944 resultados para Nuclear aircraft carriers
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"B-259298"--P. [1].
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Ferguson second from left, Magsaysay third from left. On verso: USS Shangri-La CVA-38
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Item 1005-C
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Merisodassa tapahtunut muutos – erityisesti konevoiman syrjäyttäessä purjeet ja raudan korvatessa puumateriaalin 1800-luvun loppupuolella – johti nykypäivänäkin merkittäviin merisodan teoreettisiin tarkasteluihin. Teorioihin pohjautuneet merisotataidon yleisperiaatteet saivat ensimmäisen maailmansodan aikana käytännön testauksensa. Voittajat ja häviäjät analysoivat taistelut sekä maailmalla vallinneen ripeän teknisen kehityksen, minkä seurauksena laivastojen varustelu kiihtyi uudestaan valtapolitiikan tueksi. Maailmansotien välisenä aikana pyrittiin kansainvälisin sopimuksin säätelemään suurten laivastojen, kuten Britannian, Ranskan, Italian, Japanin ja Yhdysvaltojen varustelukilpailua. Versaillesin rauhansopimus rajoitti samanaikaisesti Saksan merivoimien kokoa. Tässä työssä tutkitaan Britannian ja Saksan merivoimien varustelua ja merisotataidon kehittymistä maailmansotien välisenä aikana. Merisotataidon kehittymisen tarkastelu tapahtuu postimerkkien avulla. Postimerkki syntyi Englannissa vuonna 1840 ja sen käyttö yleistyi ympäri maailman lähes samanaikaisesti konevoimaa käyttäneiden laivojen kanssa. Postimerkkien kuva-aiheet olivat aluksi valtioiden päämiehiä, heraldiikkaa, maisemia tai abstrakteja aiheita. Vasta 1900-luvun alkupuolella kuva-aiheina saattoi olla lähes mitä vain, myös sotalaivojen kuvia. Postimerkkikokoelmastani erottuu tutkimusaiheeseen 335 merkkiä. Britannian ja Saksan kansallisarkistojen alkuperäislähteiden ja tutkimuskirjallisuuden dokumenttianalyysiin perustuvaa merisotataidon moninaista kehitystä verrataan tutkimuksessani postimerkkien kuva-aiheisiin ja niiden yksityiskohtiin 3 300 kertaa. Tällä menettelyllä pyrin selvittämään voiko postimerkkejä käyttää ja pitää merisotaidon kehityksen kattavina dokumentteina. Postimerkeissä satunnaisiksi jääneet virheet tai propaganda eivät vähennä merisotataidon kehityksen kuvaamisen dokumenttiarvoa. Postimerkkien sotalaivoihin liittyvät kuvat kattavat muutamaa laivaluokkaa lukuunottamatta molempien maiden kaikki taistelualuslajit- ja luokat. Postimerkeistä voidaan nähdä vanhat sotalaivat, niiden peruskorjaukset ja uudet luokat lentotukialuksista sukellusveneisiin. Alusten kuvat voidaan liittää Britannian kansainyhteisön muuttuneisiin strategisiin ja taktisiin tavoitteisiin niin Atlantilla kuin Kaukoidässä. Saksan merivoimien nousu Versaillesin rauhanehtojen rajoituksista ja lopulta pyrkimys Britannian kauppamerenkulun tuhoajaksi välittyy myös postimerkeistä. Yleinen sotatekninen kehitys, lentoneiden tulo merisotanäyttämölle ja aikanaan kansainvälisten tonnistorajoitusten poistuminen näkyvät postimerkeissä. Kokopostimerkin historian aikana vuoteen 2012 mennessä purjeettomien, nykyaikaisten sotalaivojen kuvia on julkaistu noin 3 350 postimerkillä, jotka on koottu Maailman suurin laivasto-osasto -postimerkkikokoelmaani noin 35 vuoden aikana
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Se quiere contribuir a que se entiendan mejor las dinámicas de seguridad de los hemisferios se planteen problemas relacionados con la integración de los Estados alrededor de los temas de seguridad y se resalte la posición geoestratégica como componente importante dentro de la seguridad.
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La retirada de los aviones Harrier, en servicio en operaciones embarcadas con Armadas de diferentes países, está basada en la perspectiva de poder sustituirlos por el F-35B, versión de operación vertical del controvertido programa Joint Strike Fighter. Este proyecto en realidad engloba el diseño de tres aviones de combate muy distintos entre sí, que, a pesar de tener una considerable parte en común, y dados sus muy diferentes requisitos, es un proyecto tremendamente complejo. Como consecuencia de todo esto, y ante el sobrecoste y los continuos retrasos acumulados en el desarrollo de un proyecto tan ambicioso, se plantean numerosas incertidumbres temporales y económicas, que hacen atractivo el estudio de posibles alternativas de menor riesgo. Esta tesis es un trabajo de investigación tecnológica que plantea el estudio de la modificación de determinados diseños de aviones de combate de operación terrestre, con idea de que puedan satisfacer los exigentes requisitos de operación desde un buque. Tras estudiar las peculiaridades de dichas operaciones, y analizar los tipos de buque y sus necesidades de modificación asociadas más importantes, se propone qué acciones a realizar, y se identifican las áreas de mayor interés, permitiendo establecer un procedimiento objetivo de comparación, con el fin de poder seleccionar los potenciales candidatos para su adaptación. Se aplica esta metodología, en particular, a dos casos de diseño de especial interés; el Eurofighter Typhoon y el Saab Gripen. En ambos, y por lo que respecta a las modificaciones planteadas, no se aprecian especiales dificultades que permitan descartar las posibilidades técnicas de su adaptación. Por último, y dada la complejidad de la consecución del objetivo final, se sugieren posibles líneas de investigación, desde completar y extender la filosofía de trabajo a otros subsistemas, al análisis de los costes de las modificaciones. ABSTRACT The Harrier fleet has been in active service in several Navies from different countries as a carrier-based aircraft. However, this aircraft may be withdrawn and replaced by the F-35B, a vertical capability version of the controversial Joint Strike Fighter (JSF) programme, which great complexity and constant development delays raise numerous uncertainties from a temporal and economical point of view. In fact, this program encompasses the design of three different fighter aircraft which, at the same time, share many similarities. All these aspects led us to undertake the analysis of other lower-risk alternatives. This thesis is a technological research work aimed at studying those design changes required for several fighter aircraft, initially designed for ground operation, in order to make them fullfil the highly demanding requirements for operating from aircraft carriers. After analizing the peculiarities of such operations, and studying different types of ships as well as their most significant modifications, specific actions to undertake are proposed, and those areas of greatest interest are identified, for the purposes of establishing an objective comparison procedure, and selecting potential candidates for this adaptation. This methodology is applied to design two specific cases of particular concern: the Eurofighter Typhoon and the Saab Gripen. In both instances, no major problems have been encountered regarding the modifications suggested. Finally, given the complexity of the analysis performed, some future research lines are outlined such as completing and extending this methodology to other subsystems, and giving an initial estimate of the modification costs.
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In recent years the People’s Republic of China has begun to exhibit a more aggressive naval policy as a result of its decision to switch its naval force from a primarily green-water fleet (coastal) to a blue-water fleet (expeditionary) (“China’s New,” n.d.). This decision has brought China to loggerheads not only with other local East and South Asian powers such as India and Japan, but also with the predominant blue-water power of the world, the United States, that sees its supremacy threatened (“When Grand,” n.d.). Why would China embark on a route that would pit it against the world naval superpower, the United States, which has a huge lead on China in terms of naval blue-water power? Why would China try to challenge and match the U.S. Navy’s eleven aircraft carriers (“The World’s,” n.d.)? What could compel China to embark on a plan that would so disrupt the balance of power in the waters around Asia? To fully understand the Chinese government’s decision, one must first look at Chinese import figures and Chinese trade routes.
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Fragile sites appear visually as nonstaining gaps on chromosomes that are inducible by specific cell culture conditions. Expansion of CGG/ CCG repeats has been shown to be the molecular basis of all five folate-sensitive fragile sites characterized molecularly so far, i.e., FRAXA, FRAXE, FRAXF, FRA11B, and FRA16A. In the present study we have refined the localization of the FRA10A folate-sensitive fragile site by fluorescence in situ hybridization. Sequence analysis of a BAC clone spanning FRA10A identified a single, imperfect, but polymorphic CGG repeat that is part of a CpG island in the 5'UTR of a novel gene named FRA10ACl. The number of CGG repeats varied in the population from 8 to 13. Expansions exceeding 200 repeat units were methylated in all FRA10A fragile site carriers tested. The FRA10ACl gene consists of 19 exons and is transcribed in the centromeric direction from the FRA10A repeat. The major transcript of similar to 1450 nt is ubiquitously expressed and codes for a highly conserved protein, FRA10ACl, of unknown function. Several splice variants leading to alternative 3' ends were identified (particularly in testis). These give rise to FRA10ACl proteins with altered COOH-termini. Immunofluorescence analysis of full-length, recombinant EGFP-tagged FRA10ACl protein showed that it was present exclusively in the nucleoplasm. We show that the expression of FRA10A, in parallel to the other cloned folate-sensitive fragile sites, is caused by an expansion and subsequent methylation of an unstable CGG trinucleotide repeat. Taking advantage of three cSNPs within the FRA10ACl gene we demonstrate that one allele of the gene is not transcribed in a FRA10A carrier. Our data also suggest that in the heterozygous state FRA10A is likely a benign folate-sensitive fragile site. (C) 2004 Elsevier Inc. All rights reserved.
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Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we describe a recessive mouse phenotype caused by the insertion of a transposable element into Ndufs4, identified by a novel combined linkage and expression analysis. Designated Ndufs4(fky), the mutation leads to aberrant transcript splicing and absence of NDUFS4 protein in all tissues tested of homozygous mice. Physical and behavioral symptoms displayed by Ndufs4(fky/fky) mice include temporary fur loss, growth retardation, unsteady gait, and abnormal body posture when suspended by the tail. Analysis of CI in Ndufs4(fky/fky) mice using blue native PAGE revealed the presence of a faster migrating crippled complex. This crippled CI was shown to lack subunits of the "N assembly module", which contains the NADH binding site, but contained two assembly factors not present in intact CI. Metabolomic analysis of the blood by tandem mass spectrometry showed increased hydroxyacylcarnitine species, implying that the CI defect leads to an imbalanced NADH/NAD(+) ratio that inhibits mitochondrial fatty acid β-oxidation.
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Praziquantel (PZQ) is a pyrazinoisoquinoline anthelmintic that was discovered in 1972 by Bayer Germany. Currently, due to its efficacy, PZQ is the drug of choice against all species of Schistosoma. Although widely used, PZQ exhibits low and erratic bioavailability because of its poor water solubility. Nanostructured lipid carriers (NLC), second-generation solid lipid nanoparticles, were developed in the 1990s to improve the bioavailability of poorly water soluble drugs. The aim of this study was to investigate nanostructured lipid carriers as a strategy to improve the efficacy. of PZQ in S. mansoni treatment. We prepared NLC2 and NLC4 by adding seventy percent glycerol monostearate (GMS) as the solid lipid, 30% oleic acid (OA) as the liquid lipid and two surfactant systems containing either soybean phosphatidylcholine/poloxamer (PC/P-407) or phosphatidylcholine/Tween 60 (PC/T60), respectively. The carriers were characterized by nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and Fourier transform-infrared spectroscopy. The safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. The results showed that the encapsulation of PZQ in NLC2 or NLC4 improved the safety profile of the drug. Treatment efficacy was evaluated on the S. mansoni BH strain. PZQ-NLC2 and PZQ-NLC4 demonstrated an improved efficacy in comparison with free PZQ. The results showed that the intestinal transport of free PZQ and PZQ-NLC2 was similar. However, we observed that the concentration of PZQ absorbed was smaller when PZQ was loaded in NLC4. The difference between the amounts of absorbed PZQ could indicate that the presence of T60 in the nanoparticles (NLC4) increased the rigid lipid matrix, prolonging release of the drug. Both systems showed considerable in vitro activity against S. mansoni, suggesting that these systems may be a promising platform for the administration of PZQ for treating schistosomiasis.
Nuclear Factor (NF) κB polymorphism is associated with heart function in patients with heart failure
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Abstract Background Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. Methods A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1 -94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. Results We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG1/ATTG1 genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG1/ATTG1 more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG1/ATTG1 carriers. Conclusion There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG1/ATTG1 genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.
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Abstract Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh2(H2cit)4, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh2(H2cit)4 induces cell death by apoptosis. Conclusions The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.
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The Epstein–Barr virus (EBV) encoded nuclear antigen (EBNA) 1 is expressed in latently infected B lymphocytes that persist for life in healthy virus carriers and is the only viral protein regularly detected in all EBV associated malignancies. The Gly-Ala repeat domain of EBNA1 was shown to inhibit in cis the presentation of major histocompatibility complex (MHC) class I restricted cytotoxic T cell epitopes from EBNA4. It appears that the majority of antigens presented via the MHC I pathway are subject to ATP-dependent ubiquitination and degradation by the proteasome. We have investigated the influence of the repeat on this process by comparing the degradation of EBNA1, EBNA4, and Gly-Ala containing EBNA4 chimeras in a cell-free system. EBNA4 was efficiently degraded in an ATP/ubiquitin/proteasome-dependent fashion whereas EBNA1 was resistant to degradation. Processing of EBNA1 was restored by deletion of the Gly-Ala domain whereas insertion of Gly-Ala repeats of various lengths and in different positions prevented the degradation of EBNA4 without appreciable effect on ubiquitination. Inhibition was also achieved by insertion of a Pro-Ala coding sequence. The results suggest that the repeat may affect MHC I restricted responses by inhibiting antigen processing via the ubiquitin/proteasome pathway. The presence of regularly interspersed Ala residues appears to be important for the effect.
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Issuance date: August 1963.
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Mode of access: Internet.