The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis

This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.

Fluvio-morphological processes of meander bends - Combining conventional field measurements, close-range remote sensing and computational modelling

Meandering rivers have been perceived to evolve rather similarly around the world independently of the location or size of the river. Despite the many consistent processes and characteristics they have also been noted to show complex and unique sets of fluviomorphological processes in which local factors play important role. These complex interactions of flow and morphology affect notably the development of the river. Comprehensive and fundamental field, flume and theoretically based studies of fluviomorphological processes in meandering rivers have been carried out especially during the latter part of the 20th century. However, as these studies have been carried out with traditional field measurements techniques their spatial and temporal resolution is not competitive to the level achievable today. The hypothesis of this study is that, by exploiting e increased spatial and temporal resolution of the data, achieved by combining conventional field measurements with a range of modern technologies, will provide new insights to the spatial patterns of the flow-sediment interaction in meandering streams, which have perceived to show notable variation in space and time. This thesis shows how the modern technologies can be combined to derive very high spatial and temporal resolution data on fluvio-morphological processes over meander bends. The flow structure over the bends is recorded in situ using acoustic Doppler current profiler (ADCP) and the spatial and temporal resolution of the flow data is enhanced using 2D and 3D CFD over various meander bends. The CFD are also exploited to simulate sediment transport. Multi-temporal terrestrial laser scanning (TLS), mobile laser scanning (MLS) and echo sounding data are used to measure the flow-based changes and formations over meander bends and to build the computational models. The spatial patterns of erosion and deposition over meander bends are analysed relative to the measured and modelled flow field and sediment transport. The results are compared with the classic theories of the processes in meander bends. Mainly, the results of this study follow well the existing theories and results of previous studies. However, some new insights regarding to the spatial and temporal patterns of the flow-sediment interaction in a natural sand-bed meander bend are provided. The results of this study show the advantages of the rapid and detailed measurements techniques and the achieved spatial and temporal resolution provided by CFD, unachievable with field measurements. The thesis also discusses the limitations which remain in the measurement and modelling methods and in understanding of fluvial geomorphology of meander bends. Further, the hydro- and morphodynamic models’ sensitivity to user-defined parameters is tested, and the modelling results are assessed against detailed field measurement. The study is implemented in the meandering sub-Arctic Pulmanki River in Finland. The river is unregulated and sand-bed and major morphological changes occur annually on the meander point bars, which are inundated only during the snow-melt-induced spring floods. The outcome of this study applies to sandbed meandering rivers in regions where normally one significant flood event occurs annually, such as Arctic areas with snow-melt induced spring floods, and where the point bars of the meander bends are inundated only during the flood events.

Semantic and fuzzy modelling for human behaviour recognition in smart spaces : a case study on ambient assisted living.

Human activity recognition in everyday environments is a critical, but challenging task in Ambient Intelligence applications to achieve proper Ambient Assisted Living, and key challenges still remain to be dealt with to realize robust methods. One of the major limitations of the Ambient Intelligence systems today is the lack of semantic models of those activities on the environment, so that the system can recognize the speci c activity being performed by the user(s) and act accordingly. In this context, this thesis addresses the general problem of knowledge representation in Smart Spaces. The main objective is to develop knowledge-based models, equipped with semantics to learn, infer and monitor human behaviours in Smart Spaces. Moreover, it is easy to recognize that some aspects of this problem have a high degree of uncertainty, and therefore, the developed models must be equipped with mechanisms to manage this type of information. A fuzzy ontology and a semantic hybrid system are presented to allow modelling and recognition of a set of complex real-life scenarios where vagueness and uncertainty are inherent to the human nature of the users that perform it. The handling of uncertain, incomplete and vague data (i.e., missing sensor readings and activity execution variations, since human behaviour is non-deterministic) is approached for the rst time through a fuzzy ontology validated on real-time settings within a hybrid data-driven and knowledgebased architecture. The semantics of activities, sub-activities and real-time object interaction are taken into consideration. The proposed framework consists of two main modules: the low-level sub-activity recognizer and the high-level activity recognizer. The rst module detects sub-activities (i.e., actions or basic activities) that take input data directly from a depth sensor (Kinect). The main contribution of this thesis tackles the second component of the hybrid system, which lays on top of the previous one, in a superior level of abstraction, and acquires the input data from the rst module's output, and executes ontological inference to provide users, activities and their in uence in the environment, with semantics. This component is thus knowledge-based, and a fuzzy ontology was designed to model the high-level activities. Since activity recognition requires context-awareness and the ability to discriminate among activities in di erent environments, the semantic framework allows for modelling common-sense knowledge in the form of a rule-based system that supports expressions close to natural language in the form of fuzzy linguistic labels. The framework advantages have been evaluated with a challenging and new public dataset, CAD-120, achieving an accuracy of 90.1% and 91.1% respectively for low and high-level activities. This entails an improvement over both, entirely data-driven approaches, and merely ontology-based approaches. As an added value, for the system to be su ciently simple and exible to be managed by non-expert users, and thus, facilitate the transfer of research to industry, a development framework composed by a programming toolbox, a hybrid crisp and fuzzy architecture, and graphical models to represent and con gure human behaviour in Smart Spaces, were developed in order to provide the framework with more usability in the nal application. As a result, human behaviour recognition can help assisting people with special needs such as in healthcare, independent elderly living, in remote rehabilitation monitoring, industrial process guideline control, and many other cases. This thesis shows use cases in these areas.

Immunity and immunosuppression in experimental visceral leishmaniasis

Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL)-2, interferon (IFN)- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF)-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

Clinical signs of pneumonia in children: association with and prediction of diagnosis by fuzzy sets theory

The present study compares the performance of stochastic and fuzzy models for the analysis of the relationship between clinical signs and diagnosis. Data obtained for 153 children concerning diagnosis (pneumonia, other non-pneumonia diseases, absence of disease) and seven clinical signs were divided into two samples, one for analysis and other for validation. The former was used to derive relations by multi-discriminant analysis (MDA) and by fuzzy max-min compositions (fuzzy), and the latter was used to assess the predictions drawn from each type of relation. MDA and fuzzy were closely similar in terms of prediction, with correct allocation of 75.7 to 78.3% of patients in the validation sample, and displaying only a single instance of disagreement: a patient with low level of toxemia was mistaken as not diseased by MDA and correctly taken as somehow ill by fuzzy. Concerning relations, each method provided different information, each revealing different aspects of the relations between clinical signs and diagnoses. Both methods agreed on pointing X-ray, dyspnea, and auscultation as better related with pneumonia, but only fuzzy was able to detect relations of heart rate, body temperature, toxemia and respiratory rate with pneumonia. Moreover, only fuzzy was able to detect a relationship between heart rate and absence of disease, which allowed the detection of six malnourished children whose diagnoses as healthy are, indeed, disputable. The conclusion is that even though fuzzy sets theory might not improve prediction, it certainly does enhance clinical knowledge since it detects relationships not visible to stochastic models.

Anti-inflammatory and antinociceptive activities of an acid fraction of the seeds of Carpotroche brasiliensis (Raddi) (Flacourtiaceae)

Carpotroche brasiliensis is a native Brazilian tree belonging to the Oncobeae tribe of Flacourtiaceae. The oil extracted from its seeds contains as major constituents the same cyclopentenyl fatty acids hydnocarpic (40.5%), chaulmoogric (14.0%) and gorlic (16.1%) acids found in the better known chaulmoogra oil prepared from the seeds of various species of Hydnocarpus (Flacourtiaceae). These acids are known to be related to the pharmacological activities of these plants and to their use as anti-leprotic agents. Although C. brasiliensis oil has been used in the treatment of leprosy, a disease that elicits inflammatory responses, the anti-inflammatory and analgesic activities of the oil and its constituents have never been characterized. We describe the anti-inflammatory and antinociceptive activities of C. brasiliensis seed oil in acute and chronic models of inflammation and in peripheral and central nociception. The mixture of acids from C. brasiliensis administered orally by gavage showed dose-dependent (10-500 mg/kg) anti-inflammatory activity in carrageenan-induced rat paw edema, inhibiting both the edema by 30-40% and the associated hyperalgesia. The acid fraction (200 mg/kg) also showed significant antinociceptive activity in acetic acid-induced constrictions (57% inhibition) and formalin-induced pain (55% inhibition of the second phase) in Swiss mice. No effects were observed in the hot-plate (100 mg/kg; N = 10), rota-road (200 mg/kg; N = 9) or adjuvant-induced arthritis (50 mg/kg daily for 7 days; N = 5) tests, the latter a chronic model of inflammation. The acid fraction of the seeds of C. brasiliensis which contains cyclopentenyl fatty acids is now shown to have significant oral anti-inflammatory and peripheral antinociceptive effects.

Molecular and cellular pathogenesis of autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disease characterized by a malformation complex which includes cystically dilated tubules in the kidneys and ductal plate malformation in the liver. The disorder is observed primarily in infancy and childhood, being responsible for significant pediatric morbidity and mortality. All typical forms of ARPKD are caused by mutations in a single gene, PKHD1 (polycystic kidney and hepatic disease 1). This gene has a minimum of 86 exons, assembled into multiple differentially spliced transcripts and has its highest level of expression in kidney, pancreas and liver. Mutational analyses revealed that all patients with both mutations associated with truncation of the longest open reading frame-encoded protein displayed the severe phenotype. This product, polyductin, is a 4,074-amino acid protein expressed in the cytoplasm, plasma membrane and primary apical cilia, a structure that has been implicated in the pathogenesis of different polycystic kidney diseases. In fact, cholangiocytes isolated from an ARPKD rat model develop shorter and dysmorphic cilia, suggesting polyductin to be important for normal ciliary morphology. Polyductin seems also to participate in tubule morphogenesis and cell mitotic orientation along the tubular axis. The recent advances in the understanding of in vitro and animal models of polycystic kidney diseases have shed light on the molecular and cellular mechanisms of cyst formation and progression, allowing the initiation of therapeutic strategy designing and promising perspectives for ARPKD patients. It is notable that vasopressin V2 receptor antagonists can inhibit/halt the renal cystic disease progression in an orthologous rat model of human ARPKD.

Prevalence of vascular-endothelial growth factor, matrix metalloproteinases and tissue inhibitors of metalloproteinases in primary breast cancer

Our objective was to determine the presence of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 and specific tissue inhibitors of matrix metalloproteinase (TIMP-1 and TIMP-2) in tumor samples obtained from patients with primary breast cancer. We attempted to correlate these findings with the status of the sentinel lymph node (SLN) and clinical-pathological characteristics such as age, tumor size, histological type, histological grade, and vascular invasion. Tumor samples from 88 patients with primary breast cancer were analyzed. The immunoreactivity of VEGF, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tumors was correlated with clinical and pathological features, as well as SLN status. Nonparametric, Mann-Whittney, Kruskal-Wallis, and Spearmann tests were used. Categorical variables were analyzed by the Pearson test. No statistically significant correlation was found between the amount of VEGF, MMP-2, MMP-9, TIMP-1, and TIMP-2 and the presence of tumor cells in the SLN. However, larger tumor diameter (P < 0.01) and the presence of vascular invasion (P < 0.01) were correlated positively with a positive SLN. A significant correlation of higher VEGF levels (P = 0.04) and lower TIMP-1 levels (P = 0.04) with ductal histology was also observed. Furthermore, lower TIMP-2 levels showed a statistically significant correlation with younger age (<50 years) and larger tumor diameter (2.0-5.0 cm). A positive SLN correlated significantly with a larger tumor diameter and the presence of vascular invasion. Higher VEGF and lower TIMP-1 levels were observed in patients with ductal tumors, while higher TIMP-1 levels were observed in lobular tumors.

Structural dynamics in the global pulp and paper industry

The pulp and paper industry is currently facing broad structural changes due to global shifts in demand and supply. These changes have significant impacts on national economies worldwide. Planted forests (especially eucalyptus) and recovered paper have quickly increased their importance as raw material for paper and paperboard production. Although advances in information and communication technologies could reduce the demand for communication papers, and the growth of paper consumption has indeed flattened in developed economies, particularly in North America and Western Europe, the consumption is increasing on a global scale. Moreover, the focal point of production and consumption is moving from the Western world to the rapidly growing markets of Southeast Asia. This study analyzes how the so-called megatrends (globalization, technological development, and increasing environmental awareness) affect the pulp and paper industry’s external environment, and seeks reliable ways to incorporate the impact of the megatrends on the models concerning the demand, trade, and use of paper and pulp. The study expands current research in several directions and points of view, for example, by applying and incorporating several quantitative methods and different models. As a result, the thesis makes a significant contribution to better understand and measure the impacts of structural changes on the pulp and paper industry. It also provides some managerial and policy implications.

Simulation model of wind turbine gearbox and lubrication system

As increasing efficiency of a wind turbine gearbox, more power can be transferred from rotor blades to generator and less power is used to cause wear and heating in the gearbox. By using a simulation model, behavior of the gearbox can be studied before creating expensive prototypes. The objective of the thesis is to model a wind turbine gearbox and its lubrication system to study power losses and heat transfer inside the gearbox and to study the simulation methods of the used software. Software used to create the simulation model is Siemens LMS Imagine.Lab AMESim, which can be used to create one-dimensional mechatronic system simulation models from different fields of engineering. When combining components from different libraries it is possible to create a simulation model, which includes mechanical, thermal and hydraulic models of the gearbox. Results for mechanical, thermal, and hydraulic simulations are presented in the thesis. Due to the large scale of the wind turbine gearbox and the amount of power transmitted, power loss calculations from AMESim software are inaccurate and power losses are modelled as constant efficiency for each gear mesh. Starting values for simulation in thermal and hydraulic simulations were chosen from test measurements and from empirical study as compact and complex design of gearbox prevents accurate test measurements. In further studies to increase the accuracy of the simulation model, components used for power loss calculations needs to be modified and values for unknown variables are needed to be solved through accurate test measurements.

Rheological behavior of corn and soy mix as feed ingredients

Foods behave as non-Newtonian fluids, but little is known about how corn and soybean mix behave under viscometric flow. In order to characterize the rheological behavior of animal feed under viscometric flow, a 70:30 (mass:mass) mixture of ground corn and soybean grains was submitted to a capillary rheometer at 3 different temperatures (80, 120, and 160 °C), different moisture levels (26.5 ± 0.08; 30.4 ± 0.31, and 33.4 ± 0.05%), and 4 shear rates (30.4; 72.9; 304.3, and 728.6/second). Different strain rates and die dimensions were used to obtain the target shear rates. The resulting data were fitted to Power Law, Casson, and Bingham models. Based on experimental data, water content, mass temperature, and the effects of shear rate on the apparent shear viscosity of corn-soy mix were fitted to a single expression (p < 0.001, R² = 0.93): η = 18,769.7 (y)-0.86 e (-9.34 U + 935 T), where y is shear rate, U is sample moisture, and T is sample temperature in Kelvin scale. As expected, such mixture presented a pseudoplastic (shear-thinning) behavior.

Chemical pattern of brazilian apples: a chemometric approach based on the Fuji and Gala varieties

The chemical composition of apple juices may be used to discriminate between the varieties for consumption and those for raw material. Fuji and Gala have a chemical pattern that can be used for this classification. Multivariate methods correlate independent continuous chemical descriptors with the categorical apple variety. Three main descriptors of apple juice were selected: malic acid, total reducing sugar and total phenolic compounds. A chemometric approach, employing PCA and SIMCA, was used to classify apple juice samples. PCA was performed with 24 juices from Fuji and Gala, and SIMCA, with 15 juices. The exploratory and predictive models recognized 88% and 64%, respectively, as belonging to a mixed domain. The apple juice from commercial fruits shows a pattern related to cv. Fuji and Gala with boundaries from 0.18 to 0.389 g.100 mL-1 (malic acid), from 8.65 to 15.18 g.100 mL-1 (total reducing sugar) and from 100 to 400 mg.L-1 (total phenolic compounds), but such boundaries were slightly shorter in the remaining set of commercial apple juices, specifically from 0.16 to 0.36 g.100 mL-1, from 9.25 to 15.5 g.100 mL-1 and from 180 to 606 mg.L-1 for acidity, reducing sugar and phenolic compounds, respectively, representing the acid, sweet and bitter tastes.

Effect of air-temperature and diet composition on the drying process of pellets for japanese abalone (Haliotis discus hannai) feeding

The aim of this research was to study the effect of air-temperature and diet composition on the mass transfer kinetics during the drying process of pellets used for Japanese Abalone (Haliotis discus hannai) feeding. In the experimental design, three temperatures were used for convective drying, as well as three different diet compositions (Diets A, B and C), in which the amount of fishmeal, spirulin, algae, fish oil and cornstarch varied. The water diffusion coefficient of the pellets was determined using the equation of Fick's second law, which resulted in values between 0.84-1.94×10-10 m²/s. The drying kinetics was modeled using Page, Modified Page, Root of time, Exponential, Logarithmic, Two-Terms, Modified Henderson-Pabis and Weibull models. In addition, two new models, referred to as 'Proposed' models 1 and 2, were used to simulate this process. According to the statistical tests applied, the models that best fitted the experimental data were Modified Henderson-Pabis, Weibull and Proposed model 2, respectively. Bifactorial analysis of variance ANOVA showed that Diet A (fishmeal 44%, spirulin 9%, fish oil 1% and cornstarch 36%) presented the highest diffusion coefficient values, which were favored by the temperature increase in the drying process.

Moisture sorption isotherms of fresh and blanched pumpkin (Cucurbita moschata)

Moisture desorption isotherms of fresh and heat blanched pumpkins (Cucurbita moschata) were determined at three temperatures (30, 50 and 70 °C), using the standard, static-gravimetric method. The GAB, Oswin, BET, Halsey, and Henderson models were tested and, with the exception of the Henderson model, showed satisfactory fits to the experimental data. The GAB model was used to analyze the fitting ability to describe the isotherm type. The shape of the desorption isotherms of fresh and blanched pumpkin at 30 and 50 °C was intermediate to types II and III, and at 70 °C it was of type II for the blanched pumpkin and close to type II for the fresh sample. The influence of blanching on the decrease in equilibrium moisture was very small compared to the fresh samples and it was related to the loss of soluble solids during the pre-treatment. The isosteric heat of sorption measures indicated that a larger amount of heat was required to remove the water from the fresh samples than from the blanched ones.

Investigation of regio- and sterochemistries of microbial biotransformation /

Epoxides can be hydrolyzed by fungi to produce chiral diols. The first part of this thesis presents an investigation of the microbial hydrolysis of aziridines comparable in structure to epoxide biotransformation substrates. Biotransformation of the aziridines 1 -methyl-2-phenyl aziridine, 2- phenylaziridine and N-methyl-7-aza bicyclo[4.1.0] heptane was studied using Beauveria sulfurescens, Aspergillus niger and Diplodia gossypina but no evidence for enzymic hydrolysis was obtained. The hydroxylation reaction performed by the fungus Beauveria sulfurescens ATCC 7159 has been studied for many years and several models describing the hydroxylating pattern exhibited by this fungus have been proposed. The second part of this thesis presents a test of the proposed models. The ability of Beauveria sulfurescens to hydroxylate thirty potential substrates was examined, and the data suggest that none of the earlier proposed models accounts for all of the bioconversion results. A possible explanation is proposed, suggesting that there is more than one enzyme responsible for the hydroxylation reactions performed by Beauveria sulfurescens.