User's point of view in using software in risk analysis

A number of works exist, that aim at assessing the reliability of software, by means of comparisons with existing data (especially results from experiments). For instance, S.R. Hanna (Earth Tech, USA) has been comparing well known experimental data (Burro, Coyote, Desert Tortoise, Goldfish...) for many years with a great number of softwares [1]. The European Authorities have taken such an initiative more recently, by means of European Projects (see [2]), dealing with the evaluation of effects from major industrial hazards, by constituting a large data base

Analyses d'accidents : une nécessité pour les analyses de danger et l'intervention en situation d'urgence ?

Lors d'accidents industriels mettant en jeu des explosions, des incendies ou des émissions de produits toxiques ou inflammables dans l'environnement, les effets à prendre en compte s'expriment en termes d'impulsions de pression, de projections de débris, de flux thermiques et de rejets de produits toxiques dans l'air, les eaux et les sols. Dans sa première partie, le présent article présente les conclusions consécutives à l'analyse de différents types d'accidents survenus en France et met en évidence l'absence de connaissances suffisantes sur le déroulement d'explosions non confinées ou partiellement confinées et sur les modalités d'émissions de produits toxiques lors d'incendies. La prise en considération de ces accidents et de bases de données sur les accidents permettra aux autorités compétentes, aux industriels, aux assureurs et aux centres techniques intéressés par ces questions de partager leurs expériences. La seconde partie aborde la validation des logiciels commerciaux de calcul des conséquences. La comparaison des résultats de l'examen des logiciels CAMEO 3.0, CHARM 6.1, PHAST 3.0 et TRACE 2.5.4. utilisés pour définir tout ou partie des effets mentionnés plus haut a permis de mettre en évidence la nécessité d'un protocole d'évaluation. Pour un tel protocole sont à retenir : la pertinence des modèles physiques, la convivialité pour l'utilisateur, le caractère adapté des bases de données et du manuel opérateur

Artificial Intelligence with Reinforcement Learning on Video-Games

Σκοπός της διπλωματικής εργασίας ήταν η υλοποίηση με λογισμικό ενός συστήματος Τεχνητής Νοημοσύνης (AI) που να μπορεί να μάθει να παίζει βίντεο-παιχνίδια. Στο πρώτο κεφάλαιο αναπτύχθηκαν περιληπτικά οι τρεις βασικοί τύποι Μηχανικής Μάθησης (ML) και επισημάνθηκε σε ποιον από αυτούς οριοθετείται το δικό μας πρόβλημα. Στο δεύτερο κεφάλαιο αναπτύχθηκε αναλυτικά η θεωρία στην οποία βασίζονται τα Νευρωνικά Δίκτυα (NN). Συγκεκριμένα αναφέρθηκαν οι νευρώνες του ανθρώπινου εγκεφάλου, οι τεχνητοί νευρώνες Perceptron και Adaline και οι τύποι των Νευρωνικών Δικτύων που μπορούν να κατασκευαστούν από μοντέρνους τεχνητούς νευρώνες. Τέλος αναπτύχθηκαν διεξοδικά τα Συνελικτικά Νευρωνικά Δίκτυα (CNN), καθώς και τα Μακρά Νευρωνικά Δίκτυα Βραχείας Μνήμης (LSTM) που χρησιμοποιήθηκαν κατά κόρον στην εργασία αυτή. Στο τρίτο κεφάλαιο αναπτύχθηκε η θεωρία της Ενισχυτικής Μάθησης. Συγκεκριμένα συζητήθηκαν οι Διαδικασίες Λήψης Αποφάσεων Markov (MDP), οι εξισώσεις Bellman, οι τύποι συστημάτων που λειτουργούν με Διαδικασίες Λήψης Αποφάσεων Markov και ο τρόπος εκπαίδευσης των συστημάτων Ενισχυτικής Μάθησης. Τέλος, παρουσιάστηκε αναλυτικά ο αλγόριθμος Ενισχυτικής Μάθησης Asynchronous Advantage Actor-Critic (A3C) της Google, που χρησιμοποιήθηκε για την κατασκευή του λογισμικού της εργασίας αυτής. Στο τέταρτο κεφάλαιο παρουσιάστηκε το παιχνίδι που χρησιμοποιήθηκε στην εκπαίδευση του λογισμικού της εργασίας. Επίσης αναλύθηκαν οι τύποι των Νευρωνικών Δικτύων που χρησιμοποιήθηκαν ως συστατικά για την υλοποίηση του δικού μας συστήματος Τεχνητής Νοημοσύνης. Στο πέμπτο και τελευταίο κεφάλαιο παρουσιάστηκαν τα πειράματα και τα αποτελέσματα της διαδικασίας εκπαίδευσης του συστήματος.The purpose of this thesis was the implementation of an Artificial Intelligence (AI) system via software so that it would learn to play video games. In the first chapter the three basic types of Machine Learning (ML) were discussed in short and the type of Machine Learning that is related to our problem was specified. In chapter two, the theory on which Neural Networks (NN) are based was reviewed in detail. In particular we referred to the neurons of the human brain, the Perceptron and Adaline artificial neurons and the types of Neural Networks that can be constructed by modern artificial neurons. Finally, Convolutional Neural Networks (CNN) were detailed, as well as the Long Short-Term Memory Neural Networks (LSTM) that were used in this thesis extensively. In chapter three, we studied the theory of Reinforcement Learning (RL). Particularly, Markov Decision Processes (MDP), Bellman equations, the type of systems which operate with Markov Decision Processes and the way of training systems of Reinforcement Learning were discussed. Finally, Google’s Asynchronous Advantage Actor-Critic (A3C) algorithm for Reinforcement Learning, used for the development of the software in this thesis, was presented in detail. In chapter four, we presented the game used for training the software of this thesis. Furthermore, the types of Neural Networks which were used as components for the implementation of our system of Artificial Intelligence were analyzed. In the fifth and final chapter, the experiments and the results of the training process of the system were presented

Απαρίθμηση Μεταθέσεων, Συμμετρικές Συναρτήσεις και το Θεώρημα Gessel-Reutenauer

Το θέμα της διπλωματικής εργασίας είναι η απαρίθμηση μεταθέσεων. Συγκεκριμένα, θέλουμε να μετρήσουμε το πλήθος των μεταθέσεων με δοσμένο κυκλικό τύπο και σύνολο καθόδων. Το κεντρικό αποτέλεσμα της εργασίας είναι το Θεώρημα Gessel-Reutenauer, το οποίο εκφράζει το ζητούμενο πλήθος μεταθέσεων ως το εσωτερικό γινόμενο δύο χαρακτήρων της συμμετρικής ομάδας, συνδέοντας έτσι, το αρχικό πρόβλημα με τις συμμετρικές συναρτήσεις. Στα πρώτα δύο κεφάλαια, εισάγονται οι βασικές έννοιες και παρουσιάζονται στοιχεία από τη θεωρία των συμμετρικών συναρτήσεων. Στο τρίτο κεφάλαιο διατυπώνεται και αποδεικνύεται το Θεώρημα Gessel-Reutenauer και δίνεται μία εφαρμογή του σε μεταθέσεις ενός συγκεκριμένου κυκλικού τύπου.The subject of this paper is permutation enumeration. In particular, we would like to count the number of permutations with given cycle structure and descent set. The main result is the Gessel-Reutenauer Teorem, which states that the number of permutation having descent set D and cycle structure λ is equal to the scalar product of two characters of the symmetric group. In the first two chapters we introduce the basic concepts along with elements of the theory of symmetric functions. In the third chapter we prove the Gessel-Reutenauer Theorem and we present one of its applications

G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription

In human and mouse, the promoter of the KRAS gene contains a nuclease hypersensitive polypurine–polypyrimidine element (NHPPE) that is essential for transcription. An interesting feature of the polypurine G-rich strand of NHPPE is its ability to assume an unusual DNA structure that, according to circular dichroism (CD) and DMS footprinting experiments, is attributed to an intramolecular parallel G-quadruplex, consisting of three G-tetrads and three loops. The human and mouse KRAS NHPPE G-rich strands display melting temperature of 64 and 73°C, respectively, as well as a K(+)-dependent capacity to arrest DNA polymerase. Photocleavage and CD experiments showed that the cationic porphyrin TMPyP4 stacks to the external G-tetrads of the KRAS quadruplexes, increasing the T(m) by ∼20°C. These findings raise the intriguing question that the G-quadruplex formed within the NHPPE of KRAS may be involved in the regulation of transcription. Indeed, transfection experiments showed that the activity of the mouse KRAS promoter is reduced to 20% of control, in the presence of the quadruplex-stabilizing TMPyP4. In addition, we found that G-rich oligonucleotides mimicking the KRAS quadruplex, but not the corresponding 4-base mutant sequences or oligonucleotides forming quadruplexes with different structures, competed with the NHPPE duplex for binding to nuclear proteins. When vector pKRS-413, containing CAT driven by the mouse KRAS promoter, and KRAS quadruplex oligonucleotides were co-transfected in 293 cells, the expression of CAT was found to be downregulated to 40% of the control. On the basis of these data, we propose that the NHPPE of KRAS exists in equilibrium between a double-stranded form favouring transcription and a folded quadruplex form, which instead inhibits transcription. Such a mechanism, which is probably adopted by other growth-related genes, provides useful hints for the rational design of anticancer drugs against the KRAS oncogene

Despite WT1 binding sites in the promoter region of human and mouse nucleoporin glycoprotein 210, WT1 does not influence expression of GP210

BACKGROUND: Glycoprotein 210 (GP210) is a transmembrane component of the nuclear pore complex of metazoans, with a short carboxyterminus protruding towards the cytoplasm. Its function is unknown, but it is considered to be a major structural component of metazoan nuclear pores. Yet, our previous findings showed pronounced differences in expression levels in embryonic mouse tissues and cell lines. In order to identify factors regulating GP210, the genomic organization of human GP210 was analyzed in silico. RESULTS: The human gene was mapped to chromosome 3 and consists of 40 exons spread over 102 kb. The deduced 1887 amino acid showed a high degree of alignment homology to previously reported orthologues. Experimentally we defined two transcription initiation sites, 18 and 29 bp upstream of the ATG start codon. The promoter region is characterized by a CpG island and several consensus binding motifs for gene regulatory transcription factors, including clustered sites associated with Sp1 and the Wilms' tumor suppressor gene zinc finger protein (WT1). In addition, distal to the translation start we found a (GT)n repetitive sequence, an element known for its ability to bind WT1. Homologies for these motifs could be identified in the corresponding mouse genomic region. However, experimental tetracycline dependent induction of WT1 in SAOS osteosarcoma cells did not influence GP210 transcription. CONCLUSION: Although mouse GP210 was identified as an early response gene during induced metanephric kidney development, and WT1 binding sites were identified in the promoter region of the human GP210 gene, experimental modulation of WT1 expression did not influence expression of GP210. Therefore, WT1 is probably not regulating GP210 expression. Instead, we suggest that the identified Sp binding sites are involved

Mutations in the C-terminus of the X protein of hepatitis B virus regulate Wnt-5a expression in hepatoma Huh7 cells: cDNA microarray and proteomic analyses

Background: The hepatitis B virus x gene (HBx) is a promiscuous transactivator implicated in the development of hepatocellular carcinoma (HCC). The present study was designed to investigate the molecular events regulated by HBx. Methods: Genomic and proteomic expression profiling was performed in Huh7 HCC cells transfected with HBx mutants with a C-terminal deletion. The gene and protein expression of wingless-type murine-mammary-tumour virus (MMTV) integration site family, member 5A (Wnt-5a) was validated by analyses of reverse transcription–polymerase chain reaction (RT–PCR), real-time RT–PCR, western blot and immunohistochemistry. Results: Differentially expressed genes and proteins were found in the transfected Huh7 HCC cells; most of them were involved in transcriptional regulation, although others including oncogenes or tumor suppressor genes, and molecules involved in cell junctions, signal transduction pathways, metabolism or the immune response were also observed. The expression of the Wnt-5a gene was elevated >10-fold in Huh7 cells transfected with the HBx3′-30 amino acid deletion mutant. However, the expression was downregulated by the transfection with the HBx3′-40 amino acid deletion mutant. The changes in Wnt-5a expression were also observed in human HCC tissues, compared with corresponding non-cancerous liver tissues. A negative correlation was found between the expression of Wnt-5a and HBx COOH mutations in HCC tissues. Conclusions: HBx mutants may participate in the development and progression of HCC, at least in part through the Wnt-5a pathway

Transcriptional regulation of miR-196b by ETS2 in gastric cancer cells

E26 transformation-specific sequence (ETS)-2 is a transcriptional modulator located on chromosome 21, alterations in its expression have been implicated with a reduced incidence of solid tumors in Down syndrome patients. MicroRNAs (miRNAs) are thought to participate in diverse biological functions; however, the regulation of miRNAs is not well characterized. Recently, we reported that miR-196b is highly expressed in gastric cancers. Herein, we demonstrate that miR-196b expression was significantly repressed by ETS2 during gastric cancer oncogenesis. We demonstrate that knockdown of endogenous ETS2 expression increases miR-196b expression. A genomic region between −751 and −824 bp upstream of the miR-196b transcriptional start site was found to be critical for the repression activity. This putative regulatory promoter region contains three potential ETS2-binding motifs. Mutations within the ETS2 binding sites blocked the repression activity of ETS2. Furthermore, knockdown of ETS2 or overexpression of miR-196b significantly induced migration and invasion in gastric cancer cells. In addition, alterations in ETS2 and miR-196b expression in gastric cancer cell lines affected the expression of epithelial–mesenchymal transition-related genes. The levels of vimentin, matrix metalloproteinase (MMP)-2 and MMP9 were drastically induced, but levels of E-cadherin were decreased in shETS2- or miR-196b-transfected cells. Our data indicate that ETS2 plays a key role in controlling the expression of miR-196b, and miR-196b may mediate the tumor suppressor effects of ETS2. We demonstrated that miR-196b was transcriptionally regulated by ETS2 and there was an inverse expression profile between miR-196b and ETS2 in clinical samples. This finding could be beneficial for the development of effective cancer diagnostic and alternative therapeutic strategies

Ets-1 Confers Cranial Features on Neural Crest Delamination

Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination

Trauma and the pathogenesis of OCD : a literature review

Thesis (MA)--Stellenbosch University, 2001ENGLISH ABSTRACT: Post-traumatic stress disorder (PTSD) is the most recognised mental disorder stemming from severe psychological trauma. One of the differential diagnoses of post-traumatic stress disorder, amongst others, is obsessive-compulsive disorder (OGD). These two disorders overlap at some point in terms of symptomatology. More specifically, both are characterized by recurrent intrusive thoughts. It has been hypothesized that trauma may also be a significant source of OGD development. OGD and PTSD are disorders that present in adulthood, as well as in childhood and adolescence. It is shown that PTSD and OGD can present comorbidly in adulthood and it is theorized that it may also be the case in childhood and adolescence. Evidence of OGD developing in the context of trauma and theories of how this might have happened are presented. It is shown how complicated it is to distinguish between OGD developing in the wake of trauma and PTSD and the importance of such a distinction.AFRIKAANSE OPSOMMING: Post-traumatiese Stresversteurig (PTSD) is een van die mees erkende sielkundigeversteurings wat ontwikkel na die blootstelling aan sielkundige trauma. Obsessiewe-kompulsieweversteuring (OGD) is, onder andere, een van die differensiële diagnoses van PTSD. Die twee versteurings oorvleuel ten opsigte van simptomalogie. Meer spesifiek word beide gekenmerk deur herhalende indringende gedagtes. Daar word tans gehipotiseer dat trauma nie net 'n rol in die ontwikkeling van PTSD speel nie maar ook 'n oorsaaklike rol het in die ontwikkeling van OGD. OGD en PTSD is versteurings wat kan voorkom tydens volwassenheid, asook tydens die kinderjare en adolessensie. Daar word bewys gedoen van PTSD en OGD wat saam voorkom gedurende volwassenheid en daar word geteoretiseer dat dit ook die geval mag wees tydens die kinderjare en adolessensie. Bewys word gelewer van OGD wat ontwikkel na blootstelling aan trauma en teorië ten opsigte van die ontwikkeling word aangebied. Die onderskeid tussen OGD wat na trauma blootstelling ontwikkel en PTSD is ingewikkeld, dog is die onderskeid baie belangrik in vele opsigte