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High-quality potassium tantalate (KTaO3, KT) single crystals are grown by a high-temperature self-flux solution modified method in which potassium carbonate (K2CO3) and boron oxide (B2O3) are utilized as a complex flux. Additions of small amounts of boron oxide, used because of its low melting temperature (450 °C) and tendency to decrease the weight losses, increased the metastable region, requiring lower temperature (≤1300 °C) for the growth of relatively large KT crystals thereby suppressing the K volatilization tendency. By changing the flux composition and flux to solute proportion growth conditions are modified. The as-grown potassium tantalate crystals exhibit a dielectric permittivity of 6600 and dielectric losses of 0.004 at 13 K and 100 kHz. These results suggest a new promising approach for growing relatively large size and high quality single crystals within KT-based system.

All types of cancer are a threat to human health and among the current therapies, the highly invasive chemotherapy is still the standard in several cases. Currently, more specific and less invasive therapies are being developed and chemodynamic therapy arose as a viable alternative. This strategy takes advantage of the tumour biochemical characteristics such as the acidic pH (∼6.0) and the high concentration of H2O2(∼50 μM–∼1 mM). In these specific conditions, nanoparticles with peroxidase-like catalytic properties can convert H2O2into highly toxic reactive oxygen species that induce oxidative stress in cancer cells. One of the remarkable advantages of chemodynamic therapy concerns the peroxidase-like activity, which only occurs in specific pH environments, as found in the tumour microenvironment. At the same time, the produced reactive oxygen species are short-lived, meaning that they will not travel outside the tumoral region, thus not affecting healthy surrounding tissues.

Photoactivated advanced oxidation processes have excellent performance in removing recalcitrant pollutants from water. However, the high operating cost associated with the energy consumption of UV lamps is a big drawback. In this work, the design and optimization of the reflector in a tube-in-tube membrane photoreactor were carried out using a ray tracing methodology to maximize the light deployed to the reactor. Simulations were carried out using different lamps/reactor arrangements with 1, 2 and 3-sided flat reflectors and with circular and parabolic geometries. Results showed that direct radiation is maximized when the distance reactor-lamps is minimized, increasing optical efficiency. On the other hand, it was observed that for the flat reflectors, the closer the furthest point of the reflector to the center of the reactor, the higher optical efficiency is achieved due to the reduction in the number of bouncing rays in the reflector. In the case of parabolic geometries, some additional considerations are necessary, since not only the distance at which the reflector is placed matters, but also its geometrical focus. The best performance is achieved for those in which the distance from the furthest point of the reflector to the center of the reactor was lower and the lamps placed near the focus of the parabola. For the studied reflector geometries, the calculated optical efficiencies when using anodized aluminum were 46.1%, 56.5%, 60.0%, 41.8%, and 65.9% for reflectors of 1, 2, and 3 sides, cylinder, and parabola, respectively. Model predictions were successfully validated using experimental ferrioxalate actinometry data, confirming the huge potential of this simple simulation methodology for photoreactor design purposes.

Background: We sought to evaluate the impact of prior cerebrovascular and/or peripheral arterial disease (PAD) on in-hospital outcomes in patients with acute coronary syndromes.Methods: From 1 October 2010 to 26 February 2016, 13,904 acute coronary syndrome patients were enrolled in a national multicentre registry. They were divided into four groups: prior stroke/transient ischaemic attack (stroke/TIA); prior PAD; prior stroke/TIA and PAD; none. The endpoints included in-hospital mortality and a composite endpoint of death, re-infarction and stroke during hospitalization.Results: 6.3% patients had prior stroke/TIA, 4.2% prior PAD and 1.4% prior stroke/TIA and PAD. Prior stroke/TIA and/or PAD patients were less likely to receive evidence-based medical therapies (dual antiplatelet therapy: stroke/TIA= 88.6%, PAD= 86.6%, stroke/TIA+PAD= 85.7%, none= 92.2%, p<0.001; β-blockers: stroke/TIA= 77.1%, PAD= 72.1%, stroke/TIA+PAD= 71.9%, none= 80.8%, p<0.001; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: stroke/TIA= 86.3%, PAD= 83.6%, stroke/TIA+PAD= 83.2%, none= 87.1%, p=0.030) and to undergo percutaneous revascularization (stroke/TIA= 52.8%, PAD= 45.6%, stroke/TIA+PAD= 43.7%, none= 67.9%, p<0.001), despite more extensive coronary artery disease (three-vessel disease: stroke/TIA= 29.1%, PAD= 38.3%, stroke/TIA+PAD= 38.3%, none= 20.2%, p<0.001). In a multivariable analysis, prior stroke/TIA+PAD was a predictor of in-hospital mortality (odds ratio= 2.828, 95% confidence interval 1.001–7.990) and prior stroke/TIA (odds ratio= 1.529, 95% confidence interval 1.056–2.211), prior PAD (odds ratio= 1.618, 95% confidence interval 1.034–2.533) and both conditions (odds ratio= 3.736, 95% confidence interval 2.002–6.974) were associated with the composite endpoint.Conclusion: A prior history of stroke/TIA and/or PAD was associated with lower use of medical therapy and coronary revascularization and with worst short-term prognosis. An individualized management may improve their poor prognosis.

In the present work, we study the hysteretic behavior in the electric-field-dependent capacitance and the current characteristics of 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3(BCZT)/ZnO bilayers deposited on 0.7 wt % Nb-doped (001)-SrTiO3(Nb:STO) substrates in a metal–ferroelectric–semiconductor (MFS) configuration. The X-ray diffraction measurements show that the BCZT and ZnO layers are highly oriented along the c-axis and have a single perovskite and wurtzite phases, respectively, whereas high-resolution transmission electron microscopy revealed very sharp Nb:STO/BCZT/ZnO interfaces. The capacitance–electric field (C–E) characteristics of the bilayers exhibit a memory window of 47 kV/cm and a capacitance decrease of 22%, at a negative bias. The later result is explained by the formation of a depletion region in the ZnO layer. Moreover, an unusual resistive switching (RS) behavior is observed in the BCZT films, where the RS ratio can be 500 times enhanced in the BCZT/ZnO bilayers. The RS enhancement can be understood by the barrier potential profile modulation at the depletion region, in the BCZT/ZnO junction, via ferroelectric polarization switching of the BCZT layer. This work builds a bridge between the hysteretic behavior observed either in the C–Eand current–electric field characteristics on a MFS structure.

Background/Objectives:Obesity is a metabolic disorder that predisposes patients to numerous diseases and has become a major global public-health concern. Animal models of diet-induced obesity (DIO) are frequently used to study obesity, but which DIO model most accurately reflects the pathology of human obesity remains unclear. In this study, we designed a diet based on the human Western diet (WD) and compared it with the cafeteria diet (CAF) and high-fat diet (HFD) in order to evaluate which diet most closely mirrors human obesity.Methods:Wistar rats were fed four different diets (WD, CAF, HFD and a low-fat diet) for 18 weeks. Metabolic parameters and gut microbiota changes were then characterized.Results:Rats fed the four different diets exhibited completely different phenotypes, highlighting the importance of diet selection. This study also revealed that WD most effectively induced obesity and obesity-related disorders, and thus proved to be a robust model of human obesity. Moreover, WD-fed rats developed obesity and obesity-related comorbidities independent of major alterations in gut microbiota composition (dysbiosis), whereas CAF-fed rats developed the greatest dysbiosis independent of obesity. We also characterized gut microbiota after feeding on these four different diets and identified five genera that might be involved in the pathogenesis of obesity.Conclusions:These data suggest that diet, and not the obese state, was the major driving force behind gut microbiota changes. Moreover, the marked dysbiosis observed in CAF-fed rats might have resulted from the presence of several additives present in the CAF diet, or even a lack of essential vitamins and minerals. Based on our findings, we recommend the use of the prototypic WD (designed here) in DIO models. Conversely, CAF could be used to investigate the effects of excessive consumption of industrially produced and highly processed foods, which are characteristic of Western society.

Objectives: The incidence of mechanical complications after acute myocardial infarction has markedly declined with the advent of reperfusion. Nevertheless there is some controversy about the equal effectiveness of the different reperfusion therapies in preventing these complications. We aimed to analyse how reperfusion therapy and treatment delay relate to the incidence of mechanical complications in a population of ST-elevation myocardial infarction (STEMI) patients.Methods: We analysed all STEMI patients included in the second phase of the Portuguese Registry on Acute Coronary Syndromes, between October 2010 and July 2015. We compared both conservative medical treatment with reperfusion therapy and thrombolysis with primary percutaneous coronary intervention for mechanical complications. We also evaluated the impact of treatment delay on mechanical complications.Results: Among 5230 STEMIs we observed 77 mechanical complications (1.5%). These were significantly more frequent in the non-reperfused patients (3.3% vs. 1.1%, P<0.001) and they were numerically higher in thrombolysis than in primary percutaneous coronary intervention patients (1.6% vs. 1.0%, respectively, P=0.282). Patients with mechanical complications had higher times from symptom onset to hospitalisation and to reperfusion. In multivariate analysis performing reperfusion therapy (odds ratio 0.52, 95% confidence interval 0.29–0.93) and a time from symptom onset to hospitalisation ?6 hours (odds ratio 2.44, 95% confidence interval 1.37–4.33) were independent predictors of mechanical complications. The type of reperfusion did not influence the occurrence of mechanical complications.Conclusion: A longer time from symptom onset to hospitalisation was associated with an increased number of mechanical complications. Timely reperfusion therapy prevented mechanical complications and no significant difference was found between thrombolysis and primary percutaneous coronary intervention.

In this work, Ba0.8Sr0.2TiO3(BST)/ITO structures were grown on glass substrate and laser assisted annealing (LAA) was performed to promote the crystallization of BST. Atomic force microscopy and X‐ray diffraction studies confirm the crack free and polycrystalline perovskite phase of BST. White light controlled resistive switching (RS) effect in Au/BST/ITO device is investigated. The device displays the electroforming‐free bipolar RS characteristics and are explained by the modulation of the width and height of barrier at the BST/ITO interface via ferroelectric polarization. Moreover, the RS effect is significantly improved under white light illumination compared to that in the dark. The enhanced RS and photovoltaic effects are explained by considering depolarization field and charge distribution at the interface. The devices exhibit stable retention characteristics with low currents (≤μA), which make them attractive for non volatile memory devices.

It is unknown whether individuals with monoclonal B-cell lymphocytosis (MBL) are at risk for adverse outcomes associated with chronic lymphocytic leukemia (CLL), such as the risk of non-hematologic cancer. We identified all locally residing individuals diagnosed with high-count MBL at Mayo Clinic between 1999 and 2009 and compared their rates of non-hematologic cancer with that of patients with CLL and two control cohorts: general medicine patients and patients who underwent clinical evaluation with flow cytometry but who had no hematologic malignancy. After excluding individuals with prior cancers, there were 107 high-count MBL cases, 132 CLL cases, 589 clinic controls and 482 flow cytometry controls. With 4.6 years median follow-up, 14 (13%) individuals with high-count MBL, 21 (4%) clinic controls (comparison MBL P<0.0001), 18 (4%) flow controls (comparison MBL P=0.0001) and 16 (12%) CLL patients (comparison MBL P=0.82) developed non-hematologic cancer. On multivariable Cox regression analysis, individuals with high-count MBL had higher risk of non-hematologic cancer compared with flow controls (hazard ratio (HR)=2.36; P=0.04) and borderline higher risk compared with clinic controls (HR=2.00; P=0.07). Patients with high-count MBL appear to be at increased risk for non-hematologic cancer, further reinforcing that high-count MBL has a distinct clinical phenotype despite low risk of progression to CLL.

The paper analyzes the effect of hydrodynamic viscous boundary layer growth over the performance of a thermal storage tank during the discharge cycle. As well established in Fluid Mechanics textbooks, a viscous boundary layer modifies the velocity profile across the tank section. Consequently, in a discharge cycle the warm water flowing outside the boundary layer (i.e., in the core region) reaches the tank bottom exit faster than that if the down flow water were flowing at the mean velocity based on the discharge flow rate, which is the usual designing and tank selection assumption. Consequently, the storage tank height must be greater than that determined using the simple mean flow velocity. Two controlling parameters appear naturally in the analysis: the Reynolds number based on tank diameter, ReØ, which is also associated with the hydrodynamic entry length, and f, which defines the position of a given contact surface from the tank entrance to the hydrodynamic entry length. Results show that the tank loss of capacity due to viscous effects may not be negligible and the selection of a height-to-diameter tank ratio is essential for minimizing those effects.

The present work aims at investigating the catalytic decomposition of N2O over CuO–CeO2single or mixed oxides prepared by different synthesis routes, i.e., impregnation, precipitation and exotemplating. To gain insight into the particular role of CeO2as well as of CuO–CeO2interactions, three different types of materials were prepared and tested for N2O decomposition both in the absence and presence of excess O2: (i) bare CeO2prepared by precipitation and exotemplating, (ii) CuO/CeO2oxides synthesized by the impregnation of CeO2samples prepared in (i) with CuO, and iii) single stage CuO–CeO2mixed oxides synthesized employing the co-precipitation and exotemplating methods. The corresponding commercial samples were also examined for comparison purposes. All materials were characterized by N2adsorption at −196 °C, X-ray diffraction (XRD), H2temperature-programmed reduction (H2-TPR), X-ray photoelectron spectroscopy (XPS), micro-Raman spectroscopy (micro-Raman) and scanning electron microscopy (SEM). The results demonstrated the key role of the preparation procedure on the direct catalytic decomposition of N2O. Among the bare CeO2samples, the best performance was obtained with the samples prepared by the precipitation method, followed by exotemplating, while commercial CeO2showed the lowest performance. All bare oxides demonstrated low N2O conversion, never exceeding 40% at 600 °C. Amongst the CuO–CeO2oxides, the optimum performance was observed for those prepared by co-precipitation, which achieved complete N2O conversion at 550 °C. In the presence of excess oxygen in the feed stream, a slight degradation is observed, with the sequence of deN2O performance remaining unchanged. The superiority of the Cu–Ce mixed oxides prepared by precipitation compared to all of the other materials can be mainly ascribed to their excellent redox properties, linked to Ce4+/Ce3+and Cu2+/Cu+redox pairs. A redox mechanism for the N2O catalytic decomposition is proposed, involving N2O adsorption on Cu+sites and their regeneration through Cu–ceria interactions.

We investigate the existence of self-organized criticality on a model to describe the failure process in fibrous materials. This model consists of identical parallel fibers which are pulled with constant velocity. The rupture probability of each fiber depends on the elastic energy of the fiber and on the number of unbroken neighboring fibers. In the brittle-ductile transition, we have observed a power law behaviour on the number of cracks versusits size. This indicates that, in this region, the model shows self-organized criticality and the fracture pattern can be a fractal. The power law exponent is not universal, but depends on the temperature and traction velocity.

This study establishes the presence of spermatodesm in the seminal vesicles of sexually mature males of Crematogaster victima(Smith). In this species, the spermatozoa are maintained together by an extracellular matrix in which the acrosomal regions are embedded. This characteristic has not yet been observed in any other Aculeata. However, the sperm morphology in this species is similar to that described for other ants. The spermatozoa measure on average 100 μm in length, and the number of sperm per bundle is up to 256. They are composed of a head formed by the acrosome and nucleus; this is followed by the flagellum, which is formed by the centriolar adjunct, an axoneme with a 9 + 9 + 2 microtubule pattern, two mitochondrial derivatives, and two accessory bodies. The acrosome is formed by the acrosomal vesicle and perforatorium. The nucleus is filled with compact chromatin with many areas of thick and non-compacted filaments. Both mitochondrial derivatives have the same shape and diameters. The presence of sperm bundles in sexually mature males differentiates C. victimafrom other ants; however, the similarities in the sperm ultrastructure support the monophyly of this insect group.

It is shown that flavor mixing of the strange and light quarks allows for existence of a much larger baryonic chemical potential window for the formation of a stable dual chiral-wave state as compared to the well-known two-flavor case. In addition, strangeness catalyzes the occurrence of a new branch of nonhomogeneous solutions at moderate densities. This case study is addressed at zero temperature within the SU(3) flavor Nambu-Jona-Lasinio model with the 't Hooft determinantal flavor mixing interaction. The modulation of the chiral condensates in the light quark sector is taken to be one dimensional, while strangeness is embedded as a homogeneous condensate in the spontaneously broken phase of chiral symmetry. A finite current quark mass for the strange quark is incorporated, while the up and down current masses are set to zero. In that case the modulation considered provides an exact analytic solution for the system. Despite the simplicity of the ansatz, the emerging phase diagram displays a very rich structure. [ABSTRACT FROM AUTHOR]

Soluble oligomers of the amyloid- peptide (AOs) accumulate in Alzheimers disease (AD) brain and have been implicated in mechanisms of pathogenesis. The neurotoxicity of AOs appears to be, at least in part, due to dysregulation of glutamate signaling. Here, we show that AOs promote extracellular accumulation of glutamate and D-serine, a co-agonist at glutamate receptors of the N-methyl-D-aspartate subtype (NMDARs), in hippocampal neuronal cultures. The increase in extracellular glutamate levels induced by AOs was blocked by the sodium channel blocker tetrodotoxin (TTX), by the NMDAR blocker ()-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) and by removal of Ca2 from the extracellular medium, indicating dependence on excitatory neuronal activity. AOs enhanced the release of pre-synaptic vesicles labeled by FM1-43 as well as spontaneous post-synaptic activity measured by whole-cell patch-clamp. Activation of inhibitory GABAA receptors by taurine blocked the increase in extracellular glutamate levels, suggesting that selective pharmacological inhibition of neuronal activity can counteract the impact of AOs on glutamate dyshomeostasis. Results reveal a novel mechanism by which A oligomers promote abnormal release of glutamate from hippocampal neurons, which may contribute to dysregulation of excitatory signaling in the brain.

When designing molecular targeted therapeutic strategies against cancer, it is important to correlate protein expression and cell viability. However, such goal can be difficult if performed in separate assays, especially when only a fraction of cells has been efficiently transfected. Therefore, the aim of the present study was to establish a flow cytometry procedure to assess simultaneously Bcl2 protein level and viability in smallcell lung cancer SCLC cells. Viability assessment was performed by staining cells with Annexin Vfluorescein isothiocyanate FITC and 7aminoactinomycin D 7AAD. Intracellular detection of Bcl2 was carried out by immunodetection with monoclonal antibodies. Regarding viability determination, the FSC7AAD plot identifies the same percentage of viable cells as the FSCAnnexin VFITC plot, although with greater sensitivity. The procedures involving cells fixation with 1 paraformaldehyde and permeabilization with digitonin, required for intracellular Bcl2 immunostaining did not compromise the association of 7ADD nor Annexin VFITC previously incubated with SCLC cells. It was therefore possible to simultaneously assess cell viability and Bcl2 protein in SCLC cells. A simple, sensitive, and versatile procedure was established for the first time for the simultaneous evaluation of cell viability and intracellular detection of Bcl2 in SCLC. © 2008 International Society for Advancement of Cytometry

We describe 2DPHOT, a general-purpose analysis environment for source detection and analysis in deep wide-field images. 2DPHOT is an automated tool to obtain both integrated and surface photometry of galaxies in an image, to perform reliable star-galaxy separation with accurate estimates of contamination at faint flux levels, and to estimate completeness of the image catalog. We describe the analysis strategy on which 2DPHOT is based, and provide a detailed description of the different algorithms implemented in the package. This new environment is intended as a dedicated tool to process the wealth of data from wide-field imaging surveys. To this end, the package is complemented by 2DGUI, an environment that allows multiple processing of data using a range of computing architectures.

The Nafion perfluorinated membranes are one of the best electrolytes used in the Proton Exchange Membrane Fuel Cell (PEMFC). Some methods have been used to study the electrical properties of Nafion; nevertheless, there are some aspects of the conduction process that are not well understood, such as the contribution of the bulk and the interfacial phenomena to the total proton conduction process. In this work the Electrochemical Impedance Spectroscopy (EIS) was employed in a four electrode system to study the protonic charge transport under conditions that simulate the operation of the PEMFC. Two Nafion membranes were evaluated to determine the relation of the activation procedure with the resistance to the protonic charge transference. The results are not only consistent with other measurements but also allow to separate the protonic charge transference process in two stages. Each stage was studied and their electrical parameters were calculated using Electrical Equivalent Circuits.

Relaxation induced by nitric oxide (NO) donors is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that caveolae are important in signal transduction and Ca(2+) homeostasis. Therefore, in the present study we investigate the integrity of caveolae in vascular smooth muscle cells (VSMCs), as well as their influence on the effects produced by NO released from both the new NO donor [Ru(NH.NHq) (terpy)NO(+)](3+) (TERPY) and sodium nitroprusside (SNP) on 2K-1C rat aorta. The potency of both TERPY and SNP was lower in the 2K-1C aorta that in the normotensive aorta [two kidney (2K)], whereas the maximal relaxant effect (ME) was similar in both 2K-1C and 2K aortas. In the 2K aorta, methyl-beta-cyclodextrin (CD) reduced both the potency of TERPY and SNP, and their ME compared with the control, but it had no effect on the potency and ME of these NO donors in 2K-1C aortas. The decrease in cytosolic Ca(2+) concentration ([Ca(2+)](c)) induced by TERPY was larger in 2K than in 2K-1C cells, and this effect was inhibited by CD in 2K cells only. Aortic VSMCs from 2K rats presented a larger number of caveolae than those from 2K-1C rats. Treatment with CD reduced the number of caveolae in both 2K and 2K-1C aortic VSMCs. Our results support the idea that caveolae play a critical role in the relaxant effect and in the decrease in [Ca(2+)](c) induced by NO, and they could be responsible for impaired aorta relaxation by NO in renal hypertensive rats.

Protein phosphorylation is a crucial post-translational modification mechanism in the regulation of synaptic organization and function. Here, we analyzed synaptosome fractions from human cerebral cortex obtained during therapeutic surgery. To minimize changes in the phosphorylation state of proteins, the tissue was homogenized within two minutes of excision. Synaptosomal proteins were digested with trypsin and phosphopeptides were isolated by immobilized metal affinity chromatography and analyzed by liquid chromatography and tandem mass spectrometry. The method allowed the detection of residues on synaptic proteins that were presumably phosphorylated in the intact cell, including synapsin 1, syntaxin 1, and SNIP, PSD-93, NCAM, GABA-B receptor, chaperone molecules, and protein kinases. Some of the residues identified are the same or homologous to sites that had been previously described to be phosphorylated in mammals whereas others appear to be novel sites which, to our knowledge, have not been reported previously. The study shows that new phosphoproteomic strategies can be used to analyze subcellular fractions from small amounts of tissue for the identification of phosphorylated residues for research and potentially for diagnostic purposes. Keywords: LC−MS/MS • IMAC • mass spectrometry • protein phosphorylation • phosphoproteomics • synaptosome • synaptic • synataxin • SNIP • GABA-B

The role of oxidative stress in electroconvulsive therapy–related effects is not well studied. The purpose of this study was to determine oxidative stress parameters in several brain structures after a single electroconvulsive seizure or multiple electroconvulsive seizures. Rats were given either a single electroconvulsive shock or a series of eight electroconvulsive shocks. Brain regions were isolated, and levels of oxidative stress in the brain tissue (cortex, hippocampus, striatum and cerebellum) were measured. We demonstrated a decrease in lipid peroxidation and protein carbonyls in the hippocampus, cerebellum, and striatum several times after a single electroconvulsive shock or multiple electroconvulsive shocks. In contrast, lipid peroxidation increases both after a single electroconvulsive shock or multiple electroconvulsive shocks in cortex. In conclusion, we demonstrate an increase in oxidative damage in cortex, in contrast to a reduction of oxidative damage in hippocampus, striatum, and cerebellum.

OBJECTIVE: To review the literature concerning the risks associated with exposure to lead and lead compounds, especially in children and in populations that are occupationally exposed. Data sources: Using 'chumbo' [lead] and 'efeitos' [effects] as search terms, two large databases, namely PubMed (United States National Library of Medicine) and LILACS (Literatura Latino-Americana e do Caribe em Ciencias da Saude [Latin American and Caribbean Literature in the Health Sciences]), were searched for studies on lead toxicity from 1988 to 2002. Other sources used to conduct the search include the web page of the United States Agency for Toxic Substances and Disease Registry, in Atlanta, Georgia, and the library of the Toxicology Laboratory of the Center for Workers' Health and Human Ecology at the National School of Public Health [Centro de Estudos da Saude de Trabalhador e Ecologia Humana, Escola Nacional de Saude Publica], Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. CONCLUSIONS: The toxic effects of lead and lead compounds have been extensively studied for over a century. In recent years, epidemiologic studies have focused primarily on the neurotoxic effects of lead on children, particularly in terms of impaired intellectual ability and behavioral problems. However, there is still insufficient information on the mechanisms of action that account for such toxicity. More in-depth studies are also needed on the effects of lead exposure on bone, the central nervous system, the cardiovascular system, the kidneys, the liver, the male and female reproductive systems, and the endocrine system. The potential teratogenicity and carcinogenicity of lead, as well as its effect on pregnancy outcomes and neonatal growth and development, also require further study. [ABSTRACT FROM AUTHOR]

Diffuse reflectance and laser-induced techniques were used to access photochemical and photophysical processes of benzil in solid supports, namely p-tert-butylcalix[n]arenes with n = 4, 6, and 8. A comparative study was performed using these results and those obtained with another electronically inert support, silicalite, which is a hydrophobic zeolite. In the latter substrate, ground-state benzil has the two carbonyl groups in an s-trans planar conformation while in the calixarenes a distribution of conformers exists, largely dominated by skew conformations where the carbonyl groups are twisted one to the other. In all substrates, room-temperature phosphorescence was obtained in air-equilibrated samples. The decay times vary greatly and the largest lifetime was obtained for benzil/p-tert-butylcalix[6]arene, showing that this host cavity well accommodates benzil, enhancing its room-temperature phosphorescence. p-tert-Butylcalix[6] and [8]arene molecules provide larger hydrophobic cavities than silicalite, and inclusion complexes are formed with these hosts and benzil as guest; p-tert-butylcalix[4]arene does not include benzil. This probe is deposited outside the calix[4] cavity, in the form of microcrystals. Triplet−triplet absorption of benzil was detected in all cases and is predominant in the silicalite channel inclusion case. Benzil ketyl radical formation occurs with inclusion in calix[6]arene and calix[8]arene. In the three cases, benzoyl radical was detected at long times (in the millisecond time scale). Product analysis and identification clearly show that the main detected degradation photoproducts in all substrates are benzoyl radical derivatives. Calix[6] and [8]arenes are able to supply hydrogen atoms that allow also another reaction, the reduction to benzoin through benzil ketyl radical formation.

A new coded modulation technique for signal sets designed combining wavelet functions and M-quadrature amplitude modulation (MQAM) is presented. Trellis-coded modulation (TCM) is implemented using the ring of integers modulo-Q as the algebraic structure of the multilevel convolutional encoder. These schemes are suitable for adaptive time–frequency unequal error protection, multiple-access and multiplexing, as well as being effective replacements for existing schemes. Wavelet-based ring-TCM schemes and MQAM ring-TCM schemes are first presented, and then combined to constitute a concatenated ring-TCM scheme. The concatenated scheme shows a coding gain of around 8 dB over uncoded BPSK, and does not require iterative decoding.

The formation of inclusion complexes of β-phenylpropiophenone and benzophenone with p-tert-butylcalix[4], [6] and [8]arenes (powdered solid samples) was studied with the use of diffuse reflectance techniques. Experimental evidence was obtained for inclusion in all cases. The benzophenone n → π* absorption band exhibits hypsochromic shifts with an increase of the calixarene ring aperture, providing evidence for an increase in cavity polarity. β-Phenylpropiophenone exhibits strong room temperature phosphorescence in contrast to its solution behaviour, and this is a clear evidence for the inclusion of this probe within the calixarene molecules. Calix[4]arene and calix[8]arene provide a more rigid environment to β-phenylpropiophenone whereas calix[6]arene appears to be more flexible. Transient absorption spectra of inclusion complexes with benzophenone (1 : 1 mol : mol, excited at 355 nm) show major triplet formation in the calix[4]arene case, while the ketyl radical of benzophenone is formed in the calix[6]arene case and is predominant in the calix[8]arene case. Phenoxyl radical transient absorption also becomes evident in the last two cases. For β-phenylpropiophenone (1 : 1 mol : mol) phenoxyl radicals are formed but no evidence was found for triplet or ketyl radical formation of this ketone in the calix[4]arene case. However, strong support for the ketyl radical of the aryl alkyl ketone was found for calix[6]arene and calix[8]arene inclusion complexes.

We report a detailed experimental study of infrared reactivity and Raman spectroscopies in strongly deuterated betaine arsenate: BA 0.08 DBA 0.92 . The temperature dependence of the frequency of the hydrogen bonds stretching modes shows a different critical behaviour for the different types of hydrogen bonds. At 163 K , there is evidence for the proton ordering in the shorter hydrogen bond. A progressive softening of the dynamical central peak revelead some aspects of an order-disorder mechanism.

Accurate X-ray measurements were performed in betaine arsenate (BA) and strongly deuterated betaine arsenate (DBA92) in the temperature range 300 to 80 K. The temperature dependence of the lattice parameters was studied and it provides a clear evidence for the existence of two phase transitions, one at 119 K and another one at 107 K. The symmetry of the low temperature phase of BA is P1n1. Nevertheless, our results are not conclusive about the symmetry of the antiferroelectric and ferroelectric phases in DBA92. The correlation lengths of the ordered phases in BA and DBA92 involve a limited number of unit cells, thus providing evidence for the existence of small polar clusters in these materials below Tc2.

Betaine potassium iodide dihydrate (BKI) is a new compound of the aminoacid betaine with a triclinic symmetry and with the space group P1 at room temperature. It undergoes a phase transition at 100 K. In this paper we report a detailed study of the dielectric relaxation and of the pyroelectric properties of this compound in the temperature range 20-300K. A microscopic interpretation of dielectric properties is presented by doing a comparison between the dielectric dispersion behaviour and the results obtained in the study of Raman scattering of BKI.

In this work a model envisaging the integrated optimization of bioreaction and downstream processing is presented. This model extends the work presented in part 1 of this pair of papers by adding ultrafiltration to process optimization. The new operational parameters include ultrafiltration time, pressure, and stirring rate. For global optimization, the model uses as constraints the final product titer and quality to be achieved after downstream processing. This extended model was validated with the same system used in part 1, i.e., PA317 cells producing a recombinant retrovirus containing the LacZ gene as a marker in stirred tanks using porous supports. Optimization of the extended model led to the conclusion that bioreaction should have two steps, batch and perfusion, similar to what was found in part 1. Ultrafiltration in a stirred cell should be performed at low pressures and stirring rates to reduce the losses of infective retroviruses. Sensitivity analysis performed on the results of the integrated optimization showed that under optimal conditions the productivity is less sensitive to the parameters related to ultrafiltration than to those associated with bioreaction. These results were interpreted as reflecting the high yield of ultrafiltration (90%). The relevance of the model extension to perform integrated optimization was also demonstrated since a restriction in the specific ultrafiltration area in downstream processing conditioned perfusion duration and perfusion rate in bioreaction. This clearly indicates that overall process optimization cannot be achieved without integrated optimization.

Although retroviruses are a promising tool for gene therapy, there are two major problems limiting the establishment of viable industrial processes:  retrovirus stability and low final yield in the supernatant. This fact emphasizes the need for an effective process optimization, not only at a genetic level but also at a bioprocess engineering level. In part 1 of this paper a mathematical model was developed to optimize the bioreaction yield by determining the best retrovirus harvest strategy in perfusion cultures. PA317 cells producing recombinant retroviruses were used to develop and test this model. Cell culture was performed in stirred tanks using porous supports. The parameters of the proposed model were experimentally determined for batch and perfusion cultures at 32 and 37 °C both with and without additives to enhance production; the model was then validated. This model allowed the determination of the optimal values of all operational variables included:  batch and perfusion duration and perfusion rate. The highest productivity (2682 virus cm^-3 h^-1) was obtained under the following conditions:  batch at 37 °C for 53 h followed by perfusion at 32 °C for 23 h with a perfusion rate of 0.107 h^-1. This value was 3.5-fold higher than the best result obtained in batch cultures for the same conditions of titer and quality. A sensitivity analysis of the parameters showed that the parameters that affect most the final productivity depend on the bioreaction phase:  cell growth in batch culture and production and product degradation in perfusion culture. In part 2 of this paper, this model is extended to the first step of downstream processing, and the addition of further steps to the process is discussed in order to achieve global process optimization.

We have observed propagating adiabatic evaporation waves in superheated liquid dodecane, C12H26. Experiments were performed with a rapid decompression apparatus at initial temperatures of 180–300°C. Saturated dodecane in a tube was suddenly depressurized by rupturing a diaphragm. Motion pictures and still photographic images, and pressure and temperature data were obtained during the evaporation event that followed depressurization. Usually, a front or wave of evaporation started at the liquid free surface and propagated into the undisturbed regions of the metastable liquid. The evaporation wave front moved with a steady mean velocity but the front itself was unstable and fluctuating in character. At low superheats, no waves were observed until a threshold superheat was exceeded. At moderate superheats, subsonic downstream states were observed. At higher superheats, the downstream flow was choked, corresponding to a Chapman–Jouguet condition. At the most extreme superheat tested, a vapour content of over 90% was estimated from the measured data, indicating a nearly complete evaporation wave. Our results are interpreted by modelling the evaporation wave as a discontinuity, or jump, between a superheated liquid state and a two-phase liquid–vapour downstream state. Reasonable agreement is found between the model and observations; however, there is a fundamental indeterminacy that prevents the prediction of the observed wave speeds.

Abstract: Recombinant fusion proteins offer important new therapeutic approaches for the future. This report describes the use of three different genetic strategies (i.e. “mono-”, “bi-” and “tri-cistronic” vectors) to achieve stable secretion from BHK cells of a glycosylated antibody-cytokine fusion protein designed for use in anti-tumour therapy. It describes selection of a robust and effective production cell line based on stability of secretion of the product, quality of mRNA and protein products and performance in in vitro bioassays for potency. The data obtained at this stage were utilised in the selection of a suitable candidate production cell line. The relative productivity and general performance of the cells in stirred tank and fixed bed culture systems indicated that a variety of cell culture technologies provided robust tools for production of a highly selected cell clone. Consistency of the product glycosylation was determined by analysis of released oligosaccharides using matrix-assisted laser desorption ionisation – time of flight mass spectrometry and high-performance anion exchange chromatography. These investigations showed consistent expression of three glycoforms of the fusion protein which varied in their relative proportions in different culture systems and at different time points in a fixed bed reactor with continuous perfusion. In conclusion, this study dealt with a range of important scientific and technical issues which are essential for regulatory approval and commercial success of a recombinant protein and elucidates some useful markers for process development for similar recombinant biologicals.

Abstract: In this work, a BHK21 clone producing a recombinant antibody/cytokine fusion protein was used to study the dependence of cell metabolism on the glucose and glutamine levels in the culture medium. Results obtained indicate that both glucose and glutamine consumptions show a Michaelis-Menten dependence on glucose and glutamine concentrations respectively. A similar dependence is also observed for lactate and ammonia productions. The estimated value of the Michaelis constant for the dependence of lactate production on glucose (K GlcLac) was 1.4 ± 0.1 mM and for the dependence of ammonia production on glutamine (K GlnAmm) was 0.25 ± 0.11 mM and 0.10 ± 0.03 mM, at glucose concentrations of 0.28 mM and 5.6 mM respectively. At very low glucose concentrations, the glucose to lactate yield decreased markedly, showing a metabolic shift towards lower lactate production. This␣metabolic shift was also confirmed by the significant increase in the specific oxygen consumption rate also observed at low glucose concentrations. Although it was␣highly dependent on glucose concentration, the oxygen consumption also increased with the increase in␣glutamine concentration. At very low glutamine concentrations, the glutamine to ammonia yield increased, showing a more efficient glutamine metabolism.