Netting neutrophils in skin wounds recruit and activate plasmacytoid dentritic cells

Les mécanismes qui régulent le processus de guérison de la peau lésée ne sont pas entièrement compris. Nous avons précédemment montré que les cellules dendritiques plasmocytoïdes (pDCs) sont normalement absentes de la peau saine mais infiltrent rapidement la peau humaine ainsi que celle des souris après une blessure cutanée. Après avoir infiltré la peau, ces pDCs sont capables de détecter les acides nucléiques par l'expression des récepteurs de type Toll 7 et 9 ce qui les active à produire de 1' interféron (IFN) de type I. Ce processus est primordial pour la re- épithélisation des blessures cutanées. Cependant, les mécanismes conduisant à l'infiltration et à 1'activation des pDCs restent inconnus. Dans notre projet, nous montrons que la chimiokine CxcllO est responsable de l'infiltration des pDCs. De façon importante, nous démontrons que les neutrophiles qui infiltrent également la peau lésée sont la source majeure de cette chimiokine. La déplétion des neutrophiles abolit d'ailleurs le recrutement des pDCs confirmant ainsi que CxcllO produit par les neutrophiles est responsable de l'infiltration des pDCs dans la peau endommagée. De façon intéressante, nous avons trouvé que CxcllO en plus de son activité chimiotactique, est capable de former des complexes avec l'ADN et d'activer ainsi les pDCs à produire de l'IFN de type I. De plus, nous avons observé que les neutrophiles qui infiltrent la peau forment des Neutrophil Extracellular Traps (NETs). Ces NETs sont constitués de filaments extracellulaires d'ADN recouverts par de nombreuses protéines principalement d'origine granulaire. D'une manière frappante, le blocage de la NETose ou l'utilisation de souris déficientes pour la formation de NETs altère le recrutement et l'activation des pDCs ainsi que la réponse inflammatoire qui en découle ainsi que le processus de re-epithélisation qui s'ensuit. En prenant en compte toutes ces données, nos résultats démontrent que suite à une blessure de la peau, les neutrophiles par la production de CxcllO contrôlent l'infiltration des pDCs dans la peau lésée et par la formation de NETs, promeuvent l'activation des pDCs. Notre étude fournit donc de nouvelles informations sur les mécanismes de guérison de la peau et ouvre de nouvelles perspectives thérapeutiques quant à la réparation tissulaire de la peau soit dans le but de l'amplifier ou de l'inhiber. -- The mechanisms that regulate healing of the injured skin are not well understood. We have previously shown that plasmacytoid dendritic cells (pDCs) are normally absent from the healthy skin, but rapidly infiltrate both murine and human skin upon injury. Upon skin infiltration, pDCs sense nucleic acids via TLR7/TLR9 and are activated to produce type I interferon (IFN), a process that is crucial for re-epithelialisation of skin wounds. However, the mechanisms that drive pDCs recruitment and activation in injured skin remain unclear. We show that CxcllO is responsible for pDCs infiltration. Importantly, we demonstrate that skin infiltrating neutrophils are the major source of this chemokine. Neutrophils depletion completely abrogated pDCs recruitment confirming that CxcllO- driven pDCs recruitment is controlled by neutrophils. Interestingly, CxcllO was also found to form complexes with DNA and to activate pDCs to produce Type I IFN in addition to its chemotactic activity. Moreover, we observed that infiltrating neutrophils release Neutrophils Extracellular Traps (NETs) composed of DNA filaments decorated with neutrophils-derived proteins. Strikingly, blocking NETosis or using mice deficient for NETs production impaired pDCs recruitment and activation as well as the subsequent inflammatory response and the re-epithelialisation process. Altogether, these data demonstrate that upon skin injury, neutrophils control pDCs infiltration into the injured skin by the release of CxcllO and via the production of NETs, they allow complex formation between CxcllO and NET-DNA leading to pDCs activation. Our findings provide new insights into the mechanisms of wound healing and open new avenues for potential therapeutic interventions to boost or inhibit wound repair in the skin.

Loss Modelling of Three-Level Inverters controlled with Space Vector Modulation Technique

The objective of this master’s thesis is to investigate the loss behavior of three-level ANPC inverter and compare it with conventional NPC inverter. The both inverters are controlled with mature space vector modulation strategy. In order to provide the comparison both accurate and detailed enough NPC and ANPC simulation models should be obtained. The similar control model of SVM is utilized for both NPC and ANPC inverter models. The principles of control algorithms, the structure and description of models are clarified. The power loss calculation model is based on practical calculation approaches with certain assumptions. The comparison between NPC and ANPC topologies is presented based on results obtained for each semiconductor device, their switching and conduction losses and efficiency of the inverters. Alternative switching states of ANPC topology allow distributing losses among the switches more evenly, than in NPC inverter. Obviously, the losses of a switching device depend on its position in the topology. Losses distribution among the components in ANPC topology allows reducing the stress on certain switches, thus losses are equally distributed among the semiconductors, however the efficiency of the inverters is the same. As a new contribution to earlier studies, the obtained models of SVM control, NPC and ANPC inverters have been built. Thus, this thesis can be used in further more complicated modelling of full-power converters for modern multi-megawatt wind energy conversion systems.

Creating SHAREDVALUE: A How-to Guide for the New Corporate (R)evolution

Competitividad y valor compartido

Structural studies and gabbro mylonitization within the Barton Bay Deformation Zone, Geraldton, Ontario /

Structures related to ductile siMple shear parallel to the Bankf ield-Tonbill Fault, define a 5km wide zone, the Barton Bay Deformation Zone. Structures present within this zone Include; simple shear fabrics S, C and C , asymmetric Z shaped folds with rotated axes, boudinage and pinch and swell structures and a subhorlzontal extension llneation. The most highly deformed rock is a gabbro mylonite which occurs in the fault zone. The deformation of this gabbro has been traced in stages from a protomylonite to an ultramylonite In which feldspar and chlorite grainslze has been reduced from over 100 microns to as little as 5 microns. Evidence from the mylonite and the surrounding structure indicates that deformation within the Barton Bay Deformation Zone is related to a regional simple shear zone, the Bankf ield-Tombill Fault. Movement along this shear zone was in a south over north oblique strike slip fashion with a dextral sense of displacement.

Sculpture by R. Bret Price and Harold Hutton Sports Center, Chapman College, Orange, California

Sculpture by R. Bret Price in front of the Harold Hutton Sports Center, 219 E. Sycamore St., Chapman College, Orange, California. The Harold Hutton Sports Center completed in 1978, is named in honor of this former trustee, and made possible by a gift from his wife, Betty Hutton Williams. Image used for holiday card by Chapman College president G. T. "Buck" Smith and his wife Joni.

Smith Hall, Chapman College, Orange, California

Smith Hall, 215 E. Palm St., Chapman College, Orange, California. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

Smith Hall, Chapman University, Orange, California

Entrance to Smith Hall, Chapman College, Orange, California. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

Smith Hall, Chapman University, Orange, California

Looking south to Smith Hall, Chapman College, Orange, California. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

Smith Hall, Chapman University, Orange, California

Looking south to front of Smith Hall, Chapman College, Orange, California. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

Smith Hall, Chapman University, Orange, California

Smith Hall, Chapman College, Orange, California, looking southwest. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

Smith Hall, Chapman University, Orange, California

View across lawn of Smith Hall, Chapman College, Orange, California. This building was completed in 1913 as the Science Building for Orange Union High School and was acquired by Chapman in 1954. In 1988 it was named in honor of former president G.T. (Buck) Smith and his wife, Joni. Buck Smith served as president of the university from 1977 to 1988. This building (2 floors, basement, 15,263 sq.ft.) houses the Psychology Department and is listed in the National Registry for Historical Buildings.

The Niagara Railway Arch (1898)

From American Society of Civil Engineers.

Own the Podium Funding and Support: The Athletes' Perspective

The purpose of this study was to understand the experiences of Canada’s high performance athletes who have benefitted from Own the Podium (OTP)-recommended funding and support leading up to an Olympic or Paralympic Games. OTP, a nonprofit agency, is responsible for determining the overall investment strategy for high performance sport in Canada through recommendations to support national sport organizations (NSOs) with the aim to improve Canadian performances at the Olympic and Paralympic Games. For this study, data were collected through in-depth interviews with eleven Canadian high performance athletes (i.e., single-sport Summer/Winter Olympians and Paralympians and recently retired athletes). Analysis of the data resulted in twelve overarching themes; resources, pressure, missing gap, results, targeting, stress, expectations, boost in confidence, OTP relationship, OTP name, pre/post OTP, and lost funding. Overall, results from this exploratory research indicate that athletes generally had a favourable perception regarding OTP-recommended funding and support.

Longitudinal changes in HIV-specific IFN-? secretion in subjects who received Remune™ vaccination prior to treatment interruption

Affiliation: Maude Loignon, Lise Cyr & Emil Toma : Département de microbiologie et immunologie, Faculté de médecine, Université de Montréal