bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation to TKI Treatment Reactivates ERK Signaling in Tyrosine Kinase–Driven Leukemias and Other Malignancies
Authors: Bruner J. Kyle , Ma Hayley S. , Li Li , Qin Alice Can Ran , Rudek Michelle A. , Jones Richard J. , Levis Mark J. , Pratz Keith W. , Pratilas Christine A. , Small Donald
Published: September 2017

FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared with either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase–driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer, and BCR–ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase–driven cancers associated with reactivation of ERK signaling in response to targeted inhibition. Cancer Res; 77(20); 5554–63. ©2017 AACR.
MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy
Authors: Beloueche-Babari Mounia , Wantuch Slawomir , Casals Galobart Teresa , Koniordou Markella , Parkes Harold G. , Arunan Vaitha , Chung Yuen-Li , Eykyn Thomas R. , Smith Paul D. , Leach Martin O.
Published: September 2017

Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux. AZD3965 also increased the levels of TCA cycle–related metabolites and 13C-glucose mitochondrial metabolism, enhancing oxidative pyruvate dehydrogenase and anaplerotic pyruvate carboxylase fluxes. Increased mitochondrial metabolism was necessary to maintain cell survival under drug stress. These effects were counteracted by coadministration of the mitochondrial complex I inhibitor metformin and the mitochondrial pyruvate carrier inhibitor UK5099. Improved bioenergetics were confirmed in vivo after dosing with AZD3965 in mouse xenograft models of human lymphoma. Our results reveal new metabolic consequences of MCT1 inhibition that might be exploited for therapeutic and pharmacodynamic purposes. Cancer Res; 77(21); 5913–24. ©2017 AACR.
TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
Authors: Deng Min , Zhang Ruixin , He Zhengxi , Qiu Qinwei , Lu Xihong , Yin Jiang , Liu Hao , Jia Xiaoting , He Zhimin
Published: September 2017

DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3′UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer. Our findings uncover a novel noncoding function for TET family proteins in facilitating gastric carcinogenesis. Cancer Res; 77(22); 6069–82. ©2017 AACR.
Upregulation of Cystathionine-β-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis
Authors: Phillips Ches'Nique M. , Zatarain John R. , Nicholls Michael E. , Porter Craig , Widen Steve G. , Thanki Ketan , Johnson Paul , Jawad Muhammad U. , Moyer Mary P. , Randall James W. , Hellmich Judith L. , Maskey Manjit , Qiu Suimin , Wood Thomas G. , Druzhyna Nadiya , Szczesny Bartosz , Módis Katalin , Szabo Csaba , Chao Celia , Hellmich Mark R.
Published: September 2017

The trans-sulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-κB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immunocompromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/−) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis. Cancer Res; 77(21); 5741–54. ©2017 AACR.
How Ribosomes Translate Cancer
Authors: Sulima Sergey O. , Hofman Isabel J.F. , De Keersmaecker Kim , Dinman Jonathan D.
Published: September 2017

A wealth of novel findings, including congenital ribosomal mutations in ribosomopathies and somatic ribosomal mutations in various cancers, have significantly increased our understanding of the relevance of ribosomes in oncogenesis. Here, we explore the growing list of mechanisms by which the ribosome is involved in carcinogenesis—from the hijacking of ribosomes by oncogenic factors and dysregulated translational control, to the effects of mutations in ribosomal components on cellular metabolism. Of clinical importance, the recent success of RNA polymerase inhibitors highlights the dependence on “onco-ribosomes” as an Achilles' heel of cancer cells and a promising target for further therapeutic intervention.

Significance: The recent discovery of somatic mutations in ribosomal proteins in several cancers has strengthened the link between ribosome defects and cancer progression, while also raising the question of which cellular mechanisms such defects exploit. Here, we discuss the emerging molecular mechanisms by which ribosomes support oncogenesis, and how this understanding is driving the design of novel therapeutic strategies. Cancer Discov; 7(10); 1069–87. ©2017 AACR.
Exploiting Drug Addiction Mechanisms to Select against MAPKi-Resistant Melanoma
Authors: Hong Aayoung , Moriceau Gatien , Sun Lu , Lomeli Shirley , Piva Marco , Damoiseaux Robert , Holmen Sheri L. , Sharpless Norman E. , Hugo Willy , Lo Roger S.
Published: September 2017

Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAFMUT or NRASMUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal–induced pERK rebound upregulated p38–FRA1–JUNB–CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos-related cell death. Specifically in MEKi-resistant NRASMUT or atypical BRAFMUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death–predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction.

Significance: Discontinuing targeted therapy may select against drug-resistant tumor clones, but drug-addiction mechanisms are ill-defined. Using melanoma resistant to but withdrawn from MAPKi, we defined a synthetic lethality between supraphysiologic levels of pERK and DNA damage. Actively promoting this synthetic lethality could rationalize sequential/rotational regimens that address evolving vulnerabilities. Cancer Discov; 8(1); 74–93. ©2017 AACR.

See related commentary by Stern, p. 20.

This article is highlighted in the In This Issue feature, p. 1
Fetal Growth and Placental Growth Factor Umbilical Cord Blood Levels
Authors: Broere-Brown Zoe A. , Schalekamp-Timmermans Sarah , Jaddoe Vincent W.V. , Steegers Eric A.P.
Published: September 2017

Objective: We assessed whether umbilical cord blood placental growth factor (PlGF) levels at delivery are associated with fetal growth. Methods: From a prospective population-based cohort study we included 3,461 live singleton births. Fetal growth was assessed by birth weight, fetal growth pattern, and fetal growth restriction (FGR; decrease in growth between the second trimester and birth of ≥40 percentiles). In all analyses the highest PlGF multiple of the median (MoM) quintile was used as the reference category. Results: Umbilical cord PlGF was neither correlated with maternal second-trimester PlGF (p = 0.08) nor placental weight (p = 0.18), suggesting that PlGF from umbilical cord blood was of fetal origin. Lower PlGF MoM quintiles were associated with a lower birth weight (lowest quintile -0.60 standard deviation [95% confidence interval -0.71 to -0.48, p for trend <0.001]) and a different fetal growth pattern (p < 0.001). Finally, lower PlGF MoM quintiles were associated with FGR (lowest quintile odds ratio 2.00 [95% confidence interval 1.25 to 3.21, p for trend <0.001]). Conclusion: Lower umbilical cord PlGF levels are associated with lower birth weight, deviating fetal growth patterns, and a higher odds of FGR. Hence, cord blood PlGF might be a promising biomarker to determine deviations in fetal growth and FGR retrospectively, enabling follow-up of these neonates.
Persistent Pulmonary Hypertension of the Newborn in Twin-Twin Transfusion Syndrome: A Case-Control Study
Authors: Gijtenbeek Manon , Haak M.C. , ten Harkel Derk Jan , te Pas Arjan B. , Middeldorp Johanna M. , Klumper Frans J.C.M. , van Geloven Nan , Oepkes Dick , Lopriore Enrico
Published: September 2017

Background: Persistent pulmonary hypertension of the newborn (PPHN) is associated with severe morbidity and mortality. Twin-twin transfusion syndrome (TTTS) is suggested to increase the risk of PPHN. Objectives: To describe the incidence of PPHN in TTTS twins and to identify risk factors in TTTS twins for the development of severe PPHN. Methods: Cases with severe PPHN were extracted from our monochorionic twin database (2002-2016). Severe PPHN was defined as severe hypoxaemia requiring mechanical ventilation and inhaled nitric oxide (iNO) treatment, confirmed by strict echocardiographic criteria. A case-control comparison within TTTS survivors was conducted to identify risk factors for PPHN. Results: The incidence of PPHN in TTTS twins was 4% (24/598, 95% confidence interval [CI] 2.7-5.9%) and 0.4% (2/493, 95% CI 0.1-1.5%) in uncomplicated monochorionic twins (odds ratio [OR] 10.3, 95% CI 2.4-43.9; p = 0.002). Two risk factors were independently associated with PPHN: severe prematurity (OR 3.3, 95% CI 1.0-11.4) and recipient status (OR 3.9, 95% CI 1.4-11.0). In TTTS recipients, another risk factor for PPHN is anaemia at birth (OR 7.2, 95% CI 1.8-29.6). Conclusion: Clinicians caring for neonates with TTTS should be aware of the 10-fold increased risk of PPHN compared to uncomplicated monochorionic twins. PPHN occurs more often in case of premature delivery and in recipient twins, particularly in the presence of anaemia at birth. As the development of severe PPHN is difficult to predict, we advise that all TTTS twins should be delivered in a tertiary care centre with iNO treatment options.
Different Clinical Courses on Long-Term Follow-Up of Age-Related Macular Degeneration Patients Treated with Intravitreal Anti-Vascular Endothelial Growth Factor Injections
Authors: Sagiv Oded , Zloto Ofira , Moroz Iris , Moisseiev Joseph
Published: September 2017

Purpose: To assess the long-term outcome of neovascular age-related macular degeneration (AMD) treated with multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections. Methods: All patients treated with over 30 intravitreal anti-VEGF injections for neovascular AMD between 2007 and 2014 were retrospectively reviewed. Results: A total of 67 eyes received 2,960 (mean 45 ± 9.1 per eye) anti-VEGF injections. Eyes with good final visual acuity (VA) had better initial VA (p = 0.020) and maintained it. Patients with moderate-to-poor final VA improved significantly after the first 3 monthly injections, and thereafter deteriorated consistently, mostly during the third (p = 0.019) and fourth (p = 0.006) years. Eyes with worse final VA had more intraretinal fluid (p = 0.05) and subretinal fibrosis (p = 0.04). Conclusion: Two distinct clinical courses were identified: good final VA was associated with initial and long-term stability of good VA; eyes with worse final VA had worse initial VA, progressive deterioration following the initial improvement, and more scarring and intraretinal fluid. This probably underscores the long-term benefits of early detection and treatment.
Heme Oxygenase Activity and Heme Binding in a Neonatal Mouse Model
Authors: Kourula Stephanie , Ang Joyce , Zhao Hui , Kalish Flora , Vandenabeele Peter , Sylvester Karl G. , Wong Ronald J. , Stevenson David K.
Published: September 2017

Background: Severe hemolytic disease of the newborn leads to the release of pro-oxidative free heme (FH). Heme oxygenase (HO) is primarily responsible for detoxifying FH. Objective: To investigate the protective effects of HO in a model of heme overload. Methods: For in vitro studies, NIH3T3 HO-1-luc cells were incubated with 10, 30, or 60 µM FH or methemalbumin (MHA). HO-1 promoter activity was assessed 3, 6, and 24 h after treatment. Cell survival was indexed by viability assays. For in vivo studies, 1- and 5-week-old wild-type (Wt) or HO-1-heterozygous (Het, HO-1+/-) mice were given 60 µmol FH or MHA/kg intraperitoneally. After 24 h, plasma aspartate aminotransferease (AST)/alanine transaminase (ALT) and hemopexin, liver HO activity, and lipid peroxidation (LP) were determined. Results: In HO-1-luc cells, HO-1 promoter activity peaked 6 h after incubation with 30 µM FH (1.6-fold) or 60 µM MHA (2.1-fold) over baseline. Twenty-four hours after exposure to 60 µM FH, a decrease in viability of 80% was found, compared with no decrease after exposure to 60 µM MHA. In 1-week-old Wt and HO-1 Het pups given 60 µmol FH/kg, HO activity significantly increased 3.5- and 3.1-fold, respectively. No changes in LP or AST/ALT levels were observed. In adult Wt and HO-1 Het mice, HO activity increased (3.0- and 2.6-fold, respectively). LP and AST levels significantly increased 28.4- and 2.7-fold, respectively, in adult HO-1 Het mice. Hemopexin levels at baseline were higher in adults compared with newborns for both Wt and Het mice. In addition, FH induced hemopexin levels in both adults and newborns, but to a lesser degree in newborns. Conclusions: FH is highly toxic in vitro, but its toxicity is abolished when bound to albumin. Newborns appear to be protected from the pro-oxidative effects of FH, which may be mediated by heme binding and a higher absolute HO activity at baseline and after FH-mediated induction.
Circulating IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 Molar Ratio Concentration and Height Outcome in Prepubertal Short Children on rhGH Treatment over Two Years of Therapy
Authors: Ballerini María Gabriela , Braslavsky Débora , Scaglia Paula Alejandra , Keselman Ana , Rodríguez María Eugenia , Martínez Alicia , Freire Analía Verónica , Domené Horacio Mario , Jasper Héctor Guillermo , Bergadá Ignacio , Ropelato María Gabriela
Published: September 2017

Objective: To investigate the occurrence of abnormally elevated values of biomarkers of growth hormone (GH) action in short children on recombinant human GH (rhGH) therapy. Methods: Sixty-three prepubertal short children were examined: 31 with GH deficiency (GHD), 25 small for gestational age (SGA), and 9 with Turner syndrome (TS). The main outcomes were the following: standard deviation score (SDS) values of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 molar ratio before, at the 1st and at the 2nd year on rhGH and Δheight (Ht)-SDS to evaluate GH treatment efficacy (adequate 1st-year ΔHt SDS: >0.4 SDS for GHD and >0.3 SDS for non-GHD). Results: Seventy-eight percent of GHD, 78% of SGA and 55% of TS children had adequate 1st-year ΔHt SDS. In GHD, 88% of IGF-I SDS and IGFBP-3 SDS that were ≤–2.0 SDS at baseline normalized on treatment. Abnormal IGF-I values >+2.0 SDS were observed in 52% of SGA and in 55% of TS patients on rhGH. Within each group, the IGF-I/IGFBP-3 molar ratio increased significantly from pretreatment and throughout therapy, remaining within normal range for most patients. ΔIGF-I/IGFBP-3 molar ratio SDS were significantly higher in children with an adequate response (p < 0.01). Conclusion: Non-GHD groups presented markedly elevated concentrations of GH biomarkers on rhGH and normal IGF-I/IGFBP-3 molar ratio in most patients. Since there is a lack of consensus regarding the molar ratio usefulness, we think that interventions towards a more physiological IGF-I serum profile should be implemented.
Leptospirosis Renal Disease: Emerging Culprit of Chronic Kidney Disease Unknown Etiology
Authors: Yang Chih-Wei
Published: September 2017

Leptospirosis is the most prevalent zoonosis affecting more than 1 million populations worldwide. Interestingly, leptospirosis endemic regions coincide with chronic kidney disease (CKD) hotspots largely due to flooding and agricultural overlaps. Acute leptospirosis induces multiple organ dysfunction including acute kidney injury and may predispose to CKD and end-stage renal disease, if not treated timely. Asymptomatic infection may carry the bacteria in the kidney and CKD progresses insidiously. Histologic finding of leptospirosis renal disease includes tubulointerstitial nephritis, interstitial fibrosis, and tubular atrophy. Proximal tubule dysfunction and hypokalemia are observed in adult male workers with leptospirosis, a characteristic similarity to CKD unknown etiology (CKDu). CKDu is a form of CKD that is not attributable to traditional risk factors clustering in agricultural communities affecting young male farmers. Kidney pathology shows a chronic tubulointerstitial disease. CKDu is being reported as an endemic nephropathy across the globe. Recent surveys suggest that asymptomatic leptospira renal colonization is an overlooked risk for renal fibrosis and CKDu. Population with anti-leptospira seropositivity is associated with lower estimated glomerular filtration rate in endemic regions and carrier may progress to CKD. Leptospirosis has been considered as a risk factor for CKDu in Sri Lanka and in Mesoamerican area. Sugarcane workers in Nicaragua showed increased anti-leptospira seropositivity and higher urinary biomarkers for kidney injury. Emerging evidence with signs of infection were reported in these endemic population, indicating that leptospira exposure could play a role in CKDu as a cause of primary kidney disease or a susceptible factor when secondary injury such as heat stress or dehydration aggravates kidney disease. Therefore, leptospirosis as an emerging culprit of CKDu deserves further in-depth investigation.
Aspectos e problemas da paisagem no desenho da pequena e média Cidade no Estado de São Paulo
Authors: Del Picchia Paulo Celso Dornelles
Published: September 2017

Aborda aspectos e problemas do desenho da paisagem das cidades pequenas e médias no estado de São Paulo baseando-se no exemplo das cidades de Brodowski, Batatais e Franca. Constata que a arquitetura paisagística foi inicialmente praticada por especialistas, destacando a presença da topiaria no desenho dos jardins. Mostra aspectos do desenho urbano e salienta a sua fragilidade diante dos processos de crescimento e mudanças urbanas. Alerta para a necessidade de um profissional especializado nos desenhos urbanos e da paisagem
A Sintaxe da Janela
Authors: Jorge Luís Antônio
Published: September 2017

A preocupação fundamenta! do trabalho é de caráter ontológico: esboçar o problema das significações apriorísticas e autônomas dos elementos que compõem a sintaxe arquitetônica. O trabalho elege um desses elementos: a janela. Este artigo parte da aproximação histórica entre a janela e a secção da pirâmide visual, construção imaginária da teoria da perspectiva renascentista. A consideração da janela na linguagem arquitetônica implica reconhecer uma ambigüidade essencial: a janela deve inserir-se ordenadamente no plano da parede - raciocínio típico da modenatura - mas também relacionar-se com a imagem vista através dela, que extrapola o plano, ressaltando a tridimensionalidade - herança da perspectiva renascentista, fundamentada no espaço euclidiano. Ver janela ou ver através da janela são alternativas que se colocam tanto ao observador interno ao edifício, quanto ao externo. Texto de duplaface, a sintaxe da janela versa sobre o relacionamento desses dois lados
Sobre o Espaço Natural e a Forma Urbana - à guisa de posfácio
Authors: Serra Geraldo G.
Published: September 2017

As dificuldades da pós-graduação e da elaboração da tese. A abordagem científica das questões formais do espaço natural e urbano. A especificidade dos estudos urbanos e o rigor terminológico. Instrumentos, técnica e tecnologia. Projeto e construção. A possibilidade dos juízos de valor sobre as adapta­ ções espaciais e suas aglomerações. As adaptações espaciais e a sua simulação: a operação com modelos
A Atividade Comercial Recriando o seu Espaço
Authors: Vargas Heliana Comin
Published: September 2017

Este artigo discute o relacionamento entre a atividade comercial varejista e o espaço urbano, em sua mais recente versão. A análise da evolução da atividade comercial, através do tempo, e do fenômeno shopping center no mundo e, principalmente, em São Paulo, demonstra que as localizações estratégicas, como fator fundamental para o desenvolvimento das atividades varejistas, estão cedendo, cada vez mais, o seu lugar às estratégias dos negócios Esta constatação indica a necessidade de se repensar as teorias locacionais então vigentes, de forma a possibilitar um controle mais eficiente sobre o desenvolvimento urbano
O Engenheiro Eusébio Stevaux e a Arquitetura Oficial Paulista, 1877-1885
Authors: Campos Eudes
Published: September 2017

Nesse artigo procura-se recuperar a figura e a obra de um engenheiro francês atuante na capital no último terço do século passado. Antes de Ramos de Azevedo, foi ele quem dominou completamente, durante certo lapso de tempo, a arquitetura oficial executada na cidade de São Paulo, chegando a atingir, sob esse ponto de vista, a condição de precursor do famoso engenheiro paulista
Técnica Sanitária e o Traçado da Cidade: ê Representações de Planta e Plano no Trabalho do Urbanismo em Pernambuco na Década de 20
Authors: Lira José Tavares Correia de
Published: September 2017

Neste artigo procuramos acompanhar as representações de plano de extensão e planta da cidade, pelas quais a engenharia sanitária estabeleceu os seus procedimentos no âmbito do urbanismo. Acompanhamos as discussões do Recife entre os anos 10 e 20, através do discurso de engenheiros como Moraes Rego, Saturnino de Brito, José Estelita e Paulo Guedes, que, atraídos pelo debate internacional, avançaram na definição de um campo separado de preocupações. Ainda que comprometidos com a eugenia e a paisagem, estes engenheiros, em suas pretensões científicas e formulações conceituais, gradualmente se afastam do campo da medicina e da arte. Os liames desse processo, exemplarmente resumidos em um tal traçado sanitário da cidade, podem ser entrevistos na analogia do corpo urbano, bem como na ligação orgânica entre solo, subsolo e superfície, tanto quanto entre a planta e o plano
O Estudo da História na formação da Aquitetura
Authors: Lemos Carlos
Published: September 2017

O presente texto procura justificar a necessidade de realizar pesquisa histórica sistemática sobre determinantes e condicionantes da opção arquitetônica que ocorre concomitantemente com a técnica construtiva e a intenção plástica na definição global da construção. Neste estudo, demonstramos através de amostras de determinantes peculiares, do meio ambiente e da sociedade, cujo conhecimento é indispensável para um perfeito entendimento do trabalho arquitetônico
Construção Escolar - desenvolvimento, políticas propostas para a escola rural visando a democratização do campo
Authors: Moreira Nanci Saraiva
Published: September 2017

Este texto apresenta a realidade da escola rural paulista e a necessidade de sua reestruturação a fim de promover uma educação escolar que possibilite a inserção do trabalhador rural, ora existente e proveniente do programa de reforma agrária, no mercado de trabalho. Para tanto expõe a necessidade de reavaliação do atual programa arquitetônico e especificação de materiais das escolas estaduais - rural e urbana - a fim de compatibilizá-los à atual proposta pedagógica e, partir daí, realizar um programa arquitetônico diferenciado para a escola rural, tendo em vista sua característica de isolamento. Realiza ainda uma reflexão quanto à necessidade de uma possível reformulação na forma de entender a escola
Historia Urbana: breve histórico da constituição de uma área de conhecimento
Authors: Silva Luís Octávio Da Silva
Published: September 2017

0 texto procura apontar e analisar os principais eventos, marcos e discussões que têm pautado a emergência da história urbana como uma área de conhecimento específica. Fundamentalmente centrado nas ocorrências e obras de repercussão internacional, este artigo tem como base principalmente a literatura britânica e americana. Isso se deve em função do papel de vanguarda que esses dois países desempenharam no desenvolvimento das análises históricas sobre a cidade, mas também pelo potencial de difusão internacional dado pela própria língua em que essas contribuições foram feitas. 0 nosso interesse, no âmbito deste trabalho, está muito mais nos marcos e referências ligados à constituição desse campo de conhecimento do que na produção historiográfica propriamente dita
O Espaço Paulista 1955 -1980
Authors: Schiffer Sueli Ramos
Published: September 2017

Procura contribuir para o entendimento dos determinantes da produção (e transforma­ ção) do espaço, em particular para o estado de São Paulo em dois estágios distintos do processo de acumulação recente. Interpreta historicamente a atuação do Estado brasileiro nestes estágios através das políticas nacionais implementadas, procurando distinguir quais interesses privilegiaram e seus efeitos na transformação do espaço paulista
Habitação Evolutiva reflexões sobre alguns casos: Possibilidades
Authors: Silva Paulo Sérgio De Sousa e
Published: September 2017

O texto refere-se à habitação evolutiva, destinada à população de baixa renda, comparando empreendimentos promovidos pela Prefeitura de São Paulo, através de duas formas diversas de produção do núcleo inicial - embrião - uma delas, a ajuda mútua, com participação intensa da população interessada e a outra baseada no trabalho exclusivo de empreiteiras especializadas
O Impacto do Sistema de Transporte sobre o Espaço Urbano e seu Controle
Authors: Nigriello Andreina
Published: September 2017

O controle do impacto sobre o espaço urbano de melhorias efetuadas no sistema de transporte pressupõe o entendimento da interação entre o uso e ocupação do solo e a acessibilidade. Essa interação e seus efeitos estão confirmados em estudos estatísticos do impacto da linha Norte-Sul do metrô de São Paulo sobre o espaço urbano. Para o controle desses efeitos são propostas algumas estratégias visando: maior justiça social na distribuição dos benefícios indiretos vinculados aos investimentos públicos no setor de transporte; a criação de novas fontes de financiamento para o setor; e a redu­ ção do afastamento da população de baixa renda das áreas diretamente atendidas pelas melhorias de transporte
Limites e Possibilidades do Planejamento Estadual Reflexões a partir da Experiência da Guanabara
Authors: Santos Angela Moulin Penalva
Published: September 2017

Este artigo discute os limites e as possibilidades do planejamento, considerado como instrumento de formulação de polfticas. As reflexões estão referidas à cidade do Rio de Janeiro que, durante os anos 60, sofreu uma verdadeira reforma urbana, derivada do impacto da realização de uma série de investimentos públicos sobre a sua estrutura urbanística
Cardiovascular Risk Factors Accelerate Progression of Vascular Aging in the General Population
Authors: Terentes-Printzios Dimitrios , Vlachopoulos Charalambos , Xaplanteris Panagiotis , Ioakeimidis Nikolaos , Aznaouridis Konstantinos , Baou Katerina , Kardara Despina , Georgiopoulos Georgios , Georgakopoulos Christos , Tousoulis Dimitrios
Published: September 2017

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular risk. We hypothesized that the number of cardiovascular risk factors determines the progression of vascular aging. One hundred forty-two subjects (mean age 51.9 years, 94 men) without established cardiovascular disease were investigated in 2 examinations over a 2-year period. Subjects were classified at baseline according to their number of risk factors (from 0 to 2 and more). Subjects had determinations of carotid-femoral pulse wave velocity, aortic augmentation index, brachial flow-mediated dilatation, and common carotid intima–media thickness and their annual absolute changes were calculated. Subjects with more risk factors had a gradual higher annual progression of pulse wave velocity (0.092 m/s/y for 0, 0.152 m/s/y for 1, and 0.352 m/s/y for 2 and more;
P
=0.007). Patients with both hypertension and dyslipidemia have 4× higher annual progression rate compared with subjects without these risk factors (0.398 m/s/y versus 0.102 m/s/y). When only subjects 55 years old and under were considered, the progression rate of augmentation index was higher in subjects with more risk factors (1.15%/y versus 1.50%/y versus 2.99%/y, respectively;
P
=0.037). No association was found with the annual change of flow-mediated dilatation or carotid intima–media thickness. In the general population, increasing number of risk factors is associated with accelerated deterioration of specific indices of vascular aging, such as pulse wave velocity and augmentation index; in contrast, flow-mediated dilatation and carotid intima–media thickness are insensitive to such changes. Accordingly, the former may be more useful for gauging vascular aging.
Russula ahmadii (Basidiomycota, Russulales), a new species in section Ingratae and its ectomycorrhiza from coniferous forests of Pakistan
Authors: JABEEN SANA , RAZAQ ABDUL , NIAZI ABDUL REHMAN KHAN , AHMAD ISHTIAQ , GREBENC TINE , KHALID ABDUL NASIR
Published: September 2017

Russula ahmadii, a new species and its ectomycorrhiza are described and illustrated from coniferous forests of Pakistan, based on morphological characteristics and molecular phylogenetic data. The species is characterized by small to medium size basidiomata, a dark brown to greyish brown, tuberculate striate, and depressed pileus with dark brown spots in the centre, a chambered stipe having brownish patches towards the base, globose to subglobose amyloid basidiospores, having covered with bifurcated verrucose ornamentation connected by partial reticulum. Its ectomycorrhiza is typical of the genus Russula and is characterized by the presence of abundant lageniform cystidia with a straight neck and branched emanating hyphae with frequent clamp connections. Phylogenetic analyses based on ITS and LSU sequences support erection of the new species. Phylogenetic network analysis revealed its close position to R. pectinatoides. ITS sequences from ectomycorrhiza of Cedrus deodara also clustered with sequences from basidiomata of R. ahmadii confirming its mycorrhizal status. Phylogenetic analyses and morphological features placed the new species in R. section Ingratae.
Bridging Operational Meteorology and Academia through Experiential Education: The Storm Prediction Center in the University of Oklahoma Classroom
Authors: Cohen Ariel E. , Thompson Richard L. , Cavallo Steven M. , Edwards Roger , Weiss Steven J. , Hart John A. , Jirak Israel L. , Bunting William F. , Rogers Jaret W. , Piltz Steven F. , Gerard Alan E. , Moore Andrew D. , Cornish Daniel J. , Boothe Alexander C. , Cohen Joel B.
Published: September 2017

During the 2014–15 academic year, the National Oceanic and Atmospheric Administration (NOAA) National Weather Service Storm Prediction Center (SPC) and the University of Oklahoma (OU) School of Meteorology jointly created the first SPC-led course at OU focused on connecting traditional theory taught in the academic curriculum with operational meteorology. This class, “Applications of Meteorological Theory to Severe-Thunderstorm Forecasting,” began in 2015. From 2015 through 2017, this spring–semester course has engaged 56 students in theoretical skills and related hands-on weather analysis and forecasting applications, taught by over a dozen meteorologists from the SPC, the NOAA National Severe Storms Laboratory, and the NOAA National Weather Service Forecast Offices. Following introductory material, which addresses many theoretical principles relevant to operational meteorology, numerous presentations and hands-on activities focused on instructors’ areas of expertise are provided to students. Topics include the following: storm-induced perturbation pressure gradients and their enhancement to supercells, tornadogenesis, tropical cyclone tornadoes, severe wind forecasting, surface and upper-air analyses and their interpretation, and forecast decision-making. This collaborative approach has strengthened bonds between meteorologists in operations, research, and academia, while introducing OU meteorology students to the vast array of severe thunderstorm forecast challenges, state-of-the-art operational and research tools, communication of high-impact weather information, and teamwork skills. The methods of collaborative instruction and experiential education have been found to strengthen both operational–academic relationships and students’ appreciation of the intricacies of severe thunderstorm forecasting, as detailed in this article.
The role of co-workers in the production of (homo)sexuality at work: A Foucauldian approach to the sexual identity processes of gay and lesbian employees
Authors: Van Laer Koen
Published: September 2017

Adopting a Foucauldian perspective that focuses on the way power contributes to ensuring that sexuality leads a discursive existence, this study investigates the role of co-workers in the production of gay and lesbian employees’ sexuality. Drawing on interviews with 31 employees who self-identify as gay or lesbian, this article makes three contributions to the literature on sexual minorities’ identities at work. First, it shows how the production of sexuality is shaped by relations of attribution, evocation and circulation, which involve sexualizing practices through which co-workers directly contribute to ensuring that employees become sexually intelligible. By shaping the way sexual identities can be managed, these practices can turn the production of sexuality into a process that is not only unmanageable, but also even unmanaged by gay and lesbian employees themselves. Second, this article shows how an important element in sexual identity management is negotiating relations of truthfulness and inclusion, and constructing the occupied sexual subject position as positive or necessary. Third, it shows the connections between these different relations, which can occur and work together to ensure that all individuals come to be linked to a clear sexual identity.
The Effects of Worry and Relaxation on Flexibility During Cognitive Restructuring
Authors: Stevens Elizabeth S. , Jendrusina Alexander A. , Legrand Alison C. , Nahin Erica R. , Kaufman Michelle Goldwin , Borkovec Thomas D. , Behar Evelyn
Published: September 2017

Worry is associated with inflexibility in cognitive, emotional, and physiological functioning. In addition, worry’s negative valence and abstract level of construal are rigid characteristics that contribute to its nonadaptive consequences. Relaxation and cognitive therapy aim to increase flexibility in chronic worriers, and may have greater efficacy when administered in combination. We examined the extent to which relaxation enhances and/or worry inhibits cognitive flexibility during a cognitive restructuring exercise in which participants generated alternative predictions for their worries. Participants ( n = 189) were randomly assigned to engage in relaxation, worry, or neutral thinking prior to cognitive restructuring. We measured the number and perceived likelihood of alternative predictions generated by participants, and coded those alternative predictions for their degree of positive valence, negative valence, and level of construal (abstractness to concreteness). Worry and relaxation did not lead to different numbers or perceived likelihood of alternative predictions. However, compared with participants with minimal symptoms of generalized anxiety disorder (GAD), those with elevated symptoms of GAD who engaged in prior worry generated alternative predictions characterized by greater negative valence and more abstractness (i.e., less concreteness). We also found that greater negative valence of alternative predictions was associated with more abstractness, whereas greater positive valence of alternative predictions was associated with more concreteness. These findings suggest that after engaging in worry, individuals with GAD may be less able to flexibly shift from the use of nonadaptive characteristics (negative valence, abstractness) associated with feared outcomes to the use of more adaptive characteristics (positive valence, concreteness) when considering alternative predictions.
Language assessment and the inseparability of lexis and grammar: Focus on the construct of speaking
Authors: Römer Ute
Published: September 2017

This paper aims to connect recent corpus research on phraseology with current language testing practice. It discusses how corpora and corpus-analytic techniques can illuminate central aspects of speech and help in conceptualizing the notion of lexicogrammar in second language speaking assessment. The description of speech and some of its core features is based on the 1.8-million-word Michigan Corpus of Academic Spoken English (MICASE) and on the 10-million-word spoken component of the British National Corpus (BNC). Analyses of word frequency and keyword lists are followed by an automatic extraction of different types of phraseological items that are particularly common in speech and serve important communicative functions. These corpus explorations provide evidence for the strong interconnectedness of lexical items and grammatical structures in natural language. Based on the assumption that the existence of lexicogrammatical patterns is of relevance for constructs of speaking tests, the paper then reviews rubrics of popular high-stakes speaking tests and critically discusses how far these rubrics capture the central aspects of spoken language identified in the corpus analyses as well as the centrality of phraseology in language. It closes with recommendations for speaking assessment in the light of this characterization of real-world spoken lexicogrammar.
Comparison of stored red blood cell washing techniques for priming extracorporeal circuits
Authors: Sasaki Jun , Tirotta Christopher , Lim Hyunsoo , Kubes Kathleen , Salvaggio Jane , Hannan Robert , Burke Redmond , Ojito Jorge
Published: September 2017

Background:

The aim of this study was to compare three different blood washing techniques and describe the differences for the composition of the washed red blood cells (RBC).

Methods:

Stored RBCs less than 5 days old were washed using three different techniques. 1) Washing with normal saline with the COBE Model 2991 blood processor in the blood bank (BB-S). 2) Washing with normal saline with the Continuous AutoTransfusion System (C.A.T.S) in the operating room (OR-S). 3) Washing with Plasma-Lyte with the C.A.T.S in the operating room (OR-PL). Then, we compared the values for hemoglobin (Hb), hematocrit (Hct), blood volume, RBC volume, lactate, glucose, sodium and potassium of the three different groups.

Results:

Forty-five units of RBCs were washed and analyzed (15 for each technique). The OR-S RBCs, when compared to the BB-S RBCs, had lower hemoglobin (g/dL) (22.8 vs 24.1, p=0.006), lower hematocrit (%) (67 vs 71, p=0.006), higher RBC volume (ml) (161 vs 130, p<0.001), higher glucose (mg/dL) (185 vs 46, p<0.001) and lower sodium (mmol/L) (153 vs 158, p<0.001). When compared to the OR-S RBCs, the OR-PL RBCs showed higher potassium (mmol/L) (5.3 vs 2, p<0.001) and lower sodium (mmol/L) (129 vs 153, p<0.001).

Conclusion:

RBCs washed with an autotransfusion device had a higher RBC volume and more physiological levels of glucose and sodium when compared with the blood processor in the blood bank. It can be an alternative option to use RBCs washed with an autotransfusion device for priming the extracorporeal circuits utilized in patients undergoing cardiac surgery.
Recanalization, reperfusion, and recirculation in stroke
Authors: Zhang John H , Obenaus Andre , Liebeskind David S , Tang Jiping , Hartman Richard , Pearce William J
Published: September 2017

Recirculation, from arterial inflow routes through venous outflow pathways, was conceptualized in stroke research 50 years ago. As new technologies were developed, blocked arteries could be reopened, capillaries could be reperfused, and the use of recanalization and reperfusion grew to dominate therapeutic strategies. These approaches overwhelmingly focused on restoration of arterial and capillary inflow, but not on veins even though venous disorders may initiate or exacerbate brain injury. In this commentary, we advance the term “recirculation” after “recanalization” and “reperfusion” as a primary concept of stroke pathophysiology that targets the restoration of both the arterial and venous cerebral circulations.
Hemodynamics and oxygen extraction in chronic large artery steno-occlusive disease: Clinical applications for predicting stroke risk
Authors: Derdeyn Colin P
Published: September 2017

Depending on the adequacy of collateral sources of blood flow, arterial stenosis or occlusion may lead to reduced perfusion pressure and ultimately reduced blood flow in the distal territory supplied by that vessel. There are two well-defined compensatory mechanisms to reduced pressure or flow – autoregulatory vasodilation and increased oxygen extraction fraction. Other changes, such as metabolic downregulation, are likely. The positive identification of autoregulatory vasodilation and increased oxygen extraction fraction in humans is an established risk factor for future ischemic stroke in some disease states such as atherosclerotic carotid stenosis and occlusion. The mechanisms by which ischemic stroke may occur are not clear, and may include an increased vulnerability to embolic events. The use of hemodynamic assessment to identify patients with occlusive vasculopathy at an increased risk for stroke is very appealing for several different patient populations, such as those with symptomatic intracranial atherosclerotic disease, moyamoya phenomenon, complete internal carotid artery occlusion, and asymptomatic cervical carotid artery stenosis. While there is very good data for stroke risk prediction in some of these groups, no intervention based on these tools has been proven effective yet. In this manuscript, we will review these topics above and identify areas for future research.
Cultural Identity in the Age of Transculturation
Authors: Um Jungsik
Published: September 2017

The term “self” refers to the subject which persists through the changing experiences of a person. We think of it at least as the center of personal identity, or the organizing function within the individual. It may be desirable to examine cultural identity if there is something like “the communal self.” Kant believed that there is a “transcendental self” which transcends our experiences. Following him, we may analogously claim that there is a communal self, which transcends the history and the culture of the community, maintaining their identity throughout time by means of providing the unity principle. Korea is a typical example of a nation whose process of transculturation is most dynamically ongoing. Such a nation should apply this concept to her current cultural situations in order to be successful in the age of globalization.
Depression and Cognitive Function in Mild Cognitive Impairment: A 1-Year Follow-Up Study
Authors: Yoon Seoyoung , Shin Cheolmin , Han Changsu
Published: September 2017

Background:

The coexistence of depression with mild cognitive impairment (MCI) seems to increase the risk of dementia. However, the explanations of that relationship have been inconsistent. We investigated cognitive profiles in patients with MCI with and without depression and whether changes in depression symptoms affect cognition longitudinally.

Methods:

For the study, 161 patients with MCI were divided into a depressed group (D+) and a nondepressed group (D−). After 1 year, we redivided the original D− group into D− and newly developed depression (Dd) groups and the D+ group into improved depression (Di) and nonimproved depression (Dn) groups. Neuropsychological tests assessing depression and cognitive domains were performed at baseline and follow-up.

Results:

When age-adjusted, the D+ group showed significantly poorer performance in general cognition and some subtests regarding memory, executive function, and attention. At the 1-year follow-up, changes in the calculation test ( P = .005) and Controlled Oral Word Test (COWAT; P = .048) were significantly different between groups. Only the Di group showed significant improvement in calculation. The Dn group showed significant decrement in COWAT that was significantly different from that of the Di group, which showed no significant change.

Discussion:

Patients with depression having MCI showed poorer cognitive function than nondepressed patients with MCI in some cognitive domains. Improvement in depression was related to improvement or prevention of decline in cognitive measures.