Proof-of-concept that network pharmacology is effective to modify development of acquired temporal lobe epilepsy

Epilepsy is a complex network phenomenon that, as yet, cannot be prevented or cured. We recently proposed network-based approaches to prevent epileptogenesis. For proof of concept we combined two drugs (levetiracetam and topiramate) for which in silico analysis of drug-protein interaction networks indicated a synergistic effect on a large functional network of epilepsy-relevant proteins. Using the intrahippocampal kainate mouse model of temporal lobe epilepsy, the drug combination was administered during the latent period before onset of spontaneous recurrent seizures (SRS). When SRS were periodically recorded by video-EEG monitoring after termination of treatment, a significant decrease in incidence and frequency of SRS was determined, indicating antiepileptogenic efficacy. Such efficacy was not observed following single drug treatment. Furthermore, a combination of levetiracetam and phenobarbital, for which in silico analysis of drug-protein interaction networks did not indicate any significant drug-drug interaction, was not effective to modify development of epilepsy. Surprisingly, the promising antiepileptogenic effect of the levetiracetam/topiramate combination was obtained in the absence of any significant neuroprotective or anti-inflammatory effects as indicated by multimodal brain imaging and histopathology. High throughput RNA-sequencing (RNA-seq) of the ipsilateral hippocampus of mice treated with the levetiracetam/topiramate combination showed that several genes that have been linked previously to epileptogenesis, were significantly differentially expressed, providing interesting entry points for future mechanistic studies. Overall, we have discovered a novel combination treatment with promise for prevention of epilepsy

Experimental investigation of mini Gurney flaps in combination with vortex generators for improved wind turbine blade performance

This wind tunnel study investigates the aerodynamic effects of mini Gurney flaps (MGFs) and their combination with vortex generators (VGs) on the performance of airfoils and wind turbine rotor blades. VGs are installed on the suction side aiming at stall delay and increased maximum lift. MGFs are thin angle profiles that are attached at the trailing edge in order to increase lift at pre-stall operation. The implementation of both these passive flow control devices is accompanied by a certain drag penalty. The wind tunnel tests are conducted at the Hermann-Föttinger Institut of the Technische Universität Berlin based on two airfoils that are characteristic of different sections of large rotor blades. Lift and drag are determined using a force balance and a wake rake, respectively, for static angles of attack between −5 and 17∘ at a Reynolds number of 1.5 million. The impact of different MGF heights including 0.25 %, 0.5 % and 1.0 % and a VG height of 1.1 % of the chord length is tested and evaluated. Furthermore, the clean and the tripped baseline cases are considered. In the latter, leading-edge transition is forced with Zig Zag (ZZ) turbulator tape. The preferred configurations are the smallest MGF on the NACA63(3)618 and the medium-sized MGF combined with VGs on the DU97W300. Next, the experimental lift and drag polar data are imported into the software QBlade in order to design a generic rotor blade. The blade performance is simulated with and without the add-ons by means of two case studies. In the first case, the retrofit application on an existing blade mitigates the adverse effects of the ZZ tape. Stall is delayed and the aerodynamic efficiency is partly recovered leading to an improvement of the power curve. In the second case, the new design application allows for the design of a more slender blade while maintaining the rotor power. This alternative blade appears to be more resistant against the adverse effects of forced leading-edge transition

Community-Based Outbreaks in Vulnerable Populations of Invasive Infections Caused by Streptococcus pneumoniae Serotypes 5 and 8 in Calgary, Canada

BACKGROUND: Outbreaks of invasive pneumococcal disease (IPD) typically occur within institutions. Beginning in 2005, we detected an increase in serotype (ST) 5 and ST8 IPD cases, predominantly in homeless persons living in an open community. METHODOLOGY/PRINCIPAL FINDINGS: CASPER (Calgary Area S. pneumoniae Epidemiology Research) surveillance study of all IPD (sterile site isolates) in our region (pop ~1,100,000). Interviews and chart reviews of all cases and all isolates phenotypically analyzed and selected isolated tested by multi-locus sequence typing (MLST). CONCLUSIONS/SIGNIFICANCE: During 2005-2007, 162 cases of ST5 IPD and 45 cases of ST8 IPD were identified. The isolates demonstrated phenotypic and genotypic clonality. The ST5 isolates were sequence type (ST) 289 and demonstrated intermediate susceptibility to TMP-SMX. The ST8 isolates were predominantly ST1268, with a susceptible antimicrobial susceptibility profile. Individuals with ST5 IPD were more likely to be middle aged (OR 2.6), homeless (OR 4.4), using illicit drugs(OR 4.8), and asthmatic(OR 2.6). Those with ST8 were more likely to be male (OR 4.4), homeless (OR 2.6), aboriginal (OR7.3), and a current smoker (OR 2.5). Overlapping outbreaks of ST5 and ST8 IPD occurred in an open community in Calgary, Canada and homelessness was a predominant risk factor. Homelessness represents a unique community in which pneumococcal outbreaks can occur

An Inhibitory Sex Pheromone Tastes Bitter for Drosophila Males

Sexual behavior requires animals to distinguish between the sexes and to respond appropriately to each of them. In Drosophila melanogaster, as in many insects, cuticular hydrocarbons are thought to be involved in sex recognition and in mating behavior, but there is no direct neuronal evidence of their pheromonal effect. Using behavioral and electrophysiological measures of responses to natural and synthetic compounds, we show that Z-7-tricosene, a Drosophila male cuticular hydrocarbon, acts as a sex pheromone and inhibits male-male courtship. These data provide the first direct demonstration that an insect cuticular hydrocarbon is detected as a sex pheromone. Intriguingly, we show that a particular type of gustatory neurons of the labial palps respond both to Z-7-tricosene and to bitter stimuli. Cross-adaptation between Z-7-tricosene and bitter stimuli further indicates that these two very different substances are processed by the same neural pathways. Furthermore, the two substances induced similar behavioral responses both in courtship and feeding tests. We conclude that the inhibitory pheromone tastes bitter to the fly

Expert considerations and consensus for using dogs to detect human SARS-CoV-2-infections

Funding Information: This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation.Peer reviewe

SYNERGISTIC USE OF OPTICAL AND RADAR DATA FOR RAPID MAPPING OF FOREST FIRES IN THE EUROPEAN MEDITERRANEAN

In a classical approach, optical data are being used for forest fire detection in a rush mode. Difficulties arise due to persistent cloud coverage, haze layers and smoke plumes. In contrast, radar measurements offer high acquisition rates because of their ability to penetrate clouds and their independence of sun illumination. However, a visual interpretation of radar data is generally less intuitive than optical imagery for an untrained image analyst. Thus the main focus of our work was to combine the advantages of both data types and to develop a robust and fast but at the same time precise and transferable algorithm for burned area detection in the European Mediterranean region. Object-based change detection approaches and a synergistic use of optical and radar data can improve detection capabilities. The optical part of the algorithm covers very high resolution satellite images (like SPOT 5) including index calculation such as MSAVI, BAI and NDSWIR in single-temporal approaches and their temporal differences in multi- temporal approaches. Within the scope of both methodologies the burned area can be detected with an accuracy higher than 90%. In line with other authors (Libonati et al., 2011; Pereira et al., 1999) our work confirms the middle infrared band as crucial for burned area detection. The radar algorithm was based on TerraSAR-X StripMap data acquired before and after the forest fires. Different polarisations (VV and HH) have been used to improve the forest fire mapping capability. In addition, a comparison of burned and unburned areas was performed using different backscatter coefficients. These change detection techniques were based on image differences, image ratios and index calculation. The image segmentation was performed by using the new calculated layers. The burned area was then classified via a threshold given by the pre- and post- disaster differences. The classification result achieved an accuracy of 78%. This result shows the limitations of burned area mapping with microwaves. Therefore a combination of the optical and the radar technique, which takes advantage of both the optical accuracy and the ability of microwaves to penetrate clouds, led to the design and implementation of a single- and multi-temporal, object-based and semi-operational tool for burned area mapping

A fuzzy logic-based approach for the detection of flooded vegetation by means of Synthetic Aperture Radar data

In this paper an algorithm designed to map flooded vegetation from synthetic aperture radar (SAR) imagery is introduced. The approach is based on fuzzy logic which enables to deal with the ambiguity of SAR data and to integrate multiple ancillary data containing topographical information, simple hydraulic considerations and land cover information. This allows the exclusion of image elements with a backscatter value similar to flooded vegetation, to significantly reduce misclassification errors. The flooded vegetation mapping procedure is tested on a flood event that occurred in Germany over parts of the Saale catchment on January 2011 using a time series of high resolution TerraSAR-X data covering the time interval from 2009 to 2015. The results show that the analysis of multi-temporal X-band data combined with ancillary data using a fuzzy logic-based approach permits the detection of flooded vegetation areas