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Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.
Background: The human ATP-binding cassette, subfamily B, member 11 (ABCB11) gene encodes the bile salt export pump, which is exclusively expressed at the canalicular membrane of hepatocytes. A frequent variant in the coding region, c.1331 T > C, leading to the amino acid exchange p.V444A, has been associated with altered serum bile salt levels in healthy individuals and predisposes homozygous carriers of the [C] allele for obstetric cholestasis. Recently, elevated bile salt levels were shown to be significantly associated with rates and risk of cirrhosis in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon-alpha2 and ribavirin, suggesting a potential role for bile salt levels in HCV treatment outcomes and in the fibrogenic evolution of HCV-related liver disease. The aim of this study was to investigate a possible association of ABCB11 c.1331 T > C with hepatitis C virus (HCV) infection and fibrosis stages as assessed by non-invasive transient elastography in a German cohort of patients.
Methods: ABCB11 c.1331 T > C genotype was determined by allelic discrimination assay in 649 HCV infected cases and 413 controls. Overall, 444 cases were staged for fibrotic progression by measurement of liver stiffness.
Results: Homo- or heterozygous presence of the frequent [C] allele was associated with HCV positivity (OR = 1.41, CI = 1.02 - 1.95, p = 0.037). No association was detectable between the ABCB11 c.1331 T > C genotype and increased liver stiffness.
Conclusions: Our data confirm that homozygous presence of the major [C] allele of ABCB11 c.1331 T > C is a genetic susceptibility factor for HCV infection, but not for liver fibrosis.
Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop- and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
We derive a shape derivative formula for the family of principal Dirichlet eigenvalues λs(Ω) of the fractional Laplacian (−Δ)s associated with bounded open sets Ω⊂RN of class C1,1. This extends, with a help of a new approach, a result in Dalibard and Gérard-Varet (Calc. Var. 19(4):976–1013, 2013) which was restricted to the case s=12. As an application, we consider the maximization problem for λs(Ω) among annular-shaped domains of fixed volume of the type B∖B¯¯¯¯′, where B is a fixed ball and B′ is ball whose position is varied within B. We prove that λs(B∖B¯¯¯¯′) is maximal when the two balls are concentric. Our approach also allows to derive similar results for the fractional torsional rigidity. More generally, we will characterize one-sided shape derivatives for best constants of a family of subcritical fractional Sobolev embeddings.
A Internet das Coisas tem revolucionado a forma de produção e reprodução do conhecimento. Trata-se de um tipo de interface comunicacional entre humanos, máquinas e objetos que, ao fundir os mundos material e informacional, suscita as seguintes questões: (1) a possibilidade de obtenção imediata de quaisquer informações implicaria na produção do pensamento crítico, em uma espécie de relação causa-efeito?; (2) se é possível acessar as informações em quaisquer tempo e espaço, quais seriam as transformações decorrentes no processo formativo dos alunos e dos professores? Justamente essas questões motivaram os autores do artigo a elaborar o seguinte objetivo: refletir criticamente sobre a revitalização do conceito de formação (Bildung ) na temporalidade e localidade da Internet das Coisas.
The extraordinary desiccation resistance of the opportunistic human pathogen Acinetobacter baumannii is a key to its survival and spread in medical care units. The accumulation of compatible solute such as glutamate, mannitol and trehalose contributes to the desiccation resistance. Here, we have used osmolarity as a tool to study the response of cells to low water activities and studied the role of a potential inorganic osmolyte, K+, in osmostress response. Growth of A. baumannii was K+-dependent and the K+-dependence increased with the osmolarity of the medium. After an osmotic upshock, cells accumulated K+ and K+ accumulation increased with the salinity of the medium. K+ uptake was reduced in the presence of glycine betaine. The intracellular pools of compatible solutes were dependent on the K+ concentration: mannitol and glutamate concentrations increased with increasing K+ concentrations whereas trehalose was highest at low K+. After osmotic upshock, cells first accumulated K+ followed by synthesis of glutamate; later, mannitol and trehalose synthesis started, accompanied with a decrease of intracellular K+ and glutamate. These experiments demonstrate K+ uptake as a first response to osmostress in A. baumannii and demonstrate a hierarchy in the time-dependent accumulation of K+ and different organic solutes.
The HADES experiment at GSI has recently provided data on the flow coefficients v1,..., v4 for protons in Au+Au reactions at Elab = 1.23 AGeV (or √sNN = 2.4 GeV). This data allows to estimate the shear viscosity over entropy density ratio, η/s at low energies via a coarse graining analysis of the UrQMD transport simulations of the flow harmonics in comparison to the experimental data. By this we can provide for the first time an estimate of η/s ≈ 0.65 ± 0.15 (or (8 ± 2)(4π)−1) at such low energies.
O problema da universalização na filosofia moral não foi de forma alguma tematizado por Adorno. Contudo, há elementos nas suas obras que nos possibilitam refletir sobre esse tema. Tendo por base os escritos de Adorno, e esta é minha tese, pode-se estudar como a ambivalência das diretrizes normativas é integrada numa teoria crítica da moral sem que se renuncie a uma pretensão de validade crítico-normativa.
Este ensaio se propõe a rastrear, no transcurso de sua vida e de seus escritos, a seguinte asserção de Adorno: "Estudei filosofia e música. Em vez de me decidir por uma, sempre tive a impressão de que perseguia a mesma coisa em ambas", e mostrar como a relação contínua e dialética entre música e filosofia foi fecunda em sua formação educacional e científica, bem como na constituição de seu original pensamento filosófico.
A new method of event characterization based on Deep Learning is presented. The PointNet models can be used for fast, online event-by-event impact parameter determination at the CBM experiment. For this study, UrQMD and the CBM detector simulation are used to generate Au+Au collision events at 10 AGeV which are then used to train and evaluate PointNet based architectures. The models can be trained on features like the hit position of particles in the CBM detector planes, tracks reconstructed from the hits or combinations thereof. The Deep Learning models reconstruct impact parameters from 2-14 fm with a mean error varying from -0.33 to 0.22 fm. For impact parameters in the range of 5-14 fm, a model which uses the combination of hit and track information of particles has a relative precision of 4-9% and a mean error of -0.33 to 0.13 fm. In the same range of impact parameters, a model with only track information has a relative precision of 4-10% and a mean error of -0.18 to 0.22 fm. This new method of event-classification is shown to be more accurate and less model dependent than conventional methods and can utilize the performance boost of modern GPU processor units.
Amide proton transfer-chemical exchange saturation transfer (APT-CEST) imaging provides important information for the diagnosis and monitoring of tumors. For such analysis, complete coverage of the brain is advantageous, especially when registration is performed with other magnetic resonance (MR) modalities, such as MR spectroscopy (MRS). However, the acquisition of Z-spectra across several slices via multislice imaging may be time-consuming. Therefore, in this paper, we present a new approach for fast multislice imaging, allowing us to acquire 16 slices per frequency offset within 8 s. The proposed fast CEST-EPI sequence employs a presaturation module, which drives the magnetization into the steady-state equilibrium for the first frequency offset. A second module, consisting of a single CEST pulse (for maintaining the steady-state) followed by an EPI acquisition, passes through a loop to acquire multiple slices and adjacent frequency offsets. Thus, the whole Z-spectrum can be recorded much faster than the conventional saturation scheme, which employs a presaturation for each single frequency offset. The validation of the CEST sequence parameters was performed by using the conventional saturation scheme. Subsequently, the proposed and a modified version of the conventional CEST sequence were compared in vitro on a phantom with different T1 times and in vivo on a brain tumor patient. No significant differences between both sequences could be found in vitro. The in vivo data yielded almost identical MTRasym contrasts for the white and gray matter as well as for tumor tissue. Our results show that the proposed fast CEST-EPI sequence allows for rapid data acquisition and provides similar CEST contrasts as the modified conventional scheme while reducing the scanning time by approximately 50%.
A new artificial regulatory system for essential genes in yeast is described. It prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers introduced into their 5'UTRs. Exploiting direct RNA–ligand interaction renders auxiliary protein factors unnecessary. Therefore, our approach is strain independent and not susceptible to interferences by heterologous expressed regulatory proteins. We use a simple PCR-based strategy, which allows easy tagging of any target gene and the level of gene expression can be adjusted due to various tc aptamer-regulated promoters. As proof of concept, five differently expressed genes were targeted, two of which could not be regulated previously. In all cases, adding tc completely prevented growth and, as shown for Nop14p, rapidly abolished de novo protein synthesis providing a powerful tool for conditional regulation of yeast gene expression.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students
O presente artigo pretende sustentar que o diagnóstico adorniano sobre perda da experiência qualitativa do tempo no expressionismo de Schoenberg pode ser desdobrado a partir da mobilização de dois conceitos da musicologia: o trabalho temático e a harmonia tonal. Ambos os conceitos estão associados a procedimentos compositivos em virtude dos quais logrou-se, na música anterior ao expressionismo, uma continuidade temporal que obedecia a uma necessidade, isto é, não contingente, ou fortuita. A dissolução da continuidade temporal na obra expressionista de Schoenberg é, portanto, resultado do abandono destes mesmos procedimentos.
O artigo propõe uma aproximação entre dois campos de pesquisa distintos, mas com notórias afinidades eletivas: o campo da arqueologia e o da estética filosófica. Pretende-se saber de que modo, no interior do pensamento dialético de Adorno, articulam-se os conceitos de pré-história e proto-história, tendo como fio condutor a temática da arte rupestre e a sua contrapartida moderna, isto é, a reprodutibilidade técnica. Tal aproximação tem como ponto de partida um instigante parágrafo da obra póstuma de Adorno, “Ästhetische Theorie”, presente na subseção assim classificada por Rolf Tiedmann como "Moderne Kunst und Industrielle Produktion", no qual Adorno afirma que há uma convergência entre a arte rupestre e a câmera fotográfica, que se daria na objetivação (Objektivation), isto é, na ação de separar o ato subjetivo do objeto que é visto. A partir desta constatação, a contribuição maior deste artigo estaria em identificar uma espécie de proto-história da reprodutibilidade técnica no mundo pré-histórico. Deste modo, numa perspectiva radicalmente dialética pode-se dizer que o progresso virtual e tecnológico sentido nas últimas décadas não representa algo qualitativamente novo na história humana, sendo apenas um desdobramento de uma tendência já contida na pré-história, algo que nos leva a crer que não conseguimos ainda superar o estado de imanência mítica denunciado amplamente por Adorno e Horkheimer na “Dialektik der Aufklärung. Para demonstrar isto o presente artigo almeja reconstruir as principais linhas de força da "Dialética do Esclarecimento", centrando na categoria de mito (Seção 1). Após, pretende apresentar a relação entre pré-história e proto-história no contexto do pensamento adorniano, especialmente nas obras e nos ensaios do período intermediário de sua bibliografia, tais como “Minima Moralia” e “Prismen” (Seção 2). Por último, deseja apresentar algumas reflexões de Adorno sobre a arte rupestre e a reprodutibilidade técnica presentes na Teoria Estética (Seção 3).
O texto trata da relação entre esfera pública e meios de comunicação de massa, no corpus bibliográfico de Jürgen Habermas, nestes 50 anos que nos separam de Strukturwandel der Öffentlichkeit (1962). O objetivo do texto é mostrar que, diferente de alguns estudos críticos, não se trata de uma lacuna investigativa - ausência, abandono ou não exploração do tema - , mas de uma abordagem secundária, implícita; que a abordagem secundária do tema está relacionada com a posição pessimista original de Habermas acerca da influência negativa dos meios de comunicação de massa, na despolitização da esfera pública; que o pessimismo de Habermas sobre os efeitos negativos dos meios de comunicação de massa mantém uma conexão interna com a orientação original da crítica da cultura de massa de Adorno. Isso significa que, apesar das reformulações e novos diagnósticos, a posição cética de Habermas quanto ao potencial democrático dos meios de comunicação de massa na repolitização da esfera pública parece não ter mudado em seus fundamentos, nestes 50 anos.
A sociedade como um todo vivencia uma crise de ordem ética, mas de uma ética, sobretudo, coletiva. As “pequenas” barbáries instalam-se silenciosamente na sociedade, fomentadas por um sistema econômico que, na sua raiz, é excludente e implacável com aqueles que não se enquadram de alguma forma nele. As pequenas banalizações das injustiças criam elementos que alertam para a possibilidade de que Auschwitz se repita, medo presente e evidenciado por Adorno nas suas obras mais importantes. Os objetivos deste trabalho são responder aos seguintes questionamentos: 1) como traduzir para o dia-a-dia da educação a desconstrução da cultura de violência e preconceito que avança em todo o mundo? 2) Como trabalhar uma pedagogia da imaginação, que seja, antes de mais nada, a condição de imaginar o outro, de imaginar-se no lugar do outro? 3) Quais as bases epistemológicas norteadoras de tal objetivo? Para tanto, verificar-se-á que, por meio da pedagogia do antipreconceito, fundamentada sobretudo no pensamento de Adorno, de Horkheimer e de Marcuse, é possível promover a interdisciplinaridade que aproxime razão de afeto e que denuncie a negação do preconceito, esclarecendo, ainda, que para se fazer uma sociedade mais humanizada torna-se impositivo passar pela desconstrução, pela compreensão e pela reconstrução da educação. Entender e esclarecer como o homem médio viabiliza as posturas excludentes e preconceituosas, impostas tanto pela condição humana quanto pelo capitalismo contemporâneo, no cotidiano da educação constitui uma de suas metas. Enfim, o trabalho propõe-se afirmar a possibilidade de uma ética para a sociedade tecnológica e de semiformação, fundamentada na pedagogia do antipreconceito, cuja finalidade seja a formação de sujeitos conscientes das limitações da ciência e do uso da tecnologia para impedir a barbárie, cuja bandeira seja a do combate à intolerância e às violências e o instrumento principal seja a imaginação.
By means of the analysis of two Theodor Adomo's texts temporal1y very distant from each other -one written in the beginning of his career, the other in his maturity -, this article shows that the essay was for him not merely a theme of reflection, but also and upmost a kind of matrix for his thought. Within this matrix, through resort to a tradition, begun, in the Modernity, with Montaigne and solidified with Leibniz and the English empiricists, Adorno seeks to build, in the last phase of his philosophy, his conception of an "Anti-system", in which the indispensable coherence of thought can be kept save from instrumentalization by the domination system.
O presente artigo discute as atuais transformações nos sistemas educacionais em todo o mundo. Tendo como foco a União Europeia (UE) e a Organização para a Cooperação e o Desenvolvimento Econômico (OCDE) como atores de políticas, seu argumento é que tais transformações implicam uma tripla "economização" da política educacional, que pode ser constatada em todos os níveis da área educacional. A importância cada vez maior dessas organizações nas questões educacionais configura uma transição para uma "constelação pós-nacional" também na área educacional, na medida em que a soberania educacional nacional está, no mínimo, passando por reajustes. No entanto, a "economização" das políticas educacionais não se limita a aproximar a educação das necessidades da economia e a transformar seus serviços em mercadorias comercializáveis. Ela também afeta o nível operacional da educação. Uma lógica de produção está sendo implementada na descrição realizada pelas próprias instituições do sistema educacional, que deixaram de ser estabelecimentos burocraticamente administrados para ser concebidos como uma atividade comercial gerencialmente controlada, uma atividade na qual uma ação empresarial se faz necessária. Esse novo tipo de administração faz surgir o problema da legitimação democrática das decisões políticas que, em termos ideais, combina três elementos: o democrático, o "expertocrático" e o ético-profissional. O artigo discute as consequências de uma mudança no equilíbrio desses três elementos no caso da Alemanha.