Spontaneous development of macular ischemia in a case of racemose hemangioma

Dimitrios Panagiotidis, Dimitrios Karagiannis, Ioannis TsoumprisSecond Ophthalmology Department of Athens University, Attikon Hospital, Athens, GreecePurpose: To report a rare case of racemose hemangioma which developed spontaneous macular ischemia.Methods: A 32-year-old healthy Caucasian lady presented complaining of recent deterioration of vision in her left eye. At presentation, her best corrected visual acuity (BCVA) was 20/20 in her right eye and counting fingers in her left eye (LE). Fundus examination and fluorescein angiography were performed. The patient had regular follow-up appointments over a period of 8 years.Results: Fundus examination and fluorescein angiography revealed findings consistent with arteriovenous communications of the retina or racemose hemangioma, in the posterior pole of the LE with the presence of macular ischemia. Complete and systemic examination was unremarkable, excluding the possibility of Wyburn-Mason syndrome. Eight years after presentation, findings and BCVA in the LE have remained stable, with no extension of the retinal ischemia or development of neovascularization.Conclusion: Although extensive retinal ischemia has been reported to result in complications such as retinal or iris neovascularization, in our case the macular ischemia has not expanded further over a period of 8 years. However, due to this macular ischemia the patient unfortunately lost her central vision.Keywords: racemose hemangioma, macular ischemia, retinal ischemi

The Effects of Corporate Bonds on Employment: Early Evidence from Greece

This study investigates the impact of corporate bonds issued by Greek listed firms on employment. Even though external financing and the effects on employment has been studied in the literature, we extend the existing literature by focusing for the first time on the specific role of corporate bonds on employment. We have collected all the relevant papers on this line of the literature and concisely report them in a table format and then use them in analyzing our results. Our empirical analysis is based on a panel dataset from 2001 to 2014 and we examine the effect of corporate bonds in the pre and post period of the Greek economic crisis, in which the banking system is vulnerable and unable to provide financing to the firms. The results suggest that corporate bonds have a positive effect on employment in the pre-crisis sample, denoting that firms hire employees and proceed to investment choices. On the contrary, during the recession, corporate bonds have a negative effect on employment. Firms reduce their costs and try to control their debt obligations by issuing corporate bonds

Epigenetic targeting of metabolic and lineage abnormality in cancer

Chromatin regulation is a major aspect of cancer development, progression, and treatment. Several small molecule inhibitors of chromatin regulators are currently used for treatment of certain hematological malignancies. However, there is still opportunity for many more patients to benefit from therapeutic approaches that target chromatin regulation, especially in the context of solid tumors. A critical unmet need is the identification of robust biomarkers that can guide the application of epigenetic inhibitors in a precise and personalized manner. In my dissertation, I aim to address this important knowledge gap by studying how perturbation of chromatin can target metabolic and lineage abnormalities in solid tumors for therapeutic benefit. To do this, I have focused on genetic and pharmacological perturbations of chromatin pathways in two cancer models: (1) lung adenocarcinoma (LUAD) with NRF2 activation and (2) neuroendocrine esophageal carcinoma (NEC). In the study on NRF2-active LUAD, we found that histone deacetylase (HDAC) inhibitors can be repurposed to reprogram the epigenomic and metabolic landscape, which leads to specific and potent anti-tumor effects in the context of NRF2 activation. Specifically, we employed a chromatin-focused genetic screen to identify dependencies on chromatin regulators. The screen revealed an NRF2-specific dependency on class I histone deacetylases. Experiments in mouse and human LUAD cell lines in vitro and in vivo indicated an NRF2-specific sensitivity to the class I HDAC inhibitor Romidepsin. Mechanistically, profiling of histone acetylation and gene expression upon Romidepsin treatment revealed a relative loss of histone H4 acetylation at promoters which was associated with reduced gene expression. Many downregulated genes were more essential for the survival of NRF2 hyperactive cancer cells, including genes involved in glutamine and serine metabolism, c-Myc and several of its targets involved in purine and pyrimidine synthesis. These transcriptional changes had corresponding effects on altering the metabolic pathways that NRF2-active cells selectively require for survival. In the study on neuroendocrine esophageal carcinoma (NEC), we identified a crucial role for epigenetic regulation of lineage fate through transcriptional control of the key epidermal transcription factor p63. This project originated from data from my collaborators that indicates a role for p63 in the suppression of basal-to-neuroendocrine identity transition in the developing esophagus. Consistently, I found that p63 is silenced in NEC through a non-genetic mechanism. Reintroducing p63 isoforms in a human NEC cell line showed that ΔNp63α was sufficient to restore squamous marker expression. An epigenetic drug screen assessing p63 gene expression and subsequent validation experiments revealed that inhibition of EZH2, a histone methyltransferase, induced expression of ΔNp63α and genes related to the squamous identity. Analysis of the chromatin state in the TP63 locus showed that EZH2 inhibition led to a loss histone H3 methylation and a gain of histone H3 acetylation and its reader BRD4. These results support the hypothesis that the squamous identity can be reactivated epigenetically in NEC through de-repression of ΔNp63α as a potential therapeutic strategy. Together, these studies contribute to our understanding of the transcriptional response to chromatin perturbation and show that this can be leveraged to modulate cell metabolism and identity, as well as to achieve therapeutic benefit in new contexts of cancer

A case of polypoidal choroidal vasculopathy. Periphery is equally important for such patients

Dimitrios A Karagiannis, Vasilios Soublis, Artemios Kandarakis1st Ophthalmology Department of Ophthalmiatrio Eye Hospital of Athens, Athens, GreeceBackground: To report a case of peripheral polypoidal choroidal vasculopathy (PCV) which was treated successfully.Methods: Interventional case report. Best-corrected visual acuity measurements (BCVA), slit-lamp examination, fundus biomicroscopy, fluorescein angiography (FFA), and indocyanine green angiography (ICGA) were performed at baseline examination and during the follow-up period. The patient underwent ICGA-guided argon laser to treat the active polyps. Results: An 82-year-old Caucasian man presented complaining of sudden deterioration of peripheral vision in his left eye (LE). His previous ocular history was associated with advanced age-related macular degeneration (AMD) involving both eyes (BE). Fundus examination revealed macular scars in BE and a large hemorrhagic pigment epithelial detachment (PED) temporal to the macula in the LE. ICGA revealed active polyps at the margins of the PED. The patient underwent ICGA-guided argon laser to treat the active polyps. Six months post-laser, the patient regained his peripheral vision with resolution of the hemorrhagic PED and remains stable until now, one year after treatment.Conclusions: Appropriate treatment and regular follow-up is important in patients with PCV and peripheral lesions even if central vision is lost.Keywords: argon laser, peripheral vision, polypoidal choroidal vasculopath

Nonlinear observer design using invariant manifolds and applications,”

Abstract-The problem of constructing (reduced-order) observers for general nonlinear systems is addressed. It is shown that an asymptotic estimate of the unknown states can be obtained by rendering attractive an appropriately selected (invariant) manifold in the extended state space. The proposed methodology is applicable to systems that are not necessarily linear in the unmeasured states. This is illustrated with two practical examples: a single-machine infinite-bus system and a perspective vision system

Προσδιορισμός νέων αναστολέων της μιτοχονδριακής ATP συνθάσης. In silico επιλογή και in vitro φαρμακολογική αξιολόγηση.

Η ATP συνθάση (επίσης γνωστή και ως F-ATPάση ή F1Fo-ATPάση) αποτελεί ένα σημαντικό σύμπλεγμα πρωτεϊνών, το οποίο έχει αποδειχτεί ότι είναι μια μικρή μοριακή μηχανή τύπου ρότορα. Ανάλογα με τις συνθήκες, το σύμπλεγμα αυτό είτε παράγει, είτε υδρολύει τριφωσφορική αδενοσίνη (ATP). Κατά την ισχαιμία του μυοκαρδίου, ο ρότορας της ATP συνθάσης αλλάζει φορά λειτουργώντας υδρολυτικά, καταναλώνοντας άσκοπα ATP και προκαλώντας δυσλειτουργία στα μιτοχόνδρια. (1) Εκλεκτική αναστολή της ATP υδρολάσης θα μπορούσε να έχει ως αποτέλεσμα την προστασία του μυοκαρδίου από βλάβες που οφείλονται στην ισχαιμία, με αποτέλεσμα η ανακάλυψη τέτοιων αναστολέων να κρίνεται ιδιαίτερα ενδιαφέρουσα. Σε αυτή την μελέτη, παρουσιάζεται o προσδιορισμός νέων αναστολέων της υδρολυτικής δράσης της ATP συνθάσης, βασισμένος σε υπολογιστικές (εικονικές) και πειραματικές μεθόδους αξιολόγησης. Για την πραγματοποίηση των εικονικών υπολογισμών αξιολόγησης κατασκευάστηκε για πρώτη φορά ένα ολιστικό μοντέλο της ATP συνθάσης των ποντικών (mus musculus) βασισμένο σε ομόλογο μοντέλο, χρησιμοποιώντας όλες τις γνωστές υπομονάδες από την Protein Data Bank (PDB). Βασισμένοι σε αυτό το μοντέλο πραγματοποιήθηκαν υπολογισμοί εικονικής αξιολόγησης πρόσδεσης-κατάταξης στοχεύοντας τα τρία κυρίαρχα ενεργά κέντρα αναστολέων, ήδη γνωστά από την βιβλιογραφία: α) το σημείο κατάλυσης του ATP-ADP β) τη θέση πρόσδεσης της ολιγομυκίνης (oligomycin) γ) την επιφάνεια που σχηματίζει η αύλακα μεταξύ των υπομονάδων 3α και 3β όπου προσδένονται γνωστά μόρια όπως η κερκετίνη και η ρεσβερατρόλη εμφανίζοντας ανασταλτική δράση. Για τη μελέτη αυτή χρησιμοποιήθηκε η συλλογή μορίων του Τμήματος Φαρμακευτικής του ΕΚΠΑ που περιέχει 2000 φυσικά και συνθετικά μόρια (Pharmalab). Εκτός από τους υπολογισμούς πρόσδεσης με την ATP συνθάση, πραγματοποιήθηκε και αξιολόγηση με βάση την ομοιότητα (similarity) του προσδέματος ως προς γνωστούς αναστολείς όπως το BMS-199264.(1) Επελέγησαν 48 μόρια και εν συνεχεία έγινε in-vitro αξιολόγηση σε απομονωμένα κλάσματα μιτοχονδρίων, προσδιορίζοντας την υδρολυτική δράση της ATP συνθάσης από τα παραγόμενα PO43-. Συγκεκριμένα, ιστοί καρδιάς από C57-BL-6 ποντίκια αποκόπηκαν αρχικά ώστε να απομονωθούν τα μιτοχόνδρια. Προκειμένου η ATP συνθάση να λειτουργήσει αντίστροφα υδρολύοντας ATP, ακολούθησε ένας κύκλος ψύξης-απόψυξης του δείγματος. Τα αποτελέσματα έδειξαν ότι 35 από τις 48 (73%) υπό εξέταση ενώσεις εμφάνισαν ποικίλες ανασταλτικές δράσεις στα 0.2 mM, επαληθεύοντας τη συνολική υπολογιστική αξιολόγηση. Μεταξύ των 35 μορίων που εμφάνισαν αναστολή, 7 μόρια εμφάνισαν κοινό σκελετό, παρουσιάζοντας ενισχυμένη δράση (αναστολή 48 – 82.5%). Η τιμή IC50 των ενώσεων αυτών μελετήθηκε περαιτέρω, επιβεβαιώνοντας ότι αυτός ο μοριακός σκελετός είναι υπεύθυνος για την ανασταλτική δράση και μπορεί να οδηγήσει σε νέες ενώσεις με πιθανή προστατευτική δράση κατά της ισχαιμίας του μυοκαρδίου.ATP synthase (also known as F-ATPase or F1Fo-ATPase) is a significant multiprotein complex, proven to be a small rotor machine, either producing or hydrolyzing adenosine triphosphate. During myocardial ischemia ATP synthase's rotor switch to hydrolyzing activity, wasting ATP and generating dysfunctional mitochondria. (1) Selective inhibition of ATP hydrolase, could be of major significance for cardioprotection and the discovery of new inhibiting agents is of particular interest for the development of new therapeutic schemes. In this work, we present the identification of inhibitors of the hydrolytic activity of ATP synthase, based on virtual and experimental screening methods. In a first step, we constructed for the first time a holistic model of ATP synthase of mus musculus based on homology modeling using all known subunits from Protein Data Bank (PDB). Based on this model, docking-scoring calculations have been performed targeting the three major inhibition sites already known from literature: a) the ATP-ADP catalytic site b) the oligomycin binding site and c) inside the surface of a groove made from loops in the 3α and 3β subunits where molecules like quercetin or resveratrol are known to bind. The workflow has been implemented on our in-house library of 2000 natural products and synthetic compounds (Pharmalab). Moreover, ligand-based virtual screening, has been carried out based on similarity calculations of the chemical library components against known binders like BMS-199264. (1) Different steps of filtering through the in silico screening provided 48 molecules that were further tested in vitro on isolated murine heart mitochondrial fractions, evaluating ATP synthase hydrolytic activity. C57-BL-6 mice’ hearts were cut to isolate mitochondria. In order ATP synthase to function hydrolyzing ATP, a freeze-thaw cycle of the sample was followed, while the production of PO43- has been finally evaluated. The results showed that 35 out of 48 (73%) tested compounds exhibited various inhibitory activities at 0.2 mM, validating our computer-based drug design method. Among 35 hits, 7 molecules appeared to have common scaffold displaying enhanced activity (48 – 82.5% inhibition). The IC50 of these compounds has been further determined, providing confirmatory evidence of the inhibitory activity of the scaffold which can lead us to a novel agent against myocardial ischemia

A case of subretinal neovascularization treated with intravitreal ranibizumab in a patient with idiopathic juxtafoveal retinal telangiectasis

A 65-year-old lady presented with decreased vision in her left eye (LE). Best corrected visual acuity (BCVA) was 1/20. Complete examination showed idiopathic juxtafoveal retinal telangiectasis associated with subretinal neovascularization and she was treated with intravitreal ranibizumab every month for three months in the LE. After four months, her BCVA increased to 3/10. Fluorescein angiography (FA) showed minimal leakage and optical coherence tomography (OCT) confirmed absence of intra- or subretinal fluid in the macula. Examinations were repeated monthly for another 12 months and showed no recurrence. Intravitreal ranibizumab showed promising results for subretinal neovascularization due to idiopathic juxtafoveal retinal telangiectasis. A prospective study with large series of patients and controls may be necessary in order to determine the effectiveness of this treatment

RF Jamming Classification Using Relative Speed Estimation in Vehicular Wireless Networks

Wireless communications are vulnerable against radio frequency (RF) interference which might be caused either intentionally or unintentionally. A particular subset of wireless networks, Vehicular Ad-hoc NETworks (VANET), which incorporate a series of safety-critical applications, may be a potential target of RF jamming with detrimental safety effects. To ensure secure communications between entities and in order to make the network robust against this type of attacks, an accurate detection scheme must be adopted. In this paper, we introduce a detection scheme that is based on supervised learning. e k-nearest neighbors (KNN) and random forest (RaFo) methods are used, including features, among which one is the metric of the variations of relative speed (VRS) between the jammer and the receiver. VRS is estimated from the combined value of the useful and the jamming signal at the receiver. e KNN-VRS and RaFo-VRS classification algorithms are able to detect various cases of denial-of-service (DoS) RF jamming attacks and differentiate those attacks from cases of interference with very high accuracy