Implementation of neural plasticity mechanisms on reconfigurable hardware for robot learning

It is often assumed that insects are “primitive” animals, without the ability to exhibit complex learning behaviour. Fortunately, their tiny brains quite often surprise us with their performance. This thesis investigates the plasticity mechanisms of the insect brain through the research method of neurorobotics, i.e., the development of a physical agent, equipped with a silicon brain. In order to implement such a brain, we have chosen to model it directly onto hardware. Not only does this allow us to take advantage of the inherent hardware parallelism, but the robot can also behave in a completely autonomous mode, without having to communicate with the software simulator of a remote machine. FPGAs offer both the option for such a lowlevel design approach and the flexibility required in computational studies of biological neural networks. With the use of VHDL (a hardware description language), we develop a simulator for neural networks, designed as a series of computational modules, running in parallel and solving the differential equations which describe neural processes. It has the ability to simulate networks with spiking neurons that follow a phenomenological model, proposed by Izhikevich, which requires only 13 operations per 1 ms of simulation. The synaptic plasticity mechanism can be either that of spike timing-dependent plasticity (STDP) or a modified version of STDP which is also affected by neuromodulators. There are no constraints, as far as the connectivity pattern is concerned. The hardware simulator is then added as a peripheral to an embedded system so that it can be more easily controlled through software and connected to a robot. We show that this hardware system is able to model networks with hundreds of neurons and with a speed performance that is better than real-time. With some slight modifications, it could also scale up to thousands of neurons, starting to approach the size of the insect brain. Subsequently, we use the simulator in order to model a neural network with an architecture inspired by the insect brain, representing the connectivity of the antennal lobe, the mushroom body and the lateral horn, structures which are part of the insect’s olfactory pathway. Our silicon brain is then attached to a robot and its limits and capabilities are tested in a series of experiments. The experiments involve tasks of associative learning inside an arena which is based on a T-maze set-up usually employed in behavioural experiments with flies. The robot is trained to associate different stimuli (or combinations of stimuli) with a punishment, as indicated by the presence of a light source. We observe that the robot can solve most of the tasks, including elemental learning, discrimination learning, biconditional discrimination and negative patterning but fails to solve the problem of positive patterning. It is concluded that the architecture of the insect’s olfactory pathway has the computational efficiency to solve even non-elemental learning tasks. However, this pattern of results does not precisely match the fly, suggesting we have not fully understood the learning mechanisms involved. Moreover, embedding the learning circuit in robot behaviour reveals that the simple version of STDP is not the appropriate mechanism which can link neural plasticity to learning behaviour. Although the modified version of STDP is more suitable, it remains problematic as well as sensitive to timing issues. Therefore, we propose that STDP might function more as a “priming” process rather than as the basic learning mechanism

Towards Climate Neutrality: A Comprehensive Overview of Sustainable Operations Management, Optimization, and Wastewater Treatment Strategies

Various studies have been conducted in the fields of sustainable operations management, optimization, and wastewater treatment, yielding unsubstantiated recovery. In the context of Europes climate neutrality vision, this paper reviews effective decarbonization strategies and proposes sustainable approaches to mitigate carbonization in various sectors such as building, energy, industry, and transportation. The study also explores the role of digitalization in decarbonization and reviews decarbonization policies that can direct governments action towards a climate-neutral society. The paper also presents a review of optimization approaches applied in the fields of science and technology, incorporating modern optimization techniques based on various peer-reviewed published research papers. It emphasizes non-conventional energy and distributed power generating systems along with the deregulated and regulated environment. Additionally, this paper critically reviews the performance and capability of micellar enhanced ultrafiltration (MEUF) process in the treatment of dye wastewater. The review presents evidence of simultaneous removal of co-existing pollutants and explores the feasibility and efficiency of biosurfactant in-stead of chemical surfactant. Lastly, the paper proposes a novel firm-regulator-consumer interaction framework to study operations decisions and interactive cooperation considering the interactions among three agents through a comprehensive literature review on sustainable operations management. The framework provides support for exploring future research opportunities

Evaluating the Inclusiveness of Artificial Intelligence Software in Enhancing Project Management Efficiency -- A Review

The rise of advanced technology in project management (PM) highlights a crucial need for inclusiveness. This work examines the enhancement of both inclusivity and efficiency in PM through technological integration, focusing on defining and measuring inclusiveness. This approach illuminates how inclusivity-centered technology can significantly elevate project outcomes. The research navigates through the challenges of achieving inclusivity, mainly biases in learning databases and the design process of these technologies, assessment of transformative potential of these technologies, particularly in automating tasks like data collection and analysis, thus enabling managers to prioritize human-centric aspects of projects. However, the integration of such technology transcends efficiency, indicating a paradigm shift in understanding their societal roles. This shift necessitates a new approach in the development of these systems to prevent perpetuating social inequalities. We proposed a methodology involving criteria development for evaluating the inclusiveness and effectiveness of these technologies. This methodical approach is vital to comprehensively address the challenges and limitations inherent in these systems. Emphasizing the importance of inclusivity, the study advocates for a balance between technological advancement and ethical considerations, calling for a holistic understanding and regulation. In conclusion, the paper underscores that while these technologies can significantly improve outcomes, their mindful integration, ensuring inclusivity, is paramount. This exploration into the ethical and practical aspects of technology in PM contributes to a more informed and balanced approach within the field

The chemokine receptor CXCR3 promotes CD8+ T cell accumulation in uninfected salivary glands but Is not necessary after Murine Cytomegalovirus infection

Recent work indicates that salivary glands are able to constitutively recruit CD8+ T cells and retain them as tissue-resident memory T cells, independently of local infection, inflammation, or Ag. To understand the mechanisms supporting T cell recruitment to the salivary gland, we compared T cell migration to the salivary gland in mice that were infected or not with murine CMV (MCMV), a herpesvirus that infects the salivary gland and promotes the accumulation of salivary gland tissue-resident memory T cells. We found that acute MCMV infection increased rapid T cell recruitment to the salivary gland but that equal numbers of activated CD8+ T cells eventually accumulated in infected and uninfected glands. T cell recruitment to uninfected salivary glands depended on chemokines and the integrin α4 Several chemokines were expressed in the salivary glands of infected and uninfected mice, and many of these could promote the migration of MCMV-specific T cells in vitro. MCMV infection increased the expression of chemokines that interact with the receptors CXCR3 and CCR5, but neither receptor was needed for T cell recruitment to the salivary gland during MCMV infection. Unexpectedly, however, the chemokine receptor CXCR3 was critical for T cell accumulation in uninfected salivary glands. Together, these data suggest that CXCR3 and the integrin α4 mediate T cell recruitment to uninfected salivary glands but that redundant mechanisms mediate T cell recruitment after MCMV infection.This work was supported by National Institutes of Health Grant AI106810 (to C.M.S.) and Portuguese Foundation for Science and Technology Grant SFRH-BD-52319-2013 (to S.C.-D.).info:eu-repo/semantics/publishedVersio

The Majority of MicroRNAs Detectable in Serum and Saliva Is Concentrated in Exosomes

There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva

Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.).publishedVersio

Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000–50,000 live female births, while partial triplications are even rarer. Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative. © 2017, American College of Rheumatolog

Gene expression regulation in Sjögren's syndrome

Το σύνδρομο Sjögren χαρακτηρίζεται από στοιχεία συστημικής αυτοανοσίας και δυσλειτουργίας και φλεγμονής στους εξωκρινείς αδένες. Η ακριβής αιτία της εξωκρινούς δυσλειτουργίας στο SS δεν έχει διασαφηνιστεί αλλά θεωρείται ότι συνεισφέρουν σημαντικά μεσολαβούμενοι από το ανοσοποιητικό αλλά και μη ανοσοποιητικοί μηχανισμοί. Η διάγνωση βασίζεται στο συνδυασμό υποκειμενικών συμπτωμάτων και αντικειμενικών σημείων όπως στεγνού στόματος ή/και ξηροφθαλμίας, παρουσίας αυτοαντισωμάτων και φλεγμονώδους διήθησης στους δευτερεύοντες σιελογόνους αδένες.Τα μόρια microRNA (miRNAs) είναι μια ομάδα μικρών μορίων RNA, μήκους 21-24 νουκλεοτιδίων, που εμπλέκονται στη ρύθμιση μιας ευρείας ποικιλίας κυτταρικών και φυσιολογικών διαδικασιών[1-3]. Ασκούν τις επιδράσεις τους με δύο μηχανισμούς: με αποδόμηση του αγγελιοφόρου RNA και διακοπή της μετάφραση. Ένα μοναδικό μόριο mRNA συνήθως μεταφράζεται σε μια μόνο πρωτεΐνη. Ωστόσο, ένα μοναδικό μόριο microRNA είναι ικανό να ρυθμίζει τη μετάφραση πολλαπλών γονιδίων που εμπλέκονται σε μια συγκεκριμένη λειτουργία. Οι αλλαγές στα επίπεδα μεμονωμένων μορίων mRNA μπορεί τελικά να τροποποιηθούν ή να εκμηδενιστούν από τη μετα-μεταφραστική ρύθμιση και έτσι να είναι λιγότερο αντιπροσωπευτικές της φυσιολογικής κατάστασης του κυττάρου σε σχέση με τα μόρια microRNA. Σε αυτή τη διατριβή παρουσιάζουμε τρείς διαφορετικές μελέτες σχετιζόμενες με το ρόλο των μορίων microRNA σto σύνδρομο Sjögren.Η πρώτη μελέτη εξερευνεί τη δυνατότητας χρήσης των μορίων microRNA ως διαγνωστικών και λειτουργικών βιοδεικτών στις αυτοάνοσες νόσους. Συγκεκριμένα, χρησιμοποιήσαμε μικροσυστοιχίες microRNA για να προσδιορίσουμε το προφίλ των δευτερευόντων σιελογόνων αδένων από άτομα ελέγχου και ασθενείς με πρωτοπαθές σύνδρομο Sjögren. Για να εκτιμηθεί η βιολογική εγκυρότητα των διαφορών στα προφίλ των μορίων microRNA μεταξύ των διαφόρων ομάδων εντοπίσαμε τις προβλεπόμενες ατραπούς–στόχους των διαφορικά εκφρασμένων μορίων microRNA χρησιμοποιώντας το πρόγραμμα Ingenuity Pathway Analysis.Η δεύτερη μελέτη εστιάζεται στην ανακάλυψη μέχρι πρότινος αγνώστων μορίων microRNA στους σιελογόνους αδένες των ασθενών με πρωτοπαθές σύνδρομο Sjögren μέσω της μεθόδου Next Generation Sequencing (NGS - Αλληλούχηση Νέας Γενιάς). Η τρίτη μελέτη εστιάζεται στα εξωσώματα από ανθρώπινη σίελο ως πηγή βιοδεικτών microRNA, παρουσιάζοντας μεθόδους για την απομόνωση των εξωσωμάτων απο σίελο μη διεγερμένης και διεγερμένης ολικής, παρωτιδικής και υπογνάθιας σιέλου

Πρόβλεψη σύνθετων γεγονότων

As analytics moves towards a model of proactive computing, the requirement for forecasting acquires more importance. Systems with forecasting capabilities can play a significant role in assisting users to make smart decisions as soon as critical situations are detected. Being able to forecast that certain patterns in a stream have a high probability of being detected before they are actually detected can help an analyst focus early on what is important and possibly take a proactive action. The need for event forecasting as a means for proactive behavior has led to proposals about how forecasting could be conceptualized and integrated within a complex event processing system. However, such proposals still remain largely at a conceptual level, without providing concrete algorithms. On the other hand, there is a substantial body of work on the related field of time-series forecasting. However, time-series analysis is usually applied on numerical data streams, where each element of the stream corresponds to a measurement of some variable of interest. Moreover, these measurements are often assumed to take place at time intervals of constant length. On the contrary, event processing systems need to be able to additionally deal with symbolic/categorical streams, where each element might be accompanied by arguments, either numerical or symbolic, arriving at unspecified timepoints. The goal of this work is to provide a theoretical basis and build a prototype system for forecasting the occurrence of complex event patterns. This will be achieved by advancing the state-of-the-art in automaton models, going beyond classical automata, so that patterns can have the expressive power required by complex event processing applications. A probabilistic framework will subsequently be used, so that the behavior of these automaton models may be quantified in a way that allows for producing forecasts with confidence. The resulting system will be evaluated against synthetic datasets (for verification purposes) and against real-world datasets in order to demonstrate the applicability of the proposed system.Όσο η ανάλυση δεδομένων κινείται προς ένα μοντέλο προδραστικού υπολογισμού, τόσο οι απαιτήσεις για τη δυνατότητα πρόβλεψης αποκτούν περισσότερη σημασία. Τα προβλεπτικά συστήματα μπορούν να βοηθήσουν σε σημαντικό βαθμό έναν χρήστη να λάβει έξυπνες αποφάσεις αμέσως μόλις εμφανιστούν κρίσιμες καταστάσεις. Η δυνατότητα να προβλεφθεί ότι ένα μοτίβο σε μια ροή δεδομένων έχει υψηλή πιθανότητα να εντοπιστεί πριν αυτό πραγματικά εντοπιστεί μπορεί να βοηθήσει έναν αναλυτή να εστιάσει από νωρίς σε ό,τι είναι σημαντικό και πιθανώς να προχωρήσει σε μια προληπτική δράση. Η ανάγκη για πρόβλεψη γεγονότων ως ένα μέσο προδραστική συμπεριφοράς έχει οδηγήσει στην εφμάνιση κάποιων προτάσεων σχετικά με το πώς η πρόβλεψη θα μπορούσε να εννοιοποιηθεί και να ενσωματωθεί εντός ενός συστήματος επεξεργασίας σύνθετων γεγονότων. Ωστόσο, αυτές οι προτάσεις έχουν παραμείνει σε ένα αφηρημένο επίπεδο, χωρίς να παρέχουν συγκεκριμένες υλοποιήσεις. Από την άλλη, υπάρχει ένα σημαντικό σώμα δουλειάς στο πεδίο της πρόβλεψης χρονο-σειρών. Όμως η ανάλυση χρονο-σειρών εφαρμόζεται συνήθως σε ροές αριθμητικών δεδομένων, όπου κάθε στοιχείο της ροής αντιστοιχεί στη μέτρηση μιας μεταβλητής. Επιπλέον, γίνεται η υπόθεση ότι τέτοιες μετρήσεις λαμβάνουν χώρα σε τακτά χρονικά διαστήματα. Αντιθέτως, τα συστήματα αναγνώρισης σύνθετων γεγονότων πρέπει να μπορούν να χειρίζονται και ροές συμβολικών / κατηγορικών δεδομένων, όπου κάθε στοιχείο μπορεί να συνοδεύεται από ορίσματα, είτε αριθμητικά είτε συμβολικά, και που καταφθάνουν σε μη τακτά διαστήματα. Ο σκοπός αυτής της διατριβής είναι να παρέχει μια θεωρητική βάση και να χτίσει ένα πρωτότυπο σύστημα πρόβλεψης σύνθετων γεγονότων. Αυτό θα καταστεί εφικτό μέσω της επέκτασης των υπαρχόντων μοντέλων αυτομάτων, πηγαίνοντας ένα βήμα παραπέρα από τα κλασσικά αυτόματα, έτσι ώστε τα μοτίβα να έχουν την εκφραστική δύναμη που απαιτείται σε εφαρμογές επεξεργασίας γεγονότων. Κατόπιν, θα αναπτυχθεί ένα πιθανοτικό πλαίσιο έτσι ώστε να μπορεί να ποσοτικοποιηθεί η συμπεριφορά αυτών των αυτομάτων με τρόπο που να επιτρέπει την εξαγωγή προβλέψεων. Το τελικό σύστημα θα αξιολογηθεί τόσο σε συνθετικά δεδομένα (για σκοπούς επαλήθευσης) όσο και σε πραγματικά δεδομένα ώστε να καταδειχθεί η χρησιμότητά του

«Η συνταγματική διάσταση των κοινόχρηστων χώρων»

Οι κοινόχρηστοι χώροι αποτελούν αγαθό ζωτικής σημασίας για τις κοινωνίες, καθώς από αυτούς εξαρτάται εν πολλοίς η ποιότητα ζωής και η υγεία των ανθρώπων. Ειδικότερα, οι χώροι αυτοί, που είναι προσβάσιμοι και ανοιχτοί σε όλες και όλους, όπως τα πάρκα, οι πλατείες, οι παραλίες, είναι απαραίτητοι για μια ελεύθερη και ολόπλευρη ανάπτυξη της προσωπικότητάς κάθε ατόμου. Παράλληλα, όμως, διαδραματίζουν κομβικό ρόλο και στην πραγμάτωση πολλών συνταγματικών- ατομικών και συλλογικών- δικαιωμάτων, όπως η ελευθερία της συνάθροισης και η ελευθερία της έκφρασης. Απολαμβάνουν οι κοινόχρηστοι χώροι συνταγματική προστασία; Κι αν ναι, υπό ποιες προϋποθέσεις μπορεί η προστασία αυτή να περιορίζεται; Με ποια άλλα έννομα αγαθά ενδέχεται να συγκρούεται και ποιες είναι οι αναγκαίες σταθμίσεις στις οποίες πρέπει να προβούν ο νομοθέτης και ο δικαστής για την επίλυση της σύγκρουσης αυτής; Τα ανωτέρω συνταγματικής τάξης ζητήματα που σχετίζονται με τους κοινόχρηστους χώρους επιχειρεί να καταγράψει η παρούσα μελέτη, μέσα από τη συνδυαστική εξέταση των νομικών ρυθμίσεων, των θεωρητικών επεξεργασιών και των συναφών νομολογιακών κρίσεων, αλλά και υπό το φως των σύγχρονων προβληματικών που ανέδειξε η οικονομική κρίση και η πανδημία του κορωνοϊού.Public spaces constitute vital goods for the societies, as people’s quality of life and health depends to a great extent on them. In particular, these spaces, such as parks, squares, beaches, which are accessible and open to everyone, are necessary for a free and well-rounded development of individuals’ personality. At the same time, they play a key role in the exercise of many constitutional - individual and collective - rights, such as freedom of assembly and freedom of expression. Αre public spaces constitutionally protected and under what conditions can this protection be restricted? Are there any other legally protected rights which may be in conflict with the rights associated with the constitutional protection of public spaces and if so what are the necessary balances that the legislature and the judge have to take into consideration in order to resolve this conflict? The present master thesis attempts to delve into the aforementioned constitutional issues related to public spaces, through the combined examination of the legal regulations, theoretical elaborations and related case law. Moreover, I have examined the legal issues regarding public spaces in light of the recent financial crisis and the coronavirus pandemic