4,885 research outputs found
System Concepts for Bi- and Multi-Static SAR Missions
The performance and capabilities of bi- and multistatic spaceborne synthetic aperture radar (SAR) are analyzed. Such systems can be optimized for a broad range of applications like frequent monitoring, wide swath imaging, single-pass cross-track interferometry, along-track interferometry, resolution enhancement or radar tomography. Further potentials arises from digital beamforming on receive, which allows to gather additional information about the direction of the scattered radar echoes. This directional information can be used to suppress interferences, to improve geometric and radiometric resolution, or to increase the unambiguous swath width. Furthermore, a coherent combination of multiple receiver signals will allow for a suppression of azimuth ambiguities. For this, a reconstruction algorithm is derived, which enables a recovery of the unambiguous Doppler spectrum also in case of non-optimum receiver aperture displacements leading to a non-uniform sampling of the SAR signal. This algorithm has also a great potential for systems relying on the displaced phase center (DPC) technique, like the high resolution wide swath (HRWS) SAR or the split antenna approach in the TerraSAR-X and Radarsat II satellites
Development of aptamer nanoparticles for treatment of retinal diseases
At more advanced states, retinal diseases such as diabetic retinopathy, age-related macular
degeneration, and retinal vessel occlusions are characterized by neovascularization, which
is usually triggered by a hypoxia episode leading to the overexpression of vascular
endothelial growth factor (VEGF) and nucleolin (NCL). The treatments available are mainly
corticosteroids or/and antibodies against some angiogenic molecules. Regarding the low
efficacy of these therapies and their side effects, aptamers are an emerging tool that can
target these proteins with high specificity, such as antibodies. Furthermore, aptamers are
easier to synthesize and present higher stability and lower immunogenicity.
AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences which can adopt
G-quadruplex (G4) structure and target NCL, a protein that can act as a co-receptor for
several growth factors. Hence, this study aimed to characterize the AT11-L0 structure and
its interaction with several ligands (stabilizing molecules or drugs) for NCL targeting. The
AT11-L0-drug/molecule complex was then incorporated in a nanoparticle to increase the
bioavailability of the aptamer-based drug in the formulation.
To achieve these objectives, we have performed biophysical studies, such as nuclear
magnetic resonance, circular dichroism, and fluorescence experiments. Following
biophysical characterization studies, we synthesised gold nanoparticles and liposomes
containing AT11-L0 aptamer-drug complex. Finally, liposomes and the encapsulated drugs
were tested on Human umbilical vein endothelial cells (HUVEC) model to assess their
antiangiogenic capacity.
The results showed that AT11-L0 aptamer-drug complex has a high stability with melting
temperatures reaching 45 ÂşC to 60 ÂşC allowing an efficient targeting of NCL with a KD in
the order of micromolar. HUVEC antiangiogenic assay showed that, although liposomes did
not promote an increase in the antiangiogenic effect of the tested drugs, C8 showed an
antiangiogenic effect that was not previously described, at lower concentration. This result
can be a basis for the development of a new therapeutic approach using C8 and G4 aptamers
targeting NCL.Em estágios mais avançados, as doenças da retina como a retinopatia diabética,
degeneração macular associada à idade e oclusões da retina são caracterizadas por
neovascularização, que pode ser desencadeada por um episódio de hipoxia que envolve a
sobre expressĂŁo do fator de crescimento endotelial vascular (VEGF) e da nucleolina (NCL).
Os tratamentos disponĂveis sĂŁo principalmente corticosteroides e/ou anticorpos especĂficos
para algumas moléculas angiogénicas. Para ultrapassar a baixa eficácia destas terapias e os
seus efeitos secundários, os aptameros surgiram como uma ferramenta emergente que, de
modo semelhante aos anticorpos, visam estas proteĂnas com elevada especificidade. AlĂ©m
disso, os aptameros são mais fáceis de sintetizar e apresentam maior estabilidade e menor
imunogenicidade.
O AT11-L0 Ă© um derivado do aptamero AS1411, composto por sequĂŞncias ricas em G, que
pode adotar estruturas em G-quadruplex e reconhecer a NCL, uma proteĂna que pode atuar
como coreceptora de vários fatores de crescimento. Assim, este estudo visou caracterizar a
estrutura do AT11-L0 e a sua interação com vários ligandos (moléculas estabilizadoras ou
fármacos), para ligar de modo especĂfico Ă NCL. Este complexo foi posteriormente
incorporado num nanossistema, para aumentar a biodisponibilidade do fármaco e do
aptamero usados na formulação.
Para alcançar estes objetivos, foram realizados estudos biofĂsicos, tais como ressonância
magnĂ©tica nuclear, dicroĂsmo circular e experiĂŞncias de fluorescĂŞncia. ApĂłs estudos de
caracterização biofĂsica, foram sintetizadas nanopartĂculas de ouro e lipossomas contendo
o complexo aptamero-fármaco. Finalmente, os lipossomas e os fármacos foram testados
num modelo de células endoteliais de veia umbilical humana (HUVEC) para analisar a sua
capacidade antiangiogénica.
Os resultados mostraram que os complexos aptamero-fármaco têm uma elevada
estabilidade térmica, com temperaturas de fusão que atingem 45 ºC a 60 ºC, permitindo
uma interação com a NCL com um KD na ordem dos micromolares. O ensaio
antiangiogénico mostrou que, embora os lipossomas não promovam um aumento do efeito
dos fármacos testados, o C8 apresentou um efeito antiangiogénico que nunca foi descrito,
mesmo quando usado em baixa concentração. Este resultado pode permitir uma nova
abordagem utilizando o C8 associado a aptameros de G4 que visem a NCL
Molecular phylogeny: pitfalls and progress
Molecular phylogeny based on nucleotide or amino acid sequence comparison has become a widespread tool for general taxonomy and evolutionary analyses. It seems the only means to establish a natural classification of microorganisms, since their phenotypic traits are not always consistent with genealogy. After an optimistic period during which comprehensive microbial evolutionary pictures appeared, the discovery of several pitfalls affecting molecular phylogenetic reconstruction challenged the general validity of this approach. In addition to biological factors, such as horizontal gene transfer, some methodological problems may produce misleading phylogenies. They are essentially (i) loss of phylogenetic signal by the accumulation of overlapping mutations, (ii) incongruity between the real evolutionary process and the assumed models of sequence evolution, and (iii) differences of evolutionary rates among species or among positions within a sequence. Here, we discuss these problems and some strategies proposed to overcome their effects
Being a choice architect in project management: the Galp energy example
In a world where managing projects is a difficult task that requires several skills to succeed, several authors studied ways to prevent a project from deviation of its desired final outcome.
This works intends to study the Choice Architecture tools presented in the book ―Nudge‖, through the development of an internal project at GALP energy, to present some key points to assess before its development, related with the need to manage the environment in which the stakeholders will work on the project. The main idea consists in preventing some behaviors and decisions that could lead the project development away from a desired outcome. Managing that environment where the choices are made is known as being a Choice Architect.
To begin, this work will focus in knowing the company GALP energy, and where specifically the project progress.
Once the global environment understood, the main project objective is unveiled, explaining the problem to be solved, the research done to solve it and how can the choice architecture be applied.
Afterward, a specific study is presented on the way the choice architecture contributed for the final solution, justifying the importance on knowing how the brain work, and how the decision biases and heuristics can contribute for the choice architecture successful influence on the elaboration and protection of a project desired solution.
To conclude, the project final result and the experience obtained from this work are explained justifying the reason that made this project to be considered a success by several persons. The reason of success is given in the end by the key clients and persons involved in the process
As reportagens futebolĂsticas e os ideais salazaristas. Representações da imprensa diária portuense na Ă©poca de conquistas internacionais (1960-1966)
Electronic structure and transport properties of atomic NiO spinvalves
Ab-initio quantum transport calculations show that short NiO chains suspended
in Ni nanocontacts present a very strong spin-polarization of the conductance.
The generalized gradient approximation we use here predicts a similiar
polarization of the conductance as the one previously computed with non-local
exchange, confirming the robustness of the result. Their use as nanoscopic
spinvalves is proposed.Comment: 2 pages, 1 figure; accepted in JMMM (Proceedings of ICM'06, Kyoto
Giant viruses, giant chimeras: The multiple evolutionary histories of Mimivirus genes
<p>Abstract</p> <p>Background</p> <p>Although capable to evolve, viruses are generally considered non-living entities because they are acellular and devoid of metabolism. However, the recent publication of the genome sequence of the Mimivirus, a giant virus that parasitises amoebas, strengthened the idea that viruses should be included in the tree of life. In fact, the first phylogenetic analyses of a few Mimivirus genes that are also present in cellular lineages suggested that it could define an independent branch in the tree of life in addition to the three domains, Bacteria, Archaea and Eucarya.</p> <p>Results</p> <p>We tested this hypothesis by carrying out detailed phylogenetic analyses for all the conserved Mimivirus genes that have homologues in cellular organisms. We found no evidence supporting Mimivirus as a new branch in the tree of life. On the contrary, our phylogenetic trees strongly suggest that Mimivirus acquired most of these genes by horizontal gene transfer (HGT) either from its amoebal hosts or from bacteria that parasitise the same hosts. The detection of HGT events involving different eukaryotic donors suggests that the spectrum of hosts of Mimivirus may be larger than currently known.</p> <p>Conclusion</p> <p>The large number of genes acquired by Mimivirus from eukaryotic and bacterial sources suggests that HGT has been an important process in the evolution of its genome and the adaptation to parasitism.</p
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