Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.     

Synthesis of the Antibiotic Precursor Thiazolyl‐7‐Aminocephalosporanic Acid in a Microstructured Flow System

The synthesis of thiazolyl‐7‐aminocephalosporanic acid, a pharmaceutical precursor of the β‐lactam antibiotic drug cefodizime, could be successfully realized in a continuous microstructured flow system. This was accomplished by changing the process window from batch, having a reaction temperature of 60 °C with a reaction time of 1 h, to a flow system at temperatures > 100 °C and reaction times of several minutes. The space‐time yield could be increased by a factor of 130.     

Crystallization of Stoichiometric SbSI Glass

Congruent crystallization of antimony sulphoiodide (SbSI) glass of stoichiometric composition, which is prepared successfully for the first time using rapid melt‐quenching, has been investigated using differential scanning calorimetry (DSC). The results for glass powder show a glass transition at 127°C and two separate exothermal peaks with maxima around 140°C and 190°C. The ratio of the intensities of the exothermal peak at ~190°C to the peak at ~140°C increases as the particle size and heating rate are increased, but their total enthalpy remains constant at 62 ± 2 J/g for all DSC runs. Surface heating of the glass induced by a 520 nm CW laser shows two contracted regions: needle‐like crystalline formations at low temperature and bulk crystallization at high temperature. The observed phenomena and DSC results suggest two different kinds of crystallization of the SbSI phase: one‐dimensional crystallization at low temperature which starts from the sample surface and three‐dimensional bulk crystallization that continues the transformation to crystalline state at higher temperatures. The origin of the two different crystallizations can be traced to the strong anisotropy of the SbSI crystal structure due to the weak van der Waals interaction between covalent‐ionic chains (Sb₂S₂I₂)_n.     

Self-healing through microencapsulated agents for protective coatings

The use of microcapsules containing healing agents, which can serve as source of self-healing for coatings, was investigated. The appropriate self-repairing coatings are designed to be used for heavy-duty corrosion protection or for the protection of moisture-sensitive substrates like wood. Microcapsules based on thermoset resins (urea–formaldehyde and melamine–formaldehyde) which contained components of different chemical natures (resins or inhibitors) were fabricated using emulsion techniques. The subsequent characterization included optical, fluorescence, and electron microscopy as well as adapted microindentation techniques to determine capsule break forces. Different model coatings were formulated making use of varying amounts of healing agent-charged microcapsules. The coated samples were then injured under controlled conditions (by Erichsen cupping in the case of steel, by simulated hail in the case of wood) and then subjected to salt spray testing (natural and accelerated), weathering, or even real-life exposure, always in comparison with a blank. The results obtained demonstrate the superiority of microcapsule-based self-healing coatings compared to classical protection formulations, and appropriate coating systems have in the meantime been successfully brought to the market.     

The influence of third-body particles on wear rate in unicondylar knee arthroplasty: a wear simulator study with bone and cement debris

The reduced intraoperative visibility of minimally invasive implanted unicondylar knee arthroplasty makes it difficult to remove bone and cement debris, which have been reported on the surface of damaged and retrieved bearings. Therefore, the aim of this study was to analyze the influence of bone and cement particles on the wear rate of unicompartmental knee prostheses in vitro. Fixed bearing unicompartmental knee prostheses were tested using a knee-wear-simulator according to the ISO standard 14243-1:2002(E) for 5.0 million cycles. Afterwards bone debris (particle size 671 ± 262 μm) were added to the test fluid in a concentration of 5 g/l for 1.5 million cycles, followed by 1.5 million cycles blended with cement debris (particle size 644 ± 186 μm) in the same concentration. Wear rate, knee-kinematics and wear-pattern were analyzed. The wear rate reached 12.5 ± 1.0 mm³/million cycles in the running-in and decreased during the steady state phase to 4.4 ± 0.91 mm³/million cycles. Bone particles resulted in a wear rate of 3.0 ± 1.27 mm³/million cycles with no influence on the wear rate compared to the steady state phase. Cement particles, however, lead to a significantly higher wear rate (25.0 ± 16.93 mm³/million cycles) compared to the steady state phase. The careful removal of extruded cement debris during implantation may help in reducing wear rate. Bone debris are suggested to have less critical influence on the prostheses wear rate.     

Landscape externalities from onshore wind power

The expansion of renewable energy is a central element of the German Federal Government's climate and energy policy. The target for 2020 is to produce 30% of the electricity from renewable energies. Wind power has been selected to be a major contributor to this change. Replacing old wind turbines by modern ones and building new turbines on land will be crucial in meeting this target. However, the expansion of onshore wind power is not universally accepted. In several regions of Germany residents are protesting against setting up new wind turbines. To determine the negative effects two choice experiments were applied in Westsachsen and Nordhessen, Germany. In both regions the externalities of wind power generation until 2020 based on today's state of technology were measured. The results show that negative landscape externalities would result from expanding wind power generation. Using latent class models three different groups of respondents experiencing different degrees of externalities were identified.     

EU renewable energy support policy: Faith or facts?

The recent EU Commission proposal for promoting the supply of power from renewable energy sources was originally based on a pan-European, harmonised tradable green certificate (TGC) scheme. We suggest, on the basis of a multi-disciplinary analysis, that a pan-EU TGC system is not the way forward for Europe. It is vital that the Commission (and the majority of Member States) avoids implementation of such policy designs put forward by a coalition of vested interests. They should instead look at, and act upon, the available evidence from those countries that have experimented with TGCs (e.g. Flanders, UK and Sweden) and design policies that stand a better chance of meeting the criteria of effectiveness, efficiency and equity. In particular, the policies must enable EU to meet the immense innovation/industrialisation challenge by inducing the development of a capital goods industry that can, eventually, diffuse a broad range of technologies that use renewable energy sources. Only then we can acquire an ability to implement an industrial revolution in the energy system in a way that broadly meets the criteria of effectiveness and dynamic efficiency.