Letteratura scientifica selezionata sul tema "333.793/2/0973"

2566 Background: Both RAS/RAF/MEK and PI3K/Akt signaling pathways are deregulated in many tumor types. Targeting both pathways may be more efficacious than targeting either pathway alone. In preclinical models, concurrent administration of GDC‑0973, a potent, selective, MEK1/2 inhibitor and GDC-0941, a potent class I PI3K inhibitor, shows improved efficacy compared to either agent alone dosed continuously or intermittently. Methods: A phase Ib dose-escalation study with 3+3 design was initiated in patients (pts) with advanced solid tumors to evaluate the safety and pharmacokinetics (PK) of oral dosing of GDC-0973 and GDC-0941. Pts received: concurrent GDC-0973 + GDC-0941 once daily (qd) on a 21 day on/7 day off (21/7) schedule; intermittent GDC-0973 on Days 1, 4, 8, 11, 15, 18 of a 28 day cycle + GDC-0941 qd on a 21/7 schedule (MEK int); or GDC-0973 + GDC-0941 qd on a 7 day on /7 day off schedule (7/7). Starting doses were 20 mg GDC-0973 + 80 mg GDC-0941 (21/7), 100 mg GDC-0973 + 130 mg GDC-0941 (MEK int); 40 mg GDC-0973 + 130 mg GDC-0941 (7/7). Serial plasma PK samples, FDG-PET, and CT scans were obtained. Results: 78 pts have enrolled. DLTs were G3 lipase (n=1), G4 CPK elevation (n=1). Compared to the 21/7 MTD of 40 mg GDC-0973 + 100 mg GDC-0941, higher doses of GDC-0973 + GDC-0941 were tolerated on the MEK int schedule. Overall, adverse events related to the study drug combination in ≥ 20% pts were diarrhea, rash, nausea, fatigue, vomiting, decreased appetite, dysgeusia, and elevated CPK. Preliminary analysis indicated PK of GDC-0973 and GDC-0941 are not altered when dosed in combination. Of 46 evaluable pts, 26 had an FDG-PET partial metabolic response (≥ 20% decrease in mean SUVmax from baseline) at ≥1 time points. Partial responses were observed in 3 pts (mBRAF melanoma, mBRAF pancreatic ca, mKRAS endometrioid ca); 5 pts had stable disease ≥ 5 months. Conclusions: Combination dosing of GDC‑0973 and GDC-0941 is generally well tolerated, with toxicities similar to those observed in single agent GDC-0973 and GDC-0941 phase 1 trials. There are early signs of anti-tumor activity. Dose escalation on MEK int and 7/7 schedules continues and updated data will be presented.

Abstract Introduction: Targeted drugs are needed for HR-MDS/AML, particularly in elderly patients and Venetoclax, approved for some CLL, gives promising results in elderly AML. Assays to predict response to treatment may enable us to deliver personalized treatment. We sought to determine the most informative assay to predict response; viability assays can directly measure the effects of reagents on growth. Progenitor assays can potentially determine if the reagents can target diseased primitive cells. PET scanning can be used to follow response to treatment. Methods: Peripheral blood (PB) or bone marrow (BM) from 7 MDS/AML patients were incubated in a) no treatment, b) ABT-199 (1 µM) (Abbvie), c) GDC-0973 (1 µM) (Genentech) or d) ABT-199+GDC-0973 (1 µM of each) and assessed for viability using the MTT assay (n=2); cell death followed using the Incucyte® Zoom System (Essen Bioscience) (n=2) or methocult progenitor assays (Stem Cell Technologies) (n=4). Having shown that RAS:BCL-2 co-localization correlated with prognosis in MDS/AML patients (Leuk Res 37:312-9, 2013), immunofluorescence was undertaken. A micro PET device dedicated to mice was used to measure BM blast proliferation. After injection of 18F-FLT(a thymidine analogue) in mice untreated (n=7) or ABT-199 (75mg/kg)+GDC-0973(10mg/kg) treated (n=5) normal FVB/N, HR-MDS mice treated with vehicle (n=4), 2-month old HR-MDS before (n=5) and 3-month old before (n=4) and after ABT-199 (75mg/kg)+GDC-0973(10mg/kg) treatment (n=8), PET imaging was performed (Inveon Siemens Medical Systems), analyzed for signal and quantified. Results: Patient details and results are summarized on Table 1. Using the MTT assay 2 PB patient samples were found to be sensitive to ABT-199 treatment (Figure 1A, AS, p=0.00042 and YA, 0.00002) and more sensitive to the combination compared to untreated (AS, p=0.00007 and YA, 0.000003). With the incucyte the BM of one patient (AE) was found to be resistant to both ABT-199 and GDC-0973, but sensitive to the combination (Figure 1B). PB and BM from patient JA were assayed for apoptosis with the incucyte and were found to be sensitive to ABT-199 with increased apoptosis, resistant to GDC-0973 with decreased apoptosis and sensitive to the combination. Four bone marrow samples were tested in the 4 conditions using the progenitor assay (Figure 1C). Three patients were sensitive to GDC-0973, inhibiting any colony formation and the fourth had reduced colony numbers. In this assay patient JA appeared to be sensitive to GDC-0973 treatment whereas the incucyte assay scored this sample to be resistant to apoptosis; thus the cytotoxic effects of GDC-0973 may not be via apoptopsis. As the progenitor assay is likely to score the primitive disease population, this assay may prove more informative than the others without prior selection. One patient (DH) was clearly resistant to ABT-199, whereas the other three (JA, CB and FL) had reduced colony growth. All patients were sensitive to the combination treatment and inhibited colony growth. The RAS:BCL-2 co-localization in the PB revealed no complex in either the Mito or PM upon treatment with ABT-199 alone and some localization in the Mito with GDC-0973. With both ABT-199 and GDC-0973, there were hardly any cells confirming the cytotoxic effects of the combination. As we have previously shown that PM co-localization of the complex is associated with drug resistance (Blood 130:2613, 2017Suppl), we used the combination on our HR-MDS mouse model, where the complex co-localizes in the PM and followed the mice by PET scanning (Figure 1D). Weak signal was visualized in the femurs of untreated and ABT-199+GDC-0973 treated FVB/N mice (FBR 1.17+/-0.34 and 1.02+/-0.08 respectively). Mild PET signal was seen in the femurs of 2 month-old HR-MDS mice, (FBR 1.79+/-0.98). Intense PET signal was seen in the femurs and proximal humerus of HR-MDS mice treated with vehicle (3 month-old, FBR=2.35+/-1.32). Low PET signals were seen in the femurs of 5/8 HR-MDS mice treated with ABT-199+GDC-0973 (FBR=1.93+/-0.84). FBRs of the 3 groups of HR-MDS mice were significantly higher than those of FBV/N groups. Conclusion: Combined Venetoclax (ABT-199) and GDC-0973 targets MDS/AML progenitors and can potentially overcome drug resistance with the disruption of the RAS:BCL-2 complex. Bone marrow disease progression in HR-MDS mice can be monitored with 18F-FLT-PET imaging; PET data shows that the combination slows down disease progression. Disclosures Padua: Abbvie: Research Funding; Genentech: Research Funding. Giraudier:Novartis: Research Funding. Konopleva:Stemline Therapeutics: Research Funding. Andreeff:Oncoceutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; United Therapeutics: Patents & Royalties: GD2 inhibition in breast cancer ; Reata: Equity Ownership; Celgene: Consultancy; Jazz Pharma: Consultancy; Oncolyze: Equity Ownership; Amgen: Consultancy, Research Funding; Eutropics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Patents & Royalties: MDM2 inhibitor activity patent, Research Funding; SentiBio: Equity Ownership; Astra Zeneca: Research Funding.

Human Vγ9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients. Hence, optimization of methods needs to be carried out for the efficient expansion of these T cells. Standardization of peripheral blood mononuclear cells (PBMCs) isolation was devised. Cytokines (interleukin 2 (IL-2) and interleukin 15 (IL-15)) and zoledronate were also standardized for different concentrations. It was found that an increased number of PBMCs were recovered when washing was done at 1100 revolution per minute (rpm). Significantly high expansion fold was (2524 ± 787 expansion fold) achieved when stimulation of PBMCs was done with 1 μM of zoledronate and both cytokines IL-2 and IL-15 supported the expansion and survival of cells ISSN 0973-2063 (online) 0973-8894 (print) Bioinformation 17(3): 460-469 (2021) ©Biomedical Informatics (2021) 461 at the concentrations of 100 IU/ml and 10 ng/ml respectively. 14-day cultures showed highly pure (91.6 ± 5.1%) and live (96.5 ± 2.5%) expanded γδ T cells. This study aimed to standardize an easy to manipulate technique for the expansion of γδ T cells, giving a higher yield.

ABSTRACTThe existence of stylistic variation between children in the early stages of language acquisition has been most frequently studied using Nelson's 0973) referential—expressive distinction. While the use of this distinction has generated a great deal of interesting research, there are a number of major problems associated with it. The present study presents a simple scheme, based on formal categories, for coding stylistic variation in the early lexicon. When applied to the first 50 and 100 words of 12 children collected between 0; 11 and 2; 3, the major dimensions of difference are found to be the relative proportion of common nouns and the relative proportion of frozen phrases. Moreover, the proportion of frozen phrases is also found to be significantly positively related to children's early productivity, suggesting that, rather than being a ‘deadend’ in early language development, the acquisition of frozen phrases may provide an alternative route into multiword speech.

Abstract Pro-survival molecules including BCL-2 play critical roles in leukemia transformation and chemoresistance. ABT-199/GDC-0199 (venetoclax) is an orally available BH3-mimetic that binds with high affinity to BCL-2, but lacks affinity for BCL-XL and MCL-1. We have recently demonstrated anti-leukemia potency of venetoclax in acute myeloid leukemia (AML) models (Pan et al. Cancer Discovery 2014). However, venetoclax poorly inhibits MCL-1, causing resistance in leukemia cells that rely on MCL-1 for survival. The RAF/MEK/ERK (MAPK) cascade is a major effector pathway in AML that is activated by upstream mutant proteins such as FLT3, KIT and RAS. Additionally, the MAPK pathway regulates BCL-2 family proteins by stabilizing anti-apoptotic MCL-1 and inactivating pro-apoptotic BIM. In this study, we evaluated the anti-tumor effects of concomitant BCL-2 and MAPK blockade by venetoclax in combination with MEK1/2 inhibitor GDC-0973 (cobimetinib).. We initially examined activity of these agents in a panel of myeloid leukemia cell lines with diverse genetic alterations (Fig. 1A). The IC50 values of cobimetinib ranged from < 0.01 µM to > 1 µM after 72 hours of drug treatment but did not correlate with the basal level of p-ERK1/2. In 7 out of 11 cell lines, combination of the agents elicited synergistic growth inhibition. Notably synergism of venetoclax with cobimetinib was observed in venetoclax-resistant cell lines (MOLM14, OCI-AML3, NB4 and THP1). Ongoing analysis of pharmacodynamic markers include transcriptome assessment by RNA sequencing, functional proteomics by reverse phase protein array (RPPA) and quantification of BCL-2:BIM and MCL-1:BIM complexes using the electrochemiluminescent ELISA assay (Meso Scale Discovery, MSD-ELISA). The preliminary MSD data revealed that BCL-2:BIM complex was disrupted in most cell lines and accumulated following cobimetinib treatment, which may be due to the disruption of MCL-1:BIM complex by inhibition of MEK (Fig. 1B). In a long-term culture of primary AML blasts in serum-free stem cell growth medium supplemented with cytokines and StemRegenin 1 (SR1) to main the immature state of leukemia cells, the combination of venetoclax and cobimetinib induced distinct apoptotic cell death, with AML #1 sensitive to venetoclax but resistant to cobimetinib. Alternatively, AML #2 and #3 samples were resistant to venetoclax but sensitive to cobimetinib and the combination of both drugs (Fig. 1C). We next investigated signaling patterns and BCL-2 family protein expression in AML stem/progenitor cells using a 34-antibody panel and time-of-flight mass cytometry (CyTOF). In AML#1, BCL-2 was expressed in leukemia blasts, with enrichment in a progenitor AML population phenotypically defined as CD45dim CD34+ CD38+ CD123+ CD33+ (Fig. 1D). The high expression level of BCL-2 and low expression of MCL-1 and BCL-XL may account for sensitivity to venetoclax in AML#1. Both basal and G-CSF- or SCF-stimulated p-ERK was efficiently down-regulated by cobimetinib; however, G-CSF-evoked p-STAT3/5 and SCF-induced p-AKT were only slightly reduced (Fig. 1E). Notably we observed increased phosphorylation of STAT5 pathway upon treatment with cobimetinib, suggesting that active MAPK signals inhibit phosphorylation of the JAK-STAT pathway, as previously reported (Krasilnikov et al. Oncogene, 2003 and Lee at al. Cancer Cell, 2014). To test the efficacy of both compounds in vivo, we injected NSG mice with genetically engineered OCI-AML3/Luc/GFP cells. Bioluminescent imaging (BLI) demonstrated significantly reduced leukemia burden in treated groups compared to controls, more prominently in the cobimetinib single agent and venetoclax plus cobimetinib co-treated mice (Fig. 1F). The efficacy study is ongoing and median survival for cobimetinib and venetoclax co-treated mice has yet to be determined (Fig. 1G). In summary, our data demonstrates that combinatorial blockade of MAPK and BCL-2 pathways is synergistic in the majority of AML cell lines tested and can overcome intrinsic resistance to venetoclax. Ongoing studies will evaluate efficacy of this combination therapy in primary human AML xenografts and elucidate mechanisms of synergy. Disclosures Leverson: AbbVie: Employment, Equity Ownership. Dail:Genentech: Employment, Equity Ownership. Phillips:AbbVie: Employment, Other: Shareholder, Patents & Royalties. Chen:Abbvie: Employment, Equity Ownership. Jin:Abbvie: Employment, Equity Ownership. Jabbour:Pfizer: Consultancy, Research Funding. Sampath:Genentech: Employment, Equity Ownership. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.

Notre recherche a pour objectif d’analyser l’insertion de la transition énergétique à l’échelle d’une région insulaire française d’outre-mer. En prenant pour territoire d’étude l’île de la Martinique, elle analyse plus spécifiquement les mutations à l’œuvre, pour le secteur énergétique, notamment de la production de l’électricité. En mobilisant le concept de gouvernance, l’étude s’inscrit dans un triple contexte de décentralisation de la compétence énergie, d’ouverture du marché de la production de l’électricité à de nouveaux opérateurs privés, et de contestations de plus en plus fréquentes de projets d’aménagement du territoire de la part de la société civile.Les recherches ont été effectuées en abordant trois axes principaux :• Le territoire et ses potentiels énergétiques valorisables ;• Les acteurs opérant la transition énergétique dans l’île ;• Les projets d’exploitation d’énergies renouvelables. Basée sur le traitement des entretiens de terrain, des documents techniques et des publications de la presse locale, notre recherche explique l’avancée et la stagnation de la réalisation de la transition énergétique en Martinique. Elle met en évidence le caractère conflictuel et non consensuel de la conception et de la définition même de la transition énergétique. Ce caractère a été confirmé au travers de plusieurs études de cas, comme les installations photovoltaïques au sol, la centrale biomasse Galion 2 ou encore le projet d’énergie thermique des mers NEMO. Répondant d’abord à des enjeux de développement, les débats relatifs à la mise en application de la transition révèlent, avant tout, que l’aménagement du territoire en moyens de production renouvelables est piloté principalement par une gouvernance locale. Celle-ci privilégie l’absence d’incidences sur les activités majeures, comme l’agriculture, le tourisme... Nos résultats montrent que le jeu d’acteurs y est fortement influencé par l’action des acteurs historiques, dessinant ainsi une forte dépendance au sentier de la production de l’électricité à partir des produits pétroliers
The purpose of this thesis is to analyze the integration of the energy transition within an Overseas Territory of France. Focusing on the island of Martinique as a case study, it analyzes in details the changes taking place in the industry of electricity production. By mobilizing the concept of governance, the study takes place under the triple context of decentralizing of energy-related decisions, opening up the electricity market to new private operators, and increasing dispute on planning emerging from civil society.This research addresses three main issues:• The territory and its exploitable energy potentials;• The actors operating the transition on the island;• Renewable energy exploitation projects. Based on a thorough analysis of technical documents, local press publications and field interviews, this research seeks to explain the reasons behind the progress or the stagnation of the energy transition in Martinique. It highlights the conflicting and non-consensual nature of its conception and definition. Various case studies, such as ground-mounted photovoltaics, the biomass power plant Galion 2 and the ocean thermal energy conversion project NEMO, provide insights on this antagonistic dynamic. Joining a vibrant conversation on the implementation of energy transition, our results reveal that regional development of renewable means of production is mainly driven by a local governance, which seeks to limit the potential impact on major activities such as agriculture, tourism... Historical stakeholders continue to influence the electricity industry, thus maintaining its dependency on petroleum products

Η παρούσα διπλωματική εργασία εκπονήθηκε με σκοπό την δημιουργία ενός μοντέλου του Εθνικού Διασυνδεδεμένου Συστήματος Μεταφοράς για το έτος 2015, στο οποίο θα συμπεριλαμβάνονται όλες οι μονάδες Ανανεώσιμων Πηγών Ενέργειας που γνωρίζομε ή υποθέτουμε ότι θα ενταχθούν στο Σύστημα μέχρι το 2015. Οι υποθέσεις αυτές έγιναν σύμφωνα με τα στοιχεία της ΜΑΣΜ 2010-2014 (όπου αναφέρονται αναλυτικά οι μονάδες παραγωγής ενέργειας συμβατικές και μη, που θα συνδεθούν ή θα αποσυρθούν από το Σύστημα), τις προβλέψεις του Εθνικού Σχεδίου Δράσης για τις ΑΠΕ (ΕΣΔ/ΑΠΕ), την σχετική μελέτη που πραγματοποιήθηκε στο Κέντρο Ανανεώσιμων Πηγών Ενέργειας (ΚΑΠΕ), καθώς από την Ρυθμιστική Αρχή Ενέργειας (ΡΑΕ) από την οποία γνωρίζουμε ποιες μονάδες βρίσκονται στο στάδιο της αδειοδοτικής διαδικασίας και επομένως η ένταξή τους στο Σύστημα είναι πολύ πιθανό να πραγματοποιηθεί στα προσεχή έτη. Η επιλογή του έτους 2015 για την μελέτη έγινε επειδή τα διαθέσιμα μέχρι σήμερα στοιχεία επιτρέπουν πιο ασφαλείς προβλέψεις για την διαμόρφωση του ηλεκτρικού Συστήματος Μεταφοράς. Παρόλο που ο τελικός στόχος από την Ευρωπαϊκή Ένωση τέθηκε για το 2020, μια απευθείας μελέτη διαμόρφωσης του Συστήματος για τότε θα ήταν επισφαλής, καθώς, όπως προαναφέρθηκε, δεν υπάρχει η απαιτούμενη πληροφορία. Άλλωστε το 2015 θα μπορούσε να θεωρηθεί ένας βασικός σταθμός καθώς θα αποτελέσει την βάση για την επίτευξη του στόχου που έχει τεθεί για το 2020. Πιο αναλυτικά η διπλωματική αυτή εργασία χωρίζεται στις παρακάτω ενότητες: ΚΕΦΑΛΑΙΟ 1Ο: ΘΕΩΡΙΑ ΣΥΣΤΗΜΑΤΩΝ ΗΛΕΚΤΡΙΚΗΣ ΕΝΕΡΓΕΙΑΣ Στο κεφάλαιο αυτό στην πρώτη ενότητα αρχικά γίνεται αναφορά στην Ανάλυση Ροής Φορτίου και στο πόσο σημαντικό ρόλο έχει η ανάλυση αυτή για την σωστή σχεδίαση και λειτουργία του ηλεκτρικού Συστήματος. Στη συνέχεια γίνεται η μαθηματική περιγραφή του προβλήματος της ανάλυσης ροής φορτίου καθώς και μια εκτενής αναφορά για τις παραδοχές και τις προϋποθέσεις που πρέπει να τηρηθούν ώστε τελικά να δουλέψει σωστά το Σύστημα ηλεκτρικής ενέργειας που πρόκειται να σχεδιαστεί. Τέλος γίνεται μια μικρή αναφορά στις αριθμητικές μεθόδους που θα χρησιμοποιηθούν ώστε να πραγματοποιηθεί η επίλυση των εξισώσεων που προέκυψαν από την ανάλυση ροής φορτίου. Στην επόμενη ενότητα του ίδιου κεφαλαίου παρουσιάζονται τα στοιχεία του Συστήματος (π.χ. ζυγοί, κυκλώματα, μηχανές, φορτία κλπ.) που περιλαμβάνονται στην βάση δεδομένων του υπολογιστικού προγράμματος που θα χρησιμοποιηθεί για την επίλυση των εξισώσεων της ανάλυσης ροής φορτίου. Στην τελευταία ενότητα αυτού του κεφαλαίου γίνεται μια μικρή παρουσίαση του προγράμματος PSS/E, που είναι και το υπολογιστικό πρόγραμμα που χρησιμοποιήθηκε στην παρούσα εργασία για την επίλυση του Συστήματος. ΚΕΦΑΛΑΙΟ 2Ο: ΕΘΝΙΚΟ ΣΧΕΔΙΟ ΔΡΑΣΗΣ ΓΙΑ ΤΙΣ ΑΠΕ ΚΑΙ ΟΙ ΣΤΟΧΟΙ ΜΕΧΡΙ ΤΟ 2020 Στην πρώτη ενότητα αυτού του κεφαλαίου παρουσιάζεται ποιο είναι το σχέδιο δράσης για τις ΑΠΕ που αφορά την χώρα μας. Στην επόμενη ενότητα αυτού του κεφαλαίου, γίνεται μια αναφορά στις προϋποθέσεις ώστε να επιτευχθούν οι στόχοι που θέτει το εθνικό σχέδιο δράσης για τις ΑΠΕ. Τέλος στην τρίτη ενότητα παρουσιάζονται αναλυτικά οι στόχοι διείσδυσης των ΑΠΕ από το 2010 έως το 2020. ΚΕΦΑΛΑΙΟ 3Ο: ΕΛΛΗΝΙΚΟ ΔΙΑΣΥΝΔΕΔΕΜΕΝΟ ΣΥΣΤΗΜΑ ΜΕΤΑΦΟΡΑΣ Στην πρώτη ενότητα του κεφαλαίου γίνεται μια αναλυτική περιγραφή του υφιστάμενου Συστήματος Μεταφοράς της χώρας. Στην δεύτερη ενότητα γίνεται αναφορά στην δυνατότητα του ηλεκτρικού δικτύου της χώρας να απορροφήσει την παραγωγή των σταθμών ΑΠΕ που πρόκειται να συνδεθούν σε αυτό. Επιπλέον γίνεται αναφορά στην διαδικασία αδειοδότησης και καθώς και στις υπόλοιπες προϋποθέσεις για την διείσδυση των ΑΠΕ στο Σύστημα. Τέλος στην τρίτη ενότητα γίνεται εφαρμογή του σχεδίου δράσης για τις ΑΠΕ στο έτος 2015, που αποτελεί και το έτος μελέτης της παρούσας εργασίας. ΚΕΦΑΛΑΙΟ 4Ο: ΔΙΑΜΟΡΦΩΣΗ ΤΟΥ ΕΛΛΗΝΙΚΟΥ ΔΙΑΣΥΝΔΕΔΕΜΕΝΟΥ ΣΥΣΤΗΜΑΤΟΣ ΜΕΤΑΦΟΡΑΣ ΗΛΕΚΤΡΙΚΗΣ ΕΝΕΡΓΕΙΑΣ ΓΙΑ ΤΟ 2015 Αρχικά στην πρώτη ενότητα παρουσιάζεται η κατανομή φορτίου στους υποσταθμούς του Συστήματος για το 2015. Στη συνέχεια (δεύτερη ενότητα), γίνεται λεπτομερής περιγραφή του Εθνικού Διασυνδεδεμένου Συστήματος Μεταφοράς (ΕΔΣΜ), όπως διαμορφώθηκε για το έτος μελέτης της εργασίας. Τέλος στην τρίτη ενότητα, φαίνεται η μελέτη του μοντέλου του Συστήματος, όπως διαμορφώθηκε για το έτος 2015, για τρία διαφορετικά ακραία σενάρια λειτουργίας. ΚΕΦΑΛΑΙΟ 5Ο: ΣΥΜΠΕΡΑΣΜΑΤΑ ΚΑΙ ΠΡΟΟΠΤΙΚΕΣ Στην πρώτη ενότητα αυτού του κεφαλαίου αναφέρονται τα γενικά συμπεράσματα που προέκυψαν από την προηγηθείσα μελέτη. Στην επόμενη ενότητα, γίνεται αναλυτική παρουσίαση των αποτελεσμάτων στης ανάλυσης ροής φορτίου για κάθε ένα από τα τρία σενάρια που μελετήθηκαν. Ενώ στην τελευταία ενότητα, γίνεται αναφορά στις προοπτικές ανάπτυξης και διαμόρφωσης του Συστήματος για το 2020, βασιζόμενοι στα αποτελέσματα που προέκυψαν από την διαμόρφωση του δικτύου για το 2015.
This thesis, entitled "Study for the development of an electric energy transmission network which incorporates Renewable Energy Sources", was conducted in order to create a model of the National Interconnected Electric Energy Transmission System, which will include all the renewable energy system units that are already known or assumed to join the system by 2015. These assumptions were made according to the data provided by the TSDS 2010-2014 (offering a detailed plan of the all the power plant units, conventional or not, which will be connected to or removed from the system), the provisions of the National Action Plan for Renewable Energy Sources (EA / RES) , the related study conducted at the Centre for Renewable Energy Sources (CRES), and the data of the Regulatory Authority for Energy (RAE), which indicated the units that are under the licensing process and therefore they are likely to be connected to the system in the years to come. Choosing the year 2015 for the study is based on the fact that the available data nowadays allows for more accurate predictions about the configuration of the electric transmission system in two years period. Although the European Union set the ultimate goal for 2020, a direct study of the system configuration at that time would be risky, since, as mentioned above, the required information is not available. Besides that, the year 2015 could be considered a basic year as it will form the basis for achieving the target set for 2020. This thesis is divided into the following sections: CHAPTER 1: SYSTEMS THEORY OF ELECTRICITY In this chapter the first section refers to Load Flow Analysis and how important this analysis is for the proper design and operation of electrical systems. Afterwards, a mathematical description of the problem of load flow analysis is presented along with a comprehensive analysis of all the assumptions and conditions that must be met, in order to guarantee that power system to be designed will finally work properly. The numerical methods used to solve the equations resulting from the load flow analysis are described briefly. The second section of this chapter contains the system components (eg. scales, circuits, machines, loads, etc.) that are included in the database of the computer program which will be used to solve the equations of the load flow analysis. The last section of this chapter is a short presentation of the PSS / E program, which is the computer program used in this thesis in order to solve the problems stated. CHAPTER 2:NATIONAL ACTION PLAN FOR RES AND GOALS SET BY 2020The first section of this chapter is a thorough description of the action plan for Renewable Energy Sources in our country. The next section of this chapter refers to the conditions that should be met in order to achieve the targets set by the National Action Plan for RES. Finally, in the third section the objectives of the adoption of the RES from 2010 to 2020 are discussed. CHAPTER 3: GREEK INTERCONNECTED TRANSFER SYSTEM The first section of this chapter is a detailed description of the existing electric energy transportation system of our country. In the second part we examine the ability of the existing electric energy network to absorb the production of the RES plants that will be to be connected to it. Furthermore, a presentation of the licensing process and all the other requirements for the adoption of RES in the existing system is provided. In the third section the implementation of the Action Plan for RES in 2015, which is the year that we examine in this thesis, is attempted. CHAPTER 4: DEVELOPMENT OF THE GREEK INTERCONNECTED ELECTRIC ENERGY TRANSFER SYSTEM FOR 2015 Initially how the load will be distributed to the system’s substation in 2015 is described in the first section. The second section is a detailed description of the National Interconnected Transmission System (EDSM) which was designed in this thesis for 2015. Finally, assuming three different extreme scenarios for the system operation an analysis of the designed model for the system, as described in the second section, is presented. CHAPTER 5: CONCLUSIONS AND PROSPECTS The first section of this chapter summarizes all the general conclusions drawn from the study conducted in this thesis. In the next section, there is a detailed presentation of the results extracted by the load flow analysis conducted for each of the three scenarios examined in the third section of Chapter 4. The last section discusses prospects for the growth and the development of the system for 2020, based on the results extracted from the network configuration that was done for 2015.This thesis was conducted by the student of Electical and Computer Engineering Department, University of Patras, Melaniti Maria-Anthia with the help of Dr. Sakellaridis Nicholas employee to CRES.

Στην παρούσα διπλωματική εργασία θα ασχοληθούμε με την αξιολόγηση της προστασίας σε κατανεμημένη παραγωγή. Γενικά η κατανεμημένη παραγωγή, καλύπτει ένα μεγάλο εύρος νέων και παραδοσιακών τεχνολογιών με μικρές μονάδες εγκατεστημένες κοντά στην κατανάλωση και πιστεύεται ότι θα συμβάλει στην κάλυψη ενός μεγάλου μέρους της ενεργειακής ζήτησης στα επόμενα χρόνια με τη δυναμική της είσοδο στην απελευθερωμένη αγορά ενέργειας. Αρχικά γίνεται μια ανασκόπηση της υφιστάμενης παγκόσμιας ενεργειακής κατάστασης. Αναλύονται οι κυριότερες τεχνολογίες παραγωγής ηλεκτρικής ενέργειας και τα καύσιμα που χρησιμοποιούνται, τα οποία κατά συντριπτική πλειοψηφία βασίζονται στους ορυκτούς πόρους. Αποτυπώνεται αφενός, η συνολική συνεισφορά αυτών στην ενεργειακή ζήτηση, αφετέρου τα παγκόσμια αποθέματα αυτών. Στη συνέχεια παρουσιάζεται η υφιστάμενη κατάσταση στον ηλεκτρικό τομέα, οι αλλαγές που συνεπάγονται με τη απελευθέρωση της αγοράς ενέργειας, καθώς και το γενικό πλαίσιο και οι ρυθμίσεις που διέπουν τον τομέα της ενέργειας με βάση τα νέα δεδομένα. Γίνεται εισαγωγή και ορισμός της κατανεμημένης παραγωγής και αναλύονται τα βασικά χαρακτηριστικά που συνθέτουν την έννοια αυτής καθώς επίσης γίνεται μια παρουσίαση των κυριότερων τεχνολογιών που ολοκληρώνουν τη κατανεμημένη παραγωγή. Στη συνέχεια ασχολούμαστε με το φαινόμενο της νησιδοποίησης. Η αύξηση της παραγωγής ισχύος από διανεμημένους παραγωγούς καθιστά την εμφάνιση του φαινομένου όλο και συχνότερη. Η ανίχνευση και διακοπή του φαινομένου είναι καθοριστικής σημασίας για την ορθή λειτουργία του Δικτύου και την ασφάλεια του προσωπικού που εργάζεται σε αυτό. Εδώ περιγράφουμε μερικές από τις πιο βασικές εφαρμοζόμενες μεθόδους ανίχνευσης και διακοπής του. Ύστερα παρουσιάζουμε τα βασικά χαρακτηριστικά των μέσων προστασίας έναντι υπερεντάσεων. Προχωράμε σε μελέτη των διατάξεων προστασίας ενός παραδείγματος μιας εγκατάστασης φωτοβολταϊκών με σκοπό τη διασφάλιση της σε περίπτωση εμφάνισης σφαλμάτων. Τέλος αναφερόμαστε σε κάποιες νέες προσεγγίσεις και μελλοντικές τάσεις και προοπτικές για τον καθορισμό των τρόπων ενσωμάτωσης ομαλών τεχνολογιών ΚΠ και τη ρύθμιση θεμάτων σχετικά με τη διασύνδεση και τη λειτουργία τους.
In this work we will do a research about the appraisal of the distributed generation .All in all the distributed generation encloses a great range of new and traditional technologies. Some of them are installed close to the consumption and it is believed that the distributed generation will contribute to cover a great part of the energy demand in the next years. In the beginning we refer to the global energy situation. We analyze the most important technologies of distributed generation and the fuels that are used which are based on the mineral resources. These fuels contribute in the energy demand and we also refer to the global store of fuel. We present the situation of the electric section today, the changes and the regulations that happen in this section day by day. What is more, it is given the meaning of the “distributed generation”, we analyze the basic characteristics of it and we present the most important technologies that complete the distributed generation. Furthermore we refer to the problem of islanding. Because of the fact that the power production is increasing lately, the problem is appeared more and more often. We must look for this phenomenon and stop it immediately in order the network work correctly and the persons who work in this part of network be safe. We describe some of the most important methods of “tracking” the islanding and stopping it. Afterwards we present the basic characteristics of the protection arrangement that we must use in case of errors and short circuits. We continue presenting an instance for a photovoltaic system installation and what sort of protection must be used in order this system to work with safe when errors happen. In the end we refer to what must be done in the future so that the technologies of distributed generation be used more and more often and much more efficiently.

This chapter intends to evaluate how mixed researches are significant knowledge producers for business management. A discussion is conducted about the trade-off around the success and restrictions offered by the dominance of quantitative methods, especially when there is interest to study supply management and logistics. Quantitative methods are essential for any kind of management, but, as more dynamics in market competition produces more complex scenarios, qualitative answers are needed, along its approaches to formulate new questions that will help organizational decision-makers to apply knowledge for their planning activities. This chapter will explore three main points: 1) how the excessive concentration on quantitative methods can restrict managerial views; 2) how any organization can apply qualitative methods to enrich results observed from quantitative, resulting in better, more sustainable decisions; and 3) how qualitative and quantitative methods, associated, can implement this approach in real cases, with an overview of mixed scientific research methodologies.