Retrograde Melanopsin Signaling Increases With Age in Retinal Degenerate Mice Lacking Rods and the Majority of Cones

PURPOSE: Following on from reports of retrograde retinal signaling in mice, we sought to investigate the influence of age and retinal location on this phenomenon using mice that lack rods and the majority of cones. METHODS: We used functional anatomy for c-fos (Fos) and tyrosine hydroxylase (TH) to measure light-driven activation of dopamine neurons along a dorsal-ventral transect in C3H/He wild-type and rodless-coneless rd/rd cl (rdcl) mice aged 3, 5, and >14 months. A parallel series of retinae from 3-month-old mice was also stained for cone opsins and melanopsin. RESULTS: Analysis by confocal microscopy revealed light-driven Fos activation in TH cells residing in the middorsal retina of the youngest rdcl mice. This region was largely devoid of residual cones but contained a large number of intrinsically photosensitive retinal ganglion cells (ipRGCs) and the highest density of melanopsin neurites. With advancing age, there was a paradoxical increase in retrograde signaling from ∼3% Fos-positive (Fos+) TH cells at 3 months to ∼36% in rdcl mice >14 months. This increased activation occurred in more central and peripheral retinal regions. CONCLUSIONS: Our data provide new insights into the anatomy and plasticity of retrograde melanopsin signaling in mice with severe rod/cone dystrophy. The increased retrograde signaling we detect may result from either an increased potency of melanopsin signaling with advancing age and/or postsynaptic modification to dopaminergic neurons

ClassActionPrediction: A Challenging Benchmark for Legal Judgment Prediction of Class Action Cases in the US

The research field of Legal Natural Language Processing (NLP) has been very active recently, with Legal Judgment Prediction (LJP) becoming one of the most extensively studied tasks. To date, most publicly released LJP datasets originate from countries with civil law. In this work, we release, for the first time, a challenging LJP dataset focused on class action cases in the US. It is the first dataset in the common law system that focuses on the harder and more realistic task involving the complaints as input instead of the often used facts summary written by the court. Additionally, we study the difficulty of the task by collecting expert human predictions, showing that even human experts can only reach 53% accuracy on this dataset. Our Longformer model clearly outperforms the human baseline (63%), despite only considering the first 2,048 tokens. Furthermore, we perform a detailed error analysis and find that the Longformer model is significantly better calibrated than the human experts. Finally, we publicly release the dataset and the code used for the experiments

Aplicação forense

O presente estudo teve lugar no Serviço de Genética e Biologia Forenses da Delegação do Centro do Instituto Nacional de Medicina Legal e Ciências Forenses, em Coimbra, com o objetivo de caracterizar a diversidade genética dos principais grupos populacionais de Moçambique, nomeadamente Macua e Changana. Para o efeito, foram analisados 15 loci STR autossómicos (D8S1779, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 e FGA assim como a amelogenina, em 160 amostras de indivíduos não aparentados de ambos os sexos das cidades de Maputo e Nampula. Foram colhidas amostras de sangue, depois da confirmação do grupo populacional e de obtido o consentimento informado. A extração do ADN foi realizada de acordo com o protocolo proposto por Walsh et al. (1991). As amostras extraídas foram amplificadas usando o kit AmpFlSTR® Identifiler® Direct (ABI). Os fragmentos amplificados foram separados por eletroforese capilar (usando um padrão interno GeneScanTM 500 Size Standard e a designação alélica foi feita utilizando um ladder alélico) no sequenciador automático ABI PRISM® 310 Genetic Analyzer. As frequências alélicas, os parâmetros estatísticos de interesse forense bem como o valor P do teste exacto de Fisher para a verificação do equilíbrio de Hardy-Weinberg, foram calculadas usando o algoritmo das cadeias de Markov no programa ARLEQUIM versão 3.11. As distâncias genéticas entre a população de Moçambique e as de alguns países de África, América Latina e Europa foram calculadas usando o programa PHYLIP versão 3.68 de acordo com o algoritmo Neighbor-Joining. Para o cálculo do valor exacto da probabilidade P das cadeias de Markov, foi usado o módulo STRUC do programa GENEPOP versão 4.1.4. A árvore filogenética foi gerada no programa TreeView versão 1.5.2. As frequências alélicas nos 15 loci STR autossómicos estão em equilíbrio de Hardy-Weinberg (P>0.05) apresentando um poder de discriminação acumulado de 0.99999999997 e uma probabilidade de exclusão a priori acumulada de 0.999999466. Não foram encontradas diferenças genéticas significativas entre a população Macua e Changana (P>0.05). A análise filogenética revela que a população de Moçambique se encontra geneticamente próxima de outras populações africanas (Angola, Guiné Equatorial, Uganda, Namíbia e Somália), distinguindo-se do grupo formado pelas populações da América Latina (Brasil, Venezuela, México, Argentina) e as europeias (Grécia, Polónia, Croácia, Servia-Montenegro, Suécia, Bélgica e Portugal). Os loci FGA e D21S11 apresentaram as variantes alélicas 16.1 e 24.3 respetivamente. Das 160 amostras analisadas, 6 exibiram um padrão trialélico no locus TPOX, sendo duas do sexo masculino e quatro do sexo feminino.This study took place at the Centre Branch of the National Institute of Legal Medicine and Forensic Sciences, Coimbra-Portugal, in order to characterise the genetic diversity of the main Mozambican´s population groups namely, Macua and Changana. For this purpose, 15 autosomal STR loci D8S1779, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA as well as amelogenin were analyzed in 160 samples from unrelated individuals of both sex from Maputo and Nampula cities. Blood samples were collected after confirmation of ethnicity and informed consent has been given. Nuclear DNA was extracted by Chelex as proposed by Walsh et al. (1991). Samples were amplified using the AmpFlSTR® Identifiler® Direct® PCR amplification kit. PCR products were detected and separated by capillary electrophoresis using an ABI PRISM® 310 Genetic Analyzer. Allelic frequencies, statistical parameters of forensic interest as well as unbiased estimates of Hardy-Weinberg exact P-value were assessed using the Markov chain algorithm with ARLEQUIN software version 3.11. Genetic distances between our population and those from Africa, Latin America and Europe were calculated using PHYLIP software version 3.68 according to neighborjoining algorithm. Locus by locus computation of unbiased estimate of exact P-values of the probability test was assessed using Markov chains algorithm with the STRUC module of GENEPOP software version 4.1.4. Philogenitic tree was visualized using TreeView Software version 1.5.2. Allele frequencies in the 15 analyzed loci are in Hardy-Weinberg equilibrium (P>0.05), the power of discrimination and combined probability of exclusion are 0.99999999997 and 0.999999466 respectively. There are no statistical differences between Macua and Changana Mozambican’s populations (P>0.05). According to philogenetic analysis, both Mozambican’s populations are genetically close to those from Africa (Angola, Uganda, Equatorial Guinea, Namibia and Somali) distinguishing themselves from Latin American (Brazil, Venezuela, Mexico and Argentina) and European (Greek, Poland, Croatia, Serbia-Montenegro, Sweden, Belgium and Portugal) populations. The allele’s variants 16.1 and 24.3 at loci FGA and D21S11 respectively, were detected. Tri-allelic patterns at TPOX locus were found in six samples from two males and four females

Redenção, liberdade e serviço: fundamentos para uma educação superior adventista - Redemption, freedom and service: the making of an Adventist higher education

Algo que chama a atenção nos escritos de Ellen G. White, entre outras coisas, é a estrutura implícita que subjaz à sua obra, onde os conceitos de redenção, liberdade e serviço são elementos centrais. Assim, o objetivo desta artigo é descrever e analisar brevemente esses conceitos, refletindo sobre suas implicações para a fundamentação da Educação Superior Adventista, caracterizando-a como possuidora de uma teoria e prática transformadoras.