MicroRNA Gene Networks in Oncogenesis

MicroRNAs are small non-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. They are involved in cellular development, differentiation, proliferation and apoptosis and play a significant role in cancer. Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. Several studies have shown that microRNAs function either as tumor suppressor genes or oncogenes, whose loss or overexpression respectively has diagnostic and prognostic significance. It seems that microRNAs act as major regulators of gene expression. In this review, we discuss microRNAs’ role in cancer and how microRNAs exert their functions through regulation of their gene targets. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets involved in apoptosis, angiogenesis and metastatic mechanisms. Matching computational prediction analysis together with microarray data seems the best method for microRNA gene target identification. MicroRNAs together with transcription factors generate a complex combinatorial code regulating gene expression. Thus, manipulation of microRNA-transcription factor gene networks may be provides a novel approach for developing cancer therapies

Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma.

Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape

Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. Methods: MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. Results: A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3’UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3’UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Conclusions: Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis

'The Degree of Despair': The Disjointed Labour Market, the Impact of the Pandemics, the Expansion of Precarious Work among Youth and Its Effects on Young People's Life Trajectories, Life Chances and Political Mentalities - Public Trust; The Case of Greece

This paper focuses on the expansion of precarious forms of employment (temporary, seasonal, part-time jobs etc.) and on the impact this expansion has on young peoples' key determinants of life course. Based on both secondary quantitative-data analysis and primary qualitative research, the paper analyzes the state of play regarding precarious work among youth both in the EU and (mainly) in Greece, while it highlights the impact of the pandemic and the subsequent Recession in the abovementioned. The paper also explores the various aspects and facets of the impact of precarious employment in young peoples' life trajectories. Key findings include: a) the strong correlation between precarious employment, social vulnerability and risk of poverty, b) the fact that, during the pandemic, the "labour market slack" in Greece hit young people aged 15-24 more than people aged 25-54, further widening their precariousness, c) that there is a wider tendency to expand and "normalize" the forms of precarious employment among youth, concerning, especially, the combination of declared and undeclared work, d) that a new labour market dualization is formed, e) that both the pandemic and the subsequent restrictive measures have had a significant impact on the majority of precarious young people, effectively causing a rupture in their already precarious life course and f) that all the abovementioned have a severe impact on key determinants of political behavior - mentalities as well as on public trust among young people. The paper is based on an ongoing Research Project, co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme "Human Resources Development, Education and Lifelong Learning 2014-2020" in the context of the project "Precarious Work and Youth in today's Greece: secondary quantitative analysis, qualitative filed research and research-based policy proposals" (MIS 5048510)

MiR-27b targets PPARγ to inhibit growth, tumor progression, and the inflammatory response in neuroblastoma cells

The PPARγ nuclear receptor pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 3′UTR of PPARγ and inhibits its mRNA and protein expression. miR-27b overexpression or PPARγ inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPARγ activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPARγ regulates NF-κB activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPARγ, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPARγ inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell-type specific differences in regulation of NHE1 and other target genes

Ο θεσμός του γάμου επί ρωμαϊκής αυτοκρατορίας

Στην παρούσα εργασία αναφερόμαστε στο θεσμό του γάμου επί Ρωμαϊκής Αυτοκρατορίας, παρατηρήσαμε ότι ο συγκεκριμένος θεσμός είναι χαρακτηριστική περίπτωση κοινωνικής σχέσης που ρυθμίζονταν καθαρά από εξωνομικούς κανόνες. Το ρωμαϊκό δίκαιο περιέχει αρκετές νομοθετικές ρυθμίσεις που αφορούν το γάμο και τις δημιουργούμενες κοινωνικές σχέσεις. Στη Ρώμη στόχος του νομοθέτη ήταν ο νόμος να αποτελεί το πρότυπο συμπεριφοράς και να εξασφαλίζει την ομαλή κοινωνική λειτουργία της Αυτοκρατορίας. Ο γάμος στη Ρώμη ήταν ένα πραγματικό γεγονός, το κύριο συστατικό του ήταν η affectio maritallis δηλαδή η επιθυμία του άνδρα και της γυναίκας να ζουν ως νόμιμοι σύζυγοι συγκατοικώντας κάτω υπό την ίδια στέγη. Ήταν το θεμέλιο της οικογένειας, του πυλώνα της Ρωμαϊκής κοινωνίας. Ο ρωμαϊκός γάμος ήταν «ένωση εντός της ίδιας κοινωνικής τάξης », δεν στηρίζονταν στον έρωτα αλλά θεωρούνταν κοινωνικό καθήκον όπως και η απόκτηση τέκνων (procreandorum causa). Eίχε διττό σκοπό α)να δημιουργηθεί τέλεια ισότητα ανάμεσα στο ζευγάρι από άποψη τιμής και αξιοπρέπειας και β) να δημιουργηθούν διάδοχοι. Αρκετά σημαντική παρακαταθήκη του ρωμαϊκού δικαίου αποτελεί η νομοθεσία του Αυτοκράτορα Αυγούστου με το νομοθετικό πρόγραμμα των: Lex Iulia de maritandis ordinibus (18π.χ.), Lex Iulia de adulteriis (18 π.χ.) και Lex Papia Poppaea (9 π.χ.) Στην εν λόγω εργασία παρουσιάζονται επίσης : η μνηστεία, οι προϋποθέσεις για τη σύναψη γάμου, θετικές οι οποίες πρέπει να συντρέχουν και αρνητικές οι οποίες πρέπει να απουσιάζουν, οι διακρίσεις των ρωμαϊκών γάμων, έθιμα καθώς επίσης και η λύση του γάμου. Το συμπέρασμα αυτής της συστηματικής μελέτης του ρωμαϊκού οικογενειακού δικαίου μας δείχνει ότι το δίκαιο του γάμου άλλοτε χρησιμοποιήθηκε για να επισπεύσει κοινωνικές αλλαγές και άλλοτε για να εμποδίσει ή να καθυστερήσει ανεπιθύμητες επερχόμενες αλλαγές.In the work presented we refer to the institution of marriage during the Roman Empire. We observed that this institution is a typical case of a social relationship that was clearly regulated by rules and regulations outside the legal system. Roman law contains several legal provisions concerning marriage and social relations. In Rome the aim of the legislator was for the law to be the model of conduct and to ensure of the smooth social functioning of the Empire. Marriage in Rome was a real event, its main ingredient was affectio maritallis, the desire of a man and a woman to live as legal spouses living together. It was the foundation of the family, the pillar of Roman society. Roman marriage was a "union within the same social class", it was not based on love but was considered a social duty like having children (procreandorum causa). It had a dual purpose a) to create perfect equality between the couple in terms of honor and dignity and b) to create successors. Quite an important legacy of Roman law is the legislation of the Emperor Augustus with the legislative program of: Lex Iulia de maritandis ordinibus (18 BC), Lex Iulia de adulteriis (18 BC) and Lex Papia Poppaea (9 BC). This work also presents: betrothal, the conditions for marriage, the positive ones that must be met and the negative ones that must be absent, the distinctions of Roman marriages, customs as well as the dissolution of the marriage. The conclusion of this systematic study of Roman family law shows us that the law of marriage was sometimes used to hasten social change and sometimes to prevent or delay unwanted impending change

Machine learning and deep learning based methods toward Industry 4.0 predictive maintenance in induction motors: Α state of the art survey

Purpose: Developments in Industry 4.0 technologies and Artificial Intelligence (AI) have enabled data-driven manufacturing. Predictive maintenance (PdM) has therefore become the prominent approach for fault detection and diagnosis (FD/D) of induction motors (IMs). The maintenance and early FD/D of IMs are critical processes, considering that they constitute the main power source in the industrial production environment. Machine learning (ML) methods have enhanced the performance and reliability of PdM. Various deep learning (DL) based FD/D methods have emerged in recent years, providing automatic feature engineering and learning and thereby alleviating drawbacks of traditional ML based methods. This paper presents a comprehensive survey of ML and DL based FD/D methods of IMs that have emerged since 2015. An overview of the main DL architectures used for this purpose is also presented. A discussion of the recent trends is given as well as future directions for research. Design/methodology/approach: A comprehensive survey has been carried out through all available publication databases using related keywords. Classification of the reviewed works has been done according to the main ML and DL techniques and algorithms Findings: DL based PdM methods have been mainly introduced and implemented for IM fault diagnosis in recent years. Novel DL FD/D methods are based on single DL techniques as well as hybrid techniques. DL methods have also been used for signal preprocessing and moreover, have been combined with traditional ML algorithms to enhance the FD/D performance in feature engineering. Publicly available datasets have been mostly used to test the performance of the developed methods, however industrial datasets should become available as well. Multi-agent system (MAS) based PdM employing ML classifiers has been explored. Several methods have investigated multiple IM faults, however, the presence of multiple faults occurring simultaneously has rarely been investigated. Originality/value: The paper presents a comprehensive review of the recent advances in PdM of IMs based on ML and DL methods that have emerged since 2015Peer Reviewe

Educational experimental setup based on laser beam scanners

We present a simple experimental setup based on two optical scanners to control a laser beam for a series of educational experiments. It was verified that this simple design, broadly used for spectacular laser-show presentations, can also significantly help the educational process for interested in physics undergraduate students mainly of art orientations, which might have a lower scientific or technological background. Comparison with an oscilloscope proved that the system accurately replicates the oscilloscope output (Lissajous figures), when two sinusoidal signals of various frequencies and phases are used as inputs. The Lissajous figures are demonstrated on the lab wall as a spectacular image that attracts the interest of the students to further study the underlying phenomena, without any need to educate them on complicated instruments such as oscilloscopes. The experiment awakens an additional motivation to study several issues related to laser radiation such as the scattering of the beam in the air, laser intensity and it is useful as an introductory experiment before presenting double-slit interference or direction of light experiments. Additionally, it can be used to measure the frequency of an unknown acoustic signal generated by a tuning fork, the phase difference between two signals and the wavelength and the velocity of sound