Effects of sex and age on genotype x environment interaction for beef cattle body weight studied using reaction norm models

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

GRAMMAR and COMMUNICATION IN PORTUGUESE AS A FOREIGN LANGUAGE A Study in the Context of Teletandem Interactions

This paper presents a study about the role of grammar in on-line interactions conducted in Portuguese and in English, between Brazilian and English-speaking interactants, with the aim of teaching Portuguese as a foreign language (PFL). The interactions occurred by means of chat and the MSN Messenger, and generated audio and video data for language analysis. Grammar is dealt with from two perspectives, an inductive and a deductive approach, so as to investigate the relevance of systematization of grammar rules in the process of learning PFL in teletandem interactions.

H-2 and H-infinity - norm control of intelligent structures using LMI techniques

Linear Matrix Inequalities (LMIs) is a powerful too] that has been used in many areas ranging from control engineering to system identification and structural design. There are many factors that make LMI appealing. One is the fact that a lot of design specifications and constrains can be formulated as LMIs [1]. Once formulated in terms of LMIs a problem can be solved efficiently by convex optimization algorithms. The basic idea of the LMI method is to formulate a given problem as an optimization problem with linear objective function and linear matrix inequalities constrains. An intelligent structure involves distributed sensors and actuators and a control law to apply localized actions, in order to minimize or reduce the response at selected conditions. The objective of this work is to implement techniques of control based on LMIs applied to smart structures.

H2 and/or H∞-norm model reduction of uncertain discrete-time systems

This paper addresses the problem of model reduction for uncertain discrete-time systems with convex bounded (polytope type) uncertainty. A reduced order precisely known model is obtained in such a way that the H2 and/or the H∞ guaranteed norm of the error between the original (uncertain) system and the reduced one is minimized. The optimization problems are formulated in terms of coupled (non-convex) LMIs - Linear Matrix Inequalities, being solved through iterative algorithms. Examples illustrate the results.

Stresses analysis in semi-elliptic leaf spring and comparison with the SAE J788 (1982) norm

In this work are presented the values found with the experimental testing, in the semi-elliptic leaf spring, utilizing 24 strain gages, distributed in five leaves of springs; these values have been compared to the calculated values found with the application of Norm SAE J788 (1982). The results showed discrepancy between the values measured and calculated and that the Norm is not indicated to determine the actuating stress in any point of any leaf of the leaf spring, but due to its simplicity and quickness of the process it presents good precision for the pre-development of the product. Copyright © 2002 Society of Automotive Engineers, Inc.

Identification of structural damage in flexible structures using system norm and neural networks

Nowadays there is great interest in damage identification using non destructive tests. Predictive maintenance is one of the most important techniques that are based on analysis of vibrations and it consists basically of monitoring the condition of structures or machines. A complete procedure should be able to detect the damage, to foresee the probable time of occurrence and to diagnosis the type of fault in order to plan the maintenance operation in a convenient form and occasion. In practical problems, it is frequent the necessity of getting the solution of non linear equations. These processes have been studied for a long time due to its great utility. Among the methods, there are different approaches, as for instance numerical methods (classic), intelligent methods (artificial neural networks), evolutions methods (genetic algorithms), and others. The characterization of damages, for better agreement, can be classified by levels. A new one uses seven levels of classification: detect the existence of the damage; detect and locate the damage; detect, locate and quantify the damages; predict the equipment's working life; auto-diagnoses; control for auto structural repair; and system of simultaneous control and monitoring. The neural networks are computational models or systems for information processing that, in a general way, can be thought as a device black box that accepts an input and produces an output. Artificial neural nets (ANN) are based on the biological neural nets and possess habilities for identification of functions and classification of standards. In this paper a methodology for structural damages location is presented. This procedure can be divided on two phases. The first one uses norms of systems to localize the damage positions. The second one uses ANN to quantify the severity of the damage. The paper concludes with a numerical application in a beam like structure with five cases of structural damages with different levels of severities. The results show the applicability of the presented methodology. A great advantage is the possibility of to apply this approach for identification of simultaneous damages.

Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that a1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the a1B and a1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent a1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that thisproperty of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed a1A-AR regulation. OXY shows functional selectivity relative to NE and PE at a1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.

Respiratory inductive plethysmography: a comparative study between isovolume maneuver calibration and qualitative diagnostic calibration in healthy volunteers assessed in different positions

Objective: To compare two methods of respiratory inductive plethysmography (RIP) calibration in three different positions. Methods: We evaluated 28 healthy subjects (18 women and 10 men), with a mean age of 25.4 +/- 3.9 years. For all of the subjects, isovolume maneuver calibration (ISOCAL) and qualitative diagnostic calibration (QDC) were used in the orthostatic, sitting, and supine positions. In order to evaluate the concordance between the two calibration methods, we used ANOVA and Bland-Altman plots. Results: The values of the constant of proportionality (X) were significantly different between ISOCAL and QDC in the three positions evaluated: 1.6 +/- 0.5 vs. 2.0 +/- 1.2, in the supine position, 2.5 +/- 0.8 vs. 0.6 +/- 0.3 in the sitting position, and 2.0 +/- 0.8 vs. 0.6 +/- 0.3 in the orthostatic position (p < 0.05 for all). Conclusions: Our results suggest that QDC is an inaccurate method for the calibration of RIP. The K values obtained with ISOCAL reveal that RIP should be calibrated for each position evaluated.

A new approach for modeling and control of nonlinear systems via norm-bounded linear differential inclusions

A systematic approach to model nonlinear systems using norm-bounded linear differential inclusions (NLDIs) is proposed in this paper. The resulting NLDI model is suitable for the application of linear control design techniques and, therefore, it is possible to fulfill certain specifications for the underlying nonlinear system, within an operating region of interest in the state-space, using a linear controller designed for this NLDI model. Hence, a procedure to design a dynamic output feedback controller for the NLDI model is also proposed in this paper. One of the main contributions of the proposed modeling and control approach is the use of the mean-value theorem to represent the nonlinear system by a linear parameter-varying model, which is then mapped into a polytopic linear differential inclusion (PLDI) within the region of interest. To avoid the combinatorial problem that is inherent of polytopic models for medium- and large-sized systems, the PLDI is transformed into an NLDI, and the whole process is carried out ensuring that all trajectories of the underlying nonlinear system are also trajectories of the resulting NLDI within the operating region of interest. Furthermore, it is also possible to choose a particular structure for the NLDI parameters to reduce the conservatism in the representation of the nonlinear system by the NLDI model, and this feature is also one important contribution of this paper. Once the NLDI representation of the nonlinear system is obtained, the paper proposes the application of a linear control design method to this representation. The design is based on quadratic Lyapunov functions and formulated as search problem over a set of bilinear matrix inequalities (BMIs), which is solved using a two-step separation procedure that maps the BMIs into a set of corresponding linear matrix inequalities. Two numerical examples are given to demonstrate the effectiveness of the proposed approach.

Ab-initio determination of x-ray absorption near edge structure (xanes) spectra in an ultrasoft and norm conserving pseudopotentials scheme

X-ray absorption spectroscopy (XAS) is a powerful means of investigation of structural and electronic properties in condensed -matter physics. Analysis of the near edge part of the XAS spectrum, the so – called X-ray Absorption Near Edge Structure (XANES), can typically provide the following information on the photoexcited atom: - Oxidation state and coordination environment. - Speciation of transition metal compounds. - Conduction band DOS projected on the excited atomic species (PDOS). Analysis of XANES spectra is greatly aided by simulations; in the most common scheme the multiple scattering framework is used with the muffin tin approximation for the scattering potential and the spectral simulation is based on a hypothetical, reference structure. This approach has the advantage of requiring relatively little computing power but in many cases the assumed structure is quite different from the actual system measured and the muffin tin approximation is not adequate for low symmetry structures or highly directional bonds. It is therefore very interesting and justified to develop alternative methods. In one approach, the spectral simulation is based on atomic coordinates obtained from a DFT (Density Functional Theory) optimized structure. In another approach, which is the object of this thesis, the XANES spectrum is calculated directly based on an ab – initio DFT calculation of the atomic and electronic structure. This method takes full advantage of the real many-electron final wavefunction that can be computed with DFT algorithms that include a core-hole in the absorbing atom to compute the final cross section. To calculate the many-electron final wavefunction the Projector Augmented Wave method (PAW) is used. In this scheme, the absorption cross section is written in function of several contributions as the many-electrons function of the finale state; it is calculated starting from pseudo-wavefunction and performing a reconstruction of the real-wavefunction by using a transform operator which contains some parameters, called partial waves and projector waves. The aim of my thesis is to apply and test the PAW methodology to the calculation of the XANES cross section. I have focused on iron and silicon structures and on some biological molecules target (myoglobin and cytochrome c). Finally other inorganic and biological systems could be taken into account for future applications of this methodology, which could become an important improvement with respect to the multiscattering approach.

Comparison of the binding and internalization properties of 12 DOTA-coupled and ¹¹¹In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607

Specific overexpression of cholecystokinin 2 (CCK2)/gastrin receptors has been demonstrated in several tumours of neuroendocrine origin. In some of these cancer types, such as medullary thyroid cancer (MTC), a sensitive diagnostic modality is still unavailable and therapeutic options for inoperable lesions are needed. Peptide receptor radionuclide therapy (PRRT) may be a viable therapeutic strategy in the management of these patients. Several CCK2R-targeted radiopharmaceuticals have been described in recent years. As part of the European Union COST Action BM0607 we studied the in vitro and in vivo characteristics of 12 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R binding peptides. In the present study, we analysed binding and internalization characteristics. Stability, biodistribution and imaging studies have been performed in parallel by other centres involved in the project.

Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists

The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.

New pansomatostatin ligands and their chelated versions: affinity profile, agonist activity, internalization, and tumor targeting

PURPOSE: Somatostatin receptor (sst) targeting is an established method to image and treat sst-positive tumors. Particularly, neuroendocrine tumors express the receptor subtype 2 in high density, but sst1, sst3, sst4, and sst5 are also expressed to some extent in different human tumors. Currently used targeting peptides mainly have sst2 affinity. We aimed at developing (radio)peptides that bind with high affinity to all receptor subtypes. EXPERIMENTAL DESIGN: Carbocyclic octapeptides were coupled with macrocyclic chelators for radiometal labeling. Affinity, internalization, and agonist potencies were determined on sst1- to sst5-expressing cell lines. Biodistribution was determined on nude mice bearing HEK-sst2 or AR4-2J and HEK-sst3 tumors. RESULTS: High affinity to all receptor subtypes was found. Y(III)-KE88 showed agonistic properties at all five sst receptor subtypes as it inhibits forskolin-stimulated cyclic AMP production. Surprisingly, very low or even absent sst2 receptor internalization was found compared with currently clinically established octapeptides, whereas the sst3 internalization was very efficient. Biodistribution studies of [(111)In]KE88 and [(67)Ga]KE88/[(68)Ga]KE88 reflected the in vitro data. In nude mice with s.c. implanted sst2 (HEK-sst2, AR4-2J)-expressing and sst3 (HEK-sst3)-expressing tumors, high and persistent uptake was found in sst3-expressing tumors, whereas the uptake in the sst2-expressing tumors was lower and showed fast washout. The kidney uptake was high but blockable by coinjection of lysine. CONCLUSION: This peptide family shows pansomatostatin potency. As radiopeptides, they are the first to show a full pansomatostatin profile. Despite some drawback, they should be useful for imaging sst2-expressing tumors with short-lived radiometals, such as (68)Ga, at early time points and for sst3-expressing tumors at later time points with longer-lived radiometals, such as (64)Cu or (86)Y.

Inductive-Capacitive Resonant Circuit Sensors for Structural Health and Environmental Monitoring

Inductive-capacitive (LC) resonant circuit sensors are low-cost, wireless, durable, simple to fabricate and battery-less. Consequently, they are well suited to sensing applications in harsh environments or in situations where large numbers of sensors are needed. They are also advantageous in applications where access to the sensor is limited or impossible or when sensors are needed on a disposable basis. Due to their many advantages, LC sensors have been used for sensing a variety of parameters including humidity, temperature, chemical concentrations, pH, stress/pressure, strain, food quality and even biological growth. However, current versions of the LC sensor technology are limited to sensing only one parameter. The purpose of this work is to develop new types of LC sensor systems that are simpler to fabricate (hence lower cost) or capable of monitoring multiple parameters simultaneously. One design presented in this work, referred to as the multi-element LC sensor, is able to measure multiple parameters simultaneously using a second capacitive element. Compared to conventional LC sensors, this design can sense multiple parameters with a higher detection range than two independent sensors while maintaining the same overall sensor footprint. In addition, the two-element sensor does not suffer from interference issues normally encountered while implementing two LC sensors in close proximity. Another design, the single-spiral inductive-capacitive sensor, utilizes the parasitic capacitance of a coil or spring structure to form a single layer LC resonant circuit. Unlike conventional LC sensors, this design is truly planar, thus simplifying its fabrication process and reducing sensor cost. Due to the simplicity of this sensor layout it will be easier and more cost-effective for embedding in common building or packaging materials during manufacturing processes, thereby adding functionality to current products (such as drywall sheets) while having a minor impact on overall unit cost. These modifications to the LC sensor design significantly improve the functionality and commercial feasibility of this technology, especially for applications where a large array of sensors or multiple sensing parameters are required.