bluuebunny/crossref_metadata_2025 huggingface dataset:
SMYD5 Controls Heterochromatin and Chromosome Integrity during Embryonic Stem Cell Differentiation
Authors: Kidder Benjamin L. , He Runsheng , Wangsa Darawalee , Padilla-Nash Hesed M. , Bernardo M. Margarida , Sheng Shijie , Ried Thomas , Zhao Keji
Published: September 2017

Epigenetic regulation of chromatin states is thought to control gene expression programs during lineage specification. However, the roles of repressive histone modifications, such as trimethylated histone lysine 20 (H4K20me3), in development and genome stability are largely unknown. Here, we show that depletion of SET and MYND domain–containing protein 5 (SMYD5), which mediates H4K20me3, leads to genome-wide decreases in H4K20me3 and H3K9me3 levels and derepression of endogenous LTR- and LINE-repetitive DNA elements during differentiation of mouse embryonic stem cells. SMYD5 depletion resulted in chromosomal aberrations and the formation of transformed cells that exhibited decreased H4K20me3 and H3K9me3 levels and an expression signature consistent with multiple human cancers. Moreover, dysregulated gene expression in SMYD5 cancer cells was associated with LTR and endogenous retrovirus elements and decreased H4K20me3. In addition, depletion of SMYD5 in human colon and lung cancer cells results in increased tumor growth and upregulation of genes overexpressed in colon and lung cancers, respectively. These findings implicate an important role for SMYD5 in maintaining chromosome integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during differentiation. Cancer Res; 77(23); 6729–45. ©2017 AACR.
Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma
Authors: Yuan Jiang , Jiang Yan-Yi , Mayakonda Anand , Huang Moli , Ding Ling-Wen , Lin Han , Yu Fenggang , Lu Yanan , Loh Thomas Kwok Seng , Chow Marilynn , Savage Samantha , Tyner Jeffrey W. , Lin De-Chen , Koeffler H. Phillip
Published: September 2017

Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced antineoplastic activities both in vitro and in vivo. An integrative analysis using both whole-transcriptome sequencing and chromatin immunoprecipitation sequencing pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2, and the long noncoding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK, and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease. Cancer Res; 77(23); 6614–26. ©2017 AACR.
Proliferating EpCAM-Positive Ductal Cells in the Inflamed Liver Give Rise to Hepatocellular Carcinoma
Authors: Matsumoto Tomonori , Takai Atsushi , Eso Yuji , Kinoshita Kazuo , Manabe Toshiaki , Seno Hiroshi , Chiba Tsutomu , Marusawa Hiroyuki
Published: September 2017

Hepatocellular carcinoma (HCC) originates from regenerating liver cells with genetic alterations in chronically inflamed liver. Ductal cells and hepatocytes proliferate for liver regeneration, and proliferating ductal cells (PDC) derived from bile ductules have long been considered putative liver stem/progenitor cells and candidate cellular origins of HCC. The potential of PDC as tumor-originating cells, however, remains controversial in contrast to accumulating evidence that HCC originates from hepatocytes. Here, we demonstrate that PDCs expressing the established surface and cancer stem cell marker EpCAM give rise to HCC in inflamed liver. EpCAM-expressing PDCs were specifically labeled in newly developed EpcamCreERT2 mice and traced in a chemically induced liver injury model. Stepwise accumulation of genetic alterations in EpCAM-positive cells was induced by the mutagenesis activity of activation-induced cytidine deaminase using conditional transgenic mice. Lineage-tracing experiments revealed that labeled PDC differentiated into cholangiocytes, but not into hepatocytes, in the chemically damaged liver. Nevertheless, EpCAM-positive PDC with genetic alterations gave rise to HCC after 8 months of chemical administration. PDC-derived HCC showed histologic characteristics of concomitant ductule-like structures resembling human cholangiolocellular carcinoma (CLC) and exhibited serial transitions from PDC-like CLC cells to hepatocyte-like HCC cells. The Wnt signaling pathway was specifically upregulated in the CLC components of PDC-derived HCC. Our findings provide direct experimental evidence that EpCAM-expressing PDC could be a cellular origin of HCC, suggesting the existence of stem/progenitor-derived hepatocarcinogenesis. Cancer Res; 77(22); 6131–43. ©2017 AACR.
Head and Neck Squamous Cell Carcinomas Are Characterized by a Stable Immune Signature Within the Primary Tumor Over Time and Space
Authors: Wood Oliver , Clarke James , Woo Jeongmin , Mirza Adal H. , Woelk Christopher H. , Thomas Gareth J. , Vijayanand Pandurangan , King Emma , Ottensmeier Christian H.
Published: September 2017

Purpose: Genetic and morphologic heterogeneity is well-documented in solid cancers. Immune cells are also variably distributed within the tumor; this heterogeneity is difficult to assess in small biopsies, and may confound our understanding of the determinants of successful immunotherapy. We examined the transcriptomic variability of the immunologic signature in head and neck squamous cell carcinoma (HNSCC) within individual tumors using transcriptomic and IHC assessments.

Experimental Design: Forty-four tumor biopsies from 16 HNSCC patients, taken at diagnosis and later at resection, were analyzed using RNA-sequencing. Variance filtering was used to identify the top 4,000 most variable genes. Principal component analysis, hierarchical clustering, and correlation analysis were performed. Gene expression of CD8A was correlated to IHC analysis.

Results: Analysis of immunologic gene expression was highly consistent in replicates from the same cancer. Across the cohort, samples from the same patient were most similar to each other, both spatially (at diagnosis) and, notably, over time (diagnostic biopsy compared with resection); comparison of global gene expression by hierarchical clustering (P ≤ 0.0001) and correlation analysis [median intrapatient r = 0.82; median interpatient r = 0.63]. CD8A gene transcript counts were highly correlated with CD8 T-cell counts by IHC (r = 0.82).

Conclusions: Our data demonstrate that in HNSCC the global tumor and adaptive immune signatures are stable between discrete parts of the same tumor and also at different timepoints. This suggests that immunologic heterogeneity may not be a key reason for failure of immunotherapy and underpins the use of transcriptomics for immunologic evaluation of novel agents in HNSCC patients. Clin Cancer Res; 23(24); 7641–9. ©2017 AACR.
Immune Activation in Early-Stage Non–Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab
Authors: Yi John S. , Ready Neal , Healy Patrick , Dumbauld Chelsae , Osborne Robyn , Berry Mark , Shoemaker Debra , Clarke Jeffrey , Crawford Jeffrey , Tong Betty , Harpole David , D'Amico Thomas A. , McSherry Frances , Dunphy Frank , McCall Shannon J. , Christensen Jared D. , Wang Xiaofei , Weinhold Kent J.
Published: September 2017

Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non–small cell lung cancer (NSCLC) patients.

Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB–IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.

Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28-dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated tumor-infiltrating lymphocytes than those observed in PBMCs. Surprisingly, we found 4 cases of preexisting tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating regulatory T cells and MDSCs.

Conclusions: This study did not meet the primary endpoint of detecting an increase in blood-based TAA T-cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early-stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunologic data from combined immune checkpoint blockade immunotherapies. Clin Cancer Res; 23(24); 7474–82. ©2017 AACR.
A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors
Authors: Jimeno Antonio , Gordon Michael , Chugh Rashmi , Messersmith Wells , Mendelson David , Dupont Jakob , Stagg Robert , Kapoun Ann M. , Xu Lu , Uttamsingh Shailaja , Brachmann Rainer K. , Smith David C.
Published: September 2017

Purpose: Wnt signaling is implicated in tumor cell dedifferentiation and cancer stem cell function. Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands. This trial evaluated ipafricept in patients with solid tumors.

Experimental design: A 3+3 design was used; ipafricept was given intravenously every 3 weeks. The objectives were determination of dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy.

Results: 26 patients were treated in seven dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15, and 20 mg/kg). No further dose escalation was pursued as PK modeling indicated that the target efficacious dose was reached at 10 mg/kg, and fragility fractures occurred at 20 mg/kg. Most common related grade 1 and 2 adverse events (AEs; ≥20% of patients) were dysgeusia, decreased appetite, fatigue, and muscle spasms. Ipafricept-related grade 3 TEAEs included hypophosphatemia and weight decrease (1 subject each, 3.8%). Ipafricept half-life was ∼4 days and had low incidence of antidrug antibody formation (7.69%) with no impact on drug exposure. Six patients had β-C-terminal telopeptide (β-CTX) doubling from baseline, which was reversible. PD modulation of Wnt pathway genes in hair follicles occurred ≥2.5 mg/kg. Two desmoid tumor and a germ cell cancer patient experienced stable disease for >6 months.

Conclusions: Ipafricept was well tolerated, with RP2D of 15 mg/kg Q3W. Prolonged SD was noted in desmoid tumor and germ cell cancer patients. Clin Cancer Res; 23(24); 7490–7. ©2017 AACR.
Vitreomacular Changes after Intravitreal Gas Injection for Idiopathic Impending or Early Macular Hole: An Optical Coherence Tomography Study
Authors: Tew Teck-Boon , Chen Ta-Ching , Yang Chang-Hao , Yang Chung-May
Published: September 2017

Purpose: To study the early changes of vitreomacular microstructure by optical coherence tomography (OCT) after intravitreal gas injection for the treatment of idiopathic impending or early full-thickness macular hole (FTMH). Methods: A retrospective, interventional case series. Results: A total of 21 eyes were included. In the impending macular hole, 8/8 achieved vitreomacular traction (VMT) release, while a macular hole developed in 1 case. On postoperative day 1, the vitreomacular configuration by OCT showed either a flattening (n = 3) or elevation (n = 1) pattern. In early FTMH, vitreomacular separation was achieved in 10/13 cases, but macular hole closure was only observed in 3 cases. On postoperative day 1, only flattening of the vitreomacular configuration was observed (n = 5). Enlargement of the macular hole was found in 4 cases. Conclusions: VMT separation can be achieved with intravitreal gas injection by mechanically stretching the posterior vitreous cortex, causing either flattening or steepening of the vitreomacular configuration. However, it did not always result in macular hole closure.
Untreated Dental Caries Is Associated with Reports of Verbal Bullying in Children 8-10 Years Old
Authors: Barasuol Jéssica C. , Soares Josiane P. , Castro Renata G. , Giacomin Angela , Gonçalves Bruna M. , Klein Daniele , Torres Fernanda M. , Borgatto Adriano F. , Ramos-Jorge Maria Letícia , Bolan Michele , Cardoso Mariane
Published: September 2017

The objective of this research was to verify the association between verbal bullying and untreated dental caries. The present cross-sectional study had a representative sample of 1,589 children, aged 8-10 years, from public schools. Information on verbal bullying related to the oral condition was obtained through a questionnaire directed to the students. Clinical data were collected by 4 calibrated examiners (kappa > 0.70) using the DMFT/dmft and PUFA/pufa indexes for caries. Socioeconomic issues were answered by those responsible. The prevalence of verbal bullying related to the oral condition was 27%. The results of the Poisson regression, in an adjusted multiple model, showed a significant association between bullying and untreated caries lesions (prevalence ratio, PR: 1.27; 95% CI: 1.07-1.52), PUFA/pufa index (PR: 1.34; 95% CI: 1.11-1.61), pulp involvement (PR: 1.35; 95% CI: 1.09-1.67), and abscess (PR: 1.74; 95% CI: 1.18-2.56). It was concluded that children with untreated dental caries had a higher prevalence of verbal bullying when compared to caries-free or disease-treated children.
The Impact of Maternal Gestational Hypertension and the Use of Anti-Hypertensives on Neonatal Myocardial Performance
Authors: Breatnach Colm R. , Monteith Cathy , McSweeney Lisa , Tully Elizabeth C. , Malone Fergal D. , Kent Etaoin , Doherty Anne , Franklin Orla , EL-Khuffash Afif
Published: September 2017

Background: Assessment of myocardial performance in neonates using advanced techniques such as deformation imaging and rotational mechanics has gained considerable interest. The applicability of these techniques for elucidating abnormal myocardial performance in various clinical scenarios is becoming established. We hypothesise that term infants born to mothers with gestational hypertension (GH) may experience impaired performance of the left and right ventricles during the early neonatal period. Objectives: We aimed to assess left and right ventricular (LV and RV) function using echocardiography in infants born to mothers with GH and compare them to a control group. Methods: Term infants (>36+6 weeks) born to mothers with GH underwent assessment to measure biventricular function using ejection fraction (EF), deformation imaging, left-ventricle rotational mechanics (apical rotation, basal rotation, twist, twist rate, and untwist rate), and right ventricle-specific functional parameters (tricuspid annular plane systolic excursion and fractional area change) in the first 48 h after birth. A control group comprising infants born to healthy mothers was used for comparison. Results: Fifteen infants with maternal GH and 30 age-matched controls were enrolled. The GH infants exhibited no differences in birthweight or LV or RV length, but they had lower EF (54 vs. 61%; p < 0.01), LV global longitudinal strain (-20 vs. -25%; p < 0.01), and LV twist (11 vs. 16°; p = 0.04). There were no differences in any of the RV functional parameters. Conclusion: Infants born to mothers with GH exhibited lower LV function than healthy controls, while RV function appeared to be preserved. This relationship warrants further exploration in a larger cohort.
Roles of TRIM32 in Corneal Epithelial Cells After Infection with Herpes Simplex Virus
Authors: Cui Hao , Liu Ying , Huang Yifei
Published: September 2017

Background: Epithelial cells play important roles as a critical barrier in protecting the cornea from microbial pathogens infection. Methods: In this study, we were aiming to investigate the role of E3 ubiquitin ligase tripartite motif protein 32 (TRIM32) in corneal epithelial cells in response to Herpes Simplex Virus type 1 (HSV-1) infection and to elucidate the underlying mechanisms. Results: We found the expression of TRIM32 was increased after infected with HSV-1 both in murine corneas and cultured human epithelial (HCE) cells. Furthermore, knockdown of the expression of TRIM32 significantly aggravated HSV-1 induced herpetic stromal keratitis (HSK) in mice and promoted the replication of HSV-1 in cultured HCE cells. We also observed that silencing of TRIM32 resulted in the decreased expression of IFN-β and suppressed activation of interferon regulatory factor 3 (IRF3) both in vivo and in vitro. Finally, we found TRIM32 positively regulate IFN-β production in corneal epithelial cells through promoting K63-linked polyubiquitination of stimulator of interferon genes (STING). Conclusion: In conclusion, our data suggested that TRIM32 as a crucial positive regulator of HSV-1 induced IFN-β production in corneal epithelial cells, and it played a predominant role in clearing HSV-1 from the cornea.
Interview with Stuart Walker
Authors: Riul Marilia , Wanderley Ingrid Moura , Santos Maria Cecilia Loschiavo dos
Published: September 2017

Stuart Walker is Professor of Design for Sustainability and Co-Director of the Imagination Lancaster design research Centre at Lancaster University. Focused on design for sustainability; product aesthetics and meaning; practice-based design research and product design that explores and expresses both human values and notions of spirituality. He was interviewed in his second visit to Brazil to attend the Conference and Workshop "Design and the national policy of solid waste: dialogues on sustainability," held in the Sustainability Laboratory (Lassu) at the University of São Paulo (USP) in 2013, an activity of the research project sponsored by CNPq: Product design, sustainability and national policy on solid waste, coordinated by Professor Maria Cecilia Loschiavo dos Santos. Through the suggested questions, Professor Stuart Walker built a severe critique of our social system of mass production and reminded us that values really matter to our journey.
Urbgrafias ou cartografias da produção de um devir cidade.
Authors: Nascimento Elaine Cristina Maia , Santos Rodrigo Gonçalves dos
Published: September 2017

O artigo trata de um fragmento da pesquisa de Mestrado em desenvolvimento sobre a relação entre os atos cotidianos de um “fazer cidade”, entendidos aqui como a relação estabelecida entre corpo e espaço em ações que constroem de forma efêmera uma relação crítica com o espaço urbano. Com base no conceito de corpografia e nas investigações situacionistas da década de 60, a pesquisa cartografa a possibilidade de urbgrafias, de escrituras do corpo nas diversas qualidades espaciais: desde o espaço físico ao espaço da vivência urbana. Dentro dessas escrituras possíveis, trato inicialmente a arte como uma possibilidade de agenciamento, forma materializada do fazer cidade dentro das intenções aqui propostas. Para tal, a necessidade do entendimento do processo de produção do espaço urbano e de ações práticas que transfigurem as ideias discutidas são tratadas aqui de forma inicial.
Estado, arquitetura e desenvolvimento. A ação habitacional do Iapi (Editora UNIFESP, Sao Paulo, 2016)
Authors: Ballent Anahi
Published: September 2017

Reseña del libro Estado, Arquitetura e Desenvolvimento. A Ação Habitacional do Iapi (Editora UNIFESP, Sao Paulo, 2016), de Nilce Aravecchia-Botas.
Preencher os vazios: sociedade e estrutura fundiária na constituição do espaço urbano de Cascavel - da "Encruzilhada" à década de 1960
Authors: Brugnago Naira Vicensi , Alves André Augusto de Almeida
Published: September 2017

Contraface daquelas que se tornam as metrópoles industriais do país, Cascavel, situada no oeste do estado do Paraná, é produto da modernização brasileira pós-1930. Partindo do debate sobre “vazios” territoriais e urbanos, o artigo retraça seu processo de ocupação e urbanização. Situa-o no entrecruzamento de episódios históricos, projetos políticos, dinâmicas econômicas, atuação de agentes públicos e privados; seu rebatimento na estrutura fundiária e na cidade, em uma sucessão de momentos e fatos que dialogam com a experiência local e nacional e revelam-se necessários ao entendimento deste processo que é o desenvolvimento do espaço.
As tendências de intervenção de caráter monumental: a experiência brasileira (1980-2010)
Authors: Nahas Patricia Viceconti
Published: September 2017

O artigo “As tendências de intervenção de caráter monumental: a experiência brasileira (1980-2010)”, vem pautada na reflexão dos recentes diálogos entre antigo e novo, permanência e inovação, preservação e mudança, que fazem parte do cenário da produção arquitetônica contemporânea em que se assiste, cada vez mais, edifícios antigos tornarem-se parte de uma nova história da cidade. A fim de discutir esse fenômeno no Brasil, o estudo definiu como recorte geográfico e temporal, a produção arquitetônica brasileira em programas de intervenção de caráter monumental no período compreendido entre os anos 1980 a 2000, partindo da constatação de que a maior parte dessa produção se afasta dos critérios prescritos pelo campo disciplinar do restauro, onde a prática dá lugar ao arbítrio e experimentação sem o rigor e juízo crítico pautado na significação da obra preexistente. Para compreender o cenário brasileiro quanto à valorização de seu patrimônio e a materialização de quais valores, quais critérios e como os desafios da intervenção e conservação dos monumentos são consumados na prática, a partir de exemplos significativos, identificamos oito tendências de intervenção representativas: Autonomia, Diferenciação, Reinterpretação, Repristino, Apropriação, Completamento, Conservação e Reintegração, criando grupos com características semelhantes entre si, não totalmente rígidos e fechados, mas que, de alguma forma, pudessem facilitar a leitura das obras e caracterizar o panorama de intervenções no cenário nacional em relação ao campo disciplinar de restauro.
Usos do primitivismo. Pedra, barro e arquitetura moderna.
Authors: Cabral Claudia Costa , Bender Helena
Published: September 2017

Apesar de problemáticas, as noções de “primitivo” e “primitivismo” foram categorias essenciais para a arte e a arquitetura moderna na América Latina, tanto para produtores (arquitetos e artistas), quanto para seus intérpretes (historiadores e críticos). Estiveram fortemente associadas tanto à contribuição latino-americana para uma modernidade universal quanto à apreciação historiográfica dessa contribuição. Este texto tem por objetivo cercar determinados “usos do primitivismo” na arquitetura sul-americana, que coincidem com a presença de materiais naturais, como a pedra e o barro, e de técnicas construtivas pré-industriais. Embora essa presença possa ser discutida apenas nos termos de uma relação com o “vernáculo”, adota-se propositalmente a noção de “primitivismo”, por exibir um impasse (de certa forma indiferente ao vernáculo) de uma ligação intelectual, e não natural, com a tradição. O trabalho finaliza com algumas notas sobre a proposta de Lucio Costa para a casa operária de Monlevade no Brasil (1936) e as alternativas do grupo Austral para a casa rural argentina (1939).
Elos possíveis entre a História das Ciências e a Educação CTS
Authors: Oliveira Rosangela Rodrigues de , Alvim Márcia Helena
Published: September 2017

Neste artigo apresentamos uma reflexão sobre a aproximação entre História das Ciências e educação CTS, objetivando a construção de uma educação científica mais crítica e reflexiva. Para isso, partimos de uma análise teórico-reflexiva, através de uma revisão da literatura. Concluímos que há um panorama bastante positivo para adotarmos uma abordagem que interligue a HC e a educação CTS. Acreditamos que esta relação promove a ruptura das fronteiras entre os saberes e direciona-se na busca de um ensino problematizador, humano e reflexivo com os objetivos de formar cidadãos mais críticos e, quiçá, capazes de transformar a sociedade.
O fenômeno da dor e entorpecimento causado pelos torpedos: história da ciência na Educação de Jovens e Adultos.
Authors: Jensen Gerda Maisa
Published: September 2017

O presente artigo tem como objetivo apresentar e comentar uma intervenção pedagógica desenvolvida em sala de aula de ciências na etapa inicial do segmento Fundamental II do Ensino Básico na modalidade Educação de Jovens e Adultos (EJA) de uma escola pública do município de São Paulo, Brasil. A intervenção pedagógica foi parte de uma pesquisa empírica realizada a partir do planejamento, elaboração, validação, implementação e avaliação de uma sequência didática (SD) baseada numa pesquisa histórica desenvolvida com esta finalidade, isto é, sem ter sido anteriormente publicada em livros didáticos ou paradidáticos atuais. A intervenção pedagógica é apresentada neste artigo a partir da sua fundamentação teórica, seguida da metodologia de pesquisa, apresentação dos planos didáticos e do material impresso baseado em fonte primária que foi utilizado em sala de aula, a análise dos dados coletados e a conclusão dessa intervenção. Tanto esta intervenção quanto a própria pesquisa empírica revelou que a História da Ciência pode ser uma ferramenta de ensino que favorece ao mesmo tempo a compreensão de conceitos de ciências e sobre aspectos da ciência e da investigação científica.
Use of the Coding Causes of Death in HIV in the classification of deaths in Northeastern Brazil
Authors: Alves Diana Neves , Bresani-Salvi Cristiane Campello , Batista Joanna d’Arc Lyra , Ximenes Ricardo Arraes de Alencar , Miranda-Filho Demócrito de Barros , Melo Heloísa Ramos Lacerda de , Albuquerque Maria de Fátima Pessoa Militão de
Published: September 2017

OBJECTIVE Describe the coding process of death causes for people living with HIV/AIDS, and classify deaths as related or unrelated to immunodeficiency by applying the Coding Causes of Death in HIV (CoDe) system. METHODS A cross-sectional study that codifies and classifies the causes of deaths occurring in a cohort of 2,372 people living with HIV/AIDS, monitored between 2007 and 2012, in two specialized HIV care services in Pernambuco. The causes of death already codified according to the International Classification of Diseases were recoded and classified as deaths related and unrelated to immunodeficiency by the CoDe system. We calculated the frequencies of the CoDe codes for the causes of death in each classification category. RESULTS There were 315 (13%) deaths during the study period; 93 (30%) were caused by an AIDS-defining illness on the Centers for Disease Control and Prevention list. A total of 232 deaths (74%) were related to immunodeficiency after application of the CoDe. Infections were the most common cause, both related (76%) and unrelated (47%) to immunodeficiency, followed by malignancies (5%) in the first group and external causes (16%), malignancies (12 %) and cardiovascular diseases (11%) in the second group. Tuberculosis comprised 70% of the immunodeficiency-defining infections. CONCLUSIONS Opportunistic infections and aging diseases were the most frequent causes of death, adding multiple disease burdens on health services. The CoDe system increases the probability of classifying deaths more accurately in people living with HIV/AIDS.
Coronary Artery Calcium Distribution Is an Independent Predictor of Incident Major Coronary Heart Disease Events
Authors: Ferencik Maros , Pencina Karol M. , Liu Ting , Ghemigian Khristine , Baltrusaitis Kristin , Massaro Joseph M. , D’Agostino Ralph B. , O’Donnell Christopher J. , Hoffmann Udo
Published: September 2017

Background—

The presence and extent of coronary artery calcium (CAC) are associated with increased risk for cardiovascular events. We determined whether information on the distribution of CAC and coronary dominance as detected by cardiac computed tomography were incremental to traditional Agatston score (AS) in predicting incident major coronary heart disease (CHD).

Methods and Results—

We assessed total AS and the presence of CAC per coronary artery, per segment, and coronary dominance by computed tomography in participants from the offspring and third-generation cohorts of the Framingham Heart Study. The primary outcome was major CHD (myocardial infarction or CHD death). We performed multivariable Cox proportional hazards analysis and calculated relative integrated discrimination improvement. In 1268 subjects (mean age, 56.2±10.3 years, 63.2% men) with AS >0 and no history of major CHD, a total of 42 major CHD events occurred during median follow-up of 7.4 years. The number of coronary arteries with CAC (hazard ratio, 1.68 per artery; 95% confidence interval, 1.10–2.57;
P
=0.02) and the presence of CAC in the proximal dominant coronary artery (hazard ratio, 2.59; 95% confidence interval, 1.15–5.83;
P
=0.02) were associated with major CHD events after multivariable adjustment for Framingham risk score and categories of AS. In addition, measures of CAC distribution improved discriminatory capacity for major CHD events (relative integrated discrimination improvement, 0.14).

Conclusions—

Distribution of coronary atherosclerosis, especially CAC in the proximal dominant coronary artery and an increased number of coronary arteries with CAC, predict major CHD events independently of the traditional AS in community-dwelling men and women.
Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity
Authors: Wing Jeffrey J. , Sánchez Brisa N. , Adar Sara D. , Meurer William J. , Morgenstern Lewis B. , Smith Melinda A. , Lisabeth Lynda D.
Published: September 2017

Background and Purpose—

Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter <2.5 μm and ozone, and their interactions with initial stroke severity.

Methods—

First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000–2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions.

Results—

Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter <2.5 μm were associated with higher odds of severe stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00–1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56–1.22;
P
interaction =0.097).

Conclusions—

Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome.
An Initialization Method Based on Hybrid Distance for k-Means Algorithm
Authors: Yang Jie , Ma Yan , Zhang Xiangfen , Li Shunbao , Zhang Yuping
Published: September 2017

The traditional [Formula: see text]-means algorithm has been widely used as a simple and efficient clustering method. However, the performance of this algorithm is highly dependent on the selection of initial cluster centers. Therefore, the method adopted for choosing initial cluster centers is extremely important. In this letter, we redefine the density of points according to the number of its neighbors, as well as the distance between points and their neighbors. In addition, we define a new distance measure that considers both Euclidean distance and density. Based on that, we propose an algorithm for selecting initial cluster centers that can dynamically adjust the weighting parameter. Furthermore, we propose a new internal clustering validation measure, the clustering validation index based on the neighbors (CVN), which can be exploited to select the optimal result among multiple clustering results. Experimental results show that the proposed algorithm outperforms existing initialization methods on real-world data sets and demonstrates the adaptability of the proposed algorithm to data sets with various characteristics.
Discrete Sparse Coding
Authors: Exarchakis Georgios , Lücke Jörg
Published: September 2017

Sparse coding algorithms with continuous latent variables have been the subject of a large number of studies. However, discrete latent spaces for sparse coding have been largely ignored. In this work, we study sparse coding with latents described by discrete instead of continuous prior distributions. We consider the general case in which the latents (while being sparse) can take on any value of a finite set of possible values and in which we learn the prior probability of any value from data. This approach can be applied to any data generated by discrete causes, and it can be applied as an approximation of continuous causes. As the prior probabilities are learned, the approach then allows for estimating the prior shape without assuming specific functional forms. To efficiently train the parameters of our probabilistic generative model, we apply a truncated expectation-maximization approach (expectation truncation) that we modify to work with a general discrete prior. We evaluate the performance of the algorithm by applying it to a variety of tasks: (1) we use artificial data to verify that the algorithm can recover the generating parameters from a random initialization, (2) use image patches of natural images and discuss the role of the prior for the extraction of image components, (3) use extracellular recordings of neurons to present a novel method of analysis for spiking neurons that includes an intuitive discretization strategy, and (4) apply the algorithm on the task of encoding audio waveforms of human speech. The diverse set of numerical experiments presented in this letter suggests that discrete sparse coding algorithms can scale efficiently to work with realistic data sets and provide novel statistical quantities to describe the structure of the data.
Why Do Similarity Matching Objectives Lead to Hebbian/Anti-Hebbian Networks?
Authors: Pehlevan Cengiz , Sengupta Anirvan M. , Chklovskii Dmitri B.
Published: September 2017

Modeling self-organization of neural networks for unsupervised learning using Hebbian and anti-Hebbian plasticity has a long history in neuroscience. Yet derivations of single-layer networks with such local learning rules from principled optimization objectives became possible only recently, with the introduction of similarity matching objectives. What explains the success of similarity matching objectives in deriving neural networks with local learning rules? Here, using dimensionality reduction as an example, we introduce several variable substitutions that illuminate the success of similarity matching. We show that the full network objective may be optimized separately for each synapse using local learning rules in both the offline and online settings. We formalize the long-standing intuition of the rivalry between Hebbian and anti-Hebbian rules by formulating a min-max optimization problem. We introduce a novel dimensionality reduction objective using fractional matrix exponents. To illustrate the generality of our approach, we apply it to a novel formulation of dimensionality reduction combined with whitening. We confirm numerically that the networks with learning rules derived from principled objectives perform better than those with heuristic learning rules.
First record of Phasmarhabditis papillosa (Nematoda: Rhabditidae) in South Africa, and its virulence against the invasive slug, Deroceras panormitanum
Authors: Pieterse Annika , Tiedt Louwrens R. , Malan Antoinette P. , Ross Jenna L.
Published: September 2017

Worldwide interest in Phasmarhabditis originates from the successful commercialisation of P. hermaphrodita as a biological control agent against molluscs in Europe. To date, P. hermaphrodita has not been isolated from South Africa and, therefore, the formulated product may not be sold locally. During a survey for mollusc-associated nematodes, P. papillosa was dissected from the slug, Deroceras reticulatum, collected from George, South Africa. The nematode was identified using a combination of morphological, morphometric, molecular and phylogenetic techniques. Virulence tests were conducted which demonstrated that P. papillosa caused significant mortality to the European invasive slug Deroceras panormitanum. Additional data are provided in the morphometrics of the infective juvenile and in the molecular identification, using the mitochondrial cytochrome c oxidase subunit I (cox1) gene. This is the first report of P. papillosa from the African continent and of its virulence against D. panormitanum.
Pentecostal Experience and the Affirmation of Ethnic Identity
Authors: Frost Michael J.
Published: September 2017

The purpose of this article is to examine the work of the Spirit in the book of Acts in relation to pentecostal experience and cultural identity among Māori in New Zealand. It discusses the many tongues of Pentecost as symbolic of the Spirit’s affirmation of ethno-linguistic diversity and explores the story of Gentile inclusion in Acts 10, where this inclusion must be worked out in the face of ethnic division. This discussion is brought to bear on the context of Māori and pentecostal church communities in New Zealand. Given the ongoing disruption of ethnic and cultural identity for Māori, this article draws on a series of interviews with Māori pentecostal church leaders, demonstrating connections between experiences of the Spirit and divine affirmation of cultural identity. Finally, these observations are discussed in relation to the work of the Spirit and the issue of ethnic identity in both Acts 2 and Acts 10.
Bishops in Communion? The Unity of the Episcopate, the Unity of the Diocese and the Unity of the Church
Authors: Avis Paul
Published: September 2017

This article addresses the current state of ecclesiological dissonance in the Church of England and analyses the theological and pastoral issues that are at stake. It tackles the two ecclesiological anomalies that now face the church and compromise its received polity. (a) The College of Bishops includes bishops who are unable to recognise the priestly and episcopal orders of their female colleagues and are unable to be in full sacramental communion with them. This situation raises the question of the ecclesial integrity of the College of Bishops: is there now a single College? (b) Some bishops are unable in conscience to recognise the priestly ordination of some clergy – male as well as female – within their diocese because these clergy are female or have been ordained by a female bishop. Is it possible for the bishop, in that situation, to exercise a full episcopal ministry in relation to those female clergy? The article goes on to explore, by means of the concepts of reception, economy and charity, whether a modus vivendi is possible that would enable the Church of England to live with these two anomalies with theological integrity.
A Jewish Child’s Portrait? The Kline Sarcophagus of Monteverde and Jewish Funerary Portraiture in Rome
Authors: Burrus Sean P.
Published: September 2017

This article examines the evidence for the use of portrait sculpture on sarcophagi belonging to members of the Jewish community of Rome. The use of the “learned figure” motif, commonly employed in Roman sarcophagus portraiture and by Jewish patrons, is highlighted, and possible creative appropriations of the trope in Jewish contexts are raised. It is further argued that, among Jewish sarcophagus patrons, the decision to include funerary portraiture went hand in hand with the decision to adopt popular and conventional Roman styles and motifs, and to engage Roman cultural and visual resources. In other words, Jewish patrons who chose sarcophagi with portraits also seem to have been the readiest to make use of the visual resources of Roman funerary culture to orchestrate self-narratives on their sarcophagi. Finally, it is cautioned that while the limited examples (five) suggest a mastery of Roman culture and a correspondingly high degree of acculturation among certain Jewish patrons, we should be wary of reading such sarcophagi as evidence of certain Jews abandoning a Jewish identity in favor of a Roman one—or the Jewish community in favor of the Roman polis and its civic structures—as narratives of funerary art never capture the totality of the deceased’s identity.
osce and the Nagorno-Karabakh Peace Process
Authors: Cavanaugh Carey
Published: September 2017

The Minsk Process for Nagorno-Karabakh has directed unprecedented engagement from key world powers on this decades-old dispute. osce’s first peacemaking effort survived a rocky start, evolving into a functional multi-faceted conflict management instrument. While the envisioned “Minsk Conference” was never held, not one of the myriad peace proposals adopted, no status determination for Nagorno-Karabakh ever made, and no refugees or lands returned, the Minsk Process may still be considered a success. Frequent criticism notwithstanding, it has kept Armenia and Azerbaijan engaged in a near continuous diplomatic dialogue, restrained large-scale fighting, and belied fears of a significant regional conflagration. That is a noteworthy achievement.
The discovery of Lepidocyrtoides Schött, 1917 (Collembola, Entomobryidae, Entomobryinae) from the New World, including three new species from Brazil and one from Australia
Authors: CIPOLA NIKOLAS GIOIA , MORAIS JOSÉ WELLINGTON DE , BELLINI BRUNO CAVALCANTE
Published: September 2017

Herein four new species of Lepidocyrtoides are described and illustrated: three from Brazilian Amazon, L. caeruleomaculatus sp. nov., L. colormutatus sp. nov. and L. bicolorangelus sp. nov., all similar to each other by macrochaetotaxy reduced; and L. hopkini sp. nov. from New South Wales, Australia. Lepidocyrtoides tapuia comb. nov. (Arlé & Guimarães) and L. villasboasi comb. nov. (Arlé & Guimarães) are redescribed and transferred from Lepidosira Schött due to projection of mesothorax over head and manubrial plate with blunt macrochaetae. Neotypes are designated to both species. The holotype of L. oliveri Liu, Chen & Greenslade is analyzed and details of the dorsal chaetotaxy are added. Keys to the five species of the genus from Brazil and six from Australia are provided. Lepidocyrtoides now is recorded from the New World, South and Southeast Asia and Oceania, and the records of Lepidosira in the American continent are excluded.
Saltmarsh flies of the genus Scorpiurus Parent from New Zealand (Insecta: Diptera: Dolichopodidae)
Authors: MASUNAGA KAZUHIRO
Published: September 2017

The saltmarsh-inhabiting fly genus Scorpiurus Parent, 1933 is revised. Contrary to the consensus of previous literature, it seems to be endemic to New Zealand. Two species are recognized: Scorpiurus thorpei sp. nov. described herein, and its previously known congener, S. aenescens Parent, 1933, which is redescribed.
Redescription and biology of Gonatopus amazonicus Olmi (Hymenoptera, Dryinidae) from Southern Brazil
Authors: MARTINS ANDRÉ L. , DOMAHOVSKI ALEXANDRE C.
Published: September 2017

Gonatopus amazonicus Olmi is redescribed and illustrated based on a single female reared from an adult parasitized leafhopper belonging to the genus Frequenamia DeLong (Cicadellidae, Deltocephalinae), collected by sweeping on Eugenia uniflora L. in Southern Brazil. This female emerged 46 days after pupation.
Marine Air Penetration in California’s Central Valley: Meteorological Drivers and the Impact of Climate Change
Authors: Wang Meina , Ullrich Paul
Published: September 2017

This study focuses on one of the most common coastal phenomena within California’s San Francisco Bay Delta and Central Valley—marine air penetration (MAP) events, which are a broad category of meteorological features that include the well-known “delta breeze.” Summertime MAP episodes, identified by an inland cooling pattern and onshore wind, are selected in both observational and reanalysis datasets using a newly developed set of objective criteria. Correlations between MAP occurrence and synoptic-scale meteorological patterns are then examined to understand the drivers of MAP. Historical data are first used to determine whether any significant trends have been observed in the frequency and character of MAP events. Future trends in MAP are then predicted on the basis of an investigation of how synoptic-scale meteorological patterns will be modified in the twenty-first century under CMIP5 climatological projections. From the analysis of historical and future MAP frequency (under RCP8.5), a weak positive trend [~0.2 days (100 yr)−1] is identified in the occurrence of sufficiently strong summertime MAP days, although further study is needed.
How Robust Is the Weakening of the Pacific Walker Circulation in CMIP5 Idealized Transient Climate Simulations?
Authors: Plesca Elina , Grützun Verena , Buehler Stefan A.
Published: September 2017

The tropical overturning circulations are likely weakening under increased CO2 forcing. However, insufficient understanding of the circulations’ dynamics diminishes the full confidence in such a response. Based on a CMIP5 idealized climate experiment, this study investigates the changes in the Pacific Walker circulation under anthropogenic forcing and the sensitivity of its weakening response to internal variability, general circulation model (GCM) configuration, and indexing method. The sensitivity to internal variability is analyzed by using a 68-member ensemble of the MPI-ESM-LR model, and the influence of model physics is analyzed by using the 28-member CMIP5 ensemble. Three simple circulation indices—based on mean sea level pressure, 500-hPa vertical velocity, and 200-hPa velocity potential—are computed for each member of the two ensembles. The study uses the output of the CMIP5 idealized transient climate simulations with 1% yr−1 CO2 increase from preindustrial level, and investigates the detected circulation response until the moment of CO2 doubling (70 yr). Depending on the indexing method, it is found that 50%–93% of the MPI-ESM-LR and 54%–75% of the CMIP5 ensemble members project significant negative trends in the circulation’s intensity. This large spread in the ensembles reduces the confidence that a weakening circulation is a robust feature of climate change. Furthermore, the similar magnitude of the spread in both ensembles shows that the Walker circulation response is strongly influenced by natural variability, even over a 70-yr period.