Modelagem molecular na caracterização eletrônica de oligopeptídeos e na descrição quântica da interação fármaco-receptor

In this dissertation, the theoretical principles governing the molecular modeling were applied for electronic characterization of oligopeptide α3 and its variants (5Q, 7Q)-α3, as well as in the quantum description of the interaction of the aminoglycoside hygromycin B and the 30S subunit of bacterial ribosome. In the first study, the linear and neutral dipeptides which make up the mentioned oligopeptides were modeled and then optimized for a structure of lower potential energy and appropriate dihedral angles. In this case, three subsequent geometric optimization processes, based on classical Newtonian theory, the semi-empirical and density functional theory (DFT), explore the energy landscape of each dipeptide during the search of ideal minimum energy structures. Finally, great conformers were described about its electrostatic potential, ionization energy (amino acids), and frontier molecular orbitals and hopping term. From the hopping terms described in this study, it was possible in subsequent studies to characterize the charge transport propertie of these peptides models. It envisioned a new biosensor technology capable of diagnosing amyloid diseases, related to an accumulation of misshapen proteins, based on the conductivity displayed by proteins of the patient. In a second step of this dissertation, a study carried out by quantum molecular modeling of the interaction energy of an antibiotic ribosomal aminoglicosídico on your receiver. It is known that the hygromycin B (hygB) is an aminoglycoside antibiotic that affects ribosomal translocation by direct interaction with the small subunit of the bacterial ribosome (30S), specifically with nucleotides in helix 44 of the 16S ribosomal RNA (16S rRNA). Due to strong electrostatic character of this connection, it was proposed an energetic investigation of the binding mechanism of this complex using different values of dielectric constants (ε = 0, 4, 10, 20 and 40), which have been widely used to study the electrostatic properties of biomolecules. For this, increasing radii centered on the hygB centroid were measured from the 30S-hygB crystal structure (1HNZ.pdb), and only the individual interaction energy of each enclosed nucleotide was determined for quantum calculations using molecular fractionation with conjugate caps (MFCC) strategy. It was noticed that the dielectric constants underestimated the energies of individual interactions, allowing the convergence state is achieved quickly. But only for ε = 40, the total binding energy of drug-receptor interaction is stabilized at r = 18A, which provided an appropriate binding pocket because it encompassed the main residues that interact more strongly with the hygB - C1403, C1404, G1405, A1493, G1494, U1495, U1498 and C1496. Thus, the dielectric constant ≈ 40 is ideal for the treatment of systems with many electrical charges. By comparing the individual binding energies of 16S rRNA nucleotides with the experimental tests that determine the minimum inhibitory concentration (MIC) of hygB, it is believed that those residues with high binding values generated bacterial resistance to the drug when mutated. With the same reasoning, since those with low interaction energy do not influence effectively the affinity of the hygB in its binding site, there is no loss of effectiveness if they were replaced.

Polimorfismos de nucleotídeo único (SNPS) dos genes PPARy2, lipase lipoproteica, receptor de LDL, apolipoproteina C3, e adiponectina podem modular o perfil lipídico de pacientes com a síndrome de Berardinelli-Seip

A Síndrome de Berardinelli-Seip (SBS) é um distúrbio raro do metabolismo dos lipídios, caracterizada pela ausência quase total de tecido adiposo subcutâneo, hipertrigliceridemia, hipoleptinemia e diabetes insulino resistente ou lipoatrófico. Sua etiologia envolve implicações hipotalâmicas, alterações nos receptores de insulina e mutações nos genes AGPAT2, Gng3lg, CAV1 e PTRF. O tecido adiposo secreta diversas substâncias, tais como: leptina, resistina, adiponectina, esteróides, TNF , IL-6, PAI-1, angiotensinogênio, IGF-1. Muitas delas estão associadas ao diabetes mellitus tipo 2, obesidade e hipertensão. Os PPARs são fatores transcricionais pertencentes à superfamília de receptores nucleares ligantes ativados. Sabe-se que o PPAR , é importante para o metabolismo lipídico e glicídico e que o ligante natural do PPAR é derivado do ácido graxo. Nesse sentido, foram avaliados 24 pacientes portadores da SBS, provenientes do Estado do Rio Grande do Norte, com a mediana das idades de 18,5 anos (0,55 a 47 a), sendo 9 (37,5 %) do gênero masculino e 15 (62,5 %) do gênero feminino. Quanto ao grupo étnico, foram classificados em caucasóides (brancos) 21 (87,5 %) e negróides 3 (12,5 %) pacientes. Foram feitas avaliações clínico-endocrinológica, bioquímica, hormonal, molecular e o estudo dos polimorfismos Adiponectina ADIPOQ, PPARγ2 Pro12Ala, LPL-PvuII, APOC3-SstI e LDLR-AvaII em portadores da SBS. Nesta população nós não encontramos nenhuma associação de parâmetros lipídicos e glicídicos com os polimorfismos LPL-PvuII, APOC3-SstI e LDLR-AvaII. Porém, observamos associação entre Adiponectina ADIPOQ e PPARγ2 Pro12Ala e níveis lipídicos mais elevados, sugerindo um papel biológico para estes fatores, indicando estudos mais aprofundados

Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1

Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM

VCO Banda Larga Integrado para Receptor a Cinco Portas

This work presents an wideband ring VCO for cognitive radio five-port based receivers. A three-stage differential topology using transmission gate was adopted in order to maintain wide and linear tuning range and a low phase-noise. Monte-Carlo analysis were performed for phase-shift response of individual stages, which is an important figure of merit in five-port works. It was observed a fairly linear correlation between control voltage and oscillation frequency in the range between 200 MHz and 1800 MHz. The VCO was preliminarily designed for IBM 130nm CMOS technology

Construção e validação de um receptor GPS para uso espacial

Global Positioning System, or simply GPS, it is a radionavigation system developed by United States for military applications, but it becames very useful for civilian using. In the last decades Brazil has developed sounding rockets and today many projects to build micro and nanosatellites has appeared. This kind of vehicles named spacecrafts or high dynamic vehicles, can use GPS for its autonome location and trajectories controls. Despite of a huge number of GPS receivers available for civilian applications, they cannot used in high dynamic vehicles due environmental issues (vibrations, temperatures, etc.) or imposed dynamic working limits. Only a few nations have the technology to build GPS receivers for spacecrafts or high dynamic vehicles is available and they imposes rules who difficult the access to this receivers. This project intends to build a GPS receiver, to install them in a payload of a sounding rocket and data collecting to verify its correct operation when at the flight conditions. The inner software to this receiver was available in source code and it was tested in a software development platform named GPS Architect. Many organizations cooperated to support this project: AEB, UFRN, IAE, INPE e CLBI. After many phases: defining working conditions, choice and searching electronic, the making of the printed boards, assembling and assembling tests; the receiver was installed in a VS30 sounding rocket launched at Centro de Lançamento da Barreira do Inferno in Natal/RN. Despite of the fact the locations data from the receiver were collected only the first 70 seconds of flight, this data confirms the correct operation of the receiver by the comparison between its positioning data and the the trajectory data from CLBI s tracking radar named ADOUR

Desenvolvimento e testes de software de um receptor de GPS para uso espacial

Spacecraft move with high speeds and suffer abrupt changes in acceleration. So, an onboard GPS receiver could calculate navigation solutions if the Doppler effect is taken into consideration during the satellite signals acquisition and tracking. Thus, for the receiver subject to such dynamic cope these shifts in the frequency signal, resulting from this effect, it is imperative to adjust its acquisition bandwidth and increase its tracking loop to a higher order. This paper presents the changes in the GPS Orion s software, an open architecture receiver produced by GEC Plessey Semiconductors, nowadays Zarlink, in order to make it able to generate navigation fix for vehicle under high dynamics, especially Low Earth Orbit satellites. GPS Architect development system, sold by the same company, supported the modifications. Furthermore, it presents GPS Monitor Aerospace s characteristics, a computational tool developed for monitoring navigation fix calculated by the GPS receiver, through graphics. Although it was not possible to simulate the software modifications implemented in the receiver in high dynamics, it was observed that the receiver worked in stationary tests, verified also in the new interface. This work also presents the results of GPS Receiver for Aerospace Applications experiment, achieved with the receiver s participation in a suborbital mission, Operation Maracati 2, in December 2010, using a digital second order carrier tracking loop. Despite an incident moments before the launch have hindered the effective navigation of the receiver, it was observed that the experiment worked properly, acquiring new satellites and tracking them during the VSB-30 rocket flight.

Limonologia e qualidade ambiental de um corpo lêntico receptor de efluentes tratados da indústria de petróleo

Environmental pollution has become a subject of public interest throughout the world. Not only have developed countries been affected by environmental problems but also the developing nations have started to suffer from the serious impacts of pollution. Within this context it is necessary to collect simplified environmental data to assist in the management of water resources by the appropriate authorities. These data are obtained through an environmental index that allows a space-time comparison of points distributed in the same aquatic body, or between different water bodies, for physico-chemical and bacteriological parameters. The aim of this present study was to determine the environmental status of the Lagoa de Baixo at Guamaré/RN, where a production unit of PETROBRAS RN/CE is located. For this purpose the Water Quality Index (WQI) was used in both an add and multiply form, the Trophic State Index (TSI) and the Environmental Quality Quotient (EQQ), as well as determining the concentrations of metals. The average values obtained for the WQI, in its two forms were 68,67 and 62,76 respectively which were inside the good qualification. According to the TSI the lagoon showed characteristics of a middle trophic state, and an impact level of regular as determined by the EQQ