IFN-γ and TNF-α synergize to inhibit CTGF expression in human lung endothelial cells.

Connective tissue growth factor (CTGF/CCN2) is an angiogenetic and profibrotic factor, acting downstream of TGF-β, involved in both airway- and vascular remodeling. While the T-helper 1 (Th1) cytokine interferon-gamma (IFN-γ) is well characterized as immune-modulatory and anti-fibrotic cytokine, the role of IFN-γ in lung endothelial cells (LEC) is less defined. Tumour necrosis factor alpha (TNF-α) is another mediator that drives vascular remodeling in inflammation by influencing CTGF expression. In the present study we investigated the influence of IFN-γ and TNF-α on CTGF expression in human LEC (HPMEC-ST1.6R) and the effect of CTGF knock down on human LEC. IFN-γ and TNF-α down-regulated CTGF in human LEC at the promoter-, transcriptional- and translational-level in a dose- and time-dependent manner. The inhibitory effect of IFN-γ on CTGF-expression could be almost completely compensated by the Jak inhibitor AG-490, showing the involvement of the Jak-Stat signaling pathway. Besides the inhibitory effect of IFN-γ and TNF-α alone on CTGF expression and LEC proliferation, these cytokines had an additive inhibitory effect on proliferation as well as on CTGF expression when administered together. To study the functional role of CTGF in LEC, endogenous CTGF expression was down-regulated by a lentiviral system. CTGF silencing in LEC by transduction of CTGF shRNA reduced cell proliferation, but did not influence the anti-proliferative effect of IFN-γ and TNF-α. In conclusion, our data demonstrated that CTGF was negatively regulated by IFN-γ in LEC in a Jak/Stat signaling pathway-dependent manner. In addition, an additive effect of IFN-γ and TNF-α on inhibition of CTGF expression and cell proliferation could be found. The inverse correlation between IFN-γ and CTGF expression in LEC could mean that screwing the Th2 response to a Th1 response with an additional IFN-γ production might be beneficial to avoid airway remodeling in asthma

The Effect of Randomness on the Mott State

We reinvestigate the competition between the Mott and the Anderson insulator state in a one-dimensional disordered fermionic system by a combination of instanton and renormalization group methods. Tracing back both the compressibility and the ac-conductivity to a vanishing kink energy of the electronic displacement field we do not find any indication for the existence of an intermediate (Mott glass) phase.Comment: 4 page

Development of a PIGE-Detection System for In-situ Inspection and Quality Assurance in the Evolution of Fast Rotating Parts in High Temperature Environment Manufactured From TiAl

Intermetallic γ-titanium aluminides are a promising material in high temperature technologies. Their high specific strength at temperatures above 700°C offers the possibility for their use as components of aerospace and automotive industries. With a specific weight of 50% of that of the widely used Ni-based superalloys TiAl is very suitable as material for fast rotating parts like turbine blades in aircraft engines and land based power stations or turbocharger rotors. Thus lower mechanical stresses and a reduced fuel consumption and CO2-emission are expected. To overcome the insufficient oxidation protection the halogen effect offers an innovative way. After surface doping using F-implantation or liquid phase-treatment with an F-containing solution and subsequent oxidation at high temperatures the formation of a protective alumina scale can be achieved. By using non-destructive ion beam analyses (PIGE, RBS) F was found at the metal/oxide interface. For analysis of large scale components a new vacuum chamber at the IKF was installed and became operative. With this prototype of in-situ quality assurance system for the F-doping of manufactured parts from TiAl some performance test measurements were done and presented in this paper.Received: 01 March 2013; Revised: 24 April 2013; Accepted: 25 April 201

A Descent Method for Equality and Inequality Constrained Multiobjective Optimization Problems

In this article we propose a descent method for equality and inequality constrained multiobjective optimization problems (MOPs) which generalizes the steepest descent method for unconstrained MOPs by Fliege and Svaiter to constrained problems by using two active set strategies. Under some regularity assumptions on the problem, we show that accumulation points of our descent method satisfy a necessary condition for local Pareto optimality. Finally, we show the typical behavior of our method in a numerical example

Influence of wind strength and direction on diffusive methane fluxes and atmospheric methane concentrations above the North Sea

Quantification of the diffusive methane fluxes between the coastal ocean and atmosphere is important to constrain the atmospheric methane budget. The determination of the fluxes in coastal waters is characterized by a high level of uncertainty. To improve the accuracy of the estimation of coastal methane fluxes, high temporal and spatial sampling frequencies of dissolved methane in seawater are required, as well as the quantification of atmospheric methane concentrations, wind speed and wind direction above the ocean. In most cases, these atmospheric data are obtained from land-based atmospheric and meteorological monitoring stations in the vicinity of the coastal ocean methane observations. In this study, we measured wind speed, wind direction and atmospheric methane directly on board three research vessels in the southern North Sea and compared the local and remote atmospheric and meteorological measurements on the quality of the flux data. In addition, we assessed the source of the atmospheric methane measured in the study area in the German Bight using air mass back-Trajectory assessments. The choice of the wind speed data source had a strong impact on the flux calculations. Fluxes based on wind data from nearby weather stations amounted to only 58 ± 34 % of values based on in situ data. Using in situ data, we calculated an average diffusive methane sea-To-Air flux of 221 ± 351 μmol m-2 d-1 (n Combining double low line 941) and 159 ± 444 μmol m-2 d-1 (n Combining double low line 3028) for our study area in September 2019 and 2020, respectively. The area-weighted diffusive flux for the entire area of Helgoland Bay (3.78 × 109 m2) was 836 ± 97 and 600 ± 111 kmol d-1 for September 2019 and 2020, respectively. Using the median value of the diffusive fluxes for these extrapolations resulted in much lower values compared to area-weighted extrapolations or mean-based extrapolations. In general, at high wind speeds, the surface water turbulence is enhanced, and the diffusive flux increases. However, this enhanced methane input is quickly diluted within the air mass. Hence, a significant correlation between the methane flux and the atmospheric concentration was observed only at wind speeds < 5 m s-1. The atmospheric methane concentration was mainly influenced by the wind direction, i.e., the origin of the transported air mass. Air masses coming from industrial regions resulted in elevated atmospheric methane concentrations, while air masses coming from the North Sea transported reduced methane levels. With our detailed study on the spatial distribution of methane fluxes we were able to provide a detailed and more realistic estimation of coastal methane fluxes

Magnetic resonance imaging analysis of the bioabsorbable Milagro™ interference screw for graft fixation in anterior cruciate ligament reconstruction

Ligament graft fixation with bioabsorbable interference screws is a standard procedure in cruciate ligament replacement. Previous screw designs may resorb incompletely, and can cause osteolysis and sterile cysts despite being implanted for several years. The aim of this study was to examine the in vivo degradation and biocompatibility of the new Milagro™ interference screw (Mitek, Norderstedt, Germany). The Milagro™ interference screw is made of 30% ß-TCP (TriCalcium phosphate) and 70% PLGA (Poly-lactic-co-glycolic acid). In the period between June 2005 and February 2006, 38 patients underwent graft fixation with Milagro™ screws in our hospital. Arthroscopic ACL reconstruction was performed using hamstring tendon grafts in all the patients. MR imaging was performed on 12 randomly selected patients out of the total of 38 at 3, 6 and 12 months after surgery. During the examination, the volume loss of the screw, tunnel enlargement, presence of osteolysis, fluid lines, edema and postoperative screw replacement by bone tissue were evaluated. There was no edema or signs of inflammation around the bone tunnels. At 3, 6 and 12 months, the tibial screws showed an average volume loss of 0, 8.1% (±7.9%) and 82.6% (±17.2%, P < 0.05), respectively. The femoral screws showed volume losses of 2.5% (±2.1%), 31.3% (±21.6%) and 92.02% (±6.3%, P < 0.05), respectively. The femoral tunnel enlargement was 47.4% (±43.8%) of the original bone tunnel volume after 12 months, and the mean tunnel volume of the tibial tunnel was −9.5% (±58.1%) compared to the original tunnel. Bone ingrowth was observed in all the patients. In conclusion, the resorption behaviour of the Milagro™ screw is closely linked to the graft healing process. The screws were rapidly resorbed after 6 months and, at 12 months, only the screw remnants were detectable. Moreover, the Milagro™ screw is biocompatible and osteoconductive, promoting bone ingrowth during resorption. Tunnel enlargement is not prevented in the first months but is reduced by bone ingrowth after 12 months

The three-way relationship of polymorphisms of porcine genes encoding terminal complement components, their differential expression, and health-related phenotypes

<p>Abstract</p> <p>Background</p> <p>The complement system is an evolutionary ancient mechanism that plays an essential role in innate immunity and contributes to the acquired immune response. Three modes of activation, known as classical, alternative and lectin pathway, lead to the initiation of a common terminal lytic pathway. The terminal complement components (TCCs: C6, C7, C8A, C8B, and C9) are encoded by the genes <it>C6</it>, <it>C7</it>, <it>C8A</it>, <it>C8B</it>, <it>C8G</it>, and <it>C9</it>. We aimed at experimentally testing the porcine genes encoding TCCs as candidate genes for immune competence and disease resistance by addressing the three-way relationship of genotype, health related phenotype, and mRNA expression.</p> <p>Results</p> <p>Comparative sequencing of cDNAs of animals of the breeds German Landrace, Piétrain, Hampshire, Duroc, Vietnamese Potbelly Pig, and Berlin Miniature Pig (BMP) revealed 30 SNPs (21 in protein domains, 12 with AA exchange). The promoter regions (each ~1.5 kb upstream the transcription start sites) of <it>C6</it>, <it>C7</it>, <it>C8A</it>, <it>C8G</it>, and <it>C9</it> exhibited 29 SNPs. Significant effects of the TCC encoding genes on hemolytic complement activity were shown in a cross of Duroc and BMP after vaccination against Mycoplasma hyopneumoniae, Aujeszky disease virus and PRRSV by analysis of variance using repeated measures mixed models. Family based association tests (FBAT) confirmed the associations. The promoter SNPs were associated with the relative abundance of TCC transcripts obtained by real time RT-PCR of 311 liver samples of commercial slaughter pigs. Complement gene expression showed significant relationship with the prevalence of acute and chronic lung lesions.</p> <p>Conclusions</p> <p>The analyses point to considerable variation of the porcine TCC genes and promote the genes as candidate genes for disease resistance.</p