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Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV) infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls), and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF) the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition.  相似文献   
74.
Whilst gamma prime (γ′) phase is the strengthening phase in Ni-based superalloys its influence on machining has been seldom investigated. This paper reports for the first time on the effect of γ′ upon machining of Ni-based superalloys when cutting with parameters yielding different cutting temperature intervals which lead to strengthening/softening effects on the workpiece (sub)surface. In-depth XRD, SEM/FIB, EBSD analysis and unique micro-pillar testing in the workpiece superficial layers indicated that with the increase of γ′ fraction the grain plastic deformation significantly decreased, while specific cutting energy can switch from low to high values influenced by the real cutting temperature.  相似文献   
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Assessment of the shear strength of an existing post‐tensioned concrete bridge with a low amount of shear reinforcement – First application of the ”Flexural Shear Crack“ model in practice In recent years it was reported several times, that within a static assessment according to current standards the shear strength of post‐tensioned bridges, which were built in Austria before 1989, cannot be fulfilled any more. However, test results prove, that especially prestressed structures have additional load bearing capacities, which cannot be reproduced with current calculation models. In the framework of a pilot project a new developed shear model (Flexural Shear Crack Model) was used. In this paper the approach as well as the main results of a statical reevaluation of an existing post‐tensioned road bridge at the Tauern Autobahn A10 will be presented.  相似文献   
77.
Oberflächig geklebte Kohlefaserlamellen (CFK) werden seit vielen Jahren zur Bauteilverstärkung eingesetzt. Die hohe Festigkeit dieser Lamellen kann aufgrund der begrenzten Zugkapazität des Betons nicht zur Gänze ausgenutzt werden. Eingeschlitzte CFK Lamellen hingegen bieten wesentliche Vorteile, die zusammen mit Vorspannung noch weiter optimiert werden können. Für den Vorspannvorgang wurde eine spezielle Verankerung, auf Basis der Composite Wedge Technik, entwickelt, die einfaches und rasches Vorspannen erlaubt. Die Verankerung ist zudem nur 8 kg schwer, was besonders vorteilhaft beim Hantieren an der Tragwerksunterseite ist. Nach dem Vorspannen wird die Verankerung entfernt, die permanente Verankerung der Lamellenenden wird durch nachträgliches Verkleben gewährleistet. Es verbleiben keine Stahlteile im oder am Bauwerk. So zeichnet sich die Konstruktion durch geringen Wartungsaufwand und hohe Dauerhaftigkeit aus. Die Effizienz der entwickelten Systeme wurde an vorgespannten Plattenstreifen experimentell untersucht. In den Untersuchungen konnte die Funktionsfähigkeit nachgewiesen werden. Strengthening using Prestressed Near Surface Mounted Strips Exernally bonded carbon fiber reinforced plastic (CFRP) strips are used since several years for strengthening of structures. The high strength of the strips cannot be exploited in most applications. Near surface mounted strips offer several advantages, which allow for further optimization together with prestressing. For the prestressing action a special anchoring device, based on the Composite Wedge Principle, was developed, which allows a simple and quick prestressing procedure. Additionally the anchorage weighs only 8 kg, which is especially beneficial when manipulations on the lower surface of the structure are necessary. The anchorage will be removed after prestressing and the permanent anchorage of the ends of the strips will be established by bond. No steel parts remain in the structure, after completing the strengthening. This results in low maintenance and a high durability. The efficiency of the developed systems and the prestressed plate strips was examined experimentally. In these investigations a perfect functionality could be demonstrated.  相似文献   
78.
New directives of the European Union require operators of waste-to-energy (WTE) plants to report the amount of electricity that is produced from renewable sources in the waste feed. Until now, the standard method to determine the portion of renewable electricity is sorting the wastes into defined fractions of fossil organic and biogenic waste components and determining the lower heating value of these fractions. Out of it the amount of electricity production from renewables is calculated. This practice is labor and cost intensive. Therefore, it is usually carried out once a year which provides only a snapshot analysis of limited significance. This paper proposes a method to calculate the portion of electricity produced from renewable materials in waste continuously by solving a set of equations. All data required are either available from literature or from operating data routinely measured in WTE plants. The advantages are statistically derived uncertainty of the result, temporal resolution of the result down to daily mean values, low implementation efforts, and virtually no operational costs. An example of the implementation of the method to a 60 000 tons per year WTE plant is given.  相似文献   
79.
The purpose of this paper is to show that indirect recursive procedures can be used for implementing real-time applications without harm, if a few conditions are met. These conditions ensure that upper bounds for space and time requirements can be derived at compile time. Moreover they are simple enough such that many important recursive algorithms can be implemented. In addition, our approach allows for concentrating on essential properties of the parameter space during space and time analysis. This is done by morphisms that transfer important properties from the original parameter space to simpler ones, which results in simpler formulas of space and time estimates.  相似文献   
80.
Most anti-cancer drug screening assays are currently performed in two dimensions, on flat, rigid surfaces. However, there are increasing indications that three-dimensional (3D) platforms provide a more realistic setting to investigate accurate morphology, growth, and sensitivity of tumor cells to chemical factors. Moreover, interstitial flow plays a pivotal role in tumor growth. Here, we present a microfluidic 3D platform to investigate behaviors of tumor cells in flow conditions with anti-migratory compounds. Our results show that interstitial flow and its direction have significant impact on migration and growth of hepatocellular carcinoma cell lines such as HepG2 and HLE. In particular, HepG2/HLE cells tend to migrate against interstitial flow, and their growth increases in interstitial flow conditions regardless of the flow direction. Furthermore, this migratory activity of HepG2 cells is enhanced when they are co-cultured with human umbilical vein endothelial cells. We also found that migration activity of HepG2 cells attenuates under hypoxic conditions. In addition, the effect of Artemisinin, an anti-migratory compound, on HepG2 cells was quantitatively analyzed. The microfluidic 3D platform described here is useful to investigate more accurately the effect of anti-migratory drugs on tumor cells and the critical influence of interstitial flow than 2D culture models.  相似文献   
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