Neuroprotekciós beavatkozásások globális ischemia modelleken: a stroke megelőzésének és terápiájának egy új megközelítése = Neuroprotective interventions on models of the global ischemia: a new approach for prevention and therapy of stroke

A projekt fő célkitűzése agyi ischemiás modelleken neuroprotektív stratégiák kidolgozása és új neuroprotektív mulekulák előállítása és kipróbálása volt. A kitűzött célt három különböző módon közelítettük meg: 1) az ischemiás attack-ot követő extrém magas agyi glutamát (Glu) szintet szisztémásan adott glutamát scavengerek alkalmazásával csökkentettük. 2) olyan kinurénsav (KYNA) analógokat szintetizáltunk, melyek könnyen átjutnak a vér-agy gáton, tehát szisztémásan adhatók, ugyanakkor a központi idegrendszerbe bejutva, az NMDA receptorokhoz kötődve, csökkentik az idegszövet-károsító hiperexcitabilitást. 3) a sejtek természetes védekező mechanizmusait aktiváló pre- és posztkondícionálási paradigmákat dolgoztunk ki. A fent részletezett három területen végzett kutatómunka lehetőséget biztosított a különböző neurodegenerítv betegségek pathomechanizmusában a közös biológiai momentumok felismerésére. A projekt keretében végzett munka az elméleti ismereteken túl, a jövőben gyakorlati (gyógyszerfejlesztési ill. klinikai) jelentőséggel is bírhat. | The main goal of this project was to develop new neuroprotective strategies and molecules on ischemic brain models. To approach this goal we used three different ways: 1) to reduce the excess glutamate (Glu) levels within the brain following an ischemic attack with administration of glutamate scavengers. 2) To develop such kynurenic acid (KYNA) analogues which are able to cross the blood-brain barrier (BBB) and able to reduce the hyperexcitability by blocking NMDA receptors. 3) To develop such pre- and postconditioning protocols which are able to activate the endogenous self-protective mechanisms resulting in neuroprotection after an ischemic attack. In the course of these studies, we had chance to realize the common elements in the pathomechanisms of different neurodegenerative disorders. Taken together our results, we hope that they may have pharmaceutical or clinical importance in the future

Vehicle Control with Cloud-aided Learning Feature: an Implementation on Indoor Platform

Safe motion together with improved economy and traveling performance levels are important requirements against automated vehicles. Thus, the design of enhanced control systems is requested, which contain conventional model-based controllers and the use of unconventional approaches, e.g., learning features and cloud-based methods. This paper proposes a hierarchical vehicle control design method with learning functions, which incorporates control in two levels, such as in cloud level and in vehicle level. The control on the cloud level is designed by using reinforcement learning, with which the maximum speed for the vehicle is achieved. The vehicle level contains a robust controller and a supervisor, with which the collision avoidance of the vehicle is guaranteed. The hierarchical control guarantees performance requirement of safe motion, i.e., collision avoidance in all scenarios, even if the connection with the cloud is lost. The proposed control on indoor Hardware-in-the-Loop platform is implemented. The effectiveness of the control and the safe motion of the vehicle under various scenarios with and without cloud connection are demonstrated. Copyright (c) 2022 The Authors. This is an open access article under the CC BY-NC-ND licens

Neuroprotective effects of repeated transient global ischemia and of kynurenine adminsitration induced by four-vessel occlusions on hippocampal CA1 neurons.

The hippocampal CA1 subfield is a brain region that is particularly sensitive to hypoxia. Although this subfield is selectively vulnerable to ischemic injuries manifested in delayed neuronal death (DND), the mechanism leading to neuronal degeneration is not fully understood. Burda recently reported that a second pathophysiological stress, applied within a suitable time, offers an opportunity for salvaging neurons in the CA1 region against DND (Neurochem. Res., 30: 1397-1405, 2005). In our study, NeuN immunohistochemistry was applied to detect survival CA1 neurons, while Fluoro-Jade B staining was used to evaluate the number of injured neurons after interventions resulting in transient global ischemia. Four groups of animals were used: 1: intact controls; 2: sham controls (2 vertebral arteries coagulated (2VAC), but 2 carotids sham-operated); 3: 2VAC + 2 carotids occluded (2CA) for 10 min; 4: 2VAC + 2CA (10 min) + 2 days later, a repeated 2CA (5 min). In group 3 (2VAC + 2CA (10 min)), marked cell destruction was found in the CA1 subfield: only 36.4% of the CA1 neurons survived. However, in group 4 (5-min second ischemic insult), the proportion of surviving cells in the CA1 region was 59.3%. There was no significant difference in CA1 cell loss between groups 1 and 2. Our findings suggest that the second ischemic stress, 2 days after the first ischemia induced by 2VAC + 2CA can be efficient in the prevention of DND. Neuroprotective effect was also found in four-vessel occlusion models after kynurenine (i.v.) administration

Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated

Searching for Translated Plagiarism with the Help of Desktop Grids

Translated or cross-lingual plagiarism is defined as the translation of someone else’s work or words without marking it as such or without giving credit to the original author. The existence of cross-lingual plagiarism is not new, but only in recent years, due to the rapid development of the natural language processing, appeared the first algorithms which tackled the difficult task of detecting it. Most of these algorithms utilize machine translation to compare texts written in different languages. We propose a different method, which can effectively detect translations between language-pairs where machine translations still produce low quality results. Our new algorithm presented in this paper is based on information retrieval (IR) and a dictionary based similarity metric. The preprocessing of the candidate documents for the IR is computationally intensive, but easily parallelizable. We propose a desktop Grid solution for this task. As the application is time sensitive and the desktop Grid peers are unreliable, a resubmission mechanism is used which assures that all jobs of a batch finish within a reasonable time period without dramatically increasing the load on the whole system

Spreading depression and evoked potentials recorded in the somatosensory cortex of the rat

Cortical spreading depression (CSD) is associated with changes in the caliber of surface blood vessels; others have described it as a phenomenon which arises spontaneously and repetitively following acute cortical injury in animals, including both focal ischemia and trauma, while yet other researchers consider it to be an electrophysiological substrate of migraine aura, which may trigger headache. Our group is involved in research into both migraine and ischemia-induced pathophysiological states. It therefore appeared reasonable to include the study of CSD in the methodological repertoire utilized in our laboratory. We introduced two models of CSD induction: CSD evoked during continuous topical KCl application and CSD induced through a single KCl microinjection into the cortical tissue. This paper describes details of these two methods and of basic parameters of CSDs

Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits.

Recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional "remapping" occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel. Using in vivo calcium imaging to longitudinally record sensory-evoked activity under light anesthesia, we did not find any increase in the number of C1 whisker-responsive neurons in the adjacent, spared D3 barrel after stroke. To promote plasticity after stroke, we also plucked all whiskers except C1 (forced use therapy). This led to an increase in the reliability of sensory-evoked responses in C1 whisker-responsive neurons but did not increase the number of C1 whisker-responsive neurons in spared surround barrels over baseline levels. Our results argue against remapping of functionality after barrel cortex stroke, but support a circuit-based mechanism for how rehabilitation may improve recovery