Numerical 3D modeling of heat transfer in human tissues for microwave radiometry monitoring of Brown fat metabolismo

Background: Brown adipose tissue (BAT) plays an important role in whole body metabolism and could potentially mediate weight gain and insulin sensitivity. Although some imaging techniques allow BAT detection, there are currently no viable methods for continuous acquisition of BAT energy expenditure. We present a non-invasive technique for long term monitoring of BAT metabolism using microwave radiometry. Methods: A multilayer 3D computational model was created in HFSS™ with 1.5 mm skin, 3-10 mm subcutaneous fat, 200 mm muscle and a BAT region (2-6 cm3) located between fat and muscle. Based on this model, a log-spiral antenna was designed and optimized to maximize reception of thermal emissions from the target (BAT). The power absorption patterns calculated in HFSS™ were combined with simulated thermal distributions computed in COMSOL® to predict radiometric signal measured from an ultra-low-noise microwave radiometer. The power received by the antenna was characterized as a function of different levels of BAT metabolism under cold and noradrenergic stimulation. Results: The optimized frequency band was 1.5-2.2 GHz, with averaged antenna efficiency of 19%. The simulated power received by the radiometric antenna increased 2-9 mdBm (noradrenergic stimulus) and 4-15 mdBm (cold stimulus) corresponding to increased 15-fold BAT metabolism. Conclusions: Results demonstrated the ability to detect thermal radiation from small volumes (2-6 cm3) of BAT located up to 12 mm deep and to monitor small changes (0.5°C) in BAT metabolism. As such, the developed miniature radiometric antenna sensor appears suitable for non-invasive long term monitoring of BAT metabolism.

Spectroscopic Studies and Characterization of a Novel Electron-Transfer Chain

A novel two-component enzyme system from Escherichia coli involving a flavorubredoxin (FlRd) and its reductase was studied in terms of spectroscopic, redox, and biochemical properties of its constituents. FlRd contains one FMN and one rubredoxin (Rd) center per monomer. To assess the role of the Rd domain, FlRd and a truncated form lacking the Rd domain (FlRd¢Rd), were characterized. FlRd contains 2.9 ( 0.5 iron atoms/subunit, whereas FlRd¢Rd contains 2.1 ( 0.6 iron atoms/subunit. While for FlRd one iron atom corresponds to the Rd center, the other two irons, also present in FlRd¢Rd, are most probably due to a di-iron site. Redox titrations of FlRd using EPR and visible spectroscopies allowed us to determine that the Rd site has a reduction potential of -140 ( 15 mV, whereas the FMN undergoes reduction via a red-semiquinone, at -140 ( 15 mV (Flox/Flsq) and -180 ( 15 mV (Flsq/Flred), at pH 7.6. The Rd site has the lowest potential ever reported for a Rd center, which may be correlated with specific amino acid substitutions close to both cysteine clusters. The gene adjacent to that encoding FlRd was found to code for an FAD-containing protein, (flavo)rubredoxin reductase (FlRd-reductase), which is capable of mediating electron transfer from NADH to DesulfoVibrio gigas Rd as well as to E. coli FlRd. Furthermore, electron donation was found to proceed through the Rd domain of FlRd as the Rd-truncated protein does not react with FlRd-reductase. In vitro, this pathway links NADH oxidation with dioxygen reduction. The possible function of this chain is discussed considering the presence of FlRd homologues in all known genomes of anaerobes and facultative aerobes.

Lighting conditions and optical filters effects on visual performance of speleologists exposed to cave environments

The aim of this study is to evaluate lighting conditions and speleologists’ visual performance using optical filters when exposed to the lighting conditions of cave environments. A crosssectional study was conducted. Twenty-three speleologists were submitted to an evaluation of visual function in a clinical lab. An examination of visual acuity, contrast sensitivity, stereoacuity and flashlight illuminance levels was also performed in 16 of the 23 speleologists at two caves deprived of natural lightning. Two organic filters (450 nm and 550 nm) were used to compare visual function with and without filters. The mean age of the speleologists was 40.65 (± 10.93) years. We detected 26.1% participants with visual impairment of which refractive error (17.4%) was the major cause. In the cave environment the majority of the speleologists used a head flashlight with a mean illuminance of 451.0 ± 305.7 lux. Binocular visual acuity (BVA) was -0.05 ± 0.15 LogMAR (20/18). BVA for distance without filter was not statistically different from BVA with 550 nm or 450 nm filters (p = 0.093). Significant improved contrast sensitivity was observed with 450 nm filters for 6 cpd (p = 0.034) and 18 cpd (p = 0.026) spatial frequencies. There were no signs and symptoms of visual pathologies related to cave exposure. Illuminance levels were adequate to the majority of the activities performed. The enhancement in contrast sensitivity with filters could potentially improve tasks related with the activities performed in the cave.

Aryleneethynylene Trimers Bearing Calix[4]arenes: synthesis, optical properties and self-assembling studies

New homoditopic bis-calix[4]arene-carbazole conjugates, armed with hydrophilic carboxylic acid functions at their lower rims, are disclosed. Evidence for their self-association in solution was gathered from solvatochromic and thermochromic studies, as well as from gel-permeation chromatography analysis. Their ability to function as highly sensitive sensors toward polar electron-deficient aromatic compounds is demonstrated.

Defective protein folding and function in metabolic disorders: studies on the mitochondrial flavoenzyme ETF

Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

The characteristic time of glucose diffusion measured for muscle tissue at optical clearing

The study of agent diffusion in biological tissues is very important to understand and characterize the optical clearing effects and mechanisms involved: tissue dehydration and refractive index matching. From measurements made to study the optical clearing, it is obvious that light scattering is reduced and that the optical properties of the tissue are controlled in the process. On the other hand, optical measurements do not allow direct determination of the diffusion properties of the agent in the tissue and some calculations are necessary to estimate those properties. This fact is imposed by the occurrence of two fluxes at optical clearing: water typically directed out of and agent directed into the tissue. When the water content in the immersion solution is approximately the same as the free water content of the tissue, a balance is established for water and the agent flux dominates. To prove this concept experimentally, we have measured the collimated transmittance of skeletal muscle samples under treatment with aqueous solutions containing different concentrations of glucose. After estimating the mean diffusion time values for each of the treatments we have represented those values as a function of glucose concentration in solution. Such a representation presents a maximum diffusion time for a water content in solution equal to the tissue free water content. Such a maximum represents the real diffusion time of glucose in the muscle and with this value we could calculate the corresponding diffusion coefficient.

Three transducers for one photodetector: essays for optical communications

Dissertation presented to obtain the PhD degree in Electrical and Computer Engineering - Electronics

Structural and functional studies of PpcA: a key protein in the electron transfer pathways of Geobacter sulfurreducens

Dissertação para obtenção do Grau de Doutor em Bioquímica, ramo de Biotecnologia

Active magneto-optical control of spontaneous emission in graphene

We investigate the spontaneous emission rate of a two-level quantum emitter near a graphene-coated substrate under the influence of an external magnetic field or strain induced pseudo-magnetic field. We demonstrate that the application of the magnetic field can substantially increase or decrease the decay rate. We show that a suppression as large as 99$\%$ in the Purcell factor is achieved even for moderate magnetic fields. The emitter's lifetime is a discontinuous function of $|{\bf B}|$, which is a direct consequence of the occurrence of discrete Landau levels in graphene. We demonstrate that, in the near-field regime, the magnetic field enables an unprecedented control of the decay pathways into which the photon/polariton can be emitted. Our findings strongly suggest that a magnetic field could act as an efficient agent for on-demand, active control of light-matter interactions in graphene at the quantum level.

Electronic structure and optical signatures of semiconducting transition metal dichalcogenide nanosheets

CONSPECTUS: Two-dimensional (2D) crystals derived from transition metal dichalcogenides (TMDs) are intriguing materials that offer a unique platform to study fundamental physical phenomena as well as to explore development of novel devices. Semiconducting group 6 TMDs such as MoS2 and WSe2 are known for their large optical absorption coefficient and their potential for high efficiency photovoltaics and photodetectors. Monolayer sheets of these compounds are flexible, stretchable, and soft semiconductors with a direct band gap in contrast to their well-known bulk crystals that are rigid and hard indirect gap semiconductors. Recent intense research has been motivated by the distinct electrical, optical, and mechanical properties of these TMD crystals in the ultimate thickness regime. As a semiconductor with a band gap in the visible to near-IR frequencies, these 2D MX2 materials (M = Mo, W; X = S, Se) exhibit distinct excitonic absorption and emission features. In this Account, we discuss how optical spectroscopy of these materials allows investigation of their electronic properties and the relaxation dynamics of excitons. We first discuss the basic electronic structure of 2D TMDs highlighting the key features of the dispersion relation. With the help of theoretical calculations, we further discuss how photoluminescence energy of direct and indirect excitons provide a guide to understanding the evolution of the electronic structure as a function of the number of layers. We also highlight the behavior of the two competing conduction valleys and their role in the optical processes. Intercalation of group 6 TMDs by alkali metals results in the structural phase transformation with corresponding semiconductor-to-metal transition. Monolayer TMDs obtained by intercalation-assisted exfoliation retains the metastable metallic phase. Mild annealing, however, destabilizes the metastable phase and gradually restores the original semiconducting phase. Interestingly, the semiconducting 2H phase, metallic 1T phase, and a charge-density-wave-like 1T' phase can coexist within a single crystalline monolayer sheet. We further discuss the electronic properties of the restacked films of chemically exfoliated MoS2. Finally, we focus on the strong optical absorption and related exciton relaxation in monolayer and bilayer MX2. Monolayer MX2 absorbs as much as 30% of incident photons in the blue region of the visible light despite being atomically thin. This giant absorption is attributed to nesting of the conduction and valence bands, which leads to diversion of optical conductivity. We describe how the relaxation pathway of excitons depends strongly on the excitation energy. Excitation at the band nesting region is of unique significance because it leads to relaxation of electrons and holes with opposite momentum and spontaneous formation of indirect excitons.

Goblet cell density association with tear function and ocular surface physiology

Purpose: To determine the relationship of goblet cell density (GCD) with tear function and ocular surface physiology. Methods: This was a cross-sectional study conducted in 35 asymptomatic subjects with mean age 23.8±3.6 years. Tear film assessment, conjunctiva and cornea examination were done in each subject. Conjunctival impression cytology was performed by applying Nitrocellulose Millipore MFTM-Membrane filter over the superior bulbar conjunctiva. The filter paper was than fixed with 96% ethanol and stained with Periodic Acid Schiff, Hematoxylin and Eosin. GCD was determined by optical microscopy. Relation between GCD and Schirmer score, tear break-up time (TBUT), bulbar redness, limbal redness and corneal staining was determined. Results: The mean GCD was 151±122 cells/mm2. GCD was found higher in eyes with higher Schirmer score but it was not significant (p = 0.75). There was a significant relationship ofGCDwith TBUT (p = 0.042). GCD was not correlated with bulbar redness (p = 0.126), and limbal redness (p = 0.054) as well as corneal staining (p = 0.079). No relationship of GCD with age and gender of the subjects (p > 0.05) was observed. Conclusion: GCD was found correlated with TBUT but no significant correlation was found with the aqueous portion of the tear, limbal as well as bulbar redness and corneal staining.

Oxygen mass transfer impact on citric acid production by Yarrowia lipolytica from crude glycerol

Production of citric acid from crude glycerol from biodiesel industry, in batch cultures of Yarrowia lipolytica W29 was performed in a lab-scale stirred tank bioreactor in order to assess the effect of oxygen mass transfer rate in this bioprocess. An empirical correlation was proposed to describe oxygen volumetric mass transfer coefficient (kLa) as a function of operating conditions (stirring speed and specific air flow rate) and cellular density. kLa increased according with a power function with specific power input and superficial gas velocity, and slightly decreased with cellular density. The increase of initial kLa from 7 h-1 to 55 h-1 led to 7.8-fold increase of citric acid final concentration. Experiments were also performed at controlled dissolved oxygen (DO) and citric acid concentration increased with DO up to 60% of saturation. Thus, due to the simpler operation setting an optimal kLa than at controlled DO, it can be concluded that kLa is an adequate parameter for the optimization of citric acid production from crude glycerol by Y. lipolytica and to be considered in bioprocess scale-up. Our empirical correlation, considering the operating conditions and cellular density, will be a valid tool for this purpose.

Connexin-36 contributes to control function of insulin-producing cells.

Connexin-36 (Cx36) is a gap junction protein expressed by the insulin-producing beta-cells. We investigated the contribution of this protein in normal beta-cell function by using a viral gene transfer approach to alter Cx36 content in the insulin-producing line of INS-1E cells and rat pancreatic islets. Transcripts for Cx43, Cx45, and Cx36 were detected by reverse transcriptase-PCR in freshly isolated pancreatic islets, whereas only a transcript for Cx36 was detected in INS-1E cells. After infection with a sense viral vector, which induced de novo Cx36 expression in the Cx-defective HeLa cells we used to control the transgene expression, Western blot, immunofluorescence, and freeze-fracture analysis showed a large increase of Cx36 within INS-1E cell membranes. In contrast, after infection with an antisense vector, Cx36 content was decreased by 80%. Glucose-induced insulin release and insulin content were decreased, whether infected INS-1E cells expressed Cx36 levels that were largely higher or lower than those observed in wild-type control cells. In both cases, basal insulin secretion was unaffected. Comparable observations on basal secretion and insulin content were made in freshly isolated rat pancreatic islets. The data indicate that large changes in Cx36 alter insulin content and, at least in INS-1E cells, also affect glucose-induced insulin release.

Food availability affects the maternal transfer of androgens and antibodies into eggs of a colonial seabird.

Mothers can improve the quality of their offspring by increasing the level of certain components in their eggs. To examine whether or not mothers increase deposition of such components in eggs as a function of food availability, we food-supplemented black-legged kittiwake females (Rissa tridactyla) before and during egg laying and compared deposition of androgens and antibodies into eggs of first and experimentally induced replacement clutches. Food-supplemented females transferred lower amounts of androgens and antibodies into eggs of induced replacement clutches than did non-food-supplemented mothers, whereas first clutches presented no differences between treatments. Our results suggest that when females are in lower condition, they transfer more androgens and antibodies into eggs to facilitate chick development despite potential long-term costs for juveniles. Females in prime condition may avoid these potential long-term costs because they can provide their chicks with more and higher quality resources.