Vortex streets behind bridge piers -Studies with Telemac-2D/3D & Telemac-AD

Water Qualit

Typ I Interferon assoziierte Rekrutierung zytotoxischer Lymphozyten beim Lichen sclerosus et atrophicus via CXCR3-CXCL10 Interaktion

Der Lichen sclerosus et atrophicus (LSA) ist eine chronisch-entzündliche Dermatose mit nicht vollständig geklärter Ätiologie, wahrscheinlich handelt es sich um eine Autoimmunerkrankung. Histologisch ist die Erkrankung durch das Bild einer so genannten „Interface-Dermatitis“ charakterisiert, bei der Lymphozyten in die obere Dermis migrieren und die basale Epidermis infiltrieren sowie möglicherweise (bisher unidentifizierte) LSA-assozierte Antigene destruieren. Langfristig führt dies zur Hyalinisierung der oberen Dermis mit Verlust funktioneller Eigenschaften der Haut. Ziel der hier vorgestellten Arbeit war es zu untersuchen, ob beim Lichen sclerosus et atrophicus Typ I Interferon-assoziierte proinflammatorische Mechanismen eine pathogenetische Rolle zur Rekrutierung von Effektorzellen in die Läsionen spielen. Dieses konnte in zurückliegenden Studien für zahlreiche verwandte Krankheitsbilder, wie den kutanen Lupus erythematodes und den Lichen ruber, gezeigt werden. Wir haben LSA-Hautbiopsien auf das Vorliegen entsprechender Entzündungsmuster untersucht, dazu wurden Hautproben von insgesamt 11 LSA Patienten sowie geeigneter Kontrollen (jeweils 5 Proben: Lupus erythematodes, atopische Dermatitis, gesunde Haut) immunhistologisch charakterisiert. In den LSA-Hautproben konnte eine überwiegend T-zelluläre Immunreaktion gezeigt werden, bei der die Rekrutierung CXCR3+ zytotoxischer Effektor-Zellen über die Induktion IFN-induzierbarer Chemokine (CXCL10) beteiligt war. CXCL10 wurde von Keratinozyten in genau den basalen Epidermisbereichen exprimiert, in welche die zytotoxischen Zellen infiltrierten. Interessanterweise konnte zudem erstmals gezeigt werden, dass zahlreiche infiltrierende Lymphozyten selbst das Chemokin CXCL10 in ihrer Granula tragen. Diese könnten einen wichtigen Mechanismus zur „Selbstrekrutierung“ dieser Zellen darstellen und somit zum typischen chronischen Verlauf der Erkrankung beitragen

Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins

Nose-to-brain delivery presents a promising alternative route compared to classical blood-brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide-alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110-150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air-liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity

Site-selective modification of proteins for the synthesis of structurally defined multivalent scaffolds

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.A combination of classical site-directed mutagenesis, genetic code engineering and bioorthogonal reactions delivered a chemically modified barstar protein with one or four carbohydrates installed at specific residues. These protein conjugates were employed in multivalent binding studies, which support the use of proteins as structurally defined scaffolds for the presentation of multivalent ligands.DFG, SFB 765, Multivalenz als chemisches Organisations- und Wirkprinzip: Neue Architekturen, Funktionen und Anwendunge

Perkins water tower and water system improvements design

The City of Perkins needs a new water tower to provide storage for fire flow for a proposed Iowa Tribe health center. The health center is expected to prompt westward residential development in the town, but the western part of the city is less developed than the east. These new developments, along with the overall future growth of the city, may require water system improvements so that the water distribution system can sustain the city. This project involves the design of a 250,000-gallon composite water tower and an in-depth water system analysis for improvement suggestions. The tower and water system designs will help the City of Perkins support the proposed health center and future development by adding additional storage for clean water and facilitating water movement for better water pressure and flow

Monitoring Temperature and Heart Rate during Surgical Field Implantation of PTT-100 Satellite Transmitters in Greenland Sea Birds

Information on cloacae temperature (CT), heart rate (HR), Isoflurane use, and oxygen flow was collected during field implantation of Platform Terminal Transmitters (PTT-) 100 satellite transmitters in Greenland sea birds. Information was obtained from 14 intracoelomic and 5 subcutaneous implantations in thick-billed murres (Uria lomvia) and 9 intracoelomic implantations in common eiders (Somateria mollissima). CT decreased in the order subcutaneous murres > intracoelomic eiders > intracoelomic murres due to the explorative exposure to the surroundings and increased heat loss (murres smaller than eiders) and were preheated to 35∘C. During all implantations, heat loss was prevented using electric heat and rescue blankets. Regarding HR, the fluctuations were most pronounced during the intracoelomic murre implantations as a result of lower PTT temperature and lower body size leading to more pronounced digital manipulations and stimulation of the pelvic nerve plexus. Based on these results, we therefore suggest that HR and CT are carefully monitored in order to adjust anaesthesia and recommend the use of an electric heat blanket and preheating of PTTs to body temperature in order to prevent unnecessary heat loss causing physiological stress to the birds

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (SE) of decline in FVC (mL/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (SE) changes in FVC at week 52 were -86.4 (21.1) mL in the placebo group and -39.1 (22.2) mL in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were -41.5 (24.0) mL in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) mL in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://www.clinicaltrials.gov), NCT02597933 and NCT03313180

Masses of the physical mesons from an effective QCD--Hamiltonian

The front form Hamiltonian for quantum chromodynamics, reduced to an effective Hamiltonian acting only in the $q\bar q$ space, is solved approximately. After coordinate transformation to usual momentum space and Fourier transformation to configuration space a second order differential equation is derived. This retarded Schr\"odinger equation is solved by variational methods and semi-analytical expressions for the masses of all 30 pseudoscalar and vector mesons are derived. In view of the direct relation to quantum chromdynamics without free parameter, the agreement with experiment is remarkable, but the approximation scheme is not adequate for the mesons with one up or down quark. The crucial point is the use of a running coupling constant $\alpha_s(Q^2)$, in a manner similar but not equal to the one of Richardson in the equal usual-time quantization. Its value is fixed at the Z mass and the 5 flavor quark masses are determined by a fit to the vector meson quarkonia.Comment: 18 pages, 4 Postscript figure

Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.

In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and αvβ3 integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer