A Hydrodynamic Method For Measuring Aqueous Nanoparticle Surface Interactions

The objectives of this research dissertation were to develop and present novel analytical methods for the quantification of surface binding interactions between aqueous nanoparticles and water-soluble organic solutes. Quantification of nanoparticle surface interactions are presented in this work as association constants where the solutes have interacted with the surface of the nanoparticles. By understanding these nanoparticle-solute interactions, in part through association constants, the scientific community will better understand how organic drugs and nanomaterials interact in the environment, as well as to understand their eventual environmental fate. The biological community, pharmaceutical, and consumer product industries also have vested interests in nanoparticle-drug interactions for nanoparticle toxicity research and in using nanomaterials as drug delivery vesicles. The presented novel analytical methods, applied to nanoparticle surface association chemistry, may prove to be useful in assisting the scientific community to understand the risks, benefits, and opportunities of nanoparticles. The development of the analytical methods presented uses a model nanoparticle, Laponite-RD (LRD). LRD was the proposed nanoparticle used to model the system and technique because of its size, 25 nm in diameter. The solutes selected to model for these studies were chosen because they are also environmentally important. Caffeine, oxytetracycline (OTC), and quinine were selected to use as models because of their environmental importance and chemical properties that can be exploited in the system. All of these chemicals are found in the environment; thus, how they interact with nanoparticles and are transported through the environment is important. The analytical methods developed utilize and a wide-bore hydrodynamic chromatography to induce a partial hydrodynamic separation between nanoparticles and dissolved solutes. Then, using deconvolution techniques, two separate elution profiles for the nanoparticle and organic solute can be obtained. Followed by a mass balance approach, association constants between LRD, our model nanoparticle, and organic solutes are calculated. These findings are the first of their kind for LRD and nanoclays in dilute dispersions.

Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis

Hydroxychloroquine (HCQ) is an antimalarial drug that is also used as a second-line treatment of rheumatoid arthritis (RA). Clinically, the use of HCQ is characterized by a long delay in the onset of action, and withdrawal of treatment is often a result of inefficacy rather than from toxicity. The slow onset of action can be attributed to the pharmacokinetics (PK) of HCQ, and wide interpatient variability is evident. Tentative relationships between concentration and effect have been made, but to date, no population PK model has been developed for HCQ. This study aimed to develop a population PK model including an estimation of the oral bioavailability of HCQ. In addition, the effects of the coadministration of methotrexate on the PK of HCQ were examined. Hydroxychloroquine blood concentration data were combined from previous pharmacokinetic studies in patients with rheumatoid arthritis. A total of 123 patients were studied, giving the data cohort from four previously published studies. Two groups of patients were included: 74 received hydroxychloroquine (HCQ) alone, and 49 received HCQ and methotrexate (MTX). All data analyses were carried out using the NONMEM program. A one-compartment PK model was supported, rather than a three-compartment model as previously published, probably because of the clustering of concentrations taken at the end of a dosing interval. The population estimate of bioavailability of 0.75 (0.07), n = 9, was consistent with literature values. The parameter values from the final model were: (Cl) over bar = 9.9 +/- 0.4 L/h, (V) over bar 605 +/- 91 L, (k(d)) over bar = 0.77 +/- 0.22 hours(-1), (t(tag)) over bar = 0.44 +/- 0.02 hours. Clearance was not affected by the presence of MTX, and, hence, steady-state drug concentrations and maintenance dosage requirements were similar. A population PK model was successfully developed for HCQ.

Calibrating photometric redshifts of luminous red galaxies

We discuss the construction of a photometric redshift catalogue of luminous red galaxies (LRGs) from the Sloan Digital Sky Survey (SDSS), emphasizing the principal steps necessary for constructing such a catalogue: (i) photometrically selecting the sample, (ii) measuring photometric redshifts and their error distributions, and (iii) estimating the true redshift distribution. We compare two photometric redshift algorithms for these data and find that they give comparable results. Calibrating against the SDSS and SDSS-2dF (Two Degree Field) spectroscopic surveys, we find that the photometric redshift accuracy is sigma similar to 0.03 for redshifts less than 0.55 and worsens at higher redshift (similar to 0.06 for z < 0.7). These errors are caused by photometric scatter, as well as systematic errors in the templates, filter curves and photometric zero-points. We also parametrize the photometric redshift error distribution with a sum of Gaussians and use this model to deconvolve the errors from the measured photometric redshift distribution to estimate the true redshift distribution. We pay special attention to the stability of this deconvolution, regularizing the method with a prior on the smoothness of the true redshift distribution. The methods that we develop are applicable to general photometric redshift surveys.

A new rapidly absorbed paracetamol tablet containing sodium bicarbonate. II. Dissolution studies and in vitro/in vivo correlation

The objective of this study was to compare the in vitro dissolution profile of a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with that of a conventional paracetamol tablet (P), and to relate these by deconvolution and mapping to in vivo release. The dissolution methods used include the standard procedure described in the USP monograph for paracetamol tablets, employing buffer at pH5.8 or 0.05 M HCl at stirrer speeds between 10 and 50 rpm. The mapping process was developed and implemented in Microsoft Excel® worksheets that iteratively calculated the optimal values of scale and shape factors which linked in vivo time to in vitro time. The in vitro-in vivo correlation (IVIVC) was carried out simultaneously for both formulations to produce common mapping factors. The USP method, using buffer at pH5.8, demonstrated no difference between the two products. However, using an acidic medium the rate of dissolution of P but not of PS decreased with decreasing stirrer speed. A significant correlation (r=0.773; p<.00001) was established between in vivo release and in vitro dissolution using the profiles obtained with 0.05 M HCl and a stirrer speed of 30 rpm. The scale factor for optimal simultaneous IVIVC in the fasting state was 2.54 and the shape factor was 0.16; corresponding values for mapping in the fed state were 3.37 and 0.13 (implying a larger in vitro-in vivo time difference but reduced shape difference in the fed state). The current IVIVC explains, in part, the observed in vivo variability of the two products. The approach to mapping may also be extended to different batches of these products, to predict the impact of any changes of in vitro dissolution on in vivo release and plasma drug concentration-time profiles.

Ionized cluster beam deposition, and thin film analysis

In 1972 the ionized cluster beam (ICB) deposition technique was introduced as a new method for thin film deposition. At that time the use of clusters was postulated to be able to enhance film nucleation and adatom surface mobility, resulting in high quality films. Although a few researchers reported singly ionized clusters containing 10$\sp2$-10$\sp3$ atoms, others were unable to repeat their work. The consensus now is that film effects in the early investigations were due to self-ion bombardment rather than clusters. Subsequently in recent work (early 1992) synthesis of large clusters of zinc without the use of a carrier gas was demonstrated by Gspann and repeated in our laboratory. Clusters resulted from very significant changes in two source parameters. Crucible pressure was increased from the earlier 2 Torr to several thousand Torr and a converging-diverging nozzle 18 mm long and 0.4 mm in diameter at the throat was used in place of the 1 mm x 1 mm nozzle used in the early work. While this is practical for zinc and other high vapor pressure materials it remains impractical for many materials of industrial interest such as gold, silver, and aluminum. The work presented here describes results using gold and silver at pressures of around 1 and 50 Torr in order to study the effect of the pressure and nozzle shape. Significant numbers of large clusters were not detected. Deposited films were studied by atomic force microscopy (AFM) for roughness analysis, and X-ray diffraction.^ Nanometer size islands of zinc deposited on flat silicon substrates by ICB were also studied by atomic force microscopy and the number of atoms/cm$\sp2$ was calculated and compared to data from Rutherford backscattering spectrometry (RBS). To improve the agreement between data from AFM and RBS, convolution and deconvolution algorithms were implemented to study and simulate the interaction between tip and sample in atomic force microscopy. The deconvolution algorithm takes into account the physical volume occupied by the tip resulting in an image that is a more accurate representation of the surface.^ One method increasingly used to study the deposited films both during the growth process and following, is ellipsometry. Ellipsometry is a surface analytical technique used to determine the optical properties and thickness of thin films. In situ measurements can be made through the windows of a deposition chamber. A method for determining the optical properties of a film, that is sensitive only to the growing film and accommodates underlying interfacial layers, multiple unknown underlayers, and other unknown substrates was developed. This method is carried out by making an initial ellipsometry measurement well past the real interface and by defining a virtual interface in the vicinity of this measurement. ^

Positron emission tomography (PET) tumor segmentation and quantification: Development of new algorithms

Tumor functional volume (FV) and its mean activity concentration (mAC) are the quantities derived from positron emission tomography (PET). These quantities are used for estimating radiation dose for a therapy, evaluating the progression of a disease and also use it as a prognostic indicator for predicting outcome. PET images have low resolution, high noise and affected by partial volume effect (PVE). Manually segmenting each tumor is very cumbersome and very hard to reproduce. To solve the above problem I developed an algorithm, called iterative deconvolution thresholding segmentation (IDTS) algorithm; the algorithm segment the tumor, measures the FV, correct for the PVE and calculates mAC. The algorithm corrects for the PVE without the need to estimate camera's point spread function (PSF); also does not require optimizing for a specific camera. My algorithm was tested in physical phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution. It was also tested on irregular shaped tumors with a heterogeneous activity profile which were acquired using physical and simulated phantom. The physical phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1-5 min). The algorithm was applied on ten clinical data where the results were compared with manual segmentation and fixed percentage thresholding method called T50 and T60 in which 50% and 60% of the maximum intensity respectively is used as threshold. The average error in FV and mAC calculation was 30% and -35% for 0.5 ml tumor. The average error FV and mAC calculation were ~5% for 16 ml tumor. The overall FV error was ∼10% for heterogeneous tumors in physical and simulated phantom data. The FV and mAC error for clinical image compared to manual segmentation was around -17% and 15% respectively. In summary my algorithm has potential to be applied on data acquired from different cameras as its not dependent on knowing the camera's PSF. The algorithm can also improve dose estimation and treatment planning.^

The Rotational Evolution and Magnetospheric Emission of the Magnetic Early B-type Stars

How do the magnetic fields of massive stars evolve over time? Are their gyrochronological ages consistent with ages inferred from evolutionary tracks? Why do most stars predicted to host Centrifugal Magnetospheres (CMs) display no H$\alpha$ emission? Does plasma escape from CMs via centrifugal breakout events, or by a steady-state leakage mechanism? This thesis investigates these questions via a population study with a sample of 51 magnetic early B-type stars. The longitudinal magnetic field \bz~was measured from Least Squares Deconvolution profiles extracted from high-resolution spectropolarimetric data. New rotational periods $P_{\rm rot}$ were determined for 15 stars from \bz, leaving only 3 stars for which $P_{\rm rot}$ is unknown. Projected rotational velocities \vsini~were measured from multiple spectral lines. Effective temperatures and surface gravities were measured via ionization balances and line profile fitting of H Balmer lines. Fundamental physical parameters, \bz, \vsini, and $P_{\rm rot}$ were then used to determine radii, masses, ages, dipole oblique rotator model, stellar wind, magnetospheric, and spindown parameters using a Monte Carlo approach that self-consistently calculates all parameters while accounting for all available constraints on stellar properties. Dipole magnetic field strengths $B_{\rm d}$ follow a log-normal distribution similar to that of Ap stars, and decline over time in a fashion consistent with the expected conservation of fossil magnetic flux. $P_{\rm rot}$ increases with fractional main sequence age, mass, and $B_{\rm d}$, as expected from magnetospheric braking. However, comparison of evolutionary track ages to maximum spindown ages $t_{\rm S,max}$ shows that initial rotation fractions may be far below critical for stars with $M_*>10 M_\odot$. Computing $t_{\rm S,max}$ with different mass-loss prescriptions indicates that the mass-loss rates of B-type stars are likely much lower than expected from extrapolation from O-type stars. Stars with H$\alpha$ in emission and absorption occupy distinct regions in the updated rotation-magnetic confinement diagram: H$\alpha$-bright stars are found to be younger, more rapidly rotating, and more strongly magnetized than the general population. Emission strength is sensitive both to the volume of the CM and to the mass-loss rate, favouring leakage over centrifugal breakout.

The VLT-FLAMES tarantula survey:XII. Rotational velocities of the single O-type stars

Context. The 30 Doradus (30 Dor) region of the Large Magellanic Cloud, also known as the Tarantula nebula, is the nearest starburst region. It contains the richest population of massive stars in the Local Group, and it is thus the best possible laboratory to investigate open questions on the formation and evolution of massive stars. Aims. Using ground-based multi-object optical spectroscopy obtained in the framework of the VLT-FLAMES Tarantula Survey (VFTS), we aim to establish the (projected) rotational velocity distribution for a sample of 216 presumably single O-type stars in 30 Dor. The sample is large enough to obtain statistically significant information and to search for variations among subpopulations - in terms of spectral type, luminosity class, and spatial location - in the field of view. Methods. We measured projected rotational velocities, 3e sin i, by means of a Fourier transform method and a profile fitting method applied to a set of isolated spectral lines. We also used an iterative deconvolution procedure to infer the probability density, P(3e), of the equatorial rotational velocity, 3e. Results. The distribution of 3e sin i shows a two-component structure: a peak around 80 km s1 and a high-velocity tail extending up to 600 km s^-1 This structure is also present in the inferred distribution P(3e) with around 80% of the sample having 0 <3e ≤ 300 km s^-1 and the other 20% distributed in the high-velocity region. The presence of the low-velocity peak is consistent with what has been found in other studies for late O- and early B-type stars. Conclusions. Most of the stars in our sample rotate with a rate less than 20% of their break-up velocity. For the bulk of the sample, mass loss in a stellar wind and/or envelope expansion is not efficient enough to significantly spin down these stars within the first few Myr of evolution. If massive-star formation results in stars rotating at birth with a large portion of their break-up velocities, an alternative braking mechanism, possibly magnetic fields, is thus required to explain the present-day rotational properties of the O-type stars in 30 Dor. The presence of a sizeable population of fast rotators is compatible with recent population synthesis computations that investigate the influence of binary evolution on the rotation rate of massive stars. Even though we have excluded stars that show significant radial velocity variations, our sample may have remained contaminated by post-interaction binary products. That the highvelocity tail may be populated primarily (and perhaps exclusively) by post-binary interaction products has important implications for the evolutionary origin of systems that produce gamma-ray bursts. © 2013 Author(s).

The VLT-FLAMES tarantula survey:X. Evidence for a bimodal distribution of rotational velocities for the single early B-type stars

Aims. Projected rotational velocities (ve sin i) have been estimated for 334 targets in the VLT-FLAMES Tarantula Survey that do not manifest significant radial velocity variations and are not supergiants. They have spectral types from approximately O9.5 to B3. The estimates have been analysed to infer the underlying rotational velocity distribution, which is critical for understanding the evolution of massive stars. Methods. Projected rotational velocities were deduced from the Fourier transforms of spectral lines, with upper limits also being obtained from profile fitting. For the narrower lined stars, metal and non-diffuse helium lines were adopted, and for the broader lined stars, both non-diffuse and diffuse helium lines; the estimates obtained using the different sets of lines are in good agreement. The uncertainty in the mean estimates is typically 4% for most targets. The iterative deconvolution procedure of Lucy has been used to deduce the probability density distribution of the rotational velocities. Results. Projected rotational velocities range up to approximately 450 kms-1 and show a bi-modal structure. This is also present in the inferred rotational velocity distribution with 25% of the sample having 0 <ve <100 km s^-1 and the high velocity component having v_e ∼ 250 km s^-1. There is no evidence from the spatial and radial velocity distributions of the two components that they represent either field and cluster populations or different episodes of star formation. Be-type stars have also been identified. Conclusions. The bi-modal rotational velocity distribution in our sample resembles that found for late-B and early-A type stars.While magnetic braking appears to be a possible mechanism for producing the low-velocity component, we can not rule out alternative explanations. © ESO 2013.

Transcallosal connectivity of the human cortical motor network

The organizational and architectural configuration of white matter pathways connecting brain regions has ramifications for all facets of the human condition, including manifestations of incipient neurodegeneration. Although diffusion tensor imaging (DTI) has been used extensively to visualize white matter connectivity, due to the widespread presence of crossing fibres, the lateral projections of the corpus callosum are not normally detected using this methodology. Detailed knowledge of the transcallosal connectivity of the human cortical motor network has therefore remained elusive. We employed constrained spherical deconvolution (CSD) tractography - an approach that is much less susceptible to the influence of crossing fibres, in order to derive complete in-vivo characterizations of white matter pathways connecting specific motor cortical regions to their counterparts and other loci in the opposite hemisphere. The revealed patterns of connectivity closely resemble those derived from anatomical tracing in primates. It was established that dorsal premotor cortex (PMd) and supplementary motor area (SMA) have extensive interhemispheric connectivity - exhibiting both dense homologous projections, and widespread structural relations with every other region in the contralateral motor network. Through this in-vivo portrayal, the importance of non-primary motor regions for interhemispheric communication is emphasized. Additionally, distinct connectivity profiles were detected for the anterior and posterior subdivisions of primary motor cortex. The present findings provide a comprehensive representation of transcallosal white matter projections in humans, and have the potential to inform the development of models and hypotheses relating structural and functional brain connectivity.

A Bias Compensated Cross-Relation approach to Thermocouple Characterisation

The measurement of fast changing temperature fluctuations is a challenging problem due to the inherent limited bandwidth of temperature sensors. This results in a measured signal that is a lagged and attenuated version of the input. Compensation can be performed provided an accurate, parameterised sensor model is available. However, to account for the in influence of the measurement environment and changing conditions such as gas velocity, the model must be estimated in-situ. The cross-relation method of blind deconvolution is one approach for in-situ characterisation of sensors. However, a drawback with the method is that it becomes positively biased and unstable at high noise levels. In this paper, the cross-relation method is cast in the discrete-time domain and a bias compensation approach is developed. It is shown that the proposed compensation scheme is robust and yields unbiased estimates with lower estimation variance than the uncompensated version. All results are verified using Monte-Carlo simulations.

A Bias Compensated Cross-Relation approach to Thermocouple Characterisation

The measurement of fast changing temperature fluctuations is a challenging problem due to the inherent limited bandwidth of temperature sensors. This results in a measured signal that is a lagged and attenuated version of the input. Compensation can be performed provided an accurate, parameterised sensor model is available. However, to account for the influence of the measurement environment and changing conditions such as gas velocity, the model must be estimated in-situ. The cross-relation method of blind deconvolution is one approach for in-situ characterisation of sensors. However, a drawback with the method is that it becomes positively biased and unstable at high noise levels. In this paper, the cross-relation method is cast in the discrete-time domain and a bias compensation approach is developed. It is shown that the proposed compensation scheme is robust and yields unbiased estimates with lower estimation variance than the uncompensated version. All results are verified using Monte-Carlo simulations.

Avaliação do impacto das condições de operação na qualidade do sinal : processamento de dados de reflexão sísmica de multicanal

Através do processamento de dados sísmicos convertem-se registos de campo em secções sísmicas com significado geológico, que revelam informações e ajudam a delinear as camadas geológicas do subsolo e identificar estruturas soterradas. Portanto, a interpretação dos dados sísmicos só é boa se o processamento também o for. Este trabalho é resultado de um estágio curricular na empresa de prospecção geofísica GeoSurveys, que consistiu principalmente em processar 18 linhas de dados de sísmica de reflexão multicanal de alta resolução adquiridas na ilha de Pulau Tekong em Singapura, que têm como finalidade investigação do solo da baia desta mesma ilha. Estes dados foram cedidos à GeoSurveys para fins académicos, caso em que se inclui esta dissertação. Para atingir os objectivos propostos que consistiam em avaliar o impacto das condições de operação na qualidade do sinal sísmico e interpretação das linhas, fez-se o processamento das linhas utilizando um fluxo processamento padrão utilizado na empresa, com recurso ao software Radex Pro. Este fluxo de processamento tem como mais-valia o método de correcções estáticas, o UHRS trim statics, além das técnicas habituais utilizadas para melhorar a resolução das secções sísmicas como é o caso da desconvolução, a atenuação de ruído através do stacking, correcções de NMO, e migração, entre outras técnicas. A interpretação das linhas sísmicas processadas foi feita no software Kingdom Suite (IHS), através da distinção da configuração interna dos reflectores em cada secção sísmica, estabelecendo deste modo as principais unidades sismo-estratigráficas e identificando as zonas de interface que delimitam os horizontes principais. Foi feito ainda um estudo geológico sumário da área de pesquisa e da evolução geodinâmica da região.

Avaliação da interação entre aflatoxina M1 e B1 com a fração proteica do leite

Dissertação composta por 02 artigos.

Processing Bio-Argo nitrate concentration at the DAC Level

The only method used to date to measure dissolved nitrate concentration (NITRATE) with sensors mounted on profiling floats is based on the absorption of light at ultraviolet wavelengths by nitrate ion (Johnson and Coletti, 2002; Johnson et al., 2010; 2013; D’Ortenzio et al., 2012). Nitrate has a modest UV absorption band with a peak near 210 nm, which overlaps with the stronger absorption band of bromide, which has a peak near 200 nm. In addition, there is a much weaker absorption due to dissolved organic matter and light scattering by particles (Ogura and Hanya, 1966). The UV spectrum thus consists of three components, bromide, nitrate and a background due to organics and particles. The background also includes thermal effects on the instrument and slow drift. All of these latter effects (organics, particles, thermal effects and drift) tend to be smooth spectra that combine to form an absorption spectrum that is linear in wavelength over relatively short wavelength spans. If the light absorption spectrum is measured in the wavelength range around 217 to 240 nm (the exact range is a bit of a decision by the operator), then the nitrate concentration can be determined. Two different instruments based on the same optical principles are in use for this purpose. The In Situ Ultraviolet Spectrophotometer (ISUS) built at MBARI or at Satlantic has been mounted inside the pressure hull of a Teledyne/Webb Research APEX and NKE Provor profiling floats and the optics penetrate through the upper end cap into the water. The Satlantic Submersible Ultraviolet Nitrate Analyzer (SUNA) is placed on the outside of APEX, Provor, and Navis profiling floats in its own pressure housing and is connected to the float through an underwater cable that provides power and communications. Power, communications between the float controller and the sensor, and data processing requirements are essentially the same for both ISUS and SUNA. There are several possible algorithms that can be used for the deconvolution of nitrate concentration from the observed UV absorption spectrum (Johnson and Coletti, 2002; Arai et al., 2008; Sakamoto et al., 2009; Zielinski et al., 2011). In addition, the default algorithm that is available in Satlantic sensors is a proprietary approach, but this is not generally used on profiling floats. There are some tradeoffs in every approach. To date almost all nitrate sensors on profiling floats have used the Temperature Compensated Salinity Subtracted (TCSS) algorithm developed by Sakamoto et al. (2009), and this document focuses on that method. It is likely that there will be further algorithm development and it is necessary that the data systems clearly identify the algorithm that is used. It is also desirable that the data system allow for recalculation of prior data sets using new algorithms. To accomplish this, the float must report not just the computed nitrate, but the observed light intensity. Then, the rule to obtain only one NITRATE parameter is, if the spectrum is present then, the NITRATE should be recalculated from the spectrum while the computation of nitrate concentration can also generate useful diagnostics of data quality.