Search results for: Elton Gimenez Rossini

Authors: Elison Eduardo Jardim Bierhals, Claudineia Brazil, Deivid Pires, Rafael Haag, Elton Gimenez Rossini

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This study evaluated the uncertainties involved in the solar radiation projections generated by the Brazilian Earth System Model (BESM) of the Weather and Climate Prediction Center (CPTEC) belonging to Coupled Model Intercomparison Phase 5 (CMIP5), with the aim of identifying efficiency in the projections for solar radiation of said model and in this way establish the viability of its use. Two different scenarios elaborated by Intergovernmental Panel on Climate Change (IPCC) were evaluated: RCP 4.5 (with more optimistic contour conditions) and 8.5 (with more pessimistic initial conditions). The method used to verify the accuracy of the present model was the Nash coefficient and the Statistical bias, as it better represents these atmospheric patterns. The BESM showed a tendency to overestimate the data ​​of solar radiation projections in most regions of the state of Rio Grande do Sul and through the validation methods adopted by this study, BESM did not present a satisfactory accuracy.

Keywords: climate changes, projections, solar radiation, uncertainty

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Authors: Elison Eduardo Jardim Bierhals, Claudineia Brazil, Deivid Pires, Rafael Haag, Elton Gimenez Rossini

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The objective of this work is to evaluate the results of solar radiation projections between 2006 and 2013 for the state of Rio Grande do Sul, Brazil. The projections are provided by the General Circulation Models (MCGs) belonging to the Coupled Model Intercomparison Phase 5 (CMIP5). In all, the results of the simulation of six models are evaluated, compared to monthly data, measured by a network of thirteen meteorological stations of the National Meteorological Institute (INMET). The performance of the models is evaluated by the Nash coefficient and the Bias. The results are presented in the form of tables, graphs and spatialization maps. The ACCESS1-0 RCP 4.5 model presented the best results for the solar radiation simulations, for the most optimistic scenario, in much of the state. The efficiency coefficients (CEF) were between 0.95 and 0.98. In the most pessimistic scenario, HADGen2-AO RCP 8.5 had the best accuracy among the analyzed models, presenting coefficients of efficiency between 0.94 and 0.98. From this validation, solar radiation projection maps were elaborated, indicating a seasonal increase of this climatic variable in some regions of the Brazilian territory, mainly in the spring.

Keywords: climate change, projections, solar radiation, validation

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Authors: Elison Eduardo Jardim Bierhals, Claudineia Brazil, Rafael Haag, Elton Rossini

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This work aims to validate and make the projections of solar energy for the Brazilian period from 2025 to 2100. As the plants designed by the HadGEM2-AO (Global Hadley Model 2 - Atmosphere) General Circulation Model UK Met Office Hadley Center, belonging to Phase 5 of the Intercomparison of Coupled Models (CMIP5). The simulation results of the model are compared with monthly data from 2006 to 2013, measured by a network of meteorological sections of the National Institute of Meteorology (INMET). The performance of HadGEM2-AO is evaluated by the efficiency coefficient (CEF) and bias. The results are shown in the table of maps and maps. HadGEM2-AO, in the most pessimistic scenario, RCP 8.5 had a very good accuracy, presenting efficiency coefficients between 0.94 and 0.98, the perfect setting being Solar radiation, which indicates a horizontal trend, is a climatic alternative for some regions of the Brazilian scenario, especially in spring.

Keywords: climate change, projections, solar radiation, scenarios climate change

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Authors: Elison Eduardo Jardim Bierhals, Claudineia Brazil, Francisco Pereira, Elton Rossini

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The use of alternative energy sources to meet energy demand reduces environmental damage. To diversify an energy matrix and to minimize global warming, a solar energy is gaining space, being an important source of renewable energy, and its potential depends on the climatic conditions of the region. Brazil presents a great solar potential for a generation of electric energy, so the knowledge of solar radiation and its characteristics are fundamental for the study of energy use. Due to the above reasons, this article aims to verify the climatic variability corresponding to the variations in solar radiation anomalies, in the face of climate change scenarios. The data used in this research are part of the Intercomparison of Interconnected Models, Phase 5 (CMIP5), which contributed to the preparation of the fifth IPCC-AR5 report. The solar radiation data were extracted from The Australian Community Climate and Earth System Simulator (ACCESS) model using the RCP 4.5 and RCP 8.5 scenarios that represent an intermediate structure and a pessimistic framework, the latter being the most worrisome in all cases. In order to allow the use of solar radiation as a source of energy in a given location and/or region, it is important, first, to determine its availability, thus justifying the importance of the study. The results pointed out, for the 75-year period (2026-2100), based on a pessimistic scenario, indicate a drop in solar radiation of the approximately 12% in the eastern region of Rio Grande do Sul. Factors that influence the pessimistic prospects of this scenario should be better observed by the responsible authorities, since they can affect the possibility to produce electricity from solar radiation.

Keywords: climate change, energy, IPCC, solar radiation

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Authors: Manoela Cabo da Silva, Elton Fernandes, Ricardo Pacheco, Heloisa Pires

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This study examined cointegration and causal relationships between economic growth and regular domestic and international passenger air transport in Brazil. Total passengers embarked and disembarked were used as a proxy for air transport activity and gross domestic product (GDP) as a proxy for economic development. The test spanned the period from 2000 to 2015 for domestic passenger traffic and from 1995 to 2015 for international traffic. The results confirm the hypothesis that there is cointegration between passenger traffic series and economic development, showing a bi-directional Granger causal relationship between domestic traffic and economic development and unidirectional influence by economic growth on international passenger air transport demand. Variance decomposition of the series showed that domestic air transport was far more important than international transport to promoting economic development in Brazil.

Keywords: air passenger transport, cointegration, economic growth, GDP, Granger causality

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Authors: V. Iakovoglou, G. N. Zaimes, M. P. Arraiza Bermúdez-Cañete, J. L. García, M. C. Giménez, C. Calderón-Guerrero, F. Ioras, I. Abrudan

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A new fast growing trend in tourism is ecotourism, in which tourists visit natural ecosystems under low impact, non-consumptive and locally oriented activities. Through these activities species and habitats are maintained and typically, underdeveloped regions are emphasized. Ecotourism provides a great alternative, especially for rural and undeveloped area. At the same time, despite its many benefits, it also poses many risks for the naturally protected areas. If ecotourism is practiced improperly degradation and irreversible damages could be the unwanted result. In addition, the lack of MSc programs in the field of Ecotourism in Europe makes it a necessity to be developed. Such an MSc program is being implemented with the lead partner the Technical University of Madrid. The entire partnership has six Universities, seven SMEs and one National Park from seven different countries all over Europe. The MSc will have 10 educational modules that will be available online and will prepare professionals that will be able to implement ecotourism in a sustainable way. Only through awareness and education a sustainable ecotourism will be achieved in the protected areas of Europe.

Keywords: ERASMUS, MSc program, protected Areas, sustainability

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Authors: Raquel Rossini, Edelvais Caldeira

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The aim of this work is to investigate the motivation for the metaphorical uses of two verb combinations: come out and take over. Drawing from cognitive semantics theories, image schemas and metaphors, it was attempted to demonstrate that: a) the metaphorical senses of both 'come out' and 'take over' extend from both the verbs and the particles central (spatial) senses in such verb combinations; and b) the particles 'out' and 'over' also contribute to the whole meaning of the verb combinations. In order to do so, a random selection of 579 concordance lines for come out and 1,412 for take over was obtained from the Corpus of Contemporary American English – COCA. One of the main procedures adopted in the present work was the establishment of verb and particle central senses. As per the research questions addressed in this study, they are as follows: a) how does the identification of trajector and landmark help reveal patterns that contribute for the identification of the semantic network of these two verb combinations?; b) what is the relationship between the schematic structures attributed to the particles and the metaphorical uses found in empirical data?; and c) what conceptual metaphors underlie the mappings from the source to the target domains? The results demonstrated that not only the lexical verbs come and take, but also the particles out and over play an important whole in the different meanings of come out and take over. Besides, image schemas and conceptual metaphors were found to be helpful in order to establish the motivations for the metaphorical uses of these linguistic structures.

Keywords: cognitive linguistics, English syntax, multi-word verbs, prepositions

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Authors: Nathalia Florencia Barros Azeredo, Josué Martins Gonçalves, Pamela De Oliveira Rossini, Koiti Araki, Lucio Angnes

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This work demonstrates the electroanalysis of uric acid (UA) at very low working potential (0 V vs Ag/AgCl) directly in body fluids such as saliva and sweat using electrodes modified with mixed -Ni0.75Zn0.25(OH)2 nanoparticles exhibiting stable electrocatalytic responses from alkaline down to weakly acidic media (pH 14 to 3 range). These materials were prepared for the first time and fully characterized by TEM, XRD, and spectroscopic techniques. The electrochemical properties of the modified electrodes were evaluated in a fast and simple procedure for uric acid analyses based on cyclic voltammetry and chronoamperometry, pushing down the detection and quantification limits (respectively of 2.3*10-8 and 7.6*10-8 mol L-1) with good repeatability (RSD = 3.2% for 30 successive analyses pH 14). Finally, the possibility of real application was demonstrated upon realization of unexpectedly robust and sensitive modified FTO (fluorine doped tin oxide) glass and screen-printed sensors for measurement of uric acid directly in real saliva and sweat samples, with no significant interference of usual concentrations of ascorbic acid, acetaminophen, lactate and glucose present in those body fluids (Fig. 1).

Keywords: nickel hydroxide, mixed catalyst, uric acid sensors, biofluids

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Authors: Silvio Ricardo Rodrigues Sanches, Bianca Cogo Barbosa, Beatriz Regina Brum, Cléber Gimenez Corrêa

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To evaluate the quality of a segmentation algorithm, the authors use subjective or objective metrics. Although subjective metrics are more accurate than objective ones, objective metrics do not require user feedback to test an algorithm. Objective metrics require subjective experiments only during their development. Subjective experiments typically display to users some videos (generated from frames with segmentation errors) that simulate the environment of an application domain. This user feedback is crucial information for metric definition. In the subjective experiments applied to develop some state-of-the-art metrics used to test segmentation algorithms, the videos displayed during the experiments did not contain audio. Audio is an essential component in applications such as videoconference and augmented reality. If the audio influences the user’s perception, using only videos without audio in subjective experiments can compromise the efficiency of an objective metric generated using data from these experiments. This work aims to identify if the audio influences the user’s perception of segmentation quality in background substitution applications with audio. The proposed approach used a subjective method based on formal video quality assessment methods. The results showed that audio influences the quality of segmentation perceived by a user.

Keywords: background substitution, influence of audio, segmentation evaluation, segmentation quality

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Authors: André Felipe Gimenez, Flávia Alessandra Ribeiro da Silva, Roberto Saverio Souza Costa

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Currently, the rural producer has been facing problems regarding environmental regularization, which is precisely why the CAR (Rural Environmental Registry) was created. CAR is an electronic registry for rural properties with the purpose of assimilating notions about legal reserve areas, permanent preservation areas, areas of limited use, stable areas, forests and remnants of native vegetation, and all rural properties in Brazil. . The objective of this work was to evaluate and compare altimetry and slope data from google Earth with a digital terrain model (MDT) generated by aerophotogrammetry, in three plots of a steep slope, for the purpose of declaration in the CAR (Rural Environmental Registry). The realization of this work is justified in these areas, in which rural landowners have doubts about the reliability of the use of the free software Google Earth to diagnose inclinations greater than 25 degrees, as recommended by federal law 12651/2012. Added to the fact that in the literature, there is a deficiency of this type of study for the purpose of declaration of the CAR. The results showed that when comparing the drone altimetry data with the Google Earth image data, in areas of high slope (above 40% slope), Google underestimated the real values of terrain slope. Thus, it is concluded that Google Earth is not reliable for diagnosing areas with an inclination greater than 25 degrees (46% declivity) for the purpose of declaration in the CAR, being essential to carry out the local topographic survey.

Keywords: MDT, drone, RPA, SiCar, photogrammetry

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Authors: Matteo Rossini, Alberto Portioli Staudacher

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The market competition is moving from the single firm to the whole supply chain one because of increasing competition and growing need for operational efficiencies and customer orientation. Supply chain management allows companies to look beyond their organizational boundaries to develop and leverage resources and capabilities of their supply chain partners. This leads to create competitive advantages in the marketplace and because of this SCM has acquired strategic importance. Lean Approach is a management strategy that focuses on reducing every type of waste present in an organization. This approach is becoming more and more popular among supply chain managers. The supply chain application of lean approach is low diffused. It is not well studied which are the impacts of lean approach principles in a supply chain context. In literature there are only few studies simulating the lean approach performance in single products supply chain. This research work studies the impacts of lean principles implementation along a supply chain. To achieve this, a simulation model of a three-echelon multiproduct product supply chain has been built. Kanban system (and several priority policies) and setup time reduction degrees are implemented in the lean-configured supply chain to apply pull and lot-sizing decrease principles respectively. To evaluate the benefits of lean approach, lean supply chain is compared with an EOQ-configured supply chain. The simulation results show that Kanban system and setup-time reduction improve inventory stock level. They also show that logistics efforts are affected to lean implementation degree. The paper concludes describing performances of lean supply chain in different contexts.

Keywords: inventory policy, Kanban, lean supply chain, simulation study, supply chain management, planning

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Authors: Zainab Al-Wazzan, Luis Gimenez, Lewis Le Vay, Manaf Behbehani

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The hatching rhythm and larval release patterns of the rocky shore crab Leptoduis exaratus was investigated in relation to the tidal cycle, the time of the day, and lunar cycle. Ovigerous females were collected from rocky shores at six sites along the Kuwait coastline between April and July of 2014. The females were kept separated in aquaria under a natural photoperiod cycle and the pattern of larval release was monitored in relation to local tidal and dial cycles. Larval release occurred mostly during the night time, and was highly synchronized with neap tides that followed full moon; at the end of the hatching period, significant larval release occurred also during spring tides. Time series analysis showed a highly significant autocorrelation and the periodicity at a peak of 14-15 days. The cross-correlation analysis between hatching and the daily low tide level suggests that larvae are released about a day before neap tide. Hatching during neap tides occurred early in the night at times of the expected ebb tide. During spring tide period (late in the season), larval release occurred later during night at tides of the ebb tide. The results of this study indicated a strong relationship between the tidal cycle, time of the day and the hatching rhythm of L. exaratus. In addition, the results suggest that water level in the intertidal zone is also playing a very important role in determining the time of the hatching. Hatching and larval release synchronize with the preferred larval environmental conditions to prevent exposing larvae to physiological or environmental stress during their early larval stages. It is also an important factor in determining the larval dispersal.

Keywords: brachyura, hatching rhythm, larvae, Kuwait

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Authors: Shilpa Varghese, Adarsh Eregowda

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Introduction: The normal development and maturation of the central nervous system is significantly influenced by thyroid hormones. Small for gestational age (SGA) babies have a distinct hormonal profile than kids born at an acceptable birth weight for gestational age, according to several studies (AGA). In SGA babies, thyroid size is larger when expressed as a percentage of body weight, indicating that low thyroid hormone levels throughout foetal life may be partially compensated for. Numerous investigations have found that compared to full-term and preterm AGA neonates, SGA babies exhibit considerably decreased thyroid plasma levels. According to our hypothesis, term and preterm SGA newborns have greater thyroid-stimulating hormone (TSH) concentrations than those that are normal for gestational age (AGA) and a higher incidence of thyroid dysfunction. Need for the study: Clinically diagnosed Assessment of term SGA babies confirming thyroid dysfunction unclear Requirement and importance of ft4 along with tsh and comparative values of ft4 in SGA babies as compared to AGA babies unclear. Inclusion criteria : SGA infants including preterm (<37 weeks of gestation) term (37-40 weeks) – comparing with preterm and term AGA infants. 3.76 7.66 0 2 4 6 8 10 12 AGA Babies SGA Babies Mean Mean TSH Comparison 2.73 1.52 0 0.5 1 1.5 2 2.5 3 3.5 4 AGA Babies SGA Babies Mean Mean FT4 Comparison Discussion : According to this study, neonates with SGA had considerably higher TSH levels than newborns with AGA. Our findings have been supported by results from earlier research. The TSH level range was established to 7.5 mU/L in the study by Bosch-Giménez et al, found greater TSH concentrations in SGA newborns. Thyroid hormone levels from newborns that are tiny for gestational age were found to be higher than AGA in our investigation. According to Franco et al., blood T4 concentrations are lower in both preterm and term SGA infants, while TSH concentrations are only noticeably greater in term SGA infants compared to AGA ones. According to our study analysis, the SGA group had considerably greater FT4 concentrations. Therefore, our findings are consistent with those of the two studies that SGA babies have a higher incidence of transient hypothyroidism and need close follow-up. Conclusions: A greater frequency of thyroid dysfunction and considerably higher TSH values within the normal range were seen in preterm and term SGA babies. The SGA babies who exhibit these characteristics should have ongoing endocrinologic testing and periodic TFTs.

Keywords: thyroid hormone, thyroid function tests, small for gestationl age, appropriate for gestational age

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Authors: Dalita G. S. M. Cavalcante, Elton A. P. dos Reis, Andressa S. Gomes, Caroline S. Danna, Leandra Ernest Kerche-Silva, Eidi Yoshihara, Aldo E. Job

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In order to minimize environmental impacts, a composite was developed from mixture of leather shavings (LE) with natural rubber (NR), which patent is already deposited. The new material created can be used in applications such as floors e heels for shoes. Besides these applications, the aim is to use this new material for the production of products for the textile industry, such as boots, gloves and bags. But the question arises, as to biocompatibility of this new material. This is justified because the structure of the leather shavings has chrome. The trivalent chromium is usually not toxic, but the hexavalent chromium can be highly toxic and genotoxic for living beings, causing damage to the DNA molecule and contributing to the formation of cancer. Based on this, the objective of this study is evaluate the possible genotoxic effects of the new composite, using as system - test two cell lines (MRC-5 and CHO-K1) by comet assay. For this, the production of the composite was performed in three proportions: for every 100 grams of NR was added 40 (E40), 50 (E50) or 60 (E60) grams of LE. The latex was collected from the rubber tree (Hevea brasiliensis). For vulcanization of the NR, activators and accelerators were used. The two cell lines were exposed to the new composite in its three proportions using elution method, that is, cells exposed to liquid extracts obtained from the composite for 24 hours. For obtaining the liquid extract, each sample of the composite was crushed into pieces and mixed with an extraction solution. The quantification of total chromium and hexavalent chromium in the extracts were performed by Optical Emission Spectrometry by Inductively Coupled Plasma (ICP-OES). The levels of DNA damage in cells exposed to both extracts were monitored by alkaline version of the comet assay. The results of the quantification of metals in ICP-OES indicated the presence of total chromium in different extracts, but were not detected presence of hexavalent chromium in any extract. Through the comet assay were not found DNA damage of the CHO-K1 cells exposed to both extracts. As for MRC-5, was found a significant increase in DNA damage in cells exposed to E50 and E60. Based on the above data, it can be asserted that the extracts obtained from the composite were highly genotoxic for MRC-5 cells. These biological responses do not appear to be related to chromium metal, since there was a predominance of trivalent chromium in the extracts, indicating that during the production process of the new composite, there was no formation of hexavalent chromium. In conclusion it can infer that the leather shavings containing chromium can be reused, thereby reducing the environmental impacts of this waste. Already on the composite indicates to its incorporation in applications that do not aim at direct contact with the human skin, and it is suggested the chain of composite production be studied, in an attempt to make it biocompatible so that it may be safely used by the textile industry.

Keywords: cell line, chrome, genotoxicity, leather, natural rubber

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Authors: El Ghazi Safae, Cherkaoui Mounia

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Within companies, emotions have been forgotten as key elements of successful management systems. Seen as factors which disturb judgment, make reckless acts or affect negatively decision-making. Since management systems were influenced by the Taylorist worker image, that made the work regular and plain, and considered employees as executing machines. However, recently, in globalized economy characterized by a variety of uncertainties, emotions are proved as useful elements, even necessary, to attend high-level management. The work of Elton Mayo and Kurt Lewin reveals the importance of emotions. Since then emotions start to attract considerable attention. These studies have shown that emotions influence, directly or indirectly, many organization processes. For example, the quality of interpersonal relationships, job satisfaction, absenteeism, stress, leadership, performance and team commitment. Emotions became fundamental and indispensable to individual yield and so on to management efficiency. The idea that a person potential is associated to Intellectual Intelligence, measured by the IQ as the main factor of social, professional and even sentimental success, was the main problematic that need to be questioned. The literature on emotional intelligence has made clear that success at work does not only depend on intellectual intelligence but also other factors. Several researches investigating emotional intelligence impact on performance showed that emotionally intelligent managers perform more, attain remarkable results, able to achieve organizational objectives, impact the mood of their subordinates and create a friendly work environment. An improvement in the emotional intelligence of managers is therefore linked to the professional development of the organization and not only to the personal development of the manager. In this context, it would be interesting to question the importance of emotional intelligence. Does it impact organizational performance? What is the importance of emotional intelligence and how it impacts organizational performance? The literature highlighted that measurement and conceptualization of emotional intelligence are difficult to define. Efforts to measure emotional intelligence have identified three models that are more prominent: the mixed model, the ability model, and the trait model. The first is considered as cognitive skill, the second relates to the mixing of emotional skills with personality-related aspects and the latter is intertwined with personality traits. But, despite strong claims about the importance of emotional intelligence in the workplace, few studies have empirically examined the impact of emotional intelligence on organizational performance, because even though the concept of performance is at the heart of all evaluation processes of companies and organizations, we observe that performance remains a multidimensional concept and many authors insist about the vagueness that surrounds the concept. Given the above, this article provides an overview of the researches related to emotional intelligence, particularly focusing on studies that investigated the impact of emotional intelligence on organizational performance to contribute to the emotional intelligence literature and highlight its importance and show how it impacts companies’ performance.

Keywords: emotions, performance, intelligence, firms

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Authors: Manon Ghislain, Timothée Bonnet, Olivier Gimenez, Olivier Dehorter, Pierre-Yves Henry

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Climatic fluctuations affect the demography of animal populations, generating changes in population size, phenology, distribution and community assemblages. However, very few studies have identified the underlying demographic processes. For short-lived species, like common passerine birds, are these changes generated by changes in adult survival or in fecundity and recruitment? This study tests for an effect of annual climatic conditions (spring and winter) on annual, local adult survival at very large spatial (a country, 252 sites), temporal (25 years) and biological (25 species) scales. The Constant Effort Site ringing has allowed the collection of capture - mark - recapture data for 100 000 adult individuals since 1989, over metropolitan France, thus documenting annual, local survival rates of the most common passerine birds. We specifically developed a set of multi-year, multi-species, multi-site Bayesian models describing variations in local survival and recapture probabilities. This method allows for a statistically powerful hierarchical assessment (global versus species-specific) of the effects of climate variables on survival. A major part of between-year variations in survival rate was common to all species (74% of between-year variance), whereas only 26% of temporal variation was species-specific. Although changing spring climate is commonly invoked as a cause of population size fluctuations, spring climatic anomalies (mean precipitation or temperature for March-August) do not impact adult survival: only 1% of between-year variation of species survival is explained by spring climatic anomalies. However, for sedentary birds, winter climatic anomalies (North Atlantic Oscillation) had a significant, quadratic effect on adult survival, birds surviving less during intermediate years than during more extreme years. For migratory birds, we do not detect an effect of winter climatic anomalies (Sahel Rainfall). We will analyze the life history traits (migration, habitat, thermal range) that could explain a different sensitivity of species to winter climate anomalies. Overall, we conclude that changes in population sizes for passerine birds are unlikely to be the consequences of climate-driven mortality (or emigration) in spring but could be induced by other demographic parameters, like fecundity.

Keywords: Bayesian approach, capture-recapture, climate anomaly, constant effort sites scheme, passerine, seasons, survival

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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