TLR7/8 in the Pathogenesis of Parkinson’s Disease

Neuroinflammation and autoimmune mechanisms have a key part in the pathogenesis of Parkinson’s disease (PD). Therefore, we evaluated the role of Toll-like receptors (TLRs) as a link between inflammation and autoimmunity in PD. An in vivo model of PD was performed by administration of 1-metil 4-fenil 1,2,3,6-tetraidro-piridina (MPTP) at the dose of 20 mg/kg every 2 h for a total administration of 80/kg, both in single Knock Out (KO) mice for TLR7, TLR 8, and TLR9 and in double KO mice for TLR 7/8^-/-. All animals were compared with WT animals used as a control group. All animals were sacrificed after 7 days form the first administration of MPTP. The genetic absence of TLR 7 and 8 modified the PD pathway, increasing the immunoreactivity for TH and DAT compared to PD groups and decreasing microglia and astrocytes activation. Moreover, the deletion of TLR7 and TLR8 significantly reduced T-cell infiltration in the substantia nigra and lymph nodes, suggesting a reduction of T-cell activation. Therefore, our result highlights a possibility that an immunotherapy approach, by using a dual antagonist of TLR 7 and 8, could be considered as a possible target to develop new therapies for Parkinson diseases.     

Global production networks: Design and operation

Industrial companies are nowadays acting in global production networks (GPNs). A comprehensive scientific overview of those networks is still missing. To close this gap, a framework for designing and operating GPNs is introduced. It structures influencing factors, challenges, enablers and outlines the need for decision support systems. The state of the art in designing and operating GPNs is reviewed. Three trends are identified that help to transform historical grown networks into changeable GPNs with a focused network footprint. In conclusion, a need for future research in forming the production strategy, designing the network footprint and managing the network is given.     

Pyrazolones Activate the Proteasome by Gating Mechanisms and Protect Neuronal Cells from β-Amyloid Toxicity

Proteasome malfunction parallels abnormal amyloid accumulation in Alzheimer's Disease (AD). Here we scrutinize a small library of pyrazolones by assaying their ability to enhance proteasome activity and protect neuronal cells from amyloid toxicity. Tube tests evidenced that aminopyrine and nifenazone behave as 20S proteasome activators. Enzyme assays carried out on an “open gate” mutant (α3ΔN) proteasome demonstrated that aminopyrine activates proteasome through binding the α-ring surfaces and influencing gating dynamics. Docking studies coupled with STD-NMR experiments showed that H-bonds and π-π stacking interactions between pyrazolones and the enzyme play a key role in bridging α1 to α2 and, alternatively, α5 to α6 subunits of the outer α-ring. Aminopyrine and nifenazone exhibit neurotrophic properties and protect differentiated human neuroblastoma SH-SY5Y cells from β-amyloid (Aβ) toxicity. ESI-MS studies confirmed that aminopyrine enhances Aβ degradation by proteasome in a dose-dependent manner. Our results suggest that some pyrazolones and, in particular, aminopyrine are promising compounds for the development of proteasome activators for AD treatment.     

Securing the Communication in Private Heterogeneous Mobile Ad hoc Networks

Mobile ad hoc networking has been a hot research topic for a decade or so, and many paradigms have been making use of it. One of these paradigms is the Personal Networks (PN). It is an emerging concept where the user’s personal devices form a virtual network which is secure and private, and reacts to changing environment and context intelligently. A fundamental property of the PN is that personal devices form private multi-hop clusters in an ad hoc manner whenever they come across each other. To this end, this paper presents a pair-wise key based scheme for forming secured private clusters in mobile ad hoc networks. The solution tackles the problem of node authentication combined with traffic encryption in relatively small ad hoc networks using proactive neighbour discovery and authentication. Additionally, the paper proves the feasibility of this solution by means of prototyping and experimental performance analysis.     

Growth and analysis of C nanotubes on ceramic polymer-additives

C nanotubes are synthesized by catalytic route on ceramic supports (Al2O3, MgO and CaO), usually utilized for polymer reinforcing/flame-retardancy, aiming at nanotube-based hybrid preparation. Chemical vapor deposition is carried out in i-C4H10+H2 atmosphere over 17 wt% Fe-catalysts upon different conditions. In order to clarify the influence of support material, calcination (450 degrees C or 750 degrees C) and reduction temperature (500 degrees C or 600 degrees C) of the catalysts, and synthesis temperature (600 degrees C or 700 degrees C), catalysts utilized and nanotubes obtained are systematically investigated by the use of several analysis techniques (electron microscopy, X-ray diffraction, thermo-gravimetry and Raman spectroscopy). The results obtained show that, in the considered range of variation, support material is the most influential parameter. The most catalytically active alumina supports allow achieving higher yields, but involve larger metallic inclusions and lower crystalline quality. Remaining supports behave oppositely. The reasons for such differences are discussed in the light of the current assessments on the nanotube growth and the results obtained are compared with those available in literature for similar catalysts.     

Coumarin-conjugated multiwalled carbon nanotubes for potential biological applications: development and characterization

This work presents a novel cascade of chemical functionalization of multiwalled carbon nanotubes which allows the conjugation with differently substituted coumarins. Aim of the present work is to synthesize new materials able to rescue cells from the adverse effect of CNT particles since pristine CNTs are practically insoluble and tend to accumulate inside cells, organs and tissues. Moreover, it was reported that single walled CNTs particles show an adverse effect on keratinocytes through an oxidative mechanism, leading to NF-kB activation. The conjugation with coumarins, known superoxide anion scavengers, could switch the cytotoxicity of the new materials. The cascade functionalization of MWCNTs by sequential steps of carboxylation, acylation, amine modification and finally, coumarin conjugation have been performed and the synthesis and the chemical properties of several f-MWCNTs-coumarins have been exploited.     

Particle size analysis of lamb meat: Effect of homogenization speed, comparison with myofibrillar fragmentation index and its relationship with shear force

The impact of homogenization speed on Particle Size (PS) results was examined using samples from the M. longissimus thoracis et lumborum (LL) of 40 lambs. One gram duplicate samples from meat aged for 1 and 5 days were homogenized at five different speeds; 11,000, 13,000, 16,000, 19,000 and 22,000 rpm. In addition to this LL samples from 30 different lamb carcases also aged for 1 and 5 days were used to study the comparison between PS and myofibrillar fragmentation index (MFI) values. In this case, 1 g duplicate samples (n = 30) were homogenized at 16,000 rpm and the other half (0.5 g samples) at 11,000 rpm (n = 30). The homogenates were then subjected to respective combinations of treatments which included either PS analysis or the determination of MFI, both with or without three cycles of centrifugation. All 140 samples of LL included 65 g blocks for subsequent shear force (SF) testing. Homogenization at 16,000 rpm provided the greatest ability to detect ageing differences for particle size between samples aged for 1 and 5 days. Particle size at the 25% quantile provided the best result for detecting differences due to ageing. It was observed that as ageing increased the mean PS decreased and was significantly (P < 0.001) less for 5 days aged samples compared to 1 day aged samples, while MFI values significantly increased (P < 0.001) as ageing period increased. When comparing the PS and MFI methods it became apparent that, as opposed to the MFI method, there was a greater coefficient of variation for the PS method which warranted a quality assurance system. Given this requirement and examination of the mean, standard deviation and the 25% quantile for PS data it was concluded that three cycles of centrifugation were not necessary and this also applied to the MFI method. There were significant correlations (P < 0.001) within the same lamb loin sample aged for a given period between mean MFI and mean PS (−0.53), mean MFI and mean SF (−0.38) and mean PS and mean SF (0.23). It was concluded that PS analysis offers significant potential for streamlining determination of myofibrillar degradation when samples are measured after homogenization at 16,000 rpm with no centrifugation.     

Company-specific quantitative evaluation of lean production methods

Small and medium-sized companies encounter enormous difficulties when trying to implement lean production methods according to the role model of the Toyota Production System. This is caused by the varying effects of lean methods on production figures depending on the production conditions concerning product variety and volumes, variation of process and set-up times, etc. This article presents approaches developed at the Institute of Production Science (wbk), Karlsruhe Institute of Technology, to evaluate and optimize the effects of lean methods in small series productions based on the quantified interdependencies with the relevant target figures. It enables the best combination of lean methods to be identified and recommendations for the efficient implementation of these lean methods.