Molecular mechanisms of Endothelial-Mesenchymal Transition in coronary artery stenosis and cardiac fibrosis

Homeostase van het endotheel – de binnenste cellaag in alle bloedvaten – speelt een belangrijke rol in het voorkomen van trombose, ontsteking en bij de regulatie van de vasculaire tonus. Dysfunctie van het endotheel is veelvoorkomend tijdens cardiovasculaire ziekten. Het is daarom belangrijk om meer inzicht te krijgen in de moleculaire mechanismen die leiden tot endotheelceldysfunctie, zodat mogelijk nieuwe aangrijpingspunten gevonden kunnen worden voor de ontwikkeling van innovatieve therapieën tegen cardiovasculaire ziekten.Averse plasticiteit van het endotheel, en de transitie van endotheel naar mesenchym (EndMT) speelt een belangrijke rol in het ontstaan van atherosclerose en de verlidtekening van het hart (cardiale fibrose). Hierbij wordt de inductie van genexpressie van mesenchymale genen niet alleen gereguleerd door de binding van transcriptiefactoren aan het DNA, maar ook door de bereikbaarheid van het DNA voor deze transcriptiefactoren, welke bepaald wordt door epigenetica. Epigenetische modificaties, door alteraties aan histon eiwitten of DNA methylatie, bepalen de toegankelijkheid van het DNA voor transcriptiefactoren. Een tweede regulatoir mechanisme wordt gevonden in microRNAs, die de translatie van messenger RNA naar eiwit posttranscriptioneel kan inhiberen.De transitie van endotheel naar mesenchym is een belangrijke component in de ontwikkeling van atherosclerose (intimale hyperplasie) en hartfalen (cardiale fibrose) en wordt gereguleerd door biomechanische krachten, zoals het patroon van de bloedstroom. In dit proefschrift hebben wij laten zien dat EndMT gereguleerd wordt door MAPK7, EZH2 en microRNAs en gevonden dat de expressie van deze moleculen gedereguleerd is in experimentele modellen voor intimale hyperplasie en in humane coronaire hartziekte. We hebben een aantal belangrijke regulatoren van EndMT geïdentificeerd die mogelijk een therapeutische effect kunnen hebben om de ontwikkeling van intimale hyperplasie of het ontstaan van hartfalen tegen te gaan. Toekomstig onderzoek moet zich op deze mogelijkheid richten.Endothelial homeostasis plays crucial role in vascular health by preventing unwarranted thrombosis, inflammation and regulating vascular tone. Endothelial dysfunction is a culprit in the development of many cardiovascular pathologies. Hence, insight into the molecular mechanisms that underlie endothelial dysfunction might allow for the discovery of innovative drugable targets to reduce the cardiovascular disease burden.Adverse endothelial plasticity and its specialized form Endothelial-Mesenchymal transition (EndMT) contributes to the development of multiple cardiovascular diseases including atherosclerosis and cardiac fibrosis. The induction of mesenchymal gene expression is not only regulated by changes in transcription factor binding to the DNA, but also by the accessibility of the DNA to these transcription factors, which is tightly regulated by epigenetics. Epigenetic modifications, through changes in histone tail modifications and DNA methylation, facilitate the compaction and decompaction of the DNA, thereby orchestrating its accessibility to transcription factors. Furthermore, transcribed genes are not always translated into proteins, as non-coding RNAs might induce posttranscriptional inhibition. Endothelial-mesenchymal transition is a crucial component of atherosclerosis and cardiac fibrosis development and shown to be modulated by fluid shear stress. In this thesis, we show that endothelial-mesenchymal transition is regulated on multiple levels by MAPK7, EZH2 and microRNAs and found dysregulation of these factors in experimental models of intimal hyperplasia and in human coronary artery disease. We uncovered a number of pivotal regulators of EndMT that might have therapeutic potential to ameliorate intimal hyperplasia and cardiac fibrosis

Prescribable mHealth apps identified from an overview of systematic reviews

AbstractMobile health apps aimed towards patients are an emerging field of mHealth. Their potential for improving self-management of chronic conditions is significant. Here, we propose a concept of “prescribable” mHealth apps, defined as apps that are currently available, proven effective, and preferably stand-alone, i.e., that do not require dedicated central servers and continuous monitoring by medical professionals. Our objectives were to conduct an overview of systematic reviews to identify such apps, assess the evidence of their effectiveness, and to determine the gaps and limitations in mHealth app research. We searched four databases from 2008 onwards and the Journal of Medical Internet Research for systematic reviews of randomized controlled trials (RCTs) of stand-alone health apps. We identified 6 systematic reviews including 23 RCTs evaluating 22 available apps that mostly addressed diabetes, mental health and obesity. Most trials were pilots with small sample size and of short duration. Risk of bias of the included reviews and trials was high. Eleven of the 23 trials showed a meaningful effect on health or surrogate outcomes attributable to apps. In conclusion, we identified only a small number of currently available stand-alone apps that have been evaluated in RCTs. The overall low quality of the evidence of effectiveness greatly limits the prescribability of health apps. mHealth apps need to be evaluated by more robust RCTs that report between-group differences before becoming prescribable. Systematic reviews should incorporate sensitivity analysis of trials with high risk of bias to better summarize the evidence, and should adhere to the relevant reporting guideline.</jats:p

A Study on the Detection of Protective Helmets for the Safety of Construction Workers

In recent years, with the rapid development of the construction industry, the number of accidents and deaths on construction sites increased, so the prevention of accidents is one of the important issues. Worker safety during construction is a major concern of the construction industry. Wearing helmets can reduce injuries among construction workers, but helmets are not always worn and used correctly for a variety of reasons. Therefore, computer vision-based automatic helmet detection systems are very important. Although many researchers have developed machine and deep learning-based motorcycle helmet detection systems, there is little research on helmet detection for construction workers. Therefore, in this research work, an automatic system for detecting the helmets of construction workers based on real-time computer vision is presented. In this study, machine learning method is used to detect helmets, and a model is trained using 1,500 images. The test results show that the average accuracy is above 95% in laboratory conditions

USING THE TWO-LEVEL MORPHOLOGY ON MODERN MONGOLIAN LINGUISTICS

This study compiles primarily the word structure of Modern Mongolian language and further more focused on the possibilities of description of Mongolian language in PC KIMMO, a two level processing method of morphological parsing. The rules file and lexicon presented in the paper describe the morphology of Mongolian words. A lexicon containing the root words of contemporary Mongolian is used in the testing. As a result the two-level morphology is determined as completely possible to be used for Mongolian linguistics. In addition PC-KIMMO description of traditional Mongolian script is considered as being possible

Temporal variation of the pseudo total content of heavy metals in Ulaanbaatar soil

This work shows some of the results of investigation into pseudo total content of heavy metals in the surface soil of Ulaanbaatar.The main objectives of this study are to (i) evaluate temporal variability of pseudo-total content of Pb, Cu, Zn, Cd, Cr, Ni, Co and Mn in surface soil of Ulaanbaatar collected from 2003 to 2018, (ii) identify the main discriminates - metals during the years 2003-2018 years and, (iii) investigate the interdependence of main discriminates on the soil reaction (pH) and soil organic matter.Due to urbanization and negative human activities, surface soil in Ulaanbaatar losing their natural features, which are changing, while the spatial and temporal distribution of heavy metals in urban surface soil is becoming irregular. In Ulaanbaatar surface soil, the mean concentration of Cu, Zn and Pb much mois very high and the mean concentration of Co is lower than background soil. In some land use zones, it was found that the mean concentraion of Zn and Cr was considerably higher than the permissible level. The pollution condition of Mn, Zn, Cr, Ni and Cd was the same in 2010-2018 and the pollution conditions of Pb, Cu and Co are different. The main discriminants are Pb, Cu and Co. In Ulaanbaatar soil, a strikingly close correlationhip was established for Cu, Pb with the soil organic matter, and for Cd, Zn, Cr with the pH, respectively