bluuebunny/crossref_metadata_2025_split huggingface dataset:
GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer
Authors: Artz Annette , Butz Stefan , Vestweber Dietmar 
Published: May 2016

Key PointsA classical TGF-β receptor pair counteracts extravasation of myeloid cells by rapidly interfering with integrin activation. GDF-15 and TGF-β1 inhibit leukocyte integrin activation by targeting the Rap-1 GTPase exchange factor CalDAG-GEF1.
Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia
Authors: Thijssen Rachel , ter Burg Johanna , Garrick Brett , van Bochove Gregor G. W. , Brown Jennifer R. , Fernandes Stacey M. , Rodríguez María Solé , Michot Jean-Marie , Hallek Michael , Eichhorst Barbara , Reinhardt Hans Christian , Bendell Johanna , Derks Ingrid A. M. , van Kampen Roel J. W. , Hege Kristen , Kersten Marie José , Trowe Torsten , Filvaroff Ellen H. , Eldering Eric , Kater Arnon P. 
Published: May 2016

Key PointsTORK/DNA-PK inhibition induces cytotoxicity and blocks signaling pathways important for CLL survival, proliferation, and drug resistance. Preliminary clinical effects of TORK/DNA-PK inhibition show 7 of 8 CLL patients with decreased lymphadenopathy.
Impact of complete molecular response on survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Short Nicholas J. , Jabbour Elias , Sasaki Koji , Patel Keyur , O’Brien Susan M. , Cortes Jorge E. , Garris Rebecca , Issa Ghayas C. , Garcia-Manero Guillermo , Luthra Rajyalakshmi , Thomas Deborah , Kantarjian Hagop , Ravandi Farhad 
Published: May 2016

Key PointsIn patients with Ph+ ALL, achievement of CMR at 3 months is independently associated with improved survival. CMR at 3 months may identify patients with Ph+ ALL who have excellent long-term outcomes without SCT in first CR.
Automatic learning of pre-miRNAs from different species
Authors: O. N. Lopes Ivani de , Schliep Alexander , de L. F. de Carvalho André P. 
Published: May 2016

Abstract
Background
Discovery of microRNAs (miRNAs) relies on predictive models for characteristic features from miRNA precursors (pre-miRNAs). The short length of miRNA genes and the lack of pronounced sequence features complicate this task. To accommodate the peculiarities of plant and animal miRNAs systems, tools for both systems have evolved differently. However, these tools are biased towards the species for which they were primarily developed and, consequently, their predictive performance on data sets from other species of the same kingdom might be lower. While these biases are intrinsic to the species, their characterization can lead to computational approaches capable of diminishing their negative effect on the accuracy of pre-miRNAs predictive models. We investigate in this study how 45 predictive models induced for data sets from 45 species, distributed in eight subphyla/classes, perform when applied to a species different from the species used in its induction.

Results
Our computational experiments show that the separability of pre-miRNAs and pseudo pre-miRNAs instances is species-dependent and no feature set performs well for all species, even within the same subphylum/class. Mitigating this species dependency, we show that an ensemble of classifiers reduced the classification errors for all 45 species. As the ensemble members were obtained using meaningful, and yet computationally viable feature sets, the ensembles also have a lower computational cost than individual classifiers that rely on energy stability parameters, which are of prohibitive computational cost in large scale applications.

Conclusion
In this study, the combination of multiple pre-miRNAs feature sets and multiple learning biases enhanced the predictive accuracy of pre-miRNAs classifiers of 45 species. This is certainly a promising approach to be incorporated in miRNA discovery tools towards more accurate and less species-dependent tools.
The material to reproduce the results from this paper can be downloaded from http://dx.doi.org/10.5281/zenodo.49754.
Single-stranded DNA binding protein Ssbp3 induces differentiation of mouse embryonic stem cells into trophoblast-like cells
Authors: Liu Jifeng , Luo Xinlong , Xu Yanli , Gu Junjie , Tang Fan , Jin Ying , Li Hui 
Published: May 2016

Abstract
Background
Intrinsic factors and extrinsic signals which control unlimited self-renewal and developmental pluripotency in embryonic stem cells (ESCs) have been extensively investigated. However, a much smaller number of factors involved in extra-embryonic trophoblast differentiation from ESCs have been studied. In this study, we investigated the role of the single-stranded DNA binding protein, Ssbp3, for the induction of trophoblast-like differentiation from mouse ESCs.

Methods
Gain- and loss-of-function experiments were carried out through overexpression or knockdown of Ssbp3 in mouse ESCs under self-renewal culture conditions. Expression levels of pluripotency and lineage markers were detected by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses. The global gene expression profile in Ssbp3-overexpressing cells was determined by affymetrix microarray. Gene ontology and pathway terms were analyzed and further validated by qRT-PCR and Western blotting. The methylation status of the Elf5 promoter in Ssbp3-overexpressing cells was detected by bisulfite sequencing. The trophoblast-like phenotype induced by Ssbp3 was also evaluated by teratoma formation and early embryo injection assays.

Results
Forced expression of Ssbp3 in mouse ESCs upregulated expression levels of lineage-associated genes, with trophoblast cell markers being the highest. In contrast, depletion of Ssbp3 attenuated the expression of trophoblast lineage marker genes induced by downregulation of Oct4 or treatment with BMP4 and bFGF in ESCs. Interestingly, global gene expression profiling analysis indicated that Ssbp3 overexpression did not significantly alter the transcript levels of pluripotency-associated transcription factors. Instead, Ssbp3 promoted the expression of early trophectoderm transcription factors such as Cdx2 and activated MAPK/Erk1/2 and TGF-β pathways. Furthermore, overexpression of Ssbp3 reduced the methylation level of the Elf5 promoter and promoted the generation of teratomas with internal hemorrhage, indicative of the presence of trophoblast cells.

Conclusions
This study identifies Ssbp3, a single-stranded DNA binding protein, as a regulator for mouse ESCs to differentiate into trophoblast-like cells. This finding is helpful to understand the regulatory networks for ESC differentiation into extra-embryonic lineages.
Deleterious assembly of the lamin A/C mutant p.S143P causes ER stress in familial dilated cardiomyopathy
Authors: West Gun , Gullmets Josef , Virtanen Laura , Li Song-Ping , Keinänen Anni , Shimi Takeshi , Mauermann Monika , Heliö Tiina , Kaartinen Maija , Ollila Laura , Kuusisto Johanna , Eriksson John E. , Goldman Robert D. , Herrmann Harald , Taimen Pekka 
Published: May 2016

ABSTRACT
Mutation of the LMNA gene, encoding nuclear lamin A and lamin C (hereafter lamin A/C), is a common cause of familial dilated cardiomyopathy (DCM). Among Finnish DCM patients, the founder mutation c.427T&gt;C (p.S143P) is the most frequently reported genetic variant. Here, we show that p.S143P lamin A/C is more nucleoplasmic and soluble than wild-type lamin A/C and accumulates into large intranuclear aggregates in a fraction of cultured patient fibroblasts as well as in cells ectopically expressing either FLAG- or GFP-tagged p.S143P lamin A. In fluorescence loss in photobleaching (FLIP) experiments, non-aggregated EGFP-tagged p.S143P lamin A was significantly more dynamic. In in vitro association studies, p.S143P lamin A failed to form appropriate filament structures but instead assembled into disorganized aggregates similar to those observed in patient cell nuclei. A whole-genome expression analysis revealed an elevated unfolded protein response (UPR) in cells expressing p.S143P lamin A/C. Additional endoplasmic reticulum (ER) stress induced by tunicamycin reduced the viability of cells expressing mutant lamin further. In summary, p.S143P lamin A/C affects normal lamina structure and influences the cellular stress response, homeostasis and viability.
Ccndbp1 is a new positive regulator of skeletal myogenesis
Authors: Huang Yan , Chen Bohong , Ye Miaoman , Liang Puping , Zhangfang Yingnan , Huang Junjiu , Liu Mingyao , Songyang Zhou , Ma Wenbin 
Published: May 2016

ABSTRACT
Skeletal myogenesis is a multistep process in which basic helix-loop-helix (bHLH) transcription factors, such as MyoD (also known as MyoD1), bind to E-boxes and activate downstream genes. Ccndbp1 is a HLH protein that lacks a DNA-binding region, and its function in skeletal myogenesis is currently unknown. We generated Ccndbp1-null mice by using CRISPR–Cas9. Notably, in Ccndbp1-null mice, the cross sectional area of the skeletal tibialis anterior muscle was smaller, and muscle regeneration ability and grip strength were impaired, compared with those of wild type. This phenotype resembled that of myofiber hypotrophy in some human myopathies or amyoplasia. Ccndbp1 expression was upregulated during C2C12 myogenesis. Ccndbp1 overexpression promoted myogenesis, whereas knockdown of Ccndbp1 inhibited myogenic differentiation. Co-transfection of Ccndbp1 with MyoD and/or E47 (encoded by TCF3) significantly enhanced E-box-dependent transcription. Furthermore, Ccndbp1 physically associated with MyoD but not E47. These data suggest that Ccndbp1 regulates muscle differentiation by interacting with MyoD and enhancing its binding to target genes. Our study newly identifies Ccndbp1 as a positive modulator of skeletal myogenic differentiation in vivo and in vitro, providing new insights in order to decipher the complex network involved in skeletal myogenic development and related diseases.
Does Unc–GFP uncover ciliary structures in the rhabdomeric eye of Drosophila?
Authors: Gottardo Marco , Callaini Giuliano , Riparbelli Maria Giovanna 
Published: May 2016

ABSTRACT
The uncoordinated (unc) gene product, a potential ortholog of mammalian orofaciodigital syndrome 1 (Ofd1), is involved in the assembly of the ciliary axoneme in Drosophila and it is, therefore, constrained to cell types that have ciliary structures, namely type 1 sensory neurons and male germ cells. Here, we show that evenly spaced Unc–GFP spots are present in the eye imaginal discs of third-instar larvae. These spots are restricted to the R8 photoreceptor cell of each ommatidium in association with mother centrioles. This finding is unexpected because the Drosophila eye is of the rhabdomeric type and would be expected to lack ciliary structures.
Novas Tecnologias Educacionais: explorando o tema ar, água e solo tendo o Scratch como ferramenta pedagógica no nível fundamental
Authors: Da Silva Luely Oliveira , Raiol Eduardo Paulo Marques , Alves Heitor Correa , Martins João Paulo Da Silva 
Published: May 2016

Conhecendo os avanços da tecnologia dentro da sociedade e principalmente, a inserção dos recursos da informática nas modalidades de ensino, pospôs-se a utilização e a investigação quanto ao uso do programa Scratch enquanto instrumento de apoio tecnológico aos professores de ciências no desenvolvimento dos conteúdos ar, água e solo no 6º ano do nível fundamental. Buscou-se compreender quais contribuições o programa utilizado trouxe para a formação de estudantes do ensino fundamental (6º ano) e professor de uma escola do Estado do Pará que atua na área de ciências. Para coleta de dados utilizou-se questionário para o professor e roteiro de observação para os alunos e aspectos físicos da escola, seguido da aplicação de uma oficina pedagógica para o público investigado. Os resultados obtidos permitiram revelar que a introdução da tecnologia em sala de aula, especificamente programa de computador Scratch foi fundamental na aprendizagem dos alunos para o referido conteúdo. Destacando que as oficinas despertaram o interesse, participação, bem como contribuiu para uma aprendizagem mais significativa dos mesmos. Considera-se que a tecnologia é um dos recursos que está em crescente utilização nos meios escolares e representa um desafio para os avanços das aprendizagens no ensino de ciências. O professor revelou a necessidade de ferramentas que motivem os estudantes e apontam falta de atividades práticas. Nesse sentido, defende-se o uso de ferramentas como o Scratch que incentiva e auxilia a aprendizagem dos discentes.
Herbário virtual e universidade: biodiversidade vegetal para ensino, pesquisa e extensão
Authors: Costa Jéssica Caroline Mendes da , Lucas Flávia Cristina Araújo , Gois Maria Antonia Ferreira , Leão Victor Miranda , Lobato Gerciene De Jesus Miranda 
Published: May 2016

Coleções botânicas documentam a identidade e distribuição das espécies vegetais, sendo essenciais tanto em trabalhos básicos quanto aplicados. O herbário Profª. Drª. Marlene Freitas da Silva (MFS), localizado na Universidade do Estado do Pará (UEPA) possui espaço consolidado desde 2011, contudo seu acervo é pouco explorado no ambiente acadêmico. Este estudo objetivou criar um Herbário Virtual para o MFS, na Universidade do Estado do Pará, visando o acesso on line de dados diversificados da biodiversidade vegetal amazônica, como forma de contribuir para maior integração e socialização de informações à sociedade. Foram realizadas entrevistas informais com aplicação de formulários semiestruturados à 48 pessoas que visitaram a exposição do herbário na Semana Acadêmica da universidade. A preparação da infraestrutura dos dados do acervo para disponibilização on line, incluiu melhorias da qualidade dos bancos de informações e imagens, criação da página virtual e instalação do Brahms on line. As verbalizações dos interlocutores exteriorizaram o desconhecimento da existência do espaço na UEPA, bem como suas reflexões acerca da importância do MFS na produção de conhecimentos, destacando sua função sociocultural. A criação do espaço virtual possibilitou maior conhecimento de toda a coleção, com 5.800 amostras, 2.700 espécies, pertencentes a 886 gêneros e 173 famílias botânicas. Ademais, há também a coleção de flores, frutos, sementes e plântulas, que estão associadas a 210 registros de exsicatas. A socialização on line da biodiversidade vegetal promoveu dentro da universidade maior valorização de bens que são patrimônios naturais da humanidade, além de contribuir com dados científicos para toda a sociedade.
Avaliação microbiológica do leite cru e pasteurizado comercializado no município de Benevides-PA.
Authors: Lima Layana Natália Carvalho de , Torres Lenice Da Silva , Silva Luana Kelly Baltazar da , Santos Rayssa Silva dos , Cruz Tatyane Myllena Souza da , Figueiredo Elaine Lopes 
Published: May 2016

O leite é um alimento com alto valor nutritivo, pois apresenta em sua constituição água, proteínas, carboidratos, lipídeos, vitaminas e sais minerais. Em virtude de sua composição rica em nutrientes, torna-se um alimento altamente perecível, sendo muito susceptível a alterações por micro-organismos deterioradores e patogênicos. Desta forma, este trabalho tem como objetivo analisar a qualidade microbiológica do leite cru e do leite pasteurizado comercializados no município de Benevides-PA. Foram realizadas análises microbiológicas de contagem padrão de bactérias aeróbias mesófilas, Coliformes Totais e Coliformes Termotolerantes. Todas as análises seguiram a metodologia descrita na Instrução Normativa nº 62, de 26 de Agosto de 2003, do Ministério da Agricultura, Pecuária e Abastecimento. As médias dos resultados microbiológicos mostraram que as amostras de leite cru apresentaram contagem máxima de Coliformes Termotolerantes e Totais. Em contrapartida, não houve contaminação de Coliformes em nenhuma amostra de leite pasteurizado. Em relação aos resultados de contagem padrão de bactérias aeróbias mesófilas, verificou-se que as médias para as amostras de leite cru e leite pasteurizado foram de 4 × 104 UFC/mL e 6,1 × 102 UFC/mL, respectivamente. Apesar da presença desses micro-organismos, as amostras encontram-se dentro do permitido pela Instrução Normativa 51. Diante dos resultados obtidos, pode-se verificar a importância da utilização da pasteurização, como tratamento térmico para garantir a qualidade da matéria prima. Palavras-chave: leite, tratamento térmico, qualidade.
A experimentação como instrumento para o ensino de titulação com uma turma de graduandos em licenciatura em Química
Authors: Portal Gomes Paulo Wender , Barbosa Muribeca Abraão De Jesus , Campos Jhonnath Moreira , Alves da Costa Ana Paula , Malato Bettina Valda , Câmara Silva Diana Do Socorro , De Souza Ronilson Freitas 
Published: May 2016

O presente trabalho teve por finalidade utilizar materiais alternativos e de baixo custo como instrumentos para utilizar experimentação de forma a propiciar uma aprendizagem significativa e contextualizada no ensino de Química. A atividade foi desenvolvida com alunos do primeiro semestre do curso de Licenciatura em Ciências Naturais - Habilitação em Química do Campus XIX da Universidade do Estado do Pará, localizado no município de Salvaterra –PA (ilha de Marajó). A estrutura alternativa para a realizar dos ensaios titulométricos foi confeccionada a partir da reutilização de materiais encontrados no dia-a-dia e pela compra de materiais descartáveis no comércio local. Foram realizados cinco ensaios titulométricos com dispersões comuns do dia-dia dos alunos: suco de frutas, extrato de tomate, mel, leite de magnésia e leite integral. Para realizar as práticas e discutir sobre os fenômenos observados a turma de 30 alunos foi dividida em grupos. Posteriormente, os alunos elaboraram um texto dissertativo, com o propósito de avaliar a validação de aprendizagem com a utilização da ferramenta alternativa. Os dados obtidos permitiram diagnosticar que todos os indivíduos envolvidos na atividade aprovaram o uso da ferramenta enquanto um recurso pedagógico para o ensino de química. Acredita-se que a utilização da experimentação a partir de materiais alternativos potencializa sua eficácia nas relações de ensino e aprendizagem em Química.
The Impact of Education Earmarking on State-Level Lottery Sales
Authors: Stivender Carol O. , Gaggl Paul , Amato Louis H. , Farrow-Chestnut Tonya E. 
Published: May 2016

Abstract
Prior research argues that lottery consumers consider how funds are to be used in making lottery purchase decisions. Possible explanations for this behavior include altruism as well as the desire of low-income families to provide educational opportunities within their community. This paper uses a panel of lottery sales for U.S. states covering the period 1980–2000 to test hypotheses regarding the impact of educational earmarking on lottery purchases. Our estimates suggest that states earmarking all or part of their revenue to education experience an increase in lottery sales between 11 % and 25 %, depending on the specification of state trends. Whether the propensity for earmarking to increase sales is viewed positively or negatively depends largely on one’s ethical and moral views of lotteries.
“To Promote the General Welfare”: Addressing Political Corruption in America
Authors: Owen Bruce M. 
Published: May 2016

Abstract
Systemic (but lawful) political corruption reduces well-being and equity in America. The original form of Madisonian democracy is no longer capable of containing such corruption. Proposals currently on the table to stem corruption are unlikely to be effective and tend to undermine basic rights. This Essay describes a new, but still Madisonian, approach—regulating the output of corrupted legislative and administrative processes, rather than the inputs. Providing for substantive ex post review of direct and delegated legislation would be far more protective of the “general welfare” of the People than other reforms, while no more or less difficult to implement. Supporting an “umpire” branch may be a dominant strategy for elites themselves.
Strategic and Tactical Totalization in the Totalitarian Epoch
Authors: MacLeod Adam J 
Published: May 2016

Abstract
This article examines the totalization of private law by public authorities. It compares and contrasts the fate of private law in totalitarian regimes with the role of private law in contemporary, non-totalitarian liberal democracies. It briefly examines the Socialist jurisprudence of the former Soviet Union and its treatment of private law. It offers an explanation why private law might be inimical to the jurisprudence of the Soviet Union and totalitarian regimes more generally. It next examines the totalization of law accomplished by segregationist regimes in the mid-twentieth century, comparing and contrasting those regimes with totalitarian regimes. Then it turns to examine instances of “tactical totalization” in our own day. Examining totalization of law as a jurisprudential, rather than political, phenomenon reveals how the totalization of legal norms can and does occur in liberal democracies, though with substantially different implications than in totalitarian regimes.
Who Can Be President of the United States?: Candidate Hillary Clinton and the Problem of Statutory Qualifications
Authors: Tillman Seth Barrett 
Published: May 2016

Abstract
Qualifications for public office restrict democratic choice, but such restrictions have a long pedigree in many jurisdictions. For example, the U.S. Constitution sets out qualifications for elected federal officials: i.e., Representative, Senator, President, and Vice President. Qualifications for those positions include provisions relating to age, citizenship, and residence. It has been long debated whether these textual qualifications are exclusive (i.e., floors and ceilings) or whether they are merely floors, which can be supplemented by additional qualifications imposed by Congress or by the States.
Once again, this issue has become topical. Former Secretary of State Hillary Clinton is a prominent candidate in now-ongoing Democratic Party primary elections. These primaries select delegates to a national convention which will choose the Democratic Party’s candidate for the 2016 popular presidential election. It has been alleged that, during her term as Secretary of State, Clinton violated a provision of the federal statute mandating government record keeping. 18 U.S.C. § 2071 provides: “Whoever, having the custody of any … record … willfully and unlawfully conceals, removes, mutilates, obliterates, falsifies, or destroys the same … shall forfeit his office and be disqualified from holding any office under the United States.”
This Article addresses two interesting interpretive challenges posed by Section 2071. First, does Section 2071’s “office under the United States” language reach the presidency? Second, if Section 2071’s “office under the United States” language encompasses the presidency, is the statute constitutional? In other words, does Congress have the power to create additional qualifications for the presidency?
Recusant Witnesses and the McCarthyite Congressional Investigations
Authors: Corbett Ross J. 
Published: May 2016

Abstract
This paper charts the Warren Court’s handling of those convicted for contempt of Congress at the urging of the House Un-American Activities Committee and the Senate Subcommittee on Internal Security. An examination of the arguments made in the Court’s various opinions—and by whom—reveals that the outcomes in these cases cannot be explained solely by the changing membership of the Court. Even when there were the votes to support the vigorous denunciations of the McCarthyite congressional investigations that found expression in dissents inspired by Watkins v. United States, the Warren Court took a more measured tone. That more measured tone was an attempt to avoid a repeat of the fractured Court amidst a public backlash that Warren had provoked with Watkins and marked a return to the Court’s pre-Watkins use of formalism to bring about the just result.