On Economic Policy Uncertainty and Sovereign Credit Rating Decisions: Panel Quantile Evidence for the Eurozone

We employ a panel quantile framework that quantifies the relative importance of quantitative and qualitative factors across the conditional distribution of sovereign credit ratings in the Eurozone area. We find that regulatory quality and competitiveness have a stronger impact for low rated countries whereas GDP per capita is a major driver of high rated countries. A reduction in the current account deficit leads to a rating or outlook upgrade for low rated countries. Economic policy uncertainty impacts negatively on credit ratings across the conditional distribution; however, the impact is stronger for the lower rated countries. In other words, the creditworthiness of low rated countries takes a much bigger ‘hit’ than that of high rated countries when European policy uncertainty is on the rise

MN-ANDALUSITE, SPESSARTINE, MN-GROSSULAR, PIEMONTITE AND MN-ZOISITE/CLINOZOISITE FROM TRIKORFO, THASSOS ISLAND, GREECE

Μυλωνιτιωμένοι πλούσιοι σε μαγγάνιο σχιστόλιθοι και ασβεστοπυριτικά στρώματα που απαντούν ως ενδιαστρώσεις εντός αμφιβολιτικής έως πρασινοσχιστολιθικής φάσης μεταμόρφωσης μαρμαρυγιακούς σχιστόλιθους στο Τρίκορφο της Θάσου, 2069 χαρακτηρίζονται από μία ασυνήθιστη Mn-ούχο παραγένεση μεταμορφικών ορυκτών τα περισσότερα από τα οποία σε ιδιαίτερα μεγάλους κρυστάλλους και σε ποικιλία πολύτιμων λίθων. Τα Mn-ούχα πυριτικά ορυκτά απαντούν τόσο σε στρώσεις παράλληλα με την φύλλωση όσο και σε φλέβες που τέμνουν τη μεταμορφική δομή. Τα ορυκτά πιεμοντίτης (έως 12.7 % κ.β. Mn2O3), Mn-ούχο επίδοτο (έως 7.8 % κ.β. Mn2O3), Mn-ούχος ανδαλουσίτης (έως 15.6 % κ.β. Mn2O3), φτωχός σε Mn ροζ κλινοζοϊσίτης/επίδοτο (έως 0.87 % κ.β. Mn2O3), φτωχός σε Mn ροζ έως κόκκινος ζοϊσίτης (έως 0.21 % κ.β. Mn2O3), σπεσσαρτίνης (έως 47.7 % κ.β. MnO) και Mn-ούχος γροσσουλάριος (έως 3.6 % κ.β. MnO), συνοδεύονται από διοψίδιο, κεροστίλβη, φλογοπίτη, μοσχοβίτη, τουρμαλίνη, αιματίτη και σιδηρούχο κυανίτη. Η παραγένεση που μελετήθηκε είναι ενδεικτική υψηλών τιμών πτητικότητας του οξυγόνου λόγω της παρουσίας προϋπάρχουσας έντονα οξειδωτικής προ-μεταμορφικής ορυκτολογικής παραγένεσης πλούσιας σε μαγγάνιο. Σχηματίσθηκε κατά την πρόδρομη μεταμόρφωση ιζηματογενών πρωτόλιθων πλούσιων σε Mn, με ακόλουθη επανισσορόπηση απο τις μέγιστες συνθήκες πίεσης και θερμοκρασίας, σχηματισμό φλεβών και μετασωμάτωσης κατά την ανάδρομη μεταμόρφωση που συνόδευσε την ανάδυση της Θάσου στο Ολιγόκαινο-Μειόκαινο. Εναλλακτικά, η προσφορά ρευστών από γρανιτοειδή κατά την διάρκεια μεταμόρφωσης επαφής δεν πρέπει να αποκλειστεί. Η περιοχή μελέτης αντιπροσωπεύει μοναδικό ορυκτολογικό Γεώτοπο. Η γεωλογική-ορυκτολογική αυτή κληρονομιά μπορεί να προστατευθεί μέσω της ίδρυσης ενός Γεωπάρκου που θα συμβάλλει επιπλέον και στην προώθηση φιλικής προς το περιβάλλον ανάπτυξης της Θάσου.Mylonitized manganiferous schists and calc-silicate layers intercalated within amphibolite- to greenschist facies mica schists from the Trikorfo area (Thassos Island, Greece), host an unusual Mn-rich paragenesis of metamorphic silicate minerals, most of them in large, gemmy crystals. The silicates occur both in layers subparallel to the foliation and within discordant veins cross-cutting the metamorphic fabric. Piemontite (up to 12.7 wt. % Mn2O3), Mn-rich epidote (up to 7.8 wt. % Mn2O3), Mn-rich andalusite (up to 15.6 wt. % Mn2O3), Mn-poor pink clinozoisite-epidote (up to 0.87 wt. % Mn2O3), Mn-poor pink zoisite (up to 0.21 wt. % Mn2O3), spessartine (up to 47.7 wt. % MnO) and Mn-rich grossular (up to 3.6 wt. % MnO) are associated with diopside, hornblende, phlogopite, muscovite, tourmaline, hematite and iron-bearing kyanite. The studied assemblages are indicative of high fO2 conditions due to the presence of highly oxidized pre-metamorphic Mn-rich mineral associations. They developed during prograde metamorphism of a Mn-rich sedimentary protolith(s), followed by re equilibration to post-peak metamorphic conditions, vein formation and metasomatism during retrograde metamorphism accompanying the exhumation of the Thassos Island during the Oligocene-Miocene. Alternatively, the skarn similar mineralogy of the calc-silicate layers could have been formed by fluids released by granitoids during contact metamorphism. The studied area represents a unique mineralogical geotope. Its geological-mineralogical heritage should be protected through establishment of a mineralogical-petrological geopark that will also promote sustainable development of the area

Organisational learning - a critical systems thinking discipline

Original Paper European Journal of Information Systems (2001) 10, 135–146; doi:10.1057/palgrave.ejis.3000394 Organisational learning—a critical systems thinking discipline P Panagiotidis1,3 and J S Edwards2,4 1Deloitte and Touche, Athens, Greece 2Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK Correspondence: Dr J S Edwards, Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK. E-mail: [email protected] 3Petros Panagiotidis is Manager responsible for the Process and Systems Integrity Services of Deloitte and Touche in Athens, Greece. He has a BSc in Business Administration and an MSc in Management Information Systems from Western International University, Phoenix, Arizona, USA; an MSc in Business Systems Analysis and Design from City University, London, UK; and a PhD degree from Aston University, Birmingham, UK. His doctorate was in Business Systems Analysis and Design. His principal interests now are in the ERP/DSS field, where he serves as project leader and project risk managment leader in the implementation of SAP and JD Edwards/Cognos in various major clients in the telecommunications and manufacturing sectors. In addition, he is responsible for the development and application of knowledge management systems and activity-based costing systems. 4John S Edwards is Senior Lecturer in Operational Research and Systems at Aston Business School, Birmingham, UK. He holds MA and PhD degrees (in mathematics and operational research respectively) from Cambridge University. His principal research interests are in knowledge management and decision support, especially methods and processes for system development. He has written more than 30 research papers on these topics, and two books, Building Knowledge-based Systems and Decision Making with Computers, both published by Pitman. Current research work includes the effect of scale of operations on knowledge management, interfacing expert systems with simulation models, process modelling in law and legal services, and a study of the use of artifical intelligence techniques in management accounting. Top of pageAbstract This paper deals with the application of critical systems thinking in the domain of organisational learning and knowledge management. Its viewpoint is that deep organisational learning only takes place when the business systems' stakeholders reflect on their actions and thus inquire about their purpose(s) in relation to the business system and the other stakeholders they perceive to exist. This is done by reflecting both on the sources of motivation and/or deception that are contained in their purpose, and also on the sources of collective motivation and/or deception that are contained in the business system's purpose. The development of an organisational information system that captures, manages and institutionalises meaningful information—a knowledge management system—cannot be separated from organisational learning practices, since it should be the result of these very practices. Although Senge's five disciplines provide a useful starting-point in looking at organisational learning, we argue for a critical systems approach, instead of an uncritical Systems Dynamics one that concentrates only on the organisational learning practices. We proceed to outline a methodology called Business Systems Purpose Analysis (BSPA) that offers a participatory structure for team and organisational learning, upon which the stakeholders can take legitimate action that is based on the force of the better argument. In addition, the organisational learning process in BSPA leads to the development of an intrinsically motivated information organisational system that allows for the institutionalisation of the learning process itself in the form of an organisational knowledge management system. This could be a specific application, or something as wide-ranging as an Enterprise Resource Planning (ERP) implementation. Examples of the use of BSPA in two ERP implementations are presented

Martian Superoxide and Peroxide O2 Release (OR) Assay: A New Technology for Terrestrial and Planetary Applications

This study presents an assay for the detection and quantification of soil metal superoxides and peroxides in regolith and soil. The O2 release (OR) assay is based on the enzymatic conversion of the hydrolysis products of metal oxides to O2, and their quantification by an O2 electrode based on the stoichiometry of the involved reactions: The intermediate product O2 from the hydrolysis of metal superoxides is converted by cytochrome c to O2, and also by superoxide dismutase (SOD) to 1/2 mol O2 and 1/2 mol H2O2, which is then converted by catalase (CAT) to 1/2 mol O2. The product H2O2 from the hydrolysis of metal peroxides and hydroperoxides is converted to 1/2 mol O2 by CAT. The assay-method was validated in a sealed sample chamber using a liquid-phase Clark-type O2 electrode with known concentrations of O2 and H2O2, and with commercial metal superoxide and peroxide mixed with Mars analogue Mojave and Atacama Desert soils. Carbonates and perchlorates, both present on Mars, do not interfere with the assay. The assay lower limit of detection, using luminescence quenching/optical sensing O2-electrodes, is 1 nmol O2 cm(exp. -3) or better. The activity of the assay enzymes SOD and cytochrome c was unaffected up to 6 Gy exposure by gamma-radiation, while CAT retained 100% and 40% of its activity at 3 and 6 Gy, respectively, demonstrating the suitability of these enzymes for planetary missions, e.g., in Mars or Europa

α-cell glucokinase suppresses glucose-regulated glucagon secretion

Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K javax.xml.bind.JAXBElement@dee6e8 channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype

Excessive Islet NO Generation in Type 2 Diabetic GK Rats Coincides with Abnormal Hormone Secretion and Is Counteracted by GLP-1

BACKGROUND: A distinctive feature of type 2 diabetes is inability of insulin-secreting beta-cells to properly respond to elevated glucose eventually leading to beta-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of beta-cell dysfunction. PRINCIPAL FINDINGS: We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon. CONCLUSION: The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms

Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

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Prognostic or predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1

Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)). Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation and the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%) and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02,p<0.01), SF3B1 (HR1.66,p=0.01) and NOTCH1 (HR1.39,p=0.03) were associated with inferior PFS in univariate analysis. Multivariate analysis confirmed the independent prognostic role of TP53 for PFS (HR1.71,p=0.04) and OS (HR2.78,p=0.02) and of SF3B1 for PFS only (HR1.52,p=0.02). Notably, NOTCH1 mutation status separates patients with a strong and a weak benefit from ofatumumab addition to CHL (NOTCH1wt:HR0.50,p<0.01, NOTCH1mut:HR0.81,p=0.45). In summary, TP53 and SF3B1 were confirmed as independent prognostic and NOTCH1 as a predictive factor for reduced ofatumumab efficacy in a randomized chemo (immune)therapy CLL trial. These results validate NGS-based mutation analysis in a multicenter trial and provide a basis for expanding molecular testing in the prognostic workup of patients with CLL. ClinicalTrials.gov registration number: NCT0074818

The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization

Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes