20 research outputs found

    The Gallery 2011

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    This is a digital copy of the print content produced by the Gallery 2011 team. The Gallery 2011 consists of a box containing a leaflet, four books, and a USB drive. The leaflet lists the works contained on the USB drive in the areas of Time Based Media and Web Design, and provides credits for the Gallery design production team. Content from the USB drive is not included. The four books contain the artistic works of students in the following genres: Core Studio/Painting, Graphic Design/Illustration, Photography/Printmaking, and Jewelry & Metals/Three Dimensional. Files for individual sections may be viewed on the detailed metadata page by clicking on the book title.https://rdw.rowan.edu/the_gallery/1005/thumbnail.jp

    A compact and cost-effective hard X-ray free-electron laser driven by a high-brightness and low-energy electron beam

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    We present the first lasing results of SwissFEL, a hard X-ray free-electron laser (FEL) that recently came into operation at the Paul Scherrer Institute in Switzerland. SwissFEL is a very stable, compact and cost-effective X-ray FEL facility driven by a low-energy and ultra-low-emittance electron beam travelling through short-period undulators. It delivers stable hard X-ray FEL radiation at 1-Ă… wavelength with pulse energies of more than 500 ÎĽJ, pulse durations of ~30 fs (root mean square) and spectral bandwidth below the per-mil level. Using special configurations, we have produced pulses shorter than 1 fs and, in a different set-up, broadband radiation with an unprecedented bandwidth of ~2%. The extremely small emittance demonstrated at SwissFEL paves the way for even more compact and affordable hard X-ray FELs, potentially boosting the number of facilities worldwide and thereby expanding the population of the scientific community that has access to X-ray FEL radiation

    Entwicklung einer Methode zur Untersuchung der biomechanischen Eigenschaften der endothelialen Oberflächensicht

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    Introduction: We have recently found in isolated human umbilical vein endothelial cells (HUVEC) that turbulent (atheroprone) vascular shear stress (VSS) down regulates endothelial connexin 40 and up regulates C6- and V1-type transient receptor potential (TRP) channels. However the mechanism for these atheroprone changes is poorly understood. We have shown that atheroprone VSS profile down regulates the synthesis of a major component of the endothelial surface layer (ESL), hyaluronan (HA). These findings together with the extensive amount of publications showing the importance of ESL in endothelial VSS sensation led us to speculate, that HA might be part of an atheroprone circulus vitiosus: in the absence of atheroprotective VSS, HA expression decreases. This leads to decrease of vascular VSS sensitivity followed by further reduction of HA expression. Thus we aimed at developing a tool to probe the properties and thickness of the surface layer of cultured HUVECs to allow investigation the role of HA for VSS related alterations of the ESL. Methods: A defocus imaging based single particle tracking application was developed. It allows tracking the 3D position of fluorescent nanobeads with a precision beyond the diffraction resolution limit. Local viscosity can be assessed by quantifying the nanobeads’ Brownian motion. Results and conclusion: For a vertical range of 4.5 µm, the validity of vertical single particle tracking was 16 nm, with a precision of about 5 nm. In the horizontal plane precision was 5 nm. In first experiments with HUVEC we could show an increase of local viscosity in a region close to the cell surface with a thickness of about 1000 nm which may correspond to the ESL. Thus, the established approach has the potential to study biophysical properties of the ESL, including thickness and viscosity. This should allow to investigate the alteration of ESL beside different pathological conditions.Einführung: In vorhergehenden Untersuchungen konnten wir zeigen, dass in isolierten Endothelzellen aus humanen Nabelschnurvenen (HUVEC) durch pulsatile Wandschubspannung bei unidirektionaler laminarer Strömung („atheroprotective flow profile“) die Expression von Konnexin40 und HAS2 induziert wird. Dagegen wird die Expression von TNFα sowie C6- und V1-Transient Rezeptor Potential (TRP) Ionkanälen bei relativ niedriger, oszillierender Wandschubspannung (atherogenes Strömungsprofil) induziert. Wir konnten auch zeigen, dass durch ein atherogenes Strömungsprofil die Synthese der wichtigsten Komponente der endothelialen Oberflächenschicht (ESL), der Hyaluronsäure (HA) unterdrückt wird. In Verbindung mit der umfangreichen Literatur über die Bedeutung des ESL für die Schubspannungsempfindlichkeit von Endothelzellen führen diese Ergebnisse zu der Vermutung, dass die ESL eine zentrale Rolle in einem proatherogenen circulus vitiosus spielen könnte: durch atherogene Strömungsbedingungen wird die HA-Synthese reduziert, dies führt zur Reduktion der ESL Dicke und der Schubspannungs-Empfindlichkeit des Endothels und damit zur weiterer Unterdrückung der Hyaluronsäureexpression. Um diese Hypothese testen zu können und die Rolle von Hyaluronsäure und Schubspannung für Veränderungen der ESL zu überprüfen, wurde eine Methode zur direkte Messung der Eigenschaften und Dicke der ESL von primären kultivierten Endothelzelle entwickelt. Methoden: Die Dicke der ESL beträgt ca. 0.5-1 µm und erfordert damit Messverfahren unterhalb der Auflösungsgrenze des Lichtmikrokops. Dies wurde durch Bestimmung des Durchmessers von Beugungsringen fluoreszierender Nanopartikel außerhalb der Fokusebene erreicht. Zur off-line Auswertung entsprechender mikroskopischer Aufnahmen erfolgte mit einem eigenen Programm zum automatisierten Einzelpartikel-Tracking. Neben der Bestimmung der Position des jeweiliges Partikels in den drei Raumachsen war so zugleich die Messung der Viskosität des umgebenden Mediums möglich. Ergebnisse und Zusammenfassung: Über einen vertikalen Bereich von 4,5 µm betrug die Validität für die Lokalisation einzelner Nanopartikel in der Senkrechten 16 nm bei einer Präzision von etwa 5 nm in der Vertikalen und 5 nm in der Horizontalen. In ersten Experimenten mit HUVECs, konnten wir einen Anstieg der Viskosität in Bereichen nahe der Zelloberfläche mit einer Schichtdicke von etwa 1000nm zeigen. Dieser Bereich könnte der endothelialen Oberflächenschicht entsprechen. Somit hat das entwickelte Verfahren das Potential, die biophysikalischen Eigenschaften der ESL, besonders Viskosität und Dicke, zu untersuchen. Damit können die wandschubspannungs-bedingten frühen Effekte der endothelialen Dysfunktion, insbesondere die Bedeutung der ESL und der Hyaluronsäure, weiter untersucht werden

    Role of the endothelial surface layer in neutrophil recruitment

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    Role of the endothelial surface layer in neutrophil recruitment.

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    Neutrophil recruitment in most tissues is limited to postcapillary venules, where E- and P-selectins are inducibly expressed by venular endothelial cells. These molecules support neutrophil rolling via binding of PSGL-1 and other ligands on neutrophils. Selectins extend ≤ 38 nm above the endothelial plasma membrane, and PSGL-1 extends to 50 nm above the neutrophil plasma membrane. However, endothelial cells are covered with an ESL composed of glycosaminoglycans that is ≥ 500 nm thick and has measurable resistance against compression. The neutrophil surface is also covered with a surface layer. These surface layers would be expected to completely shield adhesion molecules; thus, neutrophils should not be able to roll and adhere. However, in the cremaster muscle and in many other models investigated using intravital microscopy, neutrophils clearly roll, and their rolling is easily and quickly induced. This conundrum was thought to be resolved by the observation that the induction of selectins is accompanied by ESL shedding; however, ESL shedding only partially reduces the ESL thickness (to 200 nm) and thus is insufficient to expose adhesion molecules. In addition to its antiadhesive functions, the ESL also presents neutrophil arrest-inducing chemokines. ESL heparan sulfate can also bind L-selectin expressed by the neutrophils, which contributes to rolling and arrest. We conclude that ESL has both proadhesive and antiadhesive functions. However, most previous studies considered either only the proadhesive or only the antiadhesive effects of the ESL. An integrated model for the role of the ESL in neutrophil rolling, arrest, and transmigration is needed

    Effector and Regulatory T Cells Roll at High Shear Stress by Inducible Tether and Sling Formation

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    The adaptive immune response involves T cell differentiation and migration to sites of inflammation. T cell trafficking is initiated by rolling on inflamed endothelium. Tethers and slings, discovered in neutrophils, facilitate cell rolling at high shear stress. Here, we demonstrate that the ability to form tethers and slings during rolling is highly inducible in T helper 1 (Th1), Th17, and regulatory T (Treg) cells but less in Th2 cells. In vivo, endogenous Treg cells rolled stably in cremaster venules at physiological shear stress. Quantitative dynamic footprinting nanoscopy of Th1, Th17, and Treg cells uncovered the formation of multiple tethers per cell. Human Th1 cells also showed tethers and slings. RNA sequencing (RNA-seq) revealed the induction of cell migration and cytoskeletal genes in sling-forming cells. We conclude that differentiated CD4 T cells stabilize rolling by inducible tether and sling formation. These phenotypic changes approximate the adhesion phenotype of neutrophils and support CD4 T cell access to sites of inflammation

    Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis.

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    Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are β2 integrin-dependent. Integrins can extend (E(+)) and acquire a high-affinity conformation with an 'open' headpiece (H(+)). The canonical switchblade model of integrin activation proposes that the E(+) conformation precedes H(+), and the two are believed to be structurally linked. Here we show, using high-resolution quantitative dynamic footprinting (qDF) microscopy combined with a homogenous conformation-reporter binding assay in a microfluidic device, that a substantial fraction of β2 integrins on human neutrophils acquire an unexpected E(-)H(+) conformation. E(-)H(+) β2 integrins bind intercellular adhesion molecules (ICAMs) in cis, which inhibits leukocyte adhesion in vitro and in vivo. This endogenous anti-inflammatory mechanism inhibits neutrophil aggregation, accumulation and inflammation
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