Herpes Simplex Virus Ribonucleotide Reductase: Structural Features and Transcriptional Regulation

Ribonucleotide reductase (EC 1.17.4.1. ) catalyses the direct reduction of all four ribonucleotides to the corresponding deoxyribonucleotides, this reaction being the first unique step in the de novo pathway of DNA biosynthesis. The herpes simplex virus type 1 (HSV-1)-induced enzyme is composed of two non-identical subunits, termed large (RR1) and small (RR2), which are dimers of the Vmw136 (RR1) and Vmw38 (RR2) polypeptides respectively. These polypeptides are specified by two early, unspliced and 3' co-terminal mRNAs with sizes of 5.0kb (RR1 mRNA) and 1.2kb (RR2 mRNA). The work presented in this thesis has been primarily directed at obtaining the predicted amino acid sequence of the HSV-1 RR1 polypeptide. The HSV-1 RR1 and RR2 amino acid sequences were analysed for conserved structural and functional features by comparisons to equivalent polypeptides of herpesviral and cellular origin. Other studies have identified the nucleotide changes in a portion of the RR1 gene of the HSV-1 temperature-sensitive (ts) mutant tsl207 and have examined the transcriptional regulation of RR1 and RR2 mRNA expression. The Nucleotide and Predicted Amino Acid Sequence of the HSV-1 RR1 Polypeptide. The nucleotide sequence of the HSV-1 DNA region encoding the RR1 polypeptide was obtained with the M13 dideoxy/chain termination method in combination with a 'shotgun' cloning approach. The sequencing data predicted that the RR1 DNA coding region is an open reading frame (ORF) of 3414 nucleotides which encodes a polypeptide of 1137 amino acids in length. In contrast to the remainder of the RR1 polypeptide, the N-terminal region contains unique amino acid composition features and seven sets of tandemly repeated amino acid sequences. A hypothetical scheme of evolutionary events leading to the formation of this region has been postulated. Further, as this region appears not be directly involved in enzymatic activity, a possible function has been suggested on the basis of two potential nuclear localisation signals. Amino Acid Conservation between Herpesvirus and Cellular Ribonucleotide Reductases. Analysis of amino acid conservation between the HSV-1 RR1 and RR2 polypeptides with identified or proposed large (RR L) and small (RRS) subunit polypeptides of herpesviral or cellular origin was performed using computer programs. a) Comparisons of the HSV-1 RR1 polypeptide with homologue RRL polypeptides. Comparison of the HSV-1 RR1 polypeptide with the equivalent herpes simplex virus type 2 (HSV-2) polypeptide revealed that they are essentially colinear with the exception of the N-terminal regions where number of insertions or deletions were predicted. Other analyses revealed that the RR1 N-terminal region was absent from other RRL polypeptides while the colinear parts exhibited clustered homology. b) Comparisons of the HSV-1 RR2 polypeptide with homologue herpesviral RRS polypeptides. Comparisons of the HSV-1 RR2 polypeptide with homologue herpesviral RRS polypeptides revealed the existence of clustered homology. The Escherichia coli (E. coli) tyrosine residue, on which the (essential for function) stable free radical has been localised, is conserved in all the RRS polypeptides examined These comparisons strongly indicate that the herpesviral RRL and RRS polypeptides examined are the constituents of the ribonucleotide reductase activities specified by these viruses. Conserved Structural and Potential Functional Features of the Herpesviral and Cellular Ribonucleotide Reductases. To identify more precisely regions of clustered homology and to determine potential functional features of the RRL and RRS polypeptide sequences, these were aligned with the consensus template alignment program and secondary structure predictions were obtained. (Abstract shortened by ProQuest.)

The COVID-19 Pandemic and Its Effects on the Greek Tourism Sector: A Case Study of the Region of Eastern Macedonia - Thrace

The recent novel coronavirus pandemic (COVID-19 pandemic) has led to a new, multi-faceted societal, healthcare and generalized economic crisis, both at national and international levels. The measures taken to deal with the pandemic have resulted in unprecedented situations in almost all sectors of the Greek economy. This article attempted to investigate the extent of the impact of this new crisis on Greek tourism companies, focusing on the case of tourist accommodation and food services by region, since the tourism industry has been greatly afflicted. The main variable examined was the degree of decline in the turnover of the tourism businesses under discussion over the last two years, at regional and national levels. This was supplemented with comparative analyses of similar measurable data. Secondary and statistical data were obtained from the Hellenic Statistical Authority, the Hellenic Tourism Organization and databases of other related institutions. Keywords: COVID-19, tourism industry, Greek companies, tourist product, region οf Eastern Macedonia - Thrac

Primary Ewing sarcoma of the axis-C2: A case report and the review of the literature

Introduction Neck pain and torticollis are common symptoms in the pediatric population that rarely requires further investigation. However, in case symptoms persist, then a more meticulously approach should be considered. Underlying conditions such as infections, neck injury, autoimmune disorders or even cervical spine cancer should be excluded from diagnosis. Cervical spine cancer is a rare neurosurgical entity in the pediatric population and even rarer is atlantoaxial Ewing's sarcoma. In this report, we present a rare case of primary Ewing's sarcoma of the axis. Case report A 3.5-year-old female with progressive neck pain and intermittent episodes of torticollis was referred to our outpatient clinic. Imaging studies revealed a malignant tumor located on C2 vertebra. Diagnosis of Ewing's Sarcoma was confirmed via open biopsy and the patient was treated with Euro-EWING 99 chemotherapy. Conclusion Pediatric neck pain and/or torticollis should raise high suspicion for malignancy of cervical spine. Modern diagnostic means and techniques can assist in the screening and diagnosis of these tumors

Airports’ Crisis Management Processes and Stakeholders Involved

Airports are exposed to various physical incidents that can be classified as aviation and non-aviation related incidents, including terrorist attacks, bombings, natural disasters (e.g. earthquake or tsunami and man-made disasters such as terrorist attacks) etc. (Kanyi, Kamau, &amp; Mireri, 2016). In addition to this, cyber-attacks to airport operations are emerging especially with the increasing use of Information Systems (IS), such as electronic tags for baggage handling and tracking, remote check-in, smart boarding gates, faster and more reliable security screening technologies and biometric immigration controls etc. Any physical or cyber incident that causes loss of infrastructure or massive patient surge, such as natural disasters, terrorist acts, or chemical, biological, radiological, nuclear, or explosive hazards could affect the airports’ services provision and could cause overwhelming pressure. During the crisis management, several stakeholders that have different needs and requirements, get involved in the process, trying to cooperate, respond and support recovery and impact mitigation. The aim of this paper is to present a holistic security agenda that defines the stakeholders involved in the respective processes followed during the crisis management cycle. This agenda is based both on normative literature, such as relevant standards, guidelines, and practices and on knowledge and feedback extrapolated from a case study conducted in the context of the SATIE project (H2020-GA832969). &nbsp;In meeting paper’s aim, initially the normative review of the phases of the crisis management cycle (preparedness, response, recovery and mitigation) in the context of airports as well as general practices applied, are presented. Moreover, the key airport stakeholders and operation centres involved in airports operations, as well as during the crisis management are analysed. By combining the information collected, a holistic cyber and physical crisis management cycle including the stakeholders and the relevant processes are proposed. The crisis management process is taken into consideration into the SATIE project, which aims to build a security toolkit in order to protect critical air transport infrastructures against combined cyber-physical threats. This toolkit will rely on a complete set of semantic rules that will improve the interoperability between existing systems and enhanced security solutions, in order to ensure more efficient threat prevention, threat and anomaly detection, incident response and impact mitigation, across infrastructures, populations and environment.</p

Patients with Atrial Fibrillation and Chronic Kidney Disease More Often Undergo Angioplasty of Left Main Coronary Artery – a 867 Patient Study

Background/Aims: Several studies have implicated atrial fibrillation (AF) as a contributing factor in chronic kidney disease (CKD) and cardiovascular events. The prevalence of coronary artery disease (CAD) in patients with AF varies substantially from 17% to 46.5%. There are only few studies concerning renal function in population with AF undergoing coronary angiography. The aim of the present study was to assess which type of AF is dominant in CKD population scheduled for coronary angiography and if it can influence patients’ outcome, the association between renal impairment and the type of coronary procedures in AF patients and the influence of renal function on in-hospital mortality. Methods: We retrospectively studied 867 patients with AF hospitalized due to coronary angiography in two year time. The cut off value of CKD was eGFR ≤ 60 ml/min./1.73m2 evaluated by CKD-EPI formula. Results: A total of 867 patients with AF (44% women; mean age 72±10 years) were included in the analysis. The mean eGFR was 44±11ml/min./1.73m2 in patients with CKD and 89±18 ml/min./1.73m2 in patients with preserved renal function. Patients with CKD and AF were older (p&#x3c; 0.001), had more often diabetes (p=0.009), heart failure (p&#x3c; 0.001) and anaemia (p&#x3c; 0.001). Patients with CKD and AF had more often permanent type of AF (p&#x3c; 0.001). In CKD patients CHA2DS2VASc score was 4.3±1.5 and HAS-BLED score was 2.0±1.2 and it was significantly higher as compared to population with preserved renal function (p&#x3c; 0.001, p=0.02, respectively). The use of oral anticoagulation was less frequent in CKD group (p&#x3c; 0.001) although these patients had higher CHA2DS2VASc score. Patients with AF and CKD were more often admitted due to myocardial infarction (STEMI or NSTEMI) (p=0.02, p&#x3c; 0.001, respectively) and more often underwent percutaneous coronary intervention (PCI) (p=0.01). Among coronary arteries the percutaneous coronary intervention (PCI) of left main artery was done more frequently in CKD patients (p=0.01). Among CKD population in-hospital mortality was significantly higher in patients with eGFR &#x3c; 30 ml/min (p&#x3c; 0.001). Conclusion: Patients with CKD had more often permanent type of AF. Percutaneous interventions of the left main coronary artery, the only elective procedures influencing patients’ prognosis, were done more frequently in CKD patients with AF. In-hospital mortality was significantly higher in patients with severe renal impairment. Despite the higher risk of ischaemic stroke in CKD group the use of oral anticoagulation therapy was significantly less frequent and the patients were deprived of the confirmed benefits of such treatment

Numerical solution of parameterized non-linear equations and global optimization with interval analysis

In this dissertation the problem of finding reliably and with certainty all the zeros a parameterized equation f(x,fp1) = 0, of a continuously differentiate function f is considered, where [p] is an interval vector describing all the parameters of the Equation, which are formed with interval numbers. For this kind of problem, methods of Interval Analysis are used. The incentive to this scientific research was emerged from a classic numerical analysis problem the numerical solution of polynomial systems of equations using interval analysis In particular, a heuristic reordering technique of the initial polynomial systems of equations is proposed. This approach seems to improve significantly the used solver. The proposed technique, as well as the results of this publication are presented in Chapter 2 of this dissertation. In the next Chapter 3, a methodology is proposed for solving reliably and efficiently parameterized (interval) equations. Firstly, a new formulation of interval arithmetic is given and the equivalence with the classic one is proved. Then, an extension of interval Newton method is proposed and developed, based on the new formulation of interval arithmetic. The new method is able to solve not only classic non-linear equations but, non-linear parameterised (interval) equation too. In Chapter 4 a new approach on solving the Box Constrained Global Optimization problem is proposed, based on the results of Chapter 3. In details, the Box Constrained Global Optimization problem is reduced to a problem of solving interval equations. The solution of this reduction is attainable through the methodology developed in Chapter 3. In the last Chapter of this dissertation a new algorithmic approach is given for the problem of solving reliably and with certainty an interval polynomial equation of degree $n$. This approach consists in a generalization of the work of Hansen and Walster. Hansen and Walster proposed a method for solving only quadratic interval polynomial equations.Η παρούσα διδακτορική διατριβή πραγματεύεται το θέμα της αποδοτικής και με βεβαιότητα εύρεσης όλων των ριζών της παραμετρικής εξίσωσης f(x,fp1) = 0, μιας συνεχώς διαφορίσιμης συνάρτησης f με [ρ] ένα διάνυσμα που περιγράφει όλες τις παραμέτρους της παραμετρικής εξίσωσης και τυποποιούνται με τη μορφή διαστημάτων. Για την επίλυση αυτού του προβλήματος χρησιμοποιήθηκαν εργαλεία της Διαστηματικής Ανάλυσης. Το κίνητρο για την ερευνητική ενασχόληση με το παραπάνω πρόβλημα προέκυψε μέσα από ένα κλασσικό πρόβλημα αριθμητικής ανάλυσης: την αριθμητική επίλυση σύστημα των πολυωνυμικών εξισώσεων μέσω διαστηματικής ανάλυσης. Πιο συγκεκριμένα, προτάθηκε μια ευρετική τεχνική αναδιάταξης του αρχικού πολυωνυμικού συστήματος που φαίνεται να βελτιώνει σημαντικά, κάθε φορά, τον χρησιμοποιούμενο επιλυτή. Η ανάπτυξη, καθώς και τα αποτελέσματα αυτής της εργασίας αποτυπώνονται στο Κεφάλαιο 2 της παρούσας διατριβής. Στο επόμενο Κεφάλαιο 3, προτείνεται μια μεθοδολογία για την αποδοτική και αξιόπιστη επίλυση μη γραμμικών εξισώσεων με διαστηματικές παραμέτρους, δηλαδή την αποδοτική και αξιόπιστη επίλυση διαστηματικών εξισώσεων. Πρώτα, δίνεται μια νέα διατύπωση της Διαστηματικής Αριθμητικής και αποδεικνύεται η ισοδυναμία της με τον κλασσικό ορισμό. Στη συνέχεια, χρησιμοποιείται η νέα διατύπωση της Διαστηματικής Αριθμητικής ως θεωρητικό εργαλείο για την ανάπτυξη μιας επέκτασης της διαστηματικής μεθόδου Newton που δύναται να επιλύσει όχι μόνο κλασσικές μη παραμετρικές μη γραμμικές εξισώσεις, άλλα και παραμετρικές (διαστηματικές) μη γραμμικές εξισώσεις. Στο Κεφάλαιο 4 προτείνεται μια νέα προσέγγιση για την αριθμητική επίλυση του προβλήματος της Ολικής Βελτιστοποίησης με περιορισμούς διαστήματα, χρησιμοποιώντας τα αποτελέσματα του Κεφαλαίου 3. Το πρόβλημα της ολικής βελτιστοποίησης, ανάγεται σε πρόβλημα επίλυσης διαστηματικών εξισώσεων, και γίνεται εφικτή η επίλυσή του με τη βοήθεια των θεωρητικών αποτελεσμάτων και της αντίστοιχης μεθοδολογίας του Κεφαλαίου 3. Στο τελευταίο Κεφάλαιο δίνεται μια νέα αλγοριθμική προσέγγιση για το πρόβλημα της επίλυσης διαστηματικών πολυωνυμικών εξισώσεων. Η νέα αυτή προσέγγιση, βασίζεται και γενικεύει την εργασία των Hansen και Walster, οι οποίοι πρότειναν μια μέθοδο για την επίλυση διαστηματικών πολυωνυμικών εξισώσεων 2ου βαθμού

Undercover infrastructure: Dual-use arctic satellite ground stations

Private companies are launching more rockets and satellites into space than ever before, increasing the amount of space assets and infrastructure for both civilian and military use. While these dual-use technologies, such as satellite communications, provide a wide range of essential services, they can also become military targets, posing significant security risks. This paper looks at satellite ground stations in the Arctic, how they are used, and how they can be protected in the face of growing geopolitical tensions among major powers such as China, Russia and the United States

Pediatric Masked Mastoiditis Associated with Multiple Intracranial Complications

Masked mastoiditis is a distinct form of mastoiditis with little or no symptomatology, characterized by its potential to generate severe otogenic complications. Therefore, suspected masked mastoiditis should be diagnosed and treated without delay. This study reports a rare case of masked mastoiditis, manifested by multiple intracranial complications in an immunocompetent girl. The child exhibited headache and neurological symptomatology. Imaging studies revealed an epidural and a large cerebellar abscess and the patient was immediately treated with a triple antibiotic therapy. Mastoid surgery and drainage of the epidural abscess took place after the stabilization of the patient’s neurologic status, on the 3rd hospitalization day. The cerebellar abscess was treated by craniectomy and ultrasound-guided needle aspiration in the 3rd week of hospitalization. The girl was finally discharged in excellent condition. Two years later, she is still in good health, without otological or neurological sequelae. Masked mastoiditis is an insidious disease which requires increased clinical awareness and adequate imaging. Should clinical and/or radiological findings be positive, mastoidectomy must follow in order to prevent severe otogenic complications that can be triggered by masked mastoiditis