The gut-brain axis in ischemic stroke: its relevance in pathology and as a therapeutic target

The gut contains the largest reservoir of microorganisms of the human body, termed as the gut microbiota which emerges as a key pathophysiological factor in health and disease. The gut microbiota has been demonstrated to influence various brain functions along the gut-brain axis. Stroke leads to intestinal dysmotility and leakiness of the intestinal barrier which are associated with change of the gut microbiota composition and its interaction with the human host. Growing evidence over the past decade has demonstrated an important role of these post-stroke changes along the gut-brain axis to contribute to stroke pathology and be potentially druggable targets for future therapies. The impact of the gut microbiota on brain health and repair after stroke might be attributed to the diverse functions of gut bacteria in producing neuroactive compounds, modulating the host's metabolism and immune status. Therefore, a better understanding on the gut-brain axis after stroke and its integration in a broader concept of stroke pathology could open up new avenues for stroke therapy. Here, we discuss current concepts from preclinical models and human studies on the bi-directional communication along the microbiota- gut-brain axis in stroke

Disposition of14C-labelled endotelon in humans

Summary: In order to study the disposition of ENDOTELON in humans, this compound was labelled withl4C by photosynthesis. ENDOTELON consists of a complex of procyanidolic oligomers extracted from the seeds of a variety of vine cultivated in the Bordeaux wine-growing region, and is prescribed for the treatment of chronic venous insufficiency and retinal lesions. Considering the difficulty in labelling the various constituents of the product, the labelling procedure was based on providing radioactive C02 to the plant. After isolation and purification, 150 mg of active material (50 μCf) was administered orally to six healthy volunteers. Radioactivity was measured in the blood over time until 72 and 120 hours in the same subjects after drug administration. Urinary and faecal elimination was measured for a period of 167 hours. Urinary elimination of the radioactive compounds represented 12 to 27% of the administered dose and faecal elimination represented 47 to 75% depending on the subject. The radioactivity of thel4C02 eliminated in the breath was also measured, and represented around 8% of the total radioactivity for the 72-hour period after administration. Although the disposition of ENDOTELON is based on the total radioactivity measured over time, this technique allows the evaluation of the elimination rate of the product and its metabolites from the human bod

The Gut Ecosystem: A Critical Player in Stroke

The intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery

Intelligent Sensing for Robotic Re-Manufacturing in Aerospace - An Industry 4.0 Design Based Prototype

Emerging through an industry-academia collaboration between the University of Sheffield and VBC Instrument Engineering Ltd, a proposed robotic solution for remanufacturing of jet engine compressor blades is under ongoing development, producing the first tangible results for evaluation. Having successfully overcome concept adaptation, funding mechanisms, design processes, with research and development trials, the stage of concept optimization and end-user application has commenced. A variety of new challenges is emerging, with multiple parameters requiring control and intelligence. An interlinked collaboration between operational controllers, Quality Assurance (QA) and Quality Control (QC) systems, databases, safety and monitoring systems, is creating a complex network, transforming the traditional manual re-manufacturing method to an advanced intelligent modern smart-factory. Incorporating machine vision systems for characterization, inspection and fault detection, alongside advanced real-time sensor data acquisition for monitoring and evaluating the welding process, a huge amount of valuable industrial data is produced. Information regarding each individual blade is combined with data acquired from the system, embedding data analytics and the concept of ìInternet of Thingsî (IoT) into the aerospace re-manufacturing industry. The aim of this paper is to give a first insight into the challenges of the development of an Industry 4.0 prototype system and an evaluation of first results of the operational prototype

Assessing Function and Identifying Modifiers of Protein Isoaspartyl Methyltransferase in Schizosaccharomyces pombe

Thesis advisor: Clare O'ConnorProtein isoaspartyl methyltransferase (PIMT), an ancient enzyme with putative homologs in virtually all eukaryotes studied to date, is a protein repair enzyme that initiates restoration of age-damaged isoaspartyl residues back into normal amino acids. I studied the functional importance of PIMT in Schizosaccharomyces pombe, whose PIMT-encoding homolog is designated pcm2. Past studies of PIMT in other organisms had suggested that Pcm2p function could be important for viability under stress conditions. In the first part of the project, I compared the viability of a yeast strain lacking pcm2 under a variety of stress conditions, including stationary phase, heat shock, high-salt, high-sugar, high-pH, and high temperature. Based on studies of PIMT in other organisms, I expected to see reduced viability of the knockout strain during stress conditions, but no difference in cell growth or viability was observed. I also attempted to use Real-Time PCR to compare pcm2 transcription in yeast under the same stress conditions. I have not yet collected any usable data from the Real-Time PCR runs, but it has been previously shown that pcm2 transcription increases during stationary phase, heat shock, and osmotic shock. This increase in pcm2 transcription during stress with no phenotype associated with loss of pcm2 under stress conditions leads to the hypothesis that there may be a second gene whose product can compensate for loss of PIMT function. To locate and identify this gene, a synthetic lethal screen is being utilized. Currently, five potential synthetic lethal mutants have been isolated.Submitted to: Boston College. College of Arts and Sciences.Discipline: College Honors Program.Discipline: Biology

Advanced titanium welding in particle physics and aerospace engineering

The quest for answers that will unlock the mysteries of the cosmos and broaden our perception and understanding of the physical laws that govern the universe, demands studying particle collisions of high energies at particle accelerators. Monitoring of these collisions requires complex detectors whose development pushes the boundaries of engineering. In the present study advanced titanium welding is explored in the development of the new ATLAS Inner Tracker detector to be installed in line with the High-Luminosity Large Hadron Collider at CERN. Pulsed welding currents are employed to join thin titanium pipes used in the detector’s evaporative CO2 cooling system. The benefits of the low heat input enabled by the welding process are utilised in the repair and remanufacturing industry of aerospace applications. Wire arc additive manufacturing is applied in the regeneration of aerospace components providing successive material deposition on a layer-upon-layer manner. To this extent investigations and implementations related to Pulsed Gas Tungsten Arc Welding are explored in the presented work aiming to further understand, implement and advance the welding process. Assurance of the weld quality is furthered studied, as the outcome of the process depends on maintaining input parameters and welding conditions at optimum levels for the whole duration of the process. By implementing process monitoring methodologies, invaluable data are recorded whose analysis can be utilised in the detection of process disturbances and weld quality assessment

Process monitoring and industrial informatics for on-line optimization of Welding Procedure Specifications (WPS) in Gas Tungsten Arc Welding (GTAW) – Industry 4.0 for robotic additive re-manufacturing of aeroengine components

Industry 4.0, the scheme that drives the fourth industrial revolution, has been, since its conception, reshaping the manufacturing industry. To advance current industrial chains into the smart factories of the future, cyber-physical systems are monitored and communicate with each other to ensure transparent interoperability, giving birth to the emerging field of industrial informatics. To enable the repair and recycling of high value jet engine compressor blades, additive manufacturing is utilized. The complex geometries and asymmetrical wear of the blades require robotic welding systems to be trained by experienced human welding engineers in order to be able to adapt to differing components. Demonstrated in this paper, process monitoring and industrial informatics are introduced to the adaption of Welding Procedure Specifications (WPS) utilized by a developing robotic system for the additive re-manufacturing of aeroengine components. Using a novel variant of Gas Tungsten Arc Welding (GTAW), the robotic welding system under development is a product of an industry-academia collaboration between the Enabling Sciences for Intelligent Manufacturing Group (ESIM) of the University of Sheffield and VBC Instrument Engineering Ltd

Increasing transparency and reproducibility in stroke-microbiota research: A toolbox for microbiota analysis

Homeostasis of gut microbiota is crucial in maintaining human health. Alterations, or “dysbiosis”, are increasingly implicated in human diseases, such as cancer, inflammatory bowel diseases and more recently neurological disorders. In ischemic stroke patients, gut microbial profiles are markedly different compared to healthy controls, while manipulation of microbiota in animal models of stroke, modulates outcome, further implicating microbiota in stroke pathobiology. Despite this, evidence for the involvement of specific microbes or microbial products and microbial signatures have yet to be identified, likely due to differences in methodology, data analysis and confounding variables between different studies. Here, we provide a set of guidelines to enable researchers to conduct high quality, reproducible and transparent microbiota studies, focusing on 16S rRNA sequencing in the emerging subfield of the stroke-microbiota. In doing so, we aim to facilitate novel and reproducible associations between the microbiota and brain diseases including stroke, and translation into clinical practice

Pharmacokinetics/Pharmacodynamics findings after repeated Administration of ARTESUNATE thermostable suppositories (RECTOCAPS) in Vietnamese patients with uncomplicated malaria

Summary: In recent years, Artemisinin and particularly one of its derivatives — Artesunate (ART — has become an essential alternative for treatment of both uncomplicated and severe falciparum malaria in Asia and Africa as well. Therefore, these compounds are still and inccreasingly in the focus of interest because of quick acting of this drug, is able to help even unconscious to overcome the malaria attack, when administered by injection. As an alternative, RECTOCAPS have been developed and their use is meanwhile well established. From earlier studies in children, suffering from Plasmodium falciparum malaria, we obtained a high level of DHART in the blood, but as expected also a rapid decline in the levels of both DHART and ART. A second administration of ART was additionally applied 4 hours after the first administration. DHART and ART plasma levels were found to last longer on an assumed therapeutic level than those obtained after one administration only. The fever clearance and the parasitemia reduction rates were found to be effective according to this dosing regimen. In view of these findings, we decided to conduct the actual described study by administering 200 mg of ART every 3 hours (0, 3, 6 and 9 h) by the rectal route. Soft geiatine capsules (RECTOCAPS) containing 200 mg of ART GMP — type each (Artesunic acid) were administered by rectal route. Each patient received four RECTOCAPS capsules (4×200 mg of ART) over a 3 h period. 12 adult patients with uncomplicated malaria were selected. Age, weight, height, body temperature, parasite counts before treatment and their evolution until 96 h are determined. Blood samples were taken at short time intervals after starting with the first medication: 0, 30 min, 60 min, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, 48 h, 60 h, 72 h, 84 h, 96 h and 108 h. The aliquots of all the blood samples were used for performing parasite counts. Plasma obtained following the traditional procedure was kept at −40°C until analysis. HPLC technique with electrochemical detector was used for quantification of ART and DHART. From the blood concentration values of ART and DHART, the following observation can be derived: the onset of action is observed within the first half hours, therapeutic levels of the drug obtained (89 μg/ml ART compared to 84 μg/ml DHART). The DHART levels are somewhat higher than those of ART (a peak concentration after 6 h starting medication of 151 μg/ml ART as compared to 276 μg/ml DHART). The variations as a function of frequency of DHART uptake are much less marked than those observed for ART. Another finding is that after the administration, some sort of a plateau of DHART and ART is built up, lasting at least from 9 to 12 hours with DHART level of about 190 μg/ml and ART of 90 μg/ml. In the case of single-dose administration, the levels of both compounds were below the detection threshold after three hours. With regard to the parasite counts, although there were inter-individual variations, it should be noted that after 48 hours a high proportion of the patients (8 out of 12) was completely clear of parasites. Similar results were observed with regard to the body temperature (7 out of 12 returned to normal temperature 36 hours after starting the therapy). The findings of the study support the RECTOCAPS application principle resulting in effectiveness both for the velocity of drug uptake as well as for the height of plasma levels. Repeated administration of ART can extend the duration of therapeutic plasma levels of the dru

Welding process monitoring applications and industry 4.0

With the fourth industrial revolution in progress, traditional manufacturing processes are being transformed. Fusion welding is no exception from this transformation. The centuries-old manual craft is being reshaped by cyber-physical systems, turning into a digitized process governed by industrial informatics. By implementing process monitoring in welding applications invaluable data are collected that can be utilized in the new, futuristic smart factories of Industry 4.0. In this article two purposes are being served. The first is to present the status quo alongside the future trends of welding process monitoring on industrial implementation. The second is to present the results of an ongoing investigation of robotic Gas Tungsten Arc Welding (GTAW) monitoring for defect detection and characterization. Deviations from the optimal values in three welding conditions (surface integrity, shielding gas flow rate and surface contamination) were introduced during stainless steel 316L beads-on-plates welding. Acquired data during the welding process were used to extract features in order to identify correlations between the disturbances and the monitored signals