Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135

Uma reflexão sobre a vitalidade urbana das praças de Natal/RN

Squares are urban public open spaces whose use combines a number of elements that can provide their vitality, some of which can be enhanced through strategic projects. Given this general framework, the starting question which triggered this thesis: Would the elements that the literature indicate influence the vitality of the squares be perceived by their users? The hypothesis put forward was that users give priority to elements directly involved in the appropriation of space, especially the furniture and existing equipment, levels of shade and security. The focus of empirical research were public squares located in the city of Natal-RN, with the aim to identify elements that contribute to the vitality of the public squares in the city, through the relationship between spatial morphology and environmental awareness. The methodology adopted was a Case Study conducted by multimethod, using the following procedures: morphological analysis based on literature and information at three levels (radius of influence, 500m; immediate surroundings; environment itself); systematic observation (behavioral mapping centred in the location); and semi-structured interviews with users. The results showed that the public spaces more integrated in the urban areas have greater potential for use, however, its effective use depends on the perception of individuals, so that its vitality is mainly due to items identified by users as central to their continued presence in the environment because they directly affect their wellbeing and the image of the location. So some elements, notably furniture and urban equipment, are more easily detected than others, revealing that they are essential to the perception of users, so that their presence, quality and location appeared to have greater impact on use. In addition, the amount of shade and security showed as items that ensure that individuals experience public spaces more often, since the (likely) users are aware of the conservation actions or abandonment that take place on these sites, revealing itself to be potentially involved in the rescue of these spaces. Overall, the general hypothesis is only partially proven because in many situations, the vitality of squares appeared not only to be related to the elements investigated, but also additional aspects - environmental, nature, economic, social and cultural - which should also be studied.

Cruise Speed Reduction for Ground Delay Programs: A Case Study for San Francisco International Airport Arrivals

Ground Delay Programs (GDP) are sometimes cancelled before their initial planned duration and for this reason aircraft are delayed when it is no longer needed. Recovering this delay usually leads to extra fuel consumption, since the aircraft will typically depart after having absorbed on ground their assigned delay and, therefore, they will need to cruise at more fuel consuming speeds. Past research has proposed speed reduction strategy aiming at splitting the GDP-assigned delay between ground and airborne delay, while using the same fuel as in nominal conditions. Being airborne earlier, an aircraft can speed up to nominal cruise speed and recover part of the GDP delay without incurring extra fuel consumption if the GDP is cancelled earlier than planned. In this paper, all GDP initiatives that occurred in San Francisco International Airport during 2006 are studied and characterised by a K-means algorithm into three different clusters. The centroids for these three clusters have been used to simulate three different GDPs at the airport by using a realistic set of inbound traffic and the Future Air Traffic Management Concepts Evaluation Tool (FACET). The amount of delay that can be recovered using this cruise speed reduction technique, as a function of the GDP cancellation time, has been computed and compared with the delay recovered with the current concept of operations. Simulations have been conducted in calm wind situation and without considering a radius of exemption. Results indicate that when aircraft depart early and fly at the slower speed they can recover additional delays, compared to current operations where all delays are absorbed prior to take-off, in the event the GDP cancels early. There is a variability of extra delay recovered, being more significant, in relative terms, for those GDPs with a relatively low amount of demand exceeding the airport capacity.

The Kepler-454 system: a small, not-rocky inner planet, a Jovian world, and a distant companion

Kepler-454 (KOI-273) is a relatively bright (V = 11.69 mag), Sun-like star that hosts a transiting planet candidate in a 10.6 day orbit. From spectroscopy, we estimate the stellar temperature to be 5687 ± 50 K, its metallicity to be [m/H] = 0.32 ± 0.08, and the projected rotational velocity to be v sin i <2.4 km s^-1. We combine these values with a study of the asteroseismic frequencies from short cadence Kepler data to estimate the stellar mass to be , the radius to be 1.066 ± 0.012 R_o, and the age to be Gyr. We estimate the radius of the 10.6 day planet as 2.37 ± 0.13 R_⊕. Using 63 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 36 observations made with the HIRES spectrograph at the Keck Observatory, we measure the mass of this planet to be 6.8 ± 1.4 M_⊕. We also detect two additional non-transiting companions, a planet with a minimum mass of 4.46 ± 0.12 M_J in a nearly circular 524 day orbit and a massive companion with a period >10 years and mass >12.1 M_J. The 12 exoplanets with radii ⊕ and precise mass measurements appear to fall into two populations, with those ⊕ following an Earth-like composition curve and larger planets requiring a significant fraction of volatiles. With a density of 2.76 ± 0.73 g cm^-3, Kepler-454b lies near the mass transition between these two populations and requires the presence of volatiles and/or H/He gas.

Electrolytes for ceramic oxide fuel cells

The main objective of this dissertation is the development and processing of novel ionic conducting ceramic materials for use as electrolytes in proton or oxide-ion conducting solid oxide fuel cells. The research aims to develop new processing routes and/or materials offering superior electrochemical behavior, based on nanometric ceramic oxide powders prepared by mechanochemical processes. Protonic ceramic fuel cells (PCFCs) require electrolyte materials with high proton conductivity at intermediate temperatures, 500-700ºC, such as reported for perovskite zirconate oxides containing alkaline earth metal cations. In the current work, BaZrO3 containing 15 mol% of Y (BZY) was chosen as the base material for further study. Despite offering high bulk proton conductivity the widespread application of this material is limited by its poor sinterability and grain growth. Thus, minor additions of oxides of zinc, phosphorous and boron were studied as possible sintering additives. The introduction of ZnO can produce substantially enhanced densification, compared to the un-doped material, lowering the sintering temperature from 1600ºC to 1300ºC. Thus, the current work discusses the best solid solution mechanism to accommodate this sintering additive. Maximum proton conductivity was shown to be obtained in materials where the Zn additive is intentionally adopted into the base perovskite composition. P2O5 additions were shown to be less effective as a sintering additive. The presence of P2O5 was shown to impair grain growth, despite improving densification of BZY for intermediate concentrations in the range 4 – 8 mol%. Interreaction of BZY with P was also shown to have a highly detrimental effect on its electrical transport properties, decreasing both bulk and grain boundary conductivities. The densification behavior of H3BO3 added BaZrO3 (BZO) shows boron to be a very effective sintering aid. Nonetheless, in the yttrium containing analogue, BaZr0.85Y0.15O3- (BZY) the densification behavior with boron additives was shown to be less successful, yielding impaired levels of densification compared to the plain BZY. This phenomenon was shown to be related to the undesirable formation of barium borate compositions of high melting temperatures. In the last section of the work, the emerging oxide-ion conducting materials, (Ba,Sr)GeO3 doped with K, were studied. Work assessed if these materials could be formed by mechanochemical process and the role of the ionic radius of the alkaline earth metal cation on the crystallographic structure, compositional homogeneity and ionic transport. An abrupt jump in oxide-ion conductivity was shown on increasing operation temperature in both the Sr and Ba analogues.

Estudo da circunferência no ensino médio: sugestões de atividades com a utilização do software geogebra

Esta dissertação propõe sete atividades acerca do estudo da circunferência para alunos do Ensino Médio. A maioria das atividades propostas utilizam o software gratuito de geometria dinâmica GeoGebra como ferramenta de aprendizagem. Programa com diversas vantagens. Além da concepção da geometria dinâmica, a associação entre Geometria e Álgebra, relação enfatizada até no seu nome. As atividades sugeridas abordam os seguintes conteúdos: equações da circunferência (reduzida e geral), análise da equação completa do 2o grau a duas variáveis, método de completar quadrados para reestabelecimento do centro e medida do raio da circunferência, posição relativa entre ponto e circunferência, reta e circunferência e entre duas circunferências. No presente trabalho consta ainda uma análise de alguns livros didáticos para ciência do que está sendo oportunizado ao professor como subsídio para suas aulas. Associamos esta análise também com a argumentação de que o produto deste trabalho é inovador. Mostraremos também a análise das atividades que embasaram a proposta desse trabalho quando aplicadas nas turmas de 3o ano do Instituto Federal do Rio Grande do Sul - Campus Rio Grande, assim como os resultados de uma pesquisa feita sobre os conhecimentos prévios dos alunos sobre geometria do Ensino Fundamental, especificamente relacionados ao círculo.

Iron mineral structure, reactivity, and isotopic composition in a South Pacific Gyre ferromanganese nodule over 4 Ma

Deep-sea ferromanganese nodules accumulate trace elements from seawater and underlying sediment porewaters during the growth of concentric mineral layers over millions of years. These trace elements have the potential to record past ocean geochemical conditions. The goal of this study was to determine whether Fe mineral alteration occurs and how the speciation of trace elements responds to alteration over ∼3.7 Ma of marine ferromanganese nodule (MFN) formation, a timeline constrained by estimates from 9Be/10Be concentrations in the nodule material. We determined Fe-bearing phases and Fe isotope composition in a South Pacific Gyre (SPG) nodule. Specifically, the distribution patterns and speciation of trace element uptake by these Fe phases were investigated. The time interval covered by the growth of our sample of the nodule was derived from 9Be/10Be accelerator mass spectrometry (AMS). The composition and distribution of major and trace elements were mapped at various spatial scales, using micro-X-ray fluorescence (μXRF), electron microprobe analysis (EMPA), and inductively coupled plasma mass spectrometry (ICP-MS). Fe phases were characterized by micro-extended X-ray absorption fine structure (μEXAFS) spectroscopy and micro-X-ray diffraction (μXRD). Speciation of Ti and V, associated with Fe, was measured using micro-X-ray absorption near edge structure (μXANES) spectroscopy. Iron isotope composition (δ56/54Fe) in subsamples of 1-3 mm increments along the radius of the nodule was determined with multiple-collector ICP-MS (MC-ICP-MS). The SPG nodule formed through primarily hydrogeneous inputs at a rate of 4.0 ± 0.4 mm/Ma. The nodule exhibited a high diversity of Fe mineral phases: feroxyhite (δ-FeOOH), goethite (α-FeOOH), lepidocrocite (γ-FeOOH), and poorly ordered ferrihydrite-like phases. These findings provide evidence that Fe oxyhydroxides within the nodule undergo alteration to more stable phases over millions of years. Trace Ti and V were spatially correlated with Fe and found to be adsorbed to Fe-bearing minerals. Ti/Fe and V/Fe ratios, and Ti and V speciation, did not vary along the nodule radius. The δ56/54Fe values, when averaged over sample increments representing 0.25 to 0.75 Ma, were homogeneous within uncertainty along the nodule radius, at -0.12 ± 0.07 ‰ (2sd, n=10). Our results indicate that the Fe isotope composition of the nodule remained constant during nodule growth and that mineral alteration did not affect the primary Fe isotope composition of the nodule. Furthermore, the average δ56/54Fe value of -0.12 ‰ we find is consistent with Fe sourced from continental eolian particles (dust). Despite mineral alteration, the trace element partitioning of Ti and V, and Fe isotope composition, do not appear to change within the sensitivity of our measurements. These findings suggest that Fe oxyhydroxides within hydrogenetic ferromanganese nodules are out of geochemical contact with seawater once they are covered by subsequent concentric mineral layers. Even though Fe-bearing minerals are altered, trace element ratios, speciation and Fe isotope composition are preserved within the nodule.

A doorway to Borromean halo nuclei: the Samba configuration

We exploit the possibility of new configurations in three-body halo nuclei, Samba type (the neutron-core form a bound system) as a doorway to Borromean systems. The nuclei Be-12, B-15, N-23 and F-27 are of such nature, in particular N-23 with a half-life of 37.7 s and a halo radius of 6.07 fm is an excellent example of Samba-halo configuration. The fusion below the barrier of the Samba halo nuclei with heavy targets could reveal the so far elusive enhancement and a dominance of one-neutron over two-neutron transfers, in contrast to what was found recently for the Borromean halo nucleus He-6 + U-238.

Black holes as quantum bound states

We present a new quantum description for the Oppenheimer-Snyder model of gravitational collapse of a ball of dust. Starting from the geodesic equation for dust in spherical symmetry, we introduce a time-independent Schrödinger equation for the radius of the ball. The resulting spectrum is similar to that of the Hydrogen atom and Newtonian gravity. However, the non-linearity of General Relativity implies that the ground state is characterised by a principal quantum number proportional to the square of the ADM mass of the dust. For a ball with ADM mass much larger than the Planck scale, the collapse is therefore expected to end in a macroscopically large core and the singularity predicted by General Relativity is avoided. Mathematical properties of the spectrum are investigated and the ground state is found to have support essentially inside the gravitational radius, which makes it a quantum model for the matter core of Black Holes. In fact, the scaling of the ADM mass with the principal quantum number agrees with the Bekenstein area law and the corpuscular model of Black Holes. Finally, the uncertainty on the size of the ground state is interpreted within the framework of an Uncertainty Principle.

Method for determination of root curvature radius using cone-beam computed tomography images

This article describes and discusses a method to determine root curvature radius by using cone-beam computed tomography (CBCT). The severity of root canal curvature is essential to select instrument and instrumentation technique. The diagnosis and planning of root canal treatment have traditionally been made based on periapical radiography. However, the higher accuracy of CBCT images to identify anatomic and pathologic alterations compared to panoramic and periapical radiographs has been shown to reduce the incidence of false-negative results. In high-resolution images, the measurement of root curvature radius can be obtained by circumcenter. Based on 3 mathematical points determined with the working tools of Planimp® software, it is possible to calculate root curvature radius in both apical and coronal directions. The CBCT-aided method for determination of root curvature radius presented in this article is easy to perform, reproducible and allows a more reliable and predictable endodontic planning, which reflects directly on a more efficacious preparation of curved root canals.

The radius and mass of the close solar twin 18 Scorpii derived from asteroseismology and interferometry

The growing interest in solar twins is motivated by the possibility of comparing them directly to the Sun. To carry on this kind of analysis, we need to know their physical characteristics with precision. Our first objective is to use asteroseismology and interferometry on the brightest of them: 18 Sco. We observed the star during 12 nights with HARPS for seismology and used the PAVO beam-combiner at CHARA for interferometry. An average large frequency separation 134.4+/-0.3 mu Hz and angular and linear radiuses of 0.6759 +/- 0.0062 mas and 1.010 +/- 0.009 R(circle dot) were estimated. We used these values to derive the mass of the star, 1.02 +/- 0.03 M(circle dot).

Self-bound models of compact stars and recent mass-radius measurements

The exact composition of a specific class of compact stars, historically referred to as ""neutron stars,'' is still quite unknown. Possibilities ranging from hadronic to quark degrees of freedom, including self-bound versions of the latter, have been proposed. We specifically address the suitability of strange star models (including pairing interactions) in this work, in the light of new measurements available for four compact stars. The analysis shows that these data might be explained by such an exotic equation of state, actually selecting a small window in parameter space, but still new precise measurements and also further theoretical developments are needed to settle the subject.

Remote sensing the vertical profile of cloud droplet effective radius, thermodynamic phase, and temperature

Cloud-aerosol interaction is a key issue in the climate system, affecting the water cycle, the weather, and the total energy balance including the spatial and temporal distribution of latent heat release. Information on the vertical distribution of cloud droplet microphysics and thermodynamic phase as a function of temperature or height, can be correlated with details of the aerosol field to provide insight on how these particles are affecting cloud properties and their consequences to cloud lifetime, precipitation, water cycle, and general energy balance. Unfortunately, today's experimental methods still lack the observational tools that can characterize the true evolution of the cloud microphysical, spatial and temporal structure in the cloud droplet scale, and then link these characteristics to environmental factors and properties of the cloud condensation nuclei. Here we propose and demonstrate a new experimental approach (the cloud scanner instrument) that provides the microphysical information missed in current experiments and remote sensing options. Cloud scanner measurements can be performed from aircraft, ground, or satellite by scanning the side of the clouds from the base to the top, providing us with the unique opportunity of obtaining snapshots of the cloud droplet microphysical and thermodynamic states as a function of height and brightness temperature in clouds at several development stages. The brightness temperature profile of the cloud side can be directly associated with the thermodynamic phase of the droplets to provide information on the glaciation temperature as a function of different ambient conditions, aerosol concentration, and type. An aircraft prototype of the cloud scanner was built and flew in a field campaign in Brazil. The CLAIM-3D (3-Dimensional Cloud Aerosol Interaction Mission) satellite concept proposed here combines several techniques to simultaneously measure the vertical profile of cloud microphysics, thermodynamic phase, brightness temperature, and aerosol amount and type in the neighborhood of the clouds. The wide wavelength range, and the use of multi-angle polarization measurements proposed for this mission allow us to estimate the availability and characteristics of aerosol particles acting as cloud condensation nuclei, and their effects on the cloud microphysical structure. These results can provide unprecedented details on the response of cloud droplet microphysics to natural and anthropogenic aerosols in the size scale where the interaction really happens.

Treatment of scaphoid nonunion with vascularised and nonvascularised dorsal bone grafting from the distal radius

We conducted a prospective randomised study comparing the clinical, functional and radiographic results of 46 patients treated for scaphoid nonunion using a vascularised bone graft from the dorsal and distal aspect of the radius (group I), relative to 40 patients treated by means of a conventional non-vascularised bone graft from the distal radius (group II). Surgical findings included 30 sclerotic, poorly-vascularised scaphoids in group I versus 20 in group II. Bone fusion was achieved in 89.1% of group I and 72.5% of group II patients (p = 0.024). Functional results were good to excellent in 72.0% of the patients in group I and 57.5% in group II. Considering only patients with sclerotic, poorly-vascularised scaphoids, the mean final outcome scores obtained were 7.5 and 6.0 for groups I and group II, respectively. We conclude that vascularised bone grafting yields superior results and is more efficient when there is a sclerotic, poorly-vascularised proximal pole in patients in scaphoid nonunion.

LOW-INTENSITY ULTRASOUND APPLICATION IN DISTAL RADIUS METAPHYSEAL BONE DEFECTS OF DOGS

We assessed the repair of transverse, 3-mm wide bone gaps created at the distal radius in 28 dogs that were randomly divided into two 14-animal groups; one was the control group and the other received a daily, 20-min application of low-intensity pulsed ultrasound for 100 days. Sequential radiographs, histomorphometrics, bone fluorescent histology and bone vascularity assessments found that all animals from both groups obtained a stage of hypertrophic-type nonunion with fibrocartilage tissue formation throughout the region of osteotomy. However, treated animals exhibited areas of endochondral ossification within the fibrocartilage region. There was no difference in type of vascularity or the newly formed bone process obtained by tetracycline labeling. Application of low-intensity ultrasound was not capable of significantly changing the reparative process and it may not be sufficiently powerful to overcome a combination of local deleterious effects on bone healing, created by gapping, excessive motion and periosteal resection. (E-mail: jbvolpon@fmrp.usp.br) (C) 2010 World Federation for Ultrasound in Medicine & Biology.