bluuebunny/crossref_metadata_2025 huggingface dataset:
A PRODUÇÃO TEXTUAL NO LIVRO DIDÁTICO DO 9º ANO – UM OLHAR SOBRE AS PERSPECTIVAS DE APRENDIZAGEM
Authors: Stefanello Claridiane De Camargo , Arnemann Aline Rubiane , Muders Bárbara , Silva Cleiton Reisdorfer
Published: March 2018

Este trabalho tem como objetivo analisar uma unidade de Livro Didático (LD) de Língua Portuguesa do 9ª Ano, a fim de identificar quais perspectivas de aprendizagem estão marcadas linguisticamente na proposta de produção textual da unidade. Tomamos como base três perspectivas de aprendizagem: behaviorismo (SKINNER, 1974; STAATS, 1980), cognitivismo (PIAGET, 1974; CHOMSKY, 2009), sociocultural (VYGOTSKY, 2001). Retomamos os conceitos chave dessas teorias de modo a possibilitar a análise do corpus. O material de análise foi selecionado com base no Programa Nacional do Livro Didático (PNLD), sendo o LD desta análise um dos livros de maior circulação em nossas escolas, especialmente da região de trabalho dos autores. Os procedimentos de análise envolveram: a seleção de seções com orientações explícitas para o trabalho em sala de aula, dentre as quais, direcionamos o foco para a seção de produção de texto; e a busca por termos linguísticos que sugerissem ou comprovassem a manifestação de determinada perspectiva linguística. A análise do corpus indicou que os autores do LD constroem atividades didáticas com base nas perspectivas cognitivista e sociocultural.
“SISTEMA”: RELAÇÕES ENTRE AS PERSPECTIVAS DE SAUSSURE E DA GRAMÁTICA SISTÊMICO-FUNCIONAL DE HALLIDAY
Authors: Schmidt Ana Carvalho , Selbach Helena Vitalina
Published: March 2018

O Curso de Línguística Geral (CLG), compilação organizada pelos linguistas Albert Sechehaye e Charles Bailly, pode ser considerada a obra fundante da Linguística apesar das críticas e concordâncias que recebeu desde a publicação da primeira edição em 1916. Neste artigo, a partir de um trabalho inscrito no âmbito dos Estudos Linguísticos e desenvolvido no Programa de Pós-Graduação da Universidade Federal de Santa Maria, propomos um diálogo entre as perspectiva de Ferdinand de Saussure e de M. A. K. Halliday. Nosso objetivo é verificar como o conceito de “sistema” é concebido na perspectiva saussuriana e na hallidiana para investigar em que medida essas perspectivas se aproximam e/ou se distanciam, pois esse conceito mostra-se relevante em ambas. As perspectivas parecem se aproximar quanto a) ao papel das escolhas léxico-gramaticais na construção de significado, b) à língua como um sistema de linguagem, e c) à noção de sincronia versus diacronia.
EDIÇÃO FAC-SIMILAR, EDIÇÃO DIPLOMÁTICA E ASPECTOS PALEOGRÁFICOS DE QUATRO MANUSCRITOS REDIGIDOS NO RIO GRANDE DO SUL
Authors: Keller Tatiana , Wink Débora Spanamberg
Published: March 2018

Este trabalho apoia-se na Filologia e na Paleografia para realizar um estudo comparativo entre a ortografia antiga e a atual do português brasileiro. Para atingir este fim, analisaram-se quatro documentos manuscritos, todos redigidos no Rio Grande do Sul e armazenados no Arquivo Histórico Municipal de Santa Maria. O primeiro foi escrito em 1904, enquanto os outros três, em 1910. Tomando como base as edições fac-similares – fotos retiradas do acervo digital do Arquivo Histórico de Santa Maria – e as edições diplomáticas – transcrições realizadas segundo as normas de Cambraia (2005) – de cada manuscrito, fizeram-se comentários paleográficos sobre o sistema vocálico (substituições vocálicas), o sistema consonantal (encontros consonantais impróprios, consoantes duplas, substituições consonantais), o uso de diacríticos (principalmente a acentuação), a separação vocabular indevida (hipossegmentação e hipersegmentação), o uso de maiúsculas e o uso de abreviaturas. A principal distinção encontrada foi em relação às regras de uso dos sinais de acentuação.
DISCURSO, VARIAÇÃO E LETRAMENTOS NA ESCOLA: OS MODOS DE DIZER NA EDUCAÇÃO BRASILEIRA DE NORTE A SUL PELAS CÂMERAS DO DOCUMENTÁRIO “PRO DIA NASCER FELIZ”
Authors: Lima Francisco Renato , Borges Vanessa Raquel Soares , Costa Catarina De Sena Sirqueira Mendes da
Published: March 2018

Este texto adota como objeto de estudo o documentário “Pro dia nascer feliz”, de João Jardim, com o objetivo de analisar a questão da realidade da educação brasileira, de norte a sul, a partir dos aspectos teóricos de discurso, variação e letramentos que constituem os modos de ver e dizer o mundo, através da visão de mundo dos personagens. Parte-se de uma pesquisa bibliográfica de caráter qualitativo, baseada nos estudos da sociolinguística educacional (BORTONI-RICARDO, 2004/2005) e em alguns fundamentos teórico-legais do ensino da Língua Portuguesa. A análise evidencia problemas que emergem, principalmente das condições socioculturais dos protagonistas da história – professores e alunos -, os quais dizem, a seu modo, as reais condições que vivenciam na escola, a qual se tornou um espaço de conflitos, disputas e divergências sociais, que estão imbricadas na fala de cada sujeito.
A LINGUAGEM JORNALÍSTICA E O FEMININO NA GUERRA: UM OLHAR SOBRE A PRESENÇA DAS MULHERES NA COBERTURA DA GUERRA DO CONTESTADO
Authors: Grimes Suelen Ramos , Couto Nádia Regia Almeida , Formentin Claudia Nandi
Published: March 2018

Este estudo objetiva verificar a cobertura da imprensa catarinense acerca da Guerra do Contestado, mais especificamente do jornal O Dia. Dentre as edições relacionadas ao tema, foram selecionadas oito que abordam a mulher participante do conflito. A pesquisa contextualiza a guerra e também a participação feminina, fundamental em diversos aspectos, inclusive na linha de frente das batalhas.  Por meio de autores como Beauvoir, Bourdieu e Wolf as questões de gênero e construções sociais em torno do tema são evidenciadas, integrando às narrativas de historiadores e autores que se dedicaram a estudar a Guerra do Contestado, como Nilson Thomé, Delmir José Valentini e Marli Auras e fazendo um contraponto com o material encontrado nas páginas de O Dia. Com a análise percebeu-se que as mulheres não tiveram visibilidade perante a cobertura jornalística, com exceção de poucas citações em que são colocadas como vítimas ou ainda satirizadas, como acontece com as “virgens”.
Teses e dissertações em Educação Especial na região nordeste no período de 1997 a 2012
Authors: Lustosa Ana Valéria Marques Fortes
Published: March 2018

Este estudo teve por objetivo analisar teses e dissertações produzidas nos programas de pós-graduação em educação da Região Nordeste na área de Educação Especial no período de 1997 a 2012.  Para a consecução desse objetivo foram analisados os resumos da produção strictu sensu, disponíveis no Banco de Teses da CAPES e nos sites dos Programas de Pós-Graduação, com o intuito de identificar a produção científica na área por ano e por instituição, bem como para verificar os temas, procedimentos teóricos e metodológicos, locais e sujeitos mais pesquisados. A pesquisa é de natureza qualitativa, do tipo documental. Os resultados apontam que a Educação Especial ainda é um campo pouco expressivo nos Programas de Pós-Graduação em Educação da região Nordeste, quando comparada com outras áreas.
Realidade virtual como ferramenta para reabilitação: estudo de caso
Authors: Audi Mauro , Barrozo Amanda Lavagnini , Perin Bruna De Oliveira , Frota João Batista Bezerra , Braccialli Ligia Maria Presumido
Published: March 2018

As atividades desenvolvidas nas terapias físicas convencionais muitas vezes são repetitivas e produzem a falta de estímulo por parte do participante, os ambientes virtuais pode ser uma poderosa ferramenta terapêutica que proporcione motivação e torne as sessões mais prazerosas. A realidade virtual é um recurso que permite que o indivíduo utilize seus sentidos e os movimentos naturais do corpo durante os jogos virtuais, para assim promover sua interação com um ambiente virtual. O objetivo foi mensurar a satisfação de uso de jogos virtuais durante as sessões de fisioterapia. O estudo foi realizado com um voluntário com diagnóstico de traumatismo cranioencefálico. Para a intervenção foi utilizado o videogame Xbox Kinect e os jogos escolhidos requisitaram a utilização de várias habilidades corporais, dentre elas o equilíbrio. A intervenção durou um mês e dois dias, sendo que nesse período foram realizados 21 atendimentos, com tempo de terapia aproximado de 25 minutos por atendimento. Foi realizada uma entrevista semiestruturada com o participante, com roteiro prévio, apreciado por juízes. A análise qualitativa de conteúdo da entrevista revelou prazer e alegria ao realizar as atividades. De acordo com os resultados observados no estudo, concluiu-se que a realidade virtual, como meio terapêutico, foi uma atividade motivadora e possibilitou melhora do equilíbrio corporal do voluntário.
Benefícios da Intervenção Precoce para a Família de Crianças com Transtorno do Espectro do Autismo
Authors: Cossio Anelise Do Pinho , Pereira Ana Paula Da Silva , Rodriguez Rita De Cássia
Published: March 2018

O presente artigo foi desenvolvido no âmbito do Mestrado em Educação Especial, com Especialização em Intervenção Precoce, pela Universidade do Minho, em Braga, Portugal. Tem como finalidade apresentar uma revisão de pesquisas recentes, compreendidas entre os anos de 2005 a 2016, que evidenciem os benefícios da Intervenção Precoce (IP) para as famílias de crianças com Transtorno do Espectro do Autismo (TEA), no que concerne ao bem-estar e qualidade de vida, ao desenvolvimento de competências que perspectivem o controle/corresponsabilização, à melhoria do conhecimento/informação e à promoção da   participação/envolvimento da família. A conclusão desta pesquisa permite-nos compreender que a IP se traduz em resultados positivos para as famílias, permitindo-nos assim reforçar a importância da participação efetiva das famílias em todos os processos de IP, bem como promover a necessidade de avaliar estes benefícios. Esta avaliação deve ter como referência a perspectiva das famílias de modo a podermos construir práticas que sejam reforçadoras e positivas nas suas vidas.
Amy-Jill Levine and Marc Zvi Brettler, Eds. The Jewish Annotated New Testament, Second Edition
Authors: Thiessen Matthew
Published: March 2018

No abstract is available.
Ernest Bloch, Richard Wagner, and the Myth of Racial Essentialism
Authors: Klaus Aaron
Published: March 2018

Composer Ernest Bloch’s Jewish identity is ironically rooted in the notoriously anti-Semitic writings of Richard Wagner. Rather than an indication of self-loathing, Bloch’s assimilation of Wagner's ideas into his own thinking exemplifies the seductiveness of racial essentialist thought in the late nineteenth and early twentieth centuries. An examination of the effects of racial essentialism and Jewish assimilation in post-Emancipation Europe puts Bloch’s identity as a Jewish composer in context. Next, a biographical sketch of Bloch’s life sheds light on how he grappled with Judaism in his music. Finally, a discussion of Bloch’s relationship with Judaism shows the danger of defining Jewish music in racial terms.
Quick Submit i OJS 3
Authors: Frederiksen Niels Erik
Published: March 2018

Her finder du en kort gennemgang af QuickSubmit-processen.
Shell nouns in English – a personal roundup
Authors: Schmid Hans-Jörg
Published: March 2018

This paper provides a somewhat personal retrospect on work on the notion and phenomenon of shell noun. After a brief introduction I will discuss some terminological and methodological issues. Following some remarks on the classification of shell noun uses I will then report on recent work into the origin and diachronic development of shell nouns and shell-noun constructions, and discuss a number of other advances in the study of shell nouns since their introduction in the 1990s.
Constructions with shell nouns in English: their dual role in information packaging
Authors: Tárnyiková Jarmila
Published: March 2018

The focus in this paper is on structural and functional properties of a marginal type of focus formulas in English, known as N-be-that-constructions (Schmid 2001), cf. The problem is that he is jealous. They are referred to here as focus formulas with shell nouns (FFSNs). The role of the nouns in these templates is to create conceptual shells (Schmid 1997) into which the propositional content is encapsulated, with both the parts being co-referentially linked. The BNC data have revealed two manifestations of FFSNs in discourse: they occurred either as fixed utterance-initial templates (The thing is that killing got to be a habit.), or as looser configurations, co-occurring with various discourse signposts (DSs), as in Mm. well I mean there’s the the other thing is you see… My view, inspired by Schmid (2001) and outlined in Válková and Tárnyiková (2015), is that the FFSNs can have a dual role in discourse, operating either as focalizers or as discourse signposts participating in a number of pragmatic strategies associated with facework. The aim is to argue for the validity of this claim and give evidence of and reasoning for the focality loss cases.
Maria Dasca, «Entenebrats. Literatura catalana i bogeria», Barcelona, PAM, 2016, 501 pp.
Authors: Espinós Felipe Joaquim
Published: March 2018

Ressenya sobre el llibre de Maria Dasca, «Entenebrats. Literatura catalana i bogeria», Barcelona, Publicacions de l'Abadia de Montserrat, 2016, 501 pp., ISBN: 978-84-9883-863-3.
Sense of Time in A. Akhmatova’s and T.S. Eliot’s Latter Poetry (Comparative Analysis of Poem Without a Hero and Four Quartets)
Authors: Kurasova Anna
Published: March 2018

Anna Akhmatova and Thomas Stearns Eliot are considered among the most influential representatives of Modernism, Eliot - in Anglo-American Literature, and Akhmatova – in Russian. Modernism emerged at the beginning of the 20th century, seeking to point out people's failure to maintain a culture based on spiritual values,  an idea that was central to the works of Eliot and Akhmatova. By analysing and contrasting their last major poems, Four Quartets and Poem Without a Hero, this paper aims to present Eliot’s and Akhmatova’s perception of time and modernity. Faced with the tragedy of World War II, Eliot and Akhmatova turned to reflecting on notions of time and history. Despite the differences in the poets’ experiences, mentality, and background, Four Quartets and Poem Without a Hero bear a resemblance to each other in many respects and express the common for Akhmatova and Eliot perception of time. The poets saw time as a complex continuum, in which every element has its place and persistently interacts with all the other elements; thus, the past is present in our lives today and shapes our destiny. Therefore, history is not simply a sequence of past events unrelated to the present, but rather an active creator of every moment of our present lives. Establishing the immutable connection between the past, the present, and the future, the poets remind their readers of the notions of sin, guilt and responsibility. The poets also shared an attitude towards modernity, which they saw as a time of lost people who deny their past and for that reason will have no future unless they change. Therefore, in the face of eternity, which is wiser than we are capable of seeing, all that remains for humanity is acceptance and humility.
The Early Literary Reception of Ernest Hemingway in Iran
Authors: Ghasemnejad Atefeh , Anushiravani Alireza
Published: March 2018

This essay investigates the dynamics that led to the literary reception of Ernest Hemingway before the Islamic Revolution in Iran. This article deploys reception studies as a branch of Comparative Literature with a focus upon conceptions of Siegbert Salomon Prawer and the practical method of George Asselineau to unearth the ideological, political, and historical milieu that embraced Hemingway’s literary fortune in Iran. This investigation, unprecedented in the study of Iranian literature, discusses how and why Hemingway was initially received in Iran. As such, the inception of literary fortune of Ernest Hemingway in Iran is examined by the contextual features, Persian literary taste, and the translator’s incentives that paved the way for this reception. This article also uncovers the reasons for the delay in the literary reception of Hemingway in Iran and discussed why some of Hemingway’s oeuvres enjoyed recognition while others were neglected by the Iranian readership.
Attitude in Appraisal Theory: A Comparative Analysis of English Versions of Changgan Xing
Authors: Dong Tian , Lin Xiaolin
Published: March 2018

This study intends to explore the distribution of appraisal resources in the English versions of Li Bai’s poem Changgan Xing. It aims to make a comparative analysis and find out the similarities and differences of the translated poems based on J. R. Martin’s Appraisal Theory. Two classical English versions of the Chinese poem, which were translated by Ezra Pound and Xu Yuanchong, have been chosen. The distribution of attitudinal resources in the two English versions has been analyzed under the attitude system from three aspects: affect, judgment and appreciation. The distribution of polarity and explicitness in the poems has been explored as well. The study has adopted quantitative and qualitative methods to conduct a comparative analysis of the attitudinal resources in the translated poems. Further, the reasons for the differences of attitudinal resources in the translated versions have been explored. Through revealing the similarities and differences of the attitudinal resources, this study shows the applicability of the Appraisal Theory in the comparative studies of Chinese-English poems.
Audiovisual Translation:A Critical Review on Sino-western Perspectives of Film Subtitle Translation
Authors: Zhang Junchen
Published: March 2018

The paper argues the development of audiovisual translation (mainly focuses on the strand of film subtitle translation) in the West and China. Firstly, the paper discusses film translation from the perspective of the West and critically reviews the achievements produced by western researchers. Secondly, the paper analyzes film translation from Chinese perspective and outlines its change and development in Mainland China. Thirdly, some major issues exited in film translation such as cultural problems, technical issues and translation strategies are analyzed. And in the fourth part, the paper takes a unique Chinese film genre, Chinese martial arts/wuxia film (中國武俠電影), as a specific case to analyze and then further discuss the studies of film translation in the context of Chinese culture. The potential underexplored areas of translating Chinese martial arts film are also identified. Lastly, the paper argues the audiovisual translation from an inter-/multi-disciplinary angle involving film study, social-cultural study, multimodal analysis and relevant linguistic approaches and then points out the potential future trends in audiovisual translation studies. In short, there are three significances in the research. The first one is making a comparative analysis to development path of film translation between Western side and China’s side. The second is arguing the translation of Chinese wuxia film from a diachronic perspective and identifying existed research gaps. The last is pointing out the potential research trends based on the latest research progress.
The Poetic Innovation in the Poetry of Ahmed Hijazi
Authors: S. Sultan Sabbar
Published: March 2018

The contemporary Egyptian poet, critic, editor and convener of many conferences and cultural committees Ahmed Abdul Mu'tiHijazirepresents a case of dispute and discussion thanks to the selection of the material of his poems as well as the distinct shape and innovative aspects of his verse. As  will be shown in the following pages,Hijazi's version of poetic modernism is devoid of mythology, intersexuality and deliberate obfuscation or self-indulgence. Every word in his poem is aligned in a seamless mosaic that eventually succeeds in conveying the poet's message in clear and lucid but highly suggestive discourse. It is this particular side of his verse that will be highlighted  in the present study.
The first Oligocene sea turtle (Pan-Cheloniidae) record of South America
Authors: Cadena Edwin , Abella Juan , Gregori Maria
Published: March 2018

The evolution and occurrence of fossil sea turtles at the Pacific margin of South America is poorly known and restricted to Neogene (Miocene/Pliocene) findings from the Pisco Formation, Peru. Here we report and describe the first record of Oligocene (late Oligocene, ∼24 Ma) Pan-Cheloniidae sea turtle remains of South America. The fossil material corresponds to a single, isolated and well-preserved costal bone found at the Montañita/Olón locality, Santa Elena Province, Ecuador. Comparisons with other Oligocene and extant representatives allow us to confirm that belongs to a sea turtle characterized by: lack of lateral ossification, allowing the dorsal exposure of the distal end of ribs; dorsal surface of bone sculptured, changing from dense vermiculation at the vertebral scute region to anastomosing pattern of grooves at the most lateral portion of the costal. This fossil finding shows the high potential that the Ecuadorian Oligocene outcrops have in order to explore the evolution and paleobiogeography distribution of sea turtles by the time that the Pacific and the Atlantic oceans were connected via the Panama basin.
Acceleration of Brain Atrophy and Progression From Normal Cognition to Mild Cognitive Impairment
Authors: Uchida Yuto , Nishimaki Kei , Soldan Anja , Moghekar Abhay , Albert Marilyn , Oishi Kenichi
Published: October 2024

Importance

It remains unclear which risk factors accelerate brain atrophy along with a progression from normal cognition to mild cognitive impairment (MCI).

Objective

To examine risk factors associated with the acceleration of brain atrophy and progression from normal cognition to MCI based on long-term longitudinal data for middle-aged and older adults.

Design, Setting, and Participants

Data for this cohort study were extracted from the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) cohort, initiated at the National Institutes of Health from January 1, 1995, to December 31, 2005, and continued at Johns Hopkins University from January 1, 2015, to October 31, 2023. All participants were cognitively normal at baseline. The participants whose structural magnetic brain imaging (MRI) of the brain and cerebrospinal fluid (CSF) measures were available for over 10 years were included.

Exposures

Longitudinal structural MRI of the brain and measurement of CSF biomarkers for Alzheimer disease pathology (ratio of amyloid β peptide 42 [Aβ42] to Aβ40, tau phosphorylated at threonine 181, and total tau).

Main Outcomes and Measures

Annual change rates of segmental brain volumes, Kaplan-Meier survival curves plotting time to event for progression to MCI symptom onset, and hazard ratios (HRs) determined by Cox proportional hazards regression models.

Results

A total of 185 participants (mean [SD] age, 55.4 [8.4] years; 116 women [63%]) were included and followed up for a maximum of 27 years (median, 20 [IQR, 18-22] years). The groups with high levels of atrophy in the white matter and enlargement in the ventricles had an earlier progression from normal cognition to MCI symptom onset (HR for white matter, 1.86 [95% CI, 1.24-2.49]; P = .001; HR for ventricles, 1.71 [95% CI, 1.19-2.24]; P = .009). Diabetes was associated with progression to MCI (HR, 1.41 [95% CI, 1.06-1.76]; P = .04), as was a low CSF Aβ42:Aβ40 ratio (HR, 1.48 [95% CI, 1.09-1.88]; P = .04), and their combination had a higher HR of 1.55 (95% CI, 1.13-1.98]; P = .03), indicating a synergic association of diabetes and amyloid pathology with MCI progression.

Conclusions and Relevance

In this cohort study of middle-aged and older adults, higher rates of volume change in the white matter and ventricles, along with the presence of diabetes and a low CSF Aβ42:Aβ40 ratio, were identified as important risk factors for the progression to MCI. These results support the importance of identifying individuals who have accelerated brain atrophy to optimize preventive strategies for progression to MCI.
Posttraumatic Stress Disorder, Obesity, and Accelerated Epigenetic Aging Among US Military Veterans
Authors: Fischer Ian C. , Na Peter J. , Nagamatsu Sheila T. , Jeste Dilip V. , Cabrera-Mendoza Brenda , Montalvo-Ortiz Janitza L. , Krystal John H. , Polimanti Renato , Gelernter Joel , Pietrzak Robert H.
Published: October 2024

This cross-sectional study uses data from 1135 male, European-American US military veterans to assess whether risk and protective factors influenced associations between posttraumatic stress disorder and epigenetic age.
Oak declines: Reviewing the evidence for causes, management implications and research gaps
Authors: Gosling Rebecca H. , Jackson Robert W. , Elliot Matt , Nichols Christopher P.
Published: October 2024

Oak decline is a complex disorder caused by multiple stressors. Although declines have been observed across Europe since 1700, there is still a lot of uncertainty around the cause, and therefore the appropriate management techniques.

Using literature from across European oak ecosystems, this review and perspective discusses the key stressors associated with oak declines in Quercus robur L. and Q. petraea (Matt.) Liebl. in Europe and the newly described acute oak decline breaking out in the United Kingdom (and beyond), with a view to identifying important evidence gaps and management implications.

The key factors implicated in oak decline include drought, pests and pathogens. These factors can interact in positive feedback loops to increase stress and decline within oaks. Extreme frost, waterlogging, soil properties, land management, nitrogen pollution, heavy metal pollution, genetic predisposition and mycorrhizal changes could also be involved in decline, but more research is required to understand these.

In acute oak decline, necrotic lesions are caused by a bacterial complex of up to three species, and it has been observed that the presence of the wood borer Agrilus biguttatus Fabricius 1776 can amplify the symptoms.

Practical implication: The amount that each stressor contributes towards these declines and the ‘tipping points’ are largely unknown and are likely to differ between decline events, sites and even individual trees. This makes management advice provision exceedingly difficult. Historic records show oaks in decline can recover; therefore, allowing trees time and space to recover should be a priority for management practitioners. Future research recommendations for effective management of declining oaks are discussed.
Identification of fibrinogen as a plasma protein binding partner for lecanemab biosimilar IgG
Authors: Bellier Jean‐Pierre , Román Viera Andrea M. , Christiano Caitlyn , Anzai Juliana A. U. , Moreno Stephanie , Campbell Emily C. , Godwin Lucas , Li Amy , Chen Alan Y. , Alam Sarah M. , Saba Adriana , Yoo Han Bin , Yang Hyun‐Sik , Chhatwal Jasmeer P. , Selkoe Dennis J. , Liu Lei
Published: October 2024

Objective

Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half‐life, lecanemab administered as a bi‐monthly infusion (typically 10 mg/kg) has a relatively brief half‐life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half‐life. In this study, we investigated potential plasma protein binding (PPB) interaction to lecanemab using lecanemab biosimilar.

Methods

Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions of human plasma obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate plasma binders was confirmed by western blotting, ELISA, and surface plasmon resonance analysis.

Results

Using a combination of equilibrium dialysis, ELISA, and western blotting in human plasma, we first describe the presence of likely PPB partners to lecanemab biosimilar and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta.

Interpretation

In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that PPB may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.
Rethinking antisense oligonucleotide therapeutics for amyotrophic lateral sclerosis
Authors: Ito Daisuke , Okada Kensuke
Published: October 2024

Antisense oligonucleotides, which are used to silence target genes, are gaining attention as a novel drug discovery modality for proteinopathies. However, while clinical trials for neurodegenerative diseases like amyotrophic lateral sclerosis have been conducted in recent years, the results have not always been favorable. The results from a Phase III trial of the antisense oligonucleotide, that is, tofersen, which targets SOD1 mRNA, showed decreased levels of cerebrospinal fluid SOD1 and plasma neurofilament light chain but no improvements in primary clinical endpoint. Moreover, case reports pertaining to patients with amyotrophic lateral sclerosis carrying FUS and C9orf72 mutations who received antisense oligonucleotide‐based treatments have demonstrated a notable reduction in the targeted protein (thus providing the proof of mechanism) but with no discernible clinical benefits. There are several possible reasons why antisense oligonucleotides knockdown fails to achieve proof of concept, which need to be addressed: on‐target adverse effects resulting from the loss of function of target gene and irreversible neuronal death cascade due to toxic protein accumulation, among other factors. This review provides an overview of the current status and discusses the prospects of antisense oligonucleotides treatment for amyotrophic lateral sclerosis.
Plasma exchange with albumin replacement for Alzheimer's disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels
Authors: Gonzalo Ricardo , Minguet Carla , Ortiz Ana María , Bravo María Isabel , López Oscar L. , Boada Mercè , Ruiz Agustín , Costa Montserrat
Published: October 2024

Objective

There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE‐Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures.

Methods

Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14‐month schedule of PE‐Alb treatment vs. placebo [sham PE‐Alb]) were analyzed for changes from baseline for 19 inflammatory mediators (6 inflammatory cytokines, 9 chemokines, and 4 vascular injury indicators) at representative time points across the AMBAR study (lasting effects) as well as in pre‐ versus post‐PE‐Alb procedure (acute effects). Association between mediator changes and clinical outcomes reported in the AMBAR study (cognitive, functional, behavioral function, and global change tests) was assessed.

Results

PE‐Alb significantly reduced IFN‐γ, eotaxin, MIP‐1α and ICAM‐1 levels in serum, and eotaxin‐3 and MIP‐1β levels in CSF, at various time points during treatment (p < 0.05; false discovery rate‐corrected). Vascular injury indicators were the mediators mostly affected by post‐ versus pre‐PE‐Alb level reduction. Increased serum MIP‐1α levels were associated with worsening in ADAS‐Cog, CDR‐sb, and ADCS‐CGIC scores in the placebo group, but not in the PE‐Alb‐treated group.

Interpretation

Peripheral intervention could affect AD by reducing inflammatory mediators in both peripheral and central compartments. Changes in MIP‐1α due to PE‐Alb were associated with changes in clinical outcomes.
Quantitative Design of Cathode Materials for Ion Battery from a Reductionist Perspective
Authors: Gao Ang , Gu Lin
Published: October 2024

The quantitative design of functionalities for functional materials is highly attractive for materials research, which must be based on a thorough understanding of the behavior of fundamental particles. Reductionism advocates for the understanding of complex materials through dissection into the constituent parts, providing a robust framework for investigating functional materials. In an ion battery system, this review utilizes reductionism to deconstruct cathode materials into phase, atom, and even electron, building the intrinsic connections between the macroscopic properties and fundamental particles across four degrees of freedom. This aims to enable the quantitative design of cathode materials. Specifically, the microscopic origins of the macroscopic properties, that is, capacity, potential, rate, and cycling reversibility, based on lattice, charge, orbital, and spin degrees of freedom are elucidated. Additionally, current strategies are summarized and proposed future development directions for improving these properties. These insights contribute to achieving the goal of quantitative design of energy storage materials.
Stochastic Nanoroughness Inhibits and Reverses Glial Scarring In Vitro and In Vivo via a Mechanobiology Paradigm Involving Piezo‐1
Authors: Blumenthal Nils R. , Petravicz Jeremy C , Breton‐Provencher Vincent , Hu Ming , Riemenschneider Fabian , Sarem Melika , Sur Mriganka , Shastri V. Prasad
Published: October 2024

Physical insult to the central nervous system (CNS) such as during electrode insertion leads to reactive astrogliosis which in turn contributes to glial scarring (GS). To date, reducing GS in these settings has focused on pharmacological agents and variations in electrode material composition or implantation procedures, and the role of electrode surface topography has remained unexplored. Since proteoglycans, a major component of GS tissue, possesses very well‐defined (nano) topography, a role for stochastic nanoroughness in glial scar formation is theorized. Using an in vitro system, we provide proof of concept that on substrates possessing stochastic nanoroughness corresponding to that of healthy astrocytes, glial scar formation is significantly inhibited, and more importantly, can be even reversed, and it involves signaling via the stretch‐activated cation channel Piezo‐1. In vivo studies reveal an absence of astrocytes aggregation along the electrode track of chronically implanted electrodes modified with stochastic surface nanoroughness, compared to non‐modified electrodes, while signal detection within the superior colliculus remains unaffected. These findings shedlight on the crucial role of stochastic biophysical cues in modulating GS formation; and offer a promising non‐chemical approach for engineering neural biomaterials interface for the CNS.
Charge Generation and Enhancement of Key Components of Triboelectric Nanogenerators: A Review
Authors: Wang Jian , Xu Shuyan , Hu Chenguo
Published: October 2024

The past decade has witnessed remarkable progress in high‐performance Triboelectric nanogenerators (TENG) with the design and synthesis of functional dielectric materials, the exploration of novel dynamic charge transport mechanisms, and the innovative design of architecture, making it one of the most crucial technologies for energy harvesting. High output charge density is fundamental for TENG to expand its application scope and accelerate industrialization; it depends on the dynamic equilibrium of charge generation, trapping, de‐trapping, and migration within its core components. Here, this review classifies and summarizes innovative approaches to enhance the charge density of the charge generation, charge trapping, and charge collection layers. The milestone of high charge density TENG is reviewed based on material selection and innovative mechanisms. The state‐of‐the‐art principles and techniques for generating high charge density and suppressing charge decay are discussed and highlighted in detail, and the distinct charge transport mechanisms, the technologies of advanced materials preparation, and the effective charge excitation strategy are emphatically introduced. Lastly, the bottleneck and future research priorities for boosting the output charge density are summarized. A summary of these cutting‐edge developments intends to provide readers with a deep understanding of the future design of high‐output TENG.
An Antagonistic Photovoltaic Memristor for Bioinspired Active Contrast Adaptation
Authors: Gong Guodong , Zhou You , Xiong Ziyu , Sun Tao , Li Huaxin , Li Qingxiu , Zhao Wenyu , Zhang Guohua , Zhai Yongbiao , Lv Ziyu , Tan Hongwei , Zhou Ye , Han Su‐Ting
Published: October 2024

Machine vision systems that consist of cameras and image‐processing components for visual inspection and identification tasks play a critical role in various intelligent applications, including pilotless vehicles and surveillance systems. However, current systems usually possess a limited dynamic range and fixed photoresponsivity, restricting their capability of gaining high‐fidelity images when encoding a high‐contrast scene. Here, it is shown that a photovoltaic memristor incorporating two antagonistic photovoltaic junctions can autonomously adjust its response to varying light stimuli, enabling the amplification of shadows and inhibition of highlight saturation. Due to the dynamic photodoping effect at the p‐n junction with an asymmetrical profile, the photocurrent polarities of the antagonistic memristor can be changed as the light intensity increases. The light‐intensity‐dependent switchable photovoltaic behaviors match Weber's law where photosensitivity is inversely proportional to the light stimuli. An 11 × 11 memristor array is used to detect a high‐contrast scene with light intensities ranging from 1 to 5 × 104 µW cm−2, achieving a similar active contrast adaptation performance compared with the human visual systems (less than 1.2 s at 94 dB). This work paves the way for innovative neuromorphic device designs and may lead to the development of state‐of‐the‐art active visual adaptation photosensors.
Dirac‐Like Fermions Anomalous Magneto‐Transport in a Spin‐Polarized Oxide 2D Electron System
Authors: Chen Yu , D'Antuono Maria , Trama Mattia , Preziosi Daniele , Jouault Benoit , Teppe Frédéric , Consejo Christophe , Perroni Carmine A. , Citro Roberta , Stornaiuolo Daniela , Salluzzo Marco
Published: October 2024

In a 2D electron system (2DES) the breaking of the inversion, time‐reversal and bulk crystal‐field symmetries is interlaced with the effects of spin‐orbit coupling (SOC) triggering exotic quantum phenomena. Here, epitaxial engineering is used to design and realize a 2DES characterized simultaneously by ferromagnetic order, large Rashba SOC and hexagonal band warping at the (111) interfaces between LaAlO3, EuTiO3, and SrTiO3 insulators. The 2DES displays anomalous quantum corrections to the magneto‐conductance driven by the time‐reversal‐symmetry breaking occurring below the magnetic transition temperature. The results are explained by the emergence of a non‐trivial Berry phase and competing weak anti‐localization/weak localization back‐scattering of Dirac‐like fermions, mimicking the phenomenology of gapped topological insulators. These findings open perspectives for the engineering of novel spin‐polarized functional 2DES holding promises in spin‐orbitronics and topological electronics.
Durable Organic Coating‐Free Superhydrophobic Metal Surface by Paracrystalline State Formation
Authors: Yan Dandan , Xu Wenjing , Zou Tingting , Li Lin , Xu Jiapei , Zhang Ruizhi , Hu Longjin , Yang Xupeng , Ma Hui , Yang Jianjun
Published: October 2024

The chemical instability of traditional organically‐decorated superhydrophobic metal surfaces is a significant issue, severely limiting practical applications. This is due to the susceptibility of low surface energy coatings to ion permeation, decomposition, and exfoliation, especially in harsh environments. Here, organic coating‐free, durable superhydrophobic surfaces on Al alloys by developing the paracrystalline state of a bionic anthill tribe structure is successfully achieved, using femtosecond laser element‐doping microstructuring followed by repetitive annealing processes. Remarkably, the inherent superhydrophobic properties of the sample are maintained for ≈2000 h in a corrosive 3.5 wt.% NaCl aqueous solution, significantly surpassing the performance of traditional organic coatings. Moreover, this inherent superhydrophobicity remains nearly unchanged, even after rigorous electrochemical reaction measurements. Additional tests involving UV irradiation (>100 h), freezing cycles (>100 cycles), and acid/alkali resistance (>65 h) further demonstrate that the environmental adaptability of the surface far exceeds that of silane‐coated surfaces. Ab initio calculations reveal that the formation of the paracrystalline state reduces surface energy and enhances chemical stability, thereby extending the durability of the superhydrophobic metal. These findings offer a powerful strategy for utilizing atomic‐level structural rearrangements to design inherent superhydrophobic surfaces without the need for organic coatings.
Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity
Authors: Zhang Li , Zhang Demao , Liu Chengcheng , Tang Boyu , Cui Yujia , Guo Daimo , Duan Mengmeng , Tu Ying , Zheng Huiling , Ning Xinjie , Liu Yang , Chen Haoran , Huang Minglei , Niu Zhixing , Zhao Yanfang , Liu Xiaoheng , Xie Jing
Published: October 2024

The virulent bacteria‐induced host immune response dominates the occurrence and progression of periodontal diseases because of the roles of individual virulence factors from these pathogens in the initiation and spread of inflammation. Outer membrane vesicles (OMVs) as a pathogenic entity have recently attracted great attention as messenger bridges between bacteria and host tissues. Herein, the novel role of OMVs derived from Fusobacterium nucleatum in the occurrence of periodontitis is dissected. In a rat periodontitis model, it is found that OMVs derived from F. nucleatum caused deterioration of periodontitis by enhancing inflammation of the periodontium and absorption of alveolar bone, which is almost equivalent to the effect of F. nucleatum itself. Furthermore, that OMVs can independently induce periodontitis is shown. The pathogenicity of OMVs is attributed to multiple pathogenic components identified by omics. After entering human periodontal ligament stem cells (hPDLSCs) by endocytosis, OMVs activated NLRP3 inflammasomes and impaired the mineralization of hPDLSCs through NF‐κB (p65) signaling, leading to the final injury of the periodontium and damage of alveolar bone in periodontitis. These results provide a new understanding of OMVs derived from pathogens and cues for the prevention of periodontitis.
Seizure Sources Can Be Imaged from Scalp EEG by Means of Biophysically Constrained Deep Neural Networks
Authors: Sun Rui , Sohrabpour Abbas , Joseph Boney , Worrell Gregory , He Bin
Published: October 2024

Seizure localization is important for managing drug‐resistant focal epilepsy. Here, the capability of a novel deep learning‐based source imaging framework (DeepSIF) for imaging seizure activities from electroencephalogram (EEG) recordings in drug‐resistant focal epilepsy patients is investigated. The neural mass model of ictal oscillations is adopted to generate synthetic training data with spatio‐temporal‐spectra features similar to ictal dynamics. The trained DeepSIF model is rigorously validated using computer simulations and in a cohort of 33 drug‐resistant focal epilepsy patients with high‐density (76‐channel) EEG seizure recordings, by comparing DeepSIF estimates with surgical resection outcome and seizure onset zone (SOZ). These findings show that the trained DeepSIF model outperforms other methods in estimating the spatial and temporal information of origins of ictal activities. It achieves a high spatial specificity of 96% and a low spatial dispersion of 3.80 ± 5.74 mm when compared to the resection region. The source imaging results also demonstrate good coverage of SOZ, with an average distance of 10.89 ± 10.14 mm (from the SOZ to the reconstruction). These promising results suggest that DeepSIF has significant potential for advancing noninvasive imaging of the origins of ictal activities in patients with focal epilepsy, aiding management of intractable epilepsy.
High‐Density Atomic Level Defect Engineering of 2D Fe‐Based Metal‐Organic Frameworks Boosts Oxygen and Hydrogen Evolution Reactions
Authors: Zhao Xin , Wang Shixun , Cao Yanhui , Li Yun , Portniagin Arsenii S. , Tang Bing , Liu Qi , Kasák Peter , Zhao Tianshuo , Zheng Xuerong , Deng Yida , Rogach Andrey L.
Published: October 2024

Electrocatalysts based on metal‐organic frameworks (MOFs) attracted significant attention for water splitting, while the transition between MOFs and metal oxyhydroxide poses a great challenge in identifying authentic active sites and long‐term stability. Herein, we employ on‐purpose defect engineering to create high‐density atomic level defects on two‐dimensional Fe‐MOFs. The coordination number of Fe changes from 6 to 4.46, and over 28% of unsaturated Fe sites are formed in the optimized Fe‐MOF. In situ characterizations of the most optimized Fe‐MOF0.3 electrocatalyst during the oxygen evolution reaction (OER) process using Fourier transform infrared and Raman spectroscopy have revealed that some Fe unsaturated sites become oxidized with a concomitant dissociation of water molecules, causing generation of the crucial *OH intermediates and Fe oxyhydroxide. Moreover, the presence of Fe oxyhydroxide is compatible with the Volmer and Heyrovsky steps during the hydrogen evolution reaction (HER) process, which lower its energy barrier and accelerate the kinetics. As a result, the optimized Fe‐MOF electrodes delivered remarkable OER (259 mV at 10 mA cm-2) and HER (36 mV at 10 mA cm-2) performance. Our study offers comprehensive understanding of the effect of phase transformation on the electrocatalytic process of MOF‐based materials.
LIF Promotes Sec15b‐Mediated STAT3 Exosome Secretion to Maintain Stem Cell Pluripotency in Mouse Embryonic Development
Authors: Xu Li , Ji Jinjun , Wang Lingbo , Pan Jieli , Xiao Mingzhe , Zhang Chenxi , Gan Yihong , Xie Guanqun , Tan Mingdian , Wang Xinchang , Wen Chengping , Fan Yongsheng , Chin Y. Eugene
Published: October 2024

LIF maintains self‐renewal growth in mouse embryonic stem cells (mESC) by activating STAT3, which translocates into nucleus for pluripotent gene induction. However, the ERK signaling pathway activated by LIF at large counteract with pluripotent gene induction during self‐renewal growth. Here, it is reported that in mESC STAT3 undergoes multivesicular endosomes (MVEs) translocation and subsequent secretion, LIF‐activated STAT3 is acetylated on K177/180 and phosphorylated on Y293 residues within the N‐terminal coiled‐coil domain, which is responsible for the interaction between STAT3 and Secl5b, an exocyst complex component 6B (EXOC6B). STAT3 translocation into MVEs resulted in the downregulation of T202/Y204‐ERK1/2 phosphorylation and up‐regulation of S9‐GSK3β phosphorylation for maintaining mESC self‐renewal growth. STAT3 with K177R/K180R or Y293F substitution fails to execute MVEs translocation and Secl5b‐dependent secretion. Mice expressing K177RK180R substitution (STAT3mut/mut) are partially embryonic lethal. In STAT3mut/mut embryos, gene expressions related to hematological system function changed significantly and those living ones carry a series of abnormalities in the hematopoietic system. Furthermore, mice with Secl5b knockout exhibit embryonic lethality. Thus, Secl5b mediated STAT3 MVEs translocation regulates the balance of ERK and GSK3β signaling pathways and maintain mESC self‐renewal growth, which is involved in regulating the stability of hematopoietic system.