EFEITOS DO KEFIR SOBRE O TÔNUS AUTONÔMICO CARDÍACO E CONTROLE BARORREFLEXO DA PRESSÃO ARTERIAL EM RATOS ESPONTANEAMENTE HIPERTENSOS

Estudos têm demonstrado que o probiótico Kefir apresenta efeitos benéficos no tratamento da hipertensão arterial. O objetivo do presente trabalho foi avaliar a ação do tratamento crônico com Kefir sobre o tônus autonômico cardíaco e o barorreflexo arterial de ratos espontaneamente hipertensos (SHR). Metodologia: Ratos Wistar e SHR machos com 4 meses de idade foram divididos em 3 grupos Wistar, SHR e SHR-Kefir tratados por 60 dias com Kefir (0,3ml/100g), por gavagem. Os animais foram anestesiados e cateteres implantados na artéria e veia femoral para injeção de drogas e registro de pressão arterial pulsátil (PAP), pressão arterial média (PAM) e frequência cardíaca (FC), respectivamente. A contribuição relativa dos tônus autonômicos cardíacos, parassimpático e simpático foi estimada em animais acordados através de injeções in bolus de N-metil-atropina (2mg/kg) e de atenolol (2mg/kg), respectivamente. A frequência cardíaca intrínseca (FCI) foi estimada após o duplo bloqueio com os fármacos acima. A sensibilidade do barorreflexo foi testada nos animais acordados por meio de aumentos ou diminuições da pressão arterial (25 mmHg), através de injeção in bolus de fenilefrina (5 &#956;g/kg) e nitroprussiato de sódio (40 &#956;g/kg), sob bloqueio da atropina e atenolol 24 e 48 h depois, respectivamente. As análises da variabilidade da pressão arterial (VPA) e variabilidade da frequência cardíaca (VFC) foram feitas por meio de análise espectral, método autorregressivo, no domínio do tempo (variância da pressão sistólica e dos intervalos R-R) e da frequência (muito baixa, baixa e alta frequência, VLF, LF, HF, respectivamente). Ao fim dos experimentos, o coração e rins foram retirados e pesados para análise de hipertrofia. Resultados: Como esperado o grupo SHR apresentou PAS, PAD, PAM e FC (204±8, 144±4,167±4 mmHg e 355±9 bpm, p<0,05, respectivamente) elevadas, quando comparados com ratos Wistar (140±8, 88±2, 104±2 mmHg e 328±12 bpm, respectivamente). O tratamento com Kefir atenuou significativamente esses parâmetros (169±8, 116±6, 134±6 mmHg e 324±12 bpm, respectivamente). O grupo SHR mostrou hipertrofia ventricular esquerda (22±1,4 mg/mm, p<0,05) quando comparado com ratos Wistar (17,1±1,4 mg/mm, p<0,05). E o tratamento com Kefir foi capaz de reduzir essa hipertrofia quando normalizado pelo comprimento da tíbia (19±1,2 mg/mm, p<0,05) nos ratos SHR tratados. O tônus vagal no grupo Wistar foi de +120 bpm e +40 bpm no grupo SHR. O Kefir recuperou parcialmente o tônus vagal (+90 bpm) dos ratos SHR tratados. O tônus simpático no grupo wistar foi de -30 bpm e -90 bpm no grupo SHR. Nos ratos SHR tratados com Kefir o tônus simpático foi reduzido para -25 bpm. A sensibilidade do barorreflexo estava significativamente diminuída no grupo SHR (reflexo de bradicardia ~50%) bem como a contribuição relativa dos componentes vagal e simpático cardíaco quando comparados com o grupo Wistar. Nos ratos SHR tratados com Kefir, tanto o reflexo de bradicardia (~40%) quanto o ganho (~35%) melhoraram significativamente. O bloqueio com atropina basicamente aboliu o reflexo de bradicardia e o ganho do barorreflexo de maneira semelhante nos 3 grupos. O grupo SHR mostrou diminuição no reflexo de taquicardia (38%, p<0,05) e redução no ganho (32%, p<0,05), quando comparado com o grupo Wistar. Nos ratos tratados com Kefir essas respostas melhoraram (~8% e ~12%, p<0,05, respectivamente). O bloqueio com atenolol reduziu a taquicardia reflexa em SHR quando comparado com Wistar e normalizou nos SHR tratados com Kefir (7±2,8, 14±2,4 e 12±2,4 bpm, respectivamente), efeito semelhante foi observado no ganho (0,26±0,10, 0,53±0,11 e 0,46±0,12 bpm/mmHg, respectivamente). A VFC e a FC-LF estavam maiores nos animais SHR (730±150 ms2 e 82±10 ms2) quando comparadas com ratos Wistar (247±46 ms2 e 39±9 ms2) e SHR tratados com Kefir (478±80 ms2 e 56±10 ms2). Não houve diferenças na comparação dos resultados de FC-HF entre os três grupos estudados. Tanto a VPA quanto a PA-LF aumentaram significativamente nos ratos SHR (73±9 mmHg2 e 13±2 mmHg2) quando comparados com ratos Wistar (22±3 mmHg2 e 3,7±0,4 mmHg2). O tratamento com Kefir reduziu esses valores (65±8 mmHg2 e 8±2 mmHg2). Por fim, a análise do barorreflexo espontâneo mostrou diminuição significativa na sensibilidade do grupo SHR (1,36±0,09 ms2/mmHg) quando comparado com o grupo Wistar (1,75±011 ms2/mmHg). O tratamento com Kefir não melhorou esta sensibilidade (1,48±0,09 ms2/mmHg). Conclusão: Após 60 dias de tratamento com Kefir, os animais SHR apresentaram diminuição da PAS, PAD e PAM, além de redução da hipertrofia cardíaca. Além disso, o tratamento com Kefir também reverteu parcialmente a perda do tônus vagal, o aumento do tônus simpático e a disfunção barorreflexa dos animais hipertensos

Bayesian calibration and sensitivity analysis of heat transfer models for fire insulation panels

International audienc

Boundaries and Prototypes in Categorizing Direction

Projective terms such as left, right, front, back are conceptually interesting due to their flexibility of contextual usage and their central relevance to human spatial cognition. Their default acceptability areas are well known, with prototypical axes representing their most central usage and decreasing acceptability away from the axes. Previous research has shown these axes to be boundaries in certain non-linguistic tasks, indicating an inverse relationship between linguistic and non-linguistic direction concepts under specific circumstances. Given this striking mismatch, our study asks how such inverse non-linguistic concepts are represented in language, as well as how people describe their categorization. Our findings highlight two distinct grouping strategies reminiscent of theories of human categorization: prototype based or boundary based. These lead to different linguistic as well as non-linguistic patterns

Visual Similarity Perception of Directed Acyclic Graphs: A Study on Influencing Factors

While visual comparison of directed acyclic graphs (DAGs) is commonly encountered in various disciplines (e.g., finance, biology), knowledge about humans' perception of graph similarity is currently quite limited. By graph similarity perception we mean how humans perceive commonalities and differences in graphs and herewith come to a similarity judgment. As a step toward filling this gap the study reported in this paper strives to identify factors which influence the similarity perception of DAGs. In particular, we conducted a card-sorting study employing a qualitative and quantitative analysis approach to identify 1) groups of DAGs that are perceived as similar by the participants and 2) the reasons behind their choice of groups. Our results suggest that similarity is mainly influenced by the number of levels, the number of nodes on a level, and the overall shape of the graph.Comment: Graph Drawing 2017 - arXiv Version; Keywords: Graphs, Perception, Similarity, Comparison, Visualizatio

Cognitive Invariants of Geographic Event Conceptualization: What Matters and What Refines?

Behavioral experiments addressing the conceptualization of geographic events are few and far between. Our research seeks to address this deficiency by developing an experimental framework on the conceptualization of movement patterns. In this paper, we report on a critical experiment that is designed to shed light on the question of cognitively salient invariants in such conceptualization. Invariants have been identified as being critical to human information processing, particularly for the processing of dynamic information. In our experiment, we systematically address cognitive invariants of one class of geographic events: single entity movement patterns. To this end, we designed 72 animated icons that depict the movement patterns of hurricanes around two invariants: size difference and topological equivalence class movement patterns endpoints. While the endpoint hypothesis, put forth by Regier (2007), claims a particular focus of human cognition to ending relations of events, other research suggests that simplicity principles guide categorization and, additionally, that static information is easier to process than dynamic information. Our experiments show a clear picture: Size matters. Nonetheless, we also find categorization behaviors consistent with experiments in both the spatial and temporal domain, namely that topology refines these behaviors and that topological equivalence classes are categorized consistently. These results are critical steppingstones in validating spatial formalism from a cognitive perspective and cognitively grounding work on ontologies

Estimativa do índice de desconforto térmico em Planaltina-DF.

Objetivou-se com o presente trabalho analisar o índice de desconforto térmico humano (IDT) para o município de Planaltina-DF. Os dados utilizados neste estudo foram coletados pela estação meteorológica automática principal da Embrapa Cerrados, no período de 01/01/2013 á 31/12/2013, cujas coordenadas geográficas são: latitude 15°36?04??S, longitude 47°42?50??W e altitude de 1001 m. Para a determinação do índice de desconforto térmico humano proposto por Thom, foram utilizados os componentes medidos: temperatura do ar (tar) e umidade relativa do ar (UR). Com base nessas estimativas, os valores de ID foram classificados em quatro intervalos: pouco desconfortável (IDT?14,9); confortável (15,0?IDT?19,9); parcialmente confortável (20,0?IDT?26,4); muito desconfortável (IDT?26,5). Os resultados mostraram que ao longo do período estudado, constataram-se valores de IDT variando entre 16,98 e 23,78, que ocorreram nos meses de julho e setembro, respectivamente. Verificou-se ainda que o período mais crítico ocorreu entre os meses de fevereiro e setembro onde foram observados valores de IDT entre 22,75 e 23,78. Os menores valores de IDT ocorreram entre os meses de maio (17,16) e julho (16,98). Contudo, verificou-se que a condição de IDT classificado como parcialmente confortável foi a que mais ocorreu durante o ano, representando cerca de 64% das estimativas, enquanto 36% foram classificadas como confortável. Os maiores riscos de desconforto térmico humano no município de Planaltina-DF ocorreram nos meses de março e setembro. Estes resultados podem estar associados à variabilidade da radiação solar e ao baixo número de dias chuvosos que aconteceu nestes meses. Setembro é um mês característico da época seca no Cerrado. ABSTRACT: The objective of this study was analyze the human thermal discomfort index (TDI) for the city of Planaltina-DF. The data used in this study were collected by the main automatic weather station Embrapa Cerrado, in the period 01/01/2013 to 31/12/2013, the positions are: latitude 15 ° 36'04 "S, longitude 47 ° 42 '50''W and altitude 1001 m. for determining the human thermal discomfort index proposed by Thom, were used the measured components: Air temperature (tar) and relative humidity (RH). Based on these estimates, the ID values were classified into four ranges: little uncomfortable (TDI?14,9); comfortable (15,0?TDI?19,9); partially comfortable (20,0? TDI ?26,4); very uncomfortable (TDI ?26,5). The results showed that during the study period were noted TDI values ranging between 16.98 and 23.78, which occurred in the months of July and September, respectively. It was also found that the most critical period occurred between the months of February and September where TDI values were observed between 22.75 and 23.78. Smaller TDI values occurred between the months of May (17.16) and July (16.98). However, it was found that the TDI condition classified as partially comfortable was the most occurred during the year, representing about 64% of the estimates, while 36% were classified as comfortable. The greatest risk of human thermal discomfort in Planaltina DF municipality occurred in the months of March and September. These findings may be related to the variability of solar radiation and the low number of rainy days that happened in these months. September is a typical month of the dry season in the Cerrado

Discovery of 74 new bright ZZ Ceti stars in the first three years of TESS

We report the discovery of 74 new pulsating DA white dwarf stars, or ZZ Cetis, from the data obtained by the Transiting Exoplanet Survey Satellite mission, from Sectors 1 to 39, corresponding to the first 3 cycles. This includes objects from the Southern hemisphere (Sectors 1–13 and 27–39) and the Northern hemisphere (Sectors 14–26), observed with 120 s- and 20 s-cadence. Our sample likely includes 13 low-mass and one extremely low-mass white dwarf candidate, considering the mass determinations from fitting Gaia magnitudes and parallax. In addition, we present follow-up time series photometry from ground-based telescopes for 11 objects, which allowed us to detect a larger number of periods. For each object, we analysed the period spectra and performed an asteroseismological analysis, and we estimate the structure parameters of the sample, i.e. stellar mass, effective temperature, and hydrogen envelope mass. We estimate a mean asteroseismological mass of 〈Msis〉 = 0.635 ± 0.015 M⊙, excluding the candidate low or extremely low-mass objects. This value is in agreement with the mean mass using estimates from Gaia data, which is 〈Mphot〉 = 0.631 ± 0.040 M⊙, and with the mean mass of previously known ZZ Cetis of 〈M*〉 = 0.644 ± 0.034 M⊙. Our sample of 74 new bright ZZ Cetis increases the number of known ZZ Cetis by ∼20 per cent

Microenvironmental Influence on Pre-Clinical Activity of Polo-Like Kinase Inhibition in Multiple Myeloma: Implications for Clinical Translation

Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers

Where Snow is a Landmark: Route Direction Elements in Alpine Contexts

Route directions research has mostly focused on urban space so far, highlighting human concepts of street networks based on a range of recurring elements such as route segments, decision points, landmarks and actions. We explored the way route directions reflect the features of space and activity in the context of mountaineering. Alpine route directions are only rarely segmented through decision points related to reorientation; instead, segmentation is based on changing topography. Segments are described with various degrees of detail, depending on difficulty. For landmark description, direction givers refer to properties such as type of surface, dimension, colour of landscape features; terrain properties (such as snow) can also serve as landmarks. Action descriptions reflect the geometrical conceptualization of landscape features and dimensionality of space. Further, they are very rich in the semantics of manner of motion

Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation

BACKGROUND: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined. METHODS: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded normal adult human (age 33–71 years, median 44 years) tissue specimens including those from the gastrointestinal, genitourinary, hepatobiliary, endocrine, integument and lymphoid systems. Antibody specificity was verified by Western blotting of cell lysates and peptide blocking studies. Immunohistochemistry intensity was scored from undetectable to strong. RESULTS: PI3K enzymes were expressed in selected cell populations of epithelial or mesenchymal origin. Columnar epithelium and transitional epithelia were reactive but mucous secreting and stratified squamous epithelia were not. Mesenchymal elements (smooth muscle and endothelial cells) and glomerular epithelium were only expressed PI3K-C2α while ganglion cells expressed p85 and PI3K-C2β. All three enzymes were detected in macrophages, which served as an internal positive control. None of the three PI3K isozymes was detected in the stem cell/progenitor compartments or in B lymphocyte aggregates. CONCLUSIONS: Taken together, these data suggest that PI3K enzyme distribution is not ubiquitous but expressed selectively in fully differentiated, non-proliferating cells. Identification of the normal in vivo expression pattern of class IA and class II PI3K paves the way for further analyses which will clarify the role played by these enzymes in inflammatory, neoplastic and other human disease conditions