Coherence in Translation

Coherence is the trait that makes the text easily understandable to a reader. One can help create coherence in his text by creating logical and verbal bridges. Coherence is a product of many different factors, which combine to make every paragraph, sentence, and phrase contribute to the meaning of the whole piece. Coherence in translation is much more difficult to sustain than coherence in the original language simply because translators have less clues to inform them if their message is as clear as it was originally intended or not. Therefore, translators must make their patterns of coherence much more explicit and carefully planned. Coherence itself is the product of two factors – paragraph unity and sentence cohesion. Keywords: Translation, coherence, connection, transition

Predictive Stator Flux and Load Angle Control of Synchronous Reluctance Motor Drives Operating in a Wide Speed Range

This paper presents a new simplified finitecontrol- set model predictive control strategy for synchronous reluctance motors operating in the entire speed range. It is a predictive control scheme that regulates the stator flux and the load angle of the synchronous reluctance motor, incorporating the ability to operate the drive in the field-weakening region and respecting the motor voltage and current limits as well as the load angle limitation needed to operate this type of motor in the maximum torque per voltage region. The proposed control strategy possesses some attractive features, such as no need for controller calibration, no weighting factors in the cost function, good robustness against parameter mismatch, and smaller computational cost compared to more traditional finite-control-set model predictive control algorithms. Simulation and experimental results obtained using a high-efficiency synchronous reluctance motor demonstrate the effectiveness of the proposed control scheme.info:eu-repo/semantics/publishedVersio

Essays in international finance

This thesis contributes to the extant research on international finance by presenting a collection of three separate essays. The first essay tests the validity of long-run Purchasing Power Parity (PPP) in two panels of real exchange rates for 13 OECD countries (1989:07-2012:11, 1989:07-2006:12). Three panel unit root tests are applied, one that assumes cross-sectional independence, one that accounts for cross-sectional dependence using a single factor approach, and one that controls for cross-sectional dependence through a multi-factor approach. The main difference in the results is attributed to ignoring or allowing for cross-sectional dependence. The second essay also examines long-run PPP, but uses a panel cointegration test which allows for (i) heterogeneous and multiple structural breaks and (ii) crosssectional dependence. Based on a panel of 53 economies (1992:01-2014:05 ) no evidence of PPP can be found using two types of models that can be equipped/illequipped to handle the potential presence of structural breaks in the data. The third essay employs a factor approach to analyse exchange rate prediction at multiple horizons, from 1 month to two years for a panel of 10 OECD economies spanning the period 1999:01-2013:04. Two new models are proposed, that are based on the separate use of forward rates and interest rate differentials to be added in conjunction with the extracted factors. Factor-based exchange rate models were found to beat the random walk model for long horizons over the latter parts of our forecasting sample

Performance Comparison of Field-oriented Control, Direct Torque Control, and Model-predictive Control for SynRMs

Simulation studies of three synchronous reluctance motor (SynRM) control strategies are presented: field-oriented control (FOC), direct torque control (DTC), and finite-set model-predictive control (FS-MPC). FOC uses linear controllers and pulse-width modulation to control the fundamental components of the load voltages vectors. In contrast, DTC and FS-MPC are nonlinear strategies wherein the voltage vectors are directly generated in the absence of a modulator. Theoretical operating principles and control structures of these control strategies are presented. Moreover, a comparative analysis of the static and dynamic performance of the control strategies is conducted using Matlab/Simulink to identify their advantages and limitations. It is confirmed that each of the control strategies has merits and that all three of them satisfy the requirements of modern high-performance drives.info:eu-repo/semantics/publishedVersio

An encoderless high-performance synchronous reluctance motor drive

This paper presents an encoderless high-performance synchronous reluctance motor drive for traction applications. The control system is based on the active flux concept and a hybrid rotor position estimation algorithm is used, being this algorithm based on the injection of high-frequency signals at low speeds and on the position of the active flux vector for medium and high-speeds. A smooth transition algorithm between the two rotor position estimation methods is provided. Moreover, in order to improve the efficiency of the overall drive system, a loss minimization algorithm is proposed in order to reduce the motor copper losses when operating in steady-state. Experimental results obtained in the laboratory confirm the validity and adequacy of the proposed algorithms for the developed drive system.info:eu-repo/semantics/publishedVersio

Determination of sulfur in biological samples using high-resolution molecular absorption spectrometry in a graphite furnace with direct solid sampling

The determination of sulfur in biological materials using high-resolution continuum source molecular absorption spectrometry and electrothermal vaporization of the carbon monosulfide (CS) molecule has been investigated in detail using direct solid sampling. Best results have been obtained coating the platform with tungsten as a permanent modifier, adding 40 mg Pd in solution as a chemical modifier, and the only sulfur compound that showed sufficient sensitivity and thermal stability to be used for calibration purposes under the conditions established for biological materials was thiourea. A pyrolysis temperature of at least 900 C could be used and the optimum vaporization temperature was 2500 C. Under optimized conditions a limit of detection of 0.015 mg S absolute or 0.03 mg g À1 S in the solid sample, based on a sample mass of 0.5 mg could be obtained; the characteristic mass was m 0 ¼ 18 ng. Five certified biological reference materials have been analyzed using direct solid sampling and calibration against aqueous standards; the results were in agreement with the certified values on a 95% confidence interval

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

Therapeutic prospects of extracellular vesicles in cancer treatment

Extracellular vesicles (EVs) are released by all cells within the tumor microenvironment, such as endothelial cells, tumor-associated fibroblasts, pericytes and immune system cells. The EVs carry the cargo of parental cells formed of proteins and nucleic acids, which can convey cell-to-cell communication influencing the maintenance and spread of the malignant neoplasm, for example promoting angiogenesis, tumor cell invasion and immune escape. However, EVs can also suppress tumor progression, either by the direct influence of the protein and nucleic acid cargo of the EVs or via antigen presentation to immune cells as tumor derived EVs carry on their surface some of the same antigens as the donor cells. Moreover, dendritic cell-derived EVs carry MHC class I and class II/peptide complexes and are able to prime other immune system cell types and activate an anti-tumor immune response. Given the relative longevity of vesicles within the circulation and their ability to cross blood-brain barriers, modification of these unique organelles offers the potential to create new biological-tools for cancer therapy. This review examines how modification of the EV cargo has the potential to target specific tumor mechanisms responsible for tumor formation and progression to develop new therapeutic strategies and to increase the efficacy of antitumor therapies

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

Exosomal Doxorubicin and the Treatment of Breast and Ovarian Cancers

Background The application of nanotechnology in the medical field is called nanomedicine. This novel sector have got a lot of interest from many investigators nowadays due to the important development that happened in the last decades, in particular in cancer treatment. Cancer nanomedicine has been applied in different domains such as drug delivery, nanopharmaceuticals and nanodevices. The application of nanotechnology to pharmaceutical science allowed to build up system based on at least two stage vectors (drug/nanomaterial). New formulations based on that platform show often an improvement in drug pharmacokinetics (PK), bioavailability and biodistribution owing enhanced permeability and retention (EPR) effect to passively target tumor both decreasing side effect of free drug. Among natural nanovectors, exosomes (exo) were first described in 1981 as extracellular nanovesicles with a size range of 50-200 nm. Exosomes are produced by cells embedded of cellular information and represent a formidable natural cargo for long distance communication. The name "fedexosome" denotes the general idea that exosomes could deliver cargo that conveniently manipulated could be of help for patients therapy. Aims To develop exosomes loaded with doxorubicin (DOX) To test the cytotoxic effect of exoDOX (exosomal doxorubincin) in vitro using cell lines models compared to the parental drug (DOX) To test the antitumor activity and the toxic side effects of exoDOX compared to the parental DOX in in vivo experimental models To test tissue biodistribution and pharmacokinetics (PK) of exoDOX compared to DOX in vivo experimental models To define the maximum tolerated dose (MTD) of exoDOX and DOX in in vivo experimental models Materials and Methods Purified exosomes from cell lines were loaded with DOX and characterized by nanoparticle tracking analysis (NTA), Scanning/Transmission electron microscopy (SEM/TEM) and western blot. The anti-tumoral effects of exoDOX were tested in vitro (MDA-MB-231 breast, HCT-116, LoVo and DLD1 colon and STOSE ovarian cancer cell lines) and in vivo using nude and FVB/N mice as breast and ovarian cancer models. The antitumor effect was assessed by measuring the tumor volumes. The toxic effects were evaluated by following the body weight and through histopathological analyses of mice organs. The biodistribution and PK of exoDOX and DOX were assessed by mass spectrometry (LC-MS). Results • In vitro studies showed no increased cytotoxic effect (cell viability) of exoDOX compared to DOX in all the investigated cell lines . • Similar results were observed in the in vivo models indicating no significant differences in the tumor volume after treating mice with the same concentrations of exoDOX and DOX. • In vivo toxicity analysis showed a significant reduction of cardio-toxic side effects by using exoDOX compared to free DOX. Mass spectrometry studies showed that the accumulation of exoDOX in the heart was reduced by about 40% compared to free DOX when using the same concentration of active drug. ExoDOX avoids heart toxicity by partially limiting the crossing of DOX through the myocardial endothelial cells. For this reason, mice can be treated with higher concentration of exoDOX thus increasing the efficacy of DOX as demonstrated in breast and ovarian mouse tumors. - Conclusions Differently from previously published papers that focused on the efficacy of the doxorubicin encapsulated in exosomes, in this thesis for the first time, we demonstrated that unmodified exosomes loaded with DOX are less toxic than free DOX by altering the biodistribution of the drug, these results were published in Nanomedicine (Lond) Journal in 2015. ExoDOX is safer and more effective than free DOX using breast cancer model and importantly was confirmed using the first spontaneous transformed syngeneic model of high-grade serous ovarian cancer which open the road for providing a new therapeutic opportunity, which was published recently in Nanomedicine (Lond) Jounral in 2016.Introduzione L'applicazione delle nanotecnologie in medicina è chiamata nanomedicina. Questo settore è motivo di interesse da parte di molti ricercatori dovuto agli importanti avanzamenti avvenuti negli ultimi decenni, in particolare nel trattamento del cancro. In oncologia la nanomedicina è stata applicata in diversi settori quali la costruzione di nuovi sistemi di veicolazione del farmaco e nano dispositivi per la diagnosi. L'applicazione delle nanotecnologie alle scienze farmaceutiche ha permesso di costruire sistemi basati su almeno due vettori (farmaco/nanomateriali). Le nuove formulazioni spesso mostrano un miglioramento del profilo di farmacocinetica (PK), la biodisponibilità e biodistribuzione dimostrando una migliorata permeabilità e ritenzione passiva nel tumore (EPR effect) diminuendo gli effetti collaterali del farmaco libero. Tra i nanovettori naturali, gli esosomi (exo) sono stati descritti nel 1981 come nanovescicole extracellulari con una gamma di dimensioni da 50-200 nm. Gli esosomi sono prodotti dall invaginazione dalla conseguente gemmazione della membrana cellulare consentendo il caricamento di acidi nucleici e di componenti citoplasmatiche rappresentando formidabile mezzo naturale per la comunicazione a lunga distanza. Il nome "fedexosome" denota l'idea generale che exosomes potevano consegnare contenuti che adeguatamente ingegnerizzato potrebbe essere di aiuto per la terapia di pazienti. Scopo • Sviluppare esosomi caricati con doxorubicina (DOX) • Verificare l'effetto citotossico dell'exoDOX exosomal doxorubincin in vitro rispetto al farmaco libero (DOX), utilizzando modelli cellulari. • Testare l'attività antitumorale e la tossicità dell'exoDOX rispetto alla DOX libera in modelli sperimentali in vivo. • Valutare la biodistribuzione nei tessuti e la farmacocinetica (PK) dell'exoDOX rispetto al DOX in modelli sperimentali in vivo. • Definire la dose massima tollerata (MTD) dell' exoDOX e DOX in modelli sperimentali in vivo. Materiali e metodi Gli esosomi purificati da linee cellulari sono stati caricati con DOX e caratterizzati tramite nanoparticle tracking analysis (NTA), microscopia a scansione/ trasmissione elettronica (SEM/TEM) e western blot. Gli effetti anti-tumorali dell'exoDOX sono stati valutati in vitro in linee cellulari di tumore alla mammella (MDA-MB-231), colon (HCT-116, LoVo e DLD1) e ovaio (STOSE) e in vivo utilizzando topi nudi e FVB/N come modelli di tumore della mammella e dell'ovaio. L'effetto antitumorale è stato valutato misurando il volume del tumore. Gli effetti tossici sono stati determinati monitorando il peso corporeo e attraverso analisi istopatologiche degli organi dei topi. La biodistribuzione e la PK dell'exoDOX e DOX sono state definite mediante spettrometria di massa (LC-MS). Risultati • Studi in vitro hanno dimostrato un aumento dell'effetto citotossico (vitalità cellulare) dell'exoDOX rispetto alla DOX in tutte le linee cellulari esaminate. • Risultati simili sono stati ottenuti nei modelli in vivo e indicano differenze significative nel volume del tumore dopo aver trattato i topi con le stesse concentrazioni dell'exoDOX e DOX. • Le analisi della tossicità in vivo hanno mostrato una riduzione significativa degli effetti collaterali cardio-tossici dell'exoDOX rispetto alla DOX libera. Dalle analisi di spettrometria di massa è emerso un minore accumulo dell'exoDOX a livello del cuore di circa il 40% rispetto alla DOX libera a parità di concentrazione di farmaco attivo. • La minore tossicità cardiaca della exoDOX è dovuta ad un ridotto passaggio della DOX attraverso le cellule endoteliali del miocardio. Pertanto, come dimostrato in tumori alla mammella e all'ovaio, l'efficacia terapeutica della DOX può essere ottimizzata trattando i topi con una maggiore concentrazione dell' exoDOX. Conclusioni A differenza di quanto riportato in letteratura circa l'efficacia della doxorubicina incapsulata negli esosomi, dal nostro studio, pubblicato nel 2015 nella rivista Nanomedicine, emerge che: - la tossicità della DOX veicolata dagli esosomi è minore rispetto al farmaco libero; -la biodistribuzione della DOX veicolata dagli esosomi è diversa da quella del farmaco libero. In conclusione, lo studio effettuato dimostra che l'exoDOX è più biocompatibile ed efficace della DOX libera in modelli di tumore alla mammella. Inoltre, come da noi pubblicato di recente sulla rivista Nanomedicine, tale risultato è stato confermato con studi su un modello singenico di carcinoma ovarico sieroso, aprendo così la strada ad un nuovo approccio terapeutico per il cancro all'ovaio