bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic atropine administration diminishes the contribution of vasoactive intestinal polypeptide to heart rate regulation
Authors: Kuncová J , Faitová Š , Capouch J , Štengl M , Slavíková J
Published: May 2021

Vasoactive intestinal polypeptide (VIP) is implicated in the
modulation of vagal effects on the heart rate. In this study, the
impact of acute and chronic atropine administration on VIP levels
in rat heart atria was investigated in relation to heart rate in the
course of vagus nerves stimulation. Anaesthetised control and
atropinised (10 mg/kg/day for 10 days) rats pretreated with
metipranolol and phentolamine that were either given or not a
single dose of atropine were subjected to bilateral vagus nerve
stimulation (30 min: 0.7 mA, 20 Hz, 0.2 ms). VIP concentrations
in the atria were determined after each stimulation protocol. In
control rats with or without single atropine administration, the
heart rate upon vagal stimulation was higher than in atropinised
animals with or without single atropine dose, respectively. VIP
concentrations in the control atria were significantly decreased
after the stimulation; the decrease was comparable both in the
absence and presence of a single dose of atropine. Compared to
controls, VIP levels were significantly decreased after chronic
atropine treatment and they were not further reduced by vagal
stimulation and single atropine administration. Administration of
VIP antagonist completely abolished the differences in the heart
rate upon vagal stimulation between control and atropinised
groups. In conclusion, the data indicate that chronic atropine
administration affects VIP synthesis in rat heart atria and
consequently it modifies the heart rate regulation.
Temsil Yetkisinin Açıklanması
Authors: KILIÇOĞLU YILMAZ Kumru
Published: May 2021

Temsil yetkisi genel olarak TBK md.40-48’de hükme bağlanmıştır. Diğer yasalarımızda temsile ilişkin özel hükümlerin bulunduğu hallerde, özel hüküm uygulanacaktır. Bu anlamda olmak üzere, ticaret şirketlerinde temsil konusu, TTK’da her bir şirket türüne göre ayrı ayrı hükme bağlanmıştır.
Bunun dışında TBK’nın temsil ile ilgili bu genel hükümleri temsil olunanın iradesine dayanan, yani hukuksal işleme dayanan temsil ile ilgilidir. Temsil yetkisinin temsil olunanın iradesine değil, kanuna dayandığı hallerde yasal temsilden (kanuni temsilden) söz edilir. Bu tür temsil hakkında ilgili yasa hükümleri uygulanacaktır. Bu anlamda olmak üzere, velayetin söz konusu olduğu hallerde velinin, vesayetin söz konusu olduğu hallerde ise vasinin temsil yetkisi konusunda ilgili hükümlerin uygulanması söz konusu olacaktır.
Temsilde en önemli konu, temsil olunanın temsil yetkisini açıklamasıdır. Bu iradenin açıklanmadığı veya açıklanmış sayılmadığı hallerde yetkili temsilden söz edilemez.
Bu incelemede önce genel olarak temsil yetkisi; daha sonra temsil yetkisi iradesinin açıklanmasının hukuksal niteliği; taraflar arasındaki temel ilişki ile temsil ilişkisi; açıklamanın muhatabı ele alınacak; bu anlamda temsil yetkisi iradesinin temsil olunan tarafından temsilciye açıklanması ile bu iradenin üçüncü kişilere ya da hem temsilciye hem de üçüncü kişiye açıklanmasının mümkün olup olmadığı konuları üzerinde durulacaktır.
Yeni Bir Şirket Türü: Bağlı Malvarlığına Sahip Limited Şirket
Authors: ATAKAN Murat Can
Published: May 2021

Kara Avrupası’na hakim olan şirkeler hukuku ilkelerine göre, bir şirketten söz edebilmek için; sözleşme, kişi, sermaye, ortak amaç ve ortak çaba unsurlarının bir arada bulunması gerekir. Şirkete nelerin sermaye olarak getirilebileceği kanun koyucu tarafından belirlenmiştir. Sermaye içerisinde yer alan malvarlığı unsurları zamanla artarak ya da azalarak değişkenlik gösterebilmektedir. Söz konusu malvarlığı unsurlarının önemli ölçüde azalması, şirketin geleceğini de tehlikeye düşürmektedir. Özellikle aile şirketlerinde görülen ve genellikle üçüncü nesilden sonra gözlemlenen kötü yönetim şekli, şirketin zarar etmesine ve bu zararların telafisi için öncelikle ve hızlı bir şekilde malvarlığı unsurlarının satışa çıkarılmasına yol açmaktadır.
Alman hukukçu, ekonomist ve iş insanlarının kurucusu olduğu “Verantwortungseigentum Vakfı” (Stiftung Verantwortungseigentum), şirketlerdeki malvarlığı unsurları kayıplarının önüne geçebilmek ve başta aile şirketleri olmak üzere, şirketlerin nesiller boyunca devamlılığını sağlayabilmek adına yeni bir şirket türü olarak “Bağlı Malvarlığına Sahip Limited Şirket” (Die GmbH in Verantwortungseigentum ya da diğer adıyla Die Gesellschaft mit gebundenem Vermögen) fikrini ortaya atmışlardır.
Vakıf tarafından önerilen bu yeni şirket türüne göre, limited şirkete özgülenen malvarlıkları tasarruf işlemlerine konu olamayacak, bu sayede şirket malvarlıklarının satışı engellenerek nesiller boyunca devam etmesi sağlanacaktır. Bir başka deyişle pay sahiplerinin malvarlığı değerlerini satarak kendilerine fayda sağlayıp şirketin yok olmasına sebep olmaları engellenmeye çalışılmıştır.
Bir yanda şirketlerin devamlılığını sağlayabilmek adına getirilen sınırlamalar söz konusuyken, diğer tarafta başta mirasçılar olmak üzere pay sahiplerinin haklarına halel gelmemesi adına, tüm pay sahiplerinin kar payı, yönetim ve/veya genel kurula katılma hakları koruma altına alınmıştır. Bu yönüyle getirilen öneri, adeta vakıf ile sermaye şirketi arasındaki ara bir form niteliğindedir.
Vakfın önerisi olan bu yeni şirket türü, büyük tartışmalar eşliğinde Alman Parlamentosu’na gelmiştir. Çalışmamızda söz konusu öneri şirketler hukuku prensipleri temelinde ele alınmış ve gerek Türk Hukuku gerekse Alman Hukuku bakımından tasarıya ilişkin görüşlerimiz açıklanmaya çalışılmıştır.
Hume's Pious Theist: Pamphilus
Authors: Tarrant James
Published: May 2021

Pamphilus's neglected role of narrator in Hume's Dialogues Concerning Natural Religion (1779), with its twin themes of piety and world origination, is vital in appreciating the significance of the work. Pamphilus illustrates the stultifying effects of the early inculcation of piety on the creative arguments of natural religion and mirrors the contemporary institutional opposition to Hume. The DNR is not simply a brilliant dissection of divine authorship of morality and creation; it is a model of impiety. Philo's brilliant attack on the morality of the deity, the foundation of piety, and his analysis of divine models of world origination, fails to move the pious Pamphilus who finds for his tutor, Cleanthes, at the conclusion of the debate.
HEMŞİRELERİN BİLİMSEL ARAŞTIRMA SÜRECİNE İLİŞKİN DENEYİMLERİ VE KARŞILAŞTIKLARI ENGELLER
Authors: SAVCI Cemile , ŞERBETÇİ Gülser , ÖZEL Hacer
Published: May 2021

Araştırma, hemşirelerin klinik uygulama alanlarındaki bir bilimsel araştırma sürecini yönetme durumlarını, deneyimlerini, karşılaştıkları engelleri ve etkileyen faktörleri belirlemek amacıyla planlanmıştır. Tanımlayıcı tipteki araştırmanın evrenini, Nisan-Mayıs 2017 tarihleri arasında İstanbul İlinde 10 sağlık kuruluşunda görevli 1270 hemşire, örneklemini ise, 0.05 örnekleme hatası ile 295 hemşire oluşturmuştur. Veriler etik kurul onayı alınarak 18 sorudan oluşan “Yapılandırılmış Bilgi Formu” ile toplanmıştır. Veriler SPSS 22 programı kullanılarak tanımlayıcı istatistiksel yöntemlerle analiz edilmiş, önemlilik düzeyi p<0.05 olarak kabul edilmiştir. Katılımcıların %56.6’sının lisans mezunu olduğu, %51,9’unun bir bilimsel araştırma sürecini yönettiği belirlenmiştir. Daha önce bilimsel araştırma sürecini yönetmeme nedenleri; iş yükü fazlalığı (%30.2), zaman yetersizliği (%23.1), bilimsel araştırmanın nasıl yapıldığını bilmemek (%18.6) olduğu belirlenmiştir. Bilimsel araştırma sürecinde ise; araştırmanın makale olarak yazılması (%40.3), araştırma konusuna karar verme (%39.9), araştırma konusuyla ilgili kaynağa ulaşma (%33.3) konularında sıklıkla güçlük yaşadıkları saptanmıştır. Bilimsel araştırma sürecini yönetme durumunu yordamada yaşın (p<0.05), eğitim düzeyinin (p=0.000) ve bilimsel araştırma süreci hakkında eğitim alma durumunun (p=0.000) pozitif yönde istatistiksel olarak anlamlı etkisinin olduğu belirlenmiştir (p= 0.000).
Amerikan Beyaz Kelebeği, Hyphantria cunea (Drury, 1773) (Lepidoptera: Erebiidae) Erken Dönem Larvalarına Karşı Yerel Beauveria bassiana ve Metarhizium anisopliae İzolatlarının Etkinliği
Authors: KARABÖRKLÜ Salih , ALTIN Nedim , BAHADIR Aleyna
Published: May 2021

Amerikan beyaz kelebeği, Hyphantria cunea polifag bir tür olup meyve üretim sahalarında, park ve bahçeler ile ormanlık alanlarda önemli derecede zarar meydana getirmektedir. Bu çalışma, Amerikan beyaz kelebeği, H. cunea’nın erken dönem larvalarına karşı yerel Beauveria bassiana ve Metarhizium anisopliae izolatlarının öldürücü etkilerinin belirlenmesi amacıyla laboratuvar koşullarında gerçekleştirilmiştir. Beauveria bassiana ve M. anisopliae izolatları 1x105 konsantrasyonda (konidi ml- 1) püskürtme yoluyla 1. ve 2. dönem larvalara uygulanmıştır. Kontrol gruplarına ise içerisinde %0.03’lük Tween 80 bulunan saf su uygulaması yapılmıştır. Uygulamalar 7 gün boyunca takip edilmiş ve ölen larva sayıları kaydedilmiştir. Bütün denemeler dört tekrarlı olarak yürütülmüştür. Beauveria bassiana ve M. anisopliae izolatlarının 1. ve 2. dönem H. cunea larvaları üzerinde önemli oranlarda öldürücü etki gösterdiği belirlenmiştir. Beauveria bassiana YK11 ve YK14 izolatları 1. dönem H. cunea larvalarının %75’ini öldürmüşken, M. anisopliae YK38, YK43 ve YK44 izolatları ise sırasıyla %70, %77.5 ve 80’ini öldürmüştür. H. cunea’nın 2. dönem larvalarında ise B. bassiana YK11 ve YK14 izolatları sırasıyla %68.61 ve %65.83 oranında, M. anisopliae YK38, YK43 ve YK44 izolatları ise sırasıyla %55, %73.89 ve %74.17 oranında öldürücü etki göstermiştir. Hyphantria cunea ile mücadelede B. bassiana ve M. anisopliae izolatlarının kullanılabileceğine yönelik bulgular elde edilmiştir. Ancak izolatların etkinliğini artırmaya yönelik kapsamlı çalışmalara ihtiyaç duyulmaktadır.
UMA HISTÓRIA DA CRIAÇÃO DO CURSO DE MATEMÁTICA DA UNESPAR – CAMPUS DE CAMPO MOURÃO
Authors: De Almeida Miranda Clarice , Secorun dos Santos Talita , Ferreira Luciano
Published: May 2021

Neste artigo apresenta-se uma investigação sobre o movimento da criação do curso deLicenciatura em Matemática da Universidade Estadual do Paraná – UNESPAR, campus de CampoMourão – Paraná - Brasil. Buscou-se constituir uma história da criação deste curso, utilizando deinformações acerca das discussões que a antecede até a implantação do curso, na então Faculdade deCiências e Letras de Campo Mourão - PR. Com este artigo, pretende-se contribuir para a construçãode uma História do curso de Matemática da UNESPAR. Foram consideradas as fontes escritasencontradas, como decretos e atas de reuniões, e as fontes orais, originadas de duas entrevistas, umarealizada pessoalmente com três professores e uma por uma ligação para o telefone de uma professora,sendo que estas vivenciaram de alguma forma o contexto da criação do curso. Para a organização dapesquisa utilizamos a metodologia História Oral. Identificou-se, nesta investigação, o vínculo que acriação do curso de Matemática teve com as primeiras discussões da constituição da FaculdadeEstadual de Ciências e Letras de Campo Mourão como uma Universidade. O objetivo principal, quejustificou a implantação do curso em Campo Mourão, foi a carência de professores de Matemáticapara a Educação Básica na região. A Universidade Estadual de Campinas teve contribuições para aimplantação e formação do corpo docente, por meio de diálogos e especializações para os docentes docurso. A autorização do curso veio de 15 de janeiro de 1998. As principais dificuldades enfrentadascom a abertura do curso foram a falta de professores no departamento, com poucos professoresefetivos, e a não autorização para abrir concurso público.
RESOLUÇÃO DE PROBLEMAS E FORMAÇÃO DE PROFESSORES: UM MAPEAMENTO DE TESES BRASILEIRAS NO CAMPO DA EDUCAÇÃO MATEMÁTICA (2014-2019)
Authors: Nascimento Martins Kaique , Pinca Sarro Gomes Larissa , Corrêa de Paula Marlúbia , Santos de Jesus Jolúcia
Published: May 2021

O presente artigo é o resultado de uma pesquisa realizada na Biblioteca Digital Brasileira de Teses e Dissertações. Metodologicamente, optou-se pela construção de um mapa teórico, com o objetivo de levantar, descrever e analisar as temáticas que emergem nas teses brasileiras do campo da Educação Matemática que problematizam a Resolução de Problemas na formação de professores, identificadas no período de 2014 a 2019. Para isso, o processo de análise ocorreu sob a luz de três eixos: os espaços de formação e seus colaboradores; os referenciais teóricos adotados; e a forma de abordar resolução de problemas na formação de professores. De modo geral, percebe-se, até o momento desta busca, uma predominância de estudos que comunicam o uso da metodologia de ensino-aprendizagem-avaliação de Matemática através da Resolução de Problemas no contexto da formação inicial e/ou continuada de professores. Identificou-se, ainda, um maior número de estudos direcionados a professores que lecionam na Educação Básica da rede pública, em especial nos anos finais do Ensino Fundamental e do Ensino Médio.
A RELEVÂNCIA DE CONHECER E COMPREENDER A INCOMPLETUDE DA MATEMÁTICA: UM OLHAR FENOMENOLÓGICO SOBRE O TEOREMA DA INCOMPLETUDE DE GÖDEL
Authors: Lopes Pinheiro José Milton , Batistela Rosemeire de Fatima
Published: May 2021

Este artigo discute a pertinência da crise nas ciências apresentadas pelo fenomenólogoEdmund Husserl diante do teorema da incompletude de Gödel. Com essa discussão objetiva-se exporo compreendido a respeito da importância de conhecer e compreender a incompletude da Matemática.Para isso realiza-se uma pesquisa qualitativa de cunho bibliográfico buscando o dito por algunspesquisadores das áreas de Filosofia, Matemática e Educação Matemática sobre a temática aquifocada. Neste estudo, considerações sobre a importância da compreensão da incompletude daMatemática são apresentadas com direcionamento aos matemáticos e, principalmente, aos nãomatemáticos, expondo possíveis implicações desse teorema nas vivências de sala de aula,evidenciando o escopo do método de produção da Matemática e questionando a ideia de que essaciência reina suprema em um oásis que só é acessível para alguns. Com o revés produzido peloteorema da incompletude para a possibilidade de completude em Matemática, entende-se que algomuda na compreensão dos limites do método axiomático. Disso, tem-se que a incompletude, apossibilidade de mudança e a transformação não se restringe ao sujeito que trabalha com aMatemática, mas também pode ocorrer na própria Matemática, que mesmo em suas estruturas maiscomplexas pode avançar através da produção de novos conhecimentos, como pode ser observado nosestudos da história da constituição e produção dessa ciência.
MATEMÁTICA NAS ESTAÇÕES DO ANO: O USO DE MATERIAIS DIDÁTICOS NO ENSINO DE MATEMÁTICA
Authors: De Oliveira Santos Viviane , Deyvis da Silva Correia Nickson , Aprigio do Nascimento Daniela
Published: May 2021

Esse artigo tem como objetivo apresentar ações do projeto de extensão Sem mais nem menos, do Instituto de Matemática da Universidade Federal de Alagoas, na pesquisa em Ensino de Matemática, que resultaram na elaboração e aplicação de materiais didáticos que evidenciam a Matemática nas estações do ano. Tais ações partiram do questionamento sobre como estudantes da rede pública de ensino de Alagoas veem a Matemática nas estações do ano. Para responder, foi aplicado um questionário em turmas de uma escola da rede pública de ensino em Maceió-AL e, a partir dele, foram elaborados jogos e atividades. Esses materiais didáticos abordam conteúdos matemáticos, tratam de informações sobre estações do ano e aguçam curiosidade e interesse dos estudantes, motivando-os a estudar. Com a pesquisa, verificamos que estudantes participantes avançaram na percepção da Matemática existente no cotidiano, na compreensão de conteúdos matemáticos como formas geométricas, fractais, múltiplos e divisores, sequência numérica de Fibonacci, frações, simetria, volume, e no desenvolvimento de habilidades como trabalho colaborativo, criatividade e raciocínio lógico e estratégico. Acreditamos que tais materiais didáticos são importantes, pois trabalham a Matemática de forma significativa, promovem um bom ambiente de aprendizagem e podem inspirar professores a abordarem outras possibilidades para o Ensino de Matemática.
ENSINO DE ESTATÍSTICA NA LICENCIATURA EM MATEMÁTICA POR MEIO DA METODOLOGIA DA RESOLUÇÃO DE PROBLEMA
Authors: Correia Silva Giane , Dos Santos Junior Guataçara
Published: May 2021

Este artigo tem como objetivo analisar o ensino de conteúdos de Estatística realizado por meio da metodologia da resolução de problemas com acadêmicos do curso de Licenciatura em Matemática. Os procedimentos de coleta de dados foram a observação e o registro das produções dos alunos geradas no desenvolvimento de uma situação-problema abordando os conceitos de população e amostra, variáveis qualitativa e quantitativa, coleta e apresentação de dados em tabelas e gráficos e medidas de tendência central. O pressuposto teórico que fundamenta o estudo foi apoiado nas sete etapas da metodologia da resolução de problemas proposta por Onuchic. Os resultados da análise dão indicativo de que a metodologia da resolução de problemas no curso de Licenciatura em Matemática pode constituir um diferencial para o ensino de conceitos estatísticos, pois favorece um ambiente motivador e desafiador, ao mesmo tempo em que propicia condições necessárias para o envolvimento ativo do acadêmico no processo de construção de seu conhecimento. Também pode-se perceber que a metodologia da resolução de problemas pode contribuir tanto para o desenvolvimento do pensamento e raciocínio estatísticos, com vistas ao alcance do letramento estatístico, quanto despertá-lo para o uso de diferentes formas de ensinar na sua futura atuação docente.
ÁREA DE FIGURAS PLANAS: CONTRIBUIÇÕES E DESAFIOS DO ENSINO INCLUSIVO A ALUNOS SURDOS UTILIZANDO TECNOLOGIAS DIGITAIS
Authors: Cabral de Oliveira Adriele , Alves Quintanilha Jéssica , Sopeletto Carreiro Leandro , Silva Ribeiro Cristiaine
Published: May 2021

Este trabalho apresenta os resultados da pesquisa cujo objetivo geral foi investigar os desafios e as contribuições do uso das Tecnologias Digitais no processo de dedução da área de figuras planas de forma a incluir alunos surdos. Para tanto, adotou-se a abordagem qualitativa do tipo intervenção pedagógica e optou-se por utilizar os recursos lousa digital e tablet. Foi elaborada uma sequência didática, cuja experimentação foi realizada numa turma do Curso Técnico Integrado ao Ensino Médio na Modalidade Educação de Jovens e Adultos. Dentre os desafios enfrentados, destacase a questão técnica de instalação da lousa digital e o fato de algumas funções terem sido aprendidas por meio de testes realizados pelas próprias pesquisadoras. Todos os participantes disseram que não tiveram dificuldades com o uso das Tecnologias Digitais utilizadas na pesquisa e afirmaram que o software GeoGebra facilitou e a lousa digital contribuiu, respectivamente, para o processo de dedução da área de figuras planas. Quanto ao aluno surdo, este afirmou ter se sentido incluído pela proposta da pesquisa.
A Chemically Defined, Xeno- and Blood-Free Culture Medium Sustains Increased Production of Small Extracellular Vesicles From Mesenchymal Stem Cells
Authors: Figueroa-Valdés Aliosha I. , de la Fuente Catalina , Hidalgo Yessia , Vega-Letter Ana María , Tapia-Limonchi Rafael , Khoury Maroun , Alcayaga-Miranda Francisca
Published: May 2021

Cell therapy is witnessing a notable shift toward cell-free treatments based on paracrine factors, in particular, towards small extracellular vesicles (sEV), that mimic the functional effect of the parental cells. While numerous sEV-based applications are currently in advanced preclinical stages, their promised translation depends on overcoming the manufacturing hurdles posed by the large-scale production of purified sEV. Unquestionably, the culture medium used with the parental cells plays a key role in the sEV’s secretion rate and content. An essential requisite is the use of a serum-, xeno-, and blood-free medium to meet the regulatory entity requirements of clinical-grade sEV’s production. Here, we evaluated OxiumTMEXO, a regulatory complying medium, with respect to production capacity and conservation of the EV’s characteristics and functionality and the parental cell’s phenotype and viability. A comparative study was established with standard DMEM and a commercially available culture medium developed specifically for sEV production. Under similar conditions, OxiumTMEXO displayed a three-fold increase of sEV secretion, with an enrichment of particles ranging between 51 and 200 nm. These results were obtained through direct quantification from the conditioned medium to avoid the isolation method’s interference and variability and were compared to the two culture media under evaluation. The higher yield obtained was consistent with several harvest time points (2, 4, and 6 days) and different cell sources, incluiding umbilical cord-, menstrual blood-derived mesenchymal stromal cells and fibroblasts. Additionally, the stem cell phenotype and viability of the parental cell remained unchanged. Furthermore, OxiumTMEXO-sEV showed a similar expression pattern of the vesicular markers CD63, CD9, and CD81, with respect to sEV derived from the other conditions. The in vitro internalization assays in different target cell types and the pharmacokinetic profile of intraperitoneally administered sEV in vivo indicated that the higher EV production rate did not affect the uptake kinetics or the systemic biodistribution in healthy mice. In conclusion, the OxiumTMEXO medium sustains an efficient and robust production of large quantities of sEV, conserving the classic functional properties of internalization into acceptor target cells and biodistribution in vivo, supplying the amount and quality of EVs for the development of cell-free therapies.
Toxoplasma gondii Type-I ROP18 Targeting Human E3 Ligase TRIM21 for Immune Escape
Authors: Yao Lijie , Xu Liqing , Zhou Lijuan , Wu Shuizhen , Zou Weihao , Chen Min , Chen Jiating , Peng Hongjuan
Published: May 2021

Toxoplasma gondii is an intracellular pathogen that exerts its virulence through inhibiting host’s innate immune responses, which is mainly related to the type II interferon (IFN-γ) response. IFN-γ inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that T. gondii virulence factor ROP18 of the type I RH strain (TgROP18I) interacted with human TRIM21, and promoted the latter’s phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of T. gondii infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-γ in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of IκB-α with p65 to activate the IFN-γ-inducible NF-κB pathway, which might be resulted by TRIM21-IκB-α interaction. In brief, our research identified that in human cells, IFN-γ-inducible TRIM21 functioned in the innate immune responses against type III T. gondii infection; however, TgROP18I promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.
Super and Selective Adsorption of Cationic Dyes onto Carboxylate-Modified Passion Fruit Peel Biosorbent
Authors: Chen Kaiwei , Du Linlin , Gao Peng , Zheng Junli , Liu Yuanli , Lin Hua
Published: May 2021

The carboxylate-functionalized passion fruit peel (PFPCS) was an efficient and rapid biosorbent for wastewater treatment. The PFPCS exhibited excellent selectivity to the cationic dyes, where the maximum adsorption capacities for methylene blue (MB) and methyl violet (MV) were 1,775.76 mg g−1 and 3,756.33 mg g−1, respectively. And the adsorption process of MB and MV on PFPCS reached equilibrium within 20 min. Moreover, the adsorption conditions and mechanisms were investigated. The adsorption process was in good agreement with the pseudo-second-order and Langmuir isotherm models. The adsorption mechanism was also proposed to be electrostatic interaction and hydrogen bond. After six cycles of desorption-adsorption, the removal efficient of MB and MV could be kept above 95%. Thus, PFPCS was considered as a highly efficient absorbent for removing cationic dyes from polluted water due to excellent adsorption characteristics, low cost and environmental friendliness.
Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems
Authors: Murray Benjamin O. , Flores Carlos , Williams Corin , Flusberg Deborah A. , Marr Elizabeth E. , Kwiatkowska Karolina M. , Charest Joseph L. , Isenberg Brett C. , Rohn Jennifer L.
Published: May 2021

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. UropathogenicE. coli(UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority ofin vitroUTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-basedin vitromodels have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.
Data-Driven Landslide Nowcasting at the Global Scale
Authors: Stanley Thomas A. , Kirschbaum Dalia B. , Benz Garrett , Emberson Robert A. , Amatya Pukar M. , Medwedeff William , Clark Marin K.
Published: May 2021

Landslides affect nearly every country in the world each year. To better understand this global hazard, the Landslide Hazard Assessment for Situational Awareness (LHASA) model was developed previously. LHASA version 1 combines satellite precipitation estimates with a global landslide susceptibility map to produce a gridded map of potentially hazardous areas from 60° North-South every 3 h. LHASA version 1 categorizes the world’s land surface into three ratings: high, moderate, and low hazard with a single decision tree that first determines if the last seven days of rainfall were intense, then evaluates landslide susceptibility. LHASA version 2 has been developed with a data-driven approach. The global susceptibility map was replaced with a collection of explanatory variables, and two new dynamically varying quantities were added: snow and soil moisture. Along with antecedent rainfall, these variables modulated the response to current daily rainfall. In addition, the Global Landslide Catalog (GLC) was supplemented with several inventories of rainfall-triggered landslide events. These factors were incorporated into the machine-learning framework XGBoost, which was trained to predict the presence or absence of landslides over the period 2015–2018, with the years 2019–2020 reserved for model evaluation. As a result of these improvements, the new global landslide nowcast was twice as likely to predict the occurrence of historical landslides as LHASA version 1, given the same global false positive rate. Furthermore, the shift to probabilistic outputs allows users to directly manage the trade-off between false negatives and false positives, which should make the nowcast useful for a greater variety of geographic settings and applications. In a retrospective analysis, the trained model ran over a global domain for 5 years, and results for LHASA version 1 and version 2 were compared. Due to the importance of rainfall and faults in LHASA version 2, nowcasts would be issued more frequently in some tropical countries, such as Colombia and Papua New Guinea; at the same time, the new version placed less emphasis on arid regions and areas far from the Pacific Rim. LHASA version 2 provides a nearly real-time view of global landslide hazard for a variety of stakeholders.
The 2020 M6.4 Jiashi Earthquake: An Event that Occurred Under the Décollement on the Kaping Fold-and-Thrust Belt in the Southwestern Tien Shan Mountains, China
Authors: Yao Qi , Yang Wen , Jiang Xianghua , Guo Yanshuang , Liu Jie , Zhang Yongxian , Wang Hui , Ren Jing , Yu Cheng , Yue Chong , Zhao Jing
Published: May 2021

The 2020 Jiashi M6.4 earthquake occurred in the Kaping fold-and-thrust belt, a major south-verging active thin-skin system in the southwestern Chinese Tien Shan Mountain, north of the Tarim Basin. Within 50 km from the epicentral area, seismic hazard is high, as suggested by the occurrence of the 1902 Mw 7.7 Artux (Kashgar) earthquake and 1997 Jiashi strong earthquake swarm. The seismogenic structure responsible for the 2020 event is not well constrained and is a subject of debate. We relocated the 2020 Jiashi earthquake sequence and assessed the relocation uncertainties, using eight seismic velocity models and based on detailed local and regional subcrustal structures from seismic profiles. Then we compared the temporal variation in the Gutenberg–Richter b-values of the 2020 sequence with those of the 1997, 1998, and 2003 earthquake sequences. Our results show that most events cluster at depths greater than 10 km, suggesting that the events most likely occurred beneath the décollement and inside the Tarim Craton. The spatiotemporal evolution of the sequence suggests that two groups of structures at depth were involved in the 2020 sequences: NW–SE-trending lateral strike-slip faults and E–W-trending reverse faults. The b-values of the 2020 sequence exhibits relatively stable temporal evolution, unlike those of the multi-shock sequence that occurred inside the Tarim Craton. It indicates that the 2020 sequence perhaps was influenced by the stress interaction with the 10 km thick overlying strata. Our study provides a new perspective on the seismogenic structure of the earthquakes that occurred because of reactivation of ancient structures developed in a stable craton.
Ocean Circulation Model Applications for the Estuary-Coastal-Open Sea Continuum
Authors: Murawski Jens , She Jun , Mohn Christian , Frishfelds Vilnis , Nielsen Jacob Woge
Published: May 2021

Coastal zones are among the most variable environments. As such, they require adaptive water management to ensure the balance of economic and social interests with environmental concerns. High quality marine data of hydrographic conditions e.g., sea level, temperature, salinity, and currents are needed to provide a sound foundation for the decision making process. Operational models with sufficiently high forecasting quality and resolution can be used for a further extension of the marine service toward the coastal-estuary areas. The Limfjord is a large and shallow water body in Northern Jutland, connecting the North Sea in the West and the Kattegat in the East. It is currently not covered by the CMEMS service, despite its importance for sea shipping, aquaculture and mussel fisheries. In this study, we use the operational HIROMB-BOOS Model (HBM) to resolve the full Baltic-Limfjord-North Sea system with a horizontal resolution of 185.2 m in the Limfjord. The study shows several factors that are essential for successfully modeling the coastal-estuary system: (a) high computational efficiency and flexible grids to allow high resolution in the fjord, (b) an improved short wave radiation scheme to model the thermodynamics and the diurnal variability of the temperature in very shallow waters, (c) high resolution atmospheric forcing, (d) adequate river forcing, and (e) accurate bathymetry in the narrow straits. With properly resolving these issues, the system is able to provide high quality sea level forecast for storm surge warning and hydrography forecasts: temperature, salinity and currents with sufficiently good quality for ecosystem-based management. The model is able to simulate the complex spatial and temporal pattern of sea level, salinity and temperature in the Limfjord and to reproduce their diurnal, seasonal and interannual variability and stratification rather well. Its high computational efficiency makes it possible to model the transition from the basin-scales to coastal- and estuary-scales seamlessly. In total, The HBM model has been successfully extended, to include the complex estuary system of the Limfjord, and shows an adequate model performance with regards to sea level, salinity and temperature predictions, suitable for storm surge warning applications and coastal management applications.
Comprehensive Analysis of Autophagy-Associated lncRNAs Reveal Potential Prognostic Prediction in Pancreatic Cancer
Authors: Chen Guangyu , Yang Gang , Long Junyu , Yang Jinshou , Qin Cheng , Luo Wenhao , Qiu Jiangdong , Zhao Fangyu , You Lei , Zhang Taiping , Zhao Yupei
Published: May 2021

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network via Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC.
Perspectives and Emotional Experiences of Patients With Chronic Myeloid Leukemia During ENESTPath Clinical Trial and Treatment-Free Remission: Rationale and Protocol of the Italian Substudy
Authors: Borghi Lidia , Rosti Gianantonio , Maggi Alessandro , Breccia Massimo , Di Bona Eros , Iurlo Alessandra , La Barba Gaetano , Sportoletti Paolo , Albano Francesco , Galimberti Sara , Rivellini Flavia , Cambrin Giovanna Rege , Capodanno Isabella , Cuneo Antonio , Bonifacio Massimiliano , Sica Simona , Arcaini Luca , Capochiani Enrico , Minotto Claudia , Ciceri Fabio , Crugnola Monica , Di Caprio Luigi , Supekar Sharon , Elena Chiara , Baccarani Michele , Vegni Elena
Published: May 2021

Achievement of deep molecular response following treatment with a tyrosine kinase inhibitor (TKI) allows for treatment-free remission (TFR) in many patients with chronic myeloid leukemia (CML). Successful TFR is defined as the achievement of a sustained molecular response after cessation of ongoing TKI therapy. The phase 3 ENESTPath study was designed to determine the required optimal duration of consolidation treatment with the second-generation TKI, nilotinib 300 mg twice-daily, to remain in successful TFR without relapse after entering TFR for 12 months. The purpose of this Italian ‘patient’s voice CML’ substudy was to evaluate patients’ psycho-emotional characteristics and quality of life through their experiences of stopping treatment with nilotinib and entering TFR. The purpose of the present contribution is to early present the study protocol of an ongoing study to the scientific community, in order to describe the study rationale and to extensively present the study methodology. Patients aged ≥18 years with a confirmed diagnosis of Philadelphia chromosome positive BCR-ABL1+ CML in chronic phase and treated with front-line imatinib for a minimum of 24 months from the enrollment were eligible. Patients consenting to participate the substudy will have quality of life questionnaires and in-depth qualitative interviews conducted. The substudy will include both qualitative and quantitative design aspects to evaluate the psychological outcomes as assessed via patients’ emotional experience during and after stopping nilotinib therapy. Randomization is hypothesized to be a timepoint of higher psychological alert or distress when compared to consolidation and additionally any improvement in health-related quality of life (HRQoL) due to nilotinib treatment is expected across the timepoints (from consolidation, to randomization, and TFR). An association is also expected between dysfunctional coping strategies, such as detachments and certain personality traits, and psychological distress and HRQoL impairments. Better HRQoL outcomes are expected in TFR compared to the end of consolidation. This substudy is designed for in-depth assessment of all potential psycho-emotional variables and aims to determine the need for personalized patient care and counselling, and also guide clinicians to consider the psychological well-being of patients who are considering treatment termination.

NCT number: NCT01743989, EudraCT number: 2012-005124-15
Nivolumab for Metastatic Urothelial Cancer in a Renal Allograft Recipient With Subsequent Graft Rejection and Treatment Complete Remission: A Case Report
Authors: Chen Didi , Wu Xinyi , Xie Congying
Published: May 2021

Immune checkpoint inhibitors (ICIs) expanded the therapeutic options for several cancers. However, whether some special groups of patients including those with organ transplantation can receive ICIs remains unclear. In this report we presented an interesting case. A 54-year-old woman underwent kidney transplantation, developed metastasis 7 years after operation of the bladder tumor. Her disease progressed after chemotherapy and radiotherapy. Anti-PD-1 immunotherapy was then considered. After two cycles of nivolumab immunotherapy, the patient’s renal function declined rapidly. Acute allograft rejection was considered. There was no significant decrease in creatinine after glucocorticoid pulse therapy. Third course of nivolumab was given, and regularly hemodialysis was simultaneously conducted. Two weeks later, the patient showed left abdominal pain. CT scan revealed a reduction in tumor burden, while enlarged volume of kidney graft. Immunotherapy stopped. Two months after the third course, CT demonstrated a complete remission to immunotherapy. 23 months after the third course, CT showed that the swelling transplanted kidney was smaller than previous, and no recurrence was observed.
Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland
Authors: Schlapbach Luregn J. , Andre Maya C. , Grazioli Serge , Schöbi Nina , Ritz Nicole , Aebi Christoph , Agyeman Philipp , Albisetti Manuela , Bailey Douggl G. N. , Berger Christoph , Blanchard-Rohner Géraldine , Bressieux-Degueldre Sabrina , Hofer Michael , L'Huillier Arnaud G. , Marston Mark , Meyer Sauteur Patrick M. , Pachlopnik Schmid Jana , Perez Marie-Helene , Rogdo Bjarte , Trück Johannes , Woerner Andreas , Wütz Daniela , Zimmermann Petra , Levin Michael , Whittaker Elizabeth , Rimensberger Peter C. ,   the PIMS-TS working group of the Interest Group for Pediatric Neonatal Intensive Care (IGPNI) of the Swiss Society of Intensive Care and the Pediatric Infectious Diseases Group Switzerland (PIGS)
Published: May 2021

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce.

Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing.

Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance.

Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation.

Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.
Label-Free Proteomic Analysis of Smoke-Drying and Shade-Drying Processes of Postharvest Rhubarb: A Comparative Study
Authors: Liang Wei , Chen Yuan , Li Xia , Guo Fengxia , Sun Jiachen , Zhang Xuemin , Xu Bo , Gao Wenyuan
Published: May 2021

Postharvest processing plays a very important role in improving the quality of traditional Chinese medicine. According to previous studies, smoke-drying could significantly promote the accumulation of the bioactive components and pharmacological activities of rhubarb, but so far, the molecular mechanism has not been studied yet. In this research, to study the molecular mechanisms of postharvest processing for rhubarb during shade-drying and smoke-drying, label-free proteomic analyses were conducted. In total, 1,927 differentially abundant proteins (DAPs) were identified from rhubarb samples treated by different drying methods. These DAPs were mainly involved in response and defense, signal transduction, starch, carbohydrate and energy metabolism, and anthraquinone and phenolic acid biosynthesis. Smoke-drying significantly enhanced the expression of proteins involved in these metabolic pathways. Accordingly, the molecular mechanism of the accumulation of effective ingredients of rhubarb was clarified, which provided a novel insight into the biosynthesis of active ingredients that occur during the rhubarb dry process.
SARS-CoV-2 B.1.1.7 UK Variant of Concern Lineage-Related Perceptions, COVID-19 Vaccine Acceptance and Travel Worry Among Healthcare Workers
Authors: Temsah Mohamad-Hani , Barry Mazin , Aljamaan Fadi , Alhuzaimi Abdullah N. , Al-Eyadhy Ayman , Saddik Basema , Alsohime Fahad , Alhaboob Ali , Alhasan Khalid , Alaraj Ali , Halwani Rabih , Jamal Amr , Alamro Nurah , Temsah Reem , Esmaeil Samia , Alenezi Shuliweeh , Alzamil Fahad , Somily Ali M. , Al-Tawfiq Jaffar A.
Published: May 2021

Background: Healthcare workers' (HCWs') travel-related anxiety needs to be assessed in light of the emergence of SARS-CoV-2 mutations.

Methods: An online, cross-sectional questionnaire among HCWs between December 21, 2020 to January 7, 2021. The outcome variables were HCWs' knowledge and awareness of the SARS-CoV-2 B.1.1.7 lineage that was recently reported as the UK variant of concern, and its associated travel worry and Generalized Anxiety Disorder (GAD-7) score.

Results: A total of 1,058 HCWs completed the survey; 66.5% were female, 59.0% were nurses. 9.0% indicated they had been previously diagnosed with COVID-19. Regarding the B.1.1.7 lineage, almost all (97.3%) were aware of its emergence, 73.8% were aware that it is more infectious, 78.0% thought it causes more severe disease, and only 50.0% knew that current COVID-19 vaccines are effective in preventing it. Despite this, 66.7% of HCWs were not registered to receive the vaccine. HCWs' most common source of information about the new variant was social media platforms (67.0%), and this subgroup was significantly more worried about traveling. Nurses were more worried than physicians (P = 0.001).

Conclusions: Most HCWs were aware of the emergence of the SARS-CoV-2 B.1.1.7 variant and expressed substantial travel worries. Increased worry levels were found among HCWs who used social media as their main source of information, those with lower levels of COVID-19 vaccine uptake, and those with higher GAD-7 scores. The utilization of official social media platforms could improve accurate information dissemination among HCWs regarding the Pandemic's evolving mutations. Targeted vaccine campaigns are warranted to assure HCWs about the efficacy of COVID-19 vaccines toward SARS-CoV-2 variants.
Smiles as a Signal of Prosocial Behaviors Toward the Robot in the Therapeutic Setting for Children With Autism Spectrum Disorder
Authors: Kim SunKyoung , Hirokawa Masakazu , Matsuda Soichiro , Funahashi Atsushi , Suzuki Kenji
Published: May 2021

We explored how robot-assisted therapy based on smile analysis may facilitate the prosocial behaviors of children with autism spectrum disorder. Prosocial behaviors, which are actions for the benefit of others, are required to belong to society and increase the quality of life. As smiling is a candidate for predicting prosocial behaviors in robot-assisted therapy, we measured smiles by annotating behaviors that were recorded with video cameras and by classifying facial muscle activities recorded with a wearable device. While interacting with a robot, the participants experienced two situations where participants' prosocial behaviors are expected, which were supporting the robot to walk and helping the robot from falling. We first explored the overall smiles at specific timings and prosocial behaviors. Then, we explored the smiles triggered by a robot and behavior changes before engaging in prosocial behaviors. The results show that the specific timing of smiles and prosocial behaviors increased in the second session of children with autism spectrum disorder. Additionally, a smile was followed by a series of behaviors before prosocial behavior. With a proposed Bayesian model, smiling, or heading predicted prosocial behaviors with higher accuracy compared to other variables. Particularly, voluntary prosocial behaviors were observed after smiling. The findings of this exploratory study imply that smiles might be a signal of prosocial behaviors. We also suggest a probabilistic model for predicting prosocial behaviors based on smile analysis, which could be applied to personalized robot-assisted therapy by controlling a robot's movements to arouse smiles and increase the probability that a child with autism spectrum disorder will engage in prosocial behaviors.