Compensatory embryonic response to allele-specific inactivation of the murine X-linked gene Hcfc1.

Early in female mammalian embryonic development, cells randomly inactivate one of the two X chromosomes to achieve overall equal inactivation of parental X-linked alleles. Hcfc1 is a highly conserved X-linked mouse gene that encodes HCF-1 - a transcriptional co-regulator implicated in cell proliferation in tissue culture cells. By generating a Cre-recombinase inducible Hcfc1 knock-out (Hcfc1(lox)) allele in mice, we have probed the role of HCF-1 in actively proliferating embryonic cells and in cell-cycle re-entry of resting differentiated adult cells using a liver regeneration model. HCF-1 function is required for both extraembryonic and embryonic development. In heterozygous Hcfc1(lox/+) female embryos, however, embryonic epiblast-specific Cre-induced Hcfc1 deletion (creating an Hcfc1(epiKO) allele) around E5.5 is well tolerated; it leads to a mixture of HCF-1-positive and -negative epiblast cells owing to random X-chromosome inactivation of the wild-type or Hcfc1(epiKO) mutant allele. At E6.5 and E7.5, both HCF-1-positive and -negative epiblast cells proliferate, but gradually by E8.5, HCF-1-negative cells disappear owing to cell-cycle exit and apoptosis. Although generating a temporary developmental retardation, the loss of HCF-1-negative cells is tolerated, leading to viable heterozygous offspring with 100% skewed inactivation of the X-linked Hcfc1(epiKO) allele. In resting adult liver cells, the requirement for HCF-1 in cell proliferation was more evident as hepatocytes lacking HCF-1 fail to re-enter the cell cycle and thus to proliferate during liver regeneration. The survival of the heterozygous Hcfc1(epiKO/+) female embryos, even with half the cells genetically compromised, illustrates the developmental plasticity of the post-implantation mouse embryo - in this instance, permitting survival of females heterozygous for an X-linked embryonic lethal allele.

X-ray fluorescence determination of adsorbed copper on activated charcoal after glycerin complexation

X-This work shows an alternative method to copper determination by X-Ray Fluorescence (XRF). Since copper concentration in natural waters is not enough to reach XRF detection limit, a liquid-solid preconcentration procedure was proposed. Glycerin was used to complex the metal increasing its adsorption on activated charcoal. The solid phase was used to XRF determination. Several parameters were evaluated, such as, the complexation pH, the charcoal adsorption limit and the glycerin concentration. The interferences are lead and bismuth and the sensitivities decreased in the order Cu2+, Bi3+ and Pb2+. The advantages of the method are its simplicity, low cost and low spectral interference.

Síntese e caracterização dos nanocompósitos K0,1(PEO)xMoS2 (X= 0,5; 1,2)

The reaction of an aqueous solution of poly(ethylene oxide) (peo - mw 100.000) with a neutral aqueous suspension of single layers of MoS2 was studied. The single layers aqueous suspension was prepared by first intercalating lithium (using n-Butyllithium in n-hexane) and reaction of these ternary compound with water under ultrasound stirring. The suspension was washed several times with water until neutral pH. The suspension was mixed with the PEO aqueous solution in the presence of KCl. Two single phase compounds were obtained with the expansion of 4,8 and 9,0Å, attributed to the solvation of the intercalated potassium cations with mono and double layers, respectively.

Investigação espectroscópica dos carbonilos heterobimetálicos cis-[Fe(CO)4(HgX)2], X = Cl, Br,I

The series of compounds cis-[Fe(CO)4(HgX)2], X=Cl,Br,I shows an octahedral geometry around the iron atom with the two HgX groups cis to each other. In this paper the assignment for the carbonyl stretching modes and the calculation of their force constants were performed on the basis of the Cotton-Krainhanzel model. Taking into account all the data from the IR, 199Hg NMR and UV-vis spectra it is possible to verify the influence of X on the electronic densities at the metallic centers.

Statistical Inversion Theory in X-ray Tomography

In this thesis the X-ray tomography is discussed from the Bayesian statistical viewpoint. The unknown parameters are assumed random variables and as opposite to traditional methods the solution is obtained as a large sample of the distribution of all possible solutions. As an introduction to tomography an inversion formula for Radon transform is presented on a plane. The vastly used filtered backprojection algorithm is derived. The traditional regularization methods are presented sufficiently to ground the Bayesian approach. The measurements are foton counts at the detector pixels. Thus the assumption of a Poisson distributed measurement error is justified. Often the error is assumed Gaussian, altough the electronic noise caused by the measurement device can change the error structure. The assumption of Gaussian measurement error is discussed. In the thesis the use of different prior distributions in X-ray tomography is discussed. Especially in severely ill-posed problems the use of a suitable prior is the main part of the whole solution process. In the empirical part the presented prior distributions are tested using simulated measurements. The effect of different prior distributions produce are shown in the empirical part of the thesis. The use of prior is shown obligatory in case of severely ill-posed problem.

Análise por difração de raios x de filmes de óxidos cerâmicos compostos por IrO2/TiO2/CeO2

Independent of the sample form (powder or film), XRD analysis of Ir0,3Ti(0,7-x)Ce xO2, (nominal) mixtures, for x=0, shows the formation of a solid solution phase between IrO2 and TiO2, as well as the rutile phases of IrO2 and TiO2. The presence of the anatase phase of TiO2 is also confirmed. The introduction of 30 mol% CeO2 in the mixture reveals the presence of the CeO2 and Ce2O3 phases, besides the already mentioned ones, in the powder. In the film form, however, an amorphous phase is identified. When all of the TiO2 is substituded by CeO2, for both sample forms, the only phases found are IrO2, CeO2 and Ce2O3. This result suggests cerium oxides are not capable of forming solid solutions with either IrO2 or (Ir,Ti)O2 acting solely as a dispersant matrix for these phases. These results are consistent with the much higher electrochemically active surface area when CeO2 is introduced in the binary Ti/Ir0,3Ti0,7O2 mixture. It was possible to establish a relationship between the electrochemical stability of the supported films and their crystalline structure. The unexpected presence of TiO2 and Ti2O3 in the Ti/Ir0,3Ce0,7O2 (film sample) is attributed to oxidation of the Ti support during the calcination step.

Monte Carlo simulation of x-ray emission by kilovolt electron bombardment

A physical model for the simulation of x-ray emission spectra from samples irradiated with kilovolt electron beams is proposed. Inner shell ionization by electron impact is described by means of total cross sections evaluated from an optical-data model. A double differential cross section is proposed for bremsstrahlung emission, which reproduces the radiative stopping powers derived from the partial wave calculations of Kissel, Quarles and Pratt [At. Data Nucl. Data Tables 28, 381 (1983)]. These ionization and radiative cross sections have been introduced into a general-purpose Monte Carlo code, which performs simulation of coupled electron and photon transport for arbitrary materials. To improve the efficiency of the simulation, interaction forcing, a variance reduction technique, has been applied for both ionizing collisions and radiative events. The reliability of simulated x-ray spectra is analyzed by comparing simulation results with electron probe measurements.

Monte Carlo simulation of x-ray spectra generated by kilo-electron-volt electrons

We present a general algorithm for the simulation of x-ray spectra emitted from targets of arbitrary composition bombarded with kilovolt electron beams. Electron and photon transport is simulated by means of the general-purpose Monte Carlo code PENELOPE, using the standard, detailed simulation scheme. Bremsstrahlung emission is described by using a recently proposed algorithm, in which the energy of emitted photons is sampled from numerical cross-section tables, while the angular distribution of the photons is represented by an analytical expression with parameters determined by fitting benchmark shape functions obtained from partial-wave calculations. Ionization of K and L shells by electron impact is accounted for by means of ionization cross sections calculated from the distorted-wave Born approximation. The relaxation of the excited atoms following the ionization of an inner shell, which proceeds through emission of characteristic x rays and Auger electrons, is simulated until all vacancies have migrated to M and outer shells. For comparison, measurements of x-ray emission spectra generated by 20 keV electrons impinging normally on multiple bulk targets of pure elements, which span the periodic system, have been performed using an electron microprobe. Simulation results are shown to be in close agreement with these measurements.

Coordenação local do Eu(III) em híbridos orgânicos/inorgânicos emissores de luz branca

Eu3+ luminescence and EXAFS (Extended X-ray Absorption Fine Structure) results are presented for organic-inorganic hybrid gel hosts composed of a siliceous network to which small chains of oxyethylene units are covalently grafted by means of urea bridges. Coordination numbers for Eu3+ ions range from 12.8 to 9.7 with increasing Eu3+ concentration while the Eu3+-first neighbours mean distance is found to be constant at 2.48-2.49 Å in the same concentration range. Emission spectra display a broad band in the green/blue spectral region superposed to narrow lines appearing in the yellow/red region in such a way that for the eyes emission appears white. The broad band is assigned to intrinsic NH groups emission and also to electron-hole recombination in the nanosised siliceous domains. The narrow lines are assigned to intra-4f6, 5D0->7F0-4 Eu3+ transitions and from the energy position of the 7F0-4 levels a mean distance could be calculated for the Eu3+-first neighbours. The calculated results are in good agreement with the experimental ones obtained from EXAFS analysis.

Métodos matemáticos para correção de interferências espectrais e efeitos interelementos na análise quantitativa por fluorescência de raios-X

One of the main problems in quantitative analysis of complex samples by x-ray fluorescence is related to interelemental (or matrix) effects. These effects appear as a result of interactions among sample elements, affecting the x-ray emission intensity in a non-linear manner. Basically, two main effects occur; intensity absorption and enhancement. The combination of these effects can lead to serious problems. Many studies have been carried out proposing mathematical methods to correct for these effects. Basic concepts and the main correction methods are discussed here.

Estudo do efeito do cloreto em catalisadores de paládio usando a análise no infravermelho e de fotoelétrons excitados por raios x

Chloride poisoning is known as having an inhibitor effect in the activity of metal catalysis. In this work in situ infrared spectroscopy (FTIR) of adsorbed carbon monoxide and x-ray photoelectron spectroscopy (XPS) were used to investigate the effect of chloride presence in the electronic metal density in the d subshell of palladium dispersed on alumina. The chloride poisoning effect was interpreted as an electronic effect since a weak back-bonded Pd-CO was formed due to the decrease in the electronic density of the d subshell of palladium, which could be also detected by the higher Pd 3d5/2 binding energy in the chloride presence. A similar poisoning effect was also observed for chloride free Pd/Al2O3 reduced at 500 ºC, and it was interpreted based on the interaction of metal with the alumina surface. The use of molybdena/alumina binary system as support, yield a contrary effect due to the metal-support interaction.

Aplicação de alguns modelos quimiométricos à espectroscopia de fluorescência de raios-X de energia dispersiva

The objective of this work was to accomplish the simultaneous determination of some chemical elements by Energy Dispersive X-ray Fluorescence (EDXRF) Spectroscopy through multivariate calibration in several sample types. The multivariate calibration models were: Back Propagation neural network, Levemberg-Marquardt neural network and Radial Basis Function neural network, fuzzy modeling and Partial Least Squares Regression. The samples were soil standards, plant standards, and mixtures of lead and sulfur salts diluted in silica. The smallest Root Mean Square errors (RMS) were obtained with Back Propagation neural networks, which solved main EDXRF problems in a better way.

Gamma spectrometry and gamma and X-ray tomography of nuclear fuel

The purpose of gamma spectrometry and gamma and X-ray tomography of nuclear fuel is to determine both radionuclide concentration and integrity and deformation of nuclear fuel. The aims of this thesis have been to find out the basics of gamma spectrometry and tomography of nuclear fuel, to find out the operational mechanisms of gamma spectrometry and tomography equipment of nuclear fuel, and to identify problems that relate to these measurement techniques. In gamma spectrometry of nuclear fuel the gamma-ray flux emitted from unstable isotopes is measured using high-resolution gamma-ray spectroscopy. The production of unstable isotopes correlates with various physical fuel parameters. In gamma emission tomography the gamma-ray spectrum of irradiated nuclear fuel is recorded for several projections. In X-ray transmission tomography of nuclear fuel a radiation source emits a beam and the intensity, attenuated by the nuclear fuel, is registered by the detectors placed opposite. When gamma emission or X-ray transmission measurements are combined with tomographic image reconstruction methods, it is possible to create sectional images of the interior of nuclear fuel. MODHERATO is a computer code that simulates the operation of radioscopic or tomographic devices and it is used to predict and optimise the performance of imaging systems. Related to the X-ray tomography, MODHERATO simulations have been performed by the author. Gamma spectrometry and gamma and X-ray tomography are promising non-destructive examination methods for understanding fuel behaviour under normal, transient and accident conditions.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Optimization of an essentially inactive 3,4-dihydro-2H-pyrano[3,2-c]quinoline carboxylic ester derivative as acetylcholinesterase (AChE) peripheral anionic site (PAS)-binding motif by double O → NH bioisosteric replacement, combined with molecular hybridization with the AChE catalytic anionic site (CAS) inhibitor 6-chlorotacrine and molecular dynamics-driven optimization of the length of the linker has resulted in the development of the trimethylene-linked 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine6-chlorotacrine hybrid 5a as a picomolar inhibitor of human AChE (hAChE). The tetra-, penta-, and octamethylene-linked homologues 5bd have been also synthesized for comparison purposes, and found to retain the nanomolar hAChE inhibitory potency of the parent 6-chlorotacrine. Further biological profiling of hybrids 5ad has shown that they are also potent inhibitors of human butyrylcholinesterase and moderately potent Aβ42 and tau anti-aggregating agents, with IC50 values in the submicromolar and low micromolar range, respectively. Also, in vitro studies using an artificial membrane model have predicted a good brain permeability for hybrids 5ad, and hence, their ability to reach their targets in the central nervous system. The multitarget profile of the novel hybrids makes them promising leads for developing anti-Alzheimer drug candidates with more balanced biological activities.