Aspects of dose, dose rate and radioisotopes in brachytherapy of uveal melanoma

Uveal melanomas constitute melanomas arising from the choroid, the ciliary body or the iris, and in adults stands for the most common primary malignant intraocular tumor. It has a high risk of metastatic spread followed by inevitable death, and unfortunately the prognosis has not improved over the last decades. In the beginning the only considerable treatment was enucleation, i.e. removal of the entire eye. However, brachytherapy has since the 70’s become the primary treatment for medium sized tumors, and the survival rate has been shown to be equal compared to primary enucleation. The aim of our studies included in this thesis was to investigate the efficacy of today’s brachytherapy treatment regime and if any differences in ocular or patient survival could be found considering different brachytherapy aspects. When investigating only ruthenium-106 brachytherapy, no association was found between high or low dose rate and the risk of secondary enucleation, i.e. enucleation due to extensive unwanted side effects, insufficient treatment effect on the tumor or tumor relapse. In further analysis with both ruthenium-106 and iodine-125 brachytherapy included in the study and the risk of tumor related mortality considered, there was no statistical difference in outcome related to either dose or dose rate applied and we found no negative consequences for patients that received lower dose and dose rates than intended. As there is a gender difference in survival outcome for some cancers, we investigated this issue regarding uveal melanoma, but no differences could be found indicating this should be a factor to consider when planning treatment. Ruthenium-106 brachytherapy is generally used throughout Europe. In Sweden, iodine-125 for larger medium sized tumors became available 20 years after ruthenium-106 brachytherapy had begun. We therefore had a great opportunity to analyze the larger tumors treated with ruthenium-106 in the earlier years and compare them to same size tumors treated with iodine-125. There was no difference in survival between matched groups, but ruthenium-106-treated patients had a significantly higher risk of needing retreatment, thus making iodine-125 the preferred nuclide for thicker tumors. In conclusion gender is not a factor that needs considering when planning treatment for uveal melanoma. Treatment with brachytherapy is both safe and effective within the current recommended doses and dose rates. Our findings suggest that lower doses and dose rates still would be adequate, and this should be investigated further. The current protocol for radioisotope selection based on tumor thickness also seems adequate for the best possible ocular and survival outcome

Biofunctional Characteristics of Lignite Fly Ash Modified by Humates: A New Soil Conditioner

Fly ash superficially modified with humic substances from the Megalopolis lignitic power plant was prepared and evaluated for agricultural uses. UV-vis spectrophotometry and IR spectroscopy revealed that fly ash shows high sorption efficiency towards humic substances. Adsorption proceeds stepwise via strong Coulombic and hydrophophic forces of attraction between guest and host materials. Langmuir, Freundlich, BET, Harkins-Jura, and Dubinin-Radushkevich isotherm models were employed to evaluate the ongoing adsorption and shed light to the physicochemical properties of the sorbent-adsorbate system. Humic substances desorption and microbial cultivation experiments were also carried out to examine the regeneration of the humates under washing and explore the possibility of this material acclimatizing in real soil conditions, both useful for biofunctional agricultural applications

Therapeutic implications of osteoprotegerin

Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor superfamily, contributes determinatively to the bone remodeling as well as to the pathogenetic mechanism of bone malignancies and disorders of mineral metabolism. There is additional evidence that OPG can promote cell survival by inhibiting TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. A number of recent in vitro, in vivo and clinical studies have defined the role of the RANK/RANKL/OPG pathway in skeletal and vascular diseases. These works were the milestone of the deep understanding of the mechanism of OPG. This review provides an overview of the potential innovative therapeutic strategies of OPG in metastatic breast and prostate carcinoma, multiple myeloma, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis and rheumatoid arthritis. Special reference is given to the increasing evidence that RANKL and OPG may link the skeletal with the vascular system

Maschinelle Übersetzung: Die Übersetzungsschwierigkeiten am Beispiel von wissenschaftlichen Texten.

Η επιστήμη, με την οποία ασχολούμαι στη διπλωματική μου, είναι η επιστήμη της Υπολογιστικής Γλωσσολογίας. Η Υπολογιστική Γλωσσολογία είναι ένας τομέας της Γλωσσολογίας που ασχολείται με την μοντελοποίηση της φυσικής γλώσσας από υπολογιστική σκοπιά. Ένας τομέας εφαρμογής της Υπολογιστικής Γλωσσολογίας είναι η Μηχανική Μετάφραση, η οποία παίζει πολύ σημαντικό ρόλο στη μετάφραση της προφορικής ή γραπτής γλώσσας κειμένων. Η αυτόματη μετάφραση είναι μια μετάφραση ενός κειμένου που είναι σε μια γλώσσα πηγής στο αντίστοιχο κείμενο στη γλώσσα-στόχο. Στην διπλωματική μου λοιπόν, ασχολούμαι με τον τομέα της Μηχανικής Μετάφρασης, καθώς εξετάζω τις δυσκολίες που προκύπτουν κατά την εισαγωγή γερμανικών κειμένων σε μηχανή μετάφρασης και πιο συγκεκριμένα στη μηχανή μετάφρασης „Google translate”. Θα ήθελα να επισημάνω, ότι τα γερμανικά αυτά επιστημονικά κείμενα πραγματεύονται το θέμα του „Covid-19” και στη διπλωματική μου μάλιστα παρουσιάζω τα χαρακτηριστικά των κειμένων αυτών (π.χ. είδος λεξιλογίου), καθώς επίσης περιγράφω τη διαδικασία επιλογής και επεξεργασίας των κειμένων (μεθοδολογία). Αρχικά εισάγω τα γερμανικά κείμενα στο Google Translate, ώστε να γίνει η αυτόματη μετάφραση στη γλώσσα-στόχο, δηλαδή τα ελληνικά. Έπειτα εντοπίζω, κατηγοριοποιώ και σχολιάζω τα λάθη που κάνει η μηχανή μετάφρασης σε τέσσερις κατηγορίες λαθών: Προβλήματα στη γραμματική και στη σύνταξη, λεξικά κενά, λάθη στην ορολογία και τις σύνθετες λέξεις, άλλα-διάφορα μεταφραστικά λάθη. Όλη αυτή η διαδικασία πραγματοποιείται ξεχωριστά για κάθε κείμενο και αποτελεί το πρακτικό κομμάτι της διπλωματικής μου. Σχετικά με το θεωρητικό μέρος αναφέρομαι αρχικά στην θεωρία της Υπολογιστικής Γλωσσολογίας και έπειτα αναλύω την «Μηχανική Μετάφραση», «την Στατιστική Μηχανική Μετάφραση» και «την Νευρωνική Μηχανική Μετάφραση». Και φυσικά αναλύονται θεωρητικά οι Μεταφραστικές Δυσκολίες και η κατηγοριοποίησή τους. Τέλος, παραθέτω τα συμπεράσματα και τις παρατηρήσεις μου από τα λάθη που έχω εντοπίσει στην ανάλυσή μου και περιγράφω με λίγα λόγια τις πιθανές επιπτώσεις/ δυσκολίες/ προκλήσεις στο κομμάτι της Διδακτικής.The science I deal with in my diploma is the science of Computerlinguistics. Computerlinguistics is a branch of Linguistics that deals with the modeling of natural language from a computational perspective. One area of application of Computerlinguistics is Machine Translation, which plays a very important role in the translation of spoken or written language texts. Machine translation is a translation of a text that is in a source language into the corresponding text in the target language. So in my diploma, I deal with the field of Machine Translation, as I examine the difficulties that arise when entering German texts into a translation machine, and more specifically into the "Google translate" translation machine. I would like to point out that these German scientific texts deal with the topic of "Covid-19" and in my thesis I present the characteristics of these texts (e.g. type of vocabulary), as well as describe the process of selecting and editing the texts (methodology). First, I enter the German texts into Google Translate, so that the automatic translation takes place in the target language, i.e. Greek. Then I identify, categorise and comment on the mistakes made by the translation machine in four categories of mistakes: Grammar and syntax problems, lexical gaps, errors in terminology and compound words, other-miscellaneous translation errors. This whole process is carried out separately for each text and is the practical part of my thesis. Regarding the theoretical part, I first refer to the theory of Computerlinguistics and then analyze "Machine Translation", "Statistical Machine Translation" and "Neuronal Machine Translation". And of course Translation Difficulties and their categorisation are analyzed theoretically. Finally, I mention my conclusions and observations from the mistakes I have identified in my analysis and describe in a few words the possible effects/difficulties/challenges in the part of Didactics

Transfection of bovine fetal fibroblast with polyethylenimine (PEI) nanoparticles: effect of particle size and presence of fetal bovine serum on transgene delivery and cytotoxicity

The development of efficient transfection protocols for livestock cells is crucial for implementation of cell-based transgenic methods to produce genetically modified animals. We synthetized fully deacylated linear 22, 87 and 217 kDa polyethylenimine (PEI) nanoparticles and compared their transfection efficiency and cytotoxicity to commercial branched 25 kDa PEI and linear 58 kDa poly(allylamine) hydrochloride. We studied the effect of PEI size and presence of serum on transfection efficiency on primary cultures of bovine fetal fibroblasts and established cells lines (HEK 293 and Hep G2). We found that transfection efficiency was affected mainly by polymer/pDNA ratio and DNA concentration and in less extent by PEI MW. In bovine fibroblast, preincubation of PEI nanoparticles with fetal bovine serum (FBS) greatly increased percentage of cells expressing the transgene (up to 82%) while significantly decreased the polymer cytotoxic effect. 87 and 217 kDa PEI rendered the highest transfection rates in HEK 293 and Hep G2 cell lines (>50% transfected cells) with minimal cell toxicity. In conclusion, our results indicate that fully deacylated PEI of 87 and 217 kDa are useful DNA vehicles for non-viral transfection of primary cultures of bovine fetal fibroblast and HEK 293 and Hep G2 cell lines.Fil: Forcato, Diego Oscar. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Fili, Alejandro. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Alustiza, Fabrisio Eduardo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lazaro Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Bongiovanni Abel, Silvestre Manuel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Olmos Nicotra, Maria Florencia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Alessio, Ana Paula. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Rodriguez, Natalia Evelin. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Barbero, César Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Bosch, Pablo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Establishment of cell-based transposon-mediated transgenesis in cattle

Transposon-mediated transgenesis is a well-established tool for genome modification in small animal models. However, translation of this active transgenic method to large animals warrants further investigations. Here, the piggyBac (PB) and sleeping beauty (SB) transposon systems were assessed for stable gene transfer into the cattle genome. Bovine fibroblasts were transfected either with a helper-independent PB system or a binary SB system. Both transposons were highly active in bovine cells increasing the efficiency of DNA integration up to 88 times over basal nonfacilitated integrations in a colony formation assay. SB transposase catalyzed multiplex transgene integrations in fibroblast cells transfected with the helper vector and two donor vectors carrying different transgenes (fluorophore and neomycin resistance). Stably transfected fibroblasts were used for SCNT and on in vitro embryo culture, morphologically normal blastocysts that expressed the fluorophore were obtained with both transposon systems. The data indicate that transpositionis a feasible approach for genetic engineering in the cattle genome.Fil: Alessio, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Fili, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Garrels, Wiebke. Institut für Nutztiergenetik; Alemania. Gottfried Wilhelm Leibniz Universität Hannover; AlemaniaFil: Forcato, Diego Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Olmos Nicotra, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Liaudat, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Bevacqua, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Savy, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Hiriart, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Talluri, Thirumala R.. Institut für Nutztiergenetik; AlemaniaFil: Owens, Jesse B.. University of Hawaii at Manoa; Estados UnidosFil: Ivics, Zoltán. Paul-Ehrlich-Institute; AlemaniaFil: Salamone, Daniel Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; ArgentinaFil: Moisyadi, Stefan. University of Hawaii at Manoa; Estados UnidosFil: Kues, Wilfried A.. Institut für Nutztiergenetik; AlemaniaFil: Bosch, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentin

The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group

PURPOSE:To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. METHODS:Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. RESULTS:The mean age at diagnosis was 17 years (range 5.0–24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). CONCLUSIONS:We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).</p

The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group

PURPOSE:To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. METHODS:Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. RESULTS:The mean age at diagnosis was 17 years (range 5.0–24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). CONCLUSIONS:We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).</p

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

ΔΔιερεύνηση της εκκίνησης και της επίδρασης διαφορετικών λειτουργικών παραμέτρων σε αναερόβιο αντιδραστήρα ανοδικής ροής, τύπου UASB, για την επεξεργασία σύνθετων αστικών λυμάτων

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Επιστήμη και Τεχνολογία Υδατικών Πόρων