bluuebunny/crossref_metadata_2025 huggingface dataset:
A BIM-based framework for outdoor circulation rule checking
Authors: M. Abdelmohsen Sherif
Published: January 2017

This paper introduces a BIM-based framework for outdoor circulation rule checking from a geometric modeling perspective. The paper extracts rules and patterns of circulation and interaction based on site planning standards and codes. It then identifies high-level operators and 3D low-level operations involved in applicable circulation rules, and suggest methods for implementation. Mechanisms of integration between high-level operators and low-level

operations are defined for different domains of rule checking, based on three types of datasets: 1) BIM objects in outdoor settings, including agents like pedestrians, bikes, vehicles, and other objects; 2) attributes and behavior of objects, and 3) interrelations among objects, including agent-agent or agent-object intersection conflicts, agent-agent or agent-object visual access, unobstructed access, and outdoor lighting and shading.
Experiencia docente en modelamiento urbano
Authors: Cox O. Tomás , Gurovich W. Alberto
Published: January 2017

Se presenta una experiencia docente en forma de curso semestral llevada a cabo con alumnos de 4to año de la carrera de Arquitectura en la Universidad de Chile. El curso se enfoca en metodologías de modelamiento urbano que permiten abordar fenómenos desde un enfoque de abajo hacia arriba (desde el modelamiento de las decisiones de los individuos, para luego observar cómo emergen patrones a mayor escala, a partir de la simulación), lo que permite abordar de forma explícita la complejidad de la ciudad.

En este artículo se aborda una discusión sobre la necesidad de exponer a estos modelos a los alumnos, luego se detallan los modelos utilizados (Economía Regional, Segregación, Visibilidad, Evaluación Multicriterio, entre otros), para finalizar con algunos criterios de evaluación y perspectivas

a futuro. Se concluye haciendo énfasis en la importancia de incorporar nuevas herramientas de análisis cuantitativo para respaldar decisiones, pero teniendo en cuenta que no son herramientas predictivas ni reemplazan la opinión experta.
Recurv(e)sive : la arquitectura como dispositivo de memoria
Authors: Fernández G. Alberto
Published: January 2017

Recurv(e)sive es un proyecto de investigación a través del diseño. La ciudad, como estructura artificial, tiene integrada en su desarrollo ciertas similitudes con seres vivos pero a gran escala. Estas similitudes están principalmente vinculadas a reglas de crecimiento y comportamientos que mediante la acción del tiempo generan estructuras y formas que solo podemos entender con el paso de los años. El proyecto de diseño utiliza este marco de trabajo como herramienta a ser probada en un caso de estudio, comenzando por la prueba en probetas digitales conducentes a un caso real, ejemplificado en la ciudad de Valparaíso, donde espacios entre cerros pueden ser colonizados por estas microestructuras, proponiendo una nueva tipología constructiva compatible con la complejidad existente. Lo anterior Incorpora un nuevo significado a las áreas intervenidas a modo de posible folies generativas del paisaje urbano, construidas a partir de la información oculta del tejido urbano.
Investigación consciente en el proceso proyectual: una metodología de evaluación de preexistencias
Authors: Muñoz S. Gabriela , Sánchez Mauricio
Published: January 2017

A principios de este siglo, Chile experimenta un cambio respecto a la protección de su patrimonio, la ciudadanía toma conciencia del concepto “patrimonio” y del deber como sociedad de protegerlo y el Estado requiere invertir adecuadamente los recursos dedicados a su protección. Desde la arquitectura surge la interrogante: ¿cómo abordar la intervención arquitectónica en una preexistencia de forma responsable, ética y pertinente? Intervenir debe ser una operación fundada, definida a través de un soporte histórico, técnico y arquitectónico, hacerlo consciente implica entender la pertinencia de la intervención. La elaboración de un diagnóstico y la definición de criterios de intervención asociados, permitirán el desarrollo de un proyecto consistente y eficiente, repercutiendo en la ciudad con una arquitectura coherente.
Cementerio urbano en Santiago. ¿Cómo rearquitecturizar lo no deseado? Ex Industria Manufacturera Sumar, Comuna de San Joaquín, Santiago
Authors: Marín M. Valentina
Published: January 2017

En la ciudad existen hoy verdaderas manchas urbanas conformadas por equipamientos que producto del rechazo se separan de las dinámicas propias de la ciudad. El proyecto dirige la mirada hacia el estudio de un caso particular: “el cementerio como un no deseado”, como una oportunidad de revertir la segregación a la que se ha visto sometido desde épocas pasadas, y repotenciar su valor significativo, emotivo y colectivo; asumiendo los cambios tipológicos y funcionales que enfrentan hoy las estructuras funerarias.
La Universidad y el Proyecto-País Chile. Lecturas de un relato arquitectónico
Authors: Weil P. Andrés , Weil P. Verónica
Published: January 2017

El presente es un ensayo acerca del fenómeno arquitectónico que sucede en La Alameda frente a la Casa Central de la Universidad de Chile. Los autores sostienen que, debido a su contenido histórico y valor simbólico, la arquitectura de ese lugar comunica las ideas y voluntades principales que han convergido en la construcción de Chile como país. La lectura comienza al contrastar una imagen antigua con el estado actual del sector y preguntarse por los motivos de los cambios.
Conexión MiesSANAA. Sobre la intervención de Sanaa en el Pabellón de Barcelona de Mies.
Authors: Muñoz Carabias Francisco
Published: January 2017

Al margen del juego de palabras del título, la influencia de Mies en SANAA es evidente tanto en el reconocimiento de los propios arquitectos como por los últimos estudios que los vinculan. Ahondado en esta “conexión”, un ejemplo significativo es la intervención que Kazuyo Sejima + Ryue Nishizawa realizaron en el Pabellón de Barcelona a finales del año 2011. Introdujeron un muro curvo transparente de material acrílico que “casi” sin alterar el conjunto envolvía el muro de ónice de la “sala del trono”. Un gesto primario, la materialización de un recorrido, una espiral “topológica” que señalaba un centro que paradójicamente se disuelve a causa de los múltiples reflejos que la intervención provoca. Resultado: SANAA introduce un laberinto dentro de otro laberinto, desjerarquización, isotropía, y en definitiva, la “materialización” de una simetría continua, entendida esta, como principio de equivalencia en la estructura interna del espacio-tiempo según Noether. Un manifiesto iniciático que revela las intenciones futuras de los auténticos herederos de Mies. La intervención en el Pabellón alemán se convierte así en una ofrenda sobre el “altar disuelto” de lo que representa el templo de la arquitectura moderna.
Una reflexión desde los espacios públicos a la creación colectiva del espacio.
Authors: Andersen Cirera Karen
Published: January 2017

Este artículo es una reflexión sobre las motivaciones de los ciudadanos para actuar colectivamente sobre sus espacios de vida, a partir de la hipótesis de una carencia en la planificación de la ciudad para considerar las experiencias sensibles de los habitantes. Así, la falta de integración del habitante al proceso de construcción de ciudad, experiencias de vida urbana negativas, o el descontento vinculado a la invisibilidad de algunos problemas, podrían motivar a la creación espontánea de un espacio público de resistencia. La particularidad de este tipo de movimientos urbanos es la diversidad de las experiencias subjetivas que surgen de la vida urbana. Los medios de resistencia utilizados no son siempre estrategias intencionadas, a veces se trata de actos de resistencia espontáneos y creativos que cambian los órdenes establecidos. Sin embargo, los actos más intencionados como la auto-construcción también actúan como formas para desviar los órdenes dominantes de la acción urbana.
Espacios Públicos en la ciudad de Montevideo. Una mirada sobre su resignificado.
Authors: Alfonso González Fabian , Martín Rosa Juan
Published: January 2017

La evolución de las ciudades en los últimos tiempos ha llevado al desarrollo de las grandes urbes metropolitanas caracterizadas por los flujos vehiculares, grandes superficies destinadas a la producción, el consumo y el trabajo, enormes centros comerciales y sectorización de las zonas de residencia según el nivel socioeconómico. Estas pautas impactaron de tal manera que las ciudades se han fragmentado y han llevado a la casi extinción del espacio público. En contrapartida, aparecen en escena una serie de proyectos que apuntan a la inclusión, promueven la participación ciudadana, otorgan lugar a los relegados socialmente e intenta tender “puentes” en una ciudad claramente fragmentada. El presente trabajo toma 3 casos en la ciudad de Montevideo como lo son: la Plaza Liber Seregni, la Plaza Marconi y el Parque de la Amistad, como ejemplos de una metodología de intervención que ha cambiado y adaptado el significado del espacio público.
Reviewer Acknowledgements for International Business Research, Vol. 9, No. 4
Authors: Duran Kevin
Published: January 2017

International Business Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.Reviewers for Volume 9, Number 4Ahmad Shukri YazidAmaresh DasAmran AwangAndroniki KavouraAnna Paola MicheliArash RiasiFrancesco ScaleraHanna TrojanowskaIwona Gorzeń-MitkaJyoti SharmaKaren GulliverManuela Rozalia GaborMarcelino José JorgeMihaela SimionescuMiriam JankalováMohsen Malekalketab KhiabaniMonica Maria CorosMuhammad Ishtiaq IshaqPhilippe Van CauwenbergeRadoslav JankalRaphael DornierRoxanne StevensSam OkoroafoSumathisri BhoopalanTamizhjyothi KailasamUmayal Kasi  Kevin DuranOn behalf of,The Editorial Board of International Business ResearchCanadian Center of Science and Education
Reviewer Acknowledgements for International Business Research, Vol. 9, No. 7
Authors: Duran Kevin
Published: January 2017

International Business Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.Reviewers for Volume 9, Number 7 Giuseppe RussoKaren GulliverManlio Del GiudiceManuela Rozalia GaborMaria-Madela AbrudanMichaela Schaffhauser-LinzattiRosa LombardiRoxanne Helm StevensUmayal Kasi   Kevin DuranOn behalf of,The Editorial Board of International Business ResearchCanadian Center of Science and Education
Genetic Diversity of Remaining Populations of Mangaba (Hancornia speciosa Gomes) in Restingas of Brazil
Authors: Silva Ana Veruska Cruz da , Amorim Julie Anne Espíndola , Melo Marília Freitas de Vasconcelos , Ledo Ana Da Silva , Rabbani Allivia Rouse Carregosa
Published: January 2017

Mangaba (Hancornia speciosa Gomes) is a fruit species that is native to Brazil, and has social, economic and cultural importance. Knowledge of the genetic relationships between the remaining populations is essential in order to promote conservation strategies for these genetic resources. In the present study, it was evaluated the genetic diversity of 35 individuals from three remaining restingas areas in the states of Ceará (Iguape and Cascavel) and Pernambuco (Tamandaré), located in the Brazilian Northeast. Nine ISSR primers were used to determine the genetic variability. Sixty-one fully polymorphic fragments (100%) were generated. The largest (10) and smallest (5) number of fragments were obtained with the primers HB14 and HB12, respectively. The Shannon index (I = 0.40), the genetic diversity (H = 0.30), and the percentage of polymorphic loci (%P = 73.77%) were also estimated. Both the methods of UPGMA and the Principal Coordinates Analysis (PCoA) clustered individuals according to their place of origin. Genetic divergence was greater within population (64%) than between them (36%). This may indicate a strong genetic structure, i.e., the gene flow rate between populations is low, favoring inbreeding. ISSR markers were efficient for the analysis of genetic diversity, for the identification of clusters, and for the estimation of the genetic distance between and within populations.
Effort, Ability, or Difficulties? Parents’ and Teachers’ Explanations of the Malleability of Children’s Competences
Authors: Rautiainen Riitta , Raty Hannu , Kasanen Kati
Published: January 2017

This study set out to examine parents’ and teachers’ explanations of the malleability of children’s competences. Parents and teachers were asked in which aspect of schoolwork the child could improve his/her competence most and to explain why. The participants were parents and teachers of third- and sixth-grade boys and girls (n=97). The parents and teachers were found to refer to the amount of effort, motivation, and ability in their explanations of the malleability of children’s competences. The explanations concerning ability divided into those in which the child was seen as possessing ability and those in which the child was seen as lacking ability or having difficulties that prevented her/him from succeeding. The teachers perceived sixth-graders as needing more effort and motivation than third-graders did, and girls as somewhat more competent and motivated than boys. The teachers also seemed to explain children’s potential for improvement in more complex ways than the parents did.
Vida e morte na atenção primária à saúde: reflexões sobre a vivência do médico de família e comunidade ante a finitude da vida
Authors: Vieira Renata Regina , Robortella Amália Rocha , Brólio de Souza Amanda , Kerr Gustavo Shikanai , Camargo de Oliveira Janaine Aline
Published: January 2017

A Atenção Primária à Saúde (APS) possui capacidade para contribuir para que o cuidado ao final da vida seja sistêmico, humanizado e promotor de autonomia. Contudo, prestar assistência em cuidados paliativos requer da equipe um olhar complexo e multidimensional, sobretudo pela proximidade com reflexões sobre morte, perspectivas existenciais, sociais, religiosas e pessoais. Desse modo, perguntas sobre como lidar com as dimensões subjetivas de pacientes, familiares e profissionais surgem como desafio na prática clínica. Sob a perspectiva dos médicos assistentes, relatamos caso de paciente em cuidados paliativos acompanhado por uma equipe de estratégia saúde da família. Ao refletir sobre a dimensão pessoal e existencial dos profissionais, discutimos fatores que favorecem ou dificultam a assistência integral em cuidados paliativos na APS. Observamos que, apesar do desafio da assistência em termos de recursos e tempo, o diálogo na equipe e a abordagem biopsicossocial-espiritual permitiram a ressignificação do processo de cuidado, adoecimento e morte.
On the stability of ADI methods
Authors: Østerby Ole
Published: January 2017

When solving parabolic equations in two space dimensions implicit methods are preferred to the explicit method because of their better stability properties. Straightforward implementation of implicit methods require time-consuming solution of large systems of linear equations, and ADI methods are preferred instead. We expect the ADI methods to inherit the stability properties of the implicit methods they are derived from, and we demonstrate that this is partly true. The Douglas-Rachford and Peaceman-Rachford methods are absolutely stable in the sense that their growth factors are ≤ 1 in absolute value. Near jump discontinuities, however, there are differences w.r.t. how the ADI methods react to the situation: do they produce oscillations and how effectively do they damp them. We demonstrate the behaviour on two simple examples.
« Comme bouillabaisse, cela en est une bonne, M. le Président ». Les responsables politiques québécois, les relations internationales et la race (1960-1971)
Authors: Brousseau Desaulniers Antoine
Published: January 2017

L’historiographie donne à la France un rôle souvent central, parfois disproportionné à l’essor des relations internationales du Québec au cours des années 1960. L’objectif de cette étude n’est pas de remettre en cause l’importance du rapport France-Québec, mais simplement de porter le regard ailleurs, particulièrement vers les pays du tiers-monde dans le contexte des premières tentatives d’institutionnalisation de la Francophonie. Nous cherchons avant tout à explorer le rapport des responsables politiques québécois à ces pays, afin de découvrir les tenants et aboutissants des conceptions de l’Autre africain. Si les échanges diplomatiques entre le Québec, le Canada et l’Afrique francophone ont été détaillés, la question raciale reste toujours invisible.
La campagne référendaire de 1995 : un discours racialisé
Authors: Bellefeuille Carol-Ann
Published: January 2017

Lors du référendum sur l’indépendance du Québec de 1995, les souverainistes et les fédéralistes défendaient des projets nationaux que l’on affirmait distincts. Pourtant, chacune des options a construit une rhétorique mobilisant un vocabulaire et des arguments racialisés et promouvait une conception ségréguée de l’ordre international. Cet article propose une analyse nouvelle du discours référendaire dans le but d’identifier la racialisation qui teintait alors les idéaux identitaires, libéraux et nationalistes des camps du OUI et du NON.
Mach–Zehnder wavelength selective switch embedded with microring resonators
Authors: Miura Kengo , Shoji Yuya , Mizumoto Tetsuya
Published: January 2017

A wavelength selective switch is proposed for optical wavelength division multiplexing network applications with very short range interconnections. The proposed device uses a Mach–Zehnder interferometer configuration incorporating wavelength selective phase shifters composed of microring resonators between their two arms. Wavelength selectivity is provided by cascaded microring resonators, which are placed in proximity so that the increase in excess loss caused by the difference in resonant wavelengths can be minimized. An on/off switching ratio >20 dB is obtainable when the drop/through transmittance ratio of the cascaded microring resonators is >22 dB and the coupling efficiency deviation from 50% is <1% in the directional couplers constructing the Mach–Zehnder interferometer.
Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals
Authors: Sulyok Mihály , Ferenci Tamás , Makara Mihály , Horváth Gábor , Szlávik János , Rupnik Zsófia , Kormos Luca , Gerlei Zsuzsanna , Sulyok Zita , Vályi-Nagy István
Published: January 2017

Background

Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake.

Methods

We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness.

Results

Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated.

Discussion

Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.
Mental Health Service Use in a Sample of Gay, Bisexual, and other Men who have Sex with Men Living in Middlesex County, Ontario, Canada: An Exploratory Analysis
Authors: Coleman Todd A. , Bauer Greta R. , Aykroyd Gloria , Powell Leanne , Pugh Daniel
Published: January 2017

Risks of mental health issues (e.g., depression, anxiety/mood disorders, and suicidality) are found to be elevated among Canadian gay, bisexual, and men who have sex with men (GB-MSM). We studied factors impacting mental health care use in a community sample of 202 GB-MSM in London-Middlesex, Ontario. Our results show that, for the entire sample, experiences of both homophobia and internalized homonegativity are associated with increased prevalence of mental health service use over the past year, and suggest that service use is lower among immigrant GB-MSM than among those born in Canada. Implications for mental health and social service providers are discussed.
Influence of Visceral Fat on Early Postoperative Outcomes After Distal and Total Gastrectomy for Gastric Cancer
Authors: Shibata Chikashi , Ogawa Hitoshi , Koyama Kaori , Mukouda Kazuaki , Iwasashi Hajime , Araki Takaaki , Kimura Shunichi , Nakajima Natsuki
Published: January 2017

We studied the influence of visceral fat area (VFA) on early postoperative outcomes separately after distal and total gastrectomy. The influence of obesity on outcomes might differ between distal and total gastrectomy, but few studies have directly compared the effects of VFA on early postoperative results between these 2 procedures. We reviewed clinical records of 124 patients with gastric cancer undergoing curative distal or total gastrectomy. Patients were classified into 2 groups: low (<100 cm2) or high (≥100 cm2) VFA. Patient characteristics and early postoperative outcomes were compared between 2 groups separately in distal or total gastrectomy. There were 77 and 47 patients who underwent distal and total gastrectomy, respectively. After distal gastrectomy, operation time (268 ± 44 versus 239 ± 39 minutes, P < 0.05) as well as blood loss (351 ± 231 versus 239 ± 147 mL, P < 0.05) was increased in the high VFA group (N = 32) compared to the low VFA group (N = 45), but morbidity rates did not differ between the 2 groups (50% versus 36%). After total gastrectomy; operation time (285 ± 42 versus 260 ± 53 minutes, P < 0.05); blood loss (427 ± 326 versus 280 ± 179 mL, P < 0.05); rate of morbidity (56% versus 24%, P < 0.05); and intra-abdominal infection (17% versus 0%, P < 0.05) were increased in the high VFA group (N = 18) compared to the low VFA group (N = 29). These results suggest that postoperative morbidity increases after total gastrectomy but not after distal gastrectomy in patients with excessive visceral fat.
Upwelling and primary production during the U.S. GEOTRACES East Pacific Zonal Transect
Authors: Kadko David
Published: January 2017

The 2013 U.S. GEOTRACES Eastern Pacific Zonal Transect (EPZT) traversed the highly productive Peruvian coastal upwelling (PCU) region. In this work, the flux of nitrate into the euphotic zone is derived for stations within the PCU using a previously developed method whereby dilution of the water column 7Be inventory by upwelled 7Be‐free water provides a means to infer upwelling rates. Furthermore, with knowledge of upwelling rates, 7Be profiles are used to constrain vertical diffusivity within the upper thermocline. These transport terms are applied to nitrate profiles to estimate net community production between 79°W and 104°W along the EPZT, which includes the zone of active upwelling to the edge of the oligotrophic gyre. With a simple, one‐dimensional model, the calculated upwelling rates were inversely related to mixed layer temperature and ranged from 0 to 3.0 m/d. Results using a depth‐dependent upwelling rate with a component of horizontal advection are also described. Vertical diffusivities near the base of the euphotic zone were in the range 1.7–4.5 × 10−4 m2/s. These values are compared to those generated by analysis of temperature profiles. Net community production averaged 15 mmol C/m2/d for stations between 84°W and 104°W and was 134 mmol C/m2/d for the furthest inshore station at 79°W which displayed the lowest SST and greatest rate of upwelling.
Microtubule‐associated protein 1B: Novel paraneoplastic biomarker
Authors: Gadoth Avi , Kryzer Thomas J. , Fryer Jim , McKeon Andrew , Lennon Vanda A. , Pittock Sean J.
Published: January 2017

Objective

To report the identification of microtubule‐associated protein (MAP) 1B as the antigen of the previously described Purkinje cell cytoplasmic antibody type 2 (PCA‐2) antibody, its frequency, and clinical, oncological, and serological associations.

Methods

Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA‐2‐IgG–seropositive patients identified during 1993–2016. The autoantigen, defined in mouse brain lysate by Western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies. The major antigenic region was defined by Western blot using recombinant protein fragments.

Results

IgG in 95 of 96 patients’ serum or CSF (but in none of 98 healthy or disease control subjects’ serum specimens) bound to recombinant MAP1B. A minority (17.5%) of patients’ IgG also bound to MAP1A. PCA‐2 was often accompanied by additional neural autoantibody markers of small‐cell carcinoma, including collapsin response‐mediated protein 5 (CRMP5) IgG (26%) or antineuronal nuclear antibody type 1 (ANNA‐1) IgG (also known as anti‐Hu; 13%). Neurological manifestations in 95 patients were (in decreasing frequency): peripheral neuropathy, 53%; cerebellar ataxia, dysmetria, or dysarthria, 38%; and encephalopathy, 27%. Cancer (majority small‐cell lung carcinoma [SCLC]) was detected in 66 of 84 evaluated patients (79%). The MAP1B (PCA‐2) autoantibody detection rate, among approximately 70,000 patients undergoing service neural autoantibody evaluation in 2015, was 0.024%, equaling amphiphysin IgG (0.026%) and more common than ANNA‐2 (also known as anti‐Ri; 0.016%) and PCA‐Tr (also known as delta/notch‐like epidermal growth factor‐related receptor [DNER]; 0.006%).

Interpretation

MAP1B, the PCA‐2 autoantigen, represents a novel target in paraneoplastic neurological disorders and has high predictive value for SCLC. Its relatively high prevalence, compared with other recognized paraneoplastic neural autoantibodies, justifies its testing in comprehensive paraneoplastic neural autoantibody evaluation. Ann Neurol 2017;81:266–277
Total Synthesis of (−)‐Tetrodotoxin and 11‐norTTX‐6(R)‐ol
Authors: Maehara Tomoaki , Motoyama Keisuke , Toma Tatsuya , Yokoshima Satoshi , Fukuyama Tohru
Published: January 2017

The enantioselective total synthesis of (−)‐tetrodotoxin [(−)‐TTX] and 4,9‐anhydrotetrodotoxin, which are selective blockers of voltage‐gated sodium channels, was accomplished from the commercially available p‐benzoquinone. This synthesis was based on efficient stereocontrol of the six contiguous stereogenic centers on the core cyclohexane ring through Ogasawara's method, [3,3]‐sigmatropic rearrangement of an allylic cyanate, and intramolecular 1,3‐dipolar cycloaddition of a nitrile oxide. Our synthetic route was applied to the synthesis of the tetrodotoxin congeners 11‐norTTX‐6(R)‐ol and 4,9‐anhydro‐11‐norTTX‐6(R)‐ol through late‐stage modification of the common intermediate. Neutral deprotection at the final step enabled easy purification of tetrodotoxin and 11‐norTTX‐6(R)‐ol without competing dehydration to their 4,9‐anhydro forms.
Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus
Authors: Comte Denis , Karampetsou Maria P. , Yoshida Nobuya , Kis‐Toth Katalin , Kyttaris Vasileios C. , Tsokos George C.
Published: January 2017

Objective

Effector CD8+ T cell function is impaired in systemic lupus erythematosus (SLE) and is associated with a compromised ability to fight infections. Signaling lymphocytic activation molecule family member 7 (SLAMF7) engagement has been shown to enhance natural killer cell degranulation. This study was undertaken to characterize the expression and function of SLAMF7 on CD8+ T cell subsets isolated from the peripheral blood of SLE patients and healthy subjects.

Methods

CD8+ T cell subset distribution, SLAMF7 expression, and expression of cytolytic enzymes (perforin, granzyme A [GzmA], and GzmB) on cells isolated from SLE patients and healthy controls were analyzed by flow cytometry. CD107a expression and interferon‐γ (IFNγ) production in response to viral antigenic stimulation in the presence or absence of an anti‐SLAMF7 antibody were assessed by flow cytometry. Antiviral cytotoxic activity in response to SLAMF7 engagement was determined using a flow cytometry–based assay.

Results

The distribution of CD8+ T cell subsets was altered in the peripheral blood of SLE patients, with a decreased effector cell subpopulation. Memory CD8+ T cells from SLE patients displayed decreased amounts of SLAMF7, a surface receptor that characterizes effector CD8+ T cells. Ligation of SLAMF7 increased CD8+ T cell degranulation capacity and the percentage of IFNγ‐producing cells in response to antigen challenge in SLE patients and healthy controls. Moreover, SLAMF7 engagement promoted cytotoxic lysis of target cells in response to stimulation with viral antigens.

Conclusion

CD8+ T cell activation in response to viral antigens is defective in SLE patients. Activation of SLAMF7 through a specific monoclonal antibody restores CD8+ T cell antiviral effector function to normal levels and thus represents a potential therapeutic option in SLE.
Distributed Three‐Dimensional Formation Containment Control of Multiple Unmanned Aerial Vehicle Systems
Authors: Han Tao , Chi Ming , Guan Zhi‐Hong , Hu Bin , Xiao Jiang‐Wen , Huang Yuehua
Published: January 2017

This paper concentrates the distributed formation containment problems for multiple unmanned aerial vehicle (UAV) systems under both fixed directed and switching directed topologies. The objective is to introduce the formation control into the containment control research, where master UAVs should exchange information with each other to achieve and maintain a desired formation. Then, two different control protocols are proposed for the master UAVs and slave UAVs, respectively. Utilizing the algebraic graph theory and stability theory, some sufficient conditions are derived to guarantee the master UAVs complete a prespecified formation, while the states of the slave UAVs converge to a convex hull formed by those of the master UAVs. Finally, some numerical simulations are provided to verify the effectiveness of the theoretical results.
Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival
Authors: Faluyi Olusola O. , Eng Lawson , Qiu Xin , Che Jiahua , Zhang Qihuang , Cheng Dangxiao , Ying Nanjiao , Tse Alvina , Kuang Qin , Dodbiba Lorin , Renouf Daniel J. , Marsh Sharon , Savas Sevtap , Mackay Helen J. , Knox Jennifer J. , Darling Gail E. , Wong Rebecca K. S. , Xu Wei , Azad Abul Kalam , Liu Geoffrey
Published: January 2017

Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri‐miRNA, 7 pre‐miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression‐free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04–1.80]; P = 0.02), hsa‐mir‐124‐1 rs531564 (aHR = 0.60, 95% CI: [0.53–0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28–0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03–1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01–1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa‐mir‐124‐1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa‐mir‐124‐1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.
Recent Development of the Second and Third Generation Irreversible Epidermal Growth Factor Receptor Inhibitors
Authors: Han Weiwei , Du Yongli
Published: January 2017

Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non‐small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP. However, patients who were treated with the erlotinib and gefitinib will relapse because of the emergence of drug‐resistant mutations, with T790M mutations accounting for approximately 60% of all resistance. In order to overcome drug resistance, Pharmaceutical chemistry experts recently devoted great endeavors to the development of second‐generation irreversible selective inhibitors which covalently modify Cys797 or Cys773 at the ATP binding cleft. Nevertheless, these inhibitors have not reached ideal effect of experts in patients with T790M positive mutation and apparently because of the dose‐limiting toxicities associated with inhibition of wild type EGFR. A novel class of ‘third generation’ EGFR TKIs have been developed that is sensitising and T790M mutant‐specific whilst sparing WT EGFR, representing a significant breakthrough in the treatment in NSCLC patients with acquired resistance harboring these genotypes. Herein, we provides an overview of the second and third generation inhibitors currently approved, in clinical trial and also encompasses novel structures of discovery. This review mainly focuses on drug resistance, their mechanisms of action, development of structure–activity relationships and binding modes.
In Situ XRD Study on Promotional Effect of Potassium on Carburization of Spray‐dried Precipitated Fe2O3 Catalysts
Authors: Niu Liwei , Liu Xingwu , Liu Xi , Lv Zhengang , Zhang Chenghua , Wen Xiaodong , Yang Yong , Li Yongwang , Xu Jian
Published: January 2017

A study of the promotional effect of potassium on the carburization behavior of a series of spray‐dried precipitated Fe2O3 catalysts (100 Fe, 100 Fe/0.52 K, 100 Fe/1.54 K, and 100 Fe/2.4 K) has been performed by using in situ XRD. The average crystallite size evolution for species such as α‐Fe2O3, Fe3O4, χ‐Fe5C2, and θ‐Fe3C were followed. The potassium promoter clearly inhibits the reduction of α‐Fe2O3 to Fe3O4, where the decreasing binding energy in the Fe 2p3/2, O 1s and K 2p3/2 spectra from X‐ray photoelectron spectroscopy (XPS) suggests an electron density increase in Fe and O upon potassium promotion, leading to the enhanced covalency in the Fe−O bond. In terms of crystallite size during carburization, an optimum potassium loading exists in catalyst 100 Fe/0.52 K, which shows the fastest reduction to Fe3O4 with minimum crystallite sizes of around 7 to 15 nm. Potassium has no clear effect in determining the final crystallite size of χ‐Fe5C2. An arch‐shaped curve in the evolution of crystallite size of the Fe3O4 intermediate was observed, which can be explained by the activation energy difference between the bidirectional steps of the outward oxygen diffusion and the inward carbon diffusion.
Sample‐wise spectral multivariate calibration desensitized to new artifacts relative to the calibration data using a residual penalty
Authors: Kalivas John H. , Brownfield Brett , Karki Bibek J.
Published: January 2017

Calibration maintenance is an important aspect of multivariate calibration. With spectral measurements, the goal of calibration maintenance involves sustaining the predictability of a primary calibration model in new secondary conditions. Among the many methodologies, penalty‐based Tikhonov regularization variants have been successful by sample augmenting primary calibration data with a matrix of just a few secondary samples as well as operating with an additional sparse penalty to include wavelength selection. Studied in this paper is a new sample‐wise (local) Tikhonov regularization–based penalty calibration approach. Penalized is a diagonal matrix with the residual vector (relative to the primary calibration space) of the new secondary sample. Thus, the same full calibration set is used for each new sample. Changing for each secondary sample is the corresponding sample‐wise residual vector on the penalized diagonal matrix. The intent of the presented approach is to form sample‐wise regression vectors desensitized to characteristics of the new sample not present in the primary calibration set. The more distinct the secondary conditions are relative to the primary conditions, the more unsuccessful this local model updating becomes. Proposed is a sample‐wise outlier mechanism to discern when the residual penalty can or cannot be used to form a useful updated model. The residual penalty modeling and outlier detection processes require tuning parameter optimizations. A fusion approach is used to automatically select tuning parameter values. Simulated and near‐infrared data are evaluated, demonstrating the applicability of the method.
Terminal Uranium(V/VI) Nitride Activation of Carbon Dioxide and Carbon Disulfide: Factors Governing Diverse and Well‐Defined Cleavage and Redox Reactions
Authors: Cleaves Peter A. , Kefalidis Christos E. , Gardner Benedict M. , Tuna Floriana , McInnes Eric J. L. , Lewis William , Maron Laurent , Liddle Stephen T.
Published: January 2017

The reactivity of terminal uranium(V/VI) nitrides with CE2 (E=O, S) is presented. Well‐defined C=E cleavage followed by zero‐, one‐, and two‐electron redox events is observed. The uranium(V) nitride [U(TrenTIPS)(N)][K(B15C5)2] (1, TrenTIPS=N(CH2CH2NSiiPr3)3; B15C5=benzo‐15‐crown‐5) reacts with CO2 to give [U(TrenTIPS)(O)(NCO)][K(B15C5)2] (3), whereas the uranium(VI) nitride [U(TrenTIPS)(N)] (2) reacts with CO2 to give isolable [U(TrenTIPS)(O)(NCO)] (4); complex 4 rapidly decomposes to known [U(TrenTIPS)(O)] (5) with concomitant formation of N2 and CO proposed, with the latter trapped as a vanadocene adduct. In contrast, 1 reacts with CS2 to give [U(TrenTIPS)(κ2‐CS3)][K(B15C5)2] (6), 2, and [K(B15C5)2][NCS] (7), whereas 2 reacts with CS2 to give [U(TrenTIPS)(NCS)] (8) and “S”, with the latter trapped as Ph3PS. Calculated reaction profiles reveal outer‐sphere reactivity for uranium(V) but inner‐sphere mechanisms for uranium(VI); despite the wide divergence of products the initial activation of CE2 follows mechanistically related pathways, providing insight into the factors of uranium oxidation state, chalcogen, and NCE groups that govern the subsequent divergent redox reactions that include common one‐electron reactions and a less‐common two‐electron redox event. Caution, we suggest, is warranted when utilising CS2 as a reactivity surrogate for CO2.
Experimental and modelling studies of MacKay River bitumen and light n‐alkane binaries
Authors: Zirrahi Mohsen , Hassanzadeh Hassan , Abedi Jalal
Published: January 2017

Solubility of light n‐alkanes in bitumen as well as density and viscosity of the bitumen‐rich phase are the necessary data for simulation and study of the solvent‐aided thermal recovery processes of bitumen. This paper presents experimental data for MacKay River bitumen with n‐alkane solvents (methane, ethane, propane, and butane). The viscosity and density of the solvent saturated bitumen phase are measured to determine the effect of solvent dissolution on the thermo‐physical properties of bitumen. The solvent‐bitumen system is modelled using the Peng‐Robinson equation of state (PR‐EoS). Moreover, experimental viscosity and density data of solvent‐saturated bitumen are correlated. The effective density and viscosity of the dissolved solvent molecules are obtained using the experimental density and viscosity data for the bitumen‐solvent system.
Long‐term outcome following remote ischemic postconditioning during percutaneous coronary interventions—the RIP‐PCI trial long‐term follow‐up
Authors: Lavi Shahar , Abu‐Romeh Nour , Wall Sabrina , Alemayehu Mistre , Lavi Ronit
Published: January 2017

The clinical value of ischemic conditioning during percutaneous coronary intervention (PCI) and mode of administration is controversial. Our aim was to assess the long‐term effect of remote ischemic postconditioning among patients undergoing PCI. We randomized 360 patients undergoing PCI who presented with a negative troponin T at baseline into 3 groups: 2 groups received remote ischemic postconditioning (with ischemia applied to the arm in 1 group and to the thigh in the other group), and the third group acted as a control group. Remote ischemic postconditioning was applied during PCI immediately following stent deployment, by 3, 5‐minute cycles of blood pressure cuff inflation to >200 mm Hg on the arm or thigh (20 mm Hg to the arm in the control), with 5‐minute breaks between each cycle. There were no differences in baseline characteristics among the 3 groups. Periprocedural myocardial injury occurred in 33% (P = 0.64). After 1 year, there was no difference between groups in death (P = 0.91), myocardial infarction (P = 0.78), or repeat revascularization (P = 0.86). During 3 years of follow‐up, there was no difference in death, myocardial infarction, and revascularization among the groups (P = 0.45). Remote ischemic postconditioning during PCI did not affect long‐term cardiovascular outcome. A similar effect was obtained when remote ischemia was induced to the upper or lower limb.

ClinicalTrials.gov Identifier: NCT00970827
A Dual‐Modal SERS/Fluorescence Gold Nanoparticle Probe for Mitochondrial Imaging
Authors: Eling Charlotte J. , Price Thomas W. , Marshall Addison R. L. , Narda Viscomi Francesco , Robinson Peter , Firth George , Adawi Ali M. , Bouillard Jean‐Sebastien G. , Stasiuk Graeme J.
Published: January 2017

A novel SERS/fluorescent multimodal imaging probe for mitochondria has been synthesised using 12 nm diameter gold nanoparticles (AuNP) surface functionalised with a rhodamine thiol derivative ligand. The normal pH‐dependent fluorescence of the rhodamine‐based ligand is inversed when it is conjugated with the AuNP and higher emission intensity is observed at basic pH. This switch correlates to a pKa at pH 6.62, which makes it an ideal candidate for a pH‐sensitive imaging probe in the biological range (pH 6.5–7.4). The observed pH sensitivity of the ligand when attached to the AuNP is thought to be due to the formation of a spirolactam ring, going from positively charged (+18 mV) to negatively charged (−60 mV) as the pH is changed from acidic to basic. Additionally, conjugation of the ligand to the AuNP serves to enhance the Raman signal of the rhodamine ligand through surface‐enhanced Raman scattering (SERS). Confocal microscopy has shown that the probe enters HEK293 (kidney), A2780 (ovarian cancer) and Min6 (pancreatic beta) cells within an hour and a half incubation time. The probe was shown to localise in the mitochondria, thus providing a novel pH‐dependent SERS/fluorescent multimodal imaging probe for mitochondria.
Drug Development, Trial Design, and Endpoints in Oncology: Adapting to Rapidly Changing Science
Authors: Blumenthal GM , Goldberg KB , Pazdur R
Published: January 2017

As a result of enhanced understanding of genetic and immunologic underpinnings of cancer, there has been progress in development of targeted and immunotherapies in oncology. The traditional linear sequential model of drug development has evolved. Early clinical trials of breakthrough therapies often include expansion cohorts, termed "seamless drug development." The US Food and Drug Administration (FDA) uses expedited programs, such as breakthrough designation and accelerated approval ensuring that transformative therapies are available to patients earlier in the cycle of evidence generation.
Directional multivariate extremes in environmental phenomena
Authors: Torres Raúl , De Michele Carlo , Laniado Henry , Lillo Rosa E.
Published: January 2017

Several environmental phenomena can be described by different correlated variables that must be considered jointly in order to be more representative of the nature of these phenomena. For such events, identification of extremes is inappropriate if it is based on marginal analysis. Extremes have usually been linked to the notion of quantile, which is an important tool to analyze risk in the univariate setting. We propose to identify multivariate extremes and analyze environmental phenomena in terms of the directional multivariate quantile, which allows us to analyze the data considering all the variables implied in the phenomena, as well as look at the data in interesting directions that can better describe an environmental catastrophe. Because there are many references in the literature that propose extremes detection based on copula models, we also generalize the copula method by introducing the directional approach. Advantages and disadvantages of the nonparametric proposal that we introduce and the copula methods are provided in the paper. We show with simulated and real data sets how by considering the first principal component direction we can improve the visualization of extremes. Finally, two cases of study are analyzed: a synthetic case of flood risk at a dam (a three‐variable case) and a real case study of sea storms (a five‐variable case).