Ιστορική και Φιλοσοφική Προσέγγιση της έννοιας της ισότητας μεταξύ κρατών και λαών μέσα από το πρίσμα της Νεωτερικότητας. Από τη Γαλλική Επανάσταση έως και τον Γερμανικό Ιδεαλισμό.

Αντικείμενο της παρούσας μελέτης είναι η ιστορικοφιλοσοφική ανασκόπηση και εμβάθυνση της εξελικτικής πορείας της έννοιας της ισότητας και ελευθερίας των κρατών και των λαών, όπως αυτή διαμορφώθηκε από την περίοδο του Διαφωτισμού και εντεύθεν, καθώς και τα αίτια που οδήγησαν τον άνθρωπο στην αναζήτηση και θέσπιση θεσμών και κανόνων. Παρουσιάζεται η θέση του ατόμου και του κράτους, όπως αυτά διαμορφώθηκαν μέσω των ιστορικών και φιλοσοφικών ρευμάτων από τα τέλη του 17ου αι. έως και τις αρχές του 19ου αι. Εξ ίσου σημαντική είναι στην μελέτη και η έρευνα της γένεσης και της ανάγκης καθιέρωσης κανόνων του Διεθνούς Δικαίου. Κρίνεται απαραίτητο να προσεγγιστούν τα ζητήματα της μελέτης τόσο από την οπτική της ιστορικής όσο και από την οπτική της φιλοσοφικής πλευράς. Αναλύονται οι συντελεστές προαγωγής των ατομικών δικαιωμάτων του κλασικού φιλελευθερισμού. Το πρώτο κεφάλαιο εκκινεί με τη φιλοσοφική προσέγγιση της ισότητας και ελευθερίας στο προγενέστερο στάδιο της γαλλικής επανάστασης, καθώς και κατά τη διάρκεια του νεωτερισμού. Έπειτα, παρουσιάζεται η ιστορική αναδρομή της αρχής της ισότητας, η οποία ως διαχρονικό ιδεώδες έχει αποκτήσει μια σχεδόν υπερβατική σημασία. Ακροθιγώς, εξετάζονται ζητήματα που εστιάζουν στην αιτιολόγηση των δρώντων υποκειμένων κατά τη διάρκεια των «αστικών» επαναστάσεων, όπου παρατηρούνται διαρκώς μεταβαλλόμενοι πολιτικοί και κοινωνικοί θεσμοί με κύριο χαρακτηριστικό τις συλλογικές δράσεις οργάνωσης και το μετασχηματισμό μιας κοινωνίας σε έθνος-κράτος, κύριο αίτημα του οποίου υπήρξε η ισότητα. Περαιτέρω αναλύονται οι παράγοντες διαμόρφωσης του ευρωπαϊκού γίγνεσθαι του 17ου αι.. Αναλύεται η καντιανή γνώση όχι υπό την κλασική έννοια, δηλαδή ως ένα πραγματικό ον, όπως τα εμπειρικά αντικείμενα, αλλά ως ένα υπερβατολογικό ζητούμενο. Σημαντική είναι η εγελιανή τοποθέτηση για την ελευθερία, τη δικαιοσύνη και το κράτος. Το δίκαιο δύναται να πραγματωθεί μέσω του κράτους και η ελευθερία μπορεί να μεγαλουργήσει εντός της οργανωτικής δομής του δικαίου. Το κράτος αποτελεί τη συνιστώσα σύμφωνα με την οποία διαμορφώνεται η λογική και το πνεύμα. Η εγελιανή ελευθερία εάν πραγματώνεται μέσα σε μια κρατική οργανωμένη οντότητα, μπορεί να ικανοποιήσει την ελευθερία όλων των έλλογων ανθρώπων; Εάν παραστεί η ανάγκη κάλυψης των ανθρωπίνων αιτημάτων που παραμένουν ανικανοποίητοι, αυτό ως μία δυναμική άρνησης απέναντι στο «κύρος» και την αξιοπιστία των αρχών του εγελιανού κράτους, μπορεί να οδηγήσει στην κατάλυσή του, ή το κράτος αποκτά αυτή την δυνατότητα κάλυψης όλων των αναγκών, χωρίς να σταθεί μία τέτοια κατάσταση εμπόδιο στη διατήρηση της αρμονικής του λειτουργίας; Ο Έγελος, φρονεί ότι, το κράτος δεν μπορεί να υποταχθεί στην οικονομία, αλλά οφείλει να έχει τη βούληση να εφαρμόσει την οικονομική πολιτική. Η αγωνία του φιλοσόφου αφορά την ιστορική στιγμή κατάλυσης των κρατικών θεμελίων, όταν αυτά απειλούνται από τον όχλο. Η ιστορία για τον Έγελο ισοδυναμεί με την ίδια την ερμηνεία του ανθρώπινου όντος. Κατά τον Έγελο οι θεωρίες ερμηνείας της ανθρώπινης ύπαρξης δεν ανήκουν στο βάθρο των υψηλών αφηρημένων ιδεών, αλλά στον κόσμο των εννοιών, οι οποίες διαμορφώνονται εντός του πραγματικού κόσμου. Στο έργο του Φαινομενολογία του Πνεύματος, το οποίο αποτελεί έναν αναβαθμό που οδηγεί προς την Απόλυτη Αλήθεια, και ολοκληρώνεται με τα ιδανικά της Γαλλικής επανάστασης, δηλαδή την ισότητα και ελευθερία, την αδελφότητα και την κοσμικότητα, εξετάζεται η τάση της Ιστορίας να οδηγηθεί προς τον έναν σκοπό. Η πραγμάτωση του εγελιανού Πνεύματος και το τέλος της Ιστορίας, δηλώνουν ότι, όταν οι ιδεολογικοί, πολιτικοί, πολιτιστικοί και νοητικοί προσδιορισμοί του ανθρώπου έχουν ερμηνευτεί και ικανοποιήσει την φυσική τάση του ανθρώπου να κατανοήσει την ιστορία, τότε ο απολογισμός του ανθρώπου για τη φύση του είναι οριστικός. Επιπροσθέτως, αναλύεται η έννοια του κράτους ως ιστορικό προϊόν της ανθρώπινης δράσης και μαζί με αυτό εξηγείται η νέα τάξη πραγμάτων, όπως αυτή διαμορφώνεται με την βοήθεια αλλά και επίκληση του Διεθνούς Δικαίου με σκοπό την επανεξέταση των εννοιών ισότητας, ελευθερίας και δικαιοσύνης. Ακολουθεί ανάλυση των διεθνών συνθηκών μέσω των οποίων εξελίχθηκε το Διεθνές Δίκαιο στη σημερινή του μορφή, οι βασικοί πυλώνες εξέλιξής του, βάσει των οποίων συναλλάσσονται πολυποίκιλα τα κράτη και αναπτύσσονται οι ανθρώπινες σχέσεις, με απώτερο σκοπό να αναδειχθούν τα σημεία εκείνα ως κρίσιμα ζητήματα που απασχόλησαν την πολιτική, φιλοσοφική και ιστορική σκέψη διαχρονικά. Οι ιστορικοί σταθμοί εξέλιξης του Διεθνούς Δικαίου υπό το πρίσμα μιας ιστορικοφιλοσοφικής σκοπιάς αποτελούν τρόπον τινά και την προβληματική ως προς τον σκοπό της υπάρξεώς του, διότι εξ ορισμού η παγκοσμιοποίηση επιδρά ως μεταβλητή στην ανάγκη αλλαγών ή αναπροσαρμογών του. Διεξοδικώς, αναλύεται η ισότητα των λαών και το δικαίωμα τους στην αυτοδιάθεση, η κυριαρχία ως συμπληρωματική αρχή της ισότητας των κρατών και η αναζήτηση της έννοιας του κράτους στα χρόνια του Διαφωτισμού και εντεύθεν, ώστε να διαφωτιστεί, όσο το δυνατόν περισσότερο ο σκοπός ενισχύσεως των συγκεκριμένων αρχών, καθώς και κατά πόσο σήμερα τηρούνται ή όχι.The purpose of this study is the historical-philosophical review and deepening of the evolutionary course of the concept of equality and freedom of states and peoples, as shaped by the period of the Enlightenment and afterwards, as well as the causes that led man to seek and establish institutions and rules. It presents the position of the individual and the state, as they were shaped through the historical and philosophical currents of the late 17th century. until the beginning of the 19th century. Equally important is the study and research of the origins and the need to establish rules of international law. It is necessary to approach the issues of study from both a historical and a philosophical point of view. The factors promoting the individual rights of classical liberalism are analyzed. The first chapter begins with the philosophical approach to equality and freedom at the earlier stage of the French Revolution, as well as during modernity. Next, there is the historical reversal of the principle of equality, which as a timeless ideal has acquired an almost transcendental significance. At the end, issues that focus on the justification of the actors during the 'bourgeois' revolutions are examined, with the ever-changing political and social institutions being characterized by the collective actions of the organization and the transformation of a nation-state society whose main demand equality. Further elaborating on the shaping factors of 17th century European genesis. Kantian knowledge is analyzed not in the classical sense, that is, as a real being, such as empirical objects, but as a transcendental object. Important is the Hegelian stance on freedom, justice and the state. Law can be realized through the state and freedom can be enhanced within the organizational structure of law. The state is the component according to which reason and spirit are formed. Can the Hegelian freedom, if it is exercised within a state-organized entity, satisfy the freedom of all rational people? If there is a need to meet the human demands that remain unsatisfied, this as a dynamic of denial of the "authority" and credibility of the authorities of the Greater State can lead to its overthrow, or the State acquires this capacity to meet all needs, without such a situation being an obstacle to maintaining its harmonious function? Aegelos believes that the state cannot be subjugated to the economy, but must have the will to implement economic policy. The philosopher's anxiety is about the historic moment of the overthrow of state foundations when they are threatened by the mob. The story of the Angel is equivalent to the interpretation of the human being itself. According to Hegel, the theories of interpretation of human existence do not belong to the pedestal of the high abstract ideas, but to the world of concepts, which are formed within the real world. In his work. The Phenomenology of the Spirit, which is a stepping stone to Ultimate Truth, complete with the ideals of the French Revolution, namely equality and freedom, brotherhood and secularism, it examines the tendency of History to lead one purpose. The realization of the Aegean Spirit and the end of History state that when man's ideological, political, cultural and intellectual determinations have been interpreted and satisfy man's natural tendency to understand history, then man's account of nature is definitive. In addition, the concept of the state as a historical product of human action is analyzed and explained with the new order of things as it is shaped and invoked by international law in order to re-examine the concepts of equality, freedom and justice. Following is an analysis of the international contexts through which International Law has evolved in its present form, the key pillars of its evolution, on the basis of which states are transacted widely and human relations are developed, with the ultimate aim of highlighting those issues as critical political, philosophical and historical thought over time. Historical developments in international law in the light of a historical-philosophical point of view are also problematic as to the purpose of its existence, because by definition globalization has a variable effect on the need for changes or adaptations. In-depth analysis of peoples' equality and their right to self-determination, sovereignty as a complementary principle of equality of states, and the search for the concept of the state in the years of the Enlightenment and thereafter, in order to enlighten, as much as possible, the purpose of principles, and whether or not they are adhered to today

Multiple Access in the Era of Distributed Computing and Edge Intelligence

This paper focuses on the latest research and innovations in fundamental next-generation multiple access (NGMA) techniques and the coexistence with other key technologies for the sixth generation (6G) of wireless networks. In more detail, we first examine multi-access edge computing (MEC), which is critical to meeting the growing demand for data processing and computational capacity at the edge of the network, as well as network slicing. We then explore over-the-air (OTA) computing, which is considered to be an approach that provides fast and efficient computation of various functions. We also explore semantic communications, identified as an effective way to improve communication systems by focusing on the exchange of meaningful information, thus minimizing unnecessary data and increasing efficiency. The interrelationship between machine learning (ML) and multiple access technologies is also reviewed, with an emphasis on federated learning, federated distillation, split learning, reinforcement learning, and the development of ML-based multiple access protocols. Finally, the concept of digital twinning and its role in network management is discussed, highlighting how virtual replication of physical networks can lead to improvements in network efficiency and reliability

Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates and limited therapeutic options. Thus elucidation of signaling pathways involved in PDAC pathogenesis is essential for identifying novel potential therapeutic gene targets. Here, we used a systems approach to elucidate those pathways by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly downregulated in PDAC relative to control pancreatic tissues. Functional experiments revealed that FOXA2 has a tumor suppressor function through inhibition of pancreatic cancer cell growth, migration, invasion, and colony formation. In situ hybridization analysis revealed miR-199a to be significantly upregulated in pancreatic cancer. Bioinformatics and luciferase analyses showed that miR-199a negatively but directly regulates FOXA2 expression through binding in its 3′-untranslated region (UTR). Evaluation of the functional importance of miR-199a on pancreatic cancer revealed that miR-199a acts as an inhibitor of FOXA2 expression, inducing an increase in pancreatic cancer cell proliferation, migration, and invasion. Additionally, gene ontology and network analyses in PANC-1 cells treated with a small interfering RNA (siRNA) against FOXA2 revealed an enrichment for cell invasion mechanisms through PLAUR and ERK activation. FOXA2 deletion (FOXA2Δ) by using two CRISPR/Cas9 vectors in PANC-1 cells induced tumor growth in vivo resulting in upregulation of PLAUR and ERK pathways in FOXA2Δ xenograft tumors. We have identified FOXA2 as a novel tumor suppressor in pancreatic cancer and it is regulated directly by miR-199a, thereby enhancing our understanding of how microRNAs interplay with the transcription factors to affect pancreatic oncogenesis

Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration

Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and ανβ3 integrin. Screening for proteins that interact with RPTPβ/ζ and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclin-dependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration. Protein immunoprecipitation and proximity ligation assays verified p35-RPTPβ/ζ interaction and revealed the molecular association of CDK5 and RPTPβ/ζ. In endothelial cells, PTN activates CDK5 in an RPTPβ/ζ- and phosphoinositide 3-kinase (PI3K)-dependent manner. On the other hand, c-Src, ανβ3 and ERK1/2 do not mediate the PTN-induced CDK5 activation. Pharmacological and genetic inhibition of CDK5 abolished PTN-induced endothelial cell migration, suggesting that CDK5 mediates PTN stimulatory effect. A new pyrrolo[2,3-α]carbazole derivative previously identified as a CDK1 inhibitor, was found to suppress CDK5 activity and eliminate PTN stimulatory effect on cell migration, warranting its further evaluation as a new CDK5 inhibitor. Collectively, our data reveal that CDK5 is activated by PTN, in an RPTPβ/ζ-dependent manner, regulates PTN-induced cell migration and is an attractive target for the inhibition of PTN pro-angiogenic properties

Global assessment of C-reactive protein and health-related outcomes: an umbrella review of evidence from observational studies and Mendelian randomization studies.

C-reactive protein (CRP) has been studied extensively for association with a large number of non-infectious diseases and outcomes. We aimed to evaluate the breadth and validity of associations between CRP and non-infectious, chronic health outcomes and biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses and a systematic review of Mendelian randomization (MR) studies. PubMed, Scopus, and Cochrane Database of Systematic Reviews were systematically searched from inception up to March 2019. Meta-analyses of observational studies and MR studies examining associations between CRP and health outcomes were identified, excluding studies on the diagnostic value of CRP for infections. We found 113 meta-analytic comparisons of observational studies and 196 MR analyses, covering a wide range of outcomes. The overwhelming majority of the meta-analyses of observational studies reported a nominally statistically significant result (95/113, 84.1%); however, the majority of the meta-analyses displayed substantial heterogeneity (47.8%), small study effects (39.8%) or excess significance (41.6%). Only two outcomes, cardiovascular mortality and venous thromboembolism, showed convincing evidence of association with CRP levels. When examining the MR literature, we found MR studies for 53/113 outcomes examined in the observational study meta-analyses but substantial support for a causal association with CRP was not observed for any phenotype. Despite the striking amount of research on CRP, convincing evidence for associations and causal effects is remarkably limited

Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase-mediated generation of reactive oxygen species

Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and integrin alpha v beta 3 (ανβ3). In the present work, we studied the effect of PTN on the generation of reactive oxygen species (ROS) in human endothelial cells and the involvement of ROS in PTN-induced cell migration. Exogenous PTN significantly increased ROS levels in a concentration and time-dependent manner in both human endothelial and prostate cancer cells, while knockdown of endogenous PTN expression in prostate cancer cells significantly down-regulated ROS production. Suppression of RPTPβ/ζ through genetic and pharmacological approaches, or inhibition of c-src kinase activity abolished PTN-induced ROS generation. A synthetic peptide that blocks PTN–ανβ3 interaction abolished PTN-induced ROS generation, suggesting that ανβ3 is also involved. The latter was confirmed in CHO cells that do not express β3 or over-express wild-type β3 or mutant β3Y773F/Y785F. PTN increased ROS generation in cells expressing wild-type β3 but not in cells not expressing or expressing mutant β3. Phosphoinositide 3-kinase (PI3K) or Erk1/2 inhibition suppressed PTN-induced ROS production, suggesting that ROS production lays down-stream of PI3K or Erk1/2 activation by PTN. Finally, ROS scavenging and xanthine oxidase inhibition completely abolished both PTN-induced ROS generation and cell migration, while NADPH oxidase inhibition had no effect. Collectively, these data suggest that xanthine oxidase-mediated ROS production is required for PTN-induced cell migration through the cell membrane functional complex of ανβ3 and RPTPβ/ζ and activation of c-src, PI3K and ERK1/2 kinases

Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming

Objective: Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis. Design: DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo. Results: We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates. Conclusion: Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer

Rehabilitation to enable recovery from COVID-19: a rapid systematic review

Objectives: To establish the evidence for rehabilitation interventions tested in populations of patients admitted to ICU and critical care with severe respiratory illness, and consider whether the evidence is generalizable to patients with COVID-19. Methods: The authors undertook a rapid systematic review. Medline (via OvidSP), CINAHL Complete (via EBSCOhost), Cochrane Library, Cochrane Database of Systematic Reviews and CENTRAL (via Wiley), Epistemonikos (via Epistemonikos.org), PEDro (via pedro.org.au) and OTseeker (via otseeker.com) searched to 7 May 2020. The authors included systematic reviews, RCTs and qualitative studies involving adults with respiratory illness requiring intensive care who received rehabilitation to enhance or restore resulting physical impairments or function. Data were extracted by one author and checked by a second. TIDier was used to guide intervention descriptions. Study quality was assessed using Critical Skills Appraisal Programme (CASP) tools. Results: Six thousand nine hundred and three titles and abstracts were screened; 24 systematic reviews, 11 RCTs and eight qualitative studies were included. Progressive exercise programmes, early mobilisation and multicomponent interventions delivered in ICU can improve functional independence. Nutritional supplementation in addition to rehabilitation in post-ICU hospital settings may improve performance of activities of daily living. The evidence for rehabilitation after discharge from hospital following an ICU admission is inconclusive. Those receiving rehabilitation valued it, engendering hope and confidence. Conclusions: Exercise, early mobilisation and multicomponent programmes may improve recovery following ICU admission for severe respiratory illness that could be generalizable to those with COVID-19. Rehabilitation interventions can bring hope and confidence to individuals but there is a need for an individualised approach and the use of behaviour change strategies. Further research is needed in post-ICU settings and with those who have COVID-19. Registration: Open Science Framework https://osf.io/prc2