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

NASA Astrophysics Data System (ADS)

Coulibaly, Issa

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

Etude de pratiques d'enseignement relatives a la modelisation en sciences et technologies avec des enseignants du secondaire

NASA Astrophysics Data System (ADS)

Aurousseau, Emmanuelle

Les modeles sont des outils amplement utilises en sciences et technologies (S&T) afin de representer et d’expliquer un phenomene difficilement accessible, voire abstrait. La demarche de modelisation est presentee de maniere explicite dans le programme de formation de l’ecole quebecoise (PFEQ), notamment au 2eme cycle du secondaire (Quebec. Ministere de l'Education du Loisir et du Sport, 2007a). Elle fait ainsi partie des sept demarches auxquelles eleves et enseignants sont censes recourir. Cependant, de nombreuses recherches mettent en avant la difficulte des enseignants a structurer leurs pratiques d’enseignement autour des modeles et de la demarche de modelisation qui sont pourtant reconnus comme indispensables. En effet, les modeles favorisent la conciliation des champs concrets et abstraits entre lesquels le scientifique, meme en herbe, effectue des allers-retours afin de concilier le champ experimental de reference qu’il manipule et observe au champ theorique relie qu’il construit. L’objectif de cette recherche est donc de comprendre comment les modeles et la demarche de modelisation contribuent a faciliter l’articulation du concret et de l’abstrait dans l’enseignement des sciences et des technologies (S&T) au 2eme cycle du secondaire. Pour repondre a cette question, nous avons travaille avec les enseignants dans une perspective collaborative lors de groupes focalises et d’observation en classe. Ces dispositifs ont permis d’examiner les pratiques d’enseignement que quatre enseignants mettent en oeuvre en utilisant des modeles et des demarches de modelisation. L’analyse des pratiques d’enseignement et des ajustements que les enseignants envisagent dans leur pratique nous permet de degager des connaissances a la fois pour la recherche et pour la pratique des enseignants, au regard de l’utilisation des modeles et de la demarche de modelisation en S&T au secondaire.

Computational approach to estimating the effects of blood properties on changes in intra-stent flow.

PubMed

Benard, Nicolas; Perrault, Robert; Coisne, Damien

2006-08-01

In this study various blood rheological assumptions are numerically investigated for the hemodynamic properties of intra-stent flow. Non-newtonian blood properties have never been implemented in blood coronary stented flow investigation, although its effects appear essential for a correct estimation and distribution of wall shear stress (WSS) exerted by the fluid on the internal vessel surface. Our numerical model is based on a full 3D stent mesh. Rigid wall and stationary inflow conditions are applied. Newtonian behavior, non-newtonian model based on Carreau-Yasuda relation and a characteristic newtonian value defined with flow representative parameters are introduced in this research. Non-newtonian flow generates an alteration of near wall viscosity norms compared to newtonian. Maximal WSS values are located in the center part of stent pattern structure and minimal values are focused on the proximal stent wire surface. A flow rate increase emphasizes fluid perturbations, and generates a WSS rise except for interstrut area. Nevertheless, a local quantitative analysis discloses an underestimation of WSS for modelisation using a newtonian blood flow, with clinical consequence of overestimate restenosis risk area. Characteristic viscosity introduction appears to present a useful option compared to rheological modelisation based on experimental data, with computer time gain and relevant results for quantitative and qualitative WSS determination.

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

NASA Astrophysics Data System (ADS)

Beaudoin, Alexandre

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

Realisation et Applications D'un Laser a Fibre a L'erbium Monofrequence

NASA Astrophysics Data System (ADS)

Larose, Robert

L'incorporation d'ions de terres rares a l'interieur de la matrice de verre d'une fibre optique a permis l'emergence de composants amplificateurs tout-fibre. Le but de cette these consiste d'une part a analyser et a modeliser un tel dispositif et d'autre part, a fabriquer puis a caracteriser un amplificateur et un oscillateur a fibre. A l'aide d'une fibre fortement dopee a l'erbium fabriquee sur demande, on realise un laser a fibre syntonisable qui fonctionne en regime multimodes longitudinaux avec une largeur de raie de 1.5 GHz et egalement comme source monofrequencielle de largeur de raie de 70 kHz. Le laser sert ensuite a caracteriser un reseau de Bragg ecrit par photosensibilite dans une fibre optique. La technique de syntonisation permet aussi l'asservissement au fond d'une resonance de l'acetylene. Le laser garde alors la position centrale de la raie avec une erreur de moins de 1 MHz corrigeant ainsi les derives mecaniques de la cavite.

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

NASA Astrophysics Data System (ADS)

Boyer, Sylvain

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

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

NASA Astrophysics Data System (ADS)

L'Esperance, Andre

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

Function of Platelet-Induced Epithelial Attachment at Titanium Surfaces Inhibits Microbial Colonization.

PubMed

Maeno, M; Lee, C; Kim, D M; Da Silva, J; Nagai, S; Sugawara, S; Nara, Y; Kihara, H; Nagai, M

2017-06-01

The aim of this study was to evaluate the barrier function of platelet-induced epithelial sheets on titanium surfaces. The lack of functional peri-implant epithelial sealing with basal lamina (BL) attachment at the interface of the implant and the adjacent epithelium allows for bacterial invasion, which may lead to peri-implantitis. Although various approaches have been reported to combat bacterial infection by surface modifications to titanium, none of these have been successful in a clinical application. In our previous study, surface modification with protease-activated receptor 4-activating peptide (PAR4-AP), which induced platelet activation and aggregation, was successful in demonstrating epithelial attachment via BL and epithelial sheet formation on the titanium surface. We hypothesized that the platelet-induced epithelial sheet on PAR4-AP-modified titanium surfaces would reduce bacterial attachment, penetration, and invasion. Titanium surface was modified with PAR4-AP and incubated with platelet-rich plasma (PRP). The aggregated platelets released collagen IV, a critical BL component, onto the PAR4-AP-modified titanium surface. Then, human gingival epithelial cells were seeded on the modified titanium surface and formed epithelial sheets. Green fluorescent protein (GFP)-expressing Escherichia coli was cultured onto PAR4-AP-modified titanium with and without epithelial sheet formation. While Escherichia coli accumulated densely onto the PAR4-AP titanium lacking epithelial sheet, few Escherichia coli were observed on the epithelial sheet on the PAR4-AP surface. No bacterial invasion into the interface of the epithelial sheet and the titanium surface was observed. These in vitro results indicate the efficacy of a platelet-induced epithelial barrier that functions to prevent bacterial attachment, penetration, and invasion on PAR4-AP-modified titanium.

Conceptual Modeling (CM) for Military Modeling and Simulation (M&S) (Modelisation conceptuelle (MC) pour la modelisation et la simulation (M&S) militaires)

DTIC Science & Technology

2012-07-01

du monde de la modélisation et de la simulation et lui fournir des directives de mise en œuvre ; et fournir des ...définition ; rapports avec les normes ; spécification de procédure de gestion de la MC ; spécification d’artefact de MC. Considérations importantes...utilisant la présente directive comme référence. • Les VV&A (vérification, validation et acceptation) des MC doivent faire partie intégrante du

Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.

PubMed

Shetty, Praveenkumar; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P; Liu, Ming C; Shetty, Sreerama

2010-02-01

The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1-100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.

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

NASA Astrophysics Data System (ADS)

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

1996-11-01

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

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.

Protease-Activated Receptor 4 Variant p.Tyr157Cys Reduces Platelet Functional Responses and Alters Receptor Trafficking.

PubMed

Norman, Jane E; Cunningham, Margaret R; Jones, Matthew L; Walker, Mary E; Westbury, Sarah K; Sessions, Richard B; Mundell, Stuart J; Mumford, Andrew D

2016-05-01

Protease-activated receptor 4 (PAR4) is a key regulator of platelet reactivity and is encoded by F2RL3, which has abundant rare missense variants. We aimed to provide proof of principle that rare F2LR3 variants potentially affect platelet reactivity and responsiveness to PAR1 antagonist drugs and to explore underlying molecular mechanisms. We identified 6 rare F2RL3 missense variants in 236 cardiac patients, of which the variant causing a tyrosine 157 to cysteine substitution (Y157C) was predicted computationally to have the greatest effect on PAR4 structure. Y157C platelets from 3 cases showed reduced responses to PAR4-activating peptide and to α-thrombin compared with controls, but no reduction in responses to PAR1-activating peptide. Pretreatment with the PAR1 antagonist vorapaxar caused lower residual α-thrombin responses in Y157C platelets than in controls, indicating greater platelet inhibition. HEK293 cells transfected with a PAR4 Y157C expression construct had reduced PAR4 functional responses, unchanged total PAR4 expression but reduced surface expression. PAR4 Y157C was partially retained in the endoplasmic reticulum and displayed an expression pattern consistent with defective N-glycosylation. Mutagenesis of Y322, which is the putative hydrogen bond partner of Y157, also reduced PAR4 surface expression in HEK293 cells. Reduced PAR4 responses associated with Y157C result from aberrant anterograde surface receptor trafficking, in part, because of disrupted intramolecular hydrogen bonding. Characterization of PAR4 Y157C establishes that rare F2RL3 variants have the potential to markedly alter platelet PAR4 reactivity particularly after exposure to therapeutic PAR1 antagonists. © 2016 American Heart Association, Inc.

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

PubMed

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

2015-12-22

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.

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

Le recours aux modeles dans l'enseignement de la biologie au secondaire : Conceptions d'enseignantes et d'enseignants et modes d'utilisation

NASA Astrophysics Data System (ADS)

Varlet, Madeleine

Le recours aux modeles et a la modelisation est mentionne dans la documentation scientifique comme un moyen de favoriser la mise en oeuvre de pratiques d'enseignement-apprentissage constructivistes pour pallier les difficultes d'apprentissage en sciences. L'etude prealable du rapport des enseignantes et des enseignants aux modeles et a la modelisation est alors pertinente pour comprendre leurs pratiques d'enseignement et identifier des elements dont la prise en compte dans les formations initiale et disciplinaire peut contribuer au developpement d'un enseignement constructiviste des sciences. Plusieurs recherches ont porte sur ces conceptions sans faire de distinction selon les matieres enseignees, telles la physique, la chimie ou la biologie, alors que les modeles ne sont pas forcement utilises ou compris de la meme maniere dans ces differentes disciplines. Notre recherche s'est interessee aux conceptions d'enseignantes et d'enseignants de biologie au secondaire au sujet des modeles scientifiques, de quelques formes de representations de ces modeles ainsi que de leurs modes d'utilisation en classe. Les resultats, que nous avons obtenus au moyen d'une serie d'entrevues semi-dirigees, indiquent que globalement leurs conceptions au sujet des modeles sont compatibles avec celle scientifiquement admise, mais varient quant aux formes de representations des modeles. L'examen de ces conceptions temoigne d'une connaissance limitee des modeles et variable selon la matiere enseignee. Le niveau d'etudes, la formation prealable, l'experience en enseignement et un possible cloisonnement des matieres pourraient expliquer les differentes conceptions identifiees. En outre, des difficultes temporelles, conceptuelles et techniques peuvent freiner leurs tentatives de modelisation avec les eleves. Toutefois, nos resultats accreditent l'hypothese que les conceptions des enseignantes et des enseignants eux-memes au sujet des modeles, de leurs formes de representation et de leur approche constructiviste en enseignement representent les plus grands obstacles a la construction des modeles en classe. Mots-cles : Modeles et modelisation, biologie, conceptions, modes d'utilisation, constructivisme, enseignement, secondaire.

Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor.

PubMed Central

Colman, R W; Pixley, R A; Najamunnisa, S; Yan, W; Wang, J; Mazar, A; McCrae, K R

1997-01-01

The urokinase receptor (uPAR) binds urokinase-type plasminogen activator (u-PA) through specific interactions with uPAR domain 1, and vitronectin through interactions with a site within uPAR domains 2 and 3. These interactions promote the expression of cell surface plasminogen activator activity and cellular adhesion to vitronectin, respectively. High molecular weight kininogen (HK) also stimulates the expression of cell surface plasminogen activator activity through its ability to serve as an acquired receptor for prekallikrein, which, after its activation, may directly activate prourokinase. Here, we report that binding of the cleaved form of HK (HKa) to human umbilical vein endothelial cells (HUVEC) is mediated through zinc-dependent interactions with uPAR. These occur through a site within uPAR domains 2 and 3, since the binding of 125I-HKa to HUVEC is inhibited by vitronectin, anti-uPAR domain 2 and 3 antibodies and soluble, recombinant uPAR (suPAR), but not by antibody 7E3, which recognizes the beta chain of the endothelial cell vitronectin receptor (integrin alphavbeta3), or fibrinogen, another alphavbeta3 ligand. We also demonstrate the formation of a zinc-dependent complex between suPAR and HKa. Interactions of HKa with endothelial cell uPAR may underlie its ability to promote kallikrein-dependent cell surface plasmin generation, and also explain, in part, its antiadhesive properties. PMID:9294114

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.

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

NASA Astrophysics Data System (ADS)

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

1993-03-01

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

Importance of solar subsurface heating in ocean general circulation models

NASA Astrophysics Data System (ADS)

Rochford, Peter A.; Kara, A. Birol; Wallcraft, Alan J.; Arnone, Robert A.

2001-12-01

The importance of subsurface heating on surface mixed layer properties in an ocean general circulation model (OGCM) is examined using attenuation of solar irradiance with depth below the ocean surface. The depth-dependent attenuation of subsurface heating is given by global monthly mean fields for the attenuation of photosynthetically available radiation (PAR), kPAR. These global fields of kPAR are derived from Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data on the spectral diffuse attenuation coefficient at 490 nm (k490), and have been processed to have the smoothly varying and continuous coverage necessary for use in OGCM applications. These monthly fields provide the first complete global data sets of subsurface optical fields that can be used for OGCM applications of subsurface heating and bio-optical processes. The effect on global OGCM prediction of sea surface temperature (SST) and surface mixed layer depth (MLD) is examined when solar heating, as given by monthly mean kPAR and PAR fields, is included in the model. It is found that subsurface heating yields a marked increase in the SST predictive skill of the OGCM at low latitudes. No significant improvement in MLD predictive skill is obtained when including subsurface heating. Use of the monthly mean kPAR produces an SST decrease of up to 0.8°C and a MLD increase of up to only 4-5 m for climatological surface forcing, with this primarily confined to the equatorial regions. Remarkably, a constant kPAR value of 0.06 m-1, which is indicative of optically clear open ocean conditions, is found to serve very well for OGCM prediction of SST and MLD over most of the global ocean.

Mapping high-resolution incident photosynthetically active radiation over land surfaces from MODIS and GOES satellite data

NASA Astrophysics Data System (ADS)

Liang, S.; Wang, K.; Wang, D.; Townshend, J.; Running, S.; Tsay, S.

2008-05-01

Incident photosynthetically active radiation (PAR) is a key variable required by almost all terrestrial ecosystem models. Many radiation efficiency models are linearly related canopy productivity to the absorbed PAR. Unfortunately, the current incident PAR products estimated from remotely sensed data or calculated by radiation models at spatial and temporal resolutions are not sufficient for carbon cycle modeling and various applications. In this study, we aim to develop incident PAR products at one kilometer scale from multiple satellite sensors, such as Moderate Resolution Imaging Spectrometer (MODIS) and Geostationary Operational Environmental Satellite (GOES) sensor. We first developed a look-up table approach to estimate instantanerous incident PAR product from MODIS (Liang et al., 2006). The temporal observations of each pixel are used to estimate land surface reflectance and look-up tables of both aerosol and cloud are searched, based on the top-of-atmosphere reflectance and surface reflectance for determining incident PAR. The incident PAR product includes both the direct and diffuse components. The calculation of a daily integrated PAR using two different methods has also been developed (Wang, et al., 2008a). The similar algorithm has been further extended to GOES data (Wang, et al., 2008b, Zheng, et al., 2008). Extensive validation activities are conducted to evaluate the algorithms and products using the ground measurements from FLUXNET and other networks. They are also compared with other satellite products. The results indicate that our approaches can produce reasonable PAR product at 1km resolution. We have generated 1km incident PAR products over North America for several years, which are freely available to the science community. Liang, S., T. Zheng, R. Liu, H. Fang, S. C. Tsay, S. Running, (2006), Estimation of incident Photosynthetically Active Radiation from MODIS Data, Journal of Geophysical Research ¡§CAtmosphere. 111, D15208,doi:10.1029/2005JD006730. Wang, D., S. Liang, and Zheng, T., (2008a), Integrated daily PAR from MODIS. International Journal of Remote Sensing, revised. Wang, K., S. Liang, T. Zheng and D. Wang, (2008b), Simultaneous estimation of surface photosynthetically active radiation and albedo from GOES, Remote Sensing of Environment, revised. Zheng, T., S. Liang, K. Wang, (2008), Estimation of incident PAR from GOES imagery, Journal of Applied Meteorology and Climatology. in press.

Proteolytic Activation of the Protease-activated Receptor (PAR)-2 by the Glycosylphosphatidylinositol-anchored Serine Protease Testisin*

PubMed Central

Driesbaugh, Kathryn H.; Buzza, Marguerite S.; Martin, Erik W.; Conway, Gregory D.; Kao, Joseph P. Y.; Antalis, Toni M.

2015-01-01

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca2+ mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. PMID:25519908

Satellite estimation of incident photosynthetically active radiation using ultraviolet reflectance

NASA Technical Reports Server (NTRS)

Eck, Thomas F.; Dye, Dennis G.

1991-01-01

A new satellite remote sensing method for estimating the amount of photosynthetically active radiation (PAR, 400-700 nm) incident at the earth's surface is described and tested. Potential incident PAR for clear sky conditions is computed from an existing spectral model. A major advantage of the UV approach over existing visible band approaches to estimating insolation is the improved ability to discriminate clouds from high-albedo background surfaces. UV spectral reflectance data from the Total Ozone Mapping Spectrometer (TOMS) were used to test the approach for three climatically distinct, midlatitude locations. Estimates of monthly total incident PAR from the satellite technique differed from values computed from ground-based pyranometer measurements by less than 6 percent. This UV remote sensing method can be applied to estimate PAR insolation over ocean and land surfaces which are free of ice and snow.

Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

PubMed Central

Caiolfa, Valeria R.; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D.; Sutin, Jason; Digman, Michelle A.; Gratton, Enrico; Blasi, Francesco; Sidenius, Nicolai

2007-01-01

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents. PMID:18056417

SURFING BIOLOGICAL SURFACES: EXPLOITING THE NUCLEOID FOR PARTITION AND TRANSPORT IN BACTERIA

PubMed Central

Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Funnell, Barbara E.

2012-01-01

The ParA family of ATPases are responsible for transporting bacterial chromosomes, plasmids, and large protein machineries. ParAs pattern the nucleoid in vivo, but how patterning functions or is exploited in transport is of considerable debate. Here we discuss the process of self-organization into patterns on the bacterial nucleoid and explore how it relates to the molecular mechanism of ParA action. We review ParA-mediated DNA partition as a general mechanism of how ATP-driven protein gradients on biological surfaces can result in spatial organization on a mesoscale. We also discuss how the nucleoid acts as a formidable diffusion barrier for large bodies in the cell, and make the case that the ParA family evolved to overcome the barrier by exploiting the nucleoid as a matrix for movement. PMID:22934804

Inferring total canopy APAR from PAR bidirectional reflectances and vegetation indices in tallgrass prairie. [Absorbed Photosynthetically Active Radiation

NASA Technical Reports Server (NTRS)

Middleton, Elizabeth M.

1992-01-01

The fraction of photosynthetically active radiation (PAR) absorbed by a vegetated canopy (APARc) or landscape (APARs) is a critical parameter in climate processes. A grassland study examined: 1) whether APARs can be estimated from PAR bidirectional exitance fractions; and 2) whether APARs is correlated with spectral vegetation indices (SVIs). Data were acquired with a high resolution continuous spectroradiometer at 4 sun angles on grassland sites. APARs was computed from the scattered surface PAR exitance fractions. The nadir APARs value was the most variable diurnally; it provided a good estimate of the average surface APARs at 95 percent. APARc was best represented by exitance factors between 30-60* forward.

Proteolytic activation of the protease-activated receptor (PAR)-2 by the glycosylphosphatidylinositol-anchored serine protease testisin.

PubMed

Driesbaugh, Kathryn H; Buzza, Marguerite S; Martin, Erik W; Conway, Gregory D; Kao, Joseph P Y; Antalis, Toni M

2015-02-06

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca(2+) mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Etude aerodynamique d'un jet turbulent impactant une paroi concave

NASA Astrophysics Data System (ADS)

LeBlanc, Benoit

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

Surfing biological surfaces: exploiting the nucleoid for partition and transport in bacteria.

PubMed

Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Funnell, Barbara E

2012-11-01

The ParA family of ATPases is responsible for transporting bacterial chromosomes, plasmids and large protein machineries. ParAs pattern the nucleoid in vivo, but how patterning functions or is exploited in transport is of considerable debate. Here we discuss the process of self-organization into patterns on the bacterial nucleoid and explore how it relates to the molecular mechanism of ParA action. We review ParA-mediated DNA partition as a general mechanism of how ATP-driven protein gradients on biological surfaces can result in spatial organization on a mesoscale. We also discuss how the nucleoid acts as a formidable diffusion barrier for large bodies in the cell, and make the case that the ParA family evolved to overcome the barrier by exploiting the nucleoid as a matrix for movement. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

PubMed

Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

2014-01-17

The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

PubMed Central

Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

2003-01-01

The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion. PMID:14609946

Transport de paires EPR dans des structures mesoscopiques

NASA Astrophysics Data System (ADS)

Dupont, Emilie

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

Simulating Carbon Flux Dynamics with the Product of PAR Absorbed by Chlorophyll (fAPARchl)

NASA Astrophysics Data System (ADS)

Yao, T.; Zhang, Q.

2016-12-01

A common way to estimate the gross primary production (GPP) is to use the fraction of photosynthetically radiation (PAR) absorbed by vegetation (FPAR). However, only the PAR absorbed by chlorophyll of the canopy, not the PAR absorbed by the foliage or by the entire canopy, is used for photosynthesis. MODIS fAPARchl product, which refers to the fraction of PAR absorbed by chlorophyll of the canopy, is derived from Moderate Resolution Imaging Spectroradiometer (MODIS) surface reflectance by using an advanced leaf-canopy-soil-water-snow coupled radiative transfer model PROSAIL4. PROSAIL4 can retrieve surface water cover fraction, snow cover fraction, and physiologically active canopy chemistry components (chlorophyll concentration and water content), fraction of photosynthetically active radiation (PAR) absorbed by a canopy (fAPARcanopy), fraction of PAR absorbed by photosynthetic vegetation (PV) component (mainly chlorophyll) throughout the canopy (fAPARPV, i.e., fAPARchl) and fraction of PAR absorbed by non-photosynthetic vegetation (NPV) component of the canopy (fAPARNPV). We have successfully retrieved these vegetation parameters for selected areas with PROSAIL4 and the MODIS images, or simulated spectrally MODIS-like images. In this study, the product of PAR absorbed by chlorophyll (fAPARchl) has been used to simulate carbon flux over different kinds of vegetation types. The results show that MODIS fAPARchl product has the ability to better characterize phenology than current phenology model in the Community Land Model and it also will likely be able to increase the accuracy of carbon fluxes simulations.

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

PubMed

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist (P < 0.05). Protease-activated receptor 1 antagonist did not alter aPA-stimulated IL-8 mRNA expression and protein production in HCE cells. Flow cytometry and immunocytochemistry showed that aPA and SLIGRL-NH2 (PAR2 agonist) upregulated PAR2 surface protein as compared to that in unstimulated HCE cells. Thrombin, but not aPA, stimulated PAR1 surface protein in HCE cells. Acanthamoeba plasminogen activator specifically induces expression and production of IL-8 in HCE cells via PAR2 pathway, and PAR2 antagonists may be used as a therapeutic target in AK. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

PAR and UV effects on vertical migration and photosynthesis in Euglena gracilis.

PubMed

Richter, Peter; Helbling, Walter; Streb, Christine; Häder, Donat-P

2007-01-01

Recently it was shown that the unicellular flagellate Euglena gracilis changes the sign of gravitaxis from negative to positive upon excessive radiation. This sign change persists in a cell culture for hours even if subsequently transferred to dim light. To test the ecological relevance of this behavior, a vertical column experiment was performed (max. depth 65 cm) to test distribution, photosynthetic efficiency and motility in different horizons of the column (surface, 20, 40 and 65 cm). One column was covered with a UV cut-off filter, which transmits photosynthetically active radiation (PAR) only, the other with a filter which transmits PAR and UV. The columns were irradiated with a solar simulator (PAR 162 W m(-2), UV-A 32.6 W m(-2), UV-B 1.9 W m(-2)). The experiment was conducted for 10 days, normally with a light/dim light cycle of 12 h:12 h, but in some cases the light regime was changed (dim light instead of full radiation). Under irradiation the largest fraction of cells was found at the bottom of the column. The cell density decreased toward the surface. Photosynthetic efficiency, determined with a pulse amplitude modulated fluorometer, was negligible at the surface and increased toward the bottom. While the cell suspension showed a positive gravitaxis at the bottom, the cells in the 40 cm horizon were bimodally oriented (about the same percentage of cells swimming upward and downward, respectively). At 20 cm and at the surface the cells showed negative gravitaxis. Positive gravitaxis was more pronounced in the UV + PAR samples. At the surface and in the 20 and 40 cm horizons photosynthetic efficiency was better in the PAR-only samples than in the PAR + UV samples. At the bottom photosynthetic efficiency was similar in both light treatments. The data suggest that high light reverses gravitaxis of the cells, so that they move downward in the water column. At the bottom the light intensity is lower (attenuation of the water column and self shading of the cells) and the cells recover. After recovery the cells swim upward again until the negative gravitaxis is reversed again.

PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.

PubMed

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

2012-06-01

Proteinase-activated receptor 2 (PAR(2)) 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 PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Patients with RA had elevated but variable surface expression of PAR(2) 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 PAR(2) 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, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) 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 PAR(2) 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). PAR(2) 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 PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). These findings are consistent with a pathogenic role for PAR(2) in RA.

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

Traitement de surface par explosif du cuivre polycristallin : caractérisation microstructurale et comportement en fatigue plastique

NASA Astrophysics Data System (ADS)

Gerland, M.; Dufour, J. P.; Presles, H. N.; Violan, P.; Mendez, J.

1991-10-01

A new surface treatment technique with a primary explosive deposited in thin layer was applied to a polycrystalline pure copper. After treatment, surface roughness remains of high quality especially when compared to shot peened surfaces. The treated zone extends over several hundreds microns in depth and the microhardness profile exhibits a significant increasing of hardness with a maximum reaching 100% at the surface. The transmission electron microscopy shows a microstructure which changes with depth : below the surface, there is a thin recrystallized layer with very small grains followed by a region with numerous mechanical twins the density of which decreases when depth increases. Tested in fatigue with a constant plastic strain amplitude, the treated copper specimens exhibit a strong hardening from the first cycles compared to the untreated specimen ; however this initial hardening erases after 2% of the fatigue life. The fatigue resistance is not modified by the treatment. Une nouvelle technique de traitement de surface à l'aide d'un explosif primaire déposé en couche mince a été utilisée sur du cuivre pur polycristallin. L'état de surface après traitement reste de très bonne qualité, surtout comparé aux surfaces grenaillées. La zone traitée s'étend sur une profondeur de quelques centaines de microns et le profil de microdureté montre une importante augmentation de dureté avec un maximum en surface pouvant atteindre 100%. La micrcrostructure, observée par microscopie électronique en transmission, est caractérisée par une fine recristallisation en surface, puis par un abondant maclage dont la densité décroît lorsque la profondeur augmente. Testé en fatigue à déformation plastique imposée, le cuivre traité présente un fort écrouissage initial dès les premiers cycles, mais qui s'efface progressivement au cours du cyclage après 2% de la durée de vie, cette dernière n'étant pas modifiée par le traitement.

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

NASA Astrophysics Data System (ADS)

Leger, Michel T.

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

Role of the urokinase plasminogen activator receptor in mediating impaired efferocytosis of anti-SSA/Ro-bound apoptotic cardiocytes: Implications in the pathogenesis of congenital heart block.

PubMed

Briassouli, Paraskevi; Komissarova, Elena V; Clancy, Robert M; Buyon, Jill P

2010-08-06

Binding of maternal anti-Ro/La antibodies to cognate antigen expressed on apoptotic cardiocytes decreases clearance by healthy cardiocytes, which may contribute to the development of autoimmune associated congenital heart block and fatal cardiomyopathy. Given recent evidence implicating the urokinase plasminogen activator receptor (uPAR) as a "don't eat me" signal during efferocytosis, experiments addressed whether surface bound anti-Ro antibodies inhibit apoptotic cell removal via an effect on the expression/function of the urokinase-type plasminogen activator protease uPA/uPAR system. As assessed by flow cytometry and confocal microscopy, uPAR colocalizes and interacts with Ro60 on the surface of apoptotic human fetal cardiocytes. Blocking of uPAR enhances phagocytosis of apoptotic cardiocytes by healthy cardiocytes and reverses the anti-Ro60-dependent impaired clearance of apoptotic cardiocytes. Binding of anti-Ro60 antibodies to apoptotic cardiocytes results in increased uPAR expression, as well as enhanced uPA activity. The binding of anti-Ro60 did not alter other surface molecules involved in cell recognition (calreticulin, CD31, or CD47). These data suggest that increased uPAR expression and uPA activity induced by anti-Ro60 binding to the apoptotic fetal cardiocyte provide a molecular basis by which these antibodies inhibit efferocytosis and ultimately lead to scar of the fetal conduction system and working myocardium.

An interactive network of elastase, secretases, and PAR-2 protein regulates CXCR1 receptor surface expression on neutrophils.

PubMed

Bakele, Martina; Lotz-Havla, Amelie S; Jakowetz, Anja; Carevic, Melanie; Marcos, Veronica; Muntau, Ania C; Gersting, Soeren W; Hartl, Dominik

2014-07-25

CXCL8 (IL-8) recruits and activates neutrophils through the G protein-coupled chemokine receptor CXCR1. We showed previously that elastase cleaves CXCR1 and thereby impairs antibacterial host defense. However, the molecular intracellular machinery involved in this process remained undefined. Here we demonstrate by using flow cytometry, confocal microscopy, subcellular fractionation, co-immunoprecipitation, and bioluminescence resonance energy transfer that combined α- and γ-secretase activities are functionally involved in elastase-mediated regulation of CXCR1 surface expression on human neutrophils, whereas matrix metalloproteases are dispensable. We further demonstrate that PAR-2 is stored in mobilizable compartments in neutrophils. Bioluminescence resonance energy transfer and co-immunoprecipitation studies showed that secretases, PAR-2, and CXCR1 colocalize and physically interact in a novel protease/secretase-chemokine receptor network. PAR-2 blocking experiments provided evidence that elastase increased intracellular presenilin-1 expression through PAR-2 signaling. When viewed in combination, these studies establish a novel functional network of elastase, secretases, and PAR-2 that regulate CXCR1 expression on neutrophils. Interfering with this network could lead to novel therapeutic approaches in neutrophilic diseases, such as cystic fibrosis or rheumatoid arthritis.

An Interactive Network of Elastase, Secretases, and PAR-2 Protein Regulates CXCR1 Receptor Surface Expression on Neutrophils*

PubMed Central

Bakele, Martina; Lotz-Havla, Amelie S.; Jakowetz, Anja; Carevic, Melanie; Marcos, Veronica; Muntau, Ania C.; Gersting, Soeren W.; Hartl, Dominik

2014-01-01

CXCL8 (IL-8) recruits and activates neutrophils through the G protein-coupled chemokine receptor CXCR1. We showed previously that elastase cleaves CXCR1 and thereby impairs antibacterial host defense. However, the molecular intracellular machinery involved in this process remained undefined. Here we demonstrate by using flow cytometry, confocal microscopy, subcellular fractionation, co-immunoprecipitation, and bioluminescence resonance energy transfer that combined α- and γ-secretase activities are functionally involved in elastase-mediated regulation of CXCR1 surface expression on human neutrophils, whereas matrix metalloproteases are dispensable. We further demonstrate that PAR-2 is stored in mobilizable compartments in neutrophils. Bioluminescence resonance energy transfer and co-immunoprecipitation studies showed that secretases, PAR-2, and CXCR1 colocalize and physically interact in a novel protease/secretase-chemokine receptor network. PAR-2 blocking experiments provided evidence that elastase increased intracellular presenilin-1 expression through PAR-2 signaling. When viewed in combination, these studies establish a novel functional network of elastase, secretases, and PAR-2 that regulate CXCR1 expression on neutrophils. Interfering with this network could lead to novel therapeutic approaches in neutrophilic diseases, such as cystic fibrosis or rheumatoid arthritis. PMID:24914212

Comparison of linear and square superposition hardening models for the surface nanoindentation of ion-irradiated materials

NASA Astrophysics Data System (ADS)

Xiao, Xiazi; Yu, Long

2018-05-01

Linear and square superposition hardening models are compared for the surface nanoindentation of ion-irradiated materials. Hardening mechanisms of both dislocations and defects within the plasticity affected region (PAR) are considered. Four sets of experimental data for ion-irradiated materials are adopted to compare with theoretical results of the two hardening models. It is indicated that both models describe experimental data equally well when the PAR is within the irradiated layer; whereas, when the PAR is beyond the irradiated region, the square superposition hardening model performs better. Therefore, the square superposition model is recommended to characterize the hardening behavior of ion-irradiated materials.

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.

Integrating Map Algebra and Statistical Modeling for Spatio- Temporal Analysis of Monthly Mean Daily Incident Photosynthetically Active Radiation (PAR) over a Complex Terrain.

PubMed

Evrendilek, Fatih

2007-12-12

This study aims at quantifying spatio-temporal dynamics of monthly mean dailyincident photosynthetically active radiation (PAR) over a vast and complex terrain such asTurkey. The spatial interpolation method of universal kriging, and the combination ofmultiple linear regression (MLR) models and map algebra techniques were implemented togenerate surface maps of PAR with a grid resolution of 500 x 500 m as a function of fivegeographical and 14 climatic variables. Performance of the geostatistical and MLR modelswas compared using mean prediction error (MPE), root-mean-square prediction error(RMSPE), average standard prediction error (ASE), mean standardized prediction error(MSPE), root-mean-square standardized prediction error (RMSSPE), and adjustedcoefficient of determination (R² adj. ). The best-fit MLR- and universal kriging-generatedmodels of monthly mean daily PAR were validated against an independent 37-year observeddataset of 35 climate stations derived from 160 stations across Turkey by the Jackknifingmethod. The spatial variability patterns of monthly mean daily incident PAR were moreaccurately reflected in the surface maps created by the MLR-based models than in thosecreated by the universal kriging method, in particular, for spring (May) and autumn(November). The MLR-based spatial interpolation algorithms of PAR described in thisstudy indicated the significance of the multifactor approach to understanding and mappingspatio-temporal dynamics of PAR for a complex terrain over meso-scales.

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

NASA Astrophysics Data System (ADS)

Kabore, Seraphine Sawadogo

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

Evaluation de la qualite osseuse par les ondes guidees ultrasonores =

NASA Astrophysics Data System (ADS)

Abid, Alexandre

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

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

NASA Astrophysics Data System (ADS)

Francoeur, Dany

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

Time Sensitive Course of Action Development and Evaluation

DTIC Science & Technology

2010-10-01

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

Biological Rhythms Modelisation of Vigilance and Sleep in Microgravity State with COSINOR and Volterra's Kernels Methods

NASA Astrophysics Data System (ADS)

Gaudeua de Gerlicz, C.; Golding, J. G.; Bobola, Ph.; Moutarde, C.; Naji, S.

2008-06-01

The spaceflight under microgravity cause basically biological and physiological imbalance in human being. Lot of study has been yet release on this topic especially about sleep disturbances and on the circadian rhythms (alternation vigilance-sleep, body, temperature...). Factors like space motion sickness, noise, or excitement can cause severe sleep disturbances. For a stay of longer than four months in space, gradual increases in the planned duration of sleep were reported. [1] The average sleep in orbit was more than 1.5 hours shorter than the during control periods on earth, where sleep averaged 7.9 hours. [2] Alertness and calmness were unregistered yield clear circadian pattern of 24h but with a phase delay of 4h.The calmness showed a biphasic component (12h) mean sleep duration was 6.4 structured by 3-5 non REM/REM cycles. Modelisations of neurophysiologic mechanisms of stress and interactions between various physiological and psychological variables of rhythms have can be yet release with the COSINOR method. [3

Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

PubMed

Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-05-11

Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

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.

Effects of Kaolin Application on Light Absorption and Distribution, Radiation Use Efficiency and Photosynthesis of Almond and Walnut Canopies

PubMed Central

Rosati, Adolfo; Metcalf, Samuel G.; Buchner, Richard P.; Fulton, Allan E.; Lampinen, Bruce D.

2007-01-01

Background and Aims Kaolin applied as a suspension to plant canopies forms a film on leaves that increases reflection and reduces absorption of light. Photosynthesis of individual leaves is decreased while the photosynthesis of the whole canopy remains unaffected or even increases. This may result from a better distribution of light within the canopy following kaolin application, but this explanation has not been tested. The objective of this work was to study the effects of kaolin application on light distribution and absorption within tree canopies and, ultimately, on canopy photosynthesis and radiation use efficiency. Methods Photosynthetically active radiation (PAR) incident on individual leaves within the canopy of almond (Prunus dulcis) and walnut (Juglans regia) trees was measured before and after kaolin application in order to study PAR distribution within the canopy. The PAR incident on, and reflected and transmitted by, the canopy was measured on the same day for kaolin-sprayed and control trees in order to calculate canopy PAR absorption. These data were then used to model canopy photosynthesis and radiation use efficiency by a simple method proposed in previous work, based on the photosynthetic response to incident PAR of a top-canopy leaf. Key Results Kaolin increased incident PAR on surfaces of inner-canopy leaves, although there was an estimated 20 % loss in PAR reaching the photosynthetic apparatus, due to increased reflection. Assuming a 20 % loss of PAR, modelled photosynthesis and photosynthetic radiation use efficiency (PRUE) of kaolin-coated leaves decreased by only 6·3 %. This was due to (1) more beneficial PAR distribution within the kaolin-sprayed canopy, and (2) with decreasing PAR, leaf photosynthesis decreases less than proportionally, due to the curvature of the photosynthesis response-curve to PAR. The relatively small loss in canopy PRUE (per unit of incident PAR), coupled with the increased incident PAR on the leaf surface on inner-canopy leaves, resulted in an estimated increase in modelled photosynthesis of the canopy (+9 % in both walnut and almond). The small loss in PRUE (per unit of incident PAR) resulted in an increase in radiation use efficiency per unit of absorbed PAR, which more than compensated for the minor (7 %) reduction in canopy PAR absorption. Conclusions The results explain the apparently contradictory findings in the literature of positive or no effects of kaolin applications on canopy photosynthesis and yield, despite the decrease in photosynthesis by individual leaves when measured at the same PAR. PMID:17138580

Effects of kaolin application on light absorption and distribution, radiation use efficiency and photosynthesis of almond and walnut canopies.

PubMed

Rosati, Adolfo; Metcalf, Samuel G; Buchner, Richard P; Fulton, Allan E; Lampinen, Bruce D

2007-02-01

Kaolin applied as a suspension to plant canopies forms a film on leaves that increases reflection and reduces absorption of light. Photosynthesis of individual leaves is decreased while the photosynthesis of the whole canopy remains unaffected or even increases. This may result from a better distribution of light within the canopy following kaolin application, but this explanation has not been tested. The objective of this work was to study the effects of kaolin application on light distribution and absorption within tree canopies and, ultimately, on canopy photosynthesis and radiation use efficiency. Photosynthetically active radiation (PAR) incident on individual leaves within the canopy of almond (Prunus dulcis) and walnut (Juglans regia) trees was measured before and after kaolin application in order to study PAR distribution within the canopy. The PAR incident on, and reflected and transmitted by, the canopy was measured on the same day for kaolin-sprayed and control trees in order to calculate canopy PAR absorption. These data were then used to model canopy photosynthesis and radiation use efficiency by a simple method proposed in previous work, based on the photosynthetic response to incident PAR of a top-canopy leaf. Kaolin increased incident PAR on surfaces of inner-canopy leaves, although there was an estimated 20 % loss in PAR reaching the photosynthetic apparatus, due to increased reflection. Assuming a 20 % loss of PAR, modelled photosynthesis and photosynthetic radiation use efficiency (PRUE) of kaolin-coated leaves decreased by only 6.3 %. This was due to (1) more beneficial PAR distribution within the kaolin-sprayed canopy, and (2) with decreasing PAR, leaf photosynthesis decreases less than proportionally, due to the curvature of the photosynthesis response-curve to PAR. The relatively small loss in canopy PRUE (per unit of incident PAR), coupled with the increased incident PAR on the leaf surface on inner-canopy leaves, resulted in an estimated increase in modelled photosynthesis of the canopy (+9 % in both walnut and almond). The small loss in PRUE (per unit of incident PAR) resulted in an increase in radiation use efficiency per unit of absorbed PAR, which more than compensated for the minor (7 %) reduction in canopy PAR absorption. The results explain the apparently contradictory findings in the literature of positive or no effects of kaolin applications on canopy photosynthesis and yield, despite the decrease in photosynthesis by individual leaves when measured at the same PAR.

Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells.

PubMed

Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R

2012-03-27

Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37, and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150, and Arg-154), and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

Optical heterogeneous bioassay for the detection of the inflammatory biomarker suPAR

NASA Astrophysics Data System (ADS)

Tombelli, S.; Trono, C.; Adinolfi, B.; Chiavaioli, F.; Giannetti, A.; Eugen-Olsen, J.; Bernini, R.; Grimaldi, I. A.; Persichetti, G.; Testa, G.; Baldini, F.

2015-03-01

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory protein present in blood and a marker of disease presence, severity and prognosis. A heterogeneous sandwich assay is proposed for quantifying suPAR by employing a capture antibody from rat and a biotinylated detection antibody from mouse. Optical detection was achieved by a successive exposure of the biotinylated sandwich to streptavidin labelled with ATTO647N. The heterogeneous assay was implemented on a multichannel polymethylmetacrylate (PMMA) optical biochip, potentially capable of the simultaneous detection of more than one analyte. Capture antibody was immobilized on the PMMA surface of the microfluidic channel and the assay was performed with the following protocol: i) surface blocking with BSA, ii) incubation with suPAR or PBS, iii) incubation with biotinylated suPAR detection Ab and iv) incubation with streptavidin-ATTO647N. Promising preliminary results were obtained with this protocol. Moreover, an improved optical setup is proposed which avoids the mechanical scanning of the chip and consequently the in-series fluorescence excitation and read out, allowing the simultaneous measurement of the fluorescence on all the channels of the microfluidic chip.

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids

PubMed Central

Pillet, Flavien; Passot, Fanny Marie

2017-01-01

Bacterial centromeres–also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA—the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres. PMID:28562673

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

PubMed

Pillet, Flavien; Passot, Fanny Marie; Pasta, Franck; Anton Leberre, Véronique; Bouet, Jean-Yves

2017-01-01

Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

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

NASA Astrophysics Data System (ADS)

Martinez, Nicolas

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

Comparisons of luminaires: Efficacies and system design

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

Albright, L.D.; Both, A.J.

1994-12-31

After reviewing basic information, three design examples have been presented to demonstrate a process of supplemental lighting design. The sequences of each example suggest careful thought and analysis are required to obtain supplemental lighting designs that provide both high levels of PAR and suitable uniformity. The end results should suggest how an analysis can evolve to achieve desired results, and the types of tools and adjustments required. It appears possible to design research greenhouses and plant growth chambers to achieve a {+-}10% PAR uniformity using HIPS luminaires. Further, HPS luminaires (and, by extension, NEHD, etc.) are required to achieve highmore » PAR levels and have the decided advantage of providing the possibility of aiming, which reduces the region of the {open_quotes}edge effect{close_quotes}. Further, for designing plant lighting systems, a modification of the standard IES luminaire data file structure is potentially useful. Luminaire installation is an important factor to obtain PAR uniformity. Spacing and mounting height are critically important. Additionally, the mounting angle of each luminaire must be carefully adjusted to conform with design assumptions. This is true for both plant growth chambers and greenhouses. Surface reflectances are particularly important when designing for small lighted regions such as plant growth chambers and research greenhouses. It is not obvious, just from looking at a surface, what its reflectance is. It is suggested that an effort be mounted to develop valid surface reflectance data to be used by designers. The importance of the surfaces (particularly the walls) in achieving PAR uniformity suggests the importance of periodic cleaning/maintenance to retain initial reflectance values.« less

Human Modelling for Military Application (Applications militaires de la modelisation humaine)

DTIC Science & Technology

2010-10-01

techniques (rooted in the mathematics-centered analytic methods arising from World War I analyses by Lanchester 2 ). Recent requirements for research and...34Dry Shooting for Airplane Gunners - Popular Science Monthly". January 1919. p. 13-14. 2 Lanchester F.W., Mathematics in Warfare in The World of

Diffraction de rayons X sur les plaquettes de fer durcies par cyanuration

NASA Astrophysics Data System (ADS)

Popescu, M.; Hoyer, W.; Stegarescu, M.; Cornet, A.; Broll, N.

2004-11-01

Une méthode de cyanuration a été developpée pour les surfaces des plaquettes de fer, basée sur une réaction thermochimique qui conduit à la formation des couches dures sur le métal. Les échantillons ont été analysés, pour de temps différents de traitement, par diffraction de rayons X et par mesures de dureté.

Solar Irradiance Changes and Phytoplankton Productivity in Earth's Ocean Following Astrophysical Ionizing Radiation Events

NASA Astrophysics Data System (ADS)

Neale, Patrick J.; Thomas, Brian C.

2016-04-01

Two atmospheric responses to simulated astrophysical ionizing radiation events significant to life on Earth are production of odd-nitrogen species, especially NO2, and subsequent depletion of stratospheric ozone. Ozone depletion increases incident short-wavelength ultraviolet radiation (UVB, 280-315 nm) and longer (>600 nm) wavelengths of photosynthetically available radiation (PAR, 400-700 nm). On the other hand, the NO2 haze decreases atmospheric transmission in the long-wavelength UVA (315-400 nm) and short-wavelength PAR. Here, we use the results of previous simulations of incident spectral irradiance following an ionizing radiation event to predict changes in terran productivity focusing on photosynthesis of marine phytoplankton. The prediction is based on a spectral model of photosynthetic response, which was developed for the dominant genera in central regions of the ocean (Synechococcus and Prochlorococcus), and on remote-sensing-based observations of spectral water transparency, temperature, wind speed, and mixed layer depth. Predicted productivity declined after a simulated ionizing event, but the effect integrated over the water column was small. For integrations taking into account the full depth range of PAR transmission (down to 0.1% of utilizable PAR), the decrease was at most 2-3% (depending on strain), with larger effects (5-7%) for integrations just to the depth of the surface mixed layer. The deeper integrations were most affected by the decreased utilizable PAR at depth due to the NO2 haze, whereas shallower integrations were most affected by the increased surface UV. Several factors tended to dampen the magnitude of productivity responses relative to increases in surface-damaging radiation, for example, most inhibition in the modeled strains is caused by UVA and PAR, and the greatest relative increase in damaging exposure is predicted to occur in the winter when UV and productivity are low.

The protease-activated receptor-2 upregulates keratinocyte phagocytosis.

PubMed

Sharlow, E R; Paine, C S; Babiarz, L; Eisinger, M; Shapiro, S; Seiberg, M

2000-09-01

The protease-activated receptor-2 (PAR-2) belongs to the family of seven transmembrane domain receptors, which are activated by the specific enzymatic cleavage of their extracellular amino termini. Synthetic peptides corresponding to the tethered ligand domain (SLIGRL in mouse, SLIGKV in human) can activate PAR-2 without the need for receptor cleavage. PAR-2 activation is involved in cell growth, differentiation and inflammatory processes, and was shown to affect melanin and melanosome ingestion by human keratinocytes. Data presented here suggest that PAR-2 activation may regulate human keratinocyte phagocytosis. PAR-2 activation by trypsin, SLIGRL or SLIGKV increased the ability of keratinocytes to ingest fluorescently labeled microspheres or E. coli K-12 bioparticles. This PAR-2 mediated increase in keratinocyte phagocytic capability correlated with an increase in actin polymerization and *-actinin reorganization, cell surface morphological changes and increased soluble protease activity. Moreover, addition of serine protease inhibitors downmodulated both the constitutive and the PAR-2 mediated increases in phagocytosis, suggesting that serine proteases mediate this functional activity in keratinocytes. PAR-2 involvement in keratinocyte phagocytosis is a novel function for this receptor.

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

NASA Astrophysics Data System (ADS)

Bredin, Nathalie

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

Mechanisms of CDC-42 activation during contact-induced cell polarization.

PubMed

Chan, Emily; Nance, Jeremy

2013-04-01

Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure-function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts.

Mechanisms of CDC-42 activation during contact-induced cell polarization

PubMed Central

Chan, Emily; Nance, Jeremy

2013-01-01

Summary Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure–function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts. PMID:23424200

A new class of orthosteric uPAR·uPA small-molecule antagonists are allosteric inhibitors of the uPAR·vitronectin interaction.

PubMed

Liu, Degang; Zhou, Donghui; Wang, Bo; Knabe, William Eric; Meroueh, Samy O

2015-06-19

The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that is at the center of an intricate network of protein-protein interactions. Its immediate binding partners are the serine proteinase urokinase (uPA), and vitronectin (VTN), a component of the extracellular matrix. uPA and VTN bind at distinct sites on uPAR to promote extracellular matrix degradation and integrin signaling, respectively. Here, we report the discovery of a new class of pyrrolone small-molecule inhibitors of the tight ∼1 nM uPAR·uPA protein-protein interaction. These compounds were designed to bind to the uPA pocket on uPAR. The highest affinity compound, namely 7, displaced a fluorescently labeled α-helical peptide (AE147-FAM) with an inhibition constant Ki of 0.7 μM and inhibited the tight uPAR·uPAATF interaction with an IC50 of 18 μM. Biophysical studies with surface plasmon resonance showed that VTN binding is highly dependent on uPA. This cooperative binding was confirmed as 7, which binds at the uPAR·uPA interface, also inhibited the distal VTN·uPAR interaction. In cell culture, 7 blocked the uPAR·uPA interaction in uPAR-expressing human embryonic kidney (HEK-293) cells and impaired cell adhesion to VTN, a process that is mediated by integrins. As a result, 7 inhibited integrin signaling in MDA-MB-231 cancer cells as evidenced by a decrease in focal adhesion kinase (FAK) phosphorylation and Rac1 GTPase activation. Consistent with these results, 7 blocked breast MDA-MB-231 cancer cell invasion with IC50 values similar to those observed in ELISA and surface plasmon resonance competition studies. Explicit-solvent molecular dynamics simulations show that the cooperativity between uPA and VTN is attributed to stabilization of uPAR motion by uPA. In addition, free energy calculations revealed that uPA stabilizes the VTNSMB·uPAR interaction through more favorable electrostatics and entropy. Disruption of the uPAR·VTNSMB interaction by 7 is consistent with the cooperative binding to uPAR by uPA and VTN. Interestingly, the VTNSMB·uPAR interaction was less favorable in the VTNSMB·uPAR·7 complex suggesting potential cooperativity between 7 and VTN. Compound 7 provides an excellent starting point for the development of more potent derivatives to explore uPAR biology.

Establishment of Epithelial Attachment on Titanium Surface Coated with Platelet Activating Peptide

PubMed Central

Sugawara, Shiho; Maeno, Masahiko; Lee, Cliff; Nagai, Shigemi; Kim, David M.; Da Silva, John; Kondo, Hisatomo

2016-01-01

The aim of this study was to produce epithelial attachment on a typical implant abutment surface of smooth titanium. A challenging complication that hinders the success of dental implants is peri-implantitis. A common cause of peri-implantitis may results from the lack of epithelial sealing at the peri-implant collar. Histologically, epithelial sealing is recognized as the attachment of the basement membrane (BM). BM-attachment is promoted by activated platelet aggregates at surgical wound sites. On the other hand, platelets did not aggregate on smooth titanium, the surface typical of the implant abutment. We then hypothesized that epithelial BM-attachment was produced when titanium surface was modified to allow platelet aggregation. Titanium surfaces were coated with a protease activated receptor 4-activating peptide (PAR4-AP). PAR4-AP coating yielded rapid aggregation of platelets on the titanium surface. Platelet aggregates released robust amount of epithelial chemoattractants (IGF-I, TGF-β) and growth factors (EGF, VEGF) on the titanium surface. Human gingival epithelial cells, when they were co-cultured on the platelet aggregates, successfully attached to the PAR4-AP coated titanium surface with spread laminin5 positive BM and consecutive staining of the epithelial tight junction component ZO1, indicating the formation of complete epithelial sheet. These in-vitro results indicate the establishment of epithelial BM-attachment to the titanium surface. PMID:27741287

Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression.

PubMed

Ramsay, Andrew J; Dong, Ying; Hunt, Melanie L; Linn, MayLa; Samaratunga, Hemamali; Clements, Judith A; Hooper, John D

2008-05-02

Kallikrein-related peptidase 4 (KLK4) is one of the 15 members of the human KLK family and a trypsin-like, prostate cancer-associated serine protease. Signaling initiated by trypsin-like serine proteases are transduced across the plasma membrane primarily by members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Here we show, using Ca(2+) flux assays, that KLK4 signals via both PAR-1 and PAR-2 but not via PAR-4. Dose-response analysis over the enzyme concentration range 0.1-1000 nM indicated that KLK4-induced Ca(2+) mobilization via PAR-1 is more potent than via PAR-2, whereas KLK4 displayed greater efficacy via the latter PAR. We confirmed the specificity of KLK4 signaling via PAR-2 using in vitro protease cleavage assays and anti-phospho-ERK1/2/total ERK1/2 Western blot analysis of PAR-2-overexpressing and small interfering RNA-mediated receptor knockdown cell lines. Consistently, confocal microscopy analyses indicated that KLK4 initiates loss of PAR-2 from the cell surface and receptor internalization. Immunohistochemical analysis indicated the co-expression of agonist and PAR-2 in primary prostate cancer and bone metastases, suggesting that KLK4 signaling via this receptor will have pathological relevance. These data provide insight into KLK4-mediated cell signaling and suggest that signals induced by this enzyme via PARs may be important in prostate cancer.

Studies of the net surface radiative flux from satellite radiances during FIFE

NASA Technical Reports Server (NTRS)

Frouin, Robert

1993-01-01

Studies of the net surface radiative flux from satellite radiances during First ISLSCP Field Experiment (FIFE) are presented. Topics covered include: radiative transfer model validation; calibration of VISSR and AVHRR solar channels; development and refinement of algorithms to estimate downward solar and terrestrial irradiances at the surface, including photosynthetically available radiation (PAR) and surface albedo; verification of these algorithms using in situ measurements; production of maps of shortwave irradiance, surface albedo, and related products; analysis of the temporal variability of shortwave irradiance over the FIFE site; development of a spectroscopy technique to estimate atmospheric total water vapor amount; and study of optimum linear combinations of visible and near-infrared reflectances for estimating the fraction of PAR absorbed by plants.

Impact of errors in short wave radiation and its attenuation on modeled upper ocean heat content

DTIC Science & Technology

Photosynthetically available radiation (PAR) and its attenuation with the depth represent a forcing (source) term in the governing equation for the...and vertical attenuation of PAR have on the upper ocean model heat content. In the Monterey Bay area, we show that with a decrease in water clarity...attenuation coefficient. For Jerlov’s type IA water (attenuation coefficient is 0.049 m1), the relative error in surface PAR introduces an error

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

NASA Astrophysics Data System (ADS)

Mijiyawa, Faycal

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

Involvement of proteinase activated receptor-2 in the vascular response to sphingosine 1-phosphate.

PubMed

Roviezzo, Fiorentina; De Angelis, Antonella; De Gruttola, Luana; Bertolino, Antonio; Sullo, Nikol; Brancaleone, Vincenzo; Bucci, Mariarosaria; De Palma, Raffaele; Urbanek, Konrad; D'Agostino, Bruno; Ianaro, Angela; Sorrentino, Raffaella; Cirino, Giuseppe

2014-04-01

S1P (sphingosine 1-phosphate) represents one of the key latest additions to the list of vasoactive substances that modulate vascular tone. PAR-2 (proteinase activated receptor-2) has been shown to be involved in cardiovascular function. In the present study, we investigated the involvement of PAR-2 in S1P-induced effect on vascular tone. The present study has been performed by using isolated mouse aortas. Both S1P and PAR-2 agonists induced endothelium-dependent vasorelaxation. L-NAME (N(G)-nitro-L-arginine methyl ester) and wortmannin abrogated the S1P-induced vasorelaxatioin, while significantly inhibiting the PAR-2-mediated effect. Either ENMD1068, a PAR-2 antagonist, or gabexate, a serine protease inhibitor, significantly inhibited S1P-induced vasorelaxation. Aortic tissues harvested from mice overexpressing PAR-2 displayed a significant increase in vascular response to S1P as opposed to PAR-2-null mice. Immunoprecipitation and immunofluorescence studies demonstrated that S1P(1) interacted with PAR-2 and co-localized with PAR-2 on the vascular endothelial surface. Furthermore, S1P administration to vascular tissues triggered PAR-2 mobilization from the plasma membrane to the perinuclear area; S1P-induced translocation of PAR-2 was abrogated when aortic rings were pre-treated with ENMD1068 or when caveolae dysfunction occurred. Similarly, experiments performed in cultured endothelial cells (human umbilical vein endothelial cells) showed a co-localization of S1P(1) and PAR2, as well as the ability of S1P to induce PAR-2 trafficking. Our results suggest that S1P induces endothelium-dependent vasorelaxation mainly through S1P(1) and involves PAR-2 transactivation.

A method for estimating the incident PAR on inclined surfaces

NASA Astrophysics Data System (ADS)

Xie, Xiaoping; Gao, Wei; Gao, Zhiqiang

2008-08-01

A new simple model has been developed that incorporates Digital Elevation Model (DEM) and Moderate Resolution Imaging Spectroradiometer (MODIS) products to produce incident photosynthetically active radiation (PAR) for tilted surface. The method is based on a simplification of the general radiative transfer equation, which considers five major processes of attenuation of solar radiation: 1) Rayleigh scattering, 2) absorption by ozone and water vapor, 3) aerosol scattering, 4) multiple reflectance between surface and atmosphere, and 5) three terrain factors: slope and aspect, isotropic sky view factor, and additional radiation by neighbor reflectance. A comparison of the model results with observational data from the Yucheng and Changbai Mountain sites of the Chinese Ecosystem Research Network (CERN) shows the correlation coefficient as 0.929 and 0.904, respectively. A comparison of the model results with the 2006 filed measured PAR in the Yucheng and Changbai sites shows the correlation coefficient as 0.929 and 0.904, respectively, and the average percent error as 10% and 15%, respectively.

Structural Basis of Interaction between Urokinase-Type Plasminogen Activator and Its Receptor

PubMed Central

Barinka, Cyril; Parry, Graham; Callahan, Jennifer; Shaw, David E.; Kuo, Alice; Bdeir, Khalil; Cines, Douglas B.; Mazar, Andrew; Lubkowski, Jacek

2009-01-01

Summary Recent studies indicate that binding of urokinase-type plasminogen activator (uPA) to its high affinity receptor (uPAR), orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known as to the exact mode of uPAR-uPA interactions and the presumed conformational changes that accompanying uPA-uPAR engagement. Here we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell surface anchoring sequence, in complex with the amino terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 Å. We also report the 1.9 Å crystal structure of the free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR-uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding. PMID:16979660

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 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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr32922d

A New Class of Orthosteric uPAR•uPA Small-Molecule Antagonists Are Allosteric Inhibitors of the uPAR•Vitronectin Interaction

PubMed Central

Liu, Degang; Zhou, Donghui; Wang, Bo; Knabe, William Eric; Meroueh, Samy O.

2015-01-01

The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that is at the center of an intricate network of protein-protein interactions. Its immediate binding partners are the serine proteinase urokinase (uPA), and vitronectin (VTN), a component of the extracellular matrix. uPA and VTN bind at distinct sites on uPAR to promote extracellular matrix degradation and integrin signaling, respectively. Here, we report the discovery of a new class of pyrrolone small-molecule inhibitors of the tight ∼1 nM uPAR•uPA protein-protein interaction. These compounds were designed to bind to the uPA pocket on uPAR. The highest affinity compound, namely 7, displaced a fluorescently-labeled α-helical peptide (AE147-FAM) with an inhibition constant Ki of 0.7 µM and inhibited the tight uPAR•uPAATF interaction with an IC50 of 18 µM. Biophysical studies with surface plasmon resonance showed that VTN binding is highly dependent on uPA. This cooperative binding was confirmed as 7, which binds at the uPAR•uPA interface, also inhibited the distal VTN•uPAR interaction. In cell culture, 7 blocked the uPAR•uPA interaction in uPAR-expressing human embryonic kidney (HEK-293) cells, and impaired cell adhesion to VTN, a process that is mediated by integrins. As a result, 7 inhibited integrin signaling in MDA-MB-231 cancer cells as evidenced by a decrease in focal adhesion kinase (FAK) phosphorylation and Rac1 GTPase activation. Consistent with these results, 7 blocked breast MDA-MB-231 cancer cell invasion with IC50 values similar to those observed in ELISA and surface plasmon resonance competition studies. Explicit-solvent molecular dynamics simulations show that the cooperativity between uPA and VTN is attributed to stabilization of uPAR motion by uPA. In addition, free energy calculations revealed that uPA stabilizes the VTN•uPARSMB interaction through more favorable electrostatics and entropy. Disruption of the uPAR•VTNSMB interaction by 7 is consistent with the cooperative binding to uPAR by uPA and VTN. Interestingly, the VTNSMB•uPAR interaction was less favorable in the VTNSMB•uPAR•7 complex suggesting potential cooperativity between 7 and VTN. Compound 7 provides an excellent starting point for the development of more potent derivatives to explore uPAR biology. PMID:25671694

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

PubMed

Carvalho, Ricardo Filipe da Silva; Nilsson, Gunnar; Harvima, Ilkka Tapani

2010-02-01

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.

An Apical MRCK-driven Morphogenetic Pathway Controls Epithelial Polarity

PubMed Central

Zihni, Ceniz; Vlassaks, Evi; Terry, Stephen; Carlton, Jeremy; Leung, Thomas King Chor; Olson, Michael; Pichaud, Franck; Balda, Maria Susana; Matter, Karl

2017-01-01

Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown. Here we show that the Cdc42 effector MRCK activates Myosin-II at the apical pole to segregate aPKC-Par6 from junctional Par3, defining the apical domain. Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC-Par6 downregulating antagonistic RhoA-driven junctional actomyosin contractility, and drives polarization of cytosolic brush border determinants and apical morphogenesis. MRCK-activated polarized actomyosin contractility is required for apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors. Our results identify an apical origin of actomyosin-driven morphogenesis that couples cytoskeletal reorganization to PAR polarity signalling. PMID:28825699

Effet de la substitution du cuivre par du lithium sur les proprietes de l'oxyde spinelle lithium(x)cuivre(y-x)cobalt(3-y)oxygen(4) etudie pour l'electrocatalyse de la reaction de degagement de l'oxygene en milieu alcalin

NASA Astrophysics Data System (ADS)

Fatih, Khalid

L'electrolyse de l'eau demeure la seule technologie industrielle de generation de l'hydrogene et de l'oxygene tres purs sans rejet de CO2 dans l'atmosphere, ce qui le rend tres attrayant par rapport a la combustion de carburants fossiles qui provoque presentement de serieux problemes environnementaux. Dans le but d'ameliorer le rendement de ce procede, nous avons developpe de nouveaux materiaux d'anode peu couteux, a base de l'oxyde mixte CuyCo3-yO 4, qui possedent une cinetique rapide pour la reaction de degagement de l'oxygene (RDO). Cette reaction suscite un interet particulier en raison de la surtension d'activation relativement elevee a l'anode qui cause la principale perte de rendement du procede. Une etude systematique a ete effectuee sur la substitution du Cu par du Li (0 a 40%), afin d'elucider les proprietes electrocatalytiques des oxydes LixCuy-xCo3-yO4. Ces oxydes, prepares sous forme de poudres par decomposition thermique des nitrates precurseurs entre 300 et 500°C, ont montre (DRX et FTIR) une structure spinelle inverse non-stcechiometrique avec une diminution du volume de la maille cristalline. La surface specifique par BET est d'environ 6 m2 g-1. Le pcn, obtenu par titrage acido-basique, a indique une diminution de la force du lien M-OH avec le taux du Li dans l'oxyde. Les analyses par XPS, realisees sur des films d'oxyde prepares par nebulisation reactive sur un substrat lisse de nickel, revelent un enrichissement de la surface en Cu a partir de 30% Li, et la presence des cations de surface Co2+, Co3+, Cu +, Cu2+ et Cu3+. La concentration de ce dernier montre un maximum a 10 et 20% Li. Suite a la substitution du Cu par du Li, la compensation de la charge serait assuree principalement par la formation d'especes Cu3+ pour les oxydes contenant jusqu'a 20% Li, et par la formation d'especes Co3+ aux taux de substitution superieurs. Les micrographies MEB montrent une morphologie hemispherique des particules d'oxyde reparties uniformement sur le substrat de nickel avec une tendance a l'agglomeration lorsque le taux de Li est accru. Les micrographies AFM revelent une micro-porosite de ces particules d'oxyde. Les films minces deposes sur un substrat de verre ont montre une conductivite tres interessante de l'ordre de 103O-1 cm-1 pour LixCuy-x Co3-yO4 comparee a 2,8 O-1 cm-1 pour Co3O4. La spectroscopie d'impedance a permis de distinguer les processus de la surface interne des films d'oxydes de ceux de l'interface electrode/electrolyte. Les courbes Mott-Schottky (1/C2 en fonction du potentiel) montrent que les films d'oxyde se comportent comme des semi-conducteurs de type p tres dopes (degeneres). Le potentiel de bandes plates et la densite des porteurs de charge majoritaires des oxydes LixCuy-xCo3-yO4 sont de l'ordre de 0,48 a 0,52 V et 1019 a 10 20 cm-3 respectivement. Pour Co 3O4 ces parametres sont de 0,47 V et ≈10 18 cm-3. (Abstract shortened by UMI.)

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 in the spring and fall at the agricultural sites. When using the MODIS MOD17-based parameters to estimate LUE, fAPAR chl generated better agreements with GPP (r2= 0.79-0.91) than MOD15A2 fPAR (r2= 0.57-0.84).However, underestimations of GPP were also observed, especially for the crop fields. When applying the site-specific LUE max value to estimate in situ LUE, the magnitude of estimated GPP was closer to in situ GPP; this method produced a slight overestimation for the MOD15A2 fPAR at the Bartlett forest. This study highlights the importance of accurate land surface parameterizations to achieve reliable carbon monitoring capabilities from remote sensing information.

Tropopause Pressure May Explain California Droughts and Wet Period

NASA Astrophysics Data System (ADS)

Mazdiyasni, O.; AghaKouchak, A.

2017-12-01

Sea surface temperatures and teleconnection patterns such as El Nino/La Nina are considered the main culprits behind major California droughts. However, the underlying relationship between sea surface temperatures (SSTs) and precipitation anomalies is relatively weak. In 2015-2016 the most extreme El Nino did not lead to a wet season as expected, which triggered a series of studies on this topic. Here we show that tropopause level pressure in a region in the northeastern Pacific Ocean (dubbed the PARS-NEP region) plays a major role in whether California will experience a wet or dry year and often dominates the role of SST-based teleconnections. Our results indicate that pressure in the PARS-NEP region Granger-Causes precipitation in California during the wet season. We show that when pressure in the PARS-NEP region is in the lower (upper) tertile, 85% of wet seasons across California have a positive (negative) precipitation anomaly. The observed relationship between PARS-NEP and California precipitation is stronger than all the commonly used SST-based climatic indictors frequently used for understanding causes of droughts.

Team Modelling: Survey of Experimental Platforms (Modelisation d’equipes : Examen de plate-formes experimentales)

DTIC Science & Technology

2006-09-01

Control Force Agility Shared Situational Awareness Attentional Demand Interoperability Network Based Operations Effect Based Operations Speed of...Command Self Synchronization Reach Back Reach Forward Information Superiority Increased Mission Effectiveness Humansystems® Team Modelling...communication effectiveness and Distributed Mission Training (DMT) effectiveness . The NASA Ames Centre - Distributed Research Facilities platform could

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

DTIC Science & Technology

1988-06-01

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

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand.

PubMed

De Souza, Melissa; Matthews, Hayden; Lee, Jodi A; Ranson, Marie; Kelso, Michael J

2011-04-15

Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA:uPAR interaction represent promising anti-tumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC(50)1=0.8 nM, IC(50)2=33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 μM) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 μM. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC(50) >100 μM for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Solar Irradiance Changes and Phytoplankton Productivity in Earth's Ocean Following Astrophysical Ionizing Radiation Events.

PubMed

Neale, Patrick J; Thomas, Brian C

2016-04-01

Two atmospheric responses to simulated astrophysical ionizing radiation events significant to life on Earth are production of odd-nitrogen species, especially NO2, and subsequent depletion of stratospheric ozone. Ozone depletion increases incident short-wavelength ultraviolet radiation (UVB, 280-315 nm) and longer (>600 nm) wavelengths of photosynthetically available radiation (PAR, 400-700 nm). On the other hand, the NO2 haze decreases atmospheric transmission in the long-wavelength UVA (315-400 nm) and short-wavelength PAR. Here, we use the results of previous simulations of incident spectral irradiance following an ionizing radiation event to predict changes in terran productivity focusing on photosynthesis of marine phytoplankton. The prediction is based on a spectral model of photosynthetic response, which was developed for the dominant genera in central regions of the ocean (Synechococcus and Prochlorococcus), and on remote-sensing-based observations of spectral water transparency, temperature, wind speed, and mixed layer depth. Predicted productivity declined after a simulated ionizing event, but the effect integrated over the water column was small. For integrations taking into account the full depth range of PAR transmission (down to 0.1% of utilizable PAR), the decrease was at most 2-3% (depending on strain), with larger effects (5-7%) for integrations just to the depth of the surface mixed layer. The deeper integrations were most affected by the decreased utilizable PAR at depth due to the NO2 haze, whereas shallower integrations were most affected by the increased surface UV. Several factors tended to dampen the magnitude of productivity responses relative to increases in surface-damaging radiation, for example, most inhibition in the modeled strains is caused by UVA and PAR, and the greatest relative increase in damaging exposure is predicted to occur in the winter when UV and productivity are low.

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

Estimation of land photosynthetically active radiation in clear sky using MODIS atmosphere and land products

NASA Astrophysics Data System (ADS)

Xie, Xiaoping; Gao, Wei; Gao, Zhiqiang

2008-08-01

Photosynthetically active radiation (PAR) is an essential parameter in vegetation growth model and soil carbon sequestration models. A method is presented with which instantaneous PAR can be calculated with high accuracy from Moderate Resolution Imaging Spectroradiometer (MODIS) atmosphere and land products. The method is based on a simplification of the general radiative transfer equation, which considers five major processes of attenuation of solar radiation: Rayleigh scattering, absorption by ozone and water vapor, aerosol scattering, multiply reflectance between surface and atmosphere. Comparing 108 retrieveled results to filed measured PAR in Yucheng station of Chinese Ecosystem Research Network (CERN) in 2006, and the r-square of 0.855 indicates that the computed results can interpret actual PAR well.

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.

Décontamination nucléaire par laser UV

NASA Astrophysics Data System (ADS)

Delaporte, Ph.; Gastaud, M.; Marine, W.; Sentis, M.; Uteza, O.; Thouvenot, P.; Alcaraz, J. L.; Le Samedy, J. M.; Blin, D.

2003-06-01

Le développement et l'utilisation de procédés propres pour le nettoyage ou la préparation de surfaces est l'une des priorités du milieu industriel. Cet intérêt est d'autant plus grand dans le domaine du nucléaire pour lequel la réduction des déchets est un axe de recherche important. Un dispositif de décontamination nucléaire par laser UV impulsionnel a été développé et testé. Il est composé. d'un laser à excimères de 1kW, d'un faisceau de fibres optiques et d'un dispositif de récupération des particules. Les essais réalisés en milieu actif ont démontré sa capacité à nettoyer des surfaces métalliques polluées par différents radioéléments avec des facteurs de décontamination généralement supérieurs à 10. Ce dispositif permet de décontaminer de grandes surfaces de géométrie simple en réduisant fortement la génération de déchets secondaires. Il est, à ce jour et dans ces conditions d'utilisations, le procédé de décontamination par voie sèche le plus efficace.

The role of proteinase 3 (PR3) and the protease-activated receptor-2 (PAR-2) pathway in dendritic cell (DC) maturation of human-DC-like monocytes and murine DC.

PubMed

Jiang, Bo; Grage-Griebenow, Evelin; Csernok, Elena; Butherus, Kristine; Ehlers, Stefan; Gross, Wolfgang L; Holle, Julia U

2010-01-01

The aim of the study was to assess PAR-2 expression on dendritic cell (DC) subsets and other immune cells of Wegener's granulomatosis (WG) patients and healthy controls (HC) and to investigate whether Proteinase 3 (PR3, a serine protease which can activate PAR2) induces maturation of human DC-like monocytes and murine Flt-3 ligand- and GM-CSF-generated DC. Human peripheral blood cells including DC subsets and Flt-3l- and GM-CSF-generated mouse DC were analysed for expression of PAR-2 and DC maturation markers by flow cytometry before and after stimulation with PR3, trypsin, PAR-2 agonist or LPS for 24 h. There was no difference of PAR-2 expression on PMNs, monocytes, lymphocytes and DC between all WG samples and HC. However, in inactive WG, expression of PAR-2 was downregulated on the cell surface of PMNs, monocytes, lymphocytes, and CD11c+DC compared to active WG and HC. PR3 and PAR2-agonists did not induce upregulation of PAR-2 or maturation markers of human DC-like monocytes in WG and HC. Likewise, murine PR3 did not induce upregulation of PAR-2 or maturation markers in murine DC. PAR-2 expression is downregulated on human peripheral blood cells including CD11c+ DC in inactive WG compared to active WG and HC, possibly reflecting a non-activated status of these cells in inactive disease. PR3 and PAR-2- agonists did not induce maturation of human ex vivo DC-like monocytes in WG and HC and of murine DC, suggesting this pathway is not singularly involved in the maturation of these cell subsets.

Improving National Water Modeling: An Intercomparison of two High-Resolution, Continental Scale Models, CONUS-ParFlow and the National Water Model

NASA Astrophysics Data System (ADS)

Tijerina, D.; Gochis, D.; Condon, L. E.; Maxwell, R. M.

2017-12-01

Development of integrated hydrology modeling systems that couple atmospheric, land surface, and subsurface flow is growing trend in hydrologic modeling. Using an integrated modeling framework, subsurface hydrologic processes, such as lateral flow and soil moisture redistribution, are represented in a single cohesive framework with surface processes like overland flow and evapotranspiration. There is a need for these more intricate models in comprehensive hydrologic forecasting and water management over large spatial areas, specifically the Continental US (CONUS). Currently, two high-resolution, coupled hydrologic modeling applications have been developed for this domain: CONUS-ParFlow built using the integrated hydrologic model ParFlow and the National Water Model that uses the NCAR Weather Research and Forecasting hydrological extension package (WRF-Hydro). Both ParFlow and WRF-Hydro include land surface models, overland flow, and take advantage of parallelization and high-performance computing (HPC) capabilities; however, they have different approaches to overland subsurface flow and groundwater-surface water interactions. Accurately representing large domains remains a challenge considering the difficult task of representing complex hydrologic processes, computational expense, and extensive data needs; both models have accomplished this, but have differences in approach and continue to be difficult to validate. A further exploration of effective methodology to accurately represent large-scale hydrology with integrated models is needed to advance this growing field. Here we compare the outputs of CONUS-ParFlow and the National Water Model to each other and with observations to study the performance of hyper-resolution models over large domains. Models were compared over a range of scales for major watersheds within the CONUS with a specific focus on the Mississippi, Ohio, and Colorado River basins. We use a novel set of approaches and analysis for this comparison to better understand differences in process and bias. This intercomparison is a step toward better understanding how much water we have and interactions between surface and subsurface. Our goal is to advance our understanding and simulation of the hydrologic system and ultimately improve hydrologic forecasts.

BLAM (Benthic Light Availability Model): A Proposed Model of Hydrogeomorphic Controls on Light in Rivers

NASA Astrophysics Data System (ADS)

Julian, J. P.; Doyle, M. W.; Stanley, E. H.

2006-12-01

Light is vital to the dynamics of aquatic ecosystems. It drives photosynthesis and photochemical reactions, affects thermal structure, and influences behavior of aquatic biota. Despite the fundamental role of light to riverine ecosystems, light studies in rivers have been mostly neglected because i) boundary conditions (e.g., banks, riparian vegetation) make ambient light measurements difficult, and ii) the optical water quality of rivers is highly variable and difficult to characterize. We propose a benthic light availability model (BLAM) that predicts the percent of incoming photosynthetically active radiation (PAR) available at the river bed. BLAM was developed by quantifying light attenuation of the five hydrogeomorphic controls that dictate riverine light availability: topography, riparian vegetation, channel geometry, optical water quality, and water depth. BLAM was calibrated using hydrogeomorphic data and light measurements from two rivers: Deep River - a 5th-order, turbid river in central North Carolina, and Big Spring Creek - a 2nd-order, optically clear stream in central Wisconsin. We used a series of four PAR sensors to measure i) above-canopy PAR, ii) PAR above water surface, iii) PAR below water surface, and iv) PAR on stream bed. These measurements were used to develop empirical light attenuation coefficients, which were then used in combination with optical water quality measurements, shading analyses, channel surveys, and flow records to quantify the spatial and temporal variability in riverine light availability. Finally, we apply BLAM to the Baraboo River - a 6th-order, 120-mile, unimpounded river in central Wisconsin - in order to characterize light availability along the river continuum (from headwaters to mouth).

α-Enolase Causes Proinflammatory Activation of Pulmonary Microvascular Endothelial Cells and Primes Neutrophils Through Plasmin Activation of Protease-Activated Receptor 2.

PubMed

Bock, Ashley; Tucker, Nicole; Kelher, Marguerite R; Khan, Samina Y; Gonzalez, Eduardo; Wohlauer, Max; Hansen, Kirk; Dzieciatkowska, Monika; Sauaia, Angels; Banerjee, Anirban; Moore, Ernest E; Silliman, Christopher C

2015-08-01

Proinflammatory activation of vascular endothelium leading to increased surface expression of adhesion molecules and neutrophil (PMN) sequestration and subsequent activation is paramount in the development of acute lung injury and organ injury in injured patients. We hypothesize that α-enolase, which accumulates in injured patients, primes PMNs and causes proinflammatory activation of endothelial cells leading to PMN-mediated cytotoxicity. Proteomic analyses of field plasma samples from injured versus healthy patients were used for protein identification. Human pulmonary microvascular endothelial cells (HMVECs) were incubated with α-enolase or thrombin, and intercellular adhesion molecule-1 surface expression was measured by flow cytometry. A two-event in vitro model of PMN cytotoxicity HMVECs activated with α-enolase, thrombin, or buffer was used as targets for lysophosphatidylcholine-primed or buffer-treated PMNs. The PMN priming activity of α-enolase was completed, and lysates from both PMNs and HMVECs were immunoblotted for protease-activated receptor 1 (PAR-1) and PAR-2 and coprecipitation of α-enolase with PAR-2 and plasminogen/plasmin. α-Enolase increased 10.8-fold in injured patients (P < 0.05). Thrombin and α-enolase significantly increased intercellular adhesion molecule-1 surface expression on HMVECs, which was inhibited by antiproteases, induced PMN adherence, and served as the first event in the two-event model of PMN cytotoxicity. α-Enolase coprecipitated with PAR-2 and plasminogen/plasmin on HMVECs and PMNs and induced PMN priming, which was inhibited by tranexamic acid, and enzymatic activity was not required. α-Enolase increases after injury and may activate pulmonary endothelial cells and prime PMNs through plasmin activity and PAR-2 activation. Such proinflammatory endothelial activation may predispose to PMN-mediated organ injury.

Autocrine Extra-Pancreatic Trypsin 3 Secretion Promotes Cell Proliferation and Survival in Esophageal Adenocarcinoma

PubMed Central

Han, Song; Lee, Constance W.; Trevino, Jose G.; Hughes, Steven J.; Sarosi, George A.

2013-01-01

Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett’s Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (∼ 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA. PMID:24146905

Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1.

PubMed

Wang, Yan-Jie; Guo, Xiao-Long; Li, Sheng-An; Zhao, Yu-Qi; Liu, Zi-Chao; Lee, Wen-Hui; Xiang, Yang; Zhang, Yun

2014-07-01

The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study, we found that PHB localized on the platelet membrane and participated in PAR1-mediated human platelet aggregation, suggesting that PHB likely regulates the signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization and degradation is unclear. In the current study, flow cytometry revealed that PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically associates with PAR1 in a time-dependent manner following induction with PAR1-activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231 cells. Depletion of PHB by RNA interference significantly inhibited PAR1 activated internalization and led to sustained Erk1/2 phosphorylation in the HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1 degradation. These results suggest that persistent PAR1 signaling due to the absence of membrane PHB and decreased PAR1 degradation caused by the upregulation of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells highly invasive. As such, PHB may be a novel target in future anti-cancer therapeutics, or in more refined cancer malignancy diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

Magnetic activity and radial velocity filtering of young Suns: the weak-line T-Tauri stars Par 1379 and Par 2244

NASA Astrophysics Data System (ADS)

Hill, C. A.; Carmona, A.; Donati, J.-F.; Hussain, G. A. J.; Gregory, S. G.; Alencar, S. H. P.; Bouvier, J.; The Matysse Collaboration

2017-12-01

We report the results of our spectropolarimetric monitoring of the weak-line T-Tauri stars (wTTSs) Par 1379 and Par 2244, within the MaTYSSE (Magnetic Topologies of Young Stars and the Survival of close-in giant Exoplanets) programme. Both stars are of a similar mass (1.6 and 1.8 M⊙) and age (1.8 and 1.1 Myr), with Par 1379 hosting an evolved low-mass dusty circumstellar disc, and with Par 2244 showing evidence of a young debris disc. We detect profile distortions and Zeeman signatures in the unpolarized and circularly polarized lines for each star, and have modelled their rotational modulation using tomographic imaging, yielding brightness and magnetic maps. We find that Par 1379 harbours a weak (250 G), mostly poloidal field tilted 65° from the rotation axis. In contrast, Par 2244 hosts a stronger field (860 G) split 3:2 between poloidal and toroidal components, with most of the energy in higher order modes, and with the poloidal component tilted 45° from the rotation axis. Compared to the lower mass wTTSs, V819 Tau and V830 Tau, Par 2244 has a similar field strength, but is much more complex, whereas the much less complex field of Par 1379 is also much weaker than any other mapped wTTS. We find moderate surface differential rotation of 1.4× and 1.8× smaller than Solar, for Par 1379 and Par 2244, respectively. Using our tomographic maps to predict the activity-related radial velocity (RV) jitter, and filter it from the RV curves, we find RV residuals with dispersions of 0.017 and 0.086 km s-1 for Par 1379 and Par 2244, respectively. We find no evidence for close-in giant planets around either star, with 3σ upper limits of 0.56 and 3.54 MJup (at an orbital distance of 0.1 au).

NMR Investigations into Polydimethylsiloxane Adsorption on Silica Aggregates

NASA Astrophysics Data System (ADS)

Cohen Addad, J. P.; Morel, N.

1996-02-01

Adsorption properties of polydimethylsiloxane on the surface of silica aggregates are studied from chemical microanalysis combined with proton magnetic relaxation measurements and from swelling measurements performed on mixtures. It is shown that polymer molecules, observed right after the preparation of mixtures, are strongly adsorbed on about 1/4 of the silica surface, only; they form islets. It is also shown that the number of contact points of a chain with the surface is proportional to sqrt{N} during the progressive saturation of the silica surface; N is the number of monometric units in one chain. Les propriétés d'adsorption du polydimethylsiloxane sur la surface d'agrégats de silice sont étudiées par microanalyse chimique, par des mesures de relaxation magnétique des protons liés aux chaînes et par des mesures de gonflement des mélanges polymères-particules, utilisant un bon solvant. On montre qu'immédiatement après la préparation des mélanges, les chaînes solidement adsorbées n'occupent, sous la forme d'ilôts, que le quart de la surface de silice. On montre aussi que, pendant la saturation progressive de la surface, qui dure environ 3 mois à 343 K, le nombre de points de contacts d'une chaîne avec la silice est proportionnel à sqrt{N} ; N étant le nombre de maillons dans la chaîne.

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

DTIC Science & Technology

2009-09-01

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

Remote sensing of a coupled carbon-water-energy-radiation balances from the Globe to plot scales

NASA Astrophysics Data System (ADS)

Ryu, Y.; Jiang, C.; Huang, Y.; Kim, J.; Hwang, Y.; Kimm, H.; Kim, S.

2016-12-01

Advancements in near-surface and satellite remote sensing technologies have enabled us to monitor the global terrestrial ecosystems at multiple spatial and temporal scales. An emergent challenge is how to formulate a coupled water, carbon, energy, radiation, and nitrogen cycles from remote sensing. Here, we report Breathing Earth System Simulator (BESS), which coupled radiation (shortwave, longwave, PAR, diffuse PAR), carbon (gross primary productivity, ecosystem respiration, net ecosystem exchange), water (evaporation), and energy (latent and sensible heat) balances across the global land at 1 km resolution, 8 daily between 2000 and 2015 using multiple satellite remote sensing. The performance of BESS was tested against field observations (FLUXNET, BSRN) and other independent products (MPI-BGC, MODIS, GLASS). We found that the coupled model, BESS showed on par with, or better performance than the other products which computed land surface fluxes individually. Lastly, we show one plot-level study conducted in a paddy rice to demonstrate how to couple radiation, carbon, water, nitrogen balances with a series of near-surface spectral sensors.

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.

Crystals with a surface deformed by a non-epitaxial growth (in French)

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

None

1972-11-30

Ces cristaux sont obtenus par mise en contact avec un agent generateur de cristaux solides, finement divise, ayant des dimensions particulaires comprises entre moins de 44 microns et 175 microns environ, pendant un laps de temps predetermine, l'agent generateur de cristaux etant associe a une quantite suffisante d'une fraction transferable capable d'engendrer par croissance une couche non epitaxiale sur la surface du cristal de base, cette croissance ayant lieu d'une maniere sensiblement uniforme mais neanmoins non ordonnee, independante de l'orientation microscopique du cristal de base. Ces cristaux peuvent etre utilises pour des scintillateurs. (FR)

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

PubMed

De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

2016-07-01

Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

Urokinase receptor and CXCR4 are regulated by common microRNAs in leukaemia cells

PubMed Central

Alfano, Daniela; Gorrasi, Anna; Li Santi, Anna; Ricci, Patrizia; Montuori, Nunzia; Selleri, Carmine; Ragno, Pia

2015-01-01

The urokinase-type plasminogen activator (uPA) receptor (uPAR) focuses uPA proteolytic activity on the cell membrane, promoting localized degradation of extracellular matrix (ECM), and binds vitronectin (VN), mediating cell adhesion to the ECM. uPAR-bound uPA and VN induce proteolysis-independent intracellular signalling, regulating cell adhesion, migration, survival and proliferation. uPAR cross-talks with CXCR4, the receptor for the stroma-derived factor 1 chemokine. CXCR4 is crucial in the trafficking of hematopoietic stem cells from/to the bone marrow, which involves also uPAR. Both uPAR and CXCR4 are expressed in acute myeloid leukaemia (AML), with a lower expression in undifferentiated and myeloid subsets, and higher expression in myelomonocytic and promyelocytic subsets. We hypothesized a microRNA (miR)-mediated co-regulation of uPAR and CXCR4 expression, which could allow their cross-talk at the cell surface. We identified three miRs, miR-146a, miR-335 and miR-622, regulating the expression of both uPAR and CXCR4 in AML cell lines. Indeed, these miRs directly target the 3′untranslated region of both uPAR- and CXCR4-mRNAs; accordingly, uPAR/CXCR4 expression is reduced by their overexpression in AML cells and increased by their specific inhibitors. Overexpression of all three miRs impairs migration, invasion and proliferation of myelomonocytic cells. Interestingly, we observed an inverse relationship between uPAR/CXCR4 expression and miR-146a and miR-335 levels in AML blasts, suggesting their possible role in the regulation of uPAR/CXCR4 expression also in vivo. PMID:26082201

Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

PubMed Central

Bhandary, Yashodhar P.; Velusamy, Thirunavukkarasu; Shetty, Praveenkumar; Shetty, Rashmi S.; Idell, Steven; Cines, Douglas B.; Jain, Deepika; Bdeir, Khalil; Abraham, Edward; Tsuruta, Yuko; Shetty, Sreerama

2009-01-01

Rationale: Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI). Objectives: To determine the role of uPA in uPAR expression during ALI caused by sepsis. Methods: We used Western blot, Northern blot, Northwestern assay, and immunohistochemistry. Phosphate-buffered saline– and lipopolysaccharide (LPS)-treated wild-type and uPA−/− mice were used. Measurements and Main Results: Biological activities of uPA, including proteolysis, cell adhesion, migration, proliferation, and differentiation, are dependent on its association with uPAR. Bacterial endotoxin (LPS) is a major cause of pulmonary dysfunction and infection-associated mortality. The present study shows that LPS induces uPAR expression both in vitro and in vivo, and that the mechanism involves post-transcriptional stabilization of uPAR mRNA by reciprocal interaction of phosphoglycerate kinase (PGK) and heterogeneous nuclear ribonucleoprotein C (hnRNPC) with uPAR mRNA coding region and 3′ untranslated region determinants, respectively. The process involves tyrosine phosphorylation of PGK and hnRNPC. uPA−/− mice failed to induce uPAR expression after LPS treatment. In these mice, LPS treatment failed to alter the binding of PGK and hnRNPC protein with uPAR mRNA due to lack of tyrosine phosphorylation. Conclusions: Our study shows that induction of LPS-mediated uPAR expression is mediated through tyrosine phosphorylation of PGK and hnRNPC. This involves expression of uPA as an obligate intermediary. PMID:19029002

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

NASA Astrophysics Data System (ADS)

Aboutajeddine, Ahmed

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

Exact solutions to model surface and volume charge distributions

NASA Astrophysics Data System (ADS)

Mukhopadhyay, S.; Majumdar, N.; Bhattacharya, P.; Jash, A.; Bhattacharya, D. S.

2016-10-01

Many important problems in several branches of science and technology deal with charges distributed along a line, over a surface and within a volume. Recently, we have made use of new exact analytic solutions of surface charge distributions to develop the nearly exact Boundary Element Method (neBEM) toolkit. This 3D solver has been successful in removing some of the major drawbacks of the otherwise elegant Green's function approach and has been found to be very accurate throughout the computational domain, including near- and far-field regions. Use of truly distributed singularities (in contrast to nodally concentrated ones) on rectangular and right-triangular elements used for discretizing any three-dimensional geometry has essentially removed many of the numerical and physical singularities associated with the conventional BEM. In this work, we will present this toolkit and the development of several numerical models of space charge based on exact closed-form expressions. In one of the models, Particles on Surface (ParSur), the space charge inside a small elemental volume of any arbitrary shape is represented as being smeared on several surfaces representing the volume. From the studies, it can be concluded that the ParSur model is successful in getting the estimates close to those obtained using the first-principles, especially close to and within the cell. In the paper, we will show initial applications of ParSur and other models in problems related to high energy physics.

Observation de l'interaction entre atome et surface en cellule de vapeur submicrométrique

NASA Astrophysics Data System (ADS)

Dutier, G.; Saltiel, S.; Bloch, D.; Ducloy, M.; Papoyan, A.; Sarkisyan, D.

2002-06-01

Sur une cellule de vapeur d'épaisseur submicrométrique ( 300 nm), les spectres d'absorption linéaire se révèlent très peu sensibles à l'effet Doppler (les effets transitoires favorisent fortement les atomes lents), et font apparaître les effets de l'interaction van der Waals à longue portée entre atome-surface. L'étude, entreprise d'abord sur la raie de résonance D1 de Cs, est poursuivie sur une transition à deux photons vers le niveau Cs 6(D{3/2}) résonnant avec la surface de YAG de la fenêtre. Elle ouvre diverses perspectives, notamment la détection d'états liés par un puits de potentiel induit par la surface.

Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells.

PubMed

Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla; Hansson, Stefan; Casslén, Bertil

2009-02-01

Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.

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

NASA Astrophysics Data System (ADS)

Losseau, Romain

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

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

DTIC Science & Technology

1998-12-01

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

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

NASA Astrophysics Data System (ADS)

De Castilla, Hector

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

Protease-activated receptor-4 and purinergic receptor P2Y12 dimerize, co-internalize, and activate Akt signaling via endosomal recruitment of β-arrestin.

PubMed

Smith, Thomas H; Li, Julia G; Dores, Michael R; Trejo, JoAnn

2017-08-18

Vascular inflammation and thrombosis require the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor P2Y12 to coordinate β-arrestin-mediated Akt signaling, an important mediator of integrin activation. However, the mechanism by which the PAR4-P2Y12 dimer controls β-arrestin-dependent Akt signaling is not known. We now report that PAR4 and P2Y12 heterodimer internalization is required for β-arrestin recruitment to endosomes and Akt signaling. Using bioluminescence resonance energy transfer, immunofluorescence microscopy, and co-immunoprecipitation in cells expressing receptors exogenously and endogenously, we demonstrate that PAR4 and P2Y12 specifically interact and form dimers expressed at the cell surface. We also found that activation of PAR4 but not of P2Y12 drives internalization of the PAR4-P2Y12 heterodimer. Remarkably, activated PAR4 internalization was required for recruitment of β-arrestin to endocytic vesicles, which was dependent on co-expression of P2Y12. Interestingly, stimulation of the PAR4-P2Y12 heterodimer promotes β-arrestin and Akt co-localization to intracellular vesicles. Moreover, activated PAR4-P2Y12 internalization is required for sustained Akt activation. Thus, internalization of the PAR4-P2Y12 heterodimer is necessary for β-arrestin recruitment to endosomes and Akt signaling and lays the foundation for examining whether blockade of PAR4 internalization reduces integrin and platelet activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A peptide inhibitor of the urokinase/urokinase receptor system inhibits alteration of the blood-retinal barrier in diabetes.

PubMed

Navaratna, Deepti; Menicucci, Gina; Maestas, Joann; Srinivasan, Ramprasad; McGuire, Paul; Das, Arup

2008-09-01

One of the major complications of diabetes is the alteration of the blood-retinal barrier, leading to retinal edema and consequent vision loss. The aim of this study was to evaluate the role of the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system in the regulation of retinal vascular permeability. Biochemical, molecular, and histological techniques were used to examine the role of uPA and uPAR in the regulation of retinal vascular permeability in diabetic rats and cultured retinal endothelial cells. The increased retinal vascular permeability in diabetic rats was associated with a decrease in vascular endothelial (VE) -cadherin expression in retinal vessels. Treatment with the uPA/uPAR-inhibiting peptide (A6) was shown to reduce diabetes-induced permeability and the loss of VE-cadherin. The increased permeability of cultured cells in response to advanced glycation end products (AGEs) was significantly inhibited with A6. Treatment of endothelial cells with specific matrix metalloproteinases or AGEs resulted in loss of VE-cadherin from the cell surface, which could be inhibited by A6. uPA/uPAR physically interacts with AGEs/receptor for advanced glycation end products on the cell surface and regulates its activity. uPA and its receptor uPAR play important roles in the alteration of the blood-retinal barrier through proteolytic degradation of VE-cadherin. The ability of A6 to block retinal vascular permeability in diabetes suggests a potential therapeutic approach for the treatment of diabetic macular edema.

Cell painting with an engineered EPCR to augment the protein C system.

PubMed

Bouwens, Eveline A M; Stavenuiter, Fabian; Mosnier, Laurent O

2015-11-25

The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC's effects on cells. Here a caveolae-targeting glycosylphosphatidylinositol (GPI)-anchored EPCR (EPCR-GPI) was engineered to restore EPCR's bioavailability via "cell painting." The painting efficiency of EPCR-GPI on EPCR-depleted endothelial cells was time- and dose-dependent. The EPCR-GPI bioavailability after painting was long lasting since EPCR surface levels reached 400 % of wild-type cells after 2 hours and remained > 200 % for 24 hours. EPCR-GPI painting conveyed APC binding to EPCR-depleted endothelial cells where EPCR was lost due to shedding or shRNA. EPCR painting normalised PC activation on EPCR-depleted cells indicating that EPCR-GPI is functional active on painted cells. Caveolin-1 lipid rafts were enriched in EPCR after painting due to the GPI-anchor targeting caveolae. Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signalling. Therefore, EPCR-GPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR- depleted and -deficient cells.

Reconstruction d’une Carbonisation du Pouce par Lambeau Chinois

PubMed Central

Khales, A.; Achbouk, J.A.; Moussaoui, A.; Belmir, R.; Tourabi, K.; Oufkir, A.; Ihrai, H.

2010-01-01

Summary La main en tant qu’organe majeur de la préhension peut être le siège de brûlures graves qui compromettent sa fonction. Bien qu’elle ne représente que 2% de la surface corporelle la brûlure de la main est grave et difficile à traiter, vu la vulnérabilité et la complexité de son appareil locomoteur. Nous rapportons dans ce travail le cas d’un patient victime d’une carbonisation de la main. Huit mois après le parage et la couverture par lambeau inguinal, le patient bénéficie d’une reconstruction du pouce par lambeau chinois associé à une greffe osseuse. Le résultat s’est avéré satisfaisant. Le lambeau chinois prouve par son apport vasculaire et par sa facilité technique qu’il est un moyen très intéressant dans la reconstruction du pouce - ou des doigts en général - surtout dans un contexte de brûlure. PMID:21991226

Increasing cloudiness in Arctic damps the increase in phytoplankton primary production due to sea ice receding

NASA Astrophysics Data System (ADS)

Bélanger, S.; Babin, M.; Tremblay, J.-É.

2013-06-01

The Arctic Ocean and its marginal seas are among the marine regions most affected by climate change. Here we present the results of a diagnostic model used to assess the primary production (PP) trends over the 1998-2010 period at pan-Arctic, regional and local (i.e. 9.28 km resolution) scales. Photosynthetically active radiation (PAR) above and below the sea surface was estimated using precomputed look-up tables of spectral irradiance, taking as input satellite-derived cloud optical thickness and cloud fraction parameters from the International Satellite Cloud Climatology Project (ISCCP) and sea ice concentration from passive microwaves data. A spectrally resolved PP model, designed for optically complex waters, was then used to assess the PP trends at high spatial resolution. Results show that PP is rising at a rate of +2.8 TgC yr-1 (or +14% decade-1) in the circum-Arctic and +5.1 TgC yr-1 when sub-Arctic seas are considered. In contrast, incident PAR above the sea surface (PAR(0+)) has significantly decreased over the whole Arctic and sub-Arctic Seas, except over the perennially sea-ice covered waters of the Central Arctic Ocean. This fading of PAR(0+) (-8% decade-1) was caused by increasing cloudiness during summer. Meanwhile, PAR penetrating the ocean (PAR(0-)) increased only along the sea ice margin over the large Arctic continental shelf where sea ice concentration declined sharply since 1998. Overall, PAR(0-) slightly increased in the circum-Arctic (+3.4% decade-1), while it decreased when considering both Arctic and sub-Arctic Seas (-3% decade-1). We showed that rising phytoplankton biomass (i.e. chlorophyll a) normalized by the diffuse attenuation of photosynthetically usable radiation (PUR), accounted for a larger proportion of the rise in PP than did the increase in light availability due to sea-ice loss in several sectors, and particularly in perennially and seasonally open waters. Against a general backdrop of rising productivity over Arctic shelves, significant negative PP trends and the timing of phytoplankton spring-summer bloom were observed in regions known for their great biological importance such as the coastal polynyas of northern Greenland.

Extended Generation Profile - E.B.I.C. Model

NASA Astrophysics Data System (ADS)

Guermazi, S.; Toureille, A.; Grill, C.; El Jani, B.; Lakhoua, N.

1996-04-01

We have developed a model for the calculation of the induced current due to an electron beam with an extended profile. As well as the number of absorbed and diffuse electrons as a function of the depth, the generation profile takes into account the lateral diffusion and the effect of defects, dislocations and recombination surfaces. The expression from the Electron Beam Induced Current (EBIC) is obtained by solving the continuity equation in permanent regime by the Green function method. In the case of a Schottky diode Au/InP, obtained by ionic scattering followed by a quick thermal treatment, the induced current profile is compared to the theoretical profiles whose analytical expressions are given by Van Roosbroeck and Bresse. The experimental current profile, measured by S.E.M provided us with the calculation of the diffusion length of the minority carriers, L_n=1 μm. The theoretical curve obtained from the proposed model is in good agreement with the experimental one for a surface recombination velocity of 104 cm s^{-1}. Our results are found to be consistent with those obtained by other experimental techniques on the same samples. Nous avons développé un modèle de calcul du courant induit par un faisceau d'électrons avec un profil de génération élargi. Le profil de génération tient compte, en plus du nombre d'électrons absorbés et du nombre d'électrons diffusés en fonction de la profondeur, de la diffusion latérale (en prenant en considération la diffusion angulaire), de l'effet des défauts, des dislocations et de la recombinaison à la surface. L'expression analytique du courant induit E.B.I.C est déterminée par résolution de l'équation de continuité en régime permanent par la méthode des fonctions de Green. Le profil de courant induit obtenu dans le cas d'une diode Schottky Au/InP dopé p et fabriqué par implantation suivit d'un recuit, est comparé au profil de courant théorique dont l'expression analytique est explicité par Van Roosbroeck et Bresse. Le profil de courant expérimental, mesuré par un microscope électronique à balayage, nous a permis de calculer la longueur de diffusion des porteurs minoritaires L_n=1 μm. La courbe théorique, tracée à partir du modèle proposé, est en bon accord avec la courbe expérimental pour une vitesse de recombinaison à la surface de 104 cm s^{-1}. Ces résultats sont conformes avec ceux obtenus par d'autres techniques expérimentales sur les mêmes échantillons.

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

DTIC Science & Technology

2002-11-01

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

Character of intermolecular interaction in pyridine-argon complex: Ab initio potential energy surface, internal dynamics, and interrelations between SAPT energy components.

PubMed

Makarewicz, Jan; Shirkov, Leonid

2016-05-28

The pyridine-Ar (PAr) van der Waals (vdW) complex is studied using a high level ab initio method. Its structure, binding energy, and intermolecular vibrational states are determined from the analytical potential energy surface constructed from interaction energy (IE) values computed at the coupled cluster level of theory with single, double, and perturbatively included triple excitations with the augmented correlation consistent polarized valence double-ζ (aug-cc-pVDZ) basis set complemented by midbond functions. The structure of the complex at its global minimum with Ar at a distance of 3.509 Å from the pyridine plane and shifted by 0.218 Å from the center of mass towards nitrogen agrees well with the corresponding equilibrium structure derived previously from the rotational spectrum of PAr. The PAr binding energy De of 392 cm(-1) is close to that of 387 cm(-1) calculated earlier at the same ab initio level for the prototypical benzene-Ar (BAr) complex. However, under an extension of the basis set, De for PAr becomes slightly lower than De for BAr. The ab initio vdW vibrational energy levels allow us to estimate the reliability of the methods for the determination of the vdW fundamentals from the rotational spectra. To disclose the character of the intermolecular interaction in PAr, the symmetry-adapted perturbation theory (SAPT) is employed for the analysis of different physical contributions to IE. It is found that SAPT components of IE can be approximately expressed in the binding region by only two of them: the exchange repulsion and dispersion energy. The total induction effect is negligible. The interrelations between various SAPT components found for PAr are fulfilled for a few other complexes involving aromatic molecules and Ar or Ne, which indicates that they are valid for all rare gas (Rg) atoms and aromatics.

La méthode des coordonnées curvilignes appliquée à la diffraction par des réseaux dont le profil est donné par des équations paramétriques: application à la diffraction par un réseau cycloïdal The method of curvilinear coordinates applied to the problem of scattering from surface-relief gratings defined by parametric equations: application to scattering from a cycloidal grating

NASA Astrophysics Data System (ADS)

Granet, Gérard; Chandezon, Jean

1997-11-01

The method of curvilinear coordinates is formulated using the coordinate transformations given by parametric equations. As an illustration, a translation coordinate system and a relaxation coordinate system are used to calculate the reflectivities of various cycloidal profiles. We show, with this example, that parametric coordinate systems permit one to handle profiles that previously had been out of reach owing to their sharpness.

Cell painting with an engineered EPCR to augment the protein C system

PubMed Central

Bouwens, Eveline A. M.; Stavenuiter, Fabian; Mosnier, Laurent O.

2016-01-01

The protein C (PC) system conveys beneficial anticoagulant and cytoprotective effects in numerous in vivo disease models. The endothelial protein C receptor (EPCR) plays a central role in these pathways as cofactor for PC activation and by enhancing activated protein C (APC)-mediated protease-activated receptor (PAR) activation. During inflammatory disease, expression of EPCR on cell membranes is often diminished thereby limiting PC activation and APC’s effects on cells. Here a caveolae-targeting glycosylphosphatidylinositol (GPI)-anchored EPCR (EPCR-GPI) was engineered to restore EPCR’s bioavailability via “cell painting.” The painting efficiency of EPCR-GPI on EPCR-depleted endothelial cells was time- and dose-dependent. The EPCR-GPI bioavailability after painting was long lasting since EPCR surface levels reached 400% of wild-type cells after 2 hours and remained >200% for 24 hours. EPCR-GPI painting conveyed APC binding to EPCR-depleted endothelial cells where EPCR was lost due to shedding or shRNA. EPCR painting normalized PC activation on EPCR-depleted cells indicating that EPCR-GPI is functional active on painted cells. Caveolin-1 lipid rafts were enriched in EPCR after painting due to the GPI-anchor targeting caveolae. Accordingly, EPCR painting supported PAR1 and PAR3 cleavage by APC and augmented PAR1-dependent Akt phosphorylation by APC. Thus, EPCR-GPI painting achieved physiological relevant surface levels on endothelial cells, restored APC binding to EPCR-depleted cells, supported PC activation, and enhanced APC-mediated PAR cleavage and cytoprotective signaling. Therefore, EPCR-GPI provides a novel tool to restore the bioavailability and functionality of EPCR on EPCR-depleted and deficient cells. PMID:26272345

Polyester polymer alloy as a high-performance membrane.

PubMed

Igoshi, Tadaaki; Tomisawa, Narumi; Hori, Yoshinori; Jinbo, Yoichi

2011-01-01

Polyester polymer alloy (PEPA) membrane is developed as a synthetic polymermembrane. It consists of two polymers - polyethersulfone (PES) and polyarylate (PAR).The pore size in membrane can be controlled by a blend ratio of PES and PAR. One unique characteristic is that PEPA membrane has three layers of a skin layer on the inner surface, a porous layer in the membrane, and a skin layer on the outer surface, respectively. The permeability of water and substances is controlled by the skin layer on the inner surface. PEPA membrane dialyzer can be adequately considered as a high-performance dialyzer. Furthermore, the skin layer on the outer surface can block endotoxin from the dialysis fluid side. PEPA membrane can therefore be used as an endotoxin-retentive filter. The other unique characteristic is that each amount of albumin loss or β2-microglobulin removal can be controlled by an additive amount of polyvinylpyrrolidone. This means that the PEPA dialyzer can be clinically used to meet the conditions of the patient. Copyright © 2011 S. Karger AG, Basel.

Uncertainties in estimates of fAPAR for photosynthesis (fAPARPSN) in tropical, Arctic/boreal, coastal, and wetland-dominant regions when approximated with fAPARcanopy and NDVI

NASA Astrophysics Data System (ADS)

Zhang, Q.; Yao, T.

2016-12-01

The climate is affected by the land surface through regulating the exchange of mass and energy with the atmosphere. The energy that reaches the land surface has three pathways: (1) reflected into atmosphere; (2) absorbed for photosynthesis; and (3) discarded as latent and sensible heat or emitted as fluorescence. Vegetation removes CO2 from the atmosphere during the process of photosynthesis, but also releases CO2 back into the atmosphere through the process of respiration. The complex set of vegetation-soil-atmosphere interactions requires that a realistic land-surface parameterization be included in any climate model or general circulation model (GCM) to accurately simulate canopy photosynthesis and stomatal conductance.We retrieve fraction of PAR absorbed by chlorophyll (fAPARchl) with an advanced canopy-leaf-soil-snow-water coupled radiative transfer model. Most ecological models and land-surface models that simulate vegetation GPP with remote sensing data utilize fraction of PAR absorbed by the whole canopy (fAPARcanopy). However, only the PAR absorbed by chlorophyll is potentially available for photosynthesis since the PAR absorbed by non-photosynthetic vegetation section (NPV) of the canopy is not used for photosynthesis. Therefore, fAPARchl (rather than fAPARcanopy) should be utilized to estimate fAPAR for photosynthesis (fAPARPSN), and thus in GPP simulation. Globally selected sites include those sites in tropical, Arctic/boreal, coastal, and wetland-dominant regions. The fAPARchl and fAPARcanopy products for a surrounding area 50 km x 50 km of each site are mapped. The fAPARchl is utilized to estimate GPP, and compared to tower flux GPP for validation. The GPP estimation performance with fAPARchl is also compared with the GPP estimation performance with MOD15A2 FPAR. The fAPARchl product is further implemented into ecological models and land-surface models to simulate vegetation GPP. NDVI is the other proxy of fAPARPSN in GPP estimation. We quantify the uncertainties in estimates of fAPARPSN when approximated with fAPARcanopy and NDVI. The uncertainties are significant and vary spatially, temporally, and with plant functional types.

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).

3D Modelling of Urban Terrain (Modelisation 3D de milieu urbain)

DTIC Science & Technology

2011-09-01

Panel • IST Information Systems Technology Panel • NMSG NATO Modelling and Simulation Group • SAS System Analysis and Studies Panel • SCI... Systems Concepts and Integration Panel • SET Sensors and Electronics Technology Panel These bodies are made up of national representatives as well as...of a part of it may be made for individual use only. The approval of the RTA Information Management Systems Branch is required for more than one

Comportement rhéologique des systèmes mixtes biopolymères / protéines

NASA Astrophysics Data System (ADS)

Rebiha, M.; Moulai-Mostefa, N.; Sadok, A. Hadj; Sabri, N.

2005-05-01

Dans ce travail, on s'est intéressé à l'étude des effets du caséinate de sodium et du xanthane sur les propriétés rhéologiques des solutions aqueuses, préparées suivant un plan d'expériences. Les caractéristiques mécaniques obtenues sont traduites par les coefficients du modèle rhéologique de Casson, en l'occurrence la contrainte seuil, τ 0, et la viscosité plastique, η _c. Ainsi, à l'issue de la modélisation en surface de réponses, il apparaît une interaction répulsive à l'échelle structurale entre le caséinate de sodium et le xanthane, traduite par un abaissement considérable de τ 0. Cet baissement de la rigidité peut conduire à une séparation de phases, phénomène conditionné par la viscosité limite de Casson,η _c.

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model

PubMed Central

Akiyama, Tasuku; Carstens, Mirela Iodi

2011-01-01

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors. PMID:21430273

Enhanced responses of lumbar superficial dorsal horn neurons to intradermal PAR-2 agonist but not histamine in a mouse hindpaw dry skin itch model.

PubMed

Akiyama, Tasuku; Carstens, Mirela Iodi; Carstens, E

2011-06-01

Chronic itch is symptomatic of many skin conditions and systemic diseases. Little is known about pathophysiological alterations in itch-signaling neural pathways associated with chronic itch. We used a mouse model of hindpaw chronic dry skin itch to investigate properties of presumptive itch-signaling neurons. Neurons in the lumbar superficial dorsal horn ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous activity that was inhibited by scratching the plantar surface. Most spontaneously active units exhibited further increases in firing rate following intradermal injection of an agonist of the protease-activated receptor PAR-2, or histamine. The large majority of pruritogen-responsive units also responded to capsaicin and allyl isothiocyanate. For neurons ipsilateral to dry skin treatment, responses elicited by the PAR-2 agonist, but not histamine or mechanical stimuli, were significantly larger compared with neurons ipsilateral to vehicle (water) treatment or neurons recorded in naïve (untreated) mice. The spontaneous activity may signal ongoing itch, while enhanced PAR-2 agonist-evoked responses may underlie hyperknesis (enhanced itch), both of which are symptomatic of many chronic itch conditions. The enhancement of neuronal responses evoked by the PAR-2 agonist, but not by histamine or mechanical stimuli, implies that the dry skin condition selectively sensitized PAR-2 agonist-sensitive primary afferent pruriceptors.

Assessing the spatial and temporal variability of fAPAR 2-flux estimates in a temperate mixed coniferous forest

NASA Astrophysics Data System (ADS)

Putzenlechner, Birgitta; Sanchez-Azofeifa, Arturo; Ludwig, Ralf

2016-04-01

The fraction of absorbed photosynthetically active radiation (fAPAR) is recognized as one of the essential climate variables as it characterizes activity and dynamics of the Earth's terrestrial biosphere (GCOS, 2010). By linking photosynthetic active radiation (PAR) to the absorption of plants, fAPAR represents a crucial variable for describing land surface and atmosphere interactions considered in global circulation models as well as in production efficiency models for estimating terrestrial carbon balances. Recent studies report discrepancies between global fAPAR satellite products regarding both absolute values and uncertainty representation, thereby stressing the need for independent ground measurements (D'Odrico et al., 2014; Picket-Heaps et al., 2014; Tao et al., 2015). However, there is a lack of basic information to better understand the spatial and temporal bias of PAR field observations, particularly in forest ecosystems. In theory, it is known that fAPAR estimates are affected by e.g. illumination conditions, leaf area index, leaf color, background brightness, which in turn may lead to considerable bias of field measurements. However, theoretical findings lack validation in the field as well as practical recommendations for field protocols. In this study, the variability of two-flux fAPAR estimates with regards to different illumination conditions (solar zenith angles, diffuse radiation conditions) are investigated. Measurements of PAR are carried out at Graswang environmental monitoring site in Southern Germany within a temperate mixed coniferous forest. A relatively new environmental monitoring technology based on Wireless Sensor Networks (WSN) is applied, allowing for permanent synchronized measurements of transmitted PAR, thereby reducing temporal sampling bias. Transmitted PAR is obtained from 16 photon flux sensors, 1.3 m above the surface. With a reference sensor outside the forest measuring incoming PAR, a two-flux estimate based on the ratio of transmitted PAR and incoming PAR can be calculated for each 10-min timestep during daytime hours. The fAPAR time series exhibit seasonal variability (mean=0.7, sd=0.4 for the average of all PAR sensors calculated for each 10-min timestep) according to phenological development, but also considerable inter-sensor variability between single days. Standard deviations for fAPAR in mid-summer vary between 0.26 for days with overcast sky and 0.19 for clear sky conditions. Diurnal cycles of fAPAR under clear sky conditions show a sharp increase of fAPAR with increasing solar zenith angles, suggesting for an underestimation of fAPAR with low solar zenith angles as it has also been found in studies based on radiative transfer modeling (Widlowski et al., 2010). The experiences gained from the field observations contribute to a bias assessment for ground measurements as demanded by authors of recent studies on comparing global fAPAR satellite products.

Revetements antireflet-passivation a base de nitrure de silicium PECVD pour cellules solaires triple-jonction III-V/ Ge

NASA Astrophysics Data System (ADS)

Homier, Ram

Dans le contexte environnemental actuel, le photovoltaïque bénéficie de l'augmentation des efforts de recherche dans le domaine des énergies renouvelables. Pour réduire le coût de la production d'électricité par conversion directe de l'énergie lumineuse en électricité, le photovoltaïque concentré est intéressant. Le principe est de concentrer une grande quantité d'énergie lumineuse sur des petites surfaces de cellules solaires multi-jonction à haute efficacité. Lors de la fabrication d'une cellule solaire, il est essentiel d'inclure une méthode pour réduire la réflexion de la lumière à la surface du dispositif. Le design d'un revêtement antireflet (ARC) pour cellules solaires multi-jonction présente des défis à cause de la large bande d'absorption et du besoin d'égaliser le courant produit par chaque sous-cellule. Le nitrure de silicium déposé par PECVD en utilisant des conditions standards est largement utilisé dans l'industrie des cellules solaires à base de silicium. Cependant, ce diélectrique présente de l'absorption dans la plage des courtes longueurs d'onde. Nous proposons l'utilisation du nitrure de silicium déposé par PECVD basse fréquence (LFSiN) optimisé pour avoir un haut indice de réfraction et une faible absorption optique pour l'ARC pour cellules solaires triple-jonction III-V/Ge. Ce matériau peut aussi servir de couche de passivation/encapsulation. Les simulations montrent que l'ARC double couche SiO2/LFSiN peut être très efficace pour réduire les pertes par réflexion dans la plage de longueurs d'onde de la sous-cellule limitante autant pour des cellules solaires triple-jonction limitées par la sous-cellule du haut que pour celles limitées par la sous-cellule du milieu. Nous démontrons aussi que la performance de la structure est robuste par rapport aux fluctuations des paramètres des couches PECVD (épaisseurs, indice de réfraction). Mots-clés : Photovoltaïque concentré (CPV), cellules solaires multi-jonction (MJSC), revêtement antireflet (ARC), passivation des semiconducteurs III-V, nitrure de silicium (Si"Ny), PECVD.

Youth empowerment in context: exploring tensions in school-based yPAR.

PubMed

Kohfeldt, Danielle; Chhun, Lina; Grace, Sarah; Langhout, Regina Day

2011-03-01

In much of the youth empowerment literature, researchers focus on the relationship between youth and adults involved in empowerment programs while neglecting the broader social framework in which these relationships and the program itself functions. Utilizing an ecological model, the current research examines the tensions that surfaced in attempts to create an empowering setting in an after-school PAR program with fifth-graders. Challenging assumptions about youth, structural challenges, and conflicting theories of change are highlighted. Results examine the role of sociocultural context as PAR researchers attempt to create a setting in which students gain skills to become change agents within their school. The study suggests that youth empowerment is a context dependent process that requires attention to a multiplicity of factors that influence possibilities for empowerment via second order change.

Understanding and Modeling Vortical Flows to Improve the Technology Readiness Level for Military Aircraft (Comprehension et Modelisation des Flux de Vortex Pour Ameliorer le Niveau de Maturite Technologique au Profit des Avions Militaires)

DTIC Science & Technology

2009-10-01

636.7 115,418 0 2500 5000 7500 10000 12500 iterations -5 -4 -3 -2 -1 0 lo g( dρ /d t) SA EARSM EARSM + CC Hellsten EARSM Hellsten EARSM + CC DRSM...VORTEX BREAKDOWN RTO-TR-AVT-113 29 - 13 θU URo axial= (1) As a vortex passes through a normal shock, the tangential velocity is

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

DTIC Science & Technology

2009-09-01

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

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

DTIC Science & Technology

2009-09-01

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

Reconstruction de la surface de Fermi dans l'etat normal d'un supraconducteur a haute Tc: Une etude du transport electrique en champ magnetique intense

NASA Astrophysics Data System (ADS)

Le Boeuf, David

Des mesures de resistance longitudinale et de resistance de Hall en champ magnetique intense transverse (perpendiculaire aux plans CuO2) ont ete effectuees au sein de monocristaux de YBa2Cu3Oy (YBCO) demacles, ordonnes et de grande purete, afin d'etudier l'etat fondamental des supraconducteurs a haute Tc dans le regime sous-dope. Cette etude a ete realisee en fonction du dopage et de l'orientation du courant d'excitation J par rapport a l'axe orthorhombique b de la structure cristalline. Les mesures en champ magnetique intense revelent par suppression de la supraconductivite des oscillations magnetiques des resistances longitudinale et de Hall dans YBa2Cu 3O6.51 et YBa2Cu4O8. La conformite du comportement de ces oscillations quantiques au formalisme de Lifshitz-Kosevich, apporte la preuve de l'existence d'une surface de Fermi fermee a caractere quasi-2D, abritant des quasiparticules coherentes respectant la statistique de Fermi-Dirac, dans la phase pseudogap d'YBCO. La faible frequence des oscillations quantiques, combinee avec l'etude de la partie monotone de la resistance de Hall en fonction de la temperature indique que la surface de Fermi d'YBCO sous-dope comprend une petite poche de Fermi occupee par des porteurs de charge negative. Cette particularite de la surface de Fermi dans le regime sous-dope incompatible avec les calculs de structure de bande est en fort contraste avec la structure electronique presente dans le regime surdope. Cette observation implique ainsi l'existence d'un point critique quantique dans le diagramme de phase d'YBCO, au voisinage duquel la surface de Fermi doit subir une reconstruction induite par l'etablissement d'une brisure de la symetrie de translation du reseau cristallin sous-jacent. Enfin, l'etude en fonction du dopage de la resistance de Hall et de la resistance longitudinale en champ magnetique intense suggere qu'un ordre du type onde de densite (DW) est responsable de la reconstruction de la surface de Fermi. L'analogie de la phenomenologie entourant le comportement des resistances longitudinale et de Hall dans YBa2Cu3Oy, avec des systemes dans lesquels l'existence d'un ordre du type DW est etablie, notamment des cuprates a structure tetragonale a basse temperature ("Low Temperature Tetragonal", LTT), indique que l'ordre causant la reconstruction de la surface de Fermi est stabilise au voisinage du dopage p = 1/8, et est en competition directe avec la supraconductivite.

Band-engineering of TiO2 as a wide-band gap semiconductor using organic chromophore dyes

NASA Astrophysics Data System (ADS)

Wahyuningsih, S.; Kartini, I.; Ramelan, A. H.; Saputri, L. N. M. Z.; Munawaroh, H.

2017-07-01

Bond-engineering as applied to semiconductor materials refers to the manipulation of the energy bands in order to control charge transfer processes in a device. When the device in question is a photoelectrochemical cell, the charges affected by drift become the focus of the study. The ideal band gap of semiconductors for enhancement of photocatalyst activity can be lowered to match with visible light absorption and the location of conduction Band (CB) should be raised to meet the reducing capacity. Otherwise, by the addition of the chromofor organic dyes, the wide-band gab can be influences by interacation resulting between TiO2 surface and the dyes. We have done the impruvisation wide-band gap of TiO2 by the addition of organic chromophore dye, and the addition of transition metal dopand. The TiO2 morphology influence the light absorption as well as the surface modification. The organic chromophore dye was syntesized by formation complexes compound of Co(PAR)(SiPA)(PAR)= 4-(2-piridylazoresorcinol), SiPA = Silyl propil amine). The result showed that the chromophore groups adsorbed onto TiO2 surface can increase the visible light absorption of wide-band gab semiconductor. Initial absorption of a chromophore will affect light penetration into the material surfaces. The use of photonic material as a solar cell shows this phenomenon clearly from the IPCE (incident photon to current conversion efficiency) measurement data. Organic chromophore dyes of Co(PAR)(SiPA) exhibited the long wavelength absorption character compared to the N719 dye (from Dyesol).

Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia.

PubMed

Søreide, Kjetil

2008-08-01

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.

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

NASA Astrophysics Data System (ADS)

Mougenot, Bernard

2016-04-01

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

Application and Evaluation of MODIS LAI, fPAR, and Albedo Products in the WRFCMAQ System

EPA Science Inventory

Leaf area index (LAI), vegetation fraction (VF), and surface albedo are important parameters in the land surface model (LSM) for meteorology and air quality modeling systems such as WRF/CMAQ. LAI and VF control not only leaf to canopy level evapotranspiration flux scaling but al...

Field estimates of body drag coefficient on the basis of dives in passerine birds.

PubMed

Hedenström, A; Liechti, F

2001-03-01

During forward flight, a bird's body generates drag that tends to decelerate its speed. By flapping its wings, or by converting potential energy into work if gliding, the bird produces both lift and thrust to balance the pull of gravity and drag. In flight mechanics, a dimensionless number, the body drag coefficient (C(D,par)), describes the magnitude of the drag caused by the body. The drag coefficient depends on the shape (or streamlining), the surface texture of the body and the Reynolds number. It is an important variable when using flight mechanical models to estimate the potential migratory flight range and characteristic flight speeds of birds. Previous wind tunnel measurements on dead, frozen bird bodies indicated that C(D,par) is 0.4 for small birds, while large birds should have lower values of approximately 0.2. More recent studies of a few birds flying in a wind tunnel suggested that previous values probably overestimated C(D,par). We measured maximum dive speeds of passerine birds during the spring migration across the western Mediterranean. When the birds reach their top speed, the pull of gravity should balance the drag of the body (and wings), giving us an opportunity to estimate C(D,par). Our results indicate that C(D,par) decreases with increasing Reynolds number within the range 0.17-0.77, with a mean C(D,par) of 0.37 for small passerines. A somewhat lower mean value could not be excluded because diving birds may control their speed below the theoretical maximum. Our measurements therefore support the notion that 0.4 (the 'old' default value) is a realistic value of C(D,par) for small passerines.

Protease and Protease-Activated Receptor-2 Signaling in the Pathogenesis of Atopic Dermatitis

PubMed Central

Lee, Sang Eun; Jeong, Se Kyoo

2010-01-01

Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation, pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens, and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD. PMID:20879045

Identification of a Novel Regulatory Mechanism of Nutrient Transport Controlled by TORC1-Npr1-Amu1/Par32

PubMed Central

Boeckstaens, Mélanie; Merhi, Ahmad; Llinares, Elisa; Van Vooren, Pascale; Springael, Jean-Yves; Wintjens, René; Marini, Anna Maria

2015-01-01

Fine-tuning the plasma-membrane permeability to essential nutrients is fundamental to cell growth optimization. Nutritional signals including nitrogen availability are integrated by the TORC1 complex which notably regulates arrestin-mediated endocytosis of amino-acid transporters. Ammonium is a ubiquitous compound playing key physiological roles in many, if not all, organisms. In yeast, it is a preferred nitrogen source transported by three Mep proteins which are orthologues of the mammalian Rhesus factors. By combining genetic, kinetic, biochemical and cell microscopy analyses, the current study reveals a novel mechanism enabling TORC1 to regulate the inherent activity of ammonium transport proteins, independently of arrestin-mediated endocytosis, identifying the still functional orphan Amu1/Par32 as a selective regulator intermediate. We show that, under poor nitrogen supply, the TORC1 effector kinase' Npr1' promotes phosphorylation of Amu1/Par32 which appears mainly cytosolic while ammonium transport proteins are active. Upon preferred nitrogen supplementation, like glutamine or ammonium addition, TORC1 upregulation enables Npr1 inhibition and Amu1/Par32 dephosphorylation. In these conditions, as in Npr1-lacking cells, hypophosphorylated Amu1/Par32 accumulates at the cell surface and mediates the inhibition of specific ammonium transport proteins. We show that the integrity of a conserved repeated motif of Amu1/Par32 is required for the interaction with these transport proteins. This study underscores the diversity of strategies enabling TORC1-Npr1 to selectively monitor cell permeability to nutrients by discriminating between transporters to be degraded or transiently inactivated and kept stable at the plasma membrane. This study further identifies the function of Amu1/Par32 in acute control of ammonium transport in response to variations in nitrogen availability. PMID:26172854

Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC

PubMed Central

Elias, Salah; McGuire, John Russel; Yu, Hua; Humbert, Sandrine

2015-01-01

The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis. PMID:25942483

Plates-formes de microscopie et fluorescence par resonance de plasmons de surface appliquees a l'imagerie cellulaire

NASA Astrophysics Data System (ADS)

Chabot, Vincent

L'elaboration de nouveaux medicaments repose sur les etudes pharmacologiques, dont le role est d'identifier de nouveaux composes actifs ou de nouvelles cibles pharmacologiques agissant entre autres au niveau cellulaire. Recemment, la detection basee sur la resonance des plasmons de surface (SPR) a ete appliquee a l'etude de reponses cellulaires. Cette methode de detection, permettant d'observer des variations d'indice de refraction associes a de faibles changements de masse a la surface d'un metal, a l'avantage de permettre l'etude d'une population de cellules vivantes en temps reel, sans necessiter l'introduction d'agents de marquage. Pour effectuer la detection au niveau de cellules individuelles, on peut employer la microscopie SPR, qui consiste a localiser spatialement la detection par un systeme d'imagerie. Cependant, la detection basee sur la SPR est une mesure sans marquage et les signaux mesures sont attribues a une reponse moyennee des differentes sources cellulaires. Afin de mieux comprendre et identifier les composantes cellulaires generant le signal mesure en SPR, il est pertinent de combiner la microscopie SPR avec une modalite complementaire, soit l'imagerie de fluorescence. C'est dans cette problematique que s'insere ce projet de these, consistant a concevoir deux plates-formes distinctes de microscopie SPR et de fluorescence optimisees pour l'etude cellulaire, de sorte a evaluer les possibilites d'integration de ces deux modalites en un seul systeme. Des substrats adaptes pour chaque plate-forme ont ete concus et realises. Ces substrats employaient une couche d'argent passivee par l'ajout d'une mince couche d'or. La stabilite et la biocompatibilite des substrats ont ete validees pour l'etude cellulaire. Deux configurations permettant d'ameliorer la sensibilite en sondant les cellules plus profondement ont ete evaluees, soit l'emploi de plasmons de surface a longue portee et de guides d'onde a gaine metallique. La sensibilite accrue de ces configurations a aussi ete demontree pour un usage en biodetection cellulaire. Une plate-forme permettant de mesurer la spectroscopie SPR simultanement avec l'acquisition d'images de fluorescence a ete realisee. Cette plate-forme a ensuite ete validee par l'etude de reponses cellulaires suite a une stimulation pharmacologique. Puis, un systeme base sur la microscopie SPR a ete concu et caracterise. Son emploi pour l'etude de reponses au niveau de cellules individuelles a ete demontre. Finalement, les forces et faiblesses des substrats et des plates-formes realisees au cours de la these ont ete evaluees. Des possibilites d'amelioration sont mises de l'avant et l'integration des modalites de microscopie SPR et de fluorescence suite aux travaux de la these est discutee. Les realisations au cours de cette etude ont donc permis d'identifier les composantes cellulaires impliquees dans la generation du signal mesure en biodetection SPR. Mots-cles : Resonance des plasmons de surface, microscopie SPR, plasmons de surface a longue portee LRSPR, guide d'onde a gaine metallique MCWG, fluorescence exaltee par plasmons de surface SPEF, biodetection cellulaire, imagerie SPR.

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 de confirmer l'efficacite du procede de preparation de surface et d'identifier les conditions de croissance optimales. Les resultats de caracterisation indiquent que les materiaux obtenus presentent une tres faible rugosite de surface, une bonne qualite cristalline et un dopage residuel relativement important. De plus, l'interface GaAs/Ge possede une faible densite de defauts. Finalement, la diffusion d'arsenic dans le substrat de germanium est comparable aux valeurs trouvees dans la litterature pour la croissance a basse temperature avec les autres procedes d'epitaxie courants. Ces resultats confirment que la technique d'epitaxie par faisceaux chimiques (CBE) permet de produire des couches de GaAs sur Ge de qualite adequate pour la fabrication de cellules solaires a haute performance. L'apport a la communaute scientifique a ete maximise par le biais de la redaction d'un article soumis a la revue Journal of Crystal Growth et la presentation des travaux a la conference Photovoltaics Canada 2010 . Mots-cles : Epitaxie par jets chimiques, Chemical beam epitaxy, CBE, MOMBE, Germanium, GaAs, Ge

Urokinase-Type Plasminogen Activator Receptor Is Internalized by Different Mechanisms in Polarized and Nonpolarized Madin–Darby Canine Kidney Epithelial Cells

PubMed Central

Vilhardt, Frederik; Nielsen, Morten; Sandvig, Kirsten; van Deurs, Bo

1999-01-01

Accumulated data indicate that endocytosis of the glycosylphosphatidyl-inositol-anchored protein urokinase plasminogen activator receptor (uPAR) depends on binding of the ligand uPA:plasminogen activator inhibitor-1 (PAI-1) and subsequent interaction with internalization receptors of the low-density lipoprotein receptor family, which are internalized through clathrin-coated pits. This interaction is inhibited by receptor-associated protein (RAP). We show that uPAR with bound uPA:PAI-1 is capable of entering cells in a clathrin-independent process. First, HeLaK44A cells expressing mutant dynamin efficiently internalized uPA:PAI-1 under conditions in which transferrin endocytosis was blocked. Second, in polarized Madin–Darby canine kidney (MDCK) cells, which expressed human uPAR apically, the low basal rate of uPAR ligand endocytosis, which could not be inhibited by RAP, was increased by forskolin or phorbol ester (phorbol 12-myristate 13-acetate), which selectively up-regulate clathrin-independent endocytosis from the apical domain of epithelial cells. Third, in subconfluent nonpolarized MDCK cells, endocytosis of uPA:PAI-1 was only decreased marginally by RAP. At the ultrastructural level uPAR was largely excluded from clathrin-coated pits in these cells and localized in invaginated caveolae only in the presence of cross-linking antibodies. Interestingly, a larger fraction of uPAR in nonpolarized relative to polarized MDCK cells was insoluble in Triton X-100 at 0°C, and by surface labeling with biotin we also show that internalized uPAR was mainly detergent insoluble, suggesting a correlation between association with detergent-resistant membrane microdomains and higher degree of clathrin-independent endocytosis. Furthermore, by cryoimmunogold labeling we show that 5–10% of internalized uPAR in nonpolarized, but not polarized, MDCK cells is targeted to lysosomes by a mechanism that is regulated by ligand occupancy. PMID:9880335

The role of protease activation of inflammation in allergic respiratory diseases.

PubMed

Reed, Charles E; Kita, Hirohito

2004-11-01

Extracellular endogenous proteases, as well as exogenous proteases from mites and molds, react with cell-surface receptors in the airways to generate leukocyte infiltration and to amplify the response to allergens. Stimulation leads to increased intracellular Ca ++ and gene transcription. The most thoroughly investigated receptors, protease-activated receptors (PARs), are 7-transmembrane proteins coupled to G proteins. PARs are widely distributed on the cells of the airways, where they contribute to the inflammation characteristic of allergic diseases. PAR stimulation of epithelial cells opens tight junctions, causes desquamation, and produces cytokines, chemokines, and growth factors. They degranulate eosinophils and mast cells. Proteases contract bronchial smooth muscle and cause it to proliferate. PARs also promote maturation, proliferation, and collagen production of fibroblast precursors and mature fibroblasts. PAR-2, apparently the most important of the 4 PARs that have been characterized, is increased on the epithelium of patients with asthma. Trypsin, a product of injured epithelial cells, and mast cell tryptase are potent activators of PAR-2. Mast cell chymase activates PAR-1. Proteases from mites and molds appear to act through similar receptors. They amplify IgE production to allergens, degranulate eosinophils, and can generate inflammation, even in the absence of IgE. Proteases produced by Aspergillus species to support its growth are presumably responsible for the exuberant IgE, IgG, and granulomatous response of allergic bronchopulmonary aspergillosis. Similar proteases from molds germinating on the respiratory mucosa have been recently been implicated in the pathogenesis of chronic hyperplastic rhinitis and polyps and, by extension, of intrinsic asthma. Finally, proteases from mites and fungi growing in damp, water-damaged buildings might be the basis for the increased prevalence in these buildings of rhinitis, asthma, and other respiratory diseases. Future research promises to promote our understanding of the pathogenesis of allergic respiratory diseases and point the way to new therapies.

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

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

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 havemore » 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.« less

Radar response to crop residue cover and tillage application on postharvest agricultural surfaces

NASA Astrophysics Data System (ADS)

McNairn, Heather

Les informations sur les pratiques de conservation des sols comme le labourage et la gestion des residus de culture sont requises afin d'estimer avec exactitude les risques d'erosion des sols. Quoique les micro-ondes soient sensibles aux conditions d'humidite et aux proprietes geometriques des surfaces, il n'en demeure pas moins que l'on connait encore peu sur la sensibilite des micro-ondes polarisees lineaires ou des parametres polarimetriques du ROS en fonction des caracteristiques des residus. A partir de donnees prises a l'aide d'un diffusometre monte sur un camion en 1996 et lors d'une mission SIR-C menee en 1994, cette recherche a demontre que les micro-ondes sont sensibles a la fois a la quantite et au type de couverture de residus, de meme qu'a la teneur en eau des residus. La reponse des polarisations croisees lineaires et de plusieurs parametres polarimetriques, incluant la hauteur pedestre, a permis d'observer qu'une diffusion volumique importante avait lieu en presence de vegetation senescente qui se tenait debout et pour les champs non laboures. La diffusion de surface dominait cependant pour les champs avec de faibles quantites de residus et des residus plus fins. La recherche a toutefois demontre que des conditions de surface complexes etaient crees par differentes combinaisons de residus et de pratiques de labourage. Par consequent, il faudra attendre que des donnees multi-polarisees ou polarimetriques soient acquises par les capteurs prevus a bord du satellite canadien RADARSAT-2 et du satellite ENVISAT de l'Agence spatiale europeenne avant de pouvoir completement caracteriser les champs apres la recolte.

Etude de la performance des radars hautes-frequences CODAR et WERA pour la mesure des courants marins en presence partielle de glace de mer

NASA Astrophysics Data System (ADS)

Kamli, Emna

Les radars hautes-frequences (RHF) mesurent les courants marins de surface avec une portee pouvant atteindre 200 kilometres et une resolution de l'ordre du kilometre. Cette etude a pour but de caracteriser la performance des RHF, en terme de couverture spatiale, pour la mesure des courants de surface en presence partielle de glace de mer. Pour ce faire, les mesures des courants de deux radars de type CODAR sur la rive sud de l'estuaire maritime du Saint-Laurent, et d'un radar de type WERA sur la rive nord, prises pendant l'hiver 2013, ont ete utilisees. Dans un premier temps, l'aire moyenne journaliere de la zone ou les courants sont mesures par chaque radar a ete comparee a l'energie des vagues de Bragg calculee a partir des donnees brutes d'acceleration fournies par une bouee mouillee dans la zone couverte par les radars. La couverture des CODARs est dependante de la densite d'energie de Bragg, alors que la couverture du WERA y est pratiquement insensible. Un modele de fetch appele GENER a ete force par la vitesse du vent predite par le modele GEM d'Environnement Canada pour estimer la hauteur significative ainsi que la periode modale des vagues. A partir de ces parametres, la densite d'energie des vagues de Bragg a ete evaluee pendant l'hiver a l'aide du spectre theorique de Bretschneider. Ces resultats permettent d'etablir la couverture normale de chaque radar en absence de glace de mer. La concentration de glace de mer, predite par le systeme canadien operationnel de prevision glace-ocean, a ete moyennee sur les differents fetchs du vent selon la direction moyenne journaliere des vagues predites par GENER. Dans un deuxieme temps, la relation entre le ratio des couvertures journalieres obtenues pendant l'hiver 2013 et des couvertures normales de chaque radar d'une part, et la concentration moyenne journaliere de glace de mer d'autre part, a ete etablie. Le ratio des couvertures decroit avec l'augmentation de la concentration de glace de mer pour les deux types de radars, mais pour une concentration de glace de 20% la couverture du WERA est reduite de 34% alors que pour les CODARs elle est reduite de 67%. Les relations empiriques etablies entre la couverture des RHF et les parametres environnementaux (vent et glace de mer) permettront de predire la couverture que pourraient fournir des RHF installes dans d'autres regions soumises a la presence saisonniere de glace de mer.

Synthese et Caracterisation de Nanocomposites d'Argile et de Graphene Formes a Partir de Precurseurs Organiques =

NASA Astrophysics Data System (ADS)

Boussaboun, Zakariae

Les mineraux d'argile sont des catalyseurs possibles pour la formation du graphene a partir de precurseurs organiques, comme le saccharose. Les argiles sont abondantes, securitaires et economiques pour la formation du graphene. L'objectif principal de ce memoire est de demontrer qu'il est possible de synthetiser un materiau hybride contenant de l'argile et du graphene. La preparation de ces materiaux carbones a base de l'argile (bentonite et cloisite) et le saccharose a ete realisee selon deux methodes. La premiere methode est faite en trois etapes : 1) periode de contact entre l'argile et la source de carbone dans un environnement humide, 2) infiltration de la matiere carbonee et transformation au four a micro-onde, 3) chauffage a 750°C sous azote pour obtenir des materiaux carbones. Par contre la deuxieme methode est faite en deux etapes, sans micro-onde, et avec une augmentation de la quantite de source de carbone (saccharose et alginate). La caracterisation du materiau a permis de suivre les reactions de transformation de la source de carbone vers le graphene. Cette caracterisation a ete faite par la spectroscopie IRTF et Raman, l'analyse thermogravimetrique (TGA), la surface specifique (methode BET) et le microscope electronique a balayage (MEB). La conductivite electrique a ete mesuree par un spectrometre dielectrique et en fonction de la pression appliquee avec un multimetre. Le materiau realise etait incorpore dans une matrice avec un polyethylene a basse densite pour avoir un polymere avec des caracteristiques specifiques. La conductivite thermique a ete ensuite mesuree suivant la norme ASTM E1530. L'echantillon realise avec la deuxieme methode avec une proportion de bentonite pour 5 proportions de saccharose (M2 B1 : S5) signale la possibilite de produire des materiaux de graphene a partir de ressources naturelles. La surface specifique a considerablement augmente de (75,88 m2/g) pour bentonite non traiter a (139,76 m2/g) pour l'echantillon (M2 B1 : S5). Une augmentation significative de la conductivite par pression (95,3 S/m sous une pression de 6,5 MPa par rapport a 1,45*10 -3 S/m pour la bentonite) et la conductivite thermique dans le polyethylene basse densite a une concentration de 10% d'additif (0,332 W/m.K a 0,279 W/m.K) ont ete observes pour le meme echantillon M2 B1 : S5 comparativement a la bentonite non traitee. Les applications possibles sont par exemple les senseurs et les actuateurs par pression.

Immunoglobulin A with protease activity secreted in human milk activates PAR-2 receptors, of intestinal epithelial cells HT-29, and promotes beta-defensin-2 expression.

PubMed

Barrera, G J; Portillo, R; Mijares, A; Rocafull, M A; del Castillo, J R; Thomas, L E

2009-03-24

Secretory antibodies of the immunoglobulin A (sIgA) class constitute the first line of antigen-specific immune protection against pathogens and other antigens at mucosal surfaces. Although initially perceived as potentially deleterious, catalytic antibodies have been proposed to participate in the removal of metabolic wastes and in protection against infection. Here we show that the presence of sIgA endowed with serine protease-like hydrolytic activity in milk strongly correlates with PAR-2 activation in human intestinal epithelial cells. F(ab')(2) fragments of sIgA activated the epithelial cells in culture to produce beta-defensin-2 (hBD2). Intracellular Ca(2+) mobilization was induced by treatment with (1) sIgA-F(ab')(2) fragments; (2) trypsin, a recognized PAR-2 agonist; or (3) a synthetic PAR-2 agonist peptide (SLIGKV). The co-treatment with a synthetic PAR-2 antagonist peptide (FSLLRY) and sIgA-F(ab')(2) fragments eliminates the latter's effect; nevertheless, cells were not refractory to subsequent stimulation with sIgA-F(ab')(2) fragments. Both the induction of hBD-2 expression in epithelial cells and the increase in intracellular [Ca(2+)] stimulated by sIgA-F(ab')(2) fragments were inhibited by treatment with serine protease inhibitors or pertussis toxin (PTX). These findings suggest that catalytic antibodies can activate intestinal epithelial cells through G-protein-coupled PAR-2, and could actively participate in the immune system of breastfed babies inducing the production of peptides related to innate defense, such as defensins.

Incorporating GOES Satellite Photosynthetically Active Radiation (PAR) Retrievals to Improve Biogenic Emission Estimates in Texas

NASA Astrophysics Data System (ADS)

Zhang, Rui; White, Andrew T.; Pour Biazar, Arastoo; McNider, Richard T.; Cohan, Daniel S.

2018-01-01

This study examines the influence of insolation and cloud retrieval products from the Geostationary Operational Environmental Satellite (GOES) system on biogenic emission estimates and ozone simulations in Texas. Compared to surface pyranometer observations, satellite-retrieved insolation and photosynthetically active radiation (PAR) values tend to systematically correct the overestimation of downwelling shortwave radiation in the Weather Research and Forecasting (WRF) model. The correlation coefficient increases from 0.93 to 0.97, and the normalized mean error decreases from 36% to 21%. The isoprene and monoterpene emissions estimated by the Model of Emissions of Gases and Aerosols from Nature are on average 20% and 5% less, respectively, when PAR from the direct satellite retrieval is used rather than the control WRF run. The reduction in biogenic emission rates using satellite PAR reduced the predicted maximum daily 8 h ozone concentration by up to 5.3 ppbV over the Dallas-Fort Worth (DFW) region on some days. However, episode average ozone response is less sensitive, with a 0.6 ppbV decrease near DFW and 0.3 ppbV increase over East Texas. The systematic overestimation of isoprene concentrations in a WRF control case is partially corrected by using satellite PAR, which observes more clouds than are simulated by WRF. Further, assimilation of GOES-derived cloud fields in WRF improved CAMx model performance for ground-level ozone over Texas. Additionally, it was found that using satellite PAR improved the model's ability to replicate the spatial pattern of satellite-derived formaldehyde columns and aircraft-observed vertical profiles of isoprene.

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

DTIC Science & Technology

2001-07-01

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

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

DTIC Science & Technology

1999-08-01

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

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

DTIC Science & Technology

2015-05-01

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

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

DTIC Science & Technology

1989-09-01

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

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

DTIC Science & Technology

1994-09-01

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

Contribution of mycosporine-like amino acids and colored dissolved and particulate matter to sea ice optical properties and ultraviolet attenuation

PubMed Central

Uusikivi, Jari; Vähätalo, Anssi V.; Granskog, Mats A.; Sommaruga, Ruben

2010-01-01

In the Baltic Sea ice, the spectral absorption coefficients for particulate matter (PM) were about two times higher at ultraviolet wavelengths than at photosynthetically available radiation (PAR) wavelengths. PM absorption spectra included significant absorption by mycosporine-like amino acids (MAAs) between 320 and 345 nm. In the surface ice layer, the concentration of MAAs (1.37 μg L−1) was similar to that of chlorophyll a, resulting in a MAAs-to-chlorophyll a ratio as high as 0.65. Ultraviolet radiation (UVR) intensity and the ratio of UVR to PAR had a strong relationship with MAAs concentration (R2 = 0.97, n = 3) in the ice. In the surface ice layer, PM and especially MAAs dominated the absorption (absorption coefficient at 325 nm: 0.73 m−1). In the columnar ice layers, colored dissolved organic matter was the most significant absorber in the UVR (< 380 nm) (absorption coefficient at 325 nm: 1.5 m−1). Our measurements and modeling of UVR and PAR in Baltic Sea ice show that organic matter, both particulate and dissolved, influences the optical properties of sea ice and strongly modifies the UVR exposure of biological communities in and under snow-free sea ice. PMID:20585592

SURFACTANT ENHANCED PHOTO-OXIDATION OF WASTEWATERS

EPA Science Inventory

Initial research projects using the nonionic surfactant Brij-35 established that this surfactant could successfully adsolublize aromatic organic pollutants such as anthracene, naphthalene, benzoic acid, chlorophenol, and benzene onto the surface of TiO₂ par...

Response of Antarctic cryoconite microbial communities to light.

PubMed

Bagshaw, Elizabeth A; Wadham, Jemma L; Tranter, Martyn; Perkins, Rupert; Morgan, Alistair; Williamson, Christopher J; Fountain, Andrew G; Fitzsimons, Sean; Dubnick, Ashley

2016-06-01

Microbial communities on polar glacier surfaces are found dispersed on the ice surface, or concentrated in cryoconite holes and cryolakes, which are accumulations of debris covered by a layer of ice for some or all of the year. The ice lid limits the penetration of photosynthetically available radiation (PAR) to the sediment layer, since the ice attenuates up to 99% of incoming radiation. This suite of field and laboratory experiments demonstrates that PAR is an important control on primary production in cryoconite and cryolake ecosystems. Increased light intensity increased efficiency of primary production in controlled laboratory incubations of debris from the surface of Joyce Glacier, McMurdo Dry Valleys, Antarctica. However, when light intensity was increased to levels near that received on the ice surface, without the protection of an ice lid, efficiency decreased and measurements of photophysiology showed that the communities suffered light stress. The communities are therefore well adapted to low light levels. Comparison with Arctic cryoconite communities, which are typically not covered by an ice lid for the majority of the ablation season, showed that these organisms were also stressed by high light, so they must employ strategies to protect against photodamage. © FEMS 2016.

Response of Antarctic cryoconite microbial communities to light

PubMed Central

Bagshaw, Elizabeth A.; Wadham, Jemma L.; Tranter, Martyn; Perkins, Rupert; Morgan, Alistair; Williamson, Christopher J.; Fountain, Andrew G.; Fitzsimons, Sean; Dubnick, Ashley

2016-01-01

Microbial communities on polar glacier surfaces are found dispersed on the ice surface, or concentrated in cryoconite holes and cryolakes, which are accumulations of debris covered by a layer of ice for some or all of the year. The ice lid limits the penetration of photosynthetically available radiation (PAR) to the sediment layer, since the ice attenuates up to 99% of incoming radiation. This suite of field and laboratory experiments demonstrates that PAR is an important control on primary production in cryoconite and cryolake ecosystems. Increased light intensity increased efficiency of primary production in controlled laboratory incubations of debris from the surface of Joyce Glacier, McMurdo Dry Valleys, Antarctica. However, when light intensity was increased to levels near that received on the ice surface, without the protection of an ice lid, efficiency decreased and measurements of photophysiology showed that the communities suffered light stress. The communities are therefore well adapted to low light levels. Comparison with Arctic cryoconite communities, which are typically not covered by an ice lid for the majority of the ablation season, showed that these organisms were also stressed by high light, so they must employ strategies to protect against photodamage. PMID:27095815

Treatment of dystrophic calcification on a silicone intraocular lens with pars plana vitrectomy

PubMed Central

Mehta, Nitish; Goldberg, Roger A; Shah, Chirag P

2014-01-01

Purpose Dense, vision-obscuring calcification on the posterior aspect of silicone intraocular lenses (IOLs) is often not amenable to neodymium:yttrium-aluminum-garnet capsulotomy, and, in prior reports, has required IOL exchange. We report the successful removal of dense calcium deposition on the posterior surface of a three-piece silicone lens using pars plana vitrectomy (PPV). Materials and methods A 23-gauge PPV was performed using the Stellaris® vitrectomy system. A light pipe was used to retroilluminate the IOL, and a dense fibrous tissue setting with a low cut-rate and high aspiration rate was able to clear the visual axis of the dystrophic calcification without damaging the IOL optic. Results Visual acuity improved from 20/100 to 20/25. Conclusion Small-gauge PPV may be utilized to remove dense dystrophic calcium deposits on the lens surface in lieu of IOL exchange. PMID:25045246

Antarctic Ultraviolet Radiation Climatology from Total Ozone Mapping Spectrometer Data

NASA Technical Reports Server (NTRS)

Lubin, Dan

2004-01-01

This project has successfully produced a climatology of local noon spectral surface irradiance covering the Antarctic continent and the Southern Ocean, the spectral interval 290-700 nm (UV-A, UV-B, and photosynthetically active radiation, PAR), and the entire sunlit part of the year for November 1979-December 1999. Total Ozone Mapping Spectrometer (TOMS) data were used to specify column ozone abundance and UV-A (360- or 380-nm) reflectivity, and passive microwave (MW) sea ice concentrations were used to specify the surface albedo over the Southern Ocean. For this latter task, sea ice concentration retrievals from the Nimbus-7 Scanning Multichannel Microwave Radiometer (SMMR) and its successor, the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave Imager (SSM/I) were identified with ultraviolet/visible-wavelength albedos based on an empirical TOMS/MW parameterization developed for this purpose (Lubin and Morrow, 2001). The satellite retrievals of surface albedo and UV-A reflectivity were used in a delta-Eddington radiative transfer model to estimate cloud effective optical depth. These optical depth estimates were then used along with the total ozone and surface albedo to calculate the downwelling spectral UV and PAR irradiance at the surface. These spectral irradiance maps were produced for every usable day of TOMS data between 1979-1999 (every other day early in the TOMS program, daily later on).

Extended generation profile - E.B.I.C model application in the case of a PN junction

NASA Astrophysics Data System (ADS)

Guermazi, S.; Toureille, A.; Grill, C.; El Jani, B.

2000-01-01

We have developed a model for the calculation of the induced current due to an electron beam with an extended generation profile. Added to the absorbed and diffuse electrons in the depth distribution, the generation profile takes into account the lateral diffusion. The analytical expression of the electron beam induced current (EBIC) is obtained by solving the continuity equation in permanent regime by the Green function method. The induced current profile, obtained in the case of a ternary component (Ga{0.7}Al{0.3}As:N^+/Ga{0.7}Al{0.3}As:P) sulfur doped and prepared by organometallic compounds phase vapor epitaxy method, is compared to the theoretical profiles whose analytical expressions are given by Van Roosbroeck and Bresse. The experimental current profile, measured by S.E.M provided us to calculate the diffusion length of the minority carriers: L_p=1 μm in the N region and L_n=1.80 μm in the P region of the ternaire component. The theoretical curve obtained from the proposed model is in good agreement with the experimental one for a surface recombination velocity of 10^6 cm s^{-1}. Our results are found to be consistent compared to those obtained by other experimental techniques using the same samples. Nous avons développé un modèle de calcul du courant induit par un faisceau d'électrons avec un profil de génération élargi. Le profil de génération prend en compte la répartition spatiale de la diffusion et de l'absorption des électrons. L'expression analytique du courant induit (E.B.I.C) est déterminée par résolution de l'équation de continuité en régime permanent par la méthode des fonctions de Green. Le profil de courant induit obtenu dans le cas d'une jonction PN (Ga{0,7}Al{0,3}As:N^+/Ga{0,7}Al{0,3}As:P) dopée par le soufre et préparée par épitaxie à phase vapeur organo-métallique, est comparé au profil de courant théorique dont l'expression analytique est explicitée par Van Roosbroeck et Bresse. Le profil expérimental de courant E.B.I.C, mesuré par un microscope électronique à balayage, nous a permis de déterminer la longueur de diffusion des porteurs minoritaires L_p=1 μm dans la région N du composant ternaire et L_n=1,8 μm dans la région P de ce composant. La courbe théorique, tracée à partir du modèle proposé, est en bon accord avec la courbe expérimentale pour une vitesse de recombinaison à la surface de 10^6 cm s^{-1}. Ces résultats sont conformes avec ceux obtenus par d'autres techniques expérimentales sur les mêmes échantillons.

Water Relations, Diurnal Acidity Changes, and Productivity of a Cultivated Cactus, Opuntia ficus-indica.

PubMed

Acevedo, E; Badilla, I; Nobel, P S

1983-07-01

Physiological responses of the Crassulacean acid metabolism (CAM) plant Opuntia ficus-indica (Cactaceae) were studied on a commercial plantation in central Chile. Young cladodes (flattened stems) and flower buds exhibited daytime stomatal opening, whereas mature cladodes and fruit exhibited the nocturnal stomatal opening characteristic of CAM plants. Severe water stress suppressed the nocturnal stomatal opening by mature cladodes, but their high water vapor conductance occurring near dawn was not affected. Nocturnal acidity increases were not as sensitive to water stress as was the nocturnal stomatal opening. The magnitude of the nocturnal acidity increases depended on the total daily photosynthetically active radiation (PAR), being 90% PAR-saturated at 27 moles per square meter per day for a mean nighttime air temperature of 5 degrees C and at 20 moles per square meter per day for 18 degrees C. Inasmuch as the PAR received on unshaded vertical surfaces averaged about 21 moles per square meter per day, nocturnal acidity increases by the cladodes were on the verge of being PAR-limited in the field. The net assimilation rate, which was positive throughout the year, annually averaged 3.4 grams per square meter per day for 1.0- and 2.0-year-old plants. Plants that were 5.4 years old had 7.2 square meters of cladode surface area (both sides) and an annual dry weight productivity of 13 megagrams (metric tons) per hectare per year when their ground cover was 32%. This substantial productivity for a CAM plant was accompanied by the highest nocturnal acidity increase so far observed in the field, 0.78 mole H(+) per square meter.

Water Relations, Diurnal Acidity Changes, and Productivity of a Cultivated Cactus, Opuntia ficus-indica1

PubMed Central

Acevedo, Edmundo; Badilla, Ignacio; Nobel, Park S.

1983-01-01

Physiological responses of the Crassulacean acid metabolism (CAM) plant Opuntia ficus-indica (Cactaceae) were studied on a commercial plantation in central Chile. Young cladodes (flattened stems) and flower buds exhibited daytime stomatal opening, whereas mature cladodes and fruit exhibited the nocturnal stomatal opening characteristic of CAM plants. Severe water stress suppressed the nocturnal stomatal opening by mature cladodes, but their high water vapor conductance occurring near dawn was not affected. Nocturnal acidity increases were not as sensitive to water stress as was the nocturnal stomatal opening. The magnitude of the nocturnal acidity increases depended on the total daily photosynthetically active radiation (PAR), being 90% PAR-saturated at 27 moles per square meter per day for a mean nighttime air temperature of 5°C and at 20 moles per square meter per day for 18°C. Inasmuch as the PAR received on unshaded vertical surfaces averaged about 21 moles per square meter per day, nocturnal acidity increases by the cladodes were on the verge of being PAR-limited in the field. The net assimilation rate, which was positive throughout the year, annually averaged 3.4 grams per square meter per day for 1.0- and 2.0-year-old plants. Plants that were 5.4 years old had 7.2 square meters of cladode surface area (both sides) and an annual dry weight productivity of 13 megagrams (metric tons) per hectare per year when their ground cover was 32%. This substantial productivity for a CAM plant was accompanied by the highest nocturnal acidity increase so far observed in the field, 0.78 mole H+ per square meter. PMID:16663084

Effets de l'interaction avec l'oxygène sur le comportement de couches semi-conductrices de ZnO, SnO{2} et CdSe

NASA Astrophysics Data System (ADS)

Ain-Souya, A.; Ghers, M.; Haddad, A.; Tebib, W.; Rehamnia, R.; Messsalhi, A.; Bounouala, M.; Djouama, M. C.

2005-05-01

Les propriétés superficielles des matériaux solides diffèrent de celles du volume. A la surface, des défauts de différentes natures peuvent être présents. Ils permettent à la surface d'être interactive avec le milieu ambiant. Les multiples interactions entre les états de surface et des éléments du milieu extérieur peuvent modifier les propriétés superficielles. Ce travail étudie la régénération de couches semi-conductrices après adsorption isotherme d'oxygène à différentes températures effectuées entre 20 ° C et 300 ° C. Les matériaux qui ont servi à l'étude sont des couches de ZnO, SnO{2} et CdSe. Celles de CdSe ont été obtenues par co-évaporation, sous vide, de cadmium et de sélénium. Les échantillons de ZnO et SnO{2} ont été élaborés par oxydation, à des températures respectives de 450 ° C et 200 ° , de Zn et Sn déposés par électrolyse et par évaporation sous vide. Les matériaux évaporés ont été déposés sur des plaquettes en verre, les autres ont été électrodéposés sur des substrats métalliques. Les variations des propriétés électriques des couches ont été suivies par mesure de leur résistance électrique superficielle R. Les courbes LogR = f (103 /T (K)), relevées sous vide à différentes températures, sont caractéristiques d'un comportement de semi-conducteur. Des essais d'adsorption d'O{2} à différentes températures montrent des variations considérables de R. En effet, la chimisorption forte d'un gaz par une surface semi-conductrice est telle que l'échange électronique entre adsorbant et adsorbat provoque la formation d'une zone de charge d'espace modifiant la conduction superficielle. Les résultats mettent en évidence des domaines de température de plus haute sensibilité à l'oxygène. Pour le CdSe, certaines désorptions isothermes ont été suffisantes pour une régénération totale des échantillons. Les couches de ZnO ont souvent nécessité des désorptions programmées en température (D.P.T.), pour leur restauration à l'état initial, après ionosorption d'O{2}. L'exploitation des courbes de variation de R en cours de D.P.T. permet de déterminer les énergies mises en jeu. Les résultats prouvent que les réactions des états de surface avec l'oxygène sont multiénergétiques. La réactivité de ces couches vis à vis de cet élément dépend fortement de leurs conditions d'élaboration. Ainsi, ces échantillons pourraient servir à la détection de gaz réducteurs d'O{2} qui s'adsorberait par réduction de l'oxygène ionosorbé, et provoquerait un effet inverse sur la conduction, telle qu'une augmentation de la conductivité superficielle ou une diminution de la résistance d'un matériau semi-conducteur de type n. Ces variations sont importantes lorsque la concentration d'oxygène ionosorbé est grande, donc dans les domaines de température de plus haute sensibilité à l'oxygène. Ce mécanisme serait révélateur de la présence d'un gaz réducteur dans l'atmosphère et la surface d'un semi-conducteur pourrait servir d'élément sensible d'un détecteur de gaz.

Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells

NASA Technical Reports Server (NTRS)

Papadaki, M.; Ruef, J.; Nguyen, K. T.; Li, F.; Patterson, C.; Eskin, S. G.; McIntire, L. V.; Runge, M. S.

1998-01-01

Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; P<0.05) at all examined time points (2 to 24 hours). mRNA half-life studies showed that this response was not due to increased mRNA instability. tPA mRNA expression was decreased (to 10% of stationary control; P<0.05) by low shear stress after 12 hours of exposure and was increased (to 250% of stationary control; P<0.05) after 24 hours at high shear stress. The same trends in PAR-1 mRNA levels were observed in rat smooth muscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

[Cell-derived microparticles unveil their fibrinolytic and proteolytic function].

PubMed

Doeuvre, Loïc; Angles-Cano, Eduardo

2009-01-01

Cell-derived microparticles (MP) are membrane microvesicles, 0.1-1 microm in size, shed by cells following activation or during apoptosis in a variety of pathological conditions. MPs released by blood cells or by vascular endothelial cells display molecular signatures that allow their identification and functional characterization. In addition, they provide tissue factor (TF) and a procoagulant phospholipid surface. Therefore, at present, the most strongly established applied research on MPs is their procoagulant activity as a determinant of thrombotic risk in various clinical conditions. Previous studies have indicated that MPs derived from malignant cells express matrix metalloproteinases, urokinase and its receptor (uPA/uPAR) that, in the presence of plasminogen, may act in concert to degrade extracellular matrix proteins. Recently, it was shown that MPs from TNFa-stimulated endothelial cells served as a surface for interaction with plasminogen and its conversion into plasmin by the uPA/uPAR system expressed at their surface. This capacity of MPs to promote plasmin generation confers them a new profibrinolytic and proteolytic function that may be of relevance in fibrinolysis, cell migration, angiogenesis, dissemination of malignant cells, cell detachment and apoptosis.

A new species of Aspidoras Ihering (Siluriformes: Callichthyidae: Corydoradinae) from the Rio Xingu Basin, Pará, Brazil.

PubMed

Leão, Manuela D V; Britto, Marcelo R; Wosiacki, Wolmar B

2015-07-21

A new species of Aspidoras is described from an unnamed stream in the Rio Xingu Basin, Castelo de Sonhos municipality, Pará State, representing the northernmost record of the genus along the edge of the Brazilian Shield in the Amazon Basin. Aspidoras marianae is easily distinguished from all congeners in having minute odontode-bearing platelets scattered over the surface of the snout region, minute platelets between the parieto-supraoccipital process and the nuchal plate, and other shared features related to color pattern, morphometrics, meristics and morphological data. Comments about exclusive and shared features are presented.

In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development.

PubMed

Japón, M A; Rubinstein, M; Low, M J

1994-08-01

We used 35S-labeled oligonucleotides and cRNAs (riboprobes) to detect the temporal order and spatial pattern of anterior pituitary hormone gene expression in (B6CBF1 x B6CBF1)F2 fetal mice from embryonic Day 9.5 (E9.5) to postnatal Day 1 (P1). Pro-opiomelanocortin (POMC) mRNA was expressed in the basal diencephalon on Day E10.5, in the ventromedial zone of the pars distalis on Day E12.5, and in the pars intermedia on Day E14.5. The common alpha-glycoprotein subunit (alpha-GSU) mRNA first appeared in the anterior wall of Rathke's pouch on Day E11.5 and extended to the pars tuberalis and ventromedial zone of the pars distalis on Day E12.5. Thyroid-stimulating hormone-beta (TSH beta) subunit mRNA was expressed initially in both the pas tuberalis and ventromedial pars distalis on Day E14.5, with an identical spatial distribution to alpha-GSU at the time. In contrast, luteinizing hormone-beta (LH beta) subunit and follicle-stimulating hormone beta (FSH beta) subunit mRNAs were detected initially only in the ventromedial pars distalis on Days E16.5 and E17.5, respectively, in an identical distribution to each other. POMC-, alpha-GSU-, TSH beta, LH beta-, and FSH beta-positive cells within the pars distalis all increased in number and autoradiographic signal with differing degrees of spatial expansion posteriorly, laterally, and dorsally up to Day P1. POMC expression was typically the most intense and extended circumferentially to include the entire lateral and dorsal surfaces of the pars distalis. The expression of both growth hormone (GH) and prolactin (PRL) started coincidentally on Day E15.5. However PRL cells localized in the ventromedial area similarly to POMC and the glycoprotein hormone subunits, whereas GH cells were found initially in a more lateral and central distribution within the lobes of the pars distalis. Somatotrophs increased dramatically in number and autoradiographic signal, extending throughout the pars distalis except for the most peripheral layer of cells on Day E17.5. Mammotrophs also increased in number but less abundantly than somatotrophs, and PRL expression remained more confined to central-medial and ventrolateral areas of the pars distalis up to Day P1. These data demonstrate distinctive patterns of expression for each of the major anterior pituitary hormone genes during development of the mouse pituitary gland and suggest that different groups of committed cells are the immediate precursors to the terminally differentiated hormone-secreting cell types.

Impact of Biomass Burning Aerosols on the Biosphere over Amazonia

NASA Astrophysics Data System (ADS)

Malavelle, F.; Haywood, J.; Mercado, L.; Folberth, G.; Bellouin, N.

2014-12-01

Biomass burning (BB) smoke from deforestation and the burning of agricultural waste emit a complex cocktail of aerosol particles and gases. BB emissions show a regional hotspot over South America on the edges of Amazonia. These major perturbations and impacts on surface temperature, surface fluxes, chemistry, radiation, rainfall, may have significant consequent impacts on the Amazon rainforest, the largest and most productive carbon store on the planet. There is therefore potential for very significant interaction and interplay between aerosols, clouds, radiation and the biosphere in the region. Terrestrial carbon production (i.e. photosynthesis) is intimately tied to the supply of photosynthetically active radiation (PAR - i.e. wavelengths between 300-690 nm). PAR in sufficient intensity and duration is critical for plant growth. However, if a decrease in total radiation is accompanied by an increase in the component of diffuse radiation, plant productivity may increase due to higher light use efficiency per unit of PAR and less photosynthetic saturation. This effect, sometimes referred as diffuse light fertilization effect, could have increased the global land carbon sink by approximately one quarter during the global dimming period and is expected to be a least as important locally. By directly interacting with radiation, BB aerosols significantly reduce the total amount of PAR available to plant canopies. In addition, BB aerosols also play a centre role in cloud formation because they provide the necessary cloud condensation nuclei, hence indirectly altering the water cycle and the components and quantity of PAR. In this presentation, we use the recent observations from the South American Biomass Burning Analysis (SAMBBA) to explore the impact of radiation changes on the carbon cycle in the Amazon region caused by BB emissions. A parameterisation of the impact of diffuse and direct radiation upon photosynthesis rates and net primary productivity in the biosphere has been implemented within a fully coupled Earth System Model, namely the UK Met Office Hadley Centre HadGEM2-ES model. We present results from ten-year experiments (2000-2010) designed to investigate the sensitivity of the terrestrial biosphere to the burden and absorbing nature of Amazonian BB aerosols.

A High Resolution, Integrated Approach to Modeling Climate Change Impacts to a Mountain Headwaters Catchment using ParFlow

NASA Astrophysics Data System (ADS)

Pribulick, C. E.; Maxwell, R. M.; Williams, K. H.; Carroll, R. W. H.

2014-12-01

Prediction of environmental response to global climate change is paramount for regions that rely upon snowpack for their dominant water supply. Temperature increases are anticipated to be greater at higher elevations perturbing hydrologic systems that provide water to millions of downstream users. In this study, the relationships between large-scale climatic change and the corresponding small-scale hydrologic processes of mountainous terrain are investigated in the East River headwaters catchment near Gothic, CO. This catchment is emblematic of many others within the upper Colorado River Basin and covers an area of 250 square kilometers, has a topographic relief of 1420 meters, an average elevation of 3266 meters and has varying stream characteristics. This site allows for the examination of the varying effect of climate-induced changes on the hydrologic response of three different characteristic components of the catchment: a steep high-energy mountain system, a medium-grade lower-energy system and a low-grade low-energy meandering floodplain. To capture the surface and subsurface heterogeneity of this headwaters system the basin has been modeled at a 10-meter resolution using ParFlow, a parallel, integrated hydrologic model. Driven by meteorological forcing, ParFlow is able to capture land surface processes and represents surface and subsurface interactions through saturated and variably saturated heterogeneous flow. Data from Digital Elevation Models (DEMs), land cover, permeability, geologic and soil maps, and on-site meteorological stations, were prepared, analyzed and input into ParFlow as layers with a grid size comprised of 1403 by 1685 cells to best represent the small-scale, high resolution model domain. Water table depth, soil moisture, soil temperature, snowpack, runoff and local energy budget values provide useful insight into the catchments response to the Intergovernmental Panel on Climate Change (IPCC) temperature projections. In the near term, coupling this watershed model with one describing a diverse suite of subsurface elemental cycling pathways, including carbon and nitrogen, will provide an improved understanding of the response of the subsurface ecosystems to hydrologic transitions induced as a result of global climate change.

Variability of Solar Radiation and CDOM in Surface Coastal Waters of the Northwestern Mediterranean Sea.

PubMed

Sempéré, Richard; Para, Julien; Tedetti, Marc; Charrière, Bruno; Mallet, Marc

2015-01-01

Atmospheric and in-water solar radiation, including UVR-B, UVR-A and PAR, as well as chromophoric dissolved organic matter absorption [aCDOM (λ)] in surface waters were monthly measured from November 2007 to December 2008 at a coastal station in the Northwestern Mediterranean Sea (Bay of Marseilles, France). Our results showed that the UVR-B/UVR-A ratio followed the same trend in the atmosphere and at 2 m depth in the water (P < 0.0001) with an increase (eight-fold higher) during summer. The low diffuse attenuation coefficients for downward irradiance [Kd (λ)] of UVR-B, UVR-A and PAR indicated that the waters were highly transparent throughout the year. The relationships between aCDOM (λ) and Kd (λ) in this oligotrophic system suggested that CDOM contributed to UVR attenuation in the UVA domain, but also played a significant role in PAR attenuation. Mean UV doses received in the mixed layer depth were higher by a factor 1.4-33 relative to doses received at fixed depths (5 and 10 m) in summer (stratified period), while the inverse pattern was found in winter (mixing period). This shows the importance of taking into account the vertical mixing in the evaluation of UVR effects on marine organisms. © 2015 The American Society of Photobiology.

Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity

PubMed Central

Ruch, Travis R.; Bryant, David M.; Mostov, Keith E.; Engel, Joanne N.

2017-01-01

Pathogens can alter epithelial polarity by recruiting polarity proteins to the apical membrane, but how a change in protein localization is linked to polarity disruption is not clear. In this study, we used chemically induced dimerization to rapidly relocalize proteins from the cytosol to the apical surface. We demonstrate that forced apical localization of Par3, which is normally restricted to tight junctions, is sufficient to alter apical membrane identity through its interactions with phosphatidylinositol 3-kinase (PI3K) and the Rac1 guanine nucleotide exchange factor Tiam1. We further show that PI3K activity is required upstream of Rac1, and that simultaneously targeting PI3K and Tiam1 to the apical membrane has a synergistic effect on membrane remodeling. Thus, Par3 coordinates the action of PI3K and Tiam1 to define membrane identity, revealing a signaling mechanism that can be exploited by human mucosal pathogens. PMID:27881661

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

DTIC Science & Technology

1990-01-01

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

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

NASA Astrophysics Data System (ADS)

Didi, Abdessamad; Dadouch, Ahmed; Jai, Otman

2017-09-01

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

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

DTIC Science & Technology

2010-02-01

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

Long-time dynamics through parallel trajectory splicing

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

Perez, Danny; Cubuk, Ekin D.; Waterland, Amos

2015-11-24

Simulating the atomistic evolution of materials over long time scales is a longstanding challenge, especially for complex systems where the distribution of barrier heights is very heterogeneous. Such systems are difficult to investigate using conventional long-time scale techniques, and the fact that they tend to remain trapped in small regions of configuration space for extended periods of time strongly limits the physical insights gained from short simulations. We introduce a novel simulation technique, Parallel Trajectory Splicing (ParSplice), that aims at addressing this problem through the timewise parallelization of long trajectories. The computational efficiency of ParSplice stems from a speculation strategymore » whereby predictions of the future evolution of the system are leveraged to increase the amount of work that can be concurrently performed at any one time, hence improving the scalability of the method. ParSplice is also able to accurately account for, and potentially reuse, a substantial fraction of the computational work invested in the simulation. We validate the method on a simple Ag surface system and demonstrate substantial increases in efficiency compared to previous methods. As a result, we then demonstrate the power of ParSplice through the study of topology changes in Ag 42Cu 13 core–shell nanoparticles.« less

Trends in Sea Ice Cover, Sea Surface Temperature, and Chlorophyll Biomass Across a Marine Distributed Biological Observatory in the Pacific Arctic Region

NASA Astrophysics Data System (ADS)

Frey, K. E.; Grebmeier, J. M.; Cooper, L. W.; Wood, C.; Panday, P. K.

2011-12-01

The northern Bering and Chukchi Seas in the Pacific Arctic Region (PAR) are among the most productive marine ecosystems in the world and act as important carbon sinks, particularly during May and June when seasonal sea ice-associated phytoplankton blooms occur throughout the region. Recent dramatic shifts in seasonal sea ice cover across the PAR should have profound consequences for this seasonal phytoplankton production as well as the intimately linked higher trophic levels. In order to investigate ecosystem responses to these observed recent shifts in sea ice cover, the development of a prototype Distributed Biological Observatory (DBO) is now underway in the PAR. The DBO is being developed as an internationally-coordinated change detection array that allows for consistent sampling and monitoring at five spatially explicit biologically productive locations across a latitudinal gradient: (1) DBO-SLP (south of St. Lawrence Island (SLI)), (2) DBO-NBS (north of SLI), (3) DBO-SCS (southern Chukchi Sea), (4) DBO-CCS (central Chukchi Sea), and (5) DBO-BCA (Barrow Canyon Arc). Standardized measurements at many of the DBO sites were made by multiple research cruises during the 2010 and 2011 pilot years, and will be expanded with the development of the DBO in coming years. In order to provide longer-term context for the changes occurring across the PAR, we utilize multi-sensor satellite data to investigate recent trends in sea ice cover, chlorophyll biomass, and sea surface temperatures for each of the five DBO sites, as well as a sixth long-term observational site in the Bering Strait. Satellite observations show that over the past three decades, trends in sea ice cover in the PAR have been heterogeneous, with significant declines in the Chukchi Sea, slight declines in the Bering Strait region, but increases in the northern Bering Sea south of SLI. Declines in the persistence of seasonal sea ice cover in the Chukchi Sea and Bering Strait region are due to both earlier sea ice breakup and later sea ice formation. Sea surface temperatures have also shown warming, where sites show significant warming particularly during August, September, and October. Satellite-derived chlorophyll-a concentrations over the past decade have shown trends seemingly in direct response to changing sea ice conditions, with increasing trends in chlorophyll-a concentrations when sea ice declines (and vice versa). In some cases, however, satellite-derived chlorophyll-a concentrations do not show expected changes with sea ice variability, indicating that limitations on biological productivity in this region are complex and spatially heterogeneous. An understanding of these spatial and temporal complexities impacting biological productivity is needed for the accurate prediction of how overall ecosystems may be altered with further expected warming sea surface temperatures and declines in sea ice cover.

Plasmid partition system of the P1par family from the pWR100 virulence plasmid of Shigella flexneri.

PubMed

Sergueev, Kirill; Dabrazhynetskaya, Alena; Austin, Stuart

2005-05-01

P1par family members promote the active segregation of a variety of plasmids and plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB proteins, followed by a parS partition site. The large virulence plasmid pWR100 of Shigella flexneri contains a new P1par family member: pWR100par. Although typical parA and parB genes are present, the putative pWR100parS site is atypical in sequence and organization. However, pWR100parS promoted accurate plasmid partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique BoxB hexamer motifs within parS define species specificities among previously described family members. Although substantially different from P1parS from the P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As predicted, the species specificity of the two types proved identical. They also shared partition-mediated incompatibility, consistent with the proposed mechanistic link between incompatibility and species specificity. Among several informative sequence differences between pWR100parS and P1parS is the presence of a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left much of the parS activity intact. Tolerance of central inserts with integral numbers of helical DNA turns reflects the critical topology of these sites, which are bent by binding the host IHF protein.

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

NASA Astrophysics Data System (ADS)

Leroy, Pierre

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

Smart bi-metallic perovskite nanofibers as selective and reusable sensors of nano-level concentrations of non-steroidal anti-inflammatory drugs.

PubMed

Mohamed, Mona A; Hasan, Menna M; Abdullah, Ibrahim H; Abdellah, Ahmed M; Yehia, Ali M; Ahmed, Nashaat; Abbas, Walaa; Allam, Nageh K

2018-08-01

A strategy for trace-level carbon-based electrochemical sensors is investigated via exploring the interesting properties of BaNb 2 O 6 nanofibers (NFs). Utilizing adsorptive stripping square wave voltammetry (ASSWV), an electrochemical sensing platform was developed based on BaNb 2 O 6 nanofibers-modified carbon paste electrode (CPE) for the sensitive detection of lornoxicam (LOR). Different techniques were used to characterize the fabricated BaNb 2 O 6 perovskite NFs. The obtained data show the feasibility to electro-oxidize LOR and paracetamol (PAR) on the surface of the fabricated sensor. The amount of nanofiber and testing conditions were optimized using response surface methodology and ASSWV technique. The optimized BaNb 2 O 6 /CPE sensor exhibits low detection limit of 6.39 × 10 -10 mol L -1 , even in the presence of the co-formulated drug paracetamol (PAR). The sensor was successfully applied for biological applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of sea-surface photosynthetically available radiation algorithms under various sky conditions and solar elevations.

PubMed

Somayajula, Srikanth Ayyala; Devred, Emmanuel; Bélanger, Simon; Antoine, David; Vellucci, V; Babin, Marcel

2018-04-20

In this study, we report on the performance of satellite-based photosynthetically available radiation (PAR) algorithms used in published oceanic primary production models. The performance of these algorithms was evaluated using buoy observations under clear and cloudy skies, and for the particular case of low sun angles typically encountered at high latitudes or at moderate latitudes in winter. The PAR models consisted of (i) the standard one from the NASA-Ocean Biology Processing Group (OBPG), (ii) the Gregg and Carder (GC) semi-analytical clear-sky model, and (iii) look-up-tables based on the Santa Barbara DISORT atmospheric radiative transfer (SBDART) model. Various combinations of atmospheric inputs, empirical cloud corrections, and semi-analytical irradiance models yielded a total of 13 (11 + 2 developed in this study) different PAR products, which were compared with in situ measurements collected at high frequency (15 min) at a buoy site in the Mediterranean Sea (the "BOUée pour l'acquiSition d'une Série Optique à Long termE," or, "BOUSSOLE" site). An objective ranking method applied to the algorithm results indicated that seven PAR products out of 13 were well in agreement with the in situ measurements. Specifically, the OBPG method showed the best overall performance with a root mean square difference (RMSD) (bias) of 19.7% (6.6%) and 10% (6.3%) followed by the look-up-table method with a RMSD (bias) of 25.5% (6.8%) and 9.6% (2.6%) at daily and monthly scales, respectively. Among the four methods based on clear-sky PAR empirically corrected for cloud cover, the Dobson and Smith method consistently underestimated daily PAR while the Budyko formulation overestimated daily PAR. Empirically cloud-corrected methods using cloud fraction (CF) performed better under quasi-clear skies (CF<0.3) with an RMSD (bias) of 9.7%-14.8% (3.6%-11.3%) than under partially clear to cloudy skies (0.30.7), however, all methods showed larger RMSD differences (biases) ranging between 32% and 80.6% (-54.5%-8.7%). Finally, three methods tested for low sun elevations revealed systematic overestimation, and one method showed a systematic underestimation of daily PAR, with relative RMSDs as large as 50% under all sky conditions. Under partially clear to overcast conditions all the methods underestimated PAR. Model uncertainties predominantly depend on which cloud products were used.

Tailoring Wettability Through the Surface Modification of Electro-spun Polymers by Plasma and Sol-gel Treatments

DTIC Science & Technology

2014-11-01

Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2014 DRDC-RDDC-2014-R102 i...avec la surface des matériaux est d’une importance fondamentale pour de nombreux processus, dont l’adhésion, les réactions chimiques, le transport...hydrodynamique et la nettoyabilité des surfaces. Les propriétés des surfaces peuvent se situer dans une gamme allant d’un caractère hydrophile ou

Analysis of Long-Term Cloud Cover, Radiative Fluxes, and Sea Surface Temperature in the Eastern Tropical Pacific

NASA Technical Reports Server (NTRS)

Simpson, J. J.; Frouin, R.

1996-01-01

Grant activities accomplished during this reporting period are summarized. The contributions of the principle investigator are reported under four categories: (1) AHVRR (Advanced Very High Resolution Radiometer) data; (2) GOES (Geostationary Operational Environ Satellite) data; (3) system software design; and (4) ATSR (Along Track Scanning Radiometer) data. The contributions of the associate investigator are reported for:(1) longwave irradiance at the surface; (2) methods to derive surface short-wave irradiance; and (3) estimating PAR (photo-synthetically active radiation) surface. Several papers have resulted. Abstracts for each paper are provided.

Determination of the dissolution slowness surface by study of etched shapes I. Morphology of the dissolution slowness surface and theoretical etched shapes

NASA Astrophysics Data System (ADS)

Leblois, T.; Tellier, C. R.

1992-07-01

We propose a theoretical model for the anisotropic etching of crystals, in order to be applied in the micromachining. The originality of the model is due to the introduction of dissolution tensors to express the representative surface of the dissolution slowness. The knowledge of the equation of the slowness surface allows us to determine the trajectories of all the elements which compose the starting surface. It is then possible to construct the final etched shape by numerical simulation. Several examples are given in this paper which show that the final etched shapes are correlated to the extrema of the dissolution slowness. Since the slowness surface must be determined from experiments, emphasis is placed on difficulties encountered when we correlate theory to experiments. Nous avons modélisé le processus de dissolution anisotrope des cristaux en vue d'une application à la simulation des formes obtenues par photolithogravure chimique. La principale originalité de ce modèle tient à l'introduction de tenseurs de dissolution pour exprimer la surface représentative de la lenteur de dissolution. La connaissance de l'équation de la lenteur de dissolution permet de calculer les trajectoires des différents éléments constituant la surface de départ puis de reconstituer par simulation la forme dissoute. Les simulations démontrent que les formes limites des cristaux dissous sont corrélées aux extrema de la lenteur de dissolution. La détermination de la surface de la lenteur se faisant à partir de mesures expérimetales, nous nous sommes efforcés de montrer toutes les difficultés attachées à cette analyse.

Durcissement superficiel de la fonte grise Ft25 induit par un traitement de surface dans le moule

NASA Astrophysics Data System (ADS)

Bouitna, Mohamed; Boutarek-Zaourar, Naïma; Mansour, Samir; Chentouf, Samir Mourad; Mossang, Eric

2018-02-01

L'objectif de cette étude est la consolidation en surface de la fonte grise lamellaire Ft25 par un dépôt riche en manganèse en développant une méthode combinant en une seule opération l'élaboration et le traitement de surface dans le moule. Les effets de la granulométrie du ferro-manganèse (80 % Mn + 20 % Fe), ainsi que l'épaisseur des pièces en fontes sur les couches formées ont été étudiés. On a retenu trois granulométries du ferro-manganèse de 0,18 mm, 0,25 mm et 0,5 mm pour le traitement des pièces en fontes présentant des épaisseurs de 25 mm, 100 mm et 200 mm. Parmi les résultats obtenus, on distingue une consolidation des propriétés en surface induite par la formation d'une couche riche en manganèse continue et homogène. L'effet de la granulométrie du ferro-manganèse sur l'épaisseur de la couche traitée a été mis en évidence. La variation de l'épaisseur des couches formées diminue avec l'augmentation de la granulométrie du ferro-manganèse. Pour une pièce de 100 mm d'épaisseur, la couche formée est estimée à 350 μm pour une granulométrie de 0,18 alors qu'elle n'est que de 180 μm pour une granulométrie de 0,5. L'effet de l'épaisseur de la pièce n'est en revanche pas assez prononcé sur la taille des couches formées. Une amélioration nette de la résistance, à l'usure de la fonte traitée en relation avec les transformations en surface, a été mise en évidence.

METEOPOLE-FLUX: an observatory of terrestrial water, energy, and CO2 fluxes in Toulouse

NASA Astrophysics Data System (ADS)

Calvet, Jean-Christophe; Roujean, Jean-Louis; Zhang, Sibo; Maurel, William; Piguet, Bruno; Barrié, Joël; Bouhours, Gilles; Couzinier, Jacques; Garrouste, Olivier; Girres, Sandrine; Suquia, David; Tzanos, Diane

2016-04-01

The METEOPOLE-FLUX project (http://www.cnrm.meteo.fr/spip.php?article874&lang=en) aims at monitoring a large suburban set-aside field in the city of Toulouse (43.572898 N, 1.374384 E). Since June 2012, these data contribute to the international effort to monitor terrestrial ecosystems (grasslands in particular), to the validation of land surface models, and to the near real time quality monitoring of operational weather forecast models. Various variables are monitored at a subhourly rate: wind speed, air temperature, air humidity, atmospheric pressure, precipitation, turbulent fluxes (H, LE, CO2), downwelling and upwelling solar and infrared radiation, downwelling and upwelling PAR, fraction of diffuse incoming PAR, presence of water intercepted by vegetation (rain, dew), soil moisture profile, soil temperature profile, surface albedo, transmissivity of PAR in vegetation canopy. Moreover, local observations are performed using remote sensing techniques: infrared radiometry, GNSS reflectometry, and multi-band surface reflectometry using an aerosol photometer from the AERONET network. Destructive measurements of LAI, green/brown above-ground biomass, and necromass are performed twice a year. This site is characterized by a large fraction of gravels and stones in the soil, ranging from 17% to 35% in the top soil layer (down to 0.6 m), and peaking at 81% at 0.7 m. The impact of gravels and stones on thermal and moisture fluxes in the soil has not been much addressed in the past and is not represented in most land surface models. Their impact on the available water content for plant transpiration and plant growth is not much documented so far. The long term monitoring of this site will therefore improve the knowledge on land processes. The data will be used together with urban meteorological data to characterize the urban heat island. Finally, this site will be used for the CAL/VAL of various satellite products in conjunction with the SMOSMANIA soil moisture network (http://www.cnrm.meteo.fr/spip.php?article251&lang=en). The site will be presented together a first comparison of the ISBA land surface model with the observations.

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis

PubMed Central

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-01-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced lung fibrosis is diminished in both PAR-1 and PAR-2 deficient mice. We thus have been suggested that combined inactivation of PAR-1 and PAR-2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR-1 and PAR-2 agonists in the absence or presence of specific PAR-1 or PAR-2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and PAR-2 deficient mice with or without a specific PAR-1 antagonist (P1pal-12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR-1 and/or PAR-2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR-1 and PAR-2 did not show any additive effects on these pro-fibrotic responses. Strikingly, PAR-2 deficiency as well as pharmacological PAR-1 inhibition reduced bleomycin-induced pulmonary fibrosis to a similar extent. PAR-1 inhibition in PAR-2 deficient mice did not further diminish bleomycin-induced pulmonary fibrosis. Finally, we show that the PAR-1-dependent pro-fibrotic responses are inhibited by the PAR-2 specific antagonist. Targeting PAR-1 and PAR-2 simultaneously is not superior to targeting either receptor alone in bleomycin-induced pulmonary fibrosis. We postulate that the pro-fibrotic effects of PAR-1 require the presence of PAR-2. PMID:25689283

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

NASA Astrophysics Data System (ADS)

Szczota, Mickael

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

Superomniphobic Surfaces for Military Applications: Nano- and Micro-Fabrication Methods. Chapter 1: Lithographic Fabrication of Surfaces with Different Microgeometries and Investigation of Their Wetting Behaviour

DTIC Science & Technology

2011-01-01

plus important, comparativement à une échelle plus large. Les résultats indiquent qu’un effet de cette nature est attribuable à des facteurs...par un angle de contact à l’avancement plus petit et un angle de contact au retrait plus important, comparativement à une échelle plus large. Les...Methods ............................................................................................................ 10 3.1 Experimental Design

Calcul numérique des ondes de surface par une méthode de projection avec un maillage eulérien adaptatif

NASA Astrophysics Data System (ADS)

Guillou, Sylvain; Barbry, Nathaly; Nguyen, Kim Dan

A non hydrostatic vertical two-dimensional numerical model is proposed to calculate free-surface flows. This model is based on resolving the full Navier-Stokes equations by a finite-difference method coupled with Chorin's projection method. An adaptative-Eulerian grid in the sigma-coordinate system is used. The model permits the calculation of surface-waves in estuarine and coastal zones. A benchmark test relative to the soliton propagation is realised to validate the model.

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis.

PubMed

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-06-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced lung fibrosis is diminished in both PAR-1 and PAR-2 deficient mice. We thus have been suggested that combined inactivation of PAR-1 and PAR-2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR-1 and PAR-2 agonists in the absence or presence of specific PAR-1 or PAR-2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and PAR-2 deficient mice with or without a specific PAR-1 antagonist (P1pal-12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR-1 and/or PAR-2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR-1 and PAR-2 did not show any additive effects on these pro-fibrotic responses. Strikingly, PAR-2 deficiency as well as pharmacological PAR-1 inhibition reduced bleomycin-induced pulmonary fibrosis to a similar extent. PAR-1 inhibition in PAR-2 deficient mice did not further diminish bleomycin-induced pulmonary fibrosis. Finally, we show that the PAR-1-dependent pro-fibrotic responses are inhibited by the PAR-2 specific antagonist. Targeting PAR-1 and PAR-2 simultaneously is not superior to targeting either receptor alone in bleomycin-induced pulmonary fibrosis. We postulate that the pro-fibrotic effects of PAR-1 require the presence of PAR-2. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

Makarewicz, Jan, E-mail: jama@amu.edu.pl; Shirkov, Leonid

The pyridine-Ar (PAr) van der Waals (vdW) complex is studied using a high level ab initio method. Its structure, binding energy, and intermolecular vibrational states are determined from the analytical potential energy surface constructed from interaction energy (IE) values computed at the coupled cluster level of theory with single, double, and perturbatively included triple excitations with the augmented correlation consistent polarized valence double-ζ (aug-cc-pVDZ) basis set complemented by midbond functions. The structure of the complex at its global minimum with Ar at a distance of 3.509 Å from the pyridine plane and shifted by 0.218 Å from the center ofmore » mass towards nitrogen agrees well with the corresponding equilibrium structure derived previously from the rotational spectrum of PAr. The PAr binding energy D{sub e} of 392 cm{sup −1} is close to that of 387 cm{sup −1} calculated earlier at the same ab initio level for the prototypical benzene-Ar (BAr) complex. However, under an extension of the basis set, D{sub e} for PAr becomes slightly lower than D{sub e} for BAr. The ab initio vdW vibrational energy levels allow us to estimate the reliability of the methods for the determination of the vdW fundamentals from the rotational spectra. To disclose the character of the intermolecular interaction in PAr, the symmetry-adapted perturbation theory (SAPT) is employed for the analysis of different physical contributions to IE. It is found that SAPT components of IE can be approximately expressed in the binding region by only two of them: the exchange repulsion and dispersion energy. The total induction effect is negligible. The interrelations between various SAPT components found for PAr are fulfilled for a few other complexes involving aromatic molecules and Ar or Ne, which indicates that they are valid for all rare gas (Rg) atoms and aromatics.« less

Voltammetry of 6,6'-dithiodinicotinic acid on a self-assembled phospholipid monolayer prive

NASA Astrophysics Data System (ADS)

Herrero, R.; Vilariño, T.; Barriada, J. L.; Sastre de Vicente, M. E.; López-Fonseca, J. M.; Moncelli, M. R.

1999-04-01

This paper reports a voltammetric study of 6,6'-dithiodinicotinic acid (CPDS) across a biomimetic membrane system consisting of a monolayer of dioleoylphosphatidylcholine, deposited on mercury. Because of the low solubility of this compound and its potential decomposition in alkaline media, estimation of pK values for the carboxyl and amino groups of the pyridine ring of the CPDS entailed using the Hammett equation. UV spectra seem to confirm the presence of the dianionic form of CPDS above pH=3-4. Differential capacity and cyclic voltammetry measurements were made in order to characterize the voltammetric behavior directly on mercury and through a monolayer of dioleoylphosphatidylcholine. Estimation of the CPDS hydrophobicity degree from the partition coefficient in octanol/ water suggests no penetration of the dianion into the monolayer and supports the fact that the named dianion undergoes protonation at the phospholipid/solution interface to give a neutral specie which penetration into the phospholipid region, favored by its higher hydrophobicity, is followed by electrochemical reduction at the mercury surface. Nous avons étudié par voltampérométrie le comportement de l'acide 6,6'-dithiodinicotinique (CPDS) sur l'électrode de mercure couverte par une monocouche de dioleoyl-phosphatidylcholine. La caractérisation électrochimique a été effectuée par des mesures de la capacité différentielle et par voltamétrie cyclique au dessus d'un pH 3-4. Le spectre UV paraît confirmer la présence de la forme dianionique du CPDS. Cependant les données expérimentales associées à une estimation de l'hydrophobicité de la forme dianionique suggèrent que seule la forme neutre du CPDS peut être réduite sur la surface de l'électrode.

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

NASA Astrophysics Data System (ADS)

Benadja, Mounir

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

Expression of protease-activated receptor (PAR)-2, but not other PARs, is regulated by inflammatory cytokines in rat astrocytes.

PubMed

Sokolova, Elena; Aleshin, Stepan; Reiser, Georg

2012-02-01

Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS) and are believed to play an important role in normal brain functioning as well as in development of various inflammatory and neurodegenerative disorders. Pathological conditions cause altered expression of PARs in brain cells and therefore altered responsiveness to PAR activation. The exact mechanisms of regulation of PAR expression are not well studied. Here, we evaluated in rat astrocytes the influence of LPS, pro-inflammatory cytokines TNFα and IL-1β and continuous PAR activation by PAR agonists on the expression levels of PARs. These stimuli are important in inflammatory and neurological disorders, where their levels are increased. We report that LPS as well as cytokines TNFα and IL-1β affected only the PAR-2 level, but their effects were opposite. LPS and TNFα increased the functional expression of PAR-2, whereas IL-1β down-regulated the functional response of PAR-2. Agonists of PAR-1 specifically increased mRNA level of PAR-2, but not protein level. Transcript levels of other PARs were not changed after PAR-1 activation. Stimulation of the cells with PAR-2 or PAR-4 agonists did not alter PAR levels. We found that up-regulation of PAR-2 is dependent on PKC activity, mostly via its Ca²⁺-sensitive isoforms. Two transcription factors, NFκB and AP-1, are involved in up-regulation of PAR-2. These findings provide new information about the regulation of expression of PAR subtypes in brain cells. This is of importance for targeting PARs, especially PAR-2, for the treatment of CNS disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of enterococci and cow-specific qPAR markers in streams impacted by farms under different management practices

EPA Science Inventory

Nonpoint Sources (NPS) of pollution (e.g., agriculture, wildlife, urban runoff) are major contributors of microbial contaminants to surface waters. However, little is known about the behavior and the effect of environmental determinants on molecular markers of fecal contamination...

Neutrophil proteinase 3 (PR3) acts on protease-activated receptor-2 (PAR-2) to enhance vascular endothelial cell barrier function

PubMed Central

Kuckleburg, Christopher J.; Newman, Peter J.

2013-01-01

The principle role of the vascular endothelium is to present a semi-impermeable barrier to soluble factors and circulating cells, while still permitting the passage of leukocytes from the bloodstream into the tissue. The process of diapedesis involves the selective disruption of endothelial cell junctions, an event that could in theory compromise vascular integrity. It is therefore somewhat surprising that neutrophil transmigration does not significantly impair endothelial barrier function. We examined whether neutrophils might secrete factors that promote vascular integrity during the latter stages of neutrophil transmigration, and found that neutrophil proteinase 3 (PR3) – a serine protease harbored in azurophilic granules – markedly enhanced barrier function in endothelial cells. PR3 functioned in this capacity both in its soluble form and in a complex with cell-surface NB1. PR3-mediated enhancement of endothelial cell junctional integrity required its proteolytic activity, as well as endothelial cell expression of the protease-activated receptor, PAR-2. Importantly, PR3 suppressed the vascular permeability changes and disruption of junctional proteins induced by the action of PAR-1 agonists. These findings establish the potential for neutrophil-derived PR3 to play a role in reestablishing vascular integrity following leukocyte transmigration, and in protecting endothelial cells from PAR-1-induced permeability changes that occur during thrombotic and inflammatory events. PMID:23202369

Les Brulures Electriques par Haut Voltage - A Propos de 10 Cas

PubMed Central

Belmir, R.; Fejjal, N.; El Omari, M.; El Mazouz, S.; Gharib, N.; Abassi, A.; Belmahi, A.

2008-01-01

Summary Les accidents électriques par haute tension (AEHT) provoquent des brûlures profondes par effet Joule le long des axes vasculo-nerveux entre les points d'entrée et de sortie, qui sont le siège de lésions délabrantes. Les Auteurs rapportent une série de dix cas d'AEHT admis au service de chirurgie réparatrice et de brûlés de l'Hôpital Ibn Sina de Rabat à travers laquelle ils étudient les caractéristiques épidémiologiques, cliniques et thérapeutiques. Tous les patients étaient des adultes de sexe masculin dont l'âge moyen était de 31 ans. Dans 70% des cas, ces brûlures étaient secondaires à un contact avec les distributeurs d'électricité avec une surface brûlée inférieure à 20%. Le traitement des lésions électrothermiques a nécessité des interventions itératives avec amputation des segments de membres nécrosés dans 70% des cas, dont les suites étaient marquées par des séquelles fonctionnelles invalidantes. La prévention des AEHT, en particulier pour les accidents du travail au sein des professions exposées, reste fondamentale. PMID:21991124

Unsteady Aerodynamics - Fundamentals and Applications of Aircraft Dynamics. Conference Proceedings of the Joint Symposium of the Fluid Dynamics and Flight Mechanics Panels Held in Goettingen, Federal Republic of Germany on 6-9 May 1985.

DTIC Science & Technology

1985-11-01

tourbillons daxe perpendicu-V laire A l’fcoulement principal) issu d’un profil occillant en Tamis dan;, do,, condition,, dn dorochagp dynamique. 5_10...a~rodyna- - mique sur R. A partir de cette analyse experimentale, une tentative de modelisation th~sorique des effets non *lin~ laires observes aux...cisaillement A la paroi d’un profil d’aile anim6 d’un mouvament harmonique parall~le ou parpandicu- laire A 1𔄀coulement non perturb~s", EUROMECH

Modelisation of an unspecialized quadruped walking mammal.

PubMed

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

2001-12-01

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

Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

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

Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.

Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importancemore » of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.« less

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

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

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

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediatedmore » Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.« less

Etude de l'amelioration de la qualite des anodes par la modification des proprietes du brai

NASA Astrophysics Data System (ADS)

Bureau, Julie

La qualite des anodes produites se doit d'etre bonne afin d'obtenir de l'aluminium primaire tout en reduisant le cout de production du metal, la consommation d'energie et les emissions environnementales. Or, l'obtention des proprietes finales de l'anode necessite une liaison satisfaisante entre le coke et le brai. Toutefois, la matiere premiere actuelle n'assure pas forcement la compatibilite entre le coke et le brai. Une des solutions les plus prometteuses, pour ameliorer la cohesion entre ces deux materiaux, est la modification des proprietes du brai. L'objectif de ce travail consiste a modifier les proprietes du brai par l'ajout d'additifs chimiques afin d'ameliorer la mouillabilite du coke par le brai modifie pour produire des anodes de meilleure qualite. La composition chimique du brai est modifiee en utilisant des tensioactifs ou agents de modification de surface choisis dans le but d'enrichir les groupements fonctionnels susceptibles d'ameliorer la mouillabilite. L'aspect economique, l'empreinte environnementale et l'impact sur la production sont consideres dans la selection des additifs chimiques. Afin de realiser ce travail, la methodologie consiste a d'abord caracteriser les brais non modifies, les additifs chimiques et les cokes par la spectroscopie infrarouge a transformee de Fourier (FTIR) afin d'identifier les groupements chimiques presents. Puis, les brais sont modifies en ajoutant un additif chimique afin de possiblement modifier ses proprietes. Differentes quantites d'additif sont ajoutees afin d'examiner l'effet de la variation de la concentration sur les proprietes du brai modifie. La methode FTIR permet d'evaluer la composition chimique des brais modifies afin de constater si l'augmentation de la concentration d'additif enrichit les groupements fonctionnels favorisant l'adhesion coke/brai. Ensuite, la mouillabilite du coke par le brai est observee par la methode goutte- sessile. Une amelioration de la mouillabilite par la modification a l'aide d'un additif chimique signifie une possible amelioration de l'interaction entre le coke et le brai modifie. Afin de completer l'evaluation des donnees recueillies, les resultats de la FTIR et de la mouillabilite sont analyses par le reseau neuronal artificiel afin de mieux comprendre les mecanismes sous-jacents. A la lumiere des resultats obtenus, les additifs chimiques les plus prometteurs sont selectionnes afin de verifier l'effet de leur utilisation sur la qualite des anodes. Pour ce faire, des anodes de laboratoire sont produites en utilisant des brais non modifies et des brais modifies avec les additifs chimiques selectionnes. Par la suite, les anodes sont carottees afin de les caracteriser en determinant certaines de leurs proprietes physiques et chimiques. Enfin, les resultats des echantillons d'anodes faites d'un meme brai non modifie et modifie sont compares afin d'evaluer l'amelioration de la qualite des anodes. Finalement, un examen de l'impact possible de l'utilisation d'un additif chimique pour modifier le brai sur la consommation energetique et en carbone ainsi que la quantite d'aluminium produit est realise. Afin de modifier le brai, trois differents additifs chimiques sont selectionnes, soit un tensioactif et deux agents de modification de surface. L'analyse FTIR des experimentations menees sur les brais modifies demontre que deux additifs ont modifie la composition chimique des brais experimentes. L'analyse des resultats des tests goutte-sessile laisse supposer qu'un brai modifie par ces deux additifs ameliore possiblement l'interaction avec les cokes employes dans cette etude. L'analyse par reseau neuronal artificiel des donnees recueillies permet de mieux comprendre le lien entre la composition chimique d'un brai et sa capacite de mouillabilite avec un coke. La caracterisation des echantillons d'anodes produites permet d'affirmer que ces deux additifs peuvent ameliorer certaines des proprietes anodiques comparativement aux echantillons standards. L'analyse des resultats demontre que l'un des deux additifs semble donner des resultats plus prometteurs. Au final, les travaux realises au cours de ce projet demontrent qu'il est possible d'ameliorer la qualite anodique en modifiant les proprietes du brai. De plus, l'analyse des resultats obtenus fournit une meilleure comprehension des mecanismes entre un brai et un additif chimique.

Calcification of Hydrophilic Acrylic Intraocular Lenses With a Hydrophobic Surface: Laboratory Analysis of 6 Cases.

PubMed

Gartaganis, Sotirios P; Prahs, Philipp; Lazari, Eftichia D; Gartaganis, Panos S; Helbig, Horst; Koutsoukos, Petros G

2016-08-01

To investigate the nature and characteristic features of deposits causing opacification of intraocular lenses (IOLs) based on the examination of clinical findings using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX) analysis. Retrospective, observational case series. This is a multicenter study of 6 hydrophilic acrylic IOLs (Lentis LS-502-1; Oculentis GmbH, Berlin, Germany) with a hydrophobic surface that were explanted from 5 patients because of opacification. Three patients had an uncomplicated phacoemulsification. One patient underwent combined phacoemulsification and pars plana vitrectomy for retinal detachment and later silicone oil endotamponade owing to redetachment. The last patient had a pars plana vitrectomy and silicone oil instillation combined with phacoemulsification for tractive retinal detachment and diabetic retinopathy. The explanted lenses were submitted to our laboratory and were examined by SEM and EDX in order to identify the morphologic features and the composition of the deposits. SEM and EDX analyses confirmed the presence of calcific deposits in the interior of the opacified hydrophilic IOLs, with a pattern showing the formation of lumps on the surface. The lumps were due to subsurface formation of calcium phosphate crystalline deposits. The crystallite clusters seemed to diffuse from the IOL interior to the surface. We demonstrated the calcification pattern of the hydrophilic IOL (Lentis LS-502-1) with a hydrophobic surface. Although hydrophilic acrylic lenses have a hydrophobic surface, the development of calcification is a possible threat initiating from the hydrophilic subsurface of the IOLs. Copyright © 2016 Elsevier Inc. All rights reserved.

A propagating ATPase gradient drives transport of surface-confined cellular cargo

NASA Astrophysics Data System (ADS)

Vecchiarelli, Anthony; Neuman, Keir; Mizuuchi, Kiyoshi

2014-03-01

The process of DNA segregation is of central importance for all organisms. Although eukaryotic mitosis is relatively well established, the most common mechanism employed for bacterial DNA segregation has been unclear. ParA ATPases form dynamic patterns on the bacterial nucleoid, to spatially organize plasmids, chromosomes and other large cellular cargo, but the force generating mechanism has been a source of controversy and debate. A dominant view proposes that ParA-mediated transport and cargo positioning occurs via a filament-based mechanism that resembles eukaryotic mitosis. Here we present direct evidence against such models. Our cell-free reconstitution supports a non-filament-based mode of transport that may be as widely found in nature as actin filaments and microtubules.

Thrombin Receptors and Protease-Activated Receptor-2 in Human Placentation

PubMed Central

O’Brien, Peter J.; Koi, Hideki; Parry, Samuel; Brass, Lawrence F.; Strauss, Jerome F.; Wang, Li-Peng; Tomaszewski, John E.; Christenson, Lane K.

2003-01-01

Proteolysis of the thrombin receptor, protease activated receptor-1 (PAR1), may enhance normal and pathological cellular invasion, and indirect evidence suggests that activation of PAR1 expressed by invasive extravillous trophoblasts (EVTs) influences human placentation. Here we describe PAR1, PAR2, and PAR3 protein distribution in the developing human placenta and implicate PAR1 and PAR2 activation in functions central to EVT invasion. PAR1, PAR2, and PAR3 are expressed in cultured 8- to 13-week-old EVTs, and in situ in 18- to 20-week-old placental syncytiotrophoblasts and invasive trophoblasts. Thrombin, but not the PAR2 agonist peptide SLIGKV, inhibited proliferation in cultured EVTs, although both agonists stimulated phosphoinositide hydrolysis and EVT invasion through Matrigel barriers. Thrombin-induced phosphoinositide hydrolysis was completely inhibited and the thrombin effect on proliferation was prevented when PAR1 cleavage was first blocked with specific monoclonal antibodies, indicating that PAR1 is the predominant thrombin receptor on EVTs. Together these results support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation. PMID:14507634

The signaling adapter Gab1 regulates cell polarity by acting as a PAR protein scaffold

PubMed Central

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

2012-01-01

Summary 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 hypo-phosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased trans-epithelial resistance and lateral domain shortening. Conversely, GAB1 over-expression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multi-lumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a novel negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. PMID:22883624

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

NASA Astrophysics Data System (ADS)

Xing, Jacques

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

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif

PubMed Central

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-01-01

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon–helix–helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF ≈30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal ΔParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization. PMID:17261809

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif.

PubMed

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-02-06

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon-helix-helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF approximately 30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal DeltaParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization.

PAR proteins regulate maintenance-phase myosin dynamics during Caenorhabditis elegans zygote polarization

PubMed Central

Small, Lawrence E.; Dawes, Adriana T.

2017-01-01

Establishment of anterior–posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin–myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We find that PAR-3 and PAR-6 concentrate CDC-42–dependent NMY-2 in the anterior cortex, whereas PAR-2 inhibits CDC-42–dependent NMY-2 in the posterior domain by inhibiting PAR-3 and PAR-6. In addition, we find that PAR-1 and PAR-3 are necessary for inhibiting movement of NMY-2 across the cortex. PAR-1 protects NMY-2 from being moved across the cortex by forces likely originating in the cytoplasm. Meanwhile, PAR-3 stabilizes NMY-2 against PAR-2 and PAR-6 dynamics on the cortex. We find that PAR signaling fulfills two roles: localizing NMY-2 to the anterior cortex and preventing displacement of the polarized cortical actin–myosin network. PMID:28615321

Nucléation et cristallisation dans un verre de chalcogénure du syste`me As sbnd Ge sbnd Se en présence d'un agent nucléant

NASA Astrophysics Data System (ADS)

Hemeda, D.; Tilloca, G.

1988-05-01

Le phénome`ne de nucléation initiépar un agent nucléant (HfSe) dans le verre de chalcogénure As 10 Ge 30Se 60 aétéétudiépar microscopieélectronique. La nucléation se caractérise par une période de latence dont la variation suit la solution analytique proposée par Kaschiev. Plusieurs parame`tres ontétéévalués: σ, l'énergie interfaciale; A, le facteur pré-exponentiel de l'équation générale de nucléation; ΔG D, la barrie`re cinétique de nucléation. Les résultats ontétéanalysés par la méthode basée sur les données de la viscositéet l'équation générale de nucléation. Une hypothe`se sur le mécanisme de la nucléation fondée sur l'action de l'agent nucléant aétéenvisagée. Les résultats relatifs au phénome`ne de croissance indiquent que la variation du taux de croissance réduit est analoguea`celle de matériaux ayant une entropie de fusionélevée et pour lesquels le mécanisme de croissance est régi par une nucléation de surface. L'énergie d'activation de croissance calculée est différente de la valeur estimée pour le verre non nucléédans le cas de l'écoulement visqueux. Une hypothe`se aétéenvisagée pour expliquer cetécart. L'évolution avec le temps de traitement thermique de la fraction cristallisée dans les matériaux aétésuivie par la technique de diffraction X quantitative. On observe une variation de type sigmoi¨dale avec une période de latence pour les différentes températuresétudiées. La cinétique de cristallisation suit l'équation de Johnson-Mehl-Avrami. La variation du taux de réaction avec la température est décrite par une expression de type Arrhénius.

Relations between surface conductance and spectral vegetation indices at intermediate (100 m sq to 15 km sq) length scales

NASA Technical Reports Server (NTRS)

Sellers, Piers J.; Heiser, Mark D.; Hall, Forrest G.

1992-01-01

The relationship between surface conductance and spectral vegetation indices is investigated utilizing the FIFE data set, principally the surface flux station data and images from the TM instrument. It is found that the unstressed canopy conductance for a given site for a given day is near-linearly related to the incident PAR flux. Estimates of unstressed canopy conductance were acquired via a model inversion that separated the soil and vegetation contributions to evapotranspiration and made adjustments for the effects of vapor pressure deficit and soil moisture stress.

Diffuse-Illumination Systems for Growing Plants

NASA Technical Reports Server (NTRS)

May, George; Ryan, Robert

2010-01-01

Agriculture in both terrestrial and space-controlled environments relies heavily on artificial illumination for efficient photosynthesis. Plant-growth illumination systems require high photon flux in the spectral range corresponding with plant photosynthetic active radiation (PAR) (400 700 nm), high spatial uniformity to promote uniform growth, and high energy efficiency to minimize electricity usage. The proposed plant-growth system takes advantage of the highly diffuse reflective surfaces on the interior of a sphere, hemisphere, or other nearly enclosed structure that is coated with highly reflective materials. This type of surface and structure uniformly mixes discrete light sources to produce highly uniform illumination. Multiple reflections from within the domelike structures are exploited to obtain diffuse illumination, which promotes the efficient reuse of photons that have not yet been absorbed by plants. The highly reflective surfaces encourage only the plant tissue (placed inside the sphere or enclosure) to absorb the light. Discrete light sources, such as light emitting diodes (LEDs), are typically used because of their high efficiency, wavelength selection, and electronically dimmable properties. The light sources are arranged to minimize shadowing and to improve uniformity. Different wavelengths of LEDs (typically blue, green, and red) are used for photosynthesis. Wavelengths outside the PAR range can be added for plant diagnostics or for growth regulation

Investigating smoke's influence on primary production throughout the Amazon

NASA Astrophysics Data System (ADS)

Flanner, M. G.; Mahowald, N. M.; Zender, C. S.; Randerson, J. T.; Tosca, M. G.

2007-12-01

Smoke from annual burning in the Amazon causes large reduction in surface insolation and increases the diffuse fraction of photosynthetically-active radiation (PAR). These effects have competing influence on gross primary production (GPP). Recent studies indicate that the sign of net influence depends on aerosol optical depth, but the magnitude of smoke's effect on continental-scale carbon cycling is very poorly constrained and may constitute an important term of fire's net impact on carbon storage. To investigate widespread effects of Amazon smoke on surface radiation properties, we apply a version of the NCAR Community Atmosphere Model with prognostic aerosol transport, driven with re-analysis winds. Carbon aerosol emissions are derived from the Global Fire Emissions Database (GFED). We use AERONET observations to identify model biases in aerosol optical depth, single-scatter albedo, and surface radiative forcing, and prescribe new aerosol optical properties based on field observations to improve model agreement with AERONET data. Finally, we quantify a potential range of smoke-induced change in large-scale GPP based on: 1) ground measurements of GPP in the Amazon as a function of aerosol optical depth and diffuse fraction of PAR, and 2) empirical functions of ecosystem-scale photosynthesis rates currently employed in models such as the Community Land Model (CLM).

Une étude d'un système optique adaptatif en temps réel pour traitement thermique superficiel par laser de puissance A study of an adaptive real-time optical system for surface thermal treatment by a powerful laser

NASA Astrophysics Data System (ADS)

Li, Jun Chang; Merlin, J.; Chen, Qing Hua

1998-12-01

An optical system permitting modulation of the repartition of the energy of a laser beam in real time has been investigated starting from the theory of Fourier optics. Comparisons of the results obtained theoretically and experimentally were made. The thermal effects induced during the surface treatment have also been simulated.

Prediction of Aerodynamic Characteristics of Fighter Wings at High Angles of Attack.

DTIC Science & Technology

1984-03-01

potential distribution throughout the network of four points on a body surface great- ly facilitates the flow analysis procedure. Tangential velocity...expensive of computer time. For example, as quoted by McLean, using this coarsest grid network , each 0 surface of the 727-200 wing required 10 minutes of...1980. 19. Le Balleur, J.C. and Neron , M., "Calcul D’Ecoulements3 Visqueux Decolles sur Profils D’Ailes par une Approche de Couplage", AGARn CP-291

Photosynthetically active radiation (PAR) x ultraviolet radiation (UV) interact to initiate solar injury in apple

USDA-ARS?s Scientific Manuscript database

Sunburn or solar injury (SI) in apple is associated with high temperature, high visible light and ultraviolet radiation (UV). Fruit surface temperature (FST) thresholds for SI related disorders have been developed but there are no thresholds established for solar radiation. The objectives of the s...

Analysis of windsat 3rd and 4th stokes components over Arct Sea ice

USDA-ARS?s Scientific Manuscript database

WindSat has provided an opportunity to investigate the first spaceborne passive fully polarimetric observations of the Earth’s surface. In the present study, we investigated the Arctic sea ice. The passive polarimetric data is provided in the form of the modified Stokes vector consisting of four par...

Decision Support Tool Evaluation Report for Coral Reef Early Warning System (CREWS) Version 7.0

NASA Technical Reports Server (NTRS)

D'Sa, Eurico; Hall, Callie; Zanoni, Vicki; Holland, Donald; Blonski, Slawomir; Pagnutti, Mary; Spruce, Joseph P.

2004-01-01

The Coral Reef Early Warning System (CREWS) is operated by NOAA's Office of Oceanic and Atmospheric Research as part of its Coral Reef Watch program in response to the deteriorating global state of coral reef and related benthic ecosystems. In addition to sea surface temperatures (SSTs), the two most important parameters used by the CREWS network in generating coral reef bleaching alerts are 1) wind speed and direction and 2) photosynthetically available radiation (PAR). NASA remote sensing products that can enhance CREWS in these areas include SST and PAR products from the Moderate Resolution Imaging Spectroradiometer (MODIS) and wind data from the Quick Scatterometer (QuikSCAT). CREWS researchers are also interested in chlorophyll, chromophoric dissolved organic matter (CDOM), and salinity. Chlorophyll and CDOM are directly available as NASA products, while rainfall (an available NASA product) can be used as a proxy for salinity. Other potential NASA inputs include surface reflectance products from MODIS, the Advanced Spaceborne Thermal Emission and Reflection Radiometer, and Landsat. This report also identifies NASA-supported ocean circulation models and products from future satellite missions that might enchance the CREWS DST.

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

Conception et optimisation d'une peau en composite pour une aile adaptative =

NASA Astrophysics Data System (ADS)

Michaud, Francois

Les preoccupations economiques et environnementales constituent des enjeux majeurs pour le developpement de nouvelles technologies en aeronautique. C'est dans cette optique qu'est ne le projet MDO-505 intitule Morphing Architectures and Related Technologies for Wing Efficiency Improvement. L'objectif de ce projet vise a concevoir une aile adaptative active servant a ameliorer sa laminarite et ainsi reduire la consommation de carburant et les emissions de l'avion. Les travaux de recherche realises ont permis de concevoir et optimiser une peau en composite adaptative permettant d'assurer l'amelioration de la laminarite tout en conservant son integrite structurale. D'abord, une methode d'optimisation en trois etapes fut developpee avec pour objectif de minimiser la masse de la peau en composite en assurant qu'elle s'adapte par un controle actif de la surface deformable aux profils aerodynamiques desires. Le processus d'optimisation incluait egalement des contraintes de resistance, de stabilite et de rigidite de la peau en composite. Suite a l'optimisation, la peau optimisee fut simplifiee afin de faciliter la fabrication et de respecter les regles de conception de Bombardier Aeronautique. Ce processus d'optimisation a permis de concevoir une peau en composite dont les deviations ou erreurs des formes obtenues etaient grandement reduites afin de repondre au mieux aux profils aerodynamiques optimises. Les analyses aerodynamiques realisees a partir de ces formes ont predit de bonnes ameliorations de la laminarite. Par la suite, une serie de validations analytiques fut realisee afin de valider l'integrite structurale de la peau en composite suivant les methodes generalement utilisees par Bombardier Aeronautique. D'abord, une analyse comparative par elements finis a permis de valider une rigidite equivalente de l'aile adaptative a la section d'aile d'origine. Le modele par elements finis fut par la suite mis en boucle avec des feuilles de calcul afin de valider la stabilite et la resistance de la peau en composite pour les cas de chargement aerodynamique reels. En dernier lieu, une analyse de joints boulonnes fut realisee en utilisant un outil interne nomme LJ 85 BJSFM GO.v9 developpe par Bombardier Aeronautique. Ces analyses ont permis de valider numeriquement l'integrite structurale de la peau de composite pour des chargements et des admissibles de materiaux aeronautiques typiques.

Microtubules induce self-organization of polarized PAR domains in C. elegans zygotes

PubMed Central

Motegi, Fumio; Zonies, Seth; Hao, Yingsong; Cuenca, Adrian A.; Griffin, Erik; Seydoux, Geraldine

2011-01-01

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1, 2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1, 2, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3/aPKC complex to leave the cortex. Our findings illustrate how microtubules, independent of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC. PMID:21983565

PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells.

PubMed

Alvarez, M M P; Moura, G E; Machado, M F M; Viana, G M; de Souza Costa, C A; Tjäderhane, L; Nader, H B; Tersariol, I L S; Nascimento, F D

2017-12-01

Protease-activated receptors (PARs) are G protein-coupled receptors, which are activated by proteolytical cleavage of the amino-terminus and act as sensors for extracellular proteases. We hypothesized that PAR-1 and PAR-2 can be modulated by inflammatory stimulus in human dental pulp cells. PAR-1 and PAR-2 gene expression in human pulp tissue and MDPC-23 cells were analyzed by quantitative polymerase chain reaction. Monoclonal PAR-1 and PAR-2 antibodies were used to investigate the cellular expression of these receptors using Western blot, flow cytometry, and confocal microscopy in MDPC-23 cells. Immunofluorescence assays of human intact and carious teeth were performed to assess the presence of PAR-1 and PAR-2 in the dentin-pulp complex. The results show for the first time that human odontoblasts and MDPC-23 cells constitutively express PAR-1 and PAR-2. PAR-2 activation increased significantly the messenger RNA expression of matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, and MMP-14 in MDPC-23 cells ( P < 0.05), while the expression of these enzymes decreased significantly in the PAR-1 agonist group ( P < 0.05). The high-performance liquid chromatography and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis showed the presence of MMP-13 activity cleaving PAR-1 at specific, noncanonical site TLDPRS 42 ↓F 43 LL in human dental pulp tissues. Also, we detected a presence of a trypsin-like activity cleaving PAR-2 at canonical site SKGR 20 ↓S 21 LIGRL in pulp tissues. Confocal microscopy analysis of human dentin-pulp complex showed intense positive staining of PAR-1 and PAR-2 in the odontoblast processes in dentinal tubules of carious teeth compared to intact ones. The present results support the hypothesis of activation of the upregulated PAR-1 and PAR-2 by endogenous proteases abundant during the inflammatory response in dentin-pulp complex.

Protease-activated receptor (PAR)2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

PubMed

van den Hengel, Lisa G; Hellingman, Alwine A; Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M; de Vries, Margreet R; Spek, C Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H; Hamming, Jaap F; de Boer, Hetty C; Versteeg, Henri H; Quax, Paul H A

2013-01-01

In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients.

Sea Surface Temperature Influence on Terrestrial Gross Primary Production along the Southern California Current.

PubMed

Reimer, Janet J; Vargas, Rodrigo; Rivas, David; Gaxiola-Castro, Gilberto; Hernandez-Ayon, J Martin; Lara-Lara, Ruben

2015-01-01

Some land and ocean processes are related through connections (and synoptic-scale teleconnections) to the atmosphere. Synoptic-scale atmospheric (El Niño/Southern Oscillation [ENSO], Pacific Decadal Oscillation [PDO], and North Atlantic Oscillation [NAO]) decadal cycles are known to influence the global terrestrial carbon cycle. Potentially, smaller scale land-ocean connections influenced by coastal upwelling (changes in sea surface temperature) may be important for local-to-regional water-limited ecosystems where plants may benefit from air moisture transported from the ocean to terrestrial ecosystems. Here we use satellite-derived observations to test potential connections between changes in sea surface temperature (SST) in regions with strong coastal upwelling and terrestrial gross primary production (GPP) across the Baja California Peninsula. This region is characterized by an arid/semiarid climate along the southern California Current. We found that SST was correlated with the fraction of photosynthetic active radiation (fPAR; as a proxy for GPP) with lags ranging from 0 to 5 months. In contrast ENSO was not as strongly related with fPAR as SST in these coastal ecosystems. Our results show the importance of local-scale changes in SST during upwelling events, to explain the variability in GPP in coastal, water-limited ecosystems. The response of GPP to SST was spatially-dependent: colder SST in the northern areas increased GPP (likely by influencing fog formation), while warmer SST at the southern areas was associated to higher GPP (as SST is in phase with precipitation patterns). Interannual trends in fPAR are also spatially variable along the Baja California Peninsula with increasing secular trends in subtropical regions, decreasing trends in the most arid region, and no trend in the semi-arid regions. These findings suggest that studies and ecosystem process based models should consider the lateral influence of local-scale ocean processes that could influence coastal ecosystem productivity.

Sea Surface Temperature Influence on Terrestrial Gross Primary Production along the Southern California Current

PubMed Central

Reimer, Janet J.; Vargas, Rodrigo; Rivas, David; Gaxiola-Castro, Gilberto; Hernandez-Ayon, J. Martin; Lara-Lara, Ruben

2015-01-01

Some land and ocean processes are related through connections (and synoptic-scale teleconnections) to the atmosphere. Synoptic-scale atmospheric (El Niño/Southern Oscillation [ENSO], Pacific Decadal Oscillation [PDO], and North Atlantic Oscillation [NAO]) decadal cycles are known to influence the global terrestrial carbon cycle. Potentially, smaller scale land-ocean connections influenced by coastal upwelling (changes in sea surface temperature) may be important for local-to-regional water-limited ecosystems where plants may benefit from air moisture transported from the ocean to terrestrial ecosystems. Here we use satellite-derived observations to test potential connections between changes in sea surface temperature (SST) in regions with strong coastal upwelling and terrestrial gross primary production (GPP) across the Baja California Peninsula. This region is characterized by an arid/semiarid climate along the southern California Current. We found that SST was correlated with the fraction of photosynthetic active radiation (fPAR; as a proxy for GPP) with lags ranging from 0 to 5 months. In contrast ENSO was not as strongly related with fPAR as SST in these coastal ecosystems. Our results show the importance of local-scale changes in SST during upwelling events, to explain the variability in GPP in coastal, water-limited ecosystems. The response of GPP to SST was spatially-dependent: colder SST in the northern areas increased GPP (likely by influencing fog formation), while warmer SST at the southern areas was associated to higher GPP (as SST is in phase with precipitation patterns). Interannual trends in fPAR are also spatially variable along the Baja California Peninsula with increasing secular trends in subtropical regions, decreasing trends in the most arid region, and no trend in the semi-arid regions. These findings suggest that studies and ecosystem process based models should consider the lateral influence of local-scale ocean processes that could influence coastal ecosystem productivity. PMID:25923109

Phosphorylation of Mycobacterium tuberculosis ParB Participates in Regulating the ParABS Chromosome Segregation System

PubMed Central

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis. PMID:25807382

Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

PubMed

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

Elaboration de revetements nanocomposites avec des proprietes superhydrophobes, semi-conductrices et photocatalytiques

NASA Astrophysics Data System (ADS)

Madidi, Fatima Zahra

Les lignes aeriennes de transport et de distribution de l'energie electrique sont souvent exposees a diverses contraintes. Parmi celles-ci, la pollution des isolateurs constitue l'un des facteurs de premiere importance dans la fiabilite du transport d'energie. En effet, la presence de pollution sur les isolateurs lorsqu'elle est humidifiee entraine la diminution de leur performance electrique en favorisant l'apparition d'arcs de contournement. De telles pannes peuvent parfois causer des impacts socioeconomiques importants. Par ailleurs, le developpement de nouveaux revetements pour ces isolateurs peut s'averer un moyen efficace pour les proteger contre l'apparition de l'arc de contournement. Les revetements superhydrophobes ont fait l'objet de nombreuses etudes au cours de ces dernieres annees. Ces surfaces sont preparees en combinant une rugosite nano-microstructuree avec une faible energie de surface. En outre, de telles surfaces ont de nombreuses applications si elles sont durables et n'ont pas d'effets nocifs sur l'environnement. L'objectif principal de la presente etude vise d'abord l'elaboration de revetements superhydrophobes, puis l'etude de leur duree de vie, leurs proprietes dielectriques et photocatalytiques. Une grande variete de materiaux a faible energie de surface peuvent etre utilises pour le developpement de ces revetements. Dans cette recherche, le caoutchouc de silicone (CS) est employe car il presente de nombreuses proprietes, notamment une forte hydrophobie, une resistance aux rayonnements ultraviolets, et une bonne tenue au feu sans degagement de produits toxiques. Toutefois, le point faible de ces materiaux est la degradation de leurs proprietes hydrophobes. Afin d'ameliorer certaines proprietes du caoutchouc de silicone, des nanoparticules seront additionnees au polymere de base. La technique d'elaboration des revetements consiste a ajouter des nanoparticules de dioxyde de titane (TiO2) au polymere de base, par des methodes ayant un potentiel d'applications industrielles. Les parametres d'elaboration ont ete optimises afin d'obtenir des revetements stables presentant des angles de contact eleves avec des gouttelettes d'eau et de faibles hysteresis. Apres avoir obtenu des surfaces superhydrophobes, des tests de stabilite ont ete effectues dans des conditions de vieillissement accelere tels que l'immersion dans des solutions aqueuses avec differents pH et conductivites ou la degradation par rayonnement UV. Les resultats obtenus ont montre que l'ajout de nanoparticules de dioxyde de titane au caoutchouc de silicone permet d'ameliorer l'hydrophobie et la stabilite de ce polymere. Les revetements superhydrophobes obtenus ont pu maintenir leur superhydrophobicite apres plusieurs jours d'immersion dans differentes solutions aqueuses. Ils presentent aussi une bonne stabilite lorsqu'ils sont exposes aux rayons UV ainsi qu'une stabilite mecanique. De plus, on a pu developper des revetements nanocomposites et microcomposites avec de bonnes proprietes dielectriques. L'etude des proprietes photocatalytiques des revetements superhydrophobes ont montre que l'adsorption des molecules reactives (polluants) sur la surface du catalyseur (TiO2) est le parametre cle de l'activite photocatalytique. L'augmentation de la concentration de TiO2 conduit a une diminution de la concentration du polluant et par consequent a un excellent rendement photocatalytique.

Thrombin enhances herpes simplex virus infection of cells involving protease-activated receptor 1.

PubMed

Sutherland, M R; Friedman, H M; Pryzdial, E L G

2007-05-01

We have previously shown that the surface of purified herpes family viruses can initiate thrombin production by expressing host-encoded and virus-encoded procoagulant factors. These enable the virus to bypass the normal cell-regulated mechanisms for initiating coagulation, and provide a link between infection and vascular disease. In the current study we investigated why these viruses may have evolved to generate thrombin. Using cytolytic viral plaque assays, the current study examines the effect of thrombin on human umbilical vein endothelial cell (HUVEC) or human foreskin fibroblast (HFF) infection by purified herpes simplex virus type 1 (HSV1) and type 2 (HSV2). Demonstrating that the availability of thrombin is an advantage to the virus, purified thrombin added to serum-free inoculation media resulted in up to a 3-fold enhancement of infection depending on the virus strain and cell type. The effect of thrombin on HUVEC infection was generally greater than its effect on HFF. To illustrate the involvement of thrombin produced during inoculation, hirudin was shown to inhibit the infection of each HSV strain, but only when serum containing clotting factors for thrombin production was present in media. The involvement of protease-activated receptor 1 (PAR1) was supported using PAR1-activating peptides in place of thrombin and PAR1-specific antibodies to inhibit the effects of thrombin. These data show that HSV1 and HSV2 initiate thrombin production to increase the susceptibility of cells to infection through a mechanism involving PAR1-mediated cell modulation.

Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones.

PubMed

Yamada, M; Yoshida, J; Hatou, S; Yoshida, T; Minagawa, Y

2008-06-01

Staphylococcus epidermidis is one of the prominent pathogens in ocular infection. The prevalence of mutations in the quinolone resistance determining region (QRDR) area in S epidermidis isolated from the ocular surface and its association with fluoroquinolone resistance has not been fully elucidated. Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods. The MIC(90) values of levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin were 3.13, 1.56, 0.78 and 3.13 microg/ml, respectively. The MIC values of all fluoroquinolones showed a bimodal distribution (susceptible strain and less susceptible strain). Mutations with amino acid substitution in the QRDR were present in 70 (50.7%) isolates. 19 different combinations of mutations were detected: 3 isolates (2.2%) had four mutations, 8 (5.8%) had three mutations, 43 (31.2%) had double mutations and 16 (11.6%) had single mutations. Isolates with mutations in the QRDR of both gyrA and parC (n = 53) were less susceptible to fluoroquinolones. The present findings show that approximately half the S epidermidis isolates from the normal human conjunctiva have mutation(s) in the QRDR. The presence of mutations in both gyrA and parC is strongly associated with reduced susceptibility to fluoroquinolones.

PH motifs in PAR1&2 endow breast cancer growth.

PubMed

Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

2015-11-24

Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Automatic monitoring of ecosystem structure and functions using integrated low-cost near surface sensors

NASA Astrophysics Data System (ADS)

Kim, J.; Ryu, Y.; Jiang, C.; Hwang, Y.

2016-12-01

Near surface sensors are able to acquire more reliable and detailed information with higher temporal resolution than satellite observations. Conventional near surface sensors usually work individually, and thus they require considerable manpower from data collection through information extraction and sharing. Recent advances of Internet of Things (IoT) provides unprecedented opportunities to integrate various low-cost sensors as an intelligent near surface observation system for monitoring ecosystem structure and functions. In this study, we developed a Smart Surface Sensing System (4S), which can automatically collect, transfer, process and analyze data, and then publish time series results on public-available website. The system is composed of micro-computer Raspberry pi, micro-controller Arduino, multi-spectral spectrometers made from Light Emitting Diode (LED), visible and near infrared cameras, and Internet module. All components are connected with each other and Raspberry pi intelligently controls the automatic data production chain. We did intensive tests and calibrations in-lab. Then, we conducted in-situ observations at a rice paddy field and a deciduous broadleaf forest. During the whole growth season, 4S obtained landscape images, spectral reflectance in red, green, blue, and near infrared, normalized difference vegetation index (NDVI), fraction of photosynthetically active radiation (fPAR), and leaf area index (LAI) continuously. Also We compared 4S data with other independent measurements. NDVI obtained from 4S agreed well with Jaz hyperspectrometer at both diurnal and seasonal scales (R2 = 0.92, RMSE = 0.059), and 4S derived fPAR and LAI were comparable to LAI-2200 and destructive measurements in both magnitude and seasonal trajectory. We believe that the integrated low-cost near surface sensor could help research community monitoring ecosystem structure and functions closer and easier through a network system.

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

NASA Astrophysics Data System (ADS)

Pollender-Moreau, Olivier

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

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

PubMed

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

ROPES reveals past land cover and pollen productivity estimates from single pollen records

NASA Astrophysics Data System (ADS)

Theuerkauf, Martin; Couwenberg, John

2018-04-01

Quantitative reconstructions of past vegetation cover commonly require pollen productivity estimates (PPEs). PPEs are calibrated in extensive and rather cumbersome surface-sample studies, and are so far only available for selected regions. Moreover, it may be questioned whether present-day pollen-landcover relationships are valid for palaeo-situations. We here introduce the ROPES approach that simultaneously derives PPEs and mean plant abundances from single pollen records. ROPES requires pollen counts and pollen accumulation rates (PARs, grains cm-2 year-1). Pollen counts are used to reconstruct plant abundances following the REVEALS approach. The principle of ROPES is that changes in plant abundance are linearly represented in observed PAR values. For example, if the PAR of pine doubles, so should the REVEALS reconstructed abundance of pine. Consequently, if a REVEALS reconstruction is ‘correct’ (i.e. ‘correct’ PPEs are used) the ratio ‘PAR over REVEALS’ is constant for each taxon along all samples of a record. With incorrect PPEs, the ratio will instead vary. ROPES starts from random (likely incorrect) PPEs, but then adjusts them using an optimization algorithm with the aim to minimize variation in the ‘PAR over REVEALS’ ratio across the record. ROPES thus simultaneously calculates mean plant abundances and PPEs. We illustrate the approach with test applications on nine synthetic pollen records. The results show that good performance of ROPES requires data sets with high underlying variation, many samples and low noise in the PAR data. ROPES can deliver first landcover reconstructions in regions for which PPEs are not yet available. The PPEs provided by ROPES may then allow for further REVEALS-based reconstructions. Similarly, ROPES can provide insight in pollen productivity during distinct periods of the past such as the Lateglacial. We see a potential to study spatial and temporal variation in pollen productivity for example in relation to site parameters, climate and land use. It may even be possible to detect expansion of non-pollen producing areas in a landscape. Overall, ROPES will help produce more accurate landcover reconstructions and expand reconstructions into new study regions and non-analogue situations of the past. ROPES will be available within the R package DISQOVER.

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

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.

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

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 parB genes but that in at least one E. coli strain, all three genes are required for maximum stabilization. It cannot be determined from these results whether or not the stabilization effects seen with parCBA or the cer and loxP/Cre systems are strictly due to a reduction in the level of RK2 dimers and an increase in the number of plasmid monomer units or if these systems play a role in a more complex process of plasmid stabilization that requires as an essential step the resolution of plasmid dimers. PMID:9811663

A Cryptoendolithic Community in Volcanic Glass

NASA Astrophysics Data System (ADS)

Herrera, Aude; Cockell, Charles S.; Self, Stephen; Blaxter, Mark; Reitner, Joachim; Thorsteinsson, Thorsteinn; Arp, Gernot; Dröse, Wolfgang; Tindle, Andrew G.

2009-05-01

Fluorescent in situ hybridization (FISH) and 16S rDNA analysis were used to characterize the endolithic colonization of silica-rich rhyolitic glass (obsidian) in a barren terrestrial volcanic environment in Iceland. The rocks were inhabited by a diverse eubacterial assemblage. In the interior of the rock, we identified cyanobacterial and algal 16S (plastid) sequences and visualized phototrophs by FISH, which demonstrates that molecular methods can be used to characterize phototrophs at the limits of photosynthetically active radiation (PAR). Temperatures on the surface of the dark rocks can exceed 40°C but are below freezing for much of the winter. The rocks effectively shield the organisms within from ultraviolet radiation. Although PAR sufficient for photosynthesis cannot penetrate more than ˜250 μm into the solid rock, the phototrophs inhabit cavities; and we hypothesize that by weathering the rock they may contribute to the formation of cavities in a feedback process, which allows them to acquire sufficient PAR at greater depths. These observations show how pioneer phototrophs can colonize the interior of volcanic glasses and rocks, despite the opaque nature of these materials. The data show that protected microhabitats in volcanic rocky environments would have been available for phototrophs on early Earth.

A cryptoendolithic community in volcanic glass.

PubMed

Herrera, Aude; Cockell, Charles S; Self, Stephen; Blaxter, Mark; Reitner, Joachim; Thorsteinsson, Thorsteinn; Arp, Gernot; Dröse, Wolfgang; Tindle, Andrew G

2009-05-01

Fluorescent in situ hybridization (FISH) and 16S rDNA analysis were used to characterize the endolithic colonization of silica-rich rhyolitic glass (obsidian) in a barren terrestrial volcanic environment in Iceland. The rocks were inhabited by a diverse eubacterial assemblage. In the interior of the rock, we identified cyanobacterial and algal 16S (plastid) sequences and visualized phototrophs by FISH, which demonstrates that molecular methods can be used to characterize phototrophs at the limits of photosynthetically active radiation (PAR). Temperatures on the surface of the dark rocks can exceed 40 degrees C but are below freezing for much of the winter. The rocks effectively shield the organisms within from ultraviolet radiation. Although PAR sufficient for photosynthesis cannot penetrate more than approximately 250 mum into the solid rock, the phototrophs inhabit cavities; and we hypothesize that by weathering the rock they may contribute to the formation of cavities in a feedback process, which allows them to acquire sufficient PAR at greater depths. These observations show how pioneer phototrophs can colonize the interior of volcanic glasses and rocks, despite the opaque nature of these materials. The data show that protected microhabitats in volcanic rocky environments would have been available for phototrophs on early Earth.

Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.

PubMed

Ge, Shuqing; Li, Tao; Yao, Qijian; Yan, Hongling; Huiyun, Zhang; Zheng, Yanshan; Zhang, Bin; He, Shaoheng

2016-12-01

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH 2 , and PAR-2 agonist peptide tc-LIGRLO-NH 2 provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH 2 -induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH 2 , an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH 2 -induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.

PubMed

Magnussen, Synnove Norvoll; Hadler-Olsen, Elin; Costea, Daniela Elena; Berg, Eli; Jacobsen, Cristiane Cavalcanti; Mortensen, Bente; Salo, Tuula; Martinez-Zubiaurre, Inigo; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjorg

2017-05-19

Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

PubMed Central

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E.

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance. PMID:24740120

Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

PubMed

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Superomniphobic Surfaces for Military Applications: Nano- and Micro-Fabrication Methods. Chapter 2: Investigation of Wear for Superhydrophobic Surfaces and Development of New Coatings

DTIC Science & Technology

2011-01-01

Queen in Right of Canada, as represented by the Minister of National Defence, 2011 © Sa Majesté la Reine (en droit du Canada), telle que représentée par...alors que dans d’autres, elles sont faibles (Ra, Rq, Rz) et ne permettent pas d’extraire les diverses transitions qui surviennent au cours du...existe une corrélation élevée entre certains paramètres de rugosité et les étapes de transition au cours du mouillage de la surface. On observe aussi que

Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis.

PubMed

Lennerz, Jochen K; Hurov, Jonathan B; White, Lynn S; Lewandowski, Katherine T; Prior, Julie L; Planer, G James; Gereau, Robert W; Piwnica-Worms, David; Schmidt, Robert E; Piwnica-Worms, Helen

2010-11-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a(-/-) but not in control or Par-1b(-/-) mice. The intercrossing of Par-1a(-/-) with Par-1b(-/-) mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a(-/-) mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b(-/-) mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice.

Effects of leaf area index on the coupling between water table, land surface energy fluxes, and planetary boundary layer at the regional scale

NASA Astrophysics Data System (ADS)

Lu, Y.; Rihani, J.; Langensiepen, M.; Simmer, C.

2013-12-01

Vegetation plays an important role in the exchange of moisture and energy at the land surface. Previous studies indicate that vegetation increases the complexity of the feedbacks between the atmosphere and subsurface through processes such as interception, root water uptake, leaf surface evaporation, and transpiration. Vegetation cover can affect not only the interaction between water table depth and energy fluxes, but also the development of the planetary boundary layer. Leaf Area Index (LAI) is shown to be a major factor influencing these interactions. In this work, we investigate the sensitivity of water table, surface energy fluxes, and atmospheric boundary layer interactions to LAI as a model input. We particularly focus on the role LAI plays on the location and extent of transition zones of strongest coupling and how this role changes over seasonal timescales for a real catchment. The Terrestrial System Modelling Platform (TerrSysMP), developed within the Transregional Collaborative Research Centre 32 (TR32), is used in this study. TerrSysMP consists of the variably saturated groundwater model ParFlow, the land surface model Community Land Model (CLM), and the regional climate and weather forecast model COSMO (COnsortium for Small-scale Modeling). The sensitivity analysis is performed over a range of LAI values for different vegetation types as extracted from the Moderate Resolution Imaging Spectroradiometer (MODIS) dataset for the Rur catchment in Germany. In the first part of this work, effects of vegetation structure on land surface energy fluxes and their connection to water table dynamics are studied using the stand-alone CLM and the coupled subsurface-surface components of TerrSysMP (ParFlow-CLM), respectively. The interconnection between LAI and transition zones of strongest coupling are investigated and analyzed through a subsequent set of subsurface-surface-atmosphere coupled simulations implementing the full TerrSysMP model system.

Cortical thickness and surface area in neonates at high risk for schizophrenia.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

2016-01-01

Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.

Testing UK blood donors for exposure to human parvovirus 4 using a time-resolved fluorescence immunoassay to screen sera and Western blot to confirm reactive samples.

PubMed

Maple, Peter A C; Beard, Stuart; Parry, Ruth P; Brown, Kevin E

2013-10-01

Human parvovirus 4 (ParV4), a newly described member of the family Parvoviridae, like B19V, has been found in pooled plasma preparations. The extent, and significance, of ParV4 exposure in UK blood donors remain to be determined and reliable detection of ParV4 immunoglobulin (Ig)G, using validated methods, is needed. With ParV4 virus-like particles a ParV4 IgG time-resolved fluorescence immunoassay (TRFIA) was developed. There is no gold standard or reference assay for measuring ParV4 IgG and the utility of the TRFIA was first examined using a panel of sera from people who inject drugs (PWIDS)--a high-prevalence population for ParV4 infection. Western blotting was used to confirm the specificity of TRFIA-reactive sera. Two cohorts of UK blood donor sera comprising 452 sera collected in 1999 and 156 sera collected in 2009 were tested for ParV4 IgG. Additional testing for B19V IgG, hepatitis C virus antibodies (anti-HCV), and ParV4 DNA was also undertaken. The rate of ParV4 IgG seroprevalence in PWIDS was 20.7% and ParV4 IgG was positively associated with the presence of anti-HCV with 68.4% ParV4 IgG-positive sera testing anti-HCV-positive versus 17.1% ParV4 IgG-negative sera. Overall seropositivity for ParV4 IgG, in 608 UK blood donors was 4.76%. The ParV4 IgG seropositivity for sera collected in 1999 was 5.08%, compared to 3.84% for sera collected in 2009. No ParV4 IgG-positive blood donor sera had detectable ParV4 DNA. ParV4 IgG has been found in UK blood donors and this finding needs further investigation. © 2013 American Association of Blood Banks.

PAR-2 regulates dental pulp inflammation associated with caries.

PubMed

Lundy, F T; About, I; Curtis, T M; McGahon, M K; Linden, G J; Irwin, C R; El Karim, I A

2010-07-01

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Effect and mechanism of PAR-2 on the proliferation of esophageal cancer cells.

PubMed

Quanjun, D; Qingyu, Z; Qiliang, Z; Liqun, X; Jinmei, C; Ziquan, L; Shike, H

2016-11-01

Esophageal Cancer (EC) is a common malignant tumor occurred in the digestive tract. In this study, we investigated the mechanism of Protease Activated Receptor 2 (PAR-2) on the proliferation of esophageal cancer cell. Transfected esophageal cancer (EC) cell (PAR-2shRNA EC109) was established with low stable PAR-2 expression. EC109 cell was treated with PAR-2 agonist, PAR-2 anti-agonist and MAPK inhibitor respectively; Untreated EC109 cell (blank control) and PAR-2shRNA EC109 cell were used for analysis also. The mRNA expressions of PAR-2, ERK1, Cyclin D1, and c-fos in each group were detected by reverse transcript and polymerase chain reaction. Western blot was used to detect the protein expressions in each group. The cell growth curves were drawn to compare the cell growth. Compared with the blank control, the mRNA and protein expressions of PAR-2, Cyclin D1, and c-fos in PAR-2 agonist group increased significantly (p < 0.05), while decreased significantly in PAR-2shRNA EC109 cell and MAPK inhibitor group (p < 0.05). The mRNA expression of ERK1 and protein expression of p-ERK1 increased in PAR-2 agonist group, decreased in PAR-2shRNA EC109 cell and MAPK inhibitor group when compared with blank control (p < 0.05). The growth of cells was upward in PAR-2 agonist group at cell growth phase when compared with blank control, while decreased in PAR-2 shRNA EC109 cell and MAPK inhibitor group with statistical difference (p < 0.05). PAR-2 regulate cell proliferation through the MAPK pathway in esophageal carcinoma cell, and Cyclin D1, c-fos are involved in this process.

Protease-activated Receptor-4 Signaling and Trafficking Is Regulated by the Clathrin Adaptor Protein Complex-2 Independent of β-Arrestins*

PubMed Central

Smith, Thomas H.; Coronel, Luisa J.; Li, Julia G.; Dores, Michael R.; Nieman, Marvin T.; Trejo, JoAnn

2016-01-01

Protease-activated receptor-4 (PAR4) is a G protein-coupled receptor (GPCR) for thrombin and is proteolytically activated, similar to the prototypical PAR1. Due to the irreversible activation of PAR1, receptor trafficking is intimately linked to signal regulation. However, unlike PAR1, the mechanisms that control PAR4 trafficking are not known. Here, we sought to define the mechanisms that control PAR4 trafficking and signaling. In HeLa cells depleted of clathrin by siRNA, activated PAR4 failed to internalize. Consistent with clathrin-mediated endocytosis, expression of a dynamin dominant-negative K44A mutant also blocked activated PAR4 internalization. However, unlike most GPCRs, PAR4 internalization occurred independently of β-arrestins and the receptor's C-tail domain. Rather, we discovered a highly conserved tyrosine-based motif in the third intracellular loop of PAR4 and found that the clathrin adaptor protein complex-2 (AP-2) is important for internalization. Depletion of AP-2 inhibited PAR4 internalization induced by agonist. In addition, mutation of the critical residues of the tyrosine-based motif disrupted agonist-induced PAR4 internalization. Using Dami megakaryocytic cells, we confirmed that AP-2 is required for agonist-induced internalization of endogenous PAR4. Moreover, inhibition of activated PAR4 internalization enhanced ERK1/2 signaling, whereas Akt signaling was markedly diminished. These findings indicate that activated PAR4 internalization requires AP-2 and a tyrosine-based motif and occurs independent of β-arrestins, unlike most classical GPCRs. Moreover, these findings are the first to show that internalization of activated PAR4 is linked to proper ERK1/2 and Akt activation. PMID:27402844

TGF-β induced PAR-1 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone.

PubMed

Wang, Ting; Jiao, Jian; Zhang, Hao; Zhou, Wang; Li, Zhenxi; Han, Shuai; Wang, Jing; Yang, Xinghai; Huang, Quan; Wu, Zhipeng; Yan, Wangjun; Xiao, Jianru

2017-10-15

Although protease activated receptor-1 (PAR-1) has been confirmed as an oncogene in many cancers, the role of PAR-1 in giant cell tumor (GCT) of bone has been rarely reported. The mechanism of PAR-1 in tumor-induced osteoclastogenesis still remains unclear. In the present study, we detected that PAR-1 was significantly upregulated in GCT of bone compared to normal tissues, while TGF-β was also overexpressed in GCT tissues and could promote the expression of PAR-1 in a dose and time dependent manner. Using the luciferase reporter assay, we found that two downstreams of TGF-β, Smad3 and Smad4, could activate the promoter of PAR-1, which might explain the mechanism of TGF-β induced PAR-1 expression. Meanwhile, PAR-1 was also overexpressed in microvesicles from stromal cells of GCT (GCTSCs), and might be transported from GCTSCs to monocytes through microvesicles. In addition, knockout of PAR-1 by TALENs in GCTSCs inhibited tumor growth, angiogenesis and osteoclastogenesis in GCT in vitro. Using the chick CAM models, we further showed that inhibition of PAR-1 suppressed tumor growth and giant cell formation in vivo. Using microarray assay, we detected a number of genes involved in osteoclastogenesis as the possible downstreams of PAR-1, which may partly explain the mechanism of PAR-1 in GCT. In brief, for the first time, these results reveal an upstream regulatory role of TGF-β in PAR-1 expression, and PAR-1 expression promotes tumor growth, angiogenesis and osteoclast differentiation in GCT of bone. Hence, PAR-1 represents a novel potential therapeutic target for GCT of bone. © 2017 UICC.

Discovery of potent peptide-mimetic antagonists for the human thrombin receptor, protease-activated receptor-1 (PAR-1).

PubMed

Maryanoff, Bruce E; Zhang, Han-Cheng; Andrade-Gordon, Patricia; Derian, Claudia K

2003-03-01

Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G-protein-coupled receptors, which are enzymatically cleaved to expose a new extracellular N-terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease alpha-thrombin, is expressed in various tissues (e.g. platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. By using a de novo design approach, we have discovered a series of potent heterocycle-based peptide-miimetic antagonists of PAR-1, exemplified by advanced leads RWJ-56110 (22) and RWJ-58259 (32). These compounds are potent, selective PAR-1 antagonists, devoid of PAR-1 agonist and thrombin inhibitory activity: they bind to PAR-1, interfere with calcium mobilization and cellular functions associated with PAR-1, and do not affect PAR-2, PAR-3, or PAR-4. RWJ-56110 was determined to be a direct inhibitor of PAR-1 activation and internalization, without affecting PAR-1 N-terminal cleavage. At high concentrations of alpha-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, but not in human platelets; whereas, at high concentrations of TRAP-6, RWJ-56110 blocked activation responses in both cell types. This result is consistent with the presence of another thrombin receptor on human platelets, namely PAR-4. RWJ-56110 and RWJ-58259 clearly interrupt the binding of a tethered ligand to its receptor. RWJ-58259 demonstrated antirestenotic activity in a rat balloon angioplasty model and antithrombotic activity in a cynomolgus monkey arterial injury model. Such PAR-1 antagonists should not only serve as useful tools to delineate the physiological and pathophysiological roles of PAR-1, but also may have therapeutic potential for treating thrombosis and restenosis in humans.

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

The 14-3-3 Protein PAR-5 Regulates the Asymmetric localization of the LET-99 Spindle Positioning Protein

PubMed Central

Rose, Lesilee S.

2016-01-01

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in C. elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. PMID:26921457

Observation and estimation of photosynthetically active radiation in Lhasa (Tibetan Plateau)

NASA Astrophysics Data System (ADS)

Peng, Simao; Du, Qingyun; Lin, Aiwen; Hu, Bo; Xiao, Ke; Xi, Yuliang

2015-03-01

In this study, we measured photosynthetically active radiation (PAR) and global solar radiation (G) in Lhasa, located on the Tibetan Plateau, from 2006 to 2012 to examine the PAR and PAR/G (PAR fraction) seasonal characteristics. The maximum and minimum values of both PAR and the PAR fraction occurred in summer and winter, respectively. Moreover, the PAR and PAR fraction annual averages were 38.64 mol m-2 d-1 and 1.84 mol M J-1, respectively. An efficient all-weather model used for estimating PAR under various sky conditions was developed based on the relationships among PAR, the cosine of the solar zenith angle and the clearness index in Lhasa. The model also produced acceptable estimations of PAR with high accuracy at the Donghu and Sanjiang weather stations. A PAR dataset was reconstructed from G using the newly developed model for the period 1961-2012. The modelled annual mean daily PAR was approximately 37.62 mol m-2 d-1. A significant decreasing trend (-0.61 mol m-2 per decade) over the last 50 years was observed on the Tibetan Plateau; this decrease was largest in autumn (-1.024 mol m-2 per decade), and relatively small decreases were observed in summer. The results also revealed that PAR began increasing at 0.164 mol m-2 per year from 1991 to 2012, which was inconsistent with the variations of G. The proposed all-weather PAR model could be useful for ecological modelling and agricultural processes in the Tibetan Plateau region of China.

Loss of Par-1a/MARK3/C-TAK1 Kinase Leads to Reduced Adiposity, Resistance to Hepatic Steatosis, and Defective Gluconeogenesis ▿

PubMed Central

Lennerz, Jochen K.; Hurov, Jonathan B.; White, Lynn S.; Lewandowski, Katherine T.; Prior, Julie L.; Planer, G. James; Gereau, Robert W.; Piwnica-Worms, David; Schmidt, Robert E.; Piwnica-Worms, Helen

2010-01-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a−/− but not in control or Par-1b−/− mice. The intercrossing of Par-1a−/− with Par-1b−/− mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a−/− mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b−/− mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice. PMID:20733003

Radiative transfer in shrub savanna sites in Niger: Preliminary results from HAPEX-Sahel. Part 1: Modelling surface reflectance using a geometric-optical approach

NASA Technical Reports Server (NTRS)

Franklin, Janet; Duncan, Jeff; Huete, Alfredo R.; vanLeeuwen, W. J. D.; Li, Xiaowen; Begue, Agnes

1994-01-01

To use optical remote sensing to monitor land surface-climate interactions over large areas, algorithms must be developed to relate multispectral measurements to key variables controlling the exchange of matter (water, carbon dioxide) and energy between the land surface and the atmosphere. The proportion of the ground covered by vegetation and the interception of photosynthetically active radiation (PAR) by vegetation are examples of two variables related to evapotranspiration and primary production, respectively. An areal-proportion model of the multispectral reflectance of shrub savanna, composed of scattered shrubs with a grass, forb or soil understory, predicted the reflectance of two 0.5 km(exp 2) sites as the area-weighted average of the shrub and understory or 'background' reflectances. Although the shaded crown and shaded background have darker reflectances, ignoring them in the area-weighted model is not serious when shrub cover is low and solar zenith angle is small. A submodel predicted the reflectance of the shrub crown as a function of the foliage reflectance and amount of plant material within the crown, and the background reflectance scattered or transmitted through canopy gaps (referred to as a soil-plant 'spectral interaction' term). One may be able to combine these two models to estimate both the fraction of vegetation cover and interception of PAR by green vegetation in a shrub savanna.

Importance of the green color, absorption gradient, and spectral absorption of chloroplasts for the radiative energy balance of leaves.

PubMed

Kume, Atsushi

2017-05-01

Terrestrial green plants absorb photosynthetically active radiation (PAR; 400-700 nm) but do not absorb photons evenly across the PAR waveband. The spectral absorbance of photosystems and chloroplasts is lowest for green light, which occurs within the highest irradiance waveband of direct solar radiation. We demonstrate a close relationship between this phenomenon and the safe and efficient utilization of direct solar radiation in simple biophysiological models. The effects of spectral absorptance on the photon and irradiance absorption processes are evaluated using the spectra of direct and diffuse solar radiation. The radiation absorption of a leaf arises as a consequence of the absorption of chloroplasts. The photon absorption of chloroplasts is strongly dependent on the distribution of pigment concentrations and their absorbance spectra. While chloroplast movements in response to light are important mechanisms controlling PAR absorption, they are not effective for green light because chloroplasts have the lowest spectral absorptance in the waveband. With the development of palisade tissue, the incident photons per total palisade cell surface area and the absorbed photons per chloroplast decrease. The spectral absorbance of carotenoids is effective in eliminating shortwave PAR (<520 nm), which contains much of the surplus energy that is not used for photosynthesis and is dissipated as heat. The PAR absorptance of a whole leaf shows no substantial difference based on the spectra of direct or diffuse solar radiation. However, most of the near infrared radiation is unabsorbed and heat stress is greatly reduced. The incident solar radiation is too strong to be utilized for photosynthesis under the current CO 2 concentration in the terrestrial environment. Therefore, the photon absorption of a whole leaf is efficiently regulated by photosynthetic pigments with low spectral absorptance in the highest irradiance waveband and through a combination of pigment density distribution and leaf anatomical structures.

Canopy reflectance, photosynthesis, and transpiration. II - The role of biophysics in the linearity of their interdependence

NASA Technical Reports Server (NTRS)

Sellers, P. J.

1987-01-01

The ability of satellite sensor systems to estimate area-averaged canopy photosynthetic and transpirative properties is evaluated. The near linear relationship between the simple ratio (SR) and normalized difference (ND) and the surface biophysical properties of canopy photosynthetically active radiation (PAR) absorption, photosynthesis, and bulk stomatal resistance is studied. The models utilized to illustrate the processes of canopy reflectance, photosynthesis, and resistance are described. The dependence of SR, the absorbed fraction of PAR, and canopy photosynthesis and resistance on total leaf area index is analyzed. It is noted that the SR and ND vegetation indices and vegetation-dependent qualities are near-linearly related due to the proportion of leaf scattering coefficient in visible and near IR wavelength regions. The data reveal that satellite sensor systems are useful for the estimation of photosynthesis and transpirative properties.

Fundamentals of sol-gel dip-coating

NASA Astrophysics Data System (ADS)

Brinker, C. Jeffrey; Hurd, Alan J.

1994-07-01

During the process of dip-coating, the substrate is withdrawn from the sol at a constant rate. After several seconds, the process becomes steady. The entrained film thins by evaporation of solvent and gravitational draining. Because the shape of the depositing film remains constant with respect to the reservoir surface, it is possible to use analytical methods such as ellipsometry and fluorescence spectroscopy to characterize the depositing film in situ. The microstructure and properties of the film depend on the size and structure of the inorganic sol species, the magnitude of the capillary pressure exerted during drying, and the relative rates of condensation and drying. By controlling these parameters, it is possible to vary the porosity of the film over a wide range. Pendant l'opération de " dip-coating ", le substrat est retiré du sol à vitesse constante. La couche s'amincit du fait de l'évaporation du solvant et de l'écoulement gravitationnel. Après plusieurs secondes, le processus atteint un régime stationnaire. Le profil du film déposé reste alors constant par rapport à la surface du sol. On peut le caractériser in situ par des méthodes optiques telles que l'ellipsométrie et la spectroscopie de fluorescence. La texture et les propriétés de la couche dépendent de la taille et de la structure (par exemple de la dimension fractale) des espèces en solution, de l'importance de la tension capillaire pendant le séchage, et des cinétiques de condensation. En contrôlant ces paramètres, on peut faire varier la porosité de la couche dans une large gamme.

Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor: a study based on biosensor technology.

PubMed

List, K; Høyer-Hansen, G; Rønne, E; Danø, K; Behrendt, N

1999-01-01

Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interference with conformational properties of the receptor critical for ligand binding. This distinction is central when employing the antibodies as tools in the elucidation of the structure-function relationship of the protein in question. We have studied the effect of monoclonal antibodies against the urokinase plasminogen activator receptor (uPAR), a protein located on the surface of various types of malignant and normal cells which is involved in the direction of proteolytic degradation reactions in the extracellular matrix. We show that surface plasmon resonance/biomolecular interaction analysis (BIA) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former antibody efficiently blocked the receptor against subsequent ligand binding but was unable to promote the dissociation of a preformed receptor-ligand complex. The latter antibody was capable of binding the preformed complex, forming a transient trimolecular assembly, and promoting the dissociation of the uPA/uPAR complex. The continuous recording of binding and dissociation, obtained in BIA, is central in characterizing these phenomena. The identification of a non-competitive inhibitory mechanism against this receptor reveals the presence of a determinant which influences the binding properties of a remote site in the molecular structure and which could be an important target for a putative synthetic antagonist.

UV/PAR radiation and DOM properties in surface coastal waters of the Canadian shelf of the Beaufort Sea during summer 2009

NASA Astrophysics Data System (ADS)

Para, J.; Charrière, B.; Matsuoka, A.; Miller, W. L.; Rontani, J. F.; Sempéré, R.

2013-04-01

Surface waters from the Beaufort Sea in the Arctic Ocean were evaluated for dissolved organic carbon (DOC), and optical characteristics including UV (ultraviolet) radiation and PAR (photosynthetically active radiation) diffuse attenuation (Kd), and chromophoric and fluorescent dissolved organic matter (CDOM and FDOM) as part of the MALINA field campaign (30 July to 27 August). Spectral absorption coefficients (aCDOM (350 nm) (m-1)) were significantly correlated to both diffuse attenuation coefficients (Kd) in the UV-A and UV-B and to DOC concentrations. This indicates CDOM as the dominant attenuator of both UV and PAR solar radiation and suggests its use as an optical proxy for DOC concentrations in this region. While the Mackenzie input is the main driver of CDOM dynamics in low salinity waters, locally, primary production can create significant increases in CDOM. Extrapolating CDOM to DOC relationships, we estimate that ∼16% of the DOC in the Mackenzie River does not absorb radiation at 350 nm. The discharges of DOC and its chromophoric subset (CDOM) by the Mackenzie River during the MALINA cruise are estimated as ∼0.22 TgC and 0.18 TgC, respectively. Three dissolved fluorescent components (C1-C3) were identified by fluorescence excitation/emission matrix spectroscopy (EEMS) and parallel factor (PARAFAC) analysis. Our results showed an aquatic dissolved organic matter (DOM) component (C1), probably produced in the numerous lakes of the watershed, that co-dominated with a terrestrial humic-like component (C2) in the Mackenzie Delta Sector. This aquatic DOM could partially explain the high CDOM spectral slopes observed in the Beaufort Sea.

Architecture of the ParF*ParG protein complex involved in prokaryotic DNA segregation.

PubMed

Barillà, Daniela; Hayes, Finbarr

2003-07-01

The mechanism by which low copy number plasmids are segregated at cell division involves the concerted action of two plasmid-encoded proteins that assemble on a centromere-like site. This study explores the topology of the DNA segregation machinery specified by the parFG locus of TP228, a partition system which is phylogenetically distinct from more well-characterized archetypes. A variety of genetic, biochemical and biophysical strategies revealed that the ParG protein is dimeric. ParF, which is more closely related to the cell division regulator MinD than to the prototypical ParA partition protein of plasmid P1, is instead multimeric and its polymeric state appears to be modulated by ATP which correlates with the proposed ATP-binding activity of ParF. ParG interacts in a sequence-specific manner with the DNA region upstream of the parFG locus and this binding is modulated by ParF. Intriguingly, the ParF and ParG proteins form at least two types of discrete complex in the absence of this region suggesting that the assembly dynamics of these proteins onto DNA is intricate.

Transport de Particules et Atmospheres D'etoiles Magnetiques

NASA Astrophysics Data System (ADS)

LeBlanc, Francis

1995-01-01

Les phenomenes relies a la diffusion atomique dans les etoiles sont etudies de facon intensive depuis environ un quart de siecle. La diffusion peut a la fois modifier les abondances atomiques presentes ainsi qu'affecter la structure et l'evolution stellaires. Dans cette these, nous allons etudier trois phenomenes physiques relies a la diffusion. Nous avons developpe la theorie de la derive induite par la radiation afin qu'elle soit facilement applicable dans le contexte de l'astrophysique stellaire. Des calcuis detailles furent effectues afin d'evaluer l'importance de cet effet sur la diffusion relative de l'^3 He et l'^4He et montrent que la derive induite par la radiation accelere la separation de ces deux isotopes dans une etoile de temperature effective de 18000 K. Lorsque l'^4He est present, ce phenomene augmente la vitesse de derive de l'^3He qui migre vers l'exterieur ce qui fait apparai tre la surabondance de cet isotope plus tot dans l'evolution. Des calculs sur le lithium a la base de la zone convective d'une etoile avec une temperature effective de 6700 K monuent que la derive induite par la radiation n'est pas importante dans ce cas. Ce phenomene semble aussi etre negligeable pour l'oxygene dans les etoiles de type A ainsi que pour le mercure dans les etoiles de type B. Deuxiemement nous avons construit des modeles d'atmospheres d'etoiles ayant un champ magnetique horizontal et constant en incluant l'interaction entre ce champ et la diffusion ambipolaire de l'hydrogene. Cette interaction cause une compression de la zone d'ionisation de l'hydrogene. Dans un modele de temperature effective de 10,000 K, et avec log g = 4.0 la gravite effective, c'est-a-dire la gravite plus l'acceleration causee par la force de Lorentz, en presence d'un champ magnetique de 5 kG est sept fois plus grande que la gravite. Ce phenomene affecte donc fortement la structure des etoiles Ap. Cette modification de la structure des etoiles magnetiques cause un plus grand elargissement des raies de Balmer de l'hydrogene. Puisque le champ magnetique observe n'est pas uniforme a la surface des etoiles Ap, la modification de la structure causee par l'interaction entre la diffusion ambipolaire de l'hydrogene et le champ magnetique engendre une variation de l'elargissement des raies de Balmer durant une periode de rotation. La variation causee par ce phenomene est inferieure aux variations observees. D'autres facteurs tels que des gradients horizontaux et verticaux de la metallicite et de la configuration du champ magnetique peuvent aussi influencer la variation des raies de Balmer. Des ameliorations majeures furent apportees au calcul des accelerations radiatives. Grace a des bases de donnees plus completes, il est maintenant possible de calculer l'acceleration causee par la photoionisation. De plus nous avons calcule de maniere approximative l'opacite monochromatique totale qui est un ingredient essentiel au calcul de l'acceleration radiative. Des ameliorations concernant l'elargissement des raies et la distribution de l'acceleration entre les divers ions d'un element furent aussi incluses. Des calculs detailles de l'acceleration radiative sur le fer montrent qu'une abondance consistente avec les observations peut etre supportee dans les etoiles de type A et F. L'abondance de fer supportee depend de la temperature effective et de la gravite de surface de l'etoile. Les accelerations radiatives ont ete tabulees afin d'etre facilement utilisables dans des codes d'evolution stellaire.

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia.

PubMed

Gu, Y; Groome, L J; Alexander, J S; Wang, Y

2012-10-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial-specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protease Activated Receptor-2 Mediates Activated Protein C–Induced Cutaneous Wound Healing via Inhibition of p38

PubMed Central

Julovi, Sohel M.; Xue, Meilang; Dervish, Suat; Sambrook, Philip N.; March, Lyn; Jackson, Christopher John

2011-01-01

Activated protein C (APC) is a natural anticoagulant that exerts anti-inflammatory and cytoprotective properties mediated through the protease activated receptor (PAR)-1. APC can also proteolytically cleave PAR-2, although subsequent function is unknown. On the basis of recent evidence that APC promotes wound healing, the aim of this study was to determine whether APC acts through PARs to heal murine excisional wounds or to regulate human cultured keratinocyte function and to determine the signaling mechanisms. Topical administration of APC accelerated wound healing in wild-type mice and, unexpectedly, in PAR-1 knockout mice. PAR-2 knockout mice healed significantly slower than wild-type mice, and healing was not altered by adding APC, indicating that APC acts through PAR-2 to heal wounds. In cultured human primary keratinocytes, APC enhanced PAR-2, stimulated proliferation, activated phosphatidylinositol 3-kinase/Src/Akt, and inhibited phosphorylated (P)-p38. Inhibiting PAR-1 or PAR-2, by small-interfering RNA or blocking antibody, reversed APC-induced keratinocyte proliferation and Akt activation. Blocking PAR-2, but not PAR-1, reversed the inhibition of P-p38 by APC. Furthermore, inhibition of P-p38 accelerated wound healing in wild-type mice. In summary, although APC acts through both PAR-1 and PAR-2 to activate Akt and to increase keratinocyte proliferation, APC-induced murine wound healing depends on PAR-2 activity and inhibition of P-p38. PMID:21907694

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia

PubMed Central

Gu, Yang; Groome, Lynn J.; Alexander, J. Steven; Wang, Yuping

2014-01-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP-induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. PMID:22840244

Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones

PubMed Central

Yamada, M; Yoshida, J; Hatou, S; Yoshida, T; Minagawa, Y

2008-01-01

Background: Staphylococcus epidermidis is one of the prominent pathogens in ocular infection. The prevalence of mutations in the quinolone resistance determining region (QRDR) area in S epidermidis isolated from the ocular surface and its association with fluoroquinolone resistance has not been fully elucidated. Methods: Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods. Results: The MIC90 values of levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin were 3.13, 1.56, 0.78 and 3.13 μg/ml, respectively. The MIC values of all fluoroquinolones showed a bimodal distribution (susceptible strain and less susceptible strain). Mutations with amino acid substitution in the QRDR were present in 70 (50.7%) isolates. 19 different combinations of mutations were detected: 3 isolates (2.2%) had four mutations, 8 (5.8%) had three mutations, 43 (31.2%) had double mutations and 16 (11.6%) had single mutations. Isolates with mutations in the QRDR of both gyrA and parC (n = 53) were less susceptible to fluoroquinolones. Conclusions: The present findings show that approximately half the S epidermidis isolates from the normal human conjunctiva have mutation(s) in the QRDR. The presence of mutations in both gyrA and parC is strongly associated with reduced susceptibility to fluoroquinolones. PMID:18460536

An ELISA method detecting the active form of suPAR.

PubMed

Zhou, Xiaolei; Xu, Mingming; Huang, Hailong; Mazar, Andrew; Iqbal, Zafar; Yuan, Cai; Huang, Mingdong

2016-11-01

Urokinase plasminogen activator receptor (uPAR) exists in a number of formats in human plasma, including soluble uPAR (suPAR) and uPAR fragments. We developed an ELISA method to detect specifically the active form suPAR, which binds to its natural ligand uPA. The intra CV and inter CV of this ELISA assay is 8.5% and 9.6% respectively, and the assay can recover 99.74% of added recombinant suPAR from 10% plasma. This assay is quite sensitive, capable of detecting down to 15pg/ml of suPAR, and can measure suPAR concentrations in the range of 0.031-8ng/ml with high linear relationship. Plasma samples from pregnant women were also measured for the active form of suPAR with this assay, giving an averaged level of 1.39ng/ml, slightly higher than the level of pooled plasma from healthy donors (0.96ng/ml). This study demonstrates the feasibility to measure the active form of suPAR, which will likely have value in clinical applications. Copyright © 2016. Published by Elsevier B.V.

Author Correction: Spiraling pathways of global deep waters to the surface of the Southern Ocean.

PubMed

Tamsitt, Veronica; Drake, Henri F; Morrison, Adele K; Talley, Lynne D; Dufour, Carolina O; Gray, Alison R; Griffies, Stephen M; Mazloff, Matthew R; Sarmiento, Jorge L; Wang, Jinbo; Weijer, Wilbert

2018-01-15

The original version of this Article contained errors in Fig. 6. In panel a, the grey highlights obscured the curves for CESM, CM2.6 and SOSE, and the labels indicating SWIR, KP, MR, PAR, and DP were inadvertently omitted. These have now been corrected in both the PDF and HTML versions of the Article.

Illustrating harvest effects on site microclimate in a high-elevation forest stand.

Treesearch

W.B. Fowler; T.D. Anderson

1987-01-01

Three-dimensional contour surfaces were drawn for physiologically active radiation (PAR) and air and soil temperatures from measurements taken at a high-elevation site (1450 m) near the crest of the Cascade Range in central Washington. Measurements in a clearcut were compared with measurements from an adjacent uncut stand. Data for 31 days in July and August 1985...

Urokinase Receptor Counteracts Vascular Smooth Muscle Cell Functional Changes Induced by Surface Topography

PubMed Central

Kiyan, Yulia; Kurselis, Kestutis; Kiyan, Roman; Haller, Hermann; Chichkov, Boris N.; Dumler, Inna

2013-01-01

Current treatments for human coronary artery disease necessitate the development of the next generations of vascular bioimplants. Recent reports provide evidence that controlling cell orientation and morphology through topographical patterning might be beneficial for bioimplants and tissue engineering scaffolds. However, a concise understanding of cellular events underlying cell-biomaterial interaction remains missing. In this study, applying methods of laser material processing, we aimed to obtain useful markers to guide in the choice of better vascular biomaterials. Our data show that topographically treated human primary vascular smooth muscle cells (VSMC) have a distinct differentiation profile. In particular, cultivation of VSMC on the microgrooved biocompatible polymer E-shell induces VSMC modulation from synthetic to contractile phenotype and directs formation and maintaining of cell-cell communication and adhesion structures. We show that the urokinase receptor (uPAR) interferes with VSMC behavior on microstructured surfaces and serves as a critical regulator of VSMC functional fate. Our findings suggest that microtopography of the E-shell polymer could be important in determining VSMC phenotype and cytoskeleton organization. They further suggest uPAR as a useful target in the development of predictive models for clinical VSMC phenotyping on functional advanced biomaterials. PMID:23843899

The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.

PubMed

Wu, Jui-Ching; Espiritu, Eugenel B; Rose, Lesilee S

2016-04-15

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in Caenorhabditis elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. Copyright © 2016 Elsevier Inc. All rights reserved.

Tissue Factor-Factor VIIa Complex Triggers Protease Activated Receptor 2-Dependent Growth Factor Release and Migration in Ovarian Cancer

PubMed Central

Chanakira, Alice; Westmark, Pamela R.; Ong, Irene M.; Sheehan, John P.

2017-01-01

Objective Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. Methods TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expression were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists. Results Relative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4–10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present. Conclusions Enhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation. PMID:28148395

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

PubMed Central

Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van ‘t Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

2016-01-01

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. PMID:26698846

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

PubMed Central

Beatty, Alexander; Morton, Diane G.; Kemphues, Kenneth

2013-01-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6. PMID:23536568

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

Protease‐activated receptor 4: from structure to function and back again

PubMed Central

French, Shauna L

2016-01-01

Protease‐activated receptors are a family of four GPCRs (PAR1–PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first‐in‐class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein‐Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc PMID:26844674

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

PubMed

Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

2013-05-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

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

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

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 bindingmore » 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.« less

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

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

Boosen, Meike; Vetterkind, Susanne; Koplin, Ansgar

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 andmore » 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.« less

Brownian Ratchet Mechanism for Faithful Segregation of Low-Copy-Number Plasmids.

PubMed

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

2017-04-11

Bacterial plasmids are extrachromosomal DNA that provides selective advantages for bacterial survival. Plasmid partitioning can be remarkably robust. For high-copy-number plasmids, diffusion ensures that both daughter cells inherit plasmids after cell division. In contrast, most low-copy-number plasmids need to be actively partitioned by a conserved tripartite ParA-type system. ParA is an ATPase that binds to chromosomal DNA; ParB is the stimulator of the ParA ATPase and specifically binds to the plasmid at a centromere-like site, parS. ParB stimulation of the ParA ATPase releases ParA from the bacterial chromosome, after which it takes a long time to reset its DNA-binding affinity. We previously demonstrated in vitro that the ParA system can exploit this biochemical asymmetry for directed cargo transport. Multiple ParA-ParB bonds can bridge a parS-coated cargo to a DNA carpet, and they can work collectively as a Brownian ratchet that directs persistent cargo movement with a ParA-depletion zone trailing behind. By extending this model, we suggest that a similar Brownian ratchet mechanism recapitulates the full range of actively segregated plasmid motilities observed in vivo. We demonstrate that plasmid motility is tuned as the replenishment rate of the ParA-depletion zone progressively increases relative to the cargo speed, evolving from diffusion to pole-to-pole oscillation, local excursions, and, finally, immobility. When the plasmid replicates, the daughters largely display motilities similar to that of their mother, except that when the single-focus progenitor is locally excursive, the daughter foci undergo directed segregation. We show that directed segregation maximizes the fidelity of plasmid partition. Given that local excursion and directed segregation are the most commonly observed modes of plasmid motility in vivo, we suggest that the operation of the ParA-type partition system has been shaped by evolution for high fidelity of plasmid segregation. Published by Elsevier Inc.

The role of pars flaccida in human middle ear sound transmission.

PubMed

Aritomo, H; Goode, R L; Gonzalez, J

1988-04-01

The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.

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.

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

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PubMed

Jones, Shannon M; Mann, Adrien; Conrad, Kelsey; Saum, Keith; Hall, David E; McKinney, Lisa M; Robbins, Nathan; Thompson, Joel; Peairs, Abigail D; Camerer, Eric; Rayner, Katey J; Tranter, Michael; Mackman, Nigel; Owens, A Phillip

2018-06-01

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. © 2018 American Heart Association, Inc.

Resistance to Plum Pox Virus (PPV) in apricot (Prunus armeniaca L.) is associated with down-regulation of two MATHd genes.

PubMed

Zuriaga, Elena; Romero, Carlos; Blanca, Jose Miguel; Badenes, Maria Luisa

2018-01-27

Plum pox virus (PPV), causing Sharka disease, is one of the main limiting factors for Prunus production worldwide. In apricot (Prunus armeniaca L.) the major PPV resistance locus (PPVres), comprising ~ 196 kb, has been mapped to the upper part of linkage group 1. Within the PPVres, 68 genomic variants linked in coupling to PPV resistance were identified within 23 predicted transcripts according to peach genome annotation. Taking into account the predicted functions inferred from sequence homology, some members of a cluster of meprin and TRAF-C homology domain (MATHd)-containing genes were pointed as PPV resistance candidate genes. Here, we have characterized the global apricot transcriptome response to PPV-D infection identifying six PPVres locus genes (ParP-1 to ParP-6) differentially expressed in resistant/susceptible cultivars. Two of them (ParP-3 and ParP-4), that encode MATHd proteins, appear clearly down-regulated in resistant cultivars, as confirmed by qRT-PCR. Concurrently, variant calling was performed using whole-genome sequencing data of 24 apricot cultivars (10 PPV-resistant and 14 PPV-susceptible) and 2 wild relatives (PPV-susceptible). ParP-3 and ParP-4, named as Prunus armeniaca PPVres MATHd-containing genes (ParPMC), are the only 2 genes having allelic variants linked in coupling to PPV resistance. ParPMC1 has 1 nsSNP, while ParPMC2 has 15 variants, including a 5-bp deletion within the second exon that produces a frameshift mutation. ParPMC1 and ParPMC2 are adjacent and highly homologous (87.5% identity) suggesting they are paralogs originated from a tandem duplication. Cultivars carrying the ParPMC2 resistant (mutated) allele show lack of expression in both ParPMC2 and especially ParPMC1. Accordingly, we hypothesize that ParPMC2 is a pseudogene that mediates down-regulation of its functional paralog ParPMC1 by silencing. As a whole, results strongly support ParPMC1 and/or ParPMC2 as host susceptibility genes required for PPV infection which silencing may confer PPV resistance trait. This finding may facilitate resistance breeding by marker-assisted selection and pave the way for gene edition approaches in Prunus.

Leaf Area Influence on Surface Layer in a Deciduous Forest. Part 2; Detecting Leaf Area and Surface Resistance During Transition Seasons

NASA Technical Reports Server (NTRS)

Sakai, Ricardo K.; Fitzjarrald, David R.; Moore, Kathleen E.; Sicker, John W.; Munger, Willian J.; Goulden, Michael L.; Wofsy, Steven C.

1996-01-01

Temperate deciduous forest exhibit dramatic seasonal changes in surface exchange properties following on the seasonal changes in leaf area index. The canopy resistance to water vapor transport r(sub c) decreased abruptly at leaf emergence in each year but then also continued to decrease slowly during the remaining growing season due to slowly increasing LAI. Canopy resistance and PAR-albedo (albedo from photosynthetically active radiation) began to increase about one month before leaf fall with the diminishment of CO2 gradient above the canopy as well. At this time evaporation begun to be controlled as if the canopy were leafless.

Protease Activated Receptor-2 Expression and Function in Asthmatic Bronchial Smooth Muscle

PubMed Central

Gilbert, Guillaume; Carvalho, Gabrielle; Trian, Thomas; Ozier, Annaig; Gillibert-Duplantier, Jennifer; Ousova, Olga; Maurat, Elise; Thumerel, Matthieu; Quignard, Jean-François; Girodet, Pierre-Olivier; Marthan, Roger; Berger, Patrick

2014-01-01

Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation. BSM cells were obtained from both 33 control subjects and 22 asthmatic patients. PAR-2 expression was assessed by flow cytometry, western blot and quantitative RT-PCR. Calcium response, transduction pathways and proliferation were evaluated before and following PAR-2 stimulation by SLIGKV-NH2 or trypsin for 1 to 3 days. Asthmatic BSM cells expressed higher basal levels of functional PAR-2 compared to controls in terms of mRNA, protein expression and calcium response. When PAR-2 expression was increased by means of lentivirus in control BSM cells to a level similar to that of asthmatic cells, PAR-2-induced calcium response was then similar in both types of cell. However, repeated PAR-2 stimulations increased the proliferation of asthmatic BSM cells but not that of control BSM cells even following lentiviral over-expression of PAR-2. Such an increased proliferation was related to an increased phosphorylation of ERK in asthmatic BSM cells. In conclusion, we have demonstrated that asthmatic BSM cells express increased baseline levels of functional PAR-2. This higher basal level of PAR-2 accounts for the increased calcium response to PAR-2 stimulation, whereas the increased proliferation to repeated PAR-2 stimulation is related to increased ERK phosphorylation. PMID:24551046

Increased Expression of Cathelicidin by Direct Activation of Protease-Activated Receptor 2: Possible Implications on the Pathogenesis of Rosacea

PubMed Central

Kim, Ji Young; Kim, Yoon Jee; Lim, Beom Jin; Sohn, Hyo Jung; Shin, Dongyun

2014-01-01

Purpose Recent findings of increased cathelicidin protein and its proteolytic fragments in rosacea suggest a pathogenic role for cathelicidin in this disease. The relationship between cathelicidin and protease-activated receptor 2 (PAR-2) is therefore of interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosacea and to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. Materials and Methods Samples from 40 patients with clinicopathologic diagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensities of immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations between PAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelial growth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). Results Cathelicidin expression was significantly higher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in cultured keratinocytes, compared with PAR-2 control peptide treatment. Conclusion PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidin LL-37, a mediator of innate immune responses in the skin. PMID:25323904

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.

In vitro and in vivo inhibition of proangiogenic retinal phenotype by an antisense oligonucleotide downregulating uPAR expression.

PubMed

Lulli, Matteo; Cammalleri, Maurizio; Granucci, Irene; Witort, Ewa; Bono, Silvia; Di Gesualdo, Federico; Lupia, Antonella; Loffredo, Rosa; Casini, Giovanni; Dal Monte, Massimo; Capaccioli, Sergio

2017-08-26

Neoangiogenesis is the main pathogenic event involved in a variety of retinal diseases. It has been recently demonstrated that inhibiting the urokinase-type plasminogen activator receptor (uPAR) results in reduced angiogenesis in a mouse model of oxygen-induced retinopathy (OIR), establishing uPAR as a therapeutic target in proliferative retinopathies. Here, we evaluated in cultured human retinal endothelial cells (HRECs) and in OIR mice the potential of a specific antisense oligodeoxyribonucleotide (ASO) in blocking the synthesis of uPAR and in providing antiangiogenic effects. uPAR expression in HRECs was inhibited by lipofection with the phosphorotioated 5'-CGGCGGGTGACCCATGTG-3' ASO-uPAR, complementary to the initial translation site of uPAR mRNA. Inhibition of uPAR expression via ASO-uPAR was evaluated in HRECs by analyzing VEGF-induced tube formation and migration. In addition, the well-established and reproducible murine OIR model was used to induce retinal neovascularization in vivo. OIR mice were injected intraperitoneally with ASO-uPAR and retinopathy was evaluated considering the extent of the avascular area in the central retina and neovascular tuft formation. The ASO-uPAR specifically decreased uPAR mRNA and protein levels in HRECs and mitigated VEGF-induced tube formation and cell migration. Noteworthy, in OIR mice ASO-uPAR administration reduced both the avascular area and the formation of neovascular tufts. In conclusion, although the extrapolation of these experimental findings to the clinic is not straightforward, ASO-uPAR may be considered a potential therapeutic tool for treatment of proliferative retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins

PubMed Central

Ringgaard, Simon; Schirner, Kathrin; Davis, Brigid M.; Waldor, Matthew K.

2011-01-01

Stochastic processes are thought to mediate localization of membrane-associated chemotaxis signaling clusters in peritrichous bacteria. Here, we identified a new family of ParA-like ATPases (designated ParC [for partitioning chemotaxis]) encoded within chemotaxis operons of many polar-flagellated γ-proteobacteria that actively promote polar localization of chemotaxis proteins. In Vibrio cholerae, a single ParC focus is found at the flagellated old pole in newborn cells, and later bipolar ParC foci develop as the cell matures. The cell cycle-dependent redistribution of ParC occurs by its release from the old pole and subsequent relocalization at the new pole, consistent with a “diffusion and capture” model for ParC dynamics. Chemotaxis proteins encoded in the same cluster as ParC have a similar unipolar-to-bipolar transition; however, they reach the new pole after the arrival of ParC. Cells lacking ParC exhibit aberrantly localized foci of chemotaxis proteins, reduced chemotaxis, and altered motility, which likely accounts for their enhanced colonization of the proximal small intestine in an animal model of cholera. Collectively, our findings indicate that ParC promotes the efficiency of chemotactic signaling processes. In particular, ParC-facilitated development of a functional chemotaxis apparatus at the new pole readies this site for its development into a functional old pole after cell division. PMID:21764856

Proteinase activated-receptors-associated signaling in the control of gastric cancer

PubMed Central

Sedda, Silvia; Marafini, Irene; Caruso, Roberta; Pallone, Francesco; Monteleone, Giovanni

2014-01-01

Gastric cancer (GC) is the fourth most common cancer in the world and the second cause of cancer-related death. Gastric carcinogenesis is a multifactorial process, in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC cells. One such a pathway is regulated by proteinase activated-receptors (PARs), seven transmembrane-spanning domain G protein-coupled receptors, which comprise four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4) activated by various proteases. Both PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways, which sustain gastric carcinogenesis. There is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of patients. Consistently, data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC patients. In contrast, PAR-4 levels are down-regulated in GC and correlate inversely with the aggressiveness of GC, thus suggesting a negative role of this receptor in the control of GC. In this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior. PMID:25232234

PAR-2 mediates increased inflammatory cell adhesion and neointima formation following vascular injury in the mouse.

PubMed

Tennant, Gail M; Wadsworth, Roger M; Kennedy, Simon

2008-05-01

Activation of PAR-2 in the vasculature affects vascular tone and adhesion of leukocytes to the endothelium. Since adhesion of leukocytes is increased following vascular injury and is important in determining the extent of neointima formation, we hypothesised that mice lacking PAR-2 may have reduced neointima formation following vascular injury. PAR-2 activating peptides and trypsin induced endothelium-dependent relaxation of mouse carotid artery which was absent in the knockout mouse. Lack of a PAR-2 receptor did not affect lymphocyte adhesion under basal conditions, but reduced the contractile response produced by lymphocytes. Twenty-eight days after denuding injury, vessel contraction to lymphocytes was reduced in both strains while lymphocyte adhesion was significantly greater in PAR-2(+/+) mice compared to the PAR-2 knockout mice. Neointimal area was markedly reduced in the PAR-2 knockout mouse. Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation.

The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells.

PubMed

Ingangi, Vincenzo; Bifulco, Katia; Yousif, Ali Munaim; Ragone, Concetta; Motti, Maria Letizia; Rea, Domenica; Minopoli, Michele; Botti, Giovanni; Scognamiglio, Giuseppe; Fazioli, Flavio; Gallo, Michele; De Chiara, Annarosaria; Arra, Claudio; Grieco, Paolo; Carriero, Maria Vincenza

2016-08-23

The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88-92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream.

The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells

PubMed Central

Ingangi, Vincenzo; Bifulco, Katia; Yousif, Ali Munaim; Ragone, Concetta; Motti, Maria Letizia; Rea, Domenica; Minopoli, Michele; Botti, Giovanni; Scognamiglio, Giuseppe; Fazioli, Flavio; Gallo, Michele; De Chiara, Annarosaria; Arra, Claudio; Grieco, Paolo; Carriero, Maria Vincenza

2016-01-01

The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88–92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR88–92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro, the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream. PMID:27323409

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

PubMed Central

Beaulieu, Lea M.; Church, Frank C.

2014-01-01

Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1–50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified “checkerboard” analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1. PMID:17254565

[Not Available].

PubMed

Belmir, R; Fejjal, N; El Omari, M; El Mazouz, S; Gharib, N; Abassi, A; Belmahi, A

2008-09-30

Les accidents électriques par haute tension (AEHT) provoquent des brûlures profondes par effet Joule le long des axes vasculo-nerveux entre les points d'entrée et de sortie, qui sont le siège de lésions délabrantes. Les Auteurs rapportent une série de dix cas d'AEHT admis au service de chirurgie réparatrice et de brûlés de l'Hôpital Ibn Sina de Rabat à travers laquelle ils étudient les caractéristiques épidémiologiques, cliniques et thérapeutiques. Tous les patients étaient des adultes de sexe masculin dont l'âge moyen était de 31 ans. Dans 70% des cas, ces brûlures étaient secondaires à un contact avec les distributeurs d'électricité avec une surface brûlée inférieure à 20%. Le traitement des lésions électrothermiques a nécessité des interventions itératives avec amputation des segments de membres nécrosés dans 70% des cas, dont les suites étaient marquées par des séquelles fonctionnelles invalidantes. La prévention des AEHT, en particulier pour les accidents du travail au sein des professions exposées, reste fondamentale.

Heat shock proteins HSP70 and MRJ cooperatively regulate cell adhesion and migration through urokinase receptor.

PubMed

Lin, Yuli; Peng, Nana; Zhuang, Hongqin; Zhang, Di; Wang, Yao; Hua, Zi-Chun

2014-08-30

The urokinase-type plasminogen activator receptor (uPAR) is an important regulator of ECM proteolysis, cell-ECM interactions and cell signaling. uPAR and heat shock proteins HSP70 and MRJ (DNAJB6) have been implicated in tumor growth and metastasis. We have reported recently that MRJ (DNAJB6, a heat shock protein) can interact with uPAR and enhance cell adhesion. Here, we identified another heat shock protein HSP70 as a novel uPAR-interacting protein. We performed co-immunoprecipitation in human embryonic kidney (HEK) 293 and colon cancer HCT116 cells as well as immunofluorence assays in HEK293 cells stably transfected with uPAR to investigate the association of suPAR with HSP70/MRJ. To understand the biological functions of the triple complex of suPAR/HSP70/MRJ, we determined whether HSP70 and/or MRJ regulated uPAR-mediated cell invasion, migration, adhesion to vitronectin and MAPK pathway in two pair of human tumor cells (uPAR negative HEK293 cells vs HEK293 cells stably transfected with uPAR and HCT116 cells stably transfected with antisense-uPAR vs HCT116 mock cells transfected with vector only) using transwell assay, wound healing assay, quantitative RT-PCR analyzing mmp2 and mmp9 transcription levels, cell adhesion assay and Western blotting assay. HSP70 and MRJ formed a triple complex with uPAR and over-expression of MRJ enhanced the interaction between HSP70 and uPAR, while knockdown of MRJ decreased soluble uPAR in HCT116 cells (P < 0.05) and reduced the formation of the triple complex, suggesting that MRJ may act as an uPAR-specific adaptor protein to link uPAR to HSP70. Further experiments showed that knockdown of HSP70 and/or MRJ by siRNA inhibited uPAR-mediated cell adhesion to vitronectin as well as suppressed cell invasion and migration. Knockdown of HSP70 and/or MRJ inhibited expression of invasion related genes mmp2 and mmp9. Finally, HSP70 and/or MRJ up-regulated phosphorylation levels of ERK1/2 and FAK suggesting MAPK pathway was involved. All the biological function experiments in cell level showed an additive effect when HSP70 and MRJ were regulated simultaneously indicating their collaborated regulation effects on uPAR. These findings may offer a novel insight into the interactions between uPAR and HSP70/MRJ and their functions in cell adhesion and migration may provide more understanding of the roles in regulating cancer metastasis.

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology.

PubMed

Huesa, Carmen; Ortiz, Ana C; Dunning, Lynette; McGavin, Laura; Bennett, Louise; McIntosh, Kathryn; Crilly, Anne; Kurowska-Stolarska, Mariola; Plevin, Robin; van 't Hof, Rob J; Rowan, Andrew D; McInnes, Iain B; Goodyear, Carl S; Lockhart, John C; Ferrell, William R

2016-11-01

Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. OA was induced in wild-type (WT) and PAR2-deficient (PAR2 -/- ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 -/- mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 -/- mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 -/- mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 -/- mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

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

Li, Taiyuan; Liu, Dongning; Lei, Xiong

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinasemore » B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.« less

Évolution de la surface de plasticité sous chargement biaxial dans un acier inoxydable duplex

NASA Astrophysics Data System (ADS)

Aubin, V.; Quaegebeur, P.; Degallaix, S.

2002-12-01

Nous proposons une méthodologie de mesure automatique de la surface de plasticité pendant des chargements cycliques biaxiaux. La surface de plasticité est mesurée de manière discrète avec un faible offset de déformation plastique (2 10^{-5}) et des paramètres de mesure optimisés. La méthode est appliquée à un acier inoxydable duplex soumis à un trajet de chargement non-proportionnel. Les résultats montrent une distorsion et une translation de la surface de plasticité sans changement de taille. La méthode présentée permet également de vérifier la normalité de la vitesse d'écoulement plastique par rapport à la surface de plasticité.

Gallium(III)/4-(2-pyridylazo)resorcinol system in water and SDS solution: kinetics and thermodynamics.

PubMed

Biver, T; Boggioni, A; Secco, F; Venturini, M

2008-01-01

The equilibria and kinetics of the complex formation and dissociation reaction between gallium(III) and PAR [4-(2-pyridylazo)resorcinol] have been investigated in water and in the presence of SDS micelles. The reactive form of Ga(III) is GaOH2+ in both cases. The addition of SDS results in an increase of both the binding affinity and velocity, the maximum accelerating effect being observed just above the cmc value of SDS that, under the conditions of the experiments, is 5.6 x 10-3 M. At pH = 3.2, the maximum value of the equilibrium constant ratio Kapp(SDS)/Kapp(H2O) is 27.4, whereas that of the binding rate constants kf(SDS)/kf(H2O) is 16. The results are interpreted in terms of increased concentrations of the reactants on the micelle surface and on competition of PAR and SDS for GaOH2+.

TMPRSS2, a novel membrane-anchored mediator in cancer pain

PubMed Central

Lam, David K.; Dang, Dongmin; Flynn, Andrea N.; Hardt, Markus; Schmidt, Brian L.

2016-01-01

More than half of all cancer patients will suffer significant pain during the course of their disease. The strategic localization of TMPRSS2, a membrane-bound serine protease, on the cancer cell surface may allow it to mediate signal transduction between the cancer cell and its extracellular environment. Here we show TMPRSS2 expression is not only dramatically increased in the primary cancers of patients but TMPRSS2-immunopositivity is also directly correlated with cancer pain severity in these patients. TMPRSS2 induced proteolytic activity, activated trigeminal neurons, and produced marked mechanical hyperalgesia when administered into the hindpaw of wild-type mice but not in PAR2-deficient mice. Co-culture of human cancer cells with murine trigeminal neurons demonstrated co-localization of TMPRSS2 with PAR2. These results point to a novel role for a cell membrane-anchored mediator in cancer pain, as well as pain in general. PMID:25734995

A niche for cyanobacteria producing chlorophyll f within a microbial mat.

PubMed

Ohkubo, Satoshi; Miyashita, Hideaki

2017-10-01

Acquisition of additional photosynthetic pigments enables photosynthetic organisms to survive in particular niches. To reveal the ecological significance of chlorophyll (Chl) f, we investigated the distribution of Chl and cyanobacteria within two microbial mats. In a 7-mm-thick microbial mat beneath the running water of the Nakabusa hot spring, Japan, Chl f was only distributed 4.0-6.5 mm below the surface, where the intensity of far-red light (FR) was higher than that of photosynthetically active radiation (PAR). In the same mat, two ecotypes of Synechococcus and two ecotypes of Chl f-producing Leptolyngbya were detected in the upper and deeper layers, respectively. Only the Leptolyngbya strains could grow when FR was the sole light source. These results suggest that the deeper layer of the microbial mat was a habitat for Chl f-producing cyanobacteria, and Chl f enabled them to survive in a habitat with little PAR.

Quality index of the surface water of Amazonian rivers in industrial areas in Pará, Brazil.

PubMed

Medeiros, Adaelson Campelo; Faial, Kleber Raimundo Freitas; do Carmo Freitas Faial, Kelson; da Silva Lopes, Iris Danielly; de Oliveira Lima, Marcelo; Guimarães, Raphael Mendonça; Mendonça, Neyson Martins

2017-10-15

In this study was to evaluate the waters quality of the Murucupi River, located in urban agglomerate area and intense industrial activity in Barcarena City, Pará State. The Arapiranga River in Abaetetuba City was used as control area (Background), next to Barcarena. Was used the Water Quality Index (WQI) based on nine variables analized. Waters quality of the Arapiranga and Murucupi rivers were regular to good and bad to good, respectively. Anthropogenic influence on the Murucupi River was higher, mainly by the disposal of domestic effluents from the urban agglomerate and of the industrial waste tailing basins upstream of this river. Due to its less inhabited environment and further away from the area urban and industrial, the Arapiranga River was more preserved. Waters pollution of around these area is increasingly intense, and restricted its uses for various purposes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keeping Naval Guns Ready

DTIC Science & Technology

2016-03-01

Keeping Naval Guns Ready David L. Rogers Rogers is the Deputy Department Head, Systems Integration Department, Naval Surface Warfare Center Indian...maritime routes and the global economy. This protection depends on keeping these forward naval ships ready, par- ticularly their guns and ammunition...the weapons of choice for counter- ing a multitude of threats. That gun readiness is assured with responsive technical support. It is done fast, and

A Software Toolbox for Systematic Evaluation of Seismometer-Digitizer System Responses

DTIC Science & Technology

2011-09-01

characteristics (e.g., borehole vs. surface installation) instead of the actual seismic noise characteristics. Their results suggest that our best...Administration Award No. DE-FG02-09ER85548 ABSTRACT Measurement of the absolute amplitudes of a seismic signal requires accurate knowledge of...estimates seismic noise power spectral densities, and NOISETRAN, which generates a pseudo-amplitude response (PAR) for a seismic station, based on

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

PubMed

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

2017-04-07

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. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF.

PubMed

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

2005-04-06

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.

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

Evidence that compatibility of closely related replicons in Clostridium perfringens depends on linkage to parMRC-like partitioning systems of different subfamilies.

PubMed

Watts, Thomas D; Johanesen, Priscilla A; Lyras, Dena; Rood, Julian I; Adams, Vicki

2017-05-01

Clostridium perfringens produces an extensive repertoire of toxins and extracellular enzymes, many of which are intimately involved in the progression of disease and are encoded by genes on conjugative plasmids. In addition, many C. perfringens strains can carry up to five of these conjugative toxin or antimicrobial resistance plasmids, each of which has a similar 35kb backbone. This conserved backbone includes the tcp conjugation locus and the central control region (CCR), which encodes genes involved in plasmid regulation, replication and partitioning, including a parMRC partitioning locus. Most conjugative plasmids in C. perfringens have a conserved replication protein, raising questions as to how multiple, closely related plasmids are maintained within a single strain. Bioinformatics analysis has highlighted the presence of at least 10 different parMRC partitioning system families (parMRC A-J ) in these plasmids, with differences in amino acid sequence identity between each ParM family ranging from 15% to 54%. No two plasmids that encode genes belonging to the same partitioning family have been observed in a single strain, suggesting that these families represent the basis for plasmid incompatibility. In an attempt to validate the proposed parMRC incompatibility groups, genetically marked C. perfringens plasmids encoding identical parMRC C or parMRC D homologues or different combinations of parMRC A , parMRC C and parMRC D family homologues were introduced into a single strain via conjugation. The stability of each plasmid was determined using an incompatibility assay in which the plasmid profile of each strain was monitored over the course of two days in the absence of direct selection. The results showed that plasmids with identical parMRC C or parMRC D homologues were incompatible and could not coexist in the absence of external selection. By contrast, plasmids that encoded different parMRC homologues were compatible and could coexist in the same cell in the absence of selection, with the exception of strains housing parMRC C and parMRC D combinations, which showed a minor incompatibility phenotype. In conclusion, we have provided the first direct evidence of plasmid incompatibility in Clostridium spp. and have shown experimentally that the compatibility of conjugative C. perfringens plasmids correlates with the presence of parMRC-like partitioning systems of different phylogenetic subfamilies. Copyright © 2017 Elsevier Inc. All rights reserved.

An Implementation in Pascal: Translation of Prolog into Pascal.

DTIC Science & Technology

1985-06-01

for i:=1 to px do begin ifr (proc .i..relativity=O) then continue; if proc .. ) .ptype=6) hen continue;if (proc (...abegin<>O) then continue; passname...forj:=reitorn do if (j0) then continue; if (par (.>) ppe <>1) then continue; if (par .. .namie<>par(.i.).name) parle nO ype:par C.’ ntype; par Inblnd

ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype.

PubMed Central

Muñoz, R; De La Campa, A G

1996-01-01

The genes encoding the ParC and ParE subunits of topoisomerase IV of Streptococcus pneumoniae, together with the region encoding amino acids 46 to 172 (residue numbers are as in Escherichia coli) of the pneumococcal GyrA subunit, were partially characterized. The gyrA gene maps to a physical location distant from the gyrB and parC loci on the chromosome, whereas parC is closely linked to parE. Ciprofloxacin-resistant (Cpr) clinical isolates of S. pneumoniae had mutations affecting amino acid residues of the quinolone resistance-determining region of ParC (low-level Cpr) or in both quinolone resistance-determining regions of ParC and GyrA (high-level Cpr). Mutations were found in residue positions equivalent to the serine at position 83 and the aspartic acid at position 87 of the E. coli GyrA subunit. Transformation experiments suggest that ParC is the primary target of ciprofloxacin. Mutation in parC appears to be a prerequisite before mutations in gyrA can influence resistance levels. PMID:8891124

Condensin promotes the juxtaposition of DNA flanking its loading site in Bacillus subtilis

PubMed Central

Wang, Xindan; Le, Tung B.K.; Lajoie, Bryan R.; Dekker, Job; Laub, Michael T.; Rudner, David Z.

2015-01-01

SMC condensin complexes play a central role in compacting and resolving replicated chromosomes in virtually all organisms, yet how they accomplish this remains elusive. In Bacillus subtilis, condensin is loaded at centromeric parS sites, where it encircles DNA and individualizes newly replicated origins. Using chromosome conformation capture and cytological assays, we show that condensin recruitment to origin-proximal parS sites is required for the juxtaposition of the two chromosome arms. Recruitment to ectopic parS sites promotes alignment of large tracks of DNA flanking these sites. Importantly, insertion of parS sites on opposing arms indicates that these “zip-up” interactions only occur between adjacent DNA segments. Collectively, our data suggest that condensin resolves replicated origins by promoting the juxtaposition of DNA flanking parS sites, drawing sister origins in on themselves and away from each other. These results are consistent with a model in which condensin encircles the DNA flanking its loading site and then slides down, tethering the two arms together. Lengthwise condensation via loop extrusion could provide a generalizable mechanism by which condensin complexes act dynamically to individualize origins in B. subtilis and, when loaded along eukaryotic chromosomes, resolve them during mitosis. PMID:26253537

European light dosimeter network (ELDONET): 1998 data

NASA Astrophysics Data System (ADS)

Häder, D.-P.; Lebert, M.; Colombetti, G.; Figueroa, F.

2001-03-01

The European light dosimeter network of over 40 stations has been established in Europe and other continents equipped with three-channel filter dosimeters to measure solar radiation in three channels, UV-B (280-315 nm), UV-A (315-400 nm) and photosynthetically active radiation (PAR). The recorded data have been evaluated, and the monthly doses in all three channels show a strong latitudinal dependence from northern Sweden to the Canary Islands. There are a few remarkable exceptions such as the data recorded at the high mountain station on the Zugspitze (German Alps) and unequal doses at stations at comparable latitudes which indicate the impact of local weather conditions and mean sunshine hours. While generally peak values are recorded in the months of June and July, the UV-B maxima are shifted later into the year, which is due to the antagonistic functions of decreasing solar angles and increasing transparency of the atmosphere as the total column ozone decreases in the second half of the year for the Northern Hemisphere. This is supported by comparison with modelled total column ozone and satellite-based measurements. Also the ratios of UV-B:UV-A and UV-B:PAR as well as UV-A:PAR peak during the summer months, with the exception of the northernmost station at Abisko (north Sweden) where the UV-A:PAR ratio peaks in the winter months which is due to the specific photoclimatic conditions north of the polar circle. The penetration of solar radiation into the water column was found to strongly depend on the transparency of the water column. In Gran Canaria more than 10% of the surface UV-B penetrated to 4-5 m depth. The path of the solar eclipse on 11 August 1999 could be followed in several stations with different degrees of occlusion of the sun disk.

Removal of reactive red-120 and 4-(2-pyridylazo) resorcinol from aqueous samples by Fe3O4 magnetic nanoparticles using ionic liquid as modifier.

PubMed

Absalan, Ghodratollah; Asadi, Mozaffar; Kamran, Sedigheh; Sheikhian, Leila; Goltz, Douglas M

2011-08-30

The nanoparticles of Fe(3)O(4) as well as the binary nanoparticles of ionic liquid and Fe(3)O(4) (IL-Fe(3)O(4)) were synthesized for removal of reactive red 120 (RR-120) and 4-(2-pyridylazo) resorcinol (PAR) as model azo dyes from aqueous solutions. The mean size and the surface morphology of the nanoparticles were characterized by TEM, DLS, XRD, FTIR and TGA techniques. Adsorption of RR-120 and PAR was studied in a batch reactor at different experimental conditions such as nanoparticle dosage, dye concentration, pH of the solution, ionic strength, and contact time. Experimental results indicated that the IL-Fe(3)O(4) nanoparticles had removed more than 98% of both dyes under the optimum operational conditions of a dosage of 60mg, a pH of 2.5, and a contact time of 2min when initial dyes concentrations of 10-200mg L(-1) were used. The maximum adsorption capacity of IL-Fe(3)O(4) was 166.67 and 49.26mg g(-1) for RR-120 and PAR, respectively. The isotherm experiments revealed that the Langmuir model attained better fits to the equilibrium data than the Freundlich model. The Langmuir adsorption constants were 5.99 and 3.62L mg(-1) for adsorptions of RR-120 and PAR, respectively. Both adsorption processes were endothermic and dyes could be desorbed from IL-Fe(3)O(4) by using a mixed NaCl-acetone solution and adsorbent was reusable. Copyright © 2011 Elsevier B.V. All rights reserved.

Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain.

PubMed

Liu, S; Liu, Y-P; Yue, D-M; Liu, G-J

2014-03-01

Treating bone cancer pain continues to be a major clinical challenge, and the underlying mechanisms of bone cancer pain remain elusive. Protease-activated receptor 2 (PAR2) has been reported to be involved in neurogenic inflammation, nociceptive pain and hyperalgesia. Here, we investigated the role of PAR2 in bone cancer pain development. Expression of PAR2, mechanical allodynia, thermal hyperalgesia and neurochemical alterations induced by bone cancer pain were analysed in male, adult C3H/HeJ mice with tumour cell implantation (TCI). To investigate the contribution of PAR2 to bone cancer pain, PAR2 antagonist peptide and PAR2 knockout mice were used. TCI produced bone cancer-related pain behaviours. Production and persistence of these pain behaviours were well correlated with TCI-induced up-regulation of PAR2 in sciatic nerve and dorsal root ganglia (DRG). PAR2 knockout and spinal administration of PAR2 antagonist peptide prevented and/or reversed bone cancer-related pain behaviours and associated neurochemical changes in DRG and dorsal horn (DH). TCI also induced proteases release in tumour-bearing tibia, sciatic nerve and DRG. Plantar injection of supernatant from sarcoma cells induced PAR2 up-regulation and intracellular calcium [Ca(2+) ]i increase in DRG, and calcitonin gene-related peptide accumulation in DH, as well as significant thermal and mechanical hyperalgesia, which were all in PAR2-dependent manners. These findings suggest that PAR2 may be a key mediator for peripheral sensitization of bone cancer pain. Inhibiting PAR2 activation, especially during the early phase, may be a new therapy for preventing/suppressing development of bone cancer pain. © 2013 European Pain Federation - EFIC®

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain.

PubMed

Annaházi, A; Dabek, M; Gecse, K; Salvador-Cartier, C; Polizzi, A; Rosztóczy, A; Róka, R; Theodorou, V; Wittmann, T; Bueno, L; Eutamene, H

2012-01-01

Activation of proteinase-activated receptor-4 (PAR-4) from the colonic lumen has an antinociceptive effect to colorectal distension (CRD) in mice in basal conditions. We aimed to determine the functional localization of the responsible receptors and to test their role in two different hyperalgesia models. Mice received PAR-4 activating peptide (PAR-4-AP, AYPGKF-NH(2)) or vehicle intraperitoneally (IP), and abdominal EMG response to CRD was measured. The next group received PAR-4-AP intracolonically (IC) with or without 2,4,6-triaminopyrimidine, a chemical tight junction blocker, before CRD. The SCID mice were used to test the role of lymphocytes in the antihyperalgesic effect. The effects of PAR-4-AP and PAR-4-antagonist (P4pal-10) were evaluated in water avoidance stress (WAS) model and low grade 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Spinal Fos protein expression was visualized by immunohistochemistry. The antinociceptive effect of PAR-4-AP disappeared when was administrered IP, or with the blockade of colonic epithelial tight junctions, suggesting that PAR-4-AP needs to reach directly the nerve terminals in the colon. The CRD-induced spinal Fos overexpression was reduced by 43% by PAR-4-AP. The PAR-4-AP was antihyperalgesic in both hyperalgesia models and in mice with impaired lymphocytes. The PAR-4-antagonist significantly increased the TNBS, but not the WAS-induced colonic hyperalgesia. The antinociceptive effect of PAR-4-AP depends on its penetration to the colonic mucosa. The PAR-4 activation is endogenously involved as a feedback loop to attenuate inflammatory colonic hyperalgesia to CRD. © 2011 Blackwell Publishing Ltd.

Controls of Evapotranspiration and CO2 Fluxes from Scots Pine by Surface Conductance and Abiotic Factors

PubMed Central

Zha, Tianshan; Li, Chunyi; Kellomäki, Seppo; Peltola, Heli; Wang, Kai-Yun; Zhang, Yuqing

2013-01-01

Evapotranspiration (E) and CO2 flux (Fc) in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc, surface conductance (gc), and decoupling coefficient (Ω), showing similar trends to those in radiation (PAR) and vapour pressure deficit (δ). The maximum mean daily values (24-h average) for E, Fc, gc, and Ω were 1.78 mmol m−2 s−1, −11.18 µmol m−2 s−1, 6.27 mm s−1, and 0.31, respectively, with seasonal averages of 0.71 mmol m−2 s−1, −4.61 µmol m−2 s−1, 3.3 mm s−1, and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc. Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc, while vapour pressure deficit was the most important environmental factor affecting gc. Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O)−1 and a seasonal average of 7.06 μmol CO2 (μmol H2O)−1. Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition. PMID:23894401

Controls of evapotranspiration and CO2 fluxes from scots pine by surface conductance and abiotic factors.

PubMed

Zha, Tianshan; Li, Chunyi; Kellomäki, Seppo; Peltola, Heli; Wang, Kai-Yun; Zhang, Yuqing

2013-01-01

Evapotranspiration (E) and CO2 flux (Fc ) in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc , surface conductance (gc ), and decoupling coefficient (Ω), showing similar trends to those in radiation (PAR) and vapour pressure deficit (δ). The maximum mean daily values (24-h average) for E, Fc , gc , and Ω were 1.78 mmol m(-2) s(-1), -11.18 µmol m(-2) s(-1), 6.27 mm s(-1), and 0.31, respectively, with seasonal averages of 0.71 mmol m(-2) s(-1), -4.61 µmol m(-2) s(-1), 3.3 mm s(-1), and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc . Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc , while vapour pressure deficit was the most important environmental factor affecting gc . Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O)(-1) and a seasonal average of 7.06 μmol CO2 (μmol H2O)(-1). Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition.

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

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer.

PubMed

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-10-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer.

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer

PubMed Central

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-01-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer. PMID:28943918

The Role of PAR2 in TGF-β1-Induced ERK Activation and Cell Motility

PubMed Central

Ungefroren, Hendrik; Witte, David; Fiedler, Christian; Gädeken, Thomas; Kaufmann, Roland; Lehnert, Hendrik

2017-01-01

Background: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. Methods: RNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2–ALK5 physical interaction. Results: Inhibition of ERK signaling with the MEK inhibitor U0126 blunted the ability of TGF-β1 to induce migration in pancreatic cancer Panc1 cells. ERK activation in response to PAR2 agonistic peptide (PAR2–AP) was strong and rapid, while it was moderate and delayed in response to TGF-β1. Basal and TGF-β1-dependent ERK, but not SMAD activation, was blocked by U0126 in Panc1 and other cell types indicating that ERK activation is downstream or independent of SMAD signaling. Moreover, cellular depletion of PAR2 in HaCaT cells strongly inhibited TGF-β1-induced ERK activation, while the biased PAR2 agonist GB88 at 10 and 100 µM potentiated TGF-β1-dependent ERK activation and cell migration. Finally, we provide evidence for a physical interaction between PAR2 and ALK5. Our data show that both PAR2–AP- and TGF-β1-induced cell migration depend on ERK activation, that PAR2 expression is crucial for TGF-β1-induced ERK activation, and that the functional cooperation of PAR2 and TGF-β1 involves a physical interaction between PAR2 and ALK5. PMID:29261154

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

PubMed Central

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon

2015-01-01

Background Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. Objective To evaluate the basic physiological role of PAR-2 in skin. Methods We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Results Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Conclusion Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID:26273149

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

PubMed

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon; Lee, Young Ho

2015-08-01

Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. To evaluate the basic physiological role of PAR-2 in skin. We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

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

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

PubMed Central

Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

2014-01-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

PubMed

Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

2015-03-01

It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS.

Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

PubMed

Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

2015-07-01

Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

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 ).

The role of protease-activated receptor-2 on pulmonary neutrophils in the innate immune response to cockroach allergen

PubMed Central

2012-01-01

Background Serine proteases in German cockroach (GC) have been shown to mediate allergic airway inflammation through the activation of protease activated receptor (PAR)-2. Neutrophils play an important role in regulating the innate immune response, and are recruited into the airways following GC frass exposure. As such, we investigated the role of PAR-2 in airway neutrophil recruitment, activation and cytokine production following allergen exposure. Methods Wild type and PAR-2-deficient mice were administered a single intratracheal instillation of PBS or GC frass and neutrophil recruitment, expression of PAR-2, CD80, CD86, and MHC class II were assessed by flow cytometry and levels of tumor necrosis factor (TNF)α was assessed by ELISA. Uptake of AlexaFluor 405-labeled GC frass by neutrophils was performed by flow cytometry. Results Neutrophil recruitment in the lung and airways following GC frass exposure was significantly decreased in PAR-2-deficient mice compared to wild type mice. GC frass exposure increased the level of PAR-2 on pulmonary neutrophils and increased numbers of PAR-2-positive neutrophils were found in the lungs; however PAR-2 did not play a role in meditating allergen uptake. Comparing wild type and PAR-2-deficient mice, we found that a single exposure to GC frass increased levels of CD80 and CD86 on pulmonary neutrophils, an effect which was independent of PAR-2 expression. Neutrophils isolated from the whole lungs of naïve PAR-2-deficient mice treated ex vivo with GC frass produced significantly less TNFα than in similarly treated wild type neutrophils. Lastly, neutrophils were isolated from the bronchoalveolar lavage fluid of wild type and PAR-2-deficient mice following a single intratracheal exposure to GC frass. Airway neutrophils from PAR-2-deficient mice released substantially decreased levels of TNFα, suggesting a role for PAR-2 in neutrophil-derived cytokine production. Conclusions Together these data suggest PAR-2 expression can be upregulated on lung neutrophils following allergen exposure and the consequence is altered release of TNFα which could drive the early innate immune response. PMID:22954301

Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

PubMed Central

Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

2011-01-01

Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia evaluated by uPAR-immunohistochemistry.

PubMed

Laerum, Ole Didrik; Ovrebo, Kjell; Skarstein, Arne; Christensen, Ib Jarle; Alpízar-Alpízar, Warner; Helgeland, Lars; Danø, Keld; Nielsen, Boye Schnack; Illemann, Martin

2012-08-01

Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase-type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR-positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR-score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR-scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas. Copyright © 2011 UICC.

Centromere Binding and Evolution of Chromosomal Partition Systems in the Burkholderiales

PubMed Central

Passot, Fanny M.; Calderon, Virginie; Fichant, Gwennaele; Lane, David

2012-01-01

How split genomes arise and evolve in bacteria is poorly understood. Since each replicon of such genomes encodes a specific partition (Par) system, the evolution of Par systems could shed light on their evolution. The cystic fibrosis pathogen Burkholderia cenocepacia has three chromosomes (c1, c2, and c3) and one plasmid (pBC), whose compatibility depends on strictly specific interactions of the centromere sequences (parS) with their cognate binding proteins (ParB). However, the Par systems of B. cenocepacia c2, c3, and pBC share many features, suggesting that they arose within an extended family. Database searching revealed seven subfamilies of Par systems like those of B. cenocepacia. All are from plasmids and secondary chromosomes of the Burkholderiales, which reinforces the proposal of an extended family. The subfamily of the Par system of B. cenocepacia c3 includes plasmid variants with parS sequences divergent from that of c3. Using electrophoretic mobility shift assay (EMSA), we found that ParB-c3 binds specifically to centromeres of these variants, despite high DNA sequence divergence. We suggest that the Par system of B. cenocepacia c3 has preserved the features of an ancestral system. In contrast, these features have diverged variably in the plasmid descendants. One such descendant is found both in Ralstonia pickettii 12D, on a free plasmid, and in Ralstonia pickettii 12J, on a plasmid integrated into the main chromosome. These observations suggest that we are witnessing a plasmid-chromosome interaction from which a third chromosome will emerge in a two-chromosome species. PMID:22522899

Centromere binding and evolution of chromosomal partition systems in the Burkholderiales.

PubMed

Passot, Fanny M; Calderon, Virginie; Fichant, Gwennaele; Lane, David; Pasta, Franck

2012-07-01

How split genomes arise and evolve in bacteria is poorly understood. Since each replicon of such genomes encodes a specific partition (Par) system, the evolution of Par systems could shed light on their evolution. The cystic fibrosis pathogen Burkholderia cenocepacia has three chromosomes (c1, c2, and c3) and one plasmid (pBC), whose compatibility depends on strictly specific interactions of the centromere sequences (parS) with their cognate binding proteins (ParB). However, the Par systems of B. cenocepacia c2, c3, and pBC share many features, suggesting that they arose within an extended family. Database searching revealed seven subfamilies of Par systems like those of B. cenocepacia. All are from plasmids and secondary chromosomes of the Burkholderiales, which reinforces the proposal of an extended family. The subfamily of the Par system of B. cenocepacia c3 includes plasmid variants with parS sequences divergent from that of c3. Using electrophoretic mobility shift assay (EMSA), we found that ParB-c3 binds specifically to centromeres of these variants, despite high DNA sequence divergence. We suggest that the Par system of B. cenocepacia c3 has preserved the features of an ancestral system. In contrast, these features have diverged variably in the plasmid descendants. One such descendant is found both in Ralstonia pickettii 12D, on a free plasmid, and in Ralstonia pickettii 12J, on a plasmid integrated into the main chromosome. These observations suggest that we are witnessing a plasmid-chromosome interaction from which a third chromosome will emerge in a two-chromosome species.

Doxycycline directly targets PAR1 to suppress tumor progression

PubMed Central

Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-01-01

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. PMID:28187433

Doxycycline directly targets PAR1 to suppress tumor progression.

PubMed

Zhong, Weilong; Chen, Shuang; Zhang, Qiang; Xiao, Ting; Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-03-07

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials.

MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula

PubMed Central

Verdier, Jerome; Zhao, Jian; Torres-Jerez, Ivone; Ge, Shujun; Liu, Chenggang; He, Xianzhi; Mysore, Kirankumar S.; Dixon, Richard A.; Udvardi, Michael K.

2012-01-01

MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID:22307644

Dishevelled-induced phosphorylation regulates membrane localization of Par1b

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

Terabayashi, Takeshi; Funato, Yosuke; Miki, Hiroaki, E-mail: hmiki@protein.osaka-u.ac.jp

2008-10-31

Par1b is an evolutionarily conserved kinase that plays crucial roles in cell polarity. Controlling intracellular localization of Par1b is important for its biological activity. We previously reported that Wnt stimulation or expression of Dvl promotes accumulation of Par1b in the membrane (T. Terabayashi, T.J. Itoh, H. Yamaguchi, Y. Yoshimura, Y. Funato, S. Ohno, H. Miki, Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons, J. Neurosci. 27 (2007) 13098-13107). However, its molecular mechanism remains unclear. Here we show the importance of Par1b phosphorylation in the regulation of membrane localization. We find that Thr-324 ismore » phosphorylated in a Dvl-dependent manner. Interestingly, the conversion of Thr-324 to Glu results in a significant accumulation of Par1b in the membrane, without any effects on the kinase activity. Moreover, the phospho-mimicking Par1b mutant does not antagonistically function against Dvl in microtubule stabilization and neurite extension, although wildtype Par1b does. These results suggest that membrane accumulation of Par1b induced by Dvl is regulated by its phosphorylation status, which is important for Par1b to regulate the microtubule dynamics.« less

Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa.

PubMed

Inci, Kamuran; Edebo, Anders; Olbe, Lars; Casselbrant, Anna

2009-01-01

The role of duodenal reflux in gastroesophageal reflux disease (GERD) containing bile salts and pancreatic enzymes (with special attention to trypsin) is still under discussion. Proteinase-activated receptors (PARs) are a novel family and PAR-2 is a unique member of this family because it is activated by trypsin. The aim of the present study was to examine the presence and the position of the PAR-2 receptor in human esophageal mucosa in different subgroups of GERD. Distal biopsies taken from healthy controls, patients with erosive reflux disease (ERD), patients with specialized intestinal metaplasia (SIM) and adenocarcinoma were analyzed for the PAR-2 receptor with reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Gene transcripts for the PAR-2 receptor were found in all groups, with increased levels in SIM patients compared to controls. However, this visual pattern was not seen for the protein expression of the PAR-2 receptor showing no apparent quantitative differences between the groups. Immunohistochemistry revealed distinct staining for the PAR-2 receptor in the luminal part of the esophageal epithelium. The localization of the PAR-2 receptor indicates that the receptor can be cleaved and activated by trypsin in duodenogastric esophageal refluxate. The data thus suggest that the trypsin-PAR-2 pathway may be involved in the pathogenesis of GERD.

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.

Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.

PubMed

Zhang, Guoqiang; Cai, Xiaohe; López-Guisa, Jesús M; Collins, Sarah J; Eddy, Allison A

2004-08-01

The urokinase receptor (uPAR) attenuates myofibroblast recruitment and fibrosis in the kidney. This study examined the role of uPAR and its co-receptor LDL receptor-related protein (LRP) in the regulation of kidney fibroblast proliferation and extracellular signal-regulated kinase (ERK) signaling. Compared with uPAR+/+ cells, uPAR-/- kidney fibroblasts were hyperproliferative. UPAR-/- fibroblast proliferation was 60% inhibited by an ERK kinase inhibitor. LRP protein was reduced and extracellular accumulation of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) proteins were greater in uPAR-/- cultures. Addition of functional uPA protein or LRP antisense RNA significantly increased ERK signaling and cell mitosis in both genotypes. Enhanced uPAR-/- fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide. The density of cell-bound fluor-uPA was similar between uPAR-/- and uPAR+/+ fibroblasts (78 +/- 6 versus 92 +/- 16 units). These data suggest that uPAR-deficient kidney fibroblasts express lower levels of its scavenger co-receptor LRP, resulting in greater extracellular accumulation of uPA and PAI-1. Enhanced proliferation of uPAR-/- fibroblasts seems to be mediated by uPA-dependent ERK signaling via an alternative urokinase receptor.

An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells.

PubMed

Ida, Chieri; Yamashita, Sachiko; Tsukada, Masaki; Sato, Teruaki; Eguchi, Takayuki; Tanaka, Masakazu; Ogata, Shin; Fujii, Takahiro; Nishi, Yoshisuke; Ikegami, Susumu; Moss, Joel; Miwa, Masanao

2016-02-01

PolyADP-ribosylation is mediated by poly(ADP-ribose) (PAR) polymerases (PARPs) and may be involved in various cellular events, including chromosomal stability, DNA repair, transcription, cell death, and differentiation. The physiological level of PAR is difficult to determine in intact cells because of the rapid synthesis of PAR by PARPs and the breakdown of PAR by PAR-degrading enzymes, including poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3. Artifactual synthesis and/or degradation of PAR likely occurs during lysis of cells in culture. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the physiological levels of PAR in cultured cells. We immediately inactivated enzymes that catalyze the synthesis and degradation of PAR. We validated that trichloroacetic acid is suitable for inactivating PARPs, PARG, and other enzymes involved in metabolizing PAR in cultured cells during cell lysis. The PAR level in cells harvested with the standard radioimmunoprecipitation assay buffer was increased by 450-fold compared with trichloroacetic acid for lysis, presumably because of activation of PARPs by DNA damage that occurred during cell lysis. This ELISA can be used to analyze the biological functions of polyADP-ribosylation under various physiological conditions in cultured cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating post-wildfire hydrologic recovery using ParFlow in southern California

NASA Astrophysics Data System (ADS)

Lopez, S. R.; Kinoshita, A. M.; Atchley, A. L.

2016-12-01

Wildfires are naturally occurring hazards that can have catastrophic impacts. They can alter the natural processes within a watershed, such as surface runoff and subsurface water storage. Generally, post-fire hydrologic models are either one-dimensional, empirically-based models, or two-dimensional, conceptually-based models with lumped parameter distributions. These models are useful in providing runoff measurements at the watershed outlet; however, do not provide distributed hydrologic simulation at each point within the watershed. This research demonstrates how ParFlow, a three-dimensional, distributed hydrologic model can simulate post-fire hydrologic processes by representing soil burn severity (via hydrophobicity) and vegetation recovery as they vary both spatially and temporally. Using this approach, we are able to evaluate the change in post-fire water components (surface flow, lateral flow, baseflow, and evapotranspiration). This model is initially developed for a hillslope in Devil Canyon, burned in 2003 by the Old Fire in southern California (USA). The domain uses a 2m-cell size resolution over a 25 m by 25 m lateral extent. The subsurface reaches 2 m and is assigned a variable cell thickness, allowing an explicit consideration of the soil burn severity throughout the stages of recovery and vegetation regrowth. Vegetation regrowth is incorporated represented by satellite-based Enhanced Vegetation Index (EVI) products. The pre- and post-fire surface runoff, subsurface storage, and surface storage interactions are evaluated and will be used as a basis for developing a watershed-scale model. Long-term continuous simulations will advance our understanding of post-fire hydrological partitioning between water balance components and the spatial variability of watershed processes, providing improved guidance for post-fire watershed management.

Physiological Strain During Load Carrying: Effects of Mass and Type of Backpack

DTIC Science & Technology

2001-05-01

load did not significantly increase the EMG signal of the trapezius shoulder muscle (pars descenders). While walking, load carrying significantly...descending part of the right trapezius muscle was measured with two surface silver-silver chloride electrodes (PPG, Hellige), positioned on the distal...values using a previously determined RMS versus force relationship. This calibration curve between RMS of the EMG of the trapezius muscle and the force

Cumulative trauma, adversity and grief symptoms associated with fronto-temporal regions in life-course persistent delinquent boys.

PubMed

Lansing, Amy E; Virk, Agam; Notestine, Randy; Plante, Wendy Y; Fennema-Notestine, Christine

2016-08-30

Delinquent youth have substantial trauma exposure, with life-course persistent delinquents [LCPD] demonstrating notably elevated cross-diagnostic psychopathology and cognitive deficits. Because adolescents remain in the midst of brain and neurocognitive development, tailored interventions are key to improving functional outcomes. This structural magnetic resonance imaging study compared neuroanatomical profiles of 23 LCPD and 20 matched control adolescent boys. LCPD youth had smaller overall gray matter, and left hippocampal, volumes alongside less cortical surface area and folding within the left pars opercularis and supramarginal cortex. LCPD youth had more adversity-related exposures, and their higher Cumulative Trauma, Adversity and Grief [C-TAG] symptoms were associated with less surface area and folding in the pars opercularis and lingual gyrus. Neuroanatomical differences between LCPD and control youth overlap with data from both maltreatment and antisocial literatures. The affected left frontal regions also share connections to language- and executive-related functions, aligning well with LCPD youths' cognitive and behavioral difficulties. These data also dovetail with research suggesting the possibility of neurodevelopmental delays or disruptions related to cumulative adversity burden. Thus, concurrent treatment of LCPD youths' C-TAG symptoms and, cognitive deficits with overlapping neuroanatomical bases, may be most effective in improving outcomes and optimizing neurodevelopmental trajectories. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Revetements bioactifs a base de chondroitine sulfate et de facteurs de croissance pour applications vasculaires

NASA Astrophysics Data System (ADS)

Lequoy, Pauline

Malgre des avancees technologiques indeniables, l'efficacite des implants biomedicaux est encore limitee par les biomateriaux synthetiques qui les composent, notamment en raison de leur incapacite a generer une reponse biologique adequate. En particulier, la guerison tissulaire autour des implants vasculaires reste problematique. Une etude de la litterature a montre que dans le cas des endoprotheses couvertes (tuyaux polymeriques utilises pour la reparation endovasculaire des anevrismes de l'aorte abdominale), le manque de guerison observe s'explique non seulement par l'inertie des biomateriaux utilises mais aussi par le fait que l'implant est insere dans un vaisseau malade favorisant la mort des cellules par apoptose et presentant une depletion cellulaire marquee. L'hypothese a la base de ce projet est qu'un revetement bioactif pourrait ameliorer la guerison et la colonisation de l'implant par les cellules vasculaires et ainsi favoriser l'attachement de l'implant dans le vaisseau malade afin de prevenir les complications a long terme. Dans ce contexte, deux molecules anti-apoptotiques ont ete selectionnees pour developper le revetement, la chondroitine sulfate (CS), un glycosaminoglycane de la matrice extracellulaire, et le facteur de croissance de l'epiderme (EGF) qui possede egalement un role important dans la guerison tissulaire. L'un des defis de ce projet est de preserver la bioactivite de ces molecules lors de leur immobilisation dans un revetement. Pour etablir une preuve de concept, nous avons demontre qu'un revetement CS+EGF obtenu par greffage covalent permet d'ameliorer significativement la survie des cellules vasculaires humaines (cellules musculaires lisses, CMLV, et fibroblastes) sur les materiaux realistes (PET, ePTFE). Apres avoir transfere ce revetement sur des implants commerciaux en ePTFE, des tests in vivo ont demontre une amelioration de la guerison grâce au revetement bioactif, cependant la guerison n'a pas ete totale dans la cavite anevrismale. Pour ameliorer la bioactivite du revetement, un systeme de capture oriente base sur la complementarite de deux peptides (superhelices 'coiled-coil') a ete utilise pour immobiliser l'EGF sur CS. Cette immobilisation orientee a permis une meilleure efficacite de capture, ainsi qu'une augmentation marquee de la survie des CMLV par rapport au greffage covalent aleatoire utilise precedemment. De plus, les travaux realises ont permis l'avancement de la comprehension des proprietes antiadhesives selectives de CS par comparaison avec le dextrane carboxymethyle. Enfin, nous avons demontre que la polyvalence du systeme de capture oriente pour facteurs de croissance permet la co-immobilisation de deux facteurs de croissance, EGF et VEGF (facteur de croissance de l'endothelium vasculaire), et ce a des ratios variables. Les densites surfaciques ont ete optimisees par simple changement de concentration lors de l'incubation. Des etudes cellulaires avec une gamme de ratios EGF/VEGF ont revele un effet synergique des deux facteurs de croissance sur la survie des CMLV et des cellules endotheliales. Les travaux menes ont permis de developper des revetements bioactifs anti-apoptotiques qui ameliorent la survie des cellules vasculaires et constituent une avancee vers la creation d'endoprotheses bioactives. Il apparait egalement que la plateforme d'immobilisation coiled-coil presente un grand potentiel pour la construction de surfaces bioactives complexes et la comprehension du role de differents facteurs de croissance dans les comportements cellulaires.

The intracellular carboxyl tail of the PAR-2 receptor controls intracellular signaling and cell death.

PubMed

Zhu, Zhihui; Stricker, Rolf; Li, Rong yu; Zündorf, Gregor; Reiser, Georg

2015-03-01

The protease-activated receptors are a group of unique G protein-coupled receptors, including PAR-1, PAR-2, PAR-3 and PAR-4. PAR-2 is activated by multiple trypsin-like serine proteases, including trypsin, tryptase and coagulation proteases. The clusters of phosphorylation sites in the PAR-2 carboxyl tail are suggested to be important for the binding of adaptor proteins to initiate intracellular signaling to Ca(2+) and mitogen-activated protein kinases. To explore the functional role of PAR-2 carboxyl tail in controlling intracellular Ca(2+), ERK and AKT signaling, a series of truncated mutants containing different clusters of serines/threonines were generated and expressed in HEK293 cells. Firstly, we observed that lack of the complete C-terminus of PAR-2 in a mutated receptor gave a relatively low level of localization on the cell plasma membrane. Secondly, the shortened carboxyl tail containing 13 amino acids was sufficient for receptor internalization. Thirdly, the cells expressing truncation mutants showed deficits in their capacity to couple to intracellular Ca(2+) and ERK and AKT signaling upon trypsin challenge. In addition, HEK293 cells carrying different PAR-2 truncation mutants displayed decreased levels of cell survival after long-lasting trypsin stimulation. In summary, the PAR-2 carboxyl tail was found to control the receptor localization, internalization, intracellular Ca(2+) responses and signaling to ERK and AKT. The latter can be considered to be important for cell death control.

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.

Effect of Par Frying on Composition and Texture of Breaded and Battered Catfish

PubMed Central

Woods, Kristin; Lea, Jeanne M.; Brashear, Suzanne S.; Boue, Stephen M.; Daigle, Kim W.; Bett-Garber, Karen L.

2018-01-01

Catfish is often consumed as a breaded and battered fried product; however, there is increasing interest in breaded and battered baked products as a healthier alternative. Par frying can improve the texture properties of breaded and battered baked products, but there are concerns about the increase in lipid uptake from par frying. The objective of this study was to examine the effect of different batters (rice, corn, and wheat) and the effect of par frying on the composition and texture properties of baked catfish. Catfish fillets were cut strips and then coated with batters, which had similar viscosities. Half of the strips were par fried in 177 °C vegetable oil for 1 min and the other half were not par fried. Samples were baked at 177 °C for 25 min. Analysis included % batter adhesion, cooking loss, protein, lipid, ash, and moisture, plus hardness and fracture quality measured using a texture analyzer. A trained sensory panel evaluated both breading and flesh texture attributes. Results found the lipid content of par fried treatments were significantly higher for both corn and wheat batters than for non-par fried treatments. Sensory analysis indicated that the texture of the coatings in the par fried treatments were significantly greater for hardness attributes. Fillet flakiness was significantly greater in the par fried treatments and corn-based batters had moister fillet strips compared to the wheat flour batters. Texture analyzer hardness values were higher for the par fried treatments. PMID:29570660

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.

Par-4, a Gene Required for Cytoplasmic Localization and Determination of Specific Cell Types in Caenorhabditis Elegans Embryogenesis

PubMed Central

Morton, D. G.; Roos, J. M.; Kemphues, K. J.

1992-01-01

Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4;par-2 double mutant suggests that par-4 and par-2 gene products interact in this system. PMID:1582558

Vegetation Function and Physiology: Photosynthesis, Fluorescence and Non-photochemical Quenching (NPQ)

NASA Astrophysics Data System (ADS)

Zhang, Q.; Yao, T.

2017-12-01

Photosynthesis is a basic physiological function of vegetation that relies on PAR provided through photosynthetic pigments (mainly chlorophyll) for plant growth and biomass accumulation. Vegetation chlorophyll (chl) content and non-chlorophyll (non-chl) components vary with plant functional types (PFTs) and growing stages. The PAR absorbed by canopy chlorophyll (APARchl) is associated with photosynthesis (i.e., gross primary production, GPP) while the PAR absorbed by canopy non-chl components (APARnon-chl) is not associated with photosynthesis. Under non-optimal environmental conditions, vegetation is "stressed" and both photosynthesis (GPP) and light use efficiency are reduced, therefore, excess portions of APARchl are discarded as fluorescence or non-photochemical quenching (NPQ). The photochemical reflectance index (PRI) is a measurement related to NPQ. Both PRI and yield of solar induced chlorophyll fluorescence (SIFyield = SIF/APARchl) have been proposed as possible bio-indicators of LUEchl. We have successfully developed an algorithm to distinguish between chlorophyll and non-chl components of vegetation, and to retrieve fractional absorptions of PAR by chlorophyll (fAPARchl) and by non-chl components (fAPARnon-chl) with surface reflectance of MODIS bands 1 - 7. A method originally pioneered by Hanan et al. (2002) has been used to retrieve fAPAR for vegetation photosynthesis (fAPARPSN) at flux tower sites based on the light response curve of tower net ecosystem exchange (NEE) and incident PAR at low light intensity. We have also retrieved the PRI from MODIS data (bands 11 and 1) and have derived SIFyield with the Global Ozone Monitoring Experiment - 2 (GOME-2) SIF data. We find that fAPARPSN at flux tower sites matches well with site fAPARchl, and ratio fAPARnon-chl/fAPARchl varies largely. APARchl can explain >=78% variation in seasonal GPP . We disentangle the possible impact of fAPARchl on PRI from physiological stress response, disentangle the possible impact of APARchl on SIFyield from physiological stress response, and find that integrating three bio-parameters fAPARchl, PRI and SIFyield can explain >=87% variation in seasonal GPP . Therefore, quantifying fAPARchl, PRI and SIF has the best potential to monitor vegetation function and physiology.

Developing Land Surface Type Map with Biome Classification Scheme Using Suomi NPP/JPSS VIIRS Data

NASA Astrophysics Data System (ADS)

Zhang, Rui; Huang, Chengquan; Zhan, Xiwu; Jin, Huiran

2016-08-01

Accurate representation of actual terrestrial surface types at regional to global scales is an important element for a wide range of applications, such as land surface parameterization, modeling of biogeochemical cycles, and carbon cycle studies. In this study, in order to meet the requirement of the retrieval of global leaf area index (LAI) and fraction of photosynthetically active radiation absorbed by the vegetation (fPAR) and other studies, a global map generated from Suomi National Polar- orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) surface reflectance data in six major biome classes based on their canopy structures, which include: Grass/Cereal Crops, Shrubs, Broadleaf Crops, Savannas, Broadleaf Forests, and Needleleaf Forests, was created. The primary biome classes were converted from an International Geosphere-Biosphere Program (IGBP) legend global surface type data that was created in previous study, and the separation of two crop types are based on a secondary classification.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma

PubMed Central

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin

2015-01-01

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma. PMID:26658828

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

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

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 ofmore » 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.« less

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

PubMed

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin; Cameron, Lisa; Vliagoftis, Harissios

2015-01-01

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Kim, Myeong Ok; Joeng, Ji-Hyun; Chung, Seungsoo

2014-01-01

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca2+ currents (ICa-N) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca2+ currents (ICa), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on ICa. This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca2+ channel blocker, suggesting the involvement of N-type Ca2+ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited ICa–N in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca2+ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca2+ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals. PMID:25410909

PAR1 activation affects the neurotrophic properties of Schwann cells.

PubMed

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

PubMed

Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

2011-05-01

Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

Pharmacophore-based virtual screening, biological evaluation and binding mode analysis of a novel protease-activated receptor 2 antagonist

NASA Astrophysics Data System (ADS)

Cho, Nam-Chul; Seo, Seoung-Hwan; Kim, Dohee; Shin, Ji-Sun; Ju, Jeongmin; Seong, Jihye; Seo, Seon Hee; Lee, Iiyoun; Lee, Kyung-Tae; Kim, Yun Kyung; No, Kyoung Tai; Pae, Ae Nim

2016-08-01

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor, mediating inflammation and pain signaling in neurons, thus it is considered to be a potential therapeutic target for inflammatory diseases. In this study, we performed a ligand-based virtual screening of 1.6 million compounds by employing a common-feature pharmacophore model and two-dimensional similarity search to identify a new PAR2 antagonist. The common-feature pharmacophore model was established based on the biological screening results of our in-house library. The initial virtual screening yielded a total number of 47 hits, and additional biological activity tests including PAR2 antagonism and anti-inflammatory effects resulted in a promising candidate, compound 43, which demonstrated an IC50 value of 8.22 µM against PAR2. In next step, a PAR2 homology model was constructed using the crystal structure of the PAR1 as a template to explore the binding mode of the identified ligands. A molecular docking method was optimized by comparing the binding modes of a known PAR2 agonist GB110 and antagonist GB83, and applied to predict the binding mode of our hit compound 43. In-depth docking analyses revealed that the hydrophobic interaction with Phe2435.39 is crucial for PAR2 ligands to exert antagonistic activity. MD simulation results supported the predicted docking poses that PAR2 antagonist blocked a conformational rearrangement of Na+ allosteric site in contrast to PAR2 agonist that showed Na+ relocation upon GPCR activation. In conclusion, we identified new a PAR2 antagonist together with its binding mode, which provides useful insights for the design and development of PAR2 ligands.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Charge Transport in Carbon Nanotubes-Polymer Composite Photovoltaic Cells

PubMed Central

Ltaief, Adnen; Bouazizi, Abdelaziz; Davenas, Joel

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

Activation of PAR-2 elicits NO-dependent and CGRP-independent dilation of the dural artery.

PubMed

Bhatt, Deepak K; Ploug, Kenneth B; Ramachandran, Roshni; Olesen, Jes; Gupta, Saurabh

2010-06-01

The goal of this study was to determine the vascular effects of protease-activated receptor-2 (PAR-2) activation in the rat cranial vasculature. The role of PAR-2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR-2 in the neuro-vascular circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR-2 with calcitonin gene-related peptide (CGRP) and dural mast cells. We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR-2 activating peptides (PAR-2 APs; SLIGRL-NH(2), 2-Furoyl-LIGRLO-NH(2)) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme-linked immunosorbent assay. We also analyzed the presence of PAR-2 in different migraine relevant tissues by quantitative real-time PCR and Western blot analysis. PAR-2 APs and trypsin induced a dose-dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L-N(G)-Nitroarginine methyl ester, attenuated SLIGRL-NH(2) responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL-NH(2) responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL-NH(2) as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR-2 APs. mRNA and protein expression of PAR-2 were found throughout trigeminovasuclar axis. PAR-2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR-2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism.

Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

PubMed Central

Ando, Seijitsu; Otani, Hitomi; Yagi, Yasuhiro; Kawai, Kenzo; Araki, Hiromasa; Fukuhara, Shirou; Inagaki, Chiyoko

2007-01-01

Background Proteinase-activated receptors (PARs; PAR1–4) that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT) which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA) for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells). Results Stimulation of PAR with thrombin (1 U/ml) or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM) for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β). Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR) kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial-mesenchymal transition (EMT) as monitored by cell shapes, and epithelial or myofibroblast marker at least partly through EGFR transactivation via receptor-linked Src activation. PMID:17433115

Pharmacodynamics of levofloxacin against characterized ciprofloxacin-resistant Streptococcus pneumoniae.

PubMed

Lister, Philip D

2008-09-01

In a previous study, levofloxacin 750 mg eradicated 4 ciprofloxacin-resistant isolates of Streptococcus pneumoniae from an in vitro pharmacodynamic model (IVPM). However, quinolone resistance-determining region (QRDR) mutations were not detected among those isolates. This study further evaluates levofloxacin 500 mg and 750 mg against S pneumoniae strains with characterized QRDR mutations. Six isolates with levofloxacin minimum inhibitory concentrations (MICs) of 2 to 4 microg/mL were selected for this study. Strains 5401, 5409, and 5437 contained only parC mutations. Three additional strains contained 2 mutations each: strain 5429 (parC and parE ), strain 5442 (parC and gyrA), and strain 5445 (parC and gyrB). Logarithmic-phase cultures (approximately 1 x 10(7) CFU/mL) were inoculated into the peripheral compartment of the IVPM and exposed to peak free-drug concentrations achieved with levofloxacin 500 mg and 750 mg (PO) and ciprofloxacin 750 mg (PO). Elimination pharmacokinetics were simulated and changes in viable counts were measured over 30 h. Ciprofloxacin exhibited very little antibacterial activity against the 6 strains, while levofloxacin 750 mg rapidly killed and eradicated the 3 parC mutant strains and the dual parC/parE mutant strains. Although levofloxacin 500 mg initially decreased viable counts by 4.5 to 6 logs, inoculum regrowth was observed between 12 and 24 h for the 6 strains. Regrowth was not due to the selection of mutant subpopulations. The pharmacodynamics of both levofloxacin doses were substantially diminished against the 2 strains with dual mutations in both parC and gyrA/B. The rapid eradication of single parC and dual parC/parE mutants with levofloxacin 750 mg demonstrates that this dose may slow the emergence of resistance due to these mutations. The decreased efficacy of both levofloxacin doses against the double parC and gyrA/B mutants highlights the importance of preventing the development and spread of double mutants.

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration

PubMed Central

Williams, Julie C.; Lee, Rebecca D.; Doerschuk, Claire M.; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages. PMID:22175012

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration.

PubMed

Williams, Julie C; Lee, Rebecca D; Doerschuk, Claire M; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages.

PAR(2) and temporomandibular joint inflammation in the rat.

PubMed

Denadai-Souza, A; Cenac, N; Casatti, C A; Câmara, P R de Souza; Yshii, L M; Costa, S K P; Vergnolle, N; Muscará, M N

2010-10-01

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

PubMed Central

Wang, Shujie; Watanabe, Takashi; Matsuzawa, Kenji; Katsumi, Akira; Kakeno, Mai; Matsui, Toshinori; Ye, Feng; Sato, Kazuhide; Murase, Kiyoko; Sugiyama, Ikuko; Kimura, Kazushi; Mizoguchi, Akira; Ginsberg, Mark H.; Collard, John G.

2012-01-01

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration. PMID:23071154

Characterization of a point mutation in the parC gene of Mycoplasma bovirhinis associated with fluoroquinolone resistance.

PubMed

Hirose, K; Kawasaki, Y; Kotani, K; Abiko, K; Sato, H

2004-05-01

Quinolone-resistant (QR) mutants of Mycoplasma bovirhinis strain PG43 (type strain) were generated by stepwise selection in increasing concentrations of enrofloxacin (ENR). An alteration was found in the quinolone resistance-determining region (QRDR) of the parC gene coding for the ParC subunit of topoisomerase IV from these mutants, but not in the gyrA, gyrB, and parE gene coding for the GyrA and GyrB subunits of DNA gyrase and the ParE subunit of topoisomerase IV. Similarly, such an alteration in QRDR of parC was found in the field isolates of M. bovirhinis, which possessed various levels of QR. The substitution of leucine (Leu) by serine (Ser) at position 80 of QRDR of ParC was observed in both QR-mutants and QR-isolates. This is the first report of QR based on a point mutation of the parC gene in M. bovirhinis.

Police accident report forms: safety device coding and enacted laws.

PubMed

Brock, K; Lapidus, G

2008-12-01

Safety device coding on state police accident report (PAR) forms was compared with provisions in state traffic safety laws. PAR forms were obtained from all 50 states and the District of Columbia (states/DC). For seat belts, 22 states/DC had a primary seat belt enforcement law vs 50 with a PAR code. For car seats, all 51 states/DC had a law and a PAR code. For booster seats, 39 states/DC had a law vs nine with a PAR code. For motorcycle helmets, 21 states/DC had an all-age rider helmet law and another 26 a partial-age law vs 50 with a PAR code. For bicycle helmets, 21 states/DC had a partial-age rider helmet law vs 48 with a PAR code. Therefore gaps in the ability of states to fully record accident data reflective of existing state traffic safety laws are revealed. Revising the PAR forms in all states to include complete variables for safety devices should be an important priority, independent of the laws.

Differential roles of kallikrein-related peptidase 6 in malignant transformation and ΔNp63β-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma.

PubMed

Kaneko, Naoki; Kawano, Shintaro; Yasuda, Kaori; Hashiguchi, Yuma; Sakamoto, Taiki; Matsubara, Ryota; Goto, Yuichi; Jinno, Teppei; Maruse, Yasuyuki; Morioka, Masahiko; Hattori, Taichi; Tanaka, Shoichi; Tanaka, Hideaki; Kiyoshima, Tamotsu; Nakamura, Seiji

2017-12-01

We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ΔNp63β-overexpressing OSCC cells to identify genes associated with ΔNp63β-mediated EMT. Thereby, we focused on kallikrein-related peptidase (KLK) 6, most up-regulated following ΔNp63β-overexpression, that activates protease-activated receptors (PARs). In RT-PCR analyses, ΔNp63 was positively associated with KLK6 and PAR2 and negatively with PAR1 in OSCC cells. By ΔNp63 knockdown, KLK6 and PAR2 expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT-phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK was reduced, it was restored in the KLK6 knockdown OSCC cells treated with recombinant KLK6 proteins. Immunohistochemistry showed ΔNp63, KLK6, and PAR2 were more strongly expressed in the epithelial dysplasia and central region of OSCC than normal oral epithelium, whereas PAR1 expression was undetectable. Interestingly, at the invasive front of OSCC, ΔNp63, KLK6, and PAR2 were reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing KLK6 expression at the invasive front had more unfavourable prognosis. These results suggested differential roles of KLK6 in malignant transformation and EMT; high ΔNp63β expression up-regulates KLK6-PAR2 and down-regulates PAR1, inducing malignant transformation in oral epithelium with stimulating proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is down-regulated and PAR1 is up-regulated when ΔNp63β expression is decreased, leading to EMT with enhancing migration and invasion through ERK signal reduction at the invasive front. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Spatiotemporal characteristics of photosynthetically active radiation in understory of Korean pine and broadleaved mixed forest in Changbai Mountains].

PubMed

Yuan, Feng-Hui; Guan, De-Xin; Wu, Jia-Bing; Wang, An-Zhi; Shi, Ting-Ting; Zhang, Xiao-Jing

2008-02-01

Based on the data of three years successive automatic measurement with five horizontal quantum PAR sensors, this paper studied the spatiotemporal characteristics of photosynthetically active radiation (PAR) in the understory of Korean pine and broadleaved mixed forest in Changbai Mountains, in contrast with above-canopy PAR. It was found that the annual dynamics of above-canopy PAR showed two or more peaks, which was mainly affected by the weather conditions such as cloudy, foggy and rainy events. The annual dynamics of understory PAR followed the same trend of above-canopy PAR in non-growth season, but was steady and lower in numerical value in growth season. On clear days, larger differences were observed in the diurnal variation and frequency distribution of the understory PAR. As for the spatial variation of the understory PAR, the coefficient of variation (CV) was smaller in non-growth season (about 0.15) than in growth season (> 0.22), with the greatest in August. On the clear days in growth season, the understory PAR had a greater spatial variation when the solar elevation angle was between 38 degrees and 48 degrees (at 9:00-10:00 or 13:00-14:00).

Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes

PubMed Central

Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D’Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C.; Rastaldi, Maria Pia; Saleem, Moin A.; Mavilio, Domenico; Mikulak, Joanna

2015-01-01

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms’ tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur−/− mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID:26380915

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

PubMed

Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

2014-01-01

This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Role of thrombin signalling in platelets in haemostasis and thrombosis

NASA Astrophysics Data System (ADS)

Sambrano, Gilberto R.; Weiss, Ethan J.; Zheng, Yao-Wu; Huang, Wei; Coughlin, Shaun R.

2001-09-01

Platelets are critical in haemostasis and in arterial thrombosis, which causes heart attacks and other events triggered by abnormal clotting. The coagulation protease thrombin is a potent activator of platelets ex vivo. However, because thrombin also mediates fibrin deposition and because multiple agonists can trigger platelet activation, the relative importance of platelet activation by thrombin in haemostasis and thrombosis is unknown. Thrombin triggers cellular responses at least in part through protease-activated receptors (PARs). Mouse platelets express PAR3 and PAR4 (ref. 9). Here we show that platelets from PAR4-deficient mice failed to change shape, mobilize calcium, secrete ATP or aggregate in response to thrombin. This result demonstrates that PAR signalling is necessary for mouse platelet activation by thrombin and supports the model that mouse PAR3 (mPAR3) does not by itself mediate transmembrane signalling but instead acts as a cofactor for thrombin cleavage and activation of mPAR4 (ref. 10). Importantly, PAR4-deficient mice had markedly prolonged bleeding times and were protected in a model of arteriolar thrombosis. Thus platelet activation by thrombin is necessary for normal haemostasis and may be an important target in the treatment of thrombosis.

Offsets in fiber-coupled diode laser hygrometers caused by parasitic absorption effects and their prevention

NASA Astrophysics Data System (ADS)

Buchholz, B.; Ebert, V.

2014-07-01

Large systematic errors in absorption spectrometers (AS) can be caused by ‘parasitic’ optical absorption (parA) outside the measurement region. In particular, calibration-free direct tunable diode laser AS (dTDLAS) can take advantage of an effective parA-compensation to provide correct absolute values. However, parA also negatively affects calibrated AS in calibration frequency and stability. A common strategy to suppress parA in TDLAS systems is to fiber-couple the light source and even the detector. However, this can be a critical approach if the TDL spectrometer is validated/calibrated under laboratory conditions in ambient humidity and used afterwards in much drier and variable conditions, for example in aircrafts. This paper shows that, e.g., ‘hermetically sealed’ butterfly packages, despite fiber coupling, can possess fixed as well as variable parA sections. Two new methods for absolute parA-quantification in dTDLAS were developed, including a novel, fiber-coupled, parA-free I0-detector for permanent parA-monitoring. Their dependences on ambient humidity/pressure and temporal behavior were studied. For the example of a 1.4 µm dTDLAS hygrometer SEALDH-II with a commercial DFB-laser module and an extractive 1.5 m path cell, we quantified the parA-induced signal offsets and their dependence on cell pressure. The conversion of parA-uncertainty into H2O signal uncertainty was studied and an updated uncertainty budget including parA-uncertainty was derived. The studies showed that parA in commercial laser modules can cause substantial, systematic concentration offsets of ≈25 ppmv fixed and ≈100 ppmv variable offsets for one meter absorption path. Applying our parA-quantification techniques these offsets could be compensated by a factor of 20 to an overall offset uncertainty of 4.5 ppmv m-1. Finally, we developed an innovative, integrated, µ-pumped closed-loop air drying unit for the parA minimization and temporal stabilization in airborne laser hygrometers. This compact and light weight dryer eliminates the variable parA by ambient humidity in less than 120 min and is well suited for airborne applications as it fulfils all airborne operation and safety restrictions.

Neo-Positivist Intrusions, Post-Qualitative Challenges, and PAR's Generative Indeterminacies

ERIC Educational Resources Information Center

Miller, Janet L.

2017-01-01

Although committed to PAR's overarching aspirations, many advocates also have noted myriad complexities of engaging in PAR, where ambiguities and disarrays--all kinds of inconclusive evidence--can proliferate. Uncertainties especially can erupt if PAR education-focused projects are positioned, oxymoronically, as expected to produce "high…

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

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-1β 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. PMID:22731117

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

Determination of production biology of cladocera in a reservoir receiving hyperthermal effluents from a nuclear production reactor. [Par Pond

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

Vigerstad, T J

1980-01-01

The effects on zooplankton of residence in a cooling reservoir receiving hyperthermal effluents directly from a nuclear-production-reactor were studied. Rates of cladoceran population production were compared at two stations in the winter and summer of 1976 on Par Pond located on the Savannah River Plant, Aiken, SC. One station was located in an area of the reservoir directly receiving hyperthermal effluent (Station MAS) and the second was located about 4 km away in an area where surface temperatures were normal for reservoirs in the general geographical region (Station CAS). A non-parametric comparison between stations of standing stock and fecundity datamore » for Bosmina longirostris, taken for the egg ratio model, was used to observe potential hyperthermal effluent effects. There was a statistically higher incidence of deformed eggs in the Bosmina population at Station MAS in the summer. Bosmina standing stock underwent two large oscillations in the winter and three large oscillations in the summer at Station MAS compared with two in the winter and one in the summer at Station CAS. These results are consistent with almost all other Par Pond studies which have found the two stations to be essentially similar in spectra composition but with some statistically significant differences in various aspects of the biology of the species.« less

An annual cycle of phytoplankton biomass in the Arabian Sea, 1994 1995, as determined by moored optical sensors

NASA Astrophysics Data System (ADS)

Kinkade, C. S.; Marra, J.; Dickey, T. D.; Weller, R.

A surface-to-bottom mooring in the central Arabian Sea (15.5°N, 61.5°E) deployed from October 1994 to October 1995, included fluorometers, PAR irradiance sensors, Lu 683 sensors, and a spectral radiometer. An annual cycle of phytoplankton biomass was determined by transforming signals from the optical sensors into chlorophyll a (chl a). Half-yearly phytoplankton blooms with water-column stratification were observed near the end of each monsoon, as well as biomass increases in response to mesoscale flow features. During the Northeast Monsoon, the integrate water-column chl a rose from 15 to 25 mg m -2, while during the Southwest Monsoon, chl a increased from 15 to a maximum >40 mg m -2. We present an empirical relationship between the ratio of downwelling Ed443/ Ed550 (blue to green wavelength ratio) and integral euphotic zone chl a determined by moored fluorometers ( r2=0.73). There is a more significant relationship between Ed443/ Ed550 measured at one depth in the water column (65 m) and the average vertical attenuation coefficient for PAR (K PAR) between 0 and 65 m ( r2=0.845). Because biofouling was a significant problem at times, data return from any one sensor was incomplete. However, optical sensor/data intercomparison helped fill gaps while permitting investigation of the temporal variability in observed phytoplankton biomass.

Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

PubMed Central

Yang, Lily; Peng, Xiang-Hong; Wang, Y. Andrew; Wang, Xiaoxia; Cao, Zehong; Ni, Chunchun; Karna, Prasanthi; Zhang, Xinjian; Wood, William C.; Gao, Xiaohu; Nie, Shuming; Mao, Hui

2009-01-01

Purpose Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. Experimental design The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. Results ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Conclusions Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer. PMID:19584158

Assessment of satellite derived diffuse attenuation coefficients ...

EPA Pesticide Factsheets

Optical data collected in coastal waters off South Florida and in the Caribbean Sea between January 2009 and December 2010 were used to evaluate products derived with three bio-optical inversion algorithms applied to MOIDS/Aqua, MODIS/Terra, and SeaWiFS satellite observations. The products included the diffuse attenuation coefficient at 490 nm (Kd_490) and for the visible range (Kd_PAR), and euphotic depth (Zeu, corresponding to 1% of the surface incident photosynthetically available radiation or PAR). Above-water hyperspectral reflectance data collected over optically shallow waters of the Florida Keys between June 1997 and August 2011 were used to help understand algorithm performance over optically shallow waters. The in situ data covered a variety of water types in South Florida and the Caribbean Sea, ranging from deep clear waters, turbid coastal waters, and optically shallow waters (Kd_490 range of ~0.03 – 1.29m-1). An algorithm based on Inherent Optical Properties (IOPs) showed the best performance (RMSD < 13% and R2 ~1.0 for MODIS/Aqua and SeaWiFS). Two algorithms based on empirical regressions performed well for offshore clear waters, but underestimated Kd_490 and Kd_PAR in coastal waters due to high turbidity or shallow bottom contamination. Similar results were obtained when only in situ data were used to evaluate algorithm performance. The excellent agreement between satellite-derived remote sensing reflectance (Rrs) and in situ Rrs suggested that

PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis.

PubMed

Matěj, Radoslav; Smětáková, Magdalena; Vašáková, Martina; Nováková, Jana; Sterclová, Martina; Kukal, Jaromír; Olejár, Tomáš

2014-08-01

Sarcoidosis (SARC) and extrinsic allergic alveolitis (EAA) share certain markers, making a differential diagnosis difficult even with histopathological investigation. In lung tissue, proteinase-activated receptor-2 (PAR-2) is primarily investigated with regard to epithelial and inflammatory perspectives. Varying levels of certain chemokines can be a useful tool for distinguishing EAA and SARC. Thus, in the present study, differences in the levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin-4 receptor (IL-4R) and PAR-2 in bronchoalveolar lavage fluid (BALF) were compared, using an ELISA method, between 14 patients with EAA and six patients with SARC. Statistically significant higher levels of IL-4R, PAR-2 and the PAR-2/TGF-β1 and PAR-2/TNF-α ratios were observed in EAA patients as compared with SARC patients. Furthermore, the ratios of TNF-α/total protein, TGF-β1/PAR-2 and TNF-α/PAR-2 were significantly lower in EAA patients than in SARC patients. The results indicated a higher detection of PAR-2 in EAA samples in association with TNF-α and TGF-β levels. As EAA and PAR-2 in parallel belong to the Th2-mediated pathway, the results significantly indicated an association between this receptor and etiology. In addition, the results indicated that SARC is predominantly a granulomatous inflammatory disease, thus, higher levels of TNF-α are observed. Therefore, the detection of PAR-2 and investigated chemokines in BALF may serve as a useful tool in the differential diagnosis between EAA and SARC.

UV/PAR radiations and DOM properties in surface coastal waters of the Canadian shelf of the Beaufort Sea during summer 2009

NASA Astrophysics Data System (ADS)

Para, J.; Charrière, B.; Matsuoka, A.; Miller, W. L.; Rontani, J. F.; Sempéré, R.

2012-11-01

Water masses from the Beaufort Sea in the Arctic Ocean were evaluated for dissolved organic carbon (DOC), and optical characteristics including UV and PAR diffuse attenuation (Kd), and chromophoric and fluorescent dissolved organic matter (CDOM and FDOM) as part of the MALINA field campaign (30 July to 27 August). Even with relatively low mean daily solar radiation incident on the sea surface (0.12 ± 0.03, 8.46 ± 1.64 and 18.09 ± 4.20 kJ m-2 for UV-B (305 nm), UV-A (380 nm) and PAR, respectively), we report significant light penetration with 10% irradiance depths (Z10% (λ)) reaching 9.5 m for 340 nm (UV-A) radiation in the Eastern sector and 4.5 m in the Mackenzie River influenced area (Western sector). Spectral absorption coefficients (aCDOM (350 nm) (m-1)) were significantly correlated to both diffuse attenuation coefficients (Kd) in the UV-A and UV-B and to DOC concentrations. This indicates CDOM as the dominant attenuator of UV solar radiation and suggests its use as an optical proxy for DOC concentrations in this region. Extrapolating CDOM to DOC relationships, we estimate that ~ 16% of the DOC in the Mackenzie River does not absorb radiation at 350 nm. DOC and CDOM discharges by the Mackenzie River during the MALINA Cruise are estimated as ~ 0.22 TgC and 0.18 TgC, respectively. Three dissolved fluorescent components (C1-C3) were identified by fluorescence Excitation/Emission Matrix Spectroscopy (EEMS) and PARAFAC analysis. Our results showed an in-situ biological component (C1) that co-dominated with a terrestrial humic-like component (C2) in the Mackenzie Delta sector, whereas the protein-like (C3) component dominated in the saltiest waters of the North East sector.

Paraho environmental data. Part I. Process characterization. Par II. Air quality. Part III. Water quality

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

Heistand, R.N.; Atwood, R.A.; Richardson, K.L.

1980-06-01

From 1973 to 1978, Development Engineering, Inc. (DEI), a subsidiary of Paraho Development Corporation, demostrated the Paraho technology for surface oil shale retorting at Anvil Points, Colorado. A considerable amount of environmentally-related research was also conducted. This body of data represents the most comprehensive environmental data base relating to surface retorting that is currently available. In order to make this information available, the DOE Office of Environment has undertaken to compile, assemble, and publish this environmental data. The compilation has been prepared by DEI. This report includes the process characterization, air quality, and water quality categories.

Skill Assessment of a Spectral Ocean-Atmosphere Radiative Model

NASA Technical Reports Server (NTRS)

Gregg, Watson, W.; Casey, Nancy W.

2009-01-01

Ocean phytoplankton, detrital material, and water absorb and scatter light spectrally. The Ocean- Atmosphere Spectral Irradiance Model (OASIM) is intended to provide surface irradiance over the oceans with sufficient spectral resolution to support ocean ecology, biogeochemistry, and heat exchange investigations, and of sufficient duration to support inter-annual and decadal investigations. OASIM total surface irradiance (integrated 200 nm to 4 microns) was compared to in situ data and three publicly available global data products at monthly 1-degree resolution. OASIM spectrally-integrated surface irradiance had root mean square (RMS) difference= 20.1 W/sq m (about 11%), bias=1.6 W/sq m (about 0.8%), regression slope= 1.01 and correlation coefficient= 0.89, when compared to 2322 in situ observations. OASIM had the lowest bias of any of the global data products evaluated (ISCCP-FD, NCEP, and ISLSCP 11), and the best slope (nearest to unity). It had the second best RMS, and the third best correlation coefficient. OASIM total surface irradiance compared well with ISCCP-FD (RMS= 20.7 W/sq m; bias=-11.4 W/sq m, r=0.98) and ISLSCP II (RMS =25.2 W/sq m; bias= -13.8 W/sq m; r=0.97), but less well with NCEP (RMS =43.0 W/sq m ;bias=-22.6 W/sq m; x=0.91). Comparisons of OASIM photosynthetically available radiation (PAR) with PAR derived from SeaWiFS showed low bias (-1.8 mol photons /sq m/d, or about 5%), RMS (4.25 mol photons /sq m/d ' or about 12%), near unity slope (1.03) and high correlation coefficient (0.97). Coupled with previous estimates of clear sky spectral irradiance in OASIM (6.6% RMS at 1 nm resolution), these results suggest that OASIM provides reasonable estimates of surface broadband and spectral irradiance in the oceans, and can support studies on ocean ecosystems, carbon cycling, and heat exchange.

Modeling post-wildfire hydrological processes with ParFlow

NASA Astrophysics Data System (ADS)

Escobar, I. S.; Lopez, S. R.; Kinoshita, A. M.

2017-12-01

Wildfires alter the natural processes within a watershed, such as surface runoff, evapotranspiration rates, and subsurface water storage. Post-fire hydrologic models are typically one-dimensional, empirically-based models or two-dimensional, conceptually-based models with lumped parameter distributions. These models are useful for modeling and predictions at the watershed outlet; however, do not provide detailed, distributed hydrologic processes at the point scale within the watershed. This research uses ParFlow, a three-dimensional, distributed hydrologic model to simulate post-fire hydrologic processes by representing the spatial and temporal variability of soil burn severity (via hydrophobicity) and vegetation recovery. Using this approach, we are able to evaluate the change in post-fire water components (surface flow, lateral flow, baseflow, and evapotranspiration). This work builds upon previous field and remote sensing analysis conducted for the 2003 Old Fire Burn in Devil Canyon, located in southern California (USA). This model is initially developed for a hillslope defined by a 500 m by 1000 m lateral extent. The subsurface reaches 12.4 m and is assigned a variable cell thickness to explicitly consider soil burn severity throughout the stages of recovery and vegetation regrowth. We consider four slope and eight hydrophobic layer configurations. Evapotranspiration is used as a proxy for vegetation regrowth and is represented by the satellite-based Simplified Surface Energy Balance (SSEBOP) product. The pre- and post-fire surface runoff, subsurface storage, and surface storage interactions are evaluated at the point scale. Results will be used as a basis for developing and fine-tuning a watershed-scale model. Long-term simulations will advance our understanding of post-fire hydrological partitioning between water balance components and the spatial variability of watershed processes, providing improved guidance for post-fire watershed management. In reference to the presenter, Isabel Escobar: Research is funded by the NASA-DIRECT STEM Program. Travel expenses for this presentation is funded by CSU-LSAMP. CSU-LSAMP is supported by the National Science Foundation under Grant # HRD-1302873 and the CSU Office of Chancellor.

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

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…

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.

Protease Activated Receptor-2 Contributes to Heart Failure

PubMed Central

Antoniak, Silvio; Sparkenbaugh, Erica M.; Tencati, Michael; Rojas, Mauricio; Mackman, Nigel; Pawlinski, Rafal

2013-01-01

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. PMID:24312345

Matrix metalloproteases and PAR1 activation

PubMed Central

Austin, Karyn M.; Covic, Lidija

2013-01-01

Cardiovascular diseases, including atherothrombosis, are the leading cause of morbidity and mortality in the United States, Europe, and the developed world. Matrix metalloproteases (MMPs) have recently emerged as important mediators of platelet and endothelial function, and atherothrombotic disease. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that is classically activated through cleavage of the N-terminal exodomain by the serine protease thrombin. Most recently, 2 MMPs have been discovered to have agonist activity for PAR1. Unexpectedly, MMP-1 and MMP-13 cleave the N-terminal exodomain of PAR1 at noncanonical sites, which result in distinct tethered ligands that activate G-protein signaling pathways. PAR1 exhibits metalloprotease-specific signaling patterns, known as biased agonism, that produce distinct functional outputs by the cell. Here we contrast the mechanisms of canonical (thrombin) and noncanonical (MMP) PAR1 activation, the contribution of MMP-PAR1 signaling to diseases of the vasculature, and the therapeutic potential of inhibiting MMP-PAR1 signaling with MMP inhibitors, including atherothrombotic disease, in-stent restenosis, heart failure, and sepsis. PMID:23086754

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

The expression and activation of protease-activated receptor-2 correlate with skin color.

PubMed

Babiarz-Magee, Laura; Chen, Nannan; Seiberg, Miri; Lin, Connie B

2004-06-01

Skin color results from the production and distribution of melanin in the epidermis. The protease-activated receptor-2 (PAR-2), expressed on keratinocytes but not on melanocytes, is involved in melanosome uptake via phagocytosis, and modulation of PAR-2 activation affects skin color. The pattern of melanosome distribution within the epidermis is skin color-dependent. In vitro, this distribution pattern is regulated by the ethnic origin of the keratinocytes, not the melanocytes. Therefore, we hypothesized that PAR-2 may play a role in the modulation of pigmentation in a skin type-dependent manner. We examined the expression of PAR-2 and its activator, trypsin, in human skins with different pigmentary levels. Here we show that PAR-2 and trypsin are expressed in higher levels, and are differentially localized in highly pigmented, relative to lightly pigmented skins. Moreover, highly pigmented skins exhibit an increase in PAR-2-specific protease cleavage ability. Microsphere phagocytosis was more efficient in keratinocytes from highly pigmented skins, and PAR-2 induced phagocytosis resulted in more efficient microsphere ingestion and more compacted microsphere organization in dark skin-derived keratinocytes. These results demonstrate that PAR-2 expression and activity correlate with skin color, suggesting the involvement of PAR-2 in ethnic skin color phenotypes.

Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes

PubMed Central

Madhusudhan, Thati; Wang, Hongjie; Straub, Beate K.; Gröne, Elisabeth; Zhou, Qianxing; Shahzad, Khurrum; Müller-Krebs, Sandra; Schwenger, Vedat; Gerlitz, Bruce; Grinnell, Brian W.; Griffin, John H.; Reiser, Jochen; Gröne, Hermann-Josef; Esmon, Charles T.; Nawroth, Peter P.

2012-01-01

The cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a protease-activated receptor-1 (PAR-1) and endothelial protein C receptor-dependent mechanism. Conversely, the signaling mechanism through which aPC protects podocytes remains unknown. While exploring the latter, we identified a novel aPC/PAR-dependent cytoprotective signaling mechanism. In podocytes, aPC inhibits apoptosis through proteolytic activation of PAR-3 independent of endothelial protein C receptor. PAR-3 is not signaling competent itself as it requires aPCinduced heterodimerization with PAR-2 (human podocytes) or PAR-1 (mouse podocytes). This cytoprotective signaling mechanism depends on caveolin-1 dephosphorylation. In vivo aPC protects against lipopolysaccharide-induced podocyte injury and proteinuria. Genetic deletion of PAR-3 impairs the nephroprotective effect of aPC, demonstrating the crucial role of PAR-3 for aPC-dependent podocyte protection. This novel, aPC-mediated interaction of PARs demonstrates the plasticity and cell-specificity of cytoprotective aPC signaling. The evidence of specific, dynamic signaling complexes underlying aPC-mediated cytoprotection may allow the design of cell type specific targeted therapies. PMID:22117049

Par Pond vegetation status Summer 1995 -- Summary

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

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 tomore » 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.« less

Flow cytometry analysis reveals different activation profiles of thrombin- or TRAP-stimulated platelets in db/db mice. The regulatory role of PAR-3.

PubMed

Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Przygodzki, Tomasz; Watala, Cezary

2017-06-01

Recent studies have shown that it may be the concentration of thrombin, which is discriminative in determining of the mechanism of platelet activation via protease activated receptors (PARs). Whether the observed phenomenon of differentiated responses of mouse platelets to various thrombin concentrations in non-diabetic db/+ and diabetic db/db mice depends upon the concerted action of various PARs, remains to be established. We found elevated reactivity of platelets, as well as the enhanced PAR-3 expression in response to both the used concentrations of AYPGKF in db/db mice, as compared to db/+ heterozygotes. At low concentration of thrombin platelets from diabetic mice demonstrated hyperreactivity, reflected by higher expression of PAR-3. For higher thrombin concentration, blood platelets from db/db mice appeared hyporeactive, compared to db/+ animals, while no significant differences in PAR-3 expression were observed between diabetic and non-diabetic mice. The novel and previously unreported finding resulting from our study is that the increased expression of PAR-3 in response to either TRAP for PAR-4 or low thrombin (when PAR-4 is not the efficient thrombin receptor) may be one of the key events contributing to higher reactivity of platelets in db/db mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea.

PubMed

Niu, Yawen; Zhao, Guiqiu; Li, Cui; Lin, Jing; Jiang, Nan; Che, Chengye; Zhang, Jie; Xu, Qiang

2018-01-01

To determine the role of protease-activated receptor-2 (PAR-2) in cornea infected by Aspergillus fumigatus. PAR-2 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was documented by clinical score and photographs with a slit lamp. PCR, Western blot, and ELISA tested expression of PAR-2, IL-1β, TNF-α, IFN-γ, MIP-2, and p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and immunofluorescent staining. PAR-2 expression was significantly elevated by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY-NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and proinflammatory cytokine expression compared with infected control. In PMNs, PAR-2 expression was also significantly increased by A. fumigatus, which was significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited proinflammatory cytokine protein expression, as compared with that in infected control cells, which may be modified by p-ERK1/2. These data provide evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN infiltration, and proinflammatory cytokine expression through PAR-2, which may be modified by p-ERK1/2.

Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis

PubMed Central

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

2015-01-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease that remains refractory to therapy. Despite increasing evidence that protease-activated receptor 2 (PAR-2) contributes to fibrosis, its importance in pulmonary fibrosis is under debate. We addressed whether PAR-2 deficiency persistently reduces bleomycin-induced pulmonary fibrosis or merely delays disease progression and whether pharmacological PAR-2 inhibition limits experimental pulmonary fibrosis. Bleomycin was instilled intranasally into wild-type or PAR-2–deficient mice in the presence/absence of a specific PAR-2 antagonist (P2pal-18S). Pulmonary fibrosis was consistently reduced in PAR-2–deficient mice throughout the fibrotic phase, as evident from reduced Ashcroft scores (29%) and hydroxyproline levels (26%) at d 28. Moreover, P2pal-18S inhibited PAR-2–induced profibrotic responses in both murine and primary human pulmonary fibroblasts (p < 0.05). Once daily treatment with P2pal-18S reduced the severity and extent of fibrotic lesions in lungs of bleomycin-treated wild-type mice but did not further reduce fibrosis in PAR-2–deficient mice. Importantly, P2pal-18S treatment starting even 7 d after the onset of fibrosis limits pulmonary fibrosis as effectively as when treatment was started together with bleomycin instillation. Overall, PAR-2 contributes to the progression of pulmonary fibrosis, and targeting PAR-2 may be a promising therapeutic strategy for treating pulmonary fibrosis. PMID:26147947

Novel role of prostate apoptosis response-4 tumor suppressor in B-cell chronic lymphocytic leukemia.

PubMed

McKenna, Mary K; Noothi, Sunil K; Alhakeem, Sara S; Oben, Karine Z; Greene, Joseph T; Mani, Rajeswaran; Perry, Kathryn L; Collard, James P; Rivas, Jacqueline R; Hildebrandt, Gerhard; Fleischman, Roger; Durbin, Eric B; Byrd, John C; Wang, Chi; Muthusamy, Natarajan; Rangnekar, Vivek M; Bondada, Subbarao

2018-04-25

Prostate apoptosis response-4 (Par-4), a pro-apoptotic tumor suppressor protein, is down regulated in many cancers including renal cell carcinoma, glioblastoma, endometrial and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from the Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1 to S cell cycle transition. Lack of Par-4 also increased the expression of p21 and delayed CLL growth in Eμ-Tcl1 mice. Par-4 expression in CLL cells required constitutively active B-cell receptor (BCR) signaling, as inhibition of BCR signaling with FDA approved drugs caused a decrease in Par-4 mRNA and protein, and an increase in apoptosis. In particular, activities of Lyn, a Src family kinase, spleen tyrosine kinase and Bruton's tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling. Together, these results suggest that Par-4 may play a novel pro-growth rather than pro-apoptotic role in CLL and could be targeted to enhance the therapeutic effects of BCR signaling inhibitors. Copyright © 2018 American Society of Hematology.

Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis.

PubMed

Andrabi, Shaida A; Umanah, George K E; Chang, Calvin; Stevens, Daniel A; Karuppagounder, Senthilkumar S; Gagné, Jean-Philippe; Poirier, Guy G; Dawson, Valina L; Dawson, Ted M

2014-07-15

Excessive poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation kills cells via a cell-death process designated "parthanatos" in which PAR induces the mitochondrial release and nuclear translocation of apoptosis-inducing factor to initiate chromatinolysis and cell death. Accompanying the formation of PAR are the reduction of cellular NAD(+) and energetic collapse, which have been thought to be caused by the consumption of cellular NAD(+) by PARP-1. Here we show that the bioenergetic collapse following PARP-1 activation is not dependent on NAD(+) depletion. Instead PARP-1 activation initiates glycolytic defects via PAR-dependent inhibition of hexokinase, which precedes the NAD(+) depletion in N-methyl-N-nitroso-N-nitroguanidine (MNNG)-treated cortical neurons. Mitochondrial defects are observed shortly after PARP-1 activation and are mediated largely through defective glycolysis, because supplementation of the mitochondrial substrates pyruvate and glutamine reverse the PARP-1-mediated mitochondrial dysfunction. Depleting neurons of NAD(+) with FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, does not alter glycolysis or mitochondrial function. Hexokinase, the first regulatory enzyme to initiate glycolysis by converting glucose to glucose-6-phosphate, contains a strong PAR-binding motif. PAR binds to hexokinase and inhibits hexokinase activity in MNNG-treated cortical neurons. Preventing PAR formation with PAR glycohydrolase prevents the PAR-dependent inhibition of hexokinase. These results indicate that bioenergetic collapse induced by overactivation of PARP-1 is caused by PAR-dependent inhibition of glycolysis through inhibition of hexokinase.

Low and moderate photosynthetically active radiation affects the flavonol glycosides and hydroxycinnamic acid derivatives in kale (Brassica oleracea var. sabellica) dependent on two low temperatures.

PubMed

Neugart, Susanne; Fiol, Michaela; Schreiner, Monika; Rohn, Sascha; Zrenner, Rita; Kroh, Lothar W; Krumbein, Angelika

2013-11-01

Kale (Brassica oleracea var. sabellica) contains a large number of naturally occurring structurally different non-acylated and acylated flavonol glycosides as well as hydroxycinnamic acid derivatives. The objective of this study was to determine the effect of low and moderate photosynthetic active radiation (PAR) and how these levels interact with low temperature in these phenolic compounds. Juvenile kale plants were treated with PAR levels from 200 to 800 μmol m(-2) s(-1) at 5 and 10 °C under defined conditions in climate chambers. Of the investigated 20 compounds, 11 and 17 compounds were influenced by PAR and temperature, respectively. In addition, an interaction between PAR and temperature was found for eight compounds. The response of the phenolic compounds to PAR was structure-dependent. While quercetin triglycosides increased with higher PAR at 5 and 10 °C, the kaempferol triglycosides exhibited the highest concentrations at 400 μmol m(-2) s(-1). In contrast, kaempferol diglycosides exhibited the highest concentrations at increased PAR levels of 600 and 800 μmol m(-2) s(-1) at 10 °C. However, key genes of flavonol biosynthesis were influenced by temperature but remained unaffected by PAR. Furthermore, there was no interaction between the PAR level and the low temperature in the response of hydroxycinnamic acid derivatives in kale with the exception of caffeoylquinic acid, which decreased with higher PAR levels of 600 and 800 μmol m(-2) s(-1) and at a lower temperature. In conclusion, PAR and its interaction with temperature could be a suitable tool for modifying the profile of phenolic compounds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Trypsin impaired epithelial barrier function and induced IL-8 secretion through basolateral PAR-2: a lesson from a stratified squamous epithelial model.

PubMed

Shan, Jing; Oshima, Tadayuki; Chen, Xin; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

2012-11-15

Immune-mediated injury by the protease-activated receptor-2-interleukin-8 (PAR-2-IL8) pathway may underlie the development of gastroesophageal reflux disease (GERD). However, the localization of PAR-2 and the mechanism of PAR-2 activation remain unclear. This study aimed to address these questions on an esophageal stratified squamous epithelial model and in the human esophageal mucosa of GERD patients. Normal human esophageal epithelial cells were cultured with the air-liquid interface system to establish the model. SLIGKV-NH2 (PAR-2 synthetic agonist), trypsin (PAR-2 natural activator), and weak acid (pH 4, 5, and 6) were added to either the apical or basolateral compartment to evaluate their effects on transepithelial electrical resistance (TEER) and IL-8 production. PAR-2 localization was examined both in the cell model and biopsies from GERD patients by immunohistochemistry. Apical trypsin stimulation induced IL-8 accompanied by decreased TEER in vitro, whereas the effective concentration from the basolateral side was 10 times lower. SLIGKV-NH2 from basolateral but not apical stimulation induced IL-8 production. Apical weak acid stimulation did not influence TEER or IL-8 production. Immunohistochemistry showed intense reactivity of PAR-2 in the basal and suprabasal layers after stimulation with trypsin. A similar PAR-2 reactivity that was mainly located at the basal and suprabasal layers was detected in GERD patients. In conclusion, the activation of the PAR-2-IL-8 pathway probably occurred at the basal and suprabasal layers, while the esophageal epithelial barrier may influence the activation of PAR-2. Under proton pump inhibitor therapy, refluxed trypsin may remain active and be a potential agent in the pathogenesis of refractory GERD.

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

PubMed

Amiable, Nathalie; Tat, Steeve Kwan; Lajeunesse, Daniel; Duval, Nicolas; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Boileau, Christelle

2009-06-01

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively. PAR-2 modulation was investigated in OA subchondral bone osteoblasts treated with IL-1 beta (100 pg/ml), TNF-alpha (5 ng/ml), TGF-beta1 (10 ng/ml), PGE(2) (500 nM), IL-6 (10 ng/ml) and IL-17 (10 ng/ml). Membranous RANKL protein was assessed by flow cytometry, and OPG, MMP-1, MMP-9, MMP-13, IL-6 and intracellular signalling pathways by specific ELISAs. Bone resorptive activity was measured by using a co-culture model of human PBMC and OA subchondral bone osteoblasts. PAR-2 expression and production (p<0.05) were markedly increased when human OA subchondral bone osteoblasts were compared to normal. On OA osteoblasts, PAR-2 production was significantly increased by IL-1 beta, TNF-alpha and PGE(2). Activation of PAR-2 with a specific agonist, SLIGKV-NH(2), induced a significant up-regulation of MMP-1, MMP-9, IL-6, and membranous RANKL, but had no effect on MMP-13 or OPG production. Interestingly, bone resorptive activity was also significantly enhanced following PAR-2 activation. The PAR-2 effect was mediated by activation of the MAP kinases Erk1/2 and JNK. This study is the first to demonstrate that PAR-2 activation plays a role in OA subchondral bone resorption via an up-regulation of major bone remodelling factors. These results shed new light on the potential of PAR-2 as a therapeutic target in OA.

Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis.

PubMed

Chang, Li-Hsun; Pan, Shiow-Lin; Lai, Chin-Yu; Tsai, An-Chi; Teng, Che-Ming

2013-08-01

Tissue factor initiates the process of thrombosis and activates cell signaling through protease-activated receptor-2 (PAR-2). The aim of this study was to investigate the pathological role of PAR-2 signaling in pancreatic cancer. We first demonstrated that activated PAR-2 up-regulated the protein expression of both hypoxia-inducible factor-1α (HIF-1α) and HIF-2α, resulting in enhanced transcription of transforming growth factor-α (TGF-α). Down-regulation of HIFs-α by siRNA or YC-1, an HIF inhibitor, resulted in depleted levels of TGF-α protein. Furthermore, PAR-2, through integrin-linked kinase (ILK) signaling, including the p-AKT, promoted HIF protein expression. Diminishing ILK by siRNA decreased the levels of PAR-2-induced p-AKT, HIFs-α, and TGF-α; our results suggest that ILK is involved in the PAR-2-mediated TGF-α via an HIF-α-dependent pathway. Furthermore, the culture medium from PAR-2-treated pancreatic cancer cells enhanced human umbilical vein endothelial cell proliferation and tube formation, which was blocked by the MEK inhibitor, PD98059. We also found that activated PAR-2 enhanced tumor angiogenesis through the release of vascular endothelial growth factor-A (VEGF-A) from cancer cells, independent of the ILK/HIFs-α pathways. Consistent with microarray analysis, activated PAR-2 induced TGF-A and VEGF-A gene expression. In conclusion, the activation of PAR-2 signaling induced human pancreatic cancer progression through the induction of TGF-α expression by ILK/HIFs-α, as well as through MEK/VEGF-A-mediated angiogenesis, and it plays a role in the interaction between cancer progression and cancer-related thrombosis. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Effects of three types of oil dispersants on biodegradation of dispersed crude oil in water surrounding two Persian gulf provinces.

PubMed

Zolfaghari-Baghbaderani, Azadeh; Emtyazjoo, Mozhgan; Poursafa, Parinaz; Mehrabian, Sedigheh; Bijani, Samira; Farkhani, Daryoush; Mirmoghtadaee, Parisa

2012-01-01

To determine the most effective and biodegradable dispersant of spilled oil in water surrounding two Persian Gulf provinces. This study compared the effects of three dispersants, Pars 1, Pars 2, and Gamlen OD4000 on removal of oil in two Persian Gulf provinces' water. Overall, 16 stations were selected. Using the Well method, the growth rate of isolated bacteria and fungi was identified. To specify the growth rate of microorganisms and their usage of oil in the presence of the above-mentioned dispersants, as exclusive sources of carbon, the bacteria were grown in culture medium for 28 days at 120 rpm, 30°C, and their optical density was measured by spectrophotometry. Then, we tested biological oxygen demand (BOD) and chemical oxygen demand (COD) in microorganisms. The highest growth rate was documented for the growth of microorganisms on either Pars 1 or Pars 2 dispersants or their mixtures with oil. However, the culture having microorganisms grown on Pars 1 had higher BOD and COD than the other two dispersants (9200 and 16800 versus 500 and 960, P < 0.05). Mixture of oil and Pars 2 as well as oil and Pars 1 dispersants showed the highest BODs and CODs, respectively. In the Bahregan province, microorganisms grown on Pars 2 had maximum amount of BOD and COD in comparison with Pars 1 and Gamlen dispersants (7100 and 15200 versus 6000 and 10560, P < 0.05). Pars 1 and Pars 2 were the most effective dispersants with highest degradability comparing Gamlen. In each region, the most suitable compound for removing oil spill from offshores with least secondary contamination should be investigated.

Protease-Activated Receptor 4 Induces Bladder Pain through High Mobility Group Box-1

PubMed Central

Kouzoukas, Dimitrios E.; Ma, Fei; Meyer-Siegler, Katherine L.; Westlund, Karin N.; Hunt, David E.; Vera, Pedro L.

2016-01-01

Pain is the significant presenting symptom in Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS). Activation of urothelial protease activated receptor 4 (PAR4) causes pain through release of urothelial macrophage migration inhibitory factor (MIF). High Mobility Group Box-1 (HMGB1), a chromatin-binding protein, mediates bladder pain (but not inflammation) in an experimental model (cyclophosphamide) of cystitis. To determine if PAR4-induced bladder hypersensitivity depends on HMGB1 downstream, we tested whether: 1) bladder PAR4 stimulation affected urothelial HMGB1 release; 2) blocking MIF inhibited urothelial HMGB1 release; and 3) blocking HMGB1 prevented PAR4-induced bladder hypersensitivity. HMGB1 release was examined in immortalized human urothelial cultures (UROtsa) exposed to PAR4-activating peptide (PAR4-AP; 100 μM; 2 hours) or scrambled control peptide. Female C57BL/6 mice, pretreated with a HMGB1 inhibitor (glycyrrhizin: 50 mg/kg; ip) or vehicle, received intravesical PAR4-AP or a control peptide (100 μM; 1 hour) to determine 1) HMGB1 levels at 1 hour in the intravesical fluid (released HMGB1) and urothelium, and 2) abdominal hypersensitivity to von Frey filament stimulation 24 hours later. We also tested mice pretreated with a MIF blocker (ISO-1: 20 mg/kg; ip) to determine whether MIF mediated PAR4-induced urothelial HMGB1 release. PAR4-AP triggered HMGB1 release from human (in vitro) and mice (in vivo) urothelial cells. Intravesical PAR4 activation elicited abdominal hypersensitivity in mice that was prevented by blocking HMGB1. MIF inhibition prevented PAR4-mediated HMGB1 release from mouse urothelium. Urothelial MIF and HGMB1 represent novel targets for therapeutic intervention in bladder pain conditions. PMID:27010488

Population attributable risks of patient, child and organizational risk factors for perinatal mortality in hospital births.

PubMed

Poeran, Jashvant; Borsboom, Gerard J J M; de Graaf, Johanna P; Birnie, Erwin; Steegers, Eric A P; Bonsel, Gouke J

2015-04-01

The main objective of this study was to estimate the contributing role of maternal, child, and organizational risk factors in perinatal mortality by calculating their population attributable risks (PAR). The primary dataset comprised 1,020,749 singleton hospital births from ≥22 weeks' gestation (The Netherlands Perinatal Registry 2000-2008). PARs for single and grouped risk factors were estimated in four stages: (1) creating a duplicate dataset for each PAR analysis in which risk factors of interest were set to the most favorable value (e.g., all women assigned 'Western' for PAR calculation of ethnicity); (2) in the primary dataset an elaborate multilevel logistic regression model was fitted from which (3) the obtained coefficients were used to predict perinatal mortality in each duplicate dataset; (4) PARs were then estimated as the proportional change of predicted- compared to observed perinatal mortality. Additionally, PARs for grouped risk factors were estimated by using sequential values in two orders: after PAR estimation of grouped maternal risk factors, the resulting PARs for grouped child, and grouped organizational factors were estimated, and vice versa. The combined PAR of maternal, child and organizational factors is 94.4 %, i.e., when all factors are set to the most favorable value perinatal mortality is expected to be reduced with 94.4 %. Depending on the order of analysis, the PAR of maternal risk factors varies from 1.4 to 13.1 %, and for child- and organizational factors 58.7-74.0 and 7.3-34.3 %, respectively. In conclusion, the PAR of maternal-, child- and organizational factors combined is 94.4 %. Optimization of organizational factors may achieve a 34.3 % decrease in perinatal mortality.

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

PubMed Central

2012-01-01

Background The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. Methods A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. Results The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. Conclusions MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality. PMID:22321049

Effects of Three Types of Oil Dispersants on Biodegradation of Dispersed Crude Oil in Water Surrounding Two Persian Gulf Provinces

PubMed Central

Zolfaghari-Baghbaderani, Azadeh; Emtyazjoo, Mozhgan; Poursafa, Parinaz; Mehrabian, Sedigheh; Bijani, Samira; Farkhani, Daryoush; Mirmoghtadaee, Parisa

2012-01-01

Objective. To determine the most effective and biodegradable dispersant of spilled oil in water surrounding two Persian Gulf provinces. Methods. This study compared the effects of three dispersants, Pars 1, Pars 2, and Gamlen OD4000 on removal of oil in two Persian Gulf provinces' water. Overall, 16 stations were selected. Using the Well method, the growth rate of isolated bacteria and fungi was identified. To specify the growth rate of microorganisms and their usage of oil in the presence of the above-mentioned dispersants, as exclusive sources of carbon, the bacteria were grown in culture medium for 28 days at 120 rpm, 30°C, and their optical density was measured by spectrophotometry. Then, we tested biological oxygen demand (BOD) and chemical oxygen demand (COD) in microorganisms. Results. The highest growth rate was documented for the growth of microorganisms on either Pars 1 or Pars 2 dispersants or their mixtures with oil. However, the culture having microorganisms grown on Pars 1 had higher BOD and COD than the other two dispersants (9200 and 16800 versus 500 and 960, P < 0.05). Mixture of oil and Pars 2 as well as oil and Pars 1 dispersants showed the highest BODs and CODs, respectively. In the Bahregan province, microorganisms grown on Pars 2 had maximum amount of BOD and COD in comparison with Pars 1 and Gamlen dispersants (7100 and 15200 versus 6000 and 10560, P < 0.05). Conclusion. Pars 1 and Pars 2 were the most effective dispersants with highest degradability comparing Gamlen. In each region, the most suitable compound for removing oil spill from offshores with least secondary contamination should be investigated. PMID:22363352

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.

Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation

PubMed Central

2011-01-01

Background A common characteristic of allergens is that they contain proteases that can activate protease-activated receptor (PAR-2); however the mechanism by which PAR-2 regulates allergic airway inflammation is unclear. Methods Mice (wild type and PAR-2-deficient) were sensitized using German cockroach (GC) feces (frass), the isolated protease from GC frass, or through adoptive transfer of GC frass-treated bone marrow-derived dendritic cells (BMDC) and measurements of airway inflammation (cellular infiltration, cytokine expression, and mucin production), serum IgE levels and airway hyperresponsiveness (AHR) were assessed. BMDC were cultured, treated with GC frass and assessed for cytokine production. PAR-2 expression on pulmonary mDCs was determined by flow cytometry. Results Exposure to GC frass induced AHR and airway inflammation in wild type mice; however PAR-2-deficient mice had significantly attenuated responses. To directly investigate the role of the protease, we isolated the protease from GC frass and administered the endotoxin-free protease into the airways of mice in the presence of OVA. GC frass proteases were sufficient to promote the development of AHR, serum IgE, and Th2 cytokine production. PAR-2 expression on mDC was upregulated following GC frass exposure, but the presence of a functional PAR-2 did not alter antigen uptake. To determine if PAR-2 activation led to differential cytokine production, we cultured BMDC in the presence of GM-CSF and treated these cells ex vivo with GC frass. PAR-2-deficient BMDC released significantly less IL-6, IL-23 and TNFα compared to BMDC from wild type mice, suggesting PAR-2 activation was important in Th2/Th17 skewing cytokine production. To determine the role for PAR-2 on mDCs on the initiation of allergic airway inflammation, BMDCs from wild type and PAR-2-deficient mice were treated in the presence or absence of GC frass and then adoptively transferred into the airway of wild type mice. Importantly, GC frass-stimulated wild type BMDCs were sufficient to induce AHR and allergic airway inflammation, while GC frass-stimulated PAR-2-deficient BMDC had attenuated responses. Conclusions Together these data suggest an important role for allergen activation of PAR-2 on mDCs in mediating Th2/Th17 cytokine production and allergic airway responses. PMID:21936897

An assessment of phytoplankton primary productivity in the Arctic Ocean from satellite ocean color/in situ chlorophyll‐a based models

PubMed Central

Matrai, Patricia A.; Friedrichs, Marjorie A. M.; Saba, Vincent S.; Antoine, David; Ardyna, Mathieu; Asanuma, Ichio; Babin, Marcel; Bélanger, Simon; Benoît‐Gagné, Maxime; Devred, Emmanuel; Fernández‐Méndez, Mar; Gentili, Bernard; Hirawake, Toru; Kang, Sung‐Ho; Kameda, Takahiko; Katlein, Christian; Lee, Sang H.; Lee, Zhongping; Mélin, Frédéric; Scardi, Michele; Smyth, Tim J.; Tang, Shilin; Turpie, Kevin R.; Waters, Kirk J.; Westberry, Toby K.

2015-01-01

Abstract We investigated 32 net primary productivity (NPP) models by assessing skills to reproduce integrated NPP in the Arctic Ocean. The models were provided with two sources each of surface chlorophyll‐a concentration (chlorophyll), photosynthetically available radiation (PAR), sea surface temperature (SST), and mixed‐layer depth (MLD). The models were most sensitive to uncertainties in surface chlorophyll, generally performing better with in situ chlorophyll than with satellite‐derived values. They were much less sensitive to uncertainties in PAR, SST, and MLD, possibly due to relatively narrow ranges of input data and/or relatively little difference between input data sources. Regardless of type or complexity, most of the models were not able to fully reproduce the variability of in situ NPP, whereas some of them exhibited almost no bias (i.e., reproduced the mean of in situ NPP). The models performed relatively well in low‐productivity seasons as well as in sea ice‐covered/deep‐water regions. Depth‐resolved models correlated more with in situ NPP than other model types, but had a greater tendency to overestimate mean NPP whereas absorption‐based models exhibited the lowest bias associated with weaker correlation. The models performed better when a subsurface chlorophyll‐a maximum (SCM) was absent. As a group, the models overestimated mean NPP, however this was partly offset by some models underestimating NPP when a SCM was present. Our study suggests that NPP models need to be carefully tuned for the Arctic Ocean because most of the models performing relatively well were those that used Arctic‐relevant parameters. PMID:27668139

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

PubMed Central

Romeo Cardeillac, Carlos J.; Cal Castillo, Karina B.; Vilchez Larrea, Salomé C.; Sotelo Sosa, José R.; Folle Ungo, Gustavo A.; Fernández Villamil, Silvia H.

2017-01-01

Background Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells. Myelinating Schwann cells (SC) are stabilized by E-cadherin rich autotypic adherens junctions (AJ). We wondered whether PAR would map to these regions. Besides, we have demonstrated an altered microfilament pattern in peripheral nerves of Trembler-J (Tr-J) model of CMT1-E. We hypothesized that cytoplasmic PAR would accompany such modified F-actin pattern. Methods Wild-type (WT) and Tr-J mice sciatic nerves cryosections were subjected to immunohistofluorescence with anti-PAR antibodies (including antibody validation), F-actin detection with a phalloidin probe and DAPI/DNA counterstaining. Confocal image stacks were subjected to a colocalization highlighter and to semi-quantitative image analysis. Results We have shown for the first time the presence of PAR in sciatic nerves. Cytoplasmic PAR colocalized with F-actin at non-compact myelin regions in WT nerves. Moreover, in Tr-J, cytoplasmic PAR was augmented in close correlation with actin. In addition, nuclear PAR was detected in WT SC and was moderately increased in Tr-J SC. Discussion The presence of PAR associated to non-compact myelin regions (which constitute E-cadherin rich autotypic AJ/actin anchorage regions) and the co-alterations experienced by PAR and the actin cytoskeleton in epithelium and nerves, suggest that PAR may be a constitutive component of AJ/actin anchorage regions. Is PAR stabilizing the AJ-actin complexes? This question has strong implications in structural cell biology and cell signaling networks. Moreover, if PAR played a stabilizing role, such stabilization could participate in the physiological control of axonal branching. PARP and PAR alterations exist in several neurodegenerative pathologies including Alzheimer’s, Parkinson’s and Hungtington’s diseases. Conversely, PARP inhibition decreases PAR and promotes neurite outgrowth in cortical neurons in vitro. Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and in vivo. Until now such results have been interpreted in terms of nuclear PARP activity. Our results indicate for the first time the presence of PARylation in peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs and PARylation in normal and neurodegenerative conditions should be re-evaluated. PMID:28503382

Nucléation, ascension et éclatement d'une bulle de champagne

NASA Astrophysics Data System (ADS)

Liger-Belair, G.

2006-03-01

People have long been fascinated by bubbles and foams dynamics, and since the pioneering work of Leonardo da Vinci in the early 16th century, this subject has generated a huge bibliography. However, only quite recently, much interest was devoted to bubbles in Champagne wines and carbonated beverages. Since the time of the benedictine monk dom Pierre Perignon (1638-1715), champagne is the wine of celebration. This fame is largely linked to the elegance of its effervescence and foaming properties. In this book, the latest results about the chemical physics behind the bubbling properties of Champagne and sparkling wines are collected and fully illustrated. The first chapter is devoted to the history of champagne and to a presentation of the tools of the physical chemistry of interfaces needed for a whole comprehension of the book. Then, the three main steps of a fleeting champagne bubble's life are presented in chronological order, that is, the bubble nucleation on the glass wall (Chap.2), the bubble ascent and growth through the liquid matrix (Chap.3), and the bursting of bubbles at the liquid surface (Chap.4), which constitutes the most intriguing, functional, and visually appealing step. L'objectif général de ce travail consacré à l'étude des processus physicochimiques liés à l'effervescence des vins de Champagne était de décortiquer les différentes étapes de la vie d'une bulle de champagne en conditions réelles de consommation, dans une flûte. Nous résumons ci-après les principaux résultats obtenus pour chacune des étapes de la vie de la bulle, depuis sa naissance sur les parois d'une flûte, jusqu'à son éclatement en surface. Nucléation À l'aide d'une caméra rapide munie d'un objectif de microscope, nous avons pu mettre à mal une idée largement répandue. Ce ne sont pas les anfractuosités de la surface du verre ou de la flûte qui sont responsable de la nucléation hétérogène des bulles, mais des particules adsorbées sur les parois du verre ou de la flûte. Dans la majorité des cas, il s'agit de fibres de cellulose creuses dont les propriétés géométriques permettent le piégeage d'une poche d'air en leur sein au moment du versement. Un modèle de piégeage a été construit et met en avant le rôle fondamental joué par la vitesse du versement. Plus cette vitesse augmente, plus on augmente la probabilité de piéger des poches d'air au sein de ces fibres, provoquant ainsi une effervescence plus importante. La dynamique de production des bulles a également été filmée in situ à l'aide de la caméra, puis modélisée en utilisant les équations de la diffusion adaptées à la géométrie de notre fibre supposée approximativement cylindrique. Nous avons montré que le temps caractéristique de production d'une bulle par la fibre est largement gouverné par la croissance de cette petite poche de gaz par diffusion du CO{2} dissous vers la poche. Nous avons démontré que la convection du liquide joue un rôle essentiel lors du transfert de masse du CO{2} dissous vers la poche. En effet, un modèle purement diffusif ne permet pas du tout de reproduire la dynamique de croissance expérimentale de ces poches de gaz piégées au cœur des fibres. Nous avons également pu mettre en évidence des changements spectaculaires dans la dynamique de bullage de certains sites de nucléation suivis au cours du temps pendant le processus de dégazage. Ces observations font de la fibre de cellulose immergée dans le champagne le plus petit système de bullage non-linéaire observé à ce jour. Dynamique ascensionnelle Pour mesurer la vitesse d'une bulle tout au long de son trajet vers la surface libre du champagne, nous avons tiré profit de la production répétitive de bulles au niveau des sites de nucléation. Par la mise en place d'un dispositif expérimental simple qui associe une lumière stroboscopique et un appareil photographique muni de bagues macros, nous avons pu accéder à l'observation fine des trains de bulles ainsi qu'à la détermination de la vitesse ascensionnelle des bulles. Les mesures expérimentales du rayon et de la vitesse d'une bulle nous ont permis de déterminer le coefficient de traînée d'une bulle montante qui constitue une mesure indirecte de son état de surface en termes de mobilité interfaciale. Ces mesures nous ont montré que l'interface d'une bulle de champagne conserve une grande mobilité interfaciale pendant sa phase ascensionnelle, à la différence des bulles de taille fixe qui montent dans une solution de macromolécules tensioactives. C'est la faible dilution du champagne en macromolécules tensioactives et le grossissement continu des bulles pendant l'ascension qui assurent aux bulles une faible contamination de leur interface. Pour comparaison, nous avons réalisé le même type de mesures sur des bulles de bière. Le contenu en macromolécules tensioactives étant beaucoup plus important dans une bière, l'effet de dilution du matériel tensioactif à la surface des bulles lié à l'accroissement de la surface des bulles ne compense plus l'adsorption massive des tensioactifs à la surface des bulles. Contrairement aux bulles du champagne, les bulles de bière adoptent vite un comportement de type sphère rigide. Nous avons également discuté l'influence relative de certains paramètres sur la taille des bulles lorsqu'elles parviennent en surface. Il a notamment été montré que le rôle théorique joué par la température du champagne sur la taille des bulles est quasiment négligeable. Pour finir, nous avons proposé d'essayer de faire du train de bulles une sorte d'empreinte digitale du liquide effervescent dans lequel il évolue en analysant la dynamique ascensionnelle des bulles via la mesure de leur coefficient de frottement. Nous avons pu différencier à ce jour par cette méthode trois grandes familles de boissons gazeuses : les vins effervescents au sens large (champagne compris), les bières et les eaux gazeuses. Éclatement En utilisant les techniques classiques de la macrophotographie, nous avons obtenu des instantanés de la situation qui suit immédiatement la rupture du mince film liquide qui constitue la partie émergée d'une bulle isolée en surface. Nous avons ainsi pu mettre en évidence l'existence des jets de liquide engendrés par les éclatements de bulle, et leur rupture en gouttelettes suite au développement très rapide de l'instabilité de Rayleigh-Plateau. En faisant un parallèle légitime entre le pétillement des bulles à la surface du champagne et le “pétillement de l'océan”, nous avons émis l'idée que les gouttelettes de jet étaient beaucoup plus concentrées en matériel tensioactif (et potentiellement aromatique) que le cœur de phase du liquide. Il semble donc que l'éclatement de bulles joue un rôle essentiel dans l'effet exhausteur d'arômes au cours de la dégustation d'un champagne. Pendant les quelques secondes qui suivent le versement du champagne dans la flûte, nous avons également réalisé des clichés macrophotographiques et des films à haute vitesse d'éclatements de bulles en monocouche (ou radeau de bulles). Les premiers résultats de ces observations font apparaître des déformations spectaculaires dans le film liquide des bulles premières voisines littéralement aspirées par succion capillaire dans la cavité laissée vacante par la bulle centrale en train d'éclater. Ces premières images suggèrent des contraintes, dans le mince film des bulles déformées, très supérieures à celles qui existent dans le sillage d'une bulle isolée qui éclate. Nous avons également pu mettre en évidence des différences structurales entre les jets de liquide qui suivent l'éclatement des bulles isolées et celles qui éclatent dans un radeau de bulles.

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... ASSOCIATES MEMBERS OF THE BANKS Stock Requirements § 925.19 Par value and price of stock. The capital stock of each Bank shall be sold at par, unless the Board has fixed a higher price. ...

[Pseudoallergies].

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Monaco, M G; Monte, M T; Pucci, N; Rossi, M E; Vierucci, A

2001-01-01

Pseudo-allergic-reactions (PAR) are clinical manifestations including urticaria, angioedema, conjunctivitis, rhinitis, asthma, and anaphylaxis. The prevalence of PAR ranges from 0.1% to 75% according to various studies. The pathogenetic mechanism of these diseases is not immunologically mediated. Food, additives, and drugs are the main responsibilities for PAR. The diagnosis of PAR is characterized by the absence of specific IgE for the suspected products. The absence of immunological mechanisms is confirmed by in vitro and in vivo tests. The treatment of PAR is similar to that of allergic diseases (antihistamine drugs, steroids, B2 agonists, epinephrine).

Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas

PubMed Central

Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.

2010-01-01

Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident. PMID:21991216

Pathogenic activity of circulating anti-desmoglein-3 autoantibodies isolated from pemphigus vulgaris patients

PubMed Central

Boncela, Joanna; Smolarczyk, Katarzyna; Kowalewski, Cezary; Wozniak, Katarzyna; Torzecka, Jolanta Dorota; Sysa-Jedrzejowska, Anna; Cierniewski, Czesław S.; Lesiak, Aleksandra

2012-01-01

Introduction There are scarce data on immunochemical properties of pemphigus antibodies detected in clinical remission in pemphigus vulgaris (PV) patients. The aim of the study was to compare biological activity of anti-Dsg3 autoantibodies purified from the sera of PV patients in active stage and in clinical remission. Material and methods The effect of purified antibodies on expression of procaspase-3, Bax, Bcl-2, uPAR, IL-1β, IL-6, and TNF-α mRNAs in the HaCaT keratinocytes was evaluated by Western blot and RT-PCR method. Results Incubation of HaCaT cells with anti-Dsg-3 autoantibodies caused their binding to cell membranes surfaces. Anti-Dsg3 autoantibodies isolated from the patients in active stage and clinical remission showed proapoptotic effect, caused enhanced expression of analyzed proinflammatory cytokines’ mRNAs and uPAR mRNA. Conclusions Our data revealed similar pathogenic activity of anti Dsg-3 autoantibodies isolated from active and clinical remission PV patients. PMID:22662010

Modelisations et inversions tri-dimensionnelles en prospections gravimetrique et electrique

NASA Astrophysics Data System (ADS)

Boulanger, Olivier

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

Caractérisation de l'état de surface et des contraintes résiduelles engendrées par meulage

NASA Astrophysics Data System (ADS)

Gognau, D.; Blehaut, H.; Dürr, J.; Hariri, S.; Khouchaf, L.; Flahaut, P.

2002-07-01

grinding operations are generally used to prepare surfaces or improve surface state before or after welding. These operations, when carried out manually with portable machines, induce superficial work hardening, modification of the structure of material and residual stresses. An experimental study about the influence of grinding has been carried out on two metallic materials, a low carbon steel (A42-CP) and an austenitic stainless steel (316L), in order to characterise the grinding effects. Manual grinding being difficult to control (no repeatable effects), a test rig using a portable machine has been made. This test rig enables to control the grinding parameters in order to obtain repeatable grinding operations. Characterisation of the ground surfaces was made by 2D profilometry and measurements of residual stresses have been carried out with a Set-X Elphyse apparatus. The profiles of residual stresses obtained show, on the one hand, that on each material, identical grindings generate identical states of stresses and on the other hand, that materials have not the same behaviour, From a metallurgical point of view, we also observe that the grinding effects are different for both materials. The grinding of the A42 steel highlights a crushing of the grain near the surface while the 316L stainless steel grinding reveals sliding bands. Des opérations de meulage sont régulièrement effectuées sur des matériaux métalliques pour préparer les surfaces ou pour améliorer l'état de ces surfaces après soudage. Ces opérations réalisées manuellement engendrent un écrouissage superficiel, une modification de la structure du matériau et par conséquent des contraintes résiduelles. Une étude expérimentale a été menée sur un acier à bas carbone (A42-CP) et un acier inoxydable austénitique (316L) afin de caractériser les effets du meulage. Le meulage manuel étant difficile à maîtriser (effets non reproductibles), un banc d'essai utilisant une machine portative a été réalisé afin de contrôler les différents paramètres caractéristiques des opérations de meulage. Ensuite, la détermination de la rugosité des surfaces meulées s'est faite par profilornétrie 2D et les contraintes résiduelles ont été mesurées sur un appareil Set-X Elphyse. Les profils de contraintes obtenus montrent d'une part que sur un même matériau, des meulages réalisés dans les mêmes conditions aboutissent à des résultats semblables et d'autre part, que les deux matériaux utilises se comportent différemment. Ainsi, d'un point de vue métallurgique, on observe que le meulage de l'acier A42 favorise un écrasement des grains proches de la surface alors que le meulage de l'acier inoxydable 316L fait apparaître de nombreuses bandes de glissement.

Fissuration d'un composite a matrice ceramique dans une application de piece statique de turbine a gaz

NASA Astrophysics Data System (ADS)

Lebel, Larry

Une procedure experimentale a ete developpee pour caracteriser les mecanismes de deterioration et la durabilite de materiaux composites a matrice ceramique (CMC) dans une application de piece statique de turbine a gaz. Tandis que la plupart des essais de caracterisation publies sur les materiaux CMC ont ete realises sous des conditions de chargement controle, la presente recherche tente de reproduire la relaxation des contraintes qui se produit normalement dans une piece statique a haute temperature. Dans l'experience proposee, un echantillon planaire de forme haltere est chauffe de facon cyclique sur une de ses faces et refroidi sur l'autre, tout en etant contraint dans ses deplacements. La contrainte de flexion resultante au centre de l'echantillon, mesuree par une cellule de charge, correspond a la contrainte de flexion qui a ete prealablement predite au centre des panneaux d'une chambre a combustion generique. Un materiau CMC multicouche compose d'une matrice d'alumine poreuse et de fibres NextelMD 720 a ete utilise pour developper l'experience. Des essais de calibration ont d'abord ete realises en utilisant un systeme de chauffage par lampe infrarouge, atteignant jusqu'a 1160 °C a la surface de l'echantillon. Un systeme laser au CO2 a par la suite ete utilise pour realiser des essais de deterioration a haute puissance, atteignant en fin d'essai des temperatures de surface excedant la limite de 1200 °C du materiau et des differences de temperature a travers l'epaisseur de plus de 1000 °C. Sous la puissance de chauffage imposee a amplitude constante, l'accumulation de dommage a fait en sorte d'augmenter la temperature en surface et les gradients de temperature a travers le materiau. Une reduction de la contrainte dans le temps a ete observee a cause du fluage, de la fissuration et de la delamination du materiau sous la condition de confinement du deplacement, menant a une stabilisation du niveau de dommage a une certaine profondeur dependant de la contrainte thermique initiale. La procedure de caracterisation developpee s'avere etre un outil prometteur pour developper de nouveaux types de materiaux, de meme que pour comparer la durabilite de materiaux existants sous des conditions representatives de pieces statiques de turbine a gaz. None

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding.

PubMed

Wong, Pancras C; Seiffert, Dietmar; Bird, J Eileen; Watson, Carol A; Bostwick, Jeffrey S; Giancarli, Mary; Allegretto, Nick; Hua, Ji; Harden, David; Guay, Jocelyne; Callejo, Mario; Miller, Michael M; Lawrence, R Michael; Banville, Jacques; Guy, Julia; Maxwell, Brad D; Priestley, E Scott; Marinier, Anne; Wexler, Ruth R; Bouvier, Michel; Gordon, David A; Schumacher, William A; Yang, Jing

2017-01-04

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care. Copyright © 2017, American Association for the Advancement of Science.

PAR-2 inhibition reverses experimental pulmonary hypertension.

PubMed

Kwapiszewska, Grazyna; Markart, Philipp; Dahal, Bhola Kumar; Kojonazarov, Baktybek; Marsh, Leigh Matthew; Schermuly, Ralph Theo; Taube, Christian; Meinhardt, Andreas; Ghofrani, Hossein Ardeschir; Steinhoff, Martin; Seeger, Werner; Preissner, Klaus Theo; Olschewski, Andrea; Weissmann, Norbert; Wygrecka, Malgorzata

2012-04-27

A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH. In the present study we investigated the importance of protease-activated receptor (PAR)-2 and its ligand mast cell tryptase in the development of PH. Our results revealed strong increase in PAR-2 and tryptase expression in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF (hypoxia inducible factor)-1α depletion, PDGF-BB neutralizing antibody, or the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was also observed in smooth muscle cells of pulmonary vessels of mice exposed to hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase induced PASMC proliferation and migration as well as enhanced synthesis of fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent manner, suggesting that PAR-2-dependent signaling contributes to vascular remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected against hypoxia-induced PH, and PAR-2 antagonist application reversed established PH in the hypoxia mouse model. Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.

In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan

PubMed Central

Kawai, Yasuhiro; Nakura, Yukiko; Wakimoto, Tetsu; Nomiyama, Makoto; Tokuda, Tsugumichi; Takayanagi, Toshimitsu; Shiraishi, Jun; Wasada, Kenshi; Kitajima, Hiroyuki; Fujita, Tomio; Nakayama, Masahiro; Mitsuda, Nobuaki; Nakanishi, Isao; Takeuchi, Makoto

2015-01-01

Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L–GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan. PMID:25645833

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Joeng, Ji-Hyun

2014-01-01

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension. PMID:25598663

Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal Barrier: Role of the VEGF/uPAR Pathway

PubMed Central

El-Remessy, Azza B.; Franklin, Telina; Ghaley, Nagla; Yang, Jinling; Brands, Michael W.; Caldwell, Ruth B.; Behzadian, Mohamed Ali

2013-01-01

Diabetes-induced breakdown of the blood-retinal barrier (BRB) has been linked to hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and is likely mediated by an increase in oxidative stress. We have shown that VEGF increases permeability of retinal endothelial cells (REC) by inducing expression of urokinase plasminogen activator receptor (uPAR). The purpose of this study was to define the role of superoxide anion in VEGF/uPAR expression and BRB breakdown in diabetes. Studies were performed in streptozotocin diabetic rats and mice and high glucose (HG) treated REC. The superoxide dismutase (SOD) mimetic tempol blocked diabetes-induced permeability and uPAR expression in rats and the cell permeable SOD inhibited HG-induced expression of uPAR and VEGF in REC. Inhibiting VEGFR blocked HG-induced expression of VEGF and uPAR and GSK-3β phosphorylation in REC. HG caused β-catenin translocation from the plasma membrane into the cytosol and nucleus. Treatment with HG-conditioned media increased REC paracellular permeability that was blocked by anti-uPA or anti-uPAR antibodies. Moreover, deletion of uPAR blocked diabetes-induced BRB breakdown and activation of MMP-9 in mice. Together, these data indicate that diabetes-induced oxidative stress triggers BRB breakdown by a mechanism involving uPAR expression through VEGF-induced activation of the GSK3β/β-catenin signaling pathway. PMID:23951261

PAR-1/MARK: a kinase essential for maintaining the dynamic state of microtubules.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2012-01-01

The serine/threonine kinase, PAR-1, is an essential component of the evolutionary-conserved polarity-regulating system, PAR-aPKC system, which plays indispensable roles in establishing asymmetric protein distributions and cell polarity in various biological contexts (Suzuki, A. and Ohno, S. (2006). J. Cell Sci., 119: 979-987; Matenia, D. and Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332-342). PAR-1 is also known as MARK, which phosphorylates classical microtubule-associated proteins (MAPs) and detaches MAPs from microtubules (Matenia, D. and Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332-342). This MARK activity of PAR-1 suggests its role in microtubule (MT) dynamics, but surprisingly, only few studies have been carried out to address this issue. Here, we summarize our recent study on live imaging analysis of MT dynamics in PAR-1b-depleted cells, which clearly demonstrated the positive role of PAR-1b in maintaining MT dynamics (Hayashi, K., Suzuki, A., Hirai, S., Kurihara, Y., Hoogenraad, C.C., and Ohno, S. (2011). J. Neurosci., 31: 12094-12103). Importantly, our results further revealed the novel physiological function of PAR-1b in maintaining dendritic spine morphology in mature neurons.

The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

PubMed

Shih, Cheryl; Cold, Christopher J; Yang, Claire C

2013-06-01

The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Sound of Silence: RNAi in Poly (ADP-Ribose) Research

PubMed Central

Blenn, Christian; Wyrsch, Philippe; Althaus, Felix R.

2012-01-01

Poly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions. PAR synthesis is activated when PARP1 and PARP2 bind to DNA breaks and these two enzymes account for almost all PAR formation after genotoxic stress. PARG cleaves PAR molecules into free PAR and finally ADP-ribose (ADPR) moieties, both acting as messengers in cellular stress signaling. In this review, we discuss the potential of RNAi to manipulate the levels of PARPs and PARG, and consequently those of PAR and ADPR, and compare the results with those obtained after genetic or chemical disruption. PMID:24705085

The Polarity Protein Partitioning-defective 1 (PAR-1) Regulates Dendritic Spine Morphogenesis through Phosphorylating Postsynaptic Density Protein 95 (PSD-95)*

PubMed Central

Wu, Qian; DiBona, Victoria L.; Bernard, Laura P.; Zhang, Huaye

2012-01-01

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. PMID:22807451

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

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

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

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S.

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

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Rotary Transformer

NASA Technical Reports Server (NTRS)

McLyman, Colonel Wm. T.

1996-01-01

None given. From first Par: Many spacecraft (S/C) and surface rovers require the transfer of signals and power across rotating interfaces. Science instruments, antennas and solar arrays are elements needing rotary power transfer for certain (S/C) configurations. Delivery of signal and power has mainly been done by using the simplest means, the slip ring approach. This approach, although simple, leaves debris generating noise over a period of time...The rotary transformer is a good alternative to slip rings for signal and power transfer.

Final Environmental Assessment to Construct a One-quarter Mile Track with Stretching Pads and PAR Course Sheppard Air Force Base, Texas

DTIC Science & Technology

2011-05-01

recycled tires, • Addition of stretching pads comprised of 2 concrete, rubberized workout pads located around the walking track, • Install utility...surfacing made of polyurethane and recycled tires, 3. Addition of stretching pads comprised of2 concrete, rubberized workout pads located around the...Wichita Falls Public Library 600 Eleventh Street Wichita ~ails, Texas 76301 The EA, which addressed the proposed action and alternative, has been

Mecanismes d'ablation du silicium par laser ultrarapide amplifie par des nanostructures plasmoniques

NASA Astrophysics Data System (ADS)

Robitaille, Alexandre

Ultrafast laser interaction with gold nanostructures deposited onto a silicon surface produces considerable field amplification that can result in the ablation of features with dimensions smaller than the diffraction limit. This field amplification in the near field of the nanostructures has been thoroughly investigated in the literature. However, while this is the main phenomenon that permits this nanoablation, energy deposition and diffusion processes cannot be neglected to interpret experimental results. In this work, we study plasmon-enhanced femtosecond laser ablation of silicon using gold nanorods and gold nanospheres to produce sub-diffraction limit holes. Atomic force microscopy and scanning electron microscopy of such features are done and hole depth as a function of fluence is measured. Especially for gold nanorods, hole shape is inconsistent with calculated field distribution. Field distribution alone would let us believe that each nanorod would produce two holes at its both ends. We show that using a model based on a differential equations system describing carriers excitation and diffusion, both shape and depth of the nanoholes can be predicted. Importance of the diffusion process is shown to arise from the extreme localization of the deposited energy around the nanostructure, compared to what is usually the case for conventional ablation of a surface. The characteristic shape of holes is revealed as a striking signature of the energy distribution through the electron-phonon carrier density dependant interaction.

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

PubMed

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Modification of structural and transport properties in epitaxial YBa2CU3Ox films by pulsed laser irradiation

NASA Astrophysics Data System (ADS)

Chechenin, N. G.; Chernysh, A. V.; Korneev, V. V.; Monakhov, E. V.; Seleznev, B. V.

1993-12-01

Pulsed (~20 ns) laser effects in epitaxial YBa2CU3Ox/SrTiO3 thin films were investigated, using RBS/channeling for compositional and structural characterization and 4-point technique for electrical measurements. It was found that laser pulse melting and following quenching lead to a transition from a single-crystalline to a polycrystalline state in films. The formation of grain boundaries causes a room temperature electrical resistivity increase by a factor 10-40, depending on the initial film properties and on the irradiation conditions. Unlike corpuscular (ions, neutrons) irradiation, the laser pulse induced structural damage did not lead to the disappearance of HTS, which persisted up to the highest laser fluences used. It was found, that a thermal model can consistently describe the fluence dependence of disorder, depth of surface relief and helps, with a simple two-layer model, in understanding of fluence dependence of room temperature resistivity in a relatively thick film. Les effects de pulses laser (~20 ns) sur des films minces épitaxiés d'YBa2Cu3Ox/SrTiO3 ont été étudiés par rétrodiffusion Rutherford et canalisation afin de caractériser leur composition et leur structure et à l'aide de la technique des 4 points pour les mesures électriques. On a trouvé que la fusion par pulse laser suivie par une trempe entraîne une transition d'un film monocristallin vers un film polycristallin. La formation de joints de grains s'accompagne d'une augmentation d'un facteur 10-40, de la résistivité électrique à température ambiante, dépendante des propriétés initiales du film et des conditions d'irradiation. Contrairement à l'irradiation corpusculaire (ions, neutrons) l'endommagement produit par la pulse laser n'entraîne pas la disparition de la superconductivité à haute température (HTS), qui persiste jusqu'aux plus hautes doses utilisées. On a trouvé qu'un modèle thermique peut décrire de façon consistante, la profondeur de la rugosité de surface et en considérant un modèle simple à deux couches on peut comprendre la dépendance de la dose sur la résistivité à température ambiante pour des films relativement épais.

Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

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

Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho

Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promotermore » activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells treated with nicotine displayed enhanced invasiveness. ► Nicotine induces uPAR expression and, in turn, stimulates invasiveness. ► MAPK/AP-1 and ROS/NF-κB signals are involved in nicotine-induced uPAR.« less

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 oil used for finish frying is inferior, its effect will dominate. (2) The paper also shows that a significant proportion of the oil used by the processor gets expelled during finish frying. © 2011 Institute of Food Technologists®

A Surface-based Analysis of Language Lateralization and Cortical Asymmetry

PubMed Central

Greve, Douglas N.; Van der Haegen, Lise; Cai, Qing; Stufflebeam, Steven; Sabuncu, Mert R.; Fischl, Bruce; Bysbaert, Marc

2013-01-01

Among brain functions, language is one of the most lateralized. Cortical language areas are also some of the most asymmetrical in the brain. An open question is whether the asymmetry in function is linked to the asymmetry in anatomy. To address this question, we measured anatomical asymmetry in 34 participants shown with fMRI to have language dominance of the left hemisphere (LLD) and 21 participants shown to have atypical right hemisphere dominance (RLD). All participants were healthy and left-handed, and most (80%) were female. Gray matter (GM) volume asymmetry was measured using an automated surface-based technique in both ROIs and exploratory analyses. In the ROI analysis, a significant difference between LLD and RLD was found in the insula. No differences were found in planum temporale (PT), pars opercularis (POp), pars triangularis (PTr), or Heschl’s gyrus (HG). The PT, POp, insula, and HG were all significantly left lateralized in both LLD and RLD participants. Both the positive and negative ROI findings replicate a previous study using manually labeled ROIs in a different cohort [Keller, S. S., Roberts, N., Garcia-Finana, M., Mohammadi, S., Ringelstein, E. B., Knecht, S., et al. Can the language-dominant hemisphere be predicted by brain anatomy? Journal of Cognitive Neuroscience, 23, 2013–2029, 2011]. The exploratory analysis was accomplished using a new surface-based registration that aligns cortical folding patterns across both subject and hemisphere. A small but significant cluster was found in the superior temporal gyrus that overlapped with the PT. A cluster was also found in the ventral occipitotemporal cortex corresponding to the visual word recognition area. The surface-based analysis also makes it possible to disentangle the effects of GM volume, thickness, and surface area while removing the effects of curvature. For both the ROI and exploratory analyses, the difference between LLD and RLD volume laterality was most strongly driven by differences in surface area and not cortical thickness. Overall, there were surprisingly few differences in GM volume asymmetry between LLD and RLD indicating that gross morphometric asymmetry is only subtly related to functional language laterality. PMID:23701459

Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint.

PubMed

Russell, F A; Schuelert, N; Veldhoen, V E; Hollenberg, M D; McDougall, J J

2012-12-01

The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. PAR(2) 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 PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (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 PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) 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-NH(2) alone). PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

TGF-beta inhibits IL-1beta-activated PAR-2 expression through multiple pathways in human primary synovial cells.

PubMed

Tsai, Shin-Han; Sheu, Ming-Thau; Liang, Yu-Chih; Cheng, Hsiu-Tan; Fang, Sheng-Shiung; Chen, Chien-Ho

2009-10-23

To investigate the mechanism how Transforming growth factor-beta(TGF-beta) represses Interleukin-1beta (IL-1beta)-induced Proteinase-Activated Receptor-2 (PAR-2) expression in human primary synovial cells (hPSCs). Human chondrocytes and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1beta, TGF-beta1, or Connective tissue growth factor (CTGF). The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1beta induces PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by TGF-beta and was observed to persist for at least 48 hrs, suggesting that TGF-beta inhibits PAR-2 expression through multiple pathways. First of all, TGF-beta was able to inhibit PAR-2 activity by inhibiting IL-1beta-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-beta was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1beta-induced phospho-p38 level. TGF-beta could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1beta-induced PAR-2 expressed in hPSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-beta or other agents might be an ideal therapeutic target to prevent OA from progression.

Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High-Sensitivity C-Reactive Protein.

PubMed

Hayek, Salim S; Divers, Jasmin; Raad, Mohamad; Xu, Jianzhao; Bowden, Donald W; Tracy, Melissa; Reiser, Jochen; Freedman, Barry I

2018-05-01

Type 2 diabetes mellitus is a major risk factor for cardiovascular disease; however, outcomes in individual patients vary. Soluble urokinase plasminogen activator receptor (suPAR) is a bone marrow-derived signaling molecule associated with adverse cardiovascular and renal outcomes in many populations. We characterized the determinants of suPAR in African Americans with type 2 diabetes mellitus and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium (CAC), and high-sensitivity C-reactive protein (hs-CRP). We measured plasma suPAR levels in 500 African Americans with type 2 diabetes mellitus enrolled in the African American-Diabetes Heart Study. We used Kaplan-Meier curves and Cox proportional hazards models adjusting for clinical characteristics, CAC, and hs-CRP to examine the association between suPAR and all-cause mortality. Last, we report the change in C-statistics comparing the additive values of suPAR, hs-CRP, and CAC to clinical models for prediction of mortality. The suPAR levels were independently associated with female sex, smoking, insulin use, decreased kidney function, albuminuria, and CAC. After a median 6.8-year follow-up, a total of 68 deaths (13.6%) were recorded. In a model incorporating suPAR, CAC, and hs-CRP, only suPAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63-4.34). Addition of suPAR to a baseline clinical model significantly improved the C-statistic for all-cause death (Δ0.05, 95% confidence interval 0.01-0.10), whereas addition of CAC or hs-CRP did not. In African Americans with type 2 diabetes mellitus, suPAR was strongly associated with mortality and improved risk discrimination metrics beyond traditional risk factors, CAC and hs-CRP. Studies addressing the clinical usefulness of measuring suPAR concentrations are warranted. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

suPAR level is associated with myocardial impairment assessed with advanced echocardiography in patients with type 1 diabetes with normal ejection fraction and without known heart disease or end-stage renal disease.

PubMed

Theilade, Simone; Rossing, Peter; Eugen-Olsen, Jesper; Jensen, Jan S; Jensen, Magnus T

2016-06-01

Heart disease is a common fatal diabetes-related complication. Early detection of patients at particular risk of heart disease is of prime importance. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker for development of cardiovascular disease. We investigate if suPAR is associated with early myocardial impairment assessed with advanced echocardiographic methods. In an observational study on 318 patients with type 1 diabetes without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF >45%), we performed conventional, tissue Doppler and speckle tracking echocardiography, and measured plasma suPAR levels. Associations between myocardial function and suPAR levels were studied in adjusted models including significant covariates. Patients were 55±12 years (mean±s.d.) and 160 (50%) males. Median (interquartile range) suPAR was 3.4 (1.7) ng/mL and LVEF was 58±5%. suPAR levels were not associated with LVEF (P=0.11). In adjusted models, higher suPAR levels were independently associated with both impaired systolic function assessed with global longitudinal strain (GLS) and tissue velocity s', and with impaired diastolic measures a' and e'/a' (all P=0.034). In multivariable analysis including cardiovascular risk factors and both systolic and diastolic measures (GLS and e'/a'), both remained independently associated with suPAR levels (P=0.012). In patients with type 1 diabetes with normal LVEF and without known heart disease, suPAR is associated with early systolic and diastolic myocardial impairment. Our study implies that both suPAR and advanced echocardiography are useful diagnostic tools for identifying patients with diabetes at risk of future clinical heart disease, suited for intensified medical therapy. © 2016 European Society of Endocrinology.

A balance between TFPI and thrombin-mediated platelet activation is required for murine embryonic development

PubMed Central

Ellery, Paul E. R.; Maroney, Susan A.; Cooley, Brian C.; Luyendyk, James P.; Zogg, Mark; Weiler, Hartmut

2015-01-01

Tissue factor pathway inhibitor (TFPI) is a critical anticoagulant protein present in endothelium and platelets. Mice lacking TFPI (Tfpi−/−) die in utero from disseminated intravascular coagulation. They are rescued by concomitant tissue factor (TF) deficiency, demonstrating that TFPI modulates TF function in vivo. Recent studies have found TFPI inhibits prothrombinase activity during the initiation of coagulation and limits platelet accumulation during thrombus formation, implicating TFPI in modulating platelet procoagulant activity. To examine whether altered platelet function would compensate for the lack of TFPI and rescue TFPI-null embryonic lethality, Tfpi+/− mice lacking the platelet thrombin receptor, protease activated receptor 4 (PAR4; Par4−/−), or its coreceptor, PAR3, were mated. PAR3 deficiency did not rescue Tfpi−/− embryos, but >40% of expected Tfpi−/−:Par4−/− offspring survived to adulthood. Adult Tfpi−/−:Par4−/− mice did not exhibit overt thrombosis. However, they had focal sterile inflammation with fibrin(ogen) deposition in the liver and elevated plasma thrombin-antithrombin complexes, indicating activation of coagulation at baseline. Tfpi−/−:Par4−/− mice have platelet and fibrin accumulation similar to Par4−/− mice following venous electrolytic injury but were more susceptible than Par4−/− mice to TF-induced pulmonary embolism. In addition, ∼30% of the Tfpi−/−:Par4−/− mice were born with short tails. Tfpi−/−:Par4−/− mice are the first adult mice described that lack TFPI with unaltered TF. They demonstrate that TFPI physiologically modulates thrombin-dependent platelet activation in a manner that is required for successful embryonic development and identify a role for TFPI in dampening intravascular procoagulant stimuli that lead to thrombin generation, even in the absence of thrombin-mediated platelet activation. PMID:25954015

Quercetin Has Antimetastatic Effects on Gastric Cancer Cells via the Interruption of uPA/uPAR Function by Modulating NF-κb, PKC-δ, ERK1/2, and AMPKα.

PubMed

Li, Hai; Chen, Chen

2018-06-01

Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines. GC BGC823 and AGS cells were subjected to treatment with 10 μM Qu for 72 hours and uPAR knockdown, alone or in combination, before evaluating cell metastasis. The results showed that uPA activity and uPAR expression were higher in GC tissues than in pericarcinous tissues. Migratory and invasive activities of GC cell lines positively correlated with uPAR expression. Qu treatment decreased BGC823 and AGS cell migration and invasion, accompanied by reduced uPA and uPAR protein expression. Both Qu treatment and uPAR knockdown decreased matrix metalloproteinase-2 and -9 activity and blocked Pak1-Limk1-cofilin signaling. Qu treatment was associated with inhibition of NF-κb, PKC-δ, and ERK1/2, and with AMPKα activation. Specific inhibitors of NF-κb, PKC, and ERK1/2, and an AMPKα activator suppressed uPA and uPAR expression in GC cells. Collectively, Qu showed an antimetastatic effect on GC cells via the interruption of uPA/uPAR function and modulation of NF-κb, PKC-δ, ERK1/2, and AMPKα. This suggests that Qu is a promising agent against GC metastasis.

OVER-EXPRESSION OF THE THROMBIN RECEPTOR (PAR-1) IN THE PLACENTA IN PREECLAMPSIA: A MECHANISM FOR THE INTERSECTION OF COAGULATION AND INFLAMMATION

PubMed Central

EREZ, OFFER; ROMERO, ROBERTO; KIM, SUNG-SU; KIM, JUNG-SUN; KIM, YEON MEE; WILDMAN, DEREK E; THAN, NANDOR GABOR; MAZAKI-TOVI, SHALI; GOTSCH, FRANCESCA; PINELES, BETH; KUSANOVIC, JUAN PEDRO; ESPINOZA, JIMMY; MITTAL, POOJA; MAZOR, MOSHE; HASSAN, SONIA S.; KIM, CHONG JAI

2008-01-01

Objective Preeclampsia (PE) is characterized by excessive thrombin generation that has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease activated receptor-1 (PAR-1), a G-protein coupled receptor. The aim of this study was to determine whether preterm preeclampsia (PE) is associated with changes in placental expression of PAR-1. Study design This cross-sectional study included two groups matched for gestational age at delivery: 1) patients with preterm PE (<37 weeks of gestation; n=26) and 2) a control group of patients with preterm labor without intraamniotic infection (n=26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive. Results 1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with preeclampsia than in placentas from the control group [37.5% (9/24) vs. 8.7% (2/23); p=0.036, respectively]. 2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. 3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with preeclampsia and in 88.5% (23/26) of the placentas from the control group (p=1). Conclusion Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous PTL. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in preeclampsia. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme. PMID:18570113

Astrocytes Secrete Exosomes Enriched with Proapoptotic Ceramide and Prostate Apoptosis Response 4 (PAR-4)

PubMed Central

Wang, Guanghu; Dinkins, Michael; He, Qian; Zhu, Gu; Poirier, Christophe; Campbell, Andrew; Mayer-Proschel, Margot; Bieberich, Erhard

2012-01-01

Amyloid protein is well known to induce neuronal cell death, whereas only little is known about its effect on astrocytes. We found that amyloid peptides activated caspase 3 and induced apoptosis in primary cultured astrocytes, which was prevented by caspase 3 inhibition. Apoptosis was also prevented by shRNA-mediated down-regulation of PAR-4, a protein sensitizing cells to the sphingolipid ceramide. Consistent with a potentially proapoptotic effect of PAR-4 and ceramide, astrocytes surrounding amyloid plaques in brain sections of the 5xFAD mouse (and Alzheimer disease patient brain) showed caspase 3 activation and were apoptotic when co-expressing PAR-4 and ceramide. Apoptosis was not observed in astrocytes with deficient neutral sphingomyelinase 2 (nSMase2), indicating that ceramide generated by nSMase2 is critical for amyloid-induced apoptosis. Antibodies against PAR-4 and ceramide prevented amyloid-induced apoptosis in vitro and in vivo, suggesting that apoptosis was mediated by exogenous PAR-4 and ceramide, potentially associated with secreted lipid vesicles. This was confirmed by the analysis of lipid vesicles from conditioned medium showing that amyloid peptide induced the secretion of PAR-4 and C18 ceramide-enriched exosomes. Exosomes were not secreted by nSMase2-deficient astrocytes, indicating that ceramide generated by nSMase2 is critical for exosome secretion. Consistent with the ceramide composition in amyloid-induced exosomes, exogenously added C18 ceramide restored PAR-4-containing exosome secretion in nSMase2-deficient astrocytes. Moreover, isolated PAR-4/ceramide-enriched exosomes were taken up by astrocytes and induced apoptosis in the absence of amyloid peptide. Taken together, we report a novel mechanism of apoptosis induction by PAR-4/ceramide-enriched exosomes, which may critically contribute to Alzheimer disease. PMID:22532571

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.

High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression

PubMed Central

Malfettone, Andrea; Silvestris, Nicola; Saponaro, Concetta; Ranieri, Girolamo; Russo, Antonio; Caruso, Stefano; Popescu, Ondina; Simone, Giovanni; Paradiso, Angelo; Mangia, Anita

2013-01-01

Tryptase(+) mast cells (MCs), abundant in the invasive front of tumours, contribute to tissue remodelling. Indeed, protease-activated receptor-2 (PAR-2) activation by MC-tryptase is considered an oncogenic event in colorectal cancer (CRC). Recently, we have suggested NHERF1 as a potential new marker in CRC. In this study, we aimed to determine the distribution of tryptase(+) MCs and PAR-2 and to examine the relationship between PAR-2 and NHERF1, investigating their reputed usefulness as tumour markers. We studied a cohort of 115 CRC specimens including primary cancer (C) and adjacent normal mucosa (NM) by immunohistochemical double staining, analyzing the protein expression of MC-tryptase, PAR-2 and cytoplasmic NHERF1. MC density was higher in NM than in C. Tumours with high TNM stage and poor grade showed the highest MC density. A higher PAR-2 immunoreactivity characterized tumours most infiltrated by MCs compared with samples with low MC density. Furthermore, PAR-2 overexpression was associated with advanced TNM stage, poor grade and lymphovascular invasion (LVI). A positive correlation existed between tryptase(+) MC density and PAR-2 expression. Cytoplasmic NHERF1 was higher in C than in NM and overexpressing tumours resulted associated with nodal and distant metastases, poor grade and LVI. PAR-2 correlated with cytoplasmic NHERF1 and the PAR-2(+)/cytoplasmic NHERF1(+) expression immunophenotype identified tumours associated with unfavourable prognosis and aggressive clinical parameters. Our data indicate that the high density of tryptase(+) MCs at invasive margins of tumours was associated with advanced stages of CRC and was strongly correlated with PAR-2 expression. PMID:23991686