da Rosa, A. P.; Vasconcelos, P. F.; Travassos Da Rosa, E. S.; Rodrigues, S. G.; Mondet, B.; Cruz, A. C.; Sousa, M. R.; Travassos Da Rosa, J. F.

    2000-01-01

    We describe clinical and epidemiologic findings during the first epidemic of dengue fever in Belém, Pará State, Brazil, in 1996-97. Of 40,237 serum samples, 17,440 (43%) were positive for dengue by virus isolation or serologic testing. No hemorrhagic cases or deaths were reported. Mycobacterium tuberculosis PMID:10827121

  15. Leuconychie transversale induite par la manucurie: y a-t-il un apport de la dermoscopie?

    PubMed Central

    Gallouj, Salim; Mernissi, Fatima Zahra

    2014-01-01

    La leuconychie transversale induite par la manucurie est une leuconychie secondaire au microtraumatisme transmis à la matrice unguéale. Nous rapportant une observation où la dermoscopie avait un intérêt considérable pour l'orientation diagnostic. PMID:25368728

  16. Participatory Action Research: Reflections on Critical Incidents in a PAR Project.

    ERIC Educational Resources Information Center

    Santelli, Betsy; Singer, George H. S.; DiVenere, Nancy; Ginsberg, Connie; Powers, Laurie E.

    1998-01-01

    This article describes a participatory action research (PAR) project designed to evaluate Parent to Parent programs in five states. The process of developing a shared understanding of the program and of the purpose for evaluating them, along with an on-going willingness of parents and researchers to compromise, led to creative solutions to…

  17. Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles

    ERIC Educational Resources Information Center

    Johnson, Craig W.; Johnson, Ronald; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.

    2016-01-01

    Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt,…

  18. [Attenuation of photosynthetically available radiation (PAR) in Meiliang Bay under different winds and waves].

    PubMed

    Zhang, Yunlin; Qin, Boqiang; Chen, Weimin; Hu, Weiping; Gao, Guang; Zhu, Guangwei; Luo, Liancong

    2005-06-01

    Based on the successive underwater irradiance measurement in situ from Jul. 12 to 17 in 2003, the attenuation of photosynthetically available radiation (PAR) and euphotic depth in Meiliang Bay were analyzed under different winds and waves. The results showed that the downward PAR attenuation coefficients ranged from 2.63 to 4.7 m(-1), with an average of 3.63 +/- 0.47 x m(-1), and the corresponding euphotic depth ranged from 0.98 to 1.75 m, with an average of 1.29 +/- 0.18 m, which demonstrated that phytoplankton and macrophyte could not grow below 1.5 m due to the lack of adequate solar radiation. The total suspended solids resulted from wind and wave increased the attenuation of light, with the downward attenuation coefficients of PAR being 2.63, 3.72 and 4.37 x m(-1) under small, medium and large wind and wave, respectively. Significant linear correlations were found between transparence, PAR attenuation coefficient, euphotic depth and total suspended solid, especially inorganic suspended solid, while chlorophyll a was the most nonsignificant light attenuator. Multiple stepwise linear regressions showed that inorganic suspended solid was the most important light attenuator dominating the light attenuation in wind-exposed Meiliang Bay.

  19. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells

    PubMed Central

    Sarkar, Shayan; Jain, Sumeet; Rai, Vineeta; Sahoo, Dipak K.; Raha, Sumita; Suklabaidya, Sujit; Senapati, Shantibhusan; Rangnekar, Vivek M.; Maiti, Indu B.; Dey, Nrisingha

    2015-01-01

    The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT), apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era. PMID:26500666

  20. Project Plan 7930 Cell G PaR Remote Handling System Replacement

    SciTech Connect

    Kinney, Kathryn A

    2009-10-01

    For over 40 years the US Department of Energy (DOE) and its predecessors have made Californium-252 ({sup 252}Cf) available for a wide range of industries including medical, nuclear fuels, mining, military and national security. The Radiochemical Engineering Development Center (REDC) located within the Oak Ridge National Laboratory (ORNL) processes irradiated production targets from the High Flux Isotope Reactor (HFIR). Operations in Building 7930, Cell G provide over 70% of the world's demand for {sup 252}Cf. Building 7930 was constructed and equipped in the mid-1960s. Current operations for {sup 252}Cf processing in Building 7930, Cell G require use of through-the-wall manipulators and the PaR Remote Handling System. Maintenance and repairs for the manipulators is readily accomplished by removal of the manipulator and relocation to a repair shop where hands-on work can be performed in glove boxes. Contamination inside cell G does not currently allow manned entry and no provisions were created for a maintenance area inside the cell. There has been no maintenance of the PaR system or upgrades, leaving operations vulnerable should the system have a catastrophic failure. The Cell G PaR system is currently being operated in a run to failure mode. As the manipulator is now 40+ years old there is significant risk in this method of operation. In 2006 an assessment was completed that resulted in recommendations for replacing the manipulator operator control and power centers which are used to control and power the PaR manipulator in Cell G. In mid-2008 the chain for the bridge drive failed and subsequent examinations indicated several damaged links (see Figure 1). To continue operations the PaR manipulator arm is being used to push and pull the bridge as a workaround. A retrieval tool was fabricated, tested and staged inside Cell G that will allow positioning of the bridge and manipulator arm for removal from the cell should the PaR system completely fail. A fully

  1. La structure de l'eau liquide: Une etude thermique par spectroscopie infrarouge

    NASA Astrophysics Data System (ADS)

    Larouche, Pascal

    Le probleme de la structure de l'eau liquide est important car l'eau est le liquide le plus present sur Terre, et complexe, la quete d'un modele precis pour decrire comment fonctionne ce liquide ayant debute des la fin du dix-neuvieme siecle. Cette etude aborde ce probleme en etudiant l'effet de l'augmentation de la temperature sur H2O et D 2O purs a l'aide de la spectroscopie infrarouge. L'intervalle de temperatures scrute est 29--93.1°C. Les spectres enregistres sont des spectres MIR-ATR entre 650 et 6000 cm-1 . L'analyse par facteurs de ces donnees permet de montrer que deux et seulement deux facteurs principaux sont necessaires pour decomposer tous les spectres experimentaux. Ces resultats sont confirmes grace a l'analyse par facteurs de spectres de la region FIR. Par la suite, la transformation en spectres de la partie reelle n et imaginaire k de l'indice de refraction permet de combiner les donnees des regions MIR et FIR. Une fois ce calcul termine, les spectres de transmission complets de H 2O et D2O entre 25 et 90°C sont connus. Ils sont ensuite utilises pour calculer par extrapolation le spectre des especes constituant l'eau liquide, puis leur abondance en fonction de la temperature. L'extrapolation de ces abondances montre que les especes correspondent a des temperatures limites de --18 et 122°C. Par la suite, la decomposition gaussienne des spectres d'especes met en evidence la riche structure de ces objets et permet de demontrer que l'apparent deplacement du massif d'absorption OH (OD) est produit par une variation de l'intensite des bandes et non pas de leur deplacement. L'examen attentif des spectres des especes prouve qu'il n'y a pas de OH libres crees par l'augmentation de la temperature: meme a 93.1°C, chaque molecule possede quatre liens-H. Ces conclusions sont de plus confirmees par une analyse thermodynamique du passage des molecules de la phase solide a la phase gazeuse. Pour diversifier la nature des resultats experimentaux utilises, des

  2. ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data

    DOE PAGES

    Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S.; ...

    2017-02-23

    Here, a newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides,more » important for metal extraction chemistry, are parametrized using ParFit.« less

  3. Water quality, phytoplankton and zooplankton of Par Pond and Pond B. Volume 2. Phytoplankton. Final report, January 1984-June 1985

    SciTech Connect

    Chimney, M.J.; Cody, W.R.; Starkel, W.M.

    1985-08-01

    This document reports on the Par Pond and Pond B phytoplankton community. The objectives of this study were to (1) characterize the biological communities and environmental conditions in Par Pond and Pond B; (2) assess the impact and significance of entrainment losses of plankton at the Par Pond pumphouse; (3) assess the impact of heated discharge on the biotic communities throughout the reservoir; and (4) help determine if Par Pond maintains an indigenous balanced biological community as defined in state and federal regulations. A total of 368 phytoplankton taxa, representing all the major taxonomic groups characteristic of North American freshwaters, were identified from Par Pond and Pond B during this study (73 Bacillariophyta, 166 Chlorophyta, 30 Chrysophyta, 5 Cryptophyta, 47 Cyanophyta, 18 Euglenophyta, 11 phytoflaggelates and 18 Pyrrophyta).

  4. Locating the Vehicle Emissions Label

    EPA Pesticide Factsheets

    The EPA vehicle emissions label is entitled Vehicle Emission Control Information and contains the name and trademark of the manufacturer and an unconditional statement of compliance with EPA emission regulations.

  5. Biogenic Emission Inventory System (BEIS)

    EPA Pesticide Factsheets

    Biogenic Emission Inventory System (BEIS) estimates volatile organic compound (VOC) emissions from vegetation and nitric oxide (NO) emission from soils. Recent BEIS development has been restricted to the SMOKE system

  6. Vehicle and Fuel Emissions Testing

    EPA Pesticide Factsheets

    EPA's National Vehicle and Fuel Emissions Laboratory's primary responsibilities include: evaluating emission control technology; testing vehicles, engines and fuels; and determining compliance with federal emissions and fuel economy standards.

  7. Managing Air Quality - Emissions Inventories

    EPA Pesticide Factsheets

    This page describes the role of emission inventories in the air quality management process, a description of how emission inventories are developed, and where U.S. emission inventory information can be found.

  8. MOVES2014: Evaporative Emissions Report

    EPA Science Inventory

    Vehicle evaporative emissions are now modeled in EPA’s MOVES according to physical processes, permeation, tank vapor venting, liquid leaks, and refueling emissions. With this update, the following improvements are being incorporated into MOVES evaporative emissions methodology, a...

  9. MOVES2014: Evaporative Emissions Report

    EPA Science Inventory

    Vehicle evaporative emissions are now modeled in EPA’s MOVES according to physical processes, permeation, tank vapor venting, liquid leaks, and refueling emissions. With this update, the following improvements are being incorporated into MOVES evaporative emissions methodology, a...

  10. Emission Abatement System

    DOEpatents

    Bromberg, Leslie; Cohn, Daniel R.; Rabinovich, Alexander

    2003-05-13

    Emission abatement system. The system includes a source of emissions and a catalyst for receiving the emissions. Suitable catalysts are absorber catalysts and selective catalytic reduction catalysts. A plasma fuel converter generates a reducing gas from a fuel source and is connected to deliver the reducing gas into contact with the absorber catalyst for regenerating the catalyst. A preferred reducing gas is a hydrogen rich gas and a preferred plasma fuel converter is a plasmatron. It is also preferred that the absorber catalyst be adapted for absorbing NO.sub.x.

  11. Posterior assisted levitation (PAL) by using Akahoshi/Wahab irrigating pars plana levitator.

    PubMed

    Wahab, Shahid; Ahmed, Jamshed; Das Hargun, Lakhani

    2012-11-01

    To assess the outcome of irrigating Akahoshi/Wahab pars plana levitator for posterior assisted levitation in dropped nucleus during phacoemulsification. A case series. Ophthalmology Unit-III, Dow University of Health Sciences at Sindh Government Lyari General Hospital and Al-Noor Eye Hospital, Karachi, from January 2008 to December 2009. Cases of dropped nucleus during phacoemulsification were recruited. Predisposing factors and stage of phacoemulsification at which dropped nucleus were recognized. Levitator was inserted through pars plana after vitrectomy around nucleus and levitation was carried out. Follow-up was done till 6 months. Thirty two patients including 18 males (56.3%) and 14 females (43.8%) underwent pars plana levitation. Predisposing factors were pupillary miosis in 9 cases, Brunescent cataract in 7 cases, pseudoexfoliation in another 7 cases, hypermature cataract in 5 cases and extended capsulorrhexis in 4 cases. Posterior capsular rent occurred in 22 (68.8%) cases while zonular dehiscence / rupture were found in 10 cases (31.3%). Nuclei were dropped during quadrant aspiration in 10 cases (31.3%) and during chopping in 8 cases (25%). Another 5 cases (15.6%) occurred during each hydrodissection and chopping while 4 cases (12.5%) were found during sculpting of nuclei. Final best corrected visual acuity was 6/12 and better in 22 cases (68.8%) while in 10 cases (31.3%) it was 6/18 to 6/36. No complication related to pars plana levitator was observed. Posterior assisted levitation of dropped nucleus during phacoemulsification by irrigating Akahoshi/Wahab pars plana levitator is a fast and safe surgical technique.

  12. PAR2 exerts local protection against acute pancreatitis via modulation of MAP kinase and MAP kinase phosphatase signaling.

    PubMed

    Namkung, Wan; Yoon, Jae Seok; Kim, Kyung Hwan; Lee, Min Goo

    2008-11-01

    During acute pancreatitis, protease-activated receptor 2 (PAR2) can be activated by interstitially released trypsin. In the mild form of pancreatitis, PAR2 activation exerts local protection against intrapancreatic damage, whereas, in the severe form of pancreatitis, PAR2 activation mediates some systemic complications. This study aimed to identify the molecular mechanisms of PAR2-mediated protective effects against intrapancreatic damage. A mild form of acute pancreatitis was induced by an intraperitoneal injection of caerulein (40 microg/kg) in rats. Effects of PAR2 activation on intrapancreatic damage and on mitogen-activated protein (MAP) kinase signaling were assessed. Caerulein treatment activated extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) within 15 min and maintained phosphorylation of ERK and JNK for 2 h in the rat pancreas. Although PAR2 activation by the pretreatment with PAR2-activating peptide (AP) itself increased ERK phosphorylation in rat pancreas, the same treatment remarkably decreased caerulein-induced activation of ERK and JNK principally by accelerating their dephosphorylation. Inhibition of ERK and JNK phosphorylation by the pretreatment with MAP/ERK kinase (MEK) or JNK inhibitors decreased caerulein-induced pancreatic damage that was similar to the effect induced by PAR2-AP. Notably, in caerulein-treated rats, PAR2-AP cotreatment highly increased the expression of a group of MAP kinase phosphatases (MKPs) that deactivate ERK and JNK. The above results imply that downregulation of MAP kinase signaling by MKP induction is a key mechanism involved in the protective effects of PAR2 activation on caerulein-induced intrapancreatic damage.

  13. The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo

    PubMed Central

    Grace, M S; Lieu, T; Darby, B; Abogadie, F C; Veldhuis, N; Bunnett, N W; McIntyre, P

    2014-01-01

    BACKGROUND AND PURPOSE Protease-activated receptor 2 (PAR2) is expressed on nociceptive neurons, and can sensitize transient receptor potential (TRP) ion channels to amplify neurogenic inflammation and pain. The mechanisms by which this occurs are not fully understood. PAR2 causes receptor-operated activation of TRPV4 channels and TRPV4 null mice have attenuated PAR2-stimulated neurogenic inflammation and mechanical hyperalgesia. Here we investigate the intracellular signalling mechanisms underlying PAR2-induced TRPV4 channel activation and pain. EXPERIMENTAL APPROACH Responses of non-transfected and TRPV4-transfected HEK293 cells to agonists of PAR2 (trypsin and SLIGRL) and TRPV4 channels (GSK1016790A) were determined using calcium imaging. Inhibitors of TRPV4 channels (HC067047), sarcoendoplasmic reticulum calcium transport ATPase (thapsigargin), Gαq (UBO-QIC), tyrosine kinases (bafetinib and dasatinib) or PI3 kinases (wortmannin and LY294002) were used to investigate signalling mechanisms. In vivo effects of tyrosine kinase inhibitors on PAR2-induced mechanical hyperalgesia were assessed in mice. KEY RESULTS In non-transfected HEK293 cells, PAR2 activation transiently increased intracellular calcium ([Ca2+]i). Functional expression of TRPV4 channels caused a sustained increase of [Ca2+]i, inhibited by HC067047, bafetinib and wortmannin; but not by thapsigargin, UBO-QIC, dasatinib or LY294002. Bafetinib but not dasatinib inhibited PAR2-induced mechanical hyperalgesia in vivo. CONCLUSIONS AND IMPLICATIONS This study supports a role for tyrosine kinases in PAR2-mediated receptor-operated gating of TRPV4 channels, independent of Gαq stimulation. The ability of a tyrosine kinase inhibitor to diminish PAR2-induced activation of TRPV4 channels and consequent mechanical hyperalgesia identifies bafetinib (which is in development in oncology) as a potential novel analgesic therapy. PMID:24779362

  14. Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint

    PubMed Central

    Russell, FA; Schuelert, N; Veldhoen, VE; Hollenberg, MD; McDougall, JJ

    2012-01-01

    Background and Purpose The PAR2 receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR2 activation in the rat knee joint. Experimental Approach PAR2 in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR2 with its activating peptide, 2-furoyl-LIGRLO-NH2 (1–100 nmol·100 μL−1, via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR2 activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR2 activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH2 or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK1) receptors in the PAR2 responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. Key Results PAR2 were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH2 increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH2 also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH2 alone). Conclusions and Implications PAR2 receptors play an acute inflammatory role in the knee joint via TRPV1- and NK1-dependent mechanisms involving both PAR2-mediated neuronal sensitization and leukocyte trafficking. PMID:22849826

  15. Taxonomy, Traits, and Environment Determine Isoprenoid Emission from an Evergreen Tropical forest.

    NASA Astrophysics Data System (ADS)

    Taylor, T.; Alves, E. G.; Tota, J.; Oliveira Junior, R. C.; Camargo, P. B. D.; Saleska, S. R.

    2016-12-01

    Volatile isoprenoid emissions from the leaves of tropical forest trees significantly affects atmospheric chemistry, aerosols, and cloud dynamics, as well as the physiology of the emitting leaves. Emission is associated with plant tolerance to heat and drought stress. Despite a potentially central role of isoprenoid emissions in tropical forest-climate interactions, we have a poor understanding of the relationship between emissions and ecological axes of forest function. We used a custom instrument to quantify leaf isoprenoid emission rates from over 200 leaves and 80 trees at a site in the eastern Brazilian Amazon. We related standardized leaf emission capacity (EC: leaf emission rate at 1000 PAR) to tree taxonomy, height, light environment, wood traits, and leaf traits. Taxonomy was the strongest predictor of EC, and non-emitters could be found throughout the canopy. But we found that environment and leaf carbon economics constrained the upper bound of EC. For example, the relationship between EC and specific leaf area (SLA; fresh leaf area / dry mass) is described by an envelope with a decreasing upper bound on EC as SLA increases (quantile regression: 85th quantile, p<0.01). That result suggests a limitation on emissions related to leaf carbon investment strategies. EC was highest in the mid-canopy, and in leaves growing under less direct light. While inferences of ecosystem emissions focus on environmental conditions in the canopy, our results suggest that sub-canopy leaves are more responsive. This work is allowing us to develop an ecological understanding of isoprenoid emissions from forests, the basis for a predictive model of emissions that depends on both environmental factors and biological emission capacity that is grounded in plant traits and phylogeny.

  16. Aircraft Engine Emissions. [conference

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A conference on a aircraft engine emissions was held to present the results of recent and current work. Such diverse areas as components, controls, energy efficient engine designs, and noise and pollution reduction are discussed.

  17. Biogenic Emission Sources

    EPA Pesticide Factsheets

    Biogenic emissions sources come from natural sources and need to accounted for in photochemical grid models. They are computed using a model which utilizes spatial information on vegetation and land use.

  18. Fugitive emissions monitoring trends

    SciTech Connect

    Brown, K.H.

    1997-02-01

    New Clean Air Act requirements are pushing facilities to reevaluate their monitoring programs. A description of the fugitive emission guidelines is included in this article, along with ideas about monitoring.

  19. ROANOKE WOODSTOVE EMISSION TESTS

    EPA Science Inventory

    The report discusses a project, part of the Integrated Air Cancer Project Roanoke study, that characterizes and quantifies emissions generated by burning authentic Roanoke cordwood. The burning occurred in a controlled laboratory setting using two woodstoves, each operated at two...

  20. Air Emissions Inventories

    EPA Pesticide Factsheets

    This site provides access to emissions data, regulations and guidance, electronic system access, resources and tools to support trends analysis, regional, and local scale air quality modeling, regulatory impact assessments.

  1. Photon enhanced thermionic emission

    DOEpatents

    Schwede, Jared; Melosh, Nicholas; Shen, Zhixun

    2014-10-07

    Photon Enhanced Thermionic Emission (PETE) is exploited to provide improved efficiency for radiant energy conversion. A hot (greater than 200.degree. C.) semiconductor cathode is illuminated such that it emits electrons. Because the cathode is hot, significantly more electrons are emitted than would be emitted from a room temperature (or colder) cathode under the same illumination conditions. As a result of this increased electron emission, the energy conversion efficiency can be significantly increased relative to a conventional photovoltaic device. In PETE, the cathode electrons can be (and typically are) thermalized with respect to the cathode. As a result, PETE does not rely on emission of non-thermalized electrons, and is significantly easier to implement than hot-carrier emission approaches.

  2. ROANOKE WOODSTOVE EMISSION TESTS

    EPA Science Inventory

    The report discusses a project, part of the Integrated Air Cancer Project Roanoke study, that characterizes and quantifies emissions generated by burning authentic Roanoke cordwood. The burning occurred in a controlled laboratory setting using two woodstoves, each operated at two...

  3. A unifying conceptual model for the environmental responses of isoprene emissions from plants

    PubMed Central

    Morfopoulos, Catherine; Prentice, Iain C.; Keenan, Trevor F.; Friedlingstein, Pierre; Medlyn, Belinda E.; Peñuelas, Josep; Possell, Malcolm

    2013-01-01

    Background and Aims Isoprene is the most important volatile organic compound emitted by land plants in terms of abundance and environmental effects. Controls on isoprene emission rates include light, temperature, water supply and CO2 concentration. A need to quantify these controls has long been recognized. There are already models that give realistic results, but they are complex, highly empirical and require separate responses to different drivers. This study sets out to find a simpler, unifying principle. Methods A simple model is presented based on the idea of balancing demands for reducing power (derived from photosynthetic electron transport) in primary metabolism versus the secondary pathway that leads to the synthesis of isoprene. This model's ability to account for key features in a variety of experimental data sets is assessed. Key results The model simultaneously predicts the fundamental responses observed in short-term experiments, namely: (1) the decoupling between carbon assimilation and isoprene emission; (2) a continued increase in isoprene emission with photosynthetically active radiation (PAR) at high PAR, after carbon assimilation has saturated; (3) a maximum of isoprene emission at low internal CO2 concentration (ci) and an asymptotic decline thereafter with increasing ci; (4) maintenance of high isoprene emissions when carbon assimilation is restricted by drought; and (5) a temperature optimum higher than that of photosynthesis, but lower than that of isoprene synthase activity. Conclusions A simple model was used to test the hypothesis that reducing power available to the synthesis pathway for isoprene varies according to the extent to which the needs of carbon assimilation are satisfied. Despite its simplicity the model explains much in terms of the observed response of isoprene to external drivers as well as the observed decoupling between carbon assimilation and isoprene emission. The concept has the potential to improve global

  4. 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

  5. IR Plasma Emissions

    DTIC Science & Technology

    1990-04-01

    a current mailing list. Do not return copies of this report unless contractural obligations or notices on a specific document requires that it be...of the relatively cold 0? gas surrounding the fireball (i.e. 02(cold) + hv --> 20*) and the broad emission arises from shock heating of the emission...experimental data and calculations 14 and 0 data from other work35 ,36. Experimental spectra were acquired by Assous 33 in an inductively- heated

  6. Field emission electron source

    DOEpatents

    Zettl, Alexander Karlwalter; Cohen, Marvin Lou

    2000-01-01

    A novel field emitter material, field emission electron source, and commercially feasible fabrication method is described. The inventive field emission electron source produces reliable electron currents of up to 400 mA/cm.sup.2 at 200 volts. The emitter is robust and the current it produces is not sensitive to variability of vacuum or the distance between the emitter tip and the cathode. The novel emitter has a sharp turn-on near 100 volts.

  7. Uncertainties of isoprene emissions in the MEGAN model estimated for a coniferous and broad-leaved mixed forest in Southern China

    SciTech Connect

    Situ, S.; Wang, Xuemei; Guenther, Alex B.; Zhang, Yanli; Wang, Xinming; Huang, Minjuan; Fan, Qi; Xiong, Zhe

    2014-12-01

    Using local observed emission factor, meteorological data, vegetation 5 information and dynamic MODIS LAI, MEGANv2.1 was constrained to predict the isoprene emission from Dinghushan forest in the Pearl River Delta region during a field campaign in November 2008, and the uncertainties in isoprene emission estimates were quantified by the Monte Carlo approach. The results indicate that MEGAN can predict the isoprene emission reasonably during the campaign, and the mean value of isoprene emission is 2.35 mg m-2 h-1 in daytime. There are high uncertainties associated with the MEGAN inputs and calculated parameters, and the relative error can be as high as -89 to 111% for a 95% confidence interval. The emission factor of broadleaf trees and the activity factor accounting for light and temperature dependence are the most important contributors to the uncertainties in isoprene emission estimated for the Dinghushan forest during the campaign. The results also emphasize the importance of accurate observed PAR and temperature to reduce the uncertainties in isoprene emission estimated by model, because the MEGAN model activity factor accounting for light and temperature dependence is highly sensitive to PAR and temperature.

  8. Simulation de l'accretion de glace sur un obstacle bidimensionnel par la methode des bissectrices et par la modelisation des ruisselets et des gouttes de surface

    NASA Astrophysics Data System (ADS)

    Fortin, Guy

    Le LIMA (Laboratoire International des Materiaux Antigivre) en collaboration avec le CIRA (Italian Aerospace Research Centre) a developpe un logiciel simulant l'accretion de la glace en regimes sec et humide sur un objet bidimensionnel fixe. L'approche utilisee s'appuie sur les travaux de Lozowski pour les bilans energetiques, sur une etude du comportement du film d'eau, des ruisselets et des gouttes de surface pour le calcul des rugosites et des masses d'eau residuelle, ainsi que sur une methode de bissectrice pour l'evolution de la surface de glace. La contribution du CIRA a ete de fournir le logiciel pour le calcul des ecoulements et de la captation. Le bilan energetique base sur la conservation de l'energie est la sommation de la chaleur latente de fusion, d'evaporation et de sublimation, du rechauffement adiabatique et cinetique, et des pertes de chaleur par convection et conduction, ainsi que de l'evolution thermodynamique de l'eau de son etat initial a son etat final. La densite de la glace, qui a un impact important sur la simulation, est calculee a partir d'une correlation empirique developpee avec les cylindres tournants. En se basant sur les travaux de Al-Khalil et Hansman, le comportement des gouttes en regimes sec et humide a ete decrit analytiquement, ce qui a mene a determiner la hauteur maximale que peuvent atteindre les gouttes avant mouvement. Cette hauteur, appelee hauteur de mouvement, permet de determiner l'etat de l'eau sur la surface (film, ruisselets ou gouttes), ainsi que la hauteur des rugosites lorsque l'eau existe sous forme de gouttes ou de ruisselets. La hauteur de mouvement est determinee par l'equilibre entre les forces de cisaillement, induites par les effets aerodynamiques et gravitationnels evalues pour une goutte non deformee, et la force de cisaillement, induite par la tension de surface et la deformation de la goutte. Elle a ete validee en laboratoire et la precision obtenue pour la partie aerodynamique et gravitationnelle est

  9. Impacts of Light Use Efficiency and fPAR Parameterization on Gross Primary Production Modeling

    NASA Technical Reports Server (NTRS)

    Cheng, Yen-Ben; Zhang, Qingyuan; Lyapustin, Alexei I.; Wang, Yujie; Middleton, Elizabeth M.

    2014-01-01

    This study examines the impact of parameterization of two variables, light use efficiency (LUE) and the fraction of absorbed photosynthetically active radiation (fPAR or fAPAR), on gross primary production(GPP) modeling. Carbon sequestration by terrestrial plants is a key factor to a comprehensive under-standing of the carbon budget at global scale. In this context, accurate measurements and estimates of GPP will allow us to achieve improved carbon monitoring and to quantitatively assess impacts from cli-mate changes and human activities. Spaceborne remote sensing observations can provide a variety of land surface parameterizations for modeling photosynthetic activities at various spatial and temporal scales. This study utilizes a simple GPP model based on LUE concept and different land surface parameterizations to evaluate the model and monitor GPP. Two maize-soybean rotation fields in Nebraska, USA and the Bartlett Experimental Forest in New Hampshire, USA were selected for study. Tower-based eddy-covariance carbon exchange and PAR measurements were collected from the FLUXNET Synthesis Dataset. For the model parameterization, we utilized different values of LUE and the fPAR derived from various algorithms. We adapted the approach and parameters from the MODIS MOD17 Biome Properties Look-Up Table (BPLUT) to derive LUE. We also used a site-specific analytic approach with tower-based Net Ecosystem Exchange (NEE) and PAR to estimate maximum potential LUE (LUEmax) to derive LUE. For the fPAR parameter, the MODIS MOD15A2 fPAR product was used. We also utilized fAPAR chl, a parameter accounting for the fAPAR linked to the chlorophyll-containing canopy fraction. fAPAR chl was obtained by inversion of a radiative transfer model, which used the MODIS-based reflectances in bands 1-7 produced by Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm. fAPAR chl exhibited seasonal dynamics more similar with the flux tower based GPP than MOD15A2 fPAR, especially

  10. Etude par spectroscopie de Coulomb de points quantiques lateraux individuels et couples

    NASA Astrophysics Data System (ADS)

    Pioro-Ladriere, Michel

    Des points quantiques contenant un nombre discret et variable d'electrons sont formes dans un gaz bi-dimensionnel d'electrons a l'aide de grilles metalliques. Le transport electrique, le blocage de spin et la detection de charge sont employes comme outils spectroscopiques permettant de sonder les proprietes de ces nanostructures. Ces techniques permettent aussi de controler exactement le nombres d'electrons confines dans des points quantiques individuels et couples en utilisant un patron de grille judicieux. Une technique de refroidissement en tension est developpee afin de minimiser les effets parasites du bruit telegraphique. Ce type de bruit de charge deteriore la stabilite des nanostructures laterales par l'activation d'un minuscule courant de fuite entre les grilles et le gaz bi-dimensionnel. Un modele expliquant le role du refroidissement en tension sur le courant de fuite est presente. L'activation du courant de fuite est confirmee par detection de charge. Les effets des interactions entre les electrons pieges dans un point quantique sont ensuite etudies dans un regime ou il est possible de comparer les resulats experimentaux avec ceux obtenus par diagonalisation exacte. L'etude demontre que la phase associee au facteur de remplissage nu = 2 est instable au-dessus d'un nombre critique d'electrons. Cette instabilite est confirmee experimentalement par blocage de spin. On demontre aussi l'existence d'etats correles dans le regime des renversements de spin, associe au passage de la phase nu = 2 a nu = 1. Les etats correles sont identifies par spectroscopie en transport non lineaire. Cette caracterisation du diagramme de phase de points individuels permet de coupler deux points quantiques configures a nu = 2. Pour ce regime, la nanostructure se comporte comme un systeme a deux niveaux pouvant contenir entre un et quatre electrons de valence et ce, meme si le nombre total d'electrons est plus eleve. Les degres de liberte de charge et de spin des deux points

  11. Emission Characterization and Emission Inventories for the 21st Century

    EPA Science Inventory

    Emission inventories are the foundation of cost-effective air quality management strategies. A goal of the emissions community is to develop the ultimate emission inventory which would include all significant emissions from all sources, time periods and areas, with quantified un...

  12. Emission Characterization and Emission Inventories for the 21st Century

    EPA Science Inventory

    Emission inventories are the foundation of cost-effective air quality management strategies. A goal of the emissions community is to develop the ultimate emission inventory which would include all significant emissions from all sources, time periods and areas, with quantified un...

  13. 47 CFR 78.103 - Emissions and emission limitations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Emissions and emission limitations. 78.103 Section 78.103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CABLE TELEVISION RELAY SERVICE Technical Regulations § 78.103 Emissions and emission limitations. (a)...

  14. 47 CFR 78.103 - Emissions and emission limitations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Emissions and emission limitations. 78.103 Section 78.103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CABLE TELEVISION RELAY SERVICE Technical Regulations § 78.103 Emissions and emission limitations. (a)...

  15. 47 CFR 78.103 - Emissions and emission limitations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Emissions and emission limitations. 78.103 Section 78.103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CABLE TELEVISION RELAY SERVICE Technical Regulations § 78.103 Emissions and emission limitations. (a)...

  16. 47 CFR 78.103 - Emissions and emission limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Emissions and emission limitations. 78.103 Section 78.103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES CABLE TELEVISION RELAY SERVICE Technical Regulations § 78.103 Emissions and emission limitations. (a)...

  17. Imagerie Resolue dans le Temps des Photons et Neutres Metastables Emis D'une Surface Par Stimulation Electronique

    NASA Astrophysics Data System (ADS)

    Leclerc, Gregoire

    L'appareil que nous presentons ici a ete mis au point pour permettre d'accumuler des images numeriques, resolues dans le temps, de la desorption par stimulation electronique (DSE) d'ions positifs et negatifs, de photons et de neutres metastables, tout en conservant des capacites de base de diffraction d'electrons lents (DEL) et de transmission d'electrons lents (TEL). Le spectrometre comporte un monochromateur d'electrons a secteur cylindrique de 127^ circ dont l'optique de sortie permet la focalisation du faisceau d'electrons sur une large gamme d'energies. Le detecteur consiste en un empilement de galettes de microcanaux et d'une anode resistive a encodage de division de charges. La reponse spatiale du detecteur a ete calibree et plusieurs causes de non-linearite ont ete localisees et corrigees. Des methodes de correction materielle et logicielle des distorsions spatiales sont presentees. La resolution temporelle des evenements est obtenue en pulsant le faisceau d'electrons, et de facon synchrone la detection, laquelle est couplee a un micro-ordinateur. La premiere partie de ce travail est consacree a la caracterisation du spectrometre et la presentation de nombreux parametres operationnels, obtenus soit au moment de la conception, soit experimentalement. Suit la presentation de donnees de DEL et de DSE pour le systeme Ar/Pt(111) en films minces a 15K. Les sequences temporelles d'images de metastables d'Ar desorbes ont revele la presence de plusieurs populations distinctes, ayant des distributions angulaires et distributions d'energie cinetique que nous avons pu separer. Les fonctions d'excitation de l'emission de photons et de la desorption de differentes composantes de metastables, ainsi que la dependance de ces signaux sur l'epaisseur des films d'Ar, sont aussi presentees et analysees. Les techniques que nous avons developpees ont permis de cerner les mecanismes en jeu pour la desorption et la luminescence.

  18. Impact of Atmospheric Mineral Dust on the Surface Energy Balance and PAR in the NEESPI Study Domain

    NASA Astrophysics Data System (ADS)

    Sokolik, I. N.; Dickinson, R. E.; Dai, Y.

    2006-12-01

    Large uncertainties in the effects of changing atmospheric aerosols are among the major factors currently limiting our understanding of and ability to predict global climate changes. The Northern Eurasia Earth Science Partnership Initiative (NEESPI) Science Plan identifies atmospheric aerosols and pollutions and their impacts on and interactions with the Earth systems (and terrestrial ecosystem dynamics in particular) as a cross- cutting topic of special interest. Wind-blown mineral dust, being an important atmospheric constituent in the NEESPI drylands, can exert a strong radiative impact as well as trigger a multitude of complex feedbacks that remain poorly defined. Given the intimate coupling between the land processes and wind-blown atmospheric dust and their importance in the climate system, an improved understanding of how land-use/land-cover changes affect Asian dust and associated feedbacks is urgently needed to make assessments of climate change more realistic. The focus of this talk will be on the impact of atmospheric dust on the surface energy balance and photosynthetically active radiation (PAR). Both processes play a key role in the ecosystem functioning as well as overall land-atmosphere interactions, but they are rarely considered in an integrated fashion. Focusing on Central and East Asia, we present the results of extensive radiative transfer modeling in the presence of dust over the different type of land surfaces. The surface albedo and land emissivity retrieved from MODIS and ASTER, respectively, were included in the modeling. The modifications of the radiative fields are quantified and used to estimate changes of surface temperatures, surface fluxes of heat and moisture, boundary layer height, surface winds and other dust induced changes. Formulation of the possible feedbacks in the coupled land- atmospheric dust system and implications for the integrated systems modeling will be addressed.

  19. 1,25-Dihydroxyvitamin D(3) Inhibits Podocyte uPAR Expression and Reduces Proteinuria

    PubMed Central

    Liu, Shuangxin; Xie, Shaoting; Yang, Yun; Ma, Juan; Deng, Yujun; Wang, Wenjian; Xu, Lixia; Li, Ruizhao; Zhang, Li; Yu, Chunping; Shi, Wei

    2013-01-01

    Background Accumulating studies have demonstrated that 1,25-Dihydroxyvitamin D(3) (1,25(OH)2D3) reduces proteinuria and protects podocytes from injury. Recently, urokinase receptor (uPAR) and its soluble form have been shown to cause podocyte injury and focal segmental glomerulosclerosis (FSGS). Here, our findings showed that 1,25(OH)2D3 did inhibit podocyte uPAR expression and attenuate proteinuria and podocyte injury. Methodology/Principal Findings In this study, the antiproteinuric effect of 1,25(OH)2D3 was examined in the lipopolysaccharide mice model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model(NTX rats). uPAR protein expression were tested by flow cytometry, immune cytochemistry and western blot analysis, and uPAR mRNA expression by real-time quantitative PCR in cultured podocytes and kidney glomeruli isolated from mice and rats. Podocyte motility was observed by transwell migration assay and wound healing assay. Podocyte foot processes effacement was identified by transmission electron microscopy. We found that 1,25(OH)2D3 inhibited podocyte uPAR mRNA and protein synthesis in LPS-treated podocytes, LPS mice and NTX rats, along with 1,25(OH)2D3 reducing proteinuria in NTX rats and LPS mice.1,25(OH)2D3 reduced glomerulosclerosis in NTX rats and alleviated podocyte foot processes effacement in LPS mice. Transwell migration assay and wound healing assay showed that LPS-induced podocyte motility, irrespective of random or directed motility, were substantially reduced by 1,25(OH)2D3. Conclusions/Significance Our results demonstrated that 1,25(OH)2D3 inhibited podocyte uPAR expression in vitro and in vivo, which may be an unanticipated off target effect of 1,25(OH)2D3 and explain its antiproteinuric effect in the 5/6 nephrectomy rat FSGS model and the LPS mouse model of transient proteinuria. PMID:23741418

  20. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (su<