bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of autopatching with automated pipette and cell detection in vitro
Authors: Wu (吴秋雨) Qiuyu , Kolb Ilya , Callahan Brendan M. , Su Zhaolun , Stoy William , Kodandaramaiah Suhasa B. , Neve Rachael , Zeng Hongkui , Boyden Edward S. , Forest Craig R. , Chubykin Alexander A.
Published: July 2016

Patch clamp is the main technique for measuring electrical properties of individual cells. Since its discovery in 1976 by Neher and Sakmann, patch clamp has been instrumental in broadening our understanding of the fundamental properties of ion channels and synapses in neurons. The conventional patch-clamp method requires manual, precise positioning of a glass micropipette against the cell membrane of a visually identified target neuron. Subsequently, a tight “gigaseal” connection between the pipette and the cell membrane is established, and suction is applied to establish the whole cell patch configuration to perform electrophysiological recordings. This procedure is repeated manually for each individual cell, making it labor intensive and time consuming. In this article we describe the development of a new automatic patch-clamp system for brain slices, which integrates all steps of the patch-clamp process: image acquisition through a microscope, computer vision-based identification of a patch pipette and fluorescently labeled neurons, micromanipulator control, and automated patching. We validated our system in brain slices from wild-type and transgenic mice expressing channelrhodopsin 2 under the Thy1 promoter (line 18) or injected with a herpes simplex virus-expressing archaerhodopsin, ArchT. Our computer vision-based algorithm makes the fluorescent cell detection and targeting user independent. Compared with manual patching, our system is superior in both success rate and average trial duration. It provides more reliable trial-to-trial control of the patching process and improves reproducibility of experiments.
Quadruple-Negative GIST Is a Sentinel for Unrecognized Neurofibromatosis Type 1 Syndrome
Authors: Gasparotto Daniela , Rossi Sabrina , Polano Maurizio , Tamborini Elena , Lorenzetto Erica , Sbaraglia Marta , Mondello Alessia , Massani Marco , Lamon Stefano , Bracci Raffaella , Mandolesi Alessandra , Frate Elisabetta , Stanzial Franco , Agaj Jerin , Mazzoleni Guido , Pilotti Silvana , Gronchi Alessandro , Dei Tos Angelo Paolo , Maestro Roberta
Published: July 2016

Purpose: The majority of gastrointestinal stromal tumors (GIST) are driven by KIT, PDGFRA, or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple-negative GISTs.

Experimental Design: Twenty-two sporadic quadruple-negative GISTs with no prior association with Neurofibromatosis Type 1 syndrome were molecularly profiled for a panel of genes belonging to tyrosine kinase pathways or previously implicated in GISTs. For comparison purposes, 24 GISTs carrying KIT, PDGFRA, or SDH gene mutations were also analyzed. Molecular findings were correlated to clinicopathologic features.

Results: Most quadruple-negative GISTs featured intestinal localization, with a female predilection. About 60% (13/22) of quadruple-negative tumors carried NF1 pathogenic mutations, often associated with biallelic inactivation. The analysis of normal tissues, available in 11 cases, indicated the constitutional nature of the NF1 mutation in 7 of 11 cases, unveiling an unrecognized Neurofibromatosis Type 1 syndromic condition. Multifocality and a multinodular pattern of growth were common findings in NF1-mutated quadruple-negative GISTs.

Conclusions: NF1 gene mutations are frequent in quadruple-negative GISTs and are often constitutional, indicating that a significant fraction of patients with apparently sporadic quadruple-negative GISTs are affected by unrecognized Neurofibromatosis Type 1 syndrome. Hence, a diagnosis of quadruple-negative GIST, especially if multifocal or with a multinodular growth pattern and a nongastric location, should alert the clinician to a possible Neurofibromatosis Type 1 syndromic condition. Clin Cancer Res; 23(1); 273–82. ©2016 AACR.
Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth
Authors: Abu Aboud Omran , Chen Ching-Hsien , Senapedis William , Baloglu Erkan , Argueta Christian , Weiss Robert H.
Published: July 2016

Kidney cancer (or renal cell carcinoma, RCC) is the sixth most common malignancy in the United States and one of the relatively few whose incidence is increasing. Because of the near universal resistance which occurs with the use of current treatment regimens, reprogrammed metabolic pathways are being investigated as potential targets for novel therapies of this disease. Borrowing from studies on other malignancies, we have identified the PAK4 and NAD biosynthetic pathways as being essential for RCC growth. We now show, using the dual PAK4/NAMPT inhibitor KPT-9274, that interference with these signaling pathways results in reduction of G2–M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. Mechanistic studies demonstrate that inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear β-catenin as well as the Wnt/β-catenin targets cyclin D1 and c-Myc. Furthermore, NAPRT1 downregulation, which we show occurs in all RCC cell lines tested, makes this tumor highly dependent on NAMPT for its NAD requirements, such that inhibition of NAMPT by KPT-9274 leads to decreased survival of these rapidly proliferating cells. When KPT-9274 was administered in vivo to a 786-O (VHL-mut) human RCC xenograft model, there was dose-dependent inhibition of tumor growth with no apparent toxicity; KPT-9274 demonstrated the expected on-target effects in this mouse model. KPT-9274 is being evaluated in a phase I human clinical trial in solid tumors and lymphomas, which will allow this data to be rapidly translated into the clinic for the treatment of RCC. Mol Cancer Ther; 15(9); 2119–29. ©2016 AACR.
AKT1 Activation is Obligatory for Spontaneous BCC Tumor Growth in a Murine Model that Mimics Some Features of Basal Cell Nevus Syndrome
Authors: Kim Arianna L. , Back Jung Ho , Zhu Yucui , Tang Xiuwei , Yardley Nathan P. , Kim Katherine J. , Athar Mohammad , Bickers David R.
Published: July 2016

Patients with basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, develop numerous basal cell carcinomas (BCC) due to germline mutations in the tumor suppressor PTCH1 and aberrant activation of Hedgehog (Hh) signaling. Therapies targeted at components of the Hh pathway, including the smoothened (SMO) inhibitor vismodegib, can ablate these tumors clinically, but tumors recur upon drug discontinuation. Using SKH1-Ptch1+/− as a model that closely mimics the spontaneous and accelerated growth pattern of BCCs in patients with BCNS, we show that AKT1, a serine/threonine protein kinase, is intrinsically activated in keratinocytes derived from the skin of newborn Ptch1+/− mice in the absence of carcinogenic stimuli. Introducing Akt1 haplodeficiency in Ptch1+/− mice (Akt1+/− Ptch1+/−) significantly abrogated BCC growth. Similarly, pharmacological inhibition of AKT with perifosine, an alkyl phospholipid AKT inhibitor, diminished the growth of spontaneous and UV-induced BCCs. Our data demonstrate an obligatory role for AKT1 in BCC growth, and targeting AKT may help reduce BCC tumor burden in BCNS patients. Cancer Prev Res; 9(10); 794–802. ©2016 AACR.
Immune Responses Mediated by Th17 Cells in Helicobacter pylori Infection
Authors: Liu Chang , Zhang Zhengli , Zhu Meiping
Published: July 2016

T helper 17 (Th17) cells are one of the CD4+ T-cell subsets which induce a variety of diseases by secreting IL-17 and other inflammatory factors. After Helicobacter pylori (Hp) infection, cytotoxin-associated gene A and urease subunit B regulate the number of Th17 cells via induction of cell differentiation by infected macrophages, activation of MyD88 and other pathways, and by driving chemokines, which upregulates the number of both Th17 cells and regulatory T cells (Tregs) and switches towards a Treg-type immune response. Meanwhile, Th17 cells also play important roles in the response to Hp infection, participating in the clearance of Hp by recruiting neutrophils and expanding inflammatory response, causing mucosal damage and even inducing cancer. Thereby, Th17 cells participate in the occurrence and development of Hp-related diseases, such as gastritis, peptic ulcer disease and gastric cancer.
CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck
Authors: De Meulenaere Astrid , Vermassen Tijl , Aspeslagh Sandrine , Zwaenepoel Karen , Deron Philippe , Duprez Fréderic , Ferdinande Liesbeth , Rottey Sylvie
Published: July 2016

Objective: Over the last decade, efforts have been made to get a better understanding of the tumor microenvironment and the role of the immune system in it. New insights into the CD27/CD70 signaling pathway point towards a role in tumor immunology, making CD70 an attractive target for immunotherapy. Here, we evaluate CD70 expression in squamous cell carcinoma of the head and neck (SCCHN). Methods: CD70 immunohistochemistry was retrospectively performed on 95 tumor samples. Tumoral CD70 expression was scored and correlated with clinicopathological variables and overall survival (OS). Results: CD70 expression in tumor cells was observed in 66 samples (69%) and was strongly associated with tumor differentiation grade (p < 0.001). CD70 expression was also observed in tumor-associated fibroblasts and endothelial cells. Additionally, the density of tumor-infiltrating lymphocytes correlated with OS (p = 0.042). Conclusion: This study describes the tumoral expression of CD70 in SCCHN. Results highlight the role of CD70 in tumor biology and identify CD70 as a novel therapeutic target. Further research is warranted.
Mutational Spectrum of CYP24A1 Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia
Authors: Gigante Maddalena , Santangelo Luisa , Diella Sterpeta , Caridi Gianluca , Argentiero Lucia , D''Alessandro Maria Michela , Martino Marida , Stea Emma Diletta , Ardissino Gianluigi , Carbone Vincenza , Pepe Silvana , Scrutinio Domenico , Maringhini Silvio , Ghiggeri Gian Marco , Grandaliano Giuseppe , Giordano Mario , Gesualdo Loreto
Published: July 2016

Background/Aims: Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH). Methods: We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software. Results:CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls. Conclusion: To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms that CYP24A1 plays a causal role in some but not all cases of IIH (64%); (2) expands the spectrum of known CYP24A1 pathogenic mutations; (3) describes 2 hotspots detected in 50% of all Italian cases; and (4) emphasizes the importance of recognition and genetic diagnosis of CYP24A1 defects in infantile as well as adult hypercalcemia.
Diferenças imagéticas. Considerações sobre a técnica e o símbolo no contexto comunicacional
Authors: Barros Eduardo Portanova , De Carli Anelise Angeli , Fantinel Danilo
Published: July 2016

A pesquisa acadêmica que se debruça sobre os processos comunicacionais, muito frequentemente, tem escolhido como objeto de investigação os produtos da cultura visual contemporânea. A fim de contribuir para aproximações concêntricas junto aos Estudos da Imagem, este artigo pretende retomar posicionamentos teóricos a respeito de duas noções que, neste campo de pesquisa, costumam-se chamar “imagem técnica” e “imagem simbólica”. Recuperando algumas definições dos Estudos da Imagem e do Imaginário, procuramos observar as diferenças entre estas duas ordens de imagens e suas possíveis articulações. Buscamos, ainda, compreender como tais imagens se apresentam e como se dá a relação delas com a socialidade contemporânea, situando-as como motivadoras de pesquisa em Comunicação.
Como o jovem de São Paulo ouve rádio?
Authors: Gambaro Daniel
Published: July 2016

O objetivo deste artigo é demonstrar como as emissoras de rádio de São Paulo, voltadas para o público jovem e jovem adulto (até 30 anos) estão requalificando suas operações e grades de programação, como forma de atender uma nova demanda da audiência. A introdução de redes sociais na dinâmica dos programas adicionou novas possibilidades de interação entre as emissoras e uma audiência altamente conectada. Além disso, as estações passaram a oferecer mais conteúdo em seus websites: fotos, vídeos, playlists de músicas pré-configuradas, notícias segmentadas em assuntos, etc. Agora, os programas no dial também estão mudando: podemos notar uma presença maior do apresentador radiofônico durante a reprodução musical, inclusive com mais interação com a audiência. Assim, esta pesquisa apresenta como as cinco principais emissoras paulistanas de audiência jovem modificaram suas estruturas de conteúdo.
Dilma no Jô: o papel do talk show e a crítica em uma sociedade polarizada
Authors: Lery Julia
Published: July 2016

A presença de Dilma Rousseff no Programa do Jô em um momento de crise econômica e de baixa popularidade causou uma repercussão negativa e discursos de ódio voltados não só para a figura da presidenta, mas também contra Jô Soares. Neste artigo estudamos, usando o gênero televisivo como categoria analítica, as interações produzidas por essa edição do programa a partir das promessas e expectativas geradas pelo talk show – que mais do que um formato televisivo é uma maneira de mediação. Analisamos, por esse viés, a descaracterização do programa que recebe Dilma Rousseff e as críticas negativas que repercutiram na mídia tradicional, nas redes sociais e até por meio de ameaça ao apresentador.
A (in)visibilidade dos acontecimentos e a lógica do condomínio na sociedade brasileira contemporânea
Authors: Simões Paula Guimarães
Published: July 2016

O objetivo deste texto é refletir sobre o cenário de polarizações que marca o contexto brasileiro a partir do cruzamento entre dois acontecimentos ocorridos em agosto de 2015: a chacina que vitimou 18 pessoas em Osasco e Barueri, no dia 13, e as manifestações contra o governo Dilma, no dia 16. A associação entre os dois acontecimentos trouxe à tona algumas polarizações que constituem a cena pública contemporânea: entre os pró e os contra o governo do PT, entre centro e periferia, entre ricos e pobres. A análise revela traços da lógica do condomínio (DUNKER, 2015) que caracteriza nossa sociedade: uma forma de vida marcada pela segregação, em que muros impedem o diálogo e a compreensão entre os diferentes – o que é central na construção de uma sociedade democrática.
Fama e engajamento no Instagram: as celebridades e a convocação de públicos
Authors: Medeiros Fernanda Faria
Published: July 2016

Com foco no contexto atual das redes sociais brasileiras – polarizado e turbulento, a intenção deste trabalho é observar as possibilidades e tentativas de representação dos anônimos através das novas formas de interlocução que se manifestam entre as celebridades e os comuns, no ambiente digital. A ideia é fomentar a reflexão a respeito do impacto da mídia na constituição de grupos sociais ativos, analisando as investidas de representação, por parte das celebridades, em seus movimentos de convocação e de interlocução com públicos específicos. Para tanto, examinamos, na empiria, os perfis virtuais da cantora Daniela Mercury e do rapper Emicida.
Estética e informação em um vídeo de violência policial na periferia
Authors: Polydoro Felipe Da Silva
Published: July 2016

Neste artigo, analisamos detidamente um vídeo amador que documenta um episódio de violência policial em uma favela carioca, um entre tantos exemplos de registros amadores contemporâneos a revelar casos de abusos policiais nas periferias brasileiras. Este tem como traço singular o fato de que a vítima é o próprio cinegrafista. Nesta análise, tomamos como base um modo de observação exposto por Didi-Huberman (2012), que interliga aspectos documentais e estéticos na análise de imagens captadas em condições extremas, numa aproximação que enfatiza seu estatuto de acontecimento.
Apresentação do Dossiê “Polarizações”
Authors: Serelle Márcio
Published: July 2016

O Dossiê desta edição reúne textos do seminário Polarizações, realizado em novembro de 2015, em Belo Horizonte, pelo grupo de pesquisa Mídia e Narrativa, da PUC Minas, e que contou com a participação de pesquisadores de diferentes universidades brasileiras. A discussão fez-se premente em face do acirramento das polarizações políticas e sociais no período durante e imediatamente após as eleições presenciais de 2014, que deixou à mostra os contornos de uma nova direita no País, culminando no atual afastamento – seguido de intensos protestos e mobilização social – da presidenta Dilma Rousseff.
Nexos entre a redistribuição populacional e a produção imobiliária residencial nos distritos do município de São Paulo
Authors: Nakano Anderson Kazuo
Published: July 2016

Este artigo discute a relação entre as mudanças na distribuição espacial da população e a produção de empreendimentos imobiliários residenciais verticais nos distritos do Município de São Paulo. Para desenvolver essa discussão, utilizam-se dados censitários de 1991, 2000 e 2010 articulados com dados relativos à produção de prédios de apartamentos lançados durante o período entre 1998 e 2008. Esses bancos de dados serviram como base para a elaboração de metodologia que permitiu a construção da Taxa de Absorção Populacional pela Produção Imobiliária (TAPPI). A TAPPI procura estimar o quanto do Incremento Populacional (IP) ocorrido nos distritos paulistanos entre 2000 e 2010 foi absorvido pelos apartamentos lançados pelos agentes do mercado de incorporação entre 1998 e 2008. Para isso estimou-se o Incremento Populacional Potencial Promovido pelos Empreendimentos Imobiliários Residenciais Verticais (IPPPEIRV) calculado com base no número de moradores por apartamento extraído do Censo Demográfico de 2010. Concluiu-se que, de fato, o segmento da produção imobiliária voltado para a construção de prédios de apartamentos condicionou fortemente a distribuição espacial da população paulistana nos distritos centrais que tiveram uma inversão demográfica de perda para ganhos populacionais na passagem da década de 1990 para a de 2000. Não se percebeu o mesmo fenômeno nos distritos periféricos.
Patrick Geddes e a Escola Territorialista Italiana: aproximações conceituais e metodológicas. Reflexões a partir da participação de crianças na representação de valores patrimoniais da cidade de Santa Leopoldina–ES/Brasil
Authors: Andrade Bruno Amaral de , Almeida Renata Hermanny de
Published: July 2016

O estudo de Patrick Geddes sobre a criança na cidade reporta às Mostras sobre o Bem-Estar da criança, bem como ao interesse por estudos acerca das origens históricas e geográficas das cidades, a partir de fábulas ligadas às condições simples e naturais da relação do homem com o meio ambiente, por exemplo, estórias de caçador, mineiro, lenhador, pastor, camponês e pescador. A Escola Territorialista Italiana, de Alberto Magnaghi, revisita de maneira crítica e reflexiva a abordagem participativa precursora do pensamento geddesiano e desenvolve método, técnica e instrumento para a participação de crianças como atoresprotagonistas na representação e no projeto do território. Com efeito, este artigo discute a representação de valores por crianças em sítio histórico de valor patrimonial, originalmente ocupado por imigrantes de origem germânica, a cidade de Santa Leopoldina, no Estado do Espírito Santo, Brasil. Isso é feito tendo por referência desenhos elaborados por alunos de faixa etária entre 11 e 15 anos, desenvolvidos individual e coletivamente. Os desenhos, produzidos por diferentes estratégias lúdicopedagógicas, revelam maior relação afetiva com o ambiente paisagístico do que com o ambiente urbano.
2014 Jeffrey M. Hoeg Award Lecture
Authors: Zhu Yanfang Peipei , Thomas Graham D. , Hedrick Catherine C.
Published: July 2016

Monocytes and macrophages are key immune cells involved in the early progression of atherosclerosis. Transcription factors that control their development in the bone marrow are important therapeutic targets to control the numbers and functions of these cells in disease. This review highlights what is currently known about the transcription factors that are critical for monocyte development.
Do the
Apoe

−/−

and
Ldlr

−/–

Mice Yield the Same Insight on Atherogenesis?
Authors: Getz Godfrey S. , Reardon Catherine A.
Published: July 2016

Murine models of atherosclerosis are useful for investigating the environmental and genetic influences on lesion formation and composition.
Apoe

−/−

and
Ldlr

−/−

mice are the 2 most extensively used models. The models differ in important ways with respect to the precise mechanism by which their absence enhances atherosclerosis, including differences in plasma lipoproteins. The majority of the gene function studies have utilized only 1 model, with the results being generalized to atherogenic mechanisms. In only a relatively few cases have studies been conducted in both atherogenic murine models. This review will discuss important differences between the 2 atherogenic models and will point out studies that have been performed in the 2 models where results are comparable and those where different results were obtained.
Pace Mapping for the Identification of Focal Atrial Tachycardia Origin
Authors: Hayashi Kentaro , Mathew Shibu , Heeger Christian-H. , Maurer Tilman , Lemes Christine , Riedl Johannes , Sohns Christian , Saguner Ardan M. , Santoro Francesco , Reißmann Bruno , Metzner Andreas , Kuck Karl-Heinz , Ouyang Feifan
Published: July 2016

Background—

Focal atrial tachycardia (FAT) is extremely difficult to map and ablate when it is difficult to induce and nonsustained. The objective of this study is to evaluate the efficacy of pace mapping in identifying the FAT origin.

Methods and Results—

The study included 7 patients with drug-refractory FAT who experienced daily multiple episodes before ablation and presented with difficult-to-induce and nonsustained FAT and a distinct P wave morphology. Pace mapping was systematically performed in the areas of interest using 3-dimensional mapping to match the P wave morphology and paced intracardiac activation sequence recorded from multiple catheters. The anatomic origins of FAT were the right pulmonary vein (PV) in 3 patients, mitral annulus, crista terminalis, tricuspid annulus, and right-sided PV via a posterior conduction of previous PV isolation. In all patients, pace mapping obtained best-matched P wave morphology in ≥11/12 leads of surface ECG at the successful ablation site, and paced intracardiac activation sequence was identical to that of induced FAT. Focal ablation was delivered in 4 patients, including non-PV FAT in 3 and FAT in 1, via posterior gap along the previous right-sided PV isolation, and circumferential right-sided PV isolation was performed in the other 3 patients. No FAT was induced at the end of the procedure. All patients were free of arrhythmias without antiarrhythmic drugs during the 8.4±5.6-month follow-up.

Conclusions—

The combination of paced P wave morphology and intracardiac activation sequence can be used for the identification of FAT origin in patients with difficult-to-induce and nonsustained FAT.
T1 Mapping in Characterizing Myocardial Disease
Authors: Puntmann Valentina O. , Peker Elif , Chandrashekhar Y. , Nagel Eike
Published: July 2016

Cardiovascular magnetic resonance provides insights into myocardial structure and function noninvasively, with high diagnostic accuracy and without ionizing radiation. Myocardial tissue characterization in particular gives cardiovascular magnetic resonance a prime role among all the noninvasive cardiovascular investigations. Late gadolinium enhancement imaging is an established method for visualizing replacement scar, providing diagnostic and prognostic information in a variety of cardiac conditions. Late gadolinium enhancement, however, relies on the regional segregation of tissue characteristics to generate the imaging contrast. Thus, myocardial pathology that is diffuse in nature and affecting the myocardium in a rather uniform and global distribution is not well visualized with late gadolinium enhancement. Examples include diffuse myocardial inflammation, fibrosis, hypertrophy, and infiltration. T1 mapping is a novel technique allowing to diagnose these diffuse conditions by measurement of T1 values, which directly correspond to variation in intrinsic myocardial tissue properties. In addition to providing clinically meaningful indices, T1-mapping measurements also allow for an estimation of extracellular space by calculation of extracellular volume fraction. Multiple lines of evidence suggest a central role for T1 mapping in detection of diffuse myocardial disease in early disease stages and complements late gadolinium enhancement in visualization of the regional changes in common advanced myocardial disease. As a quantifiable measure, it may allow grading of disease activity, monitoring progress, and guiding treatment, potentially as a fast contrast-free clinical application. We present an overview of clinically relevant technical aspects of acquisition and processing, and the current state of art and evidence, supporting its clinical use.
Functional Importance of a Proteoglycan Coreceptor in Pathologic Lymphangiogenesis
Authors: Johns Scott C. , Yin Xin , Jeltsch Michael , Bishop Joseph R. , Schuksz Manuela , El Ghazal Roland , Wilcox-Adelman Sarah A. , Alitalo Kari , Fuster Mark M.
Published: July 2016

Rationale:

Lymphatic vessel growth is mediated by major prolymphangiogenic factors, such as vascular endothelial growth factor (VEGF-C) and VEGF-D, among other endothelial effectors. Heparan sulfate is a linear polysaccharide expressed on proteoglycan core proteins on cell membranes and matrix, playing roles in angiogenesis, although little is known about any function(s) in lymphatic remodeling in vivo.

Objective:

To explore the genetic basis and mechanisms, whereby heparan sulfate proteoglycans mediate pathological lymphatic remodeling.

Methods and Results:

Lymphatic endothelial deficiency in the major heparan sulfate biosynthetic enzyme
N
-deacetylase/
N
-sulfotransferase-1 (Ndst1; involved in glycan-chain sulfation) was associated with reduced lymphangiogenesis in pathological models, including spontaneous neoplasia. Mouse mutants demonstrated tumor-associated lymphatic vessels with apoptotic nuclei. Mutant lymphatic endothelia demonstrated impaired mitogen (Erk) and survival (Akt) pathway signaling and reduced VEGF-C–mediated protection from starvation-induced apoptosis. Lymphatic endothelial-specific
Ndst1
deficiency (in
Ndst1
f/f
Prox1

+/
Cre
ERT2

mice) was sufficient to inhibit VEGF-C–dependent lymphangiogenesis. Lymphatic heparan sulfate deficiency reduced phosphorylation of the major lymphatic growth receptor VEGF receptor-3 in response to multiple VEGF-C species. Syndecan-4 was the dominantly expressed heparan sulfate proteoglycan in mouse lymphatic endothelia, and pathological lymphangiogenesis was impaired in
Sdc4
(−/−)
mice. On the lymphatic cell surface, VEGF-C induced robust association between syndecan-4 and VEGF receptor-3, which was sensitive to glycan disruption. Moreover, VEGF receptor-3 mitogen and survival signaling was reduced in the setting of
Ndst1
or
Sdc4
deficiency.

Conclusions:

These findings demonstrate the genetic importance of heparan sulfate and the major lymphatic proteoglycan syndecan-4 in pathological lymphatic remodeling. This may introduce novel future strategies to alter pathological lymphatic-vascular remodeling.
Prognostic Determinants of Coronary Atherosclerosis in Stable Ischemic Heart Disease
Authors: Ahmadi Amir , Stone Gregg W. , Leipsic Jonathon , Shaw Leslee J. , Villines Todd C. , Kern Morton J. , Hecht Harvey , Erlinge David , Ben-Yehuda Ori , Maehara Akiko , Arbustini Eloisa , Serruys Patrick , Garcia-Garcia Hector M. , Narula Jagat
Published: July 2016

Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease.
Acute Kidney Injury Definition and In‐Hospital Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST‐Segment Elevation Myocardial Infarction
Authors: Marenzi Giancarlo , Cosentino Nicola , Moltrasio Marco , Rubino Mara , Crimi Gabriele , Buratti Stefano , Grazi Marco , Milazzo Valentina , Somaschini Alberto , Camporotondo Rita , Cornara Stefano , De Metrio Monica , Bonomi Alice , Veglia Fabrizio , De Ferrari Gaetano M. , Bartorelli Antonio L.
Published: July 2016

Background

Acute kidney injury (AKI) has been associated with increased mortality in
ST
‐segment elevation myocardial infarction. We compared the mortality predictive accuracy of the 3
AKI
definitions used most widely for patients with
ST
‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Methods and Results

We included 3771 patients with
ST
‐segment elevation myocardial infarction treated with primary percutaneous coronary intervention at 2 Italian hospitals.
AKI
incidence was evaluated according to creatinine increases of ≥25% (
AKI
‐25), ≥0.3 mg/dL (
AKI
‐0.3), and ≥0.5 mg/dL (
AKI
‐0.5). The primary end point was in‐hospital mortality. Overall, 557 (15%), 522 (14%), and 270 (7%) patients developed
AKI
‐25,
AKI
‐0.3, and
AKI
‐0.5, respectively (
P
<0.01). All
AKI
definitions independently predicted in‐hospital mortality (adjusted odds ratio 4.9 [95%
CI
3.1–7.8], 5.4 [95%
CI
3.3–8.6], and 8.3 [95%
CI
5.1–13.3], respectively;
P
<0.01 for all). At receiver operating characteristic analysis, the addition of each
AKI
definition to combined clinical predictors of mortality (age, sex, left ventricular ejection fraction, admission creatinine, creatine kinase‐
MB
peak) found at stepwise analysis significantly improved mortality prognostication (area under the curve increased from 0.89 for clinical predictor combination alone to 0.92 for
AKI
‐25, 0.92 for
AKI
‐0.3, and 0.93 for
AKI
‐0.5;
P
<0.01 for all). At reclassification analysis,
AKI
‐0.5 added to clinical predictors, provided the highest score in mortality (net reclassification improvement +10% versus
AKI
‐0.3 [
P
=0.01] and +8% versus
AKI
‐25 [
P
=0.05]).

Conclusions

Each
AKI
definition significantly improved the mortality prediction beyond major clinical variables.
AKI
‐0.5 showed a mortality discrimination advantage, suggesting it should be the preferred definition in studies addressing
ST
‐segment elevation myocardial infarction and focusing on short‐term mortality.
70-kDa Heat Shock Protein Downregulates Dynamin in Experimental Stroke
Authors: Kim Jong Youl , Kim Nuri , Zheng Zhen , Lee Jong Eun , Yenari Midori A.
Published: July 2016

Background and Purpose—

The 70-kDa heat shock protein (Hsp70) protects brain cells in models of cerebral ischemia. Proteomic screening of mice subjected to middle cerebral artery occlusion identified dynamin as a major downregulated protein in Hsp70-overexpressing mice (Hsp70 transgenic mice). Dynamin-1 is expressed in neurons and participates in neurotransmission, but also transports the death receptor Fas to the cell surface, where it can be bound by its ligand and lead to apoptosis.

Methods—

Mice were subjected to distal middle cerebral artery occlusion. Neuro-2a cells were subjected to oxygen glucose deprivation. Hsp70 transgenic and Hsp70-deficient (Hsp70 knockout) mice were compared with wild-type mice for histological and behavioral outcomes. Some mice and neuro-2a cell cultures were given dynasore, a dynamin inhibitor.

Results—

Hsp70 transgenic mice had better outcomes, whereas Hsp70 knockout mice had worse outcomes compared with wild-type mice. This correlated with decreased and increased dynamin expression, respectively. Dynamin colocalized to neurons and Fas, with higher Fas levels and increased caspase-8 expression. Hsp70 induction in neuro-2a cells was protected from oxygen glucose deprivation, while downregulating dynamin and Fas expression. Further, dynamin inhibition was found to be neuroprotective.

Conclusions—

Dynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking. Dynamin should be explored as a new therapeutic target for neuroprotection.
The Geometry of Plasticity-Induced Sensitization in Isoinhibitory Rate Motifs
Authors: Kumar Gautam , Ching ShiNung
Published: July 2016

A well-known phenomenon in sensory perception is desensitization, wherein behavioral responses to persistent stimuli become attenuated over time. In this letter, our focus is on studying mechanisms through which desensitization may be mediated at the network level and, specifically, how sensitivity changes arise as a function of long-term plasticity. Our principal object of study is a generic isoinhibitory motif: a small excitatory-inhibitory network with recurrent inhibition. Such a motif is of interest due to its overrepresentation in laminar sensory network architectures. Here, we introduce a sensitivity analysis derived from control theory in which we characterize the fixed-energy reachable set of the motif. This set describes the regions of the phase-space that are more easily (in terms of stimulus energy) accessed, thus providing a holistic assessment of sensitivity. We specifically focus on how the geometry of this set changes due to repetitive application of a persistent stimulus. We find that for certain motif dynamics, this geometry contracts along the stimulus orientation while expanding in orthogonal directions. In other words, the motif not only desensitizes to the persistent input, but heightens its responsiveness (sensitizes) to those that are orthogonal. We develop a perturbation analysis that links this sensitization to both plasticity-induced changes in synaptic weights and the intrinsic dynamics of the network, highlighting that the effect is not purely due to weight-dependent disinhibition. Instead, this effect depends on the relative neuronal time constants and the consequent stimulus-induced drift that arises in the motif phase-space. For tightly distributed (but random) parameter ranges, sensitization is quite generic and manifests in larger recurrent E-I networks within which the motif is embedded.
Taxonomic review of the genus Isometopus (Hemiptera: Miridae: Isometopinae) from the Korean Peninsula, with description of a new species
Authors: KIM JUNGGON , JUNG SUNGHOON
Published: July 2016

The genus Isometopus is reviewed from the Korean Peninsula with a new species: I. jejuensis sp. nov. I. japonicus Hasegawa, 1946 is also reported from South Korea for the first time. Genital structures of male and female of I. japonicus are illustrated and described for the first time. Last instar of I. japonicas is also described. Biological notes such as host plants and morphological characters are provided with the photographs and illustrations. A key to the Korean Isometopus species is also provided.
Obesity Stigma and Negative Perceptions of Political Leadership Competence
Authors: Bresnahan Mary , Zhuang Jie , Zhu Yi , Anderson Jennifer , Nelson Joshua
Published: July 2016

This study investigated whether the leadership competence of an overweight candidate is affected by exposure to weight-stigmatizing and nonstigmatizing messages. Participants read one of four messages—a weight stigma, a health stigma, a competence, or a stigma-reducing message. Fat phobia, weight controllability, partisanship, political activism, and voting behaviors were also measured. Weight controllability bias interacted with the weight stigma message to produce lower evaluations of political leadership competence. Weight controllability also correlated with higher levels of fat phobia regardless of message exposure. The evidence suggests making stigmatizing comments in print/online against a candidate based on a physical characteristic like large size negatively biases public perceptions of political leadership competence. This study of negative competence evaluation directed toward a real politician confirms the findings of earlier experimental studies with fictitious fat politicians.
Emerging Patterns of Stigma Management Communication Strategies Among Burn Survivors and Relational Partners
Authors: Noltensmeyer Candy J. , Meisenbach Rebecca J.
Published: July 2016

Despite recent theorizing on stigma management relevant to interpersonal settings and health communication, few studies have considered how people make sense of and discursively manage stigma in daily interaction. Burn survivors and relational partners present a unique population of potentially stigmatized individuals. Using in-depth interviews from participants across the United States, this study used Meisenbach’s stigma management communication model to explore the stigma management experiences of both burn survivors and relational partners. Results indicated that survivors managed stigma using four patterns of strategies: Accepters, Situational Adopters, Challengers, and Dissembling Challengers. Relational partners employed a distinct fifth pattern of strategies to manage their partner’s burn stigma. Furthermore, survivors made strategic choices about stigma management strategies based on relational and contextual factors, including prior stigma exposure or compounding stigmas. Overall, these findings have implications for the practical management of stigma, advancement of the stigma management communication model, and consideration of the interpersonal context.
Market Power, Exclusive Rights, and Substitution Effects in Sports
Authors: Mills Brian M. , Winfree Jason A.
Published: July 2016

This articles argues that consumers of professional sports leagues are not always better off with more sellers because market power can be exerted in many ways. In the presence of one governing body, allowing individual firms to sell a product can be more harmful than a monopoly. Some recent antitrust lawsuits dealing with North American sports leagues have focused on collective sales through the league compared with competitive sales through teams. This paper gives examples where it is not clear that team sales are better than league sales. Furthermore, we argue that market power depends largely on fan substitution within and across leagues, including NCAA sports. We give a summary of recent research in the area of fan substitution, and suggest directions for future work on understanding substitutability and impacts on market power of professional and collegiate sports teams.
The evolution of public–private partnership in Ireland: a sustainable pathway?
Authors: Sheppard Gail , Beck Matthias
Published: July 2016

Ireland is a latecomer to public–private partnerships, having only adopted them in 1998. Prior to the credit crisis, Ireland followed the UK model, with public–private partnerships being implemented in transport, education, housing/urban regeneration and water/wastewater. Having stalled during the credit crisis, public–private partnerships have recently been reactivated with the domestic infrastructure stimulus programme. The focus of this article is on Ireland as a younger participant in public–private partnerships and the nexus between adoption patterns and the sustainability characteristics of Irish public–private partnerships. Using document analysis and exploratory interviews, the article examines the reasons for Ireland's interest in public–private partnerships, which cannot be attributed to economic rationales alone. We consider three explanations: voluntary adoption – where the UK model was closely followed as part of a domestic modernisation agenda; coercive adoption – where public–private partnership policy was forced upon public sector organisations; and institutional isomorphism – where institutional creation and change around public–private partnerships were promoted to help public sector organisations gain institutional legitimacy. We find evidence of all three patterns, with coercive adoption becoming more relevant in recent years, which is likely to adversely affect sustainability unless incentives for voluntary adoption are strengthened and institutional capacity building is boosted.

Points for practitioners

There are many reasons why public sector organisations procure via public–private partnerships, and motivations can change over time. In Ireland, public–private partnership adoption changed from being largely voluntary to increasingly coercive. Irrespective of motives, public–private partnership procurement must be underpinned by incentives and institutional enabling mechanisms, which should be strengthened to make Ireland's public–private partnership strategy sustainable.
Recovering the Liturgical Background to Christian Atonement: The Approach of James Alison and Joseph Ratzinger
Authors: Hodge Joel
Published: July 2016

This essay explores a contemporary approach to Christian atonement theology based on the liturgical background to New Testament understandings of the Cross and Resurrection. This approach offers an important way of critiquing and undermining violently sacrificial understandings of the atonement that place the emphasis for violence on God, such as penal substitutionary theories. The essay outlines this liturgical approach to atonement theology based on the work of Joseph Ratzinger and James Alison, and as it is reflected in the New Testament. A liturgical approach captures the encounter- and event-nature of the atonement as presented in the New Testament, rather than theorizing the atonement into a rigid, rational system. We argue that Alison’s identification of atonement as humans undergoing Jesus’ atoning action as forgiving victim is complemented and deepened by Ratzinger’s Christological perspective that this atoning action involves becoming part of Christ’s sacrificial way of being, on the basis of a divine initiative.
Modeling of fatigue hysteresis behavior in carbon fiber-reinforced ceramic–matrix composites under multiple loading stress levels
Authors: Li Longbiao
Published: July 2016

The fatigue hysteresis behavior in fiber-reinforced ceramic–matrix composites under multiple loading stress levels has been investigated. Based on the fatigue damage mechanism of fiber slipping relative to matrix in the interface debonded region upon unloading/reloading, the fatigue hysteresis loops models corresponding to different interface slip cases under multiple loading stress levels have been derived. The fatigue hysteresis loss energy and interface slip corresponding to single/multiple loading stress levels and different loading sequences have been investigated. The fatigue hysteresis loops of unidirectional SiC/CAS−II composite under multiple loading stress levels have been predicted.
Smart control of cotton fabric comfort by cross-linking thermo-responsive poly(2-(2-methoxyethoxy) ethoxyethyl methacrylate-co-ethylene glycol methacrylate)
Authors: Chen Yangyi , An Jie , Zhong Qi , Müller-Buschbaum Peter , Wang Jiping
Published: July 2016

The smart control of cotton fabric comfort by cross-linking thermo-responsive random copolymer is investigated. The monomers 2-(2-methoxyethoxy) ethoxyethyl methacrylate (MEO2MA) and ethylene glycol methacrylate (EGMA) with a molar ratio of 17:3 are selected to synthesize the thermo-responsive random copolymer poly(2-(2-methoxyethoxy) ethoxyethyl methacrylate- co-ethylene glycol methacrylate), abbreviated as P(MEO2MA- co-EGMA). By using citric acid as a cross-linking agent, the obtained P(MEO2MA- co-EGMA) is successfully immobilized onto cotton fabrics. Smart control is achieved from the thermo-responsive behavior of the copolymer. Cross-linked P(MEO2MA- co-EGMA) will collapse when the ambient temperature exceeds its transition temperature. Therefore, the formerly compact P(MEO2MA- co-EGMA) layer will switch to a porous structure, and the air/moisture permeability of the textiles is enhanced. As the comfort of the textiles is closely related to the air/moisture permeability, a smart control of the cotton fabric comfort can be realized. In addition, the softness of cotton fabrics with and without thermo-responsive polymers does not show a prominent change, even when the applied solution concentration is as high as 16% (wt%). On the contrary, the stiffness of the cotton fabric coated with poly( N-isopropylacrylamide) (PNIPAM) is significantly higher than the original cotton fabric, indicating that homo PNIPAM is less suitable for textiles used in daily lives. Moreover, the whiteness and mechanical properties are studied and stay unchanged after cross-linking. As a consequence, the introduction of P(MEO2MA- co-EGMA) into textiles can provide textiles with smart control of cotton comfort, and it will not influence the wearabilities of the textiles.
Feasibility Testing of the Alert for AFib Intervention
Authors: McCabe Pamela J. , Douglas Kristin Vickers , Barton Debra L. , Austin Christine , Delgado Adriana , DeVon Holli A.
Published: July 2016

Improving early detection and treatment of atrial fibrillation (AF) is critical because untreated AF is a major contributor to stroke and heart failure. We sought to generate knowledge about the feasibility of conducting a randomized controlled trial to test the effect of the Alert for AFib intervention on knowledge, attitudes, and beliefs about treatment-seeking for signs and symptoms of AF. Adults ≥65 years old (96% White) at risk for developing AF were randomized to receive the Alert for AFib intervention ( n = 40) or an attention control session ( n = 40). Feasibility goals for recruitment, participant retention, adherence, perceived satisfaction and burden, and intervention fidelity were met. From baseline to study completion, knowledge ( p = .005) and attitudes ( p < .001) about treatment-seeking improved more in the intervention group compared with the control group. Results support testing the effectiveness of the Alert for AFib intervention in a large trial.