LA ESTRATEGIA DE LOS PAÍSES SURAMERICANOS EN EL SECTOR DE LA DEFENSA EN EL NUEVO MILENIO

In the last years, several reforms in the defence sector of South America have been scheduled; and in some cases, those reforms have been executed. Two important regional institutions were created: The Union of South American Nations (UNASUR) and its Defence Council (CDS). These two organizations do not have decision power yet, but in 2008 and in 2012, they faced and solved a regional crisis. In 2008, the Colombian raid against FARC’s group in Ecuadorian territory and the “coup d’etat” in Paraguay in 2012. In both cases, the CDS approved the measures of mutual trust, which represent a necessary step for future regional integration in this sector. It is important to analyse the diplomatic relations between these three countries involved in the crisis of 2008 (Colombia, Ecuador, and Venezuela). However, the main attention is dedicated to the analysis of the situation in Argentina, Brazil, and Chile. These Countries represent three different strategies in the defence sector. Argentina faces a critical situation; first of all, there are no clear strategy to develop its defence sector. Second, this country has a constant lack of funds. Third, their armed forces have very old equipment. Brazil is the economic power of the region. The country has planned a big strategy to modernize its armed forces, but it does not have sufficient funds for financing all its programs at the same time. Chile, called the Israel of South America, has a clear strategy to develop its defence sector and it has adequate funds for its acquisitions. It is the only country in the region that respects the quality standards of North Atlantic Treaty Organization (NATO)

Bioprocessing of bacteriophages and bacteriocins: continuous culture and downstream purification

Antimicrobial resistance poses a major problem to health and new alternatives to antibiotics are required. Bacteriophages are viruses able to selectively kill bacteria and they can be exploited to treat infections. Another alternative to antibiotics that can be used to treat bacterial infections are bacteriocins, which are proteins produced by bacteria, meant to kill other strains competing for the same nourishment source. Future industrial demand for large quantities of bacteriophages and bacteriocins imposes the development of a scalable production platform.In this PhD thesis, research on bioprocessing of bacteriophages K and T3 and one bacteriocin belonging to the subcategory of colicins, E9, has been conducted. The aims were to find the parameters involved in production of phages and colicin E9 using shake flasks and then exploiting them to perform continuous production of both phages and colicin E9 and showing the different outcomes when using complex medium (LB) and a synthetic medium (SM) using glucose as only carbon source.For the colicin E9 bioprocessing, tests for expression were carried out to measure when and for how long to induce for optimal protein production and the best conditions for production were an induction of 3 h with 1 mM of IPTG in LB medium and >10 h of induction with 1 mM of IPTG in SM. These parameters were used for continuous production of colicin E9 that was carried out using a chemostat. Optimal dilution rates were used to ensure maximum productivity and a production of 1 mg mL-1 of colicin E9 was achieved using either LB and synthetic medium. Then, the influence of flowrates and of different growth media on the first step of purification was assessed using affinity chromatography, showing that the synthetic medium allowed higher recovery of the product in the chromatography step.Bioprocessing of the phages K and T3 was carried out in shake flasks and 5L fermenters, researching the best parameters for producing the highest titres. The effect on the final titre of a variety of multiplicities of infection (MOI), the ratio of phages out of bacteria at the moment of infection, was evaluated. For both phages the MOI that ensured the highest phage titre, 1011 PFU mL-1, was 0.01. The parameters measured were then used for continuous production of bacteriophage T3.Continuous phage T3 production was carried out using a novel reactors layout, composed by 3 separated stages. This set up allowed to divide the production of the host cells, carried out in the first reactor, from the infection, carried out in the second reactor, and from the final amplification step, carried out in the third reactor. The synthetic medium with glucose as only carbon source and the dilution rate (D, the volume of media that flows in the reactor per hour) were used to control the growth rate of the host, which strongly influenced the final production of bacteriophages. Different Diiiwere tested, from 0.1 to 0.6 h-1 and the independent control of the dilution rate of the first and the second reactor allowed to produce phage lysates at the same concentrations as in batch process, reaching a constant production of 2x1011 PFU mL-1 when D = 0.5 h-1 was used in the first reactor.Moreover, research on the downstream process of phage bioprocessing was conducted, aiming to reduce the host cell protein burden from phage samples using scalable techniques. The purification of bacteriophages from complex medium was performed using ultrafiltration in batch mode in a stirred cell (SC) and in using tangential flow filtration (TFF). The high shear stress produced SC decreased the viability of the tailed phage K of 2 log10 in 2 h and the positive effects of purification were cancelled by the loss of titre. Phage T3, which has a short tail, showed no side effects due to shear stress. TFF was then tested and both phage K and T3 were purified without significant viability loss. Size exclusion chromatography was used to assess the final protein concentration and showed a decrease of host cell protein load in both phages samples purified by ultrafiltration. Samples of both phages were mixed with a positively charged resin used for anion exchange chromatography and it was shown that phages that have been filtered using ultrafiltration can bind 10 times more than phages of the lysate.The main aim of purification phages produced from Gram-negative bacteria, such as T3, was to reduce the endotoxin levels (or lipopolysaccharide, LPS). Endotoxins are a major contaminant that can cause serious problems if administered and must be removed from drug products. The target was to bring the LPS levels from the initial concentration of 5x106 EU mL-1 (Endotoxin Units per mL) below the limit of 5 EU mL-1. Endotoxin removal was performed using ultrafiltration and liquid-liquid extraction (LLE).The first method tested was the TFF ultrafiltration, carried out in batch mode or in diafiltration mode. Batch ultrafiltration showed a decrease of LPS of 2 log10, either starting from a phage T3 sample from LB or from SM. Diafiltration TFF reached 3 log10 reduction of LPS in both LB or SM samples, but in LB samples it took 20 h and in SM samples only 4 h, showing how a chemically defined medium could improve the purification of phages produced from Gram-negative hosts.The other method tested to further reduce LPS concentration was liquid-liquid extraction, using 1- octanol as organic phase. Many different conditions of LLE were tested, such as length of contact time between aqueous and organic phases, different mixing methods and number of extractions. Liquid- liquid extraction using octanol ensured a reduction of endotoxins of 4 log10 from the initial concentration. This technique was then followed by ion exchange chromatography, which allowed to reach a final concentration of 102 EU mL-1.ivFinally, analysis on how endotoxins concentrations affected the aggregation of phage T3 were performed, showing how phage T3 aggregates in presence of endotoxins whilst it has a low polidspersivity at low endotoxins concentrations.This thesis showed how is it possible to produce bacteriophages and an antimicrobial protein at high concentrations using a continuous production mode and a chemically defined medium. The positive effects of the synthetic medium on the downstream steps were also illustrated, such as a lower burden for ion exchange columns and a faster reduction of endotoxin concentration from the samples.</div

Mining published lists of cancer related microarray experiments: Identification of a gene expression signature having a critical role in cell-cycle control

BACKGROUND: Routine application of gene expression microarray technology is rapidly producing large amounts of data that necessitate new approaches of analysis. The analysis of a specific microarray experiment profits enormously from cross-comparing to other experiments. This process is generally performed by numerical meta-analysis of published data where the researcher chooses the datasets to be analyzed based on assumptions about the biological relations of published datasets to his own data, thus severely limiting the possibility of finding surprising connections. Here we propose using a repository of published gene lists for the identification of interesting datasets to be subjected to more detailed numerical analysis. RESULTS: We have compiled lists of genes that have been reported as differentially regulated in cancer related microarray studies. We searched these gene lists for statistically significant overlaps with lists of genes regulated by the tumor suppressors p16 and pRB. We identified a highly significant overlap of p16 and pRB target genes with genes regulated by the EWS/FLI fusion protein. Detailed numerical analysis of these data identified two sets of genes with clearly distinct roles in the G1/S and the G2/M phases of the cell cycle, as measured by enrichment of Gene Ontology categories. CONCLUSION: We show that mining of published gene lists in the absence of numerical detail about gene expression levels constitutes a fast, easy to perform, widely applicable, and unbiased route towards the identification of biologically related gene expression microarray datasets

La Geopolítica Del Terrorismo En Tiempos De ISIS

During the last years, Islamic State has expanded its military capabilities and controls a large portion of Iraq and Syria. Religious terrorism is the principal argument in international relations, but there is not a clear definition of terrorism and the countries do not find a common strategy to fight against this threat. In this article, an analysis of terrorism from a geopolitics perspective is presented with a description of the main difficulties to define this phenomenon. At the same time, there is a description of the events that allow to ISIS to expand terror and define itself as a State. This State is transforming the map of the Middle East. The Iraqi crisis contained due to fighting ISIS can lead to the division of the country into three parts: Kurdistan, Sunni Iraq, and Chita Iraq. Finally, there is an analysis of the different interests of the coalitions that fight against ISIS; the first coalition is led by Russia and the second coalition is led by the United States of America

Cambios en el sector de defensa colombiano entre los períodos de Uribe y Santos y el actual proceso de paz

Hasta hace algunos años un proceso de paz en Colombia parecía un hecho imposible. Sin embargo, actualmente en La Habana se está llevando a cabo un diálogo entre el gobierno de Bogotá y las Farc. Esto ha sido posible porque las fuerzas armadas han recuperado el control de la mayor parte del territorio nacional afectando así a las Farc. Para conseguir este resultado, Colombia ha desarrollado una estrategia en el sector de la defensa que empezó con el Plan Colombia, firmado por los presidentes Clinton y Pastrana en 1999. Casi 14 años después las fuerzas armadas han completado su plan de actualización y se han transformado en un instrumento antiguerrilla de excelencia mundial. Estos logros han sido alcanzados por los dos últimos presidentes, Uribe y Santos, que con mano firme establecieron una línea de conducta en el sector de la defensa. Las decisiones tomadas por el actual presidente y su predecesor tienen puntos positivos y negativos. La herencia de la guerra civil y de las estrategias para terminarla es difícil de analizar y Colombia tiene el deber histórico de hacerlo. Este artículo analiza los cambios en el sector de la defensa de Colombia bajo las presidencias de Uribe y Santos y la posibilidad actual de creer en un futuro de paz.

Sui waterfront di Venezia: la valorizzazione del patrimonio industriale per i bisogni della citta

Venezia ha una duplice eredità portuale: quella di quando era tutta città porto, e aveva dato luogo nel suo baricentro, il bacino di San Marco, ad un possente sistema di attrezzature e di manufatti per la navigazione e il ricovero delle merci; e quella di quando trasferì il suo porto sul proprio confine occidentale, concentrandolo in un luogo specializzato collegato alla terraferma dalla ferrovia. Vedremo quindi come questo processo ha preso forma, e come abbia portato ad un duplice insieme di iniziative di preservazione e valorizzazione delle strutture abbandonate.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Plan Propio de Investigación de la UM

Legitimidad y política : notas acerca de ciò che resta della democrazia.

La obra de Geminello Preterossi es difícil de reseñar: es un texto profundo, que se fundamenta en un bagaje teórico de notable trascendencia; se basa en una tesis unitaria, pero que se desenvuelve en un amplio abanico de temas examinados con rigor y pasión; en fin, Cio che resta della democrazia es una obra que no se sustrae a las consecuencias de una mirada critica, honesta, que juega a cartas vistas sobre la base del doble registro teórico y político

Il Settore della Difesa Sud Americano. Argentina, Brasile e Cile.

Per quanto riguarda gli stanziamenti alla difesa, la diversità dei top spenders regionali indica molto bene quanto il quadro possa essere frammentato: il Brasile ha una grande quantità di denaro da investire ma una scarsa capacità di spesa ed una pianificazione che spesso lascia parecchio a desiderare; il Venezuela, a causa dell’embargo degli Stati Uniti sull’esportazione di materiale bellico che contenga tecnologia statunitense, ha deciso di rivolgersi alla Russia indebitandosi fino al collo ed ormai è prossimo alla paralisi economica; la Colombia, impegnata in una 40ennale guerra contro le FARC (Fuerzas Armadas Revolucionarias de Colombia), preferisce investire gran parte del suo bilancio in mezzi che facilitino le operazioni di contro insurgency; l’Argentina, il secondo Paese per estensione territoriale, ha delle spese militari molto basse che permettono a stento il normale funzionamento delle forze armate; il Cile, per i suoi stanziamenti costanti negli anni, per la capacità di pianificazione e per la qualità del materiale acquisito, si è guadagnato l’appellativo di Israele del Sud America. Le sue forze armate sono le uniche, nella regione, che soddisfano gli standard NATO e recentemente il Paese ha firmato un memorandum d’intesa con l’Unione Europea per schierare le sue truppe in missioni di pace sotto egida UE. I Paesi della regione hanno aumentato, con il ritorno alla democrazia, la loro partecipazione alle missioni di pace internazionali; questa decisione è stata prese in particolare per due motivi: dare una valvola di sfogo ai militari evitando così conati golpisti all’interno delle forze armate; incamerare fondi da reinvestire nel settore della difesa. L’ONU, infatti, garantisce lauti rimborsi a tutti gli Stati che inviano truppe. L’esperienza maturata, in questo settore, è stata sfruttata dai governi sud americani nella gestione della missione di Pace ad Haiti (MINUSTAH). Per prendere le decisioni inerenti questa operazione, i Paesi Sud americani hanno istituito un meccanismo ad hoc il 2xn (dove 2 indica i rappresentanti della difesa e degli affari esteri ed n il numero dei Paesi partecipanti). Questo strumento ha permesso di resistere alle forti pressioni esterne che chiedevano un intervento più deciso delle forze armate all’indomani del terremoto; pressanti richieste furono fatte, in particolare, dagli Stati Uniti. Con la loro capacità di non perdere mai di vista l’obiettivo finale, cioè ridare ad Haiti un governo civile ed un’infrastruttura moderna che permetta all’economia di svilupparsi, i Paesi sud americani non solo hanno dimostrato grande capacità di gestione ma anche che non basta essere tra i principali sovvenzionatori di un’organizzazione internazionale per aver ragione. Proprio i rapporti con gli Stati Uniti sono al centro di acceso dibattito in Sud America. Venezuela e Colombia sono chiaramente i due contendenti più vivaci; il primo molto spesso accusa il secondo di essere un servitore dei gringos. Gli Stati Uniti con la riattivazione della IV Flotta hanno arrecato un ulteriore duro danno alla loro reputazione nella regione. I compiti di questa forza militare sono quelli di pattugliare i mari del Sud America alla ricerca di pirati e terroristi; due minacce che la regione non avverta nel modo più assoluto. Il risultato di questa sconcertante scelta, dell’amministrazione Bush, ha portato alla formazione di un fronte di critiche che va dal Venezuela al Cile passando per Brasile ed Argentina ed ha ulteriormente alienato le simpatie delle Colombia che invece appoggiava tale decisione. L’Ecuador decise di non rinnovare il contratto alla marina statunitense che si vide costretta a chiudere la sua unica base in Sud America; uno strano soccorso provenne dal Perù che permise alle navi battenti bandiera a stelle e strisce di entrare nei suoi porti. Questa concessione avvenne poco dopo che il Perù aveva deferito il Cile d’innanzi alla Corte Internazionale dell’Aja per la risoluzione delle dispute sul confine marittimo. Sebbene tutti gli esperti, con cui ho parlato, escludano una concatenazione degli eventi, la scelta dei tempi risulta sospetta

LA ESTRATEGIA DE LOS PAÍSES SURAMERICANOS EN EL SECTOR DE LA DEFENSA EN EL NUEVO MILENIO

In the last years, several reforms in the defence sector of South America have been scheduled; and in some cases, those reforms have been executed. Two important regional institutions were created: The Union of South American Nations (UNASUR) and its Defence Council (CDS). These two organizations do not have decision power yet, but in 2008 and in 2012, they faced and solved a regional crisis. In 2008, the Colombian raid against FARC’s group in Ecuadorian territory and the “coup d’etat” in Paraguay in 2012. In both cases, the CDS approved the measures of mutual trust, which represent a necessary step for future regional integration in this sector. It is important to analyse the diplomatic relations between these three countries involved in the crisis of 2008 (Colombia, Ecuador, and Venezuela). However, the main attention is dedicated to the analysis of the situation in Argentina, Brazil, and Chile. These Countries represent three different strategies in the defence sector. Argentina faces a critical situation; first of all, there are no clear strategy to develop its defence sector. Second, this country has a constant lack of funds. Third, their armed forces have very old equipment. Brazil is the economic power of the region. The country has planned a big strategy to modernize its armed forces, but it does not have sufficient funds for financing all its programs at the same time. Chile, called the Israel of South America, has a clear strategy to develop its defence sector and it has adequate funds for its acquisitions. It is the only country in the region that respects the quality standards of North Atlantic Treaty Organization (NATO)