Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

A Multinomial Model of Event-Based Prospective Memory.

Prospective memory is remembering to perform an action in the future. The authors introduce the 1st formal model of event-based prospective memory, namely, a multinomial model that includes 2 separate parameters related to prospective memory processes. The 1st measures preparatory attentional processes, and the 2nd measures retrospective memory processes. The model was validated in 4 experiments. Manipulations of instructions to place importance on either the prospective memory task or the background task (Experiments 1 and 2) and manipulations of distinctiveness of prospective memory targets (Experiment 2) had expected effects on model parameters, as did a manipulation of the difficulty of prospective memory target encoding (Experiments 3 and 4). An alternative model was also evaluated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Machining of reproducible flaws corresponding to fatigue cracks for fracture mechanics tests of components and welded joints

In connection with the analysis and the development of failure concepts in fracture mechanics for quasistatic loaded components and elastic-plastic behaviour of the material, tests are also carried out with welded and/or complex shaped specimens or structures. Thereby the difficulty arises of generating reproducible flaws in the form of fatigue precracks in definite positions in the components, respectively in the welded joint. It is reported exemplarily about experiments on different CT25 and CCT specimens and on a pressure vessel which contained a fatigue pre-crack, a 0.2 mm saw cut or notches with notch root radius ≤ ≥ 0.1 mm as flaws. The comparison of the results with regard to J-integral at initiation of stable crack, J_i, and J_R curves shows that under certain conditions the 0.2 mm saw cut (notch root radius ≤ ≤ 0.02 mm) is a useful alternative, if reproducible generation of a fatigue pre-crack will not be successful or too expensive. The tests were carried out on StE 460 and on a welded joint of this steel at 25 ± 2°C.     

Heat-integrated reactor concepts for catalytic reforming and automotive exhaust purification

Optimal solutions in environmental catalysis require a well-coordinated development of catalysts and of process design. This contribution is devoted to energy integrated design concepts for fuel reforming and for automotive exhaust purification. The examples presented demonstrate the importance of an innovative process design for optimal utilization of existing catalysts and show the potential of future developments.

New concepts for steam reforming through the efficient coupling of the endothermic reforming reaction with an exothermic combustion reaction are discussed in the first part. These concepts have been implemented for methanol steam reforming in a counter-current reactor with distributed side feed of burner gas and for methane steam reforming in a modular reactor with a co-current reaction section for the endothermic and the combustion reaction and attached counter-current heat exchangers. Both applications employ the so-called folded sheet reactor design, which ensures an excellent heat transfer between the reforming and combustion channels and efficient heat recovery.

A similar design solution is introduced for the apparently different case of automotive exhaust purification. The proposed concept aims at decoupling exhaust after-treatment from engine control. Its main component is a counter-current heat exchanger with integrated purification stages for HC-oxidation, NO_X storage and reduction and soot filtering. A small catalytic burner at the hot end of the heat exchanger provides both heat and oxidizing or reducing agents on demand. A new soot filter design allows for safe soot filter regeneration.     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Support Vector machine and duration-aware conditional random field for identification of spatio-temporal activity patterns by combined indoor positioning and heart rate sensors

Tracking the spatio-temporal activity is highly relevant for domains like security, health, and quality management. Since animal welfare became a topic in politics and legislation locomotion patterns of livestock have received increasing interest. In contrast to the monitoring of pedestrians cattle activity tracking poses special challenges to both sensors and data analysis. Interesting states are not directly observable by a single sensor. In addition, sensors must be accepted by cattle and need to be robust enough to cope with a rough environment. In this article, we introduce the novel combination of heart rate and positioning sensors. Attached to neck and chest they are less interfering than accelerometers at the ankles. Exploiting the potential of such combined sensor system that records locomotion and non-spatial information from the heart rate sensor however is challenging. We introduce a novel two level method for the activity tracking focused on the duration and sequence of activity states. We combine Support Vector Machine (SVM) with Conditional Random Field (CRF) and extend Conditional Random fields by an explicit representation of duration. The SVM characterizes local activity states, whereas the CRF addresses sequences of local states to sequences incorporating spatial and non-spatial contextual knowledge. This combination provides a reliable and comprehensive identification of defined activity patterns, as well as their chronology and durations, suitable for the integration in an activity data base. This data base is used to extract physiological parameters and promises insights into internal states such as fitness, well-being and stress. Interestingly we were able to demonstrate a significant correlation between resting pulse rate and the day of pregnancy.     

Shared WiFi-Communities – User Generated Infrastructure am Beispiel von FON

Shared WiFi-Communities emerge when users share their private Wireless Fidelity with others and in return get free internet access via community members’ internet connection. Supply of wireless capacity and demand for WLAN usually are coordinated by a central authority therewith users can find specific hosts within the community. Initial players that conduct commercial WiFi-Communities established their position in the market. The international market leader with 170,000 hotspots worldwide is FON. The commercial success of shared WiFi-communities (e.g. FON) depends on the adoption of a special router or modifications of the existing WLAN-infrastructure. More importantly it is essential that users permanently offer broadband capacity to the community. Only then net effects can durably generate enhanced usage benefits. A survey of 268 German FON users reveals that the community shows a high level of cohesion. Users barely vary from the default setting concerning shared bandwidth of the router. Additionally most interviewees offer their WLAN 24 hours a day. Despite the possibility of earning money with the wireless capacity most users do not offer bandwidth with a purely economic ambition. Although the market potential of shared WiFi communities appears tremendous legal obstructions and technical restraints exacerbate penetration.