bluuebunny/crossref_metadata_2025 huggingface dataset:
After Crisis? – The Only Way: Economics for Sustainable Development
Authors: Kostka Mestwin Stanisław
Published: January 2014

The aim of the paper is to justify why contemporary economics must be reoriented from the direction of Economic Growth to the direction of Sustainable Development. Human society is at a deadly curve. The Economic crisis is only one slice of Gordon’s Knot of Crises of our Civilization. The Economy is facing system challenges without precedence. Reasons for this situation are different fetishes of present positive and normative economics. The au­thor explores the main aspects of diagnoses, prognoses, analyses, assessments, and present solutions concerning economy. Of fundamental importance are: the essence of the global cri­sis, new challenges facing Western civilization in the near future, and fundamental misunder­standings in the proposed solutions of crucial problems. The one chance for an adequate solu­tion to the critical situation is the Strategy of Sustainable Development. In Poland this strategy is absent in mainstream economics as a theory of economy and as the foundation of rational policy. It concerns a very broad front of economic sciences and economic technologies. Eco­nomic academic education is also not adequate to the very serious situation facing graduates in the future. Consciousness, knowledge and abilities of economic professionals are good for the past, not for the nearest future. In Poland, an additional problem is a lack of common eco­nomic academic education in English. Present economics and economy must be verified with many original (not translated) settlements and conclusions concerning sustainable develop­ment from economics and from other sciences and from reality outside economy. Of crucial importance have been settlements and conclusions of ecology and of sociology on the basis of information technologies.
Aportaciones al desarrollo ecoturístico sostenible, a partir de las relaciones intersectoriales en áreas protegidas. Experiencia Parque Nacional Viñales, Cuba
Authors: Pérez Iverilys , Ramírez Pérez Jorge Freddy
Published: January 2014

En el campo de la ciencia se ha venido gestando una revolución con relación al desarrollo sostenible local; es evidente que la actividad turística brinda hoy la posibilidad de poner en práctica esta experiencia. El desarrollo local sostenible con manejo turístico, es una vía de progreso y de autogestión para las localidades, sin descartar la necesidad de la integración de los demás sectores presentes en la localidad. La gestión en las localidades pretende lograr una vinculación armónica entre las dimensiones económica, ambiental, social y cultural. Hoy el Parque Nacional Viñales, Cuba, constituye un ejemplo de desarrollo local sostenible continuado, fundamentado en el manejo de su patrimonio natural y socio cultural, logrado a través de un adecuado manejo turístico, entre sus actores, constituyendo hoy un escenario apropiado para la ejecución de actividades de planificación con plena participación de la población local. Por ello se pretende analizar el desarrollo local integral, a partir del manejo ecoturístico de un área natural, con categoría de manejo (Parque Nacional Viñales), a través de un procedimiento, basado en diferentes dimensiones, las cuales expresan la viabilidad de la actividad ecoturística sostenible en función del progreso local.
Rab5 and Rab4 Regulate Axon Elongation in theXenopusVisual System
Authors: Falk Julien , Konopacki Filip A. , Zivraj Krishna H. , Holt Christine E.
Published: January 2014

The elongation rate of axons is tightly regulated during development. Recycling of the plasma membrane is known to regulate axon extension; however, the specific molecules involved in recycling within the growth cone have not been fully characterized. Here, we investigated whether the small GTPases Rab4 and Rab5 involved in short-loop recycling regulate the extension ofXenopusretinal axons. We report that, in growth cones, Rab5 and Rab4 proteins localize to endosomes, which accumulate markers that are constitutively recycled. Fluorescence recovery after photo-bleaching experiments showed that Rab5 and Rab4 are recruited to endosomes in the growth cone, suggesting that they control recycling locally. Dynamic image analysis revealed that Rab4-positive carriers can bud off from Rab5 endosomes and move to the periphery of the growth cone, suggesting that both Rab5 and Rab4 contribute to recycling within the growth cone. Inhibition of Rab4 function with dominant-negative Rab4 or Rab4 morpholino and constitutive activation of Rab5 decreases the elongation of retinal axonsin vitroandin vivo, but, unexpectedly, does not disrupt axon pathfinding. Thus, Rab5- and Rab4-mediated control of endosome trafficking appears to be crucial for axon growth. Collectively, our results suggest that recycling from Rab5-positive endosomes via Rab4 occurs within the growth cone and thereby supports axon elongation.
Neto Auxiliary Protein Interactions Regulate Kainate and NMDA Receptor Subunit Localization at Mossy Fiber–CA3 Pyramidal Cell Synapses
Authors: Wyeth Megan S. , Pelkey Kenneth A. , Petralia Ronald S. , Salter Michael W. , McInnes Roderick R. , McBain Chris J.
Published: January 2014

Neto1 and Neto2 auxiliary subunits coassemble with NMDA receptors (NMDARs) and kainate receptors (KARs) to modulate their function. In the hippocampus, Neto1 enhances the amplitude and prolongs the kinetics of KAR-mediated currents at mossy fiber (MF)–CA3 pyramidal cell synapses. However, whether Neto1 trafficks KARs to synapses or simply alters channel properties is unresolved. Therefore, postembedding electron microscopy was performed to investigate the localization of GluK2/3 subunits at MF–CA3 synapses in Neto-null mice. Postsynaptic GluK2/3 Immunogold labeling was substantially reduced in Neto-null mice compared with wild types. Moreover, spontaneous KAR-mediated synaptic currents and metabotropic KAR signaling were absent in CA3 pyramidal cells of Neto-null mice. A similar loss of ionotropic and metabotropic KAR function was observed in Neto1, but not Neto2, single knock-out mice, specifically implicating Neto1 in regulating CA3 pyramidal cell KAR localization and function. Additional controversy pertains to the role of Neto proteins in modulating synaptic NMDARs. While Immunogold labeling for GluN2A at MF–CA3 synapses was comparable between wild-type and Neto-null mice, labeling for postsynaptic GluN2B was robustly increased in Neto-null mice. Accordingly, NMDAR-mediated currents at MF–CA3 synapses exhibited increased sensitivity to a GluN2B-selective antagonist in Neto1 knockouts relative to wild types. Thus, despite preservation of the overall MF–CA3 synaptic NMDAR-mediated current, loss of Neto1 alters NMDAR subunit composition. These results confirm that Neto protein interactions regulate synaptic localization of KAR and NMDAR subunits at MF–CA3 synapses, with implications for both ionotropic and metabotropic glutamatergic recruitment of the CA3 network.
Religious Representation in Secular Singapore
Authors: Abdullah Walid Jumblatt
Published: January 2014

This paper investigates the nature of secularism practiced by the Singapore state, focusing on the two main Islamic organizations, MUIS and Pergas. I postulate that the state uses “muscular” and “calibrated” secularism to manage them, and co-opts them either formally or informally. The two organizations agree to such an arrangement.
Rheological Characterization of Starch Gelatinization: Effects of plasticizer/starch ratio and clay content in corn-starch/glycerol thermoplastic starch (TPS)
Authors: Lara Sandra , Salcedo Felipe
Published: January 2014

This work presents a systematic rheological study of the gelatinization process of corn-starch plasticized with glycerol, showing the effects of the glycerol/starch ratio, water/starch ratio, and clay (montmorillonite) content. Gelatinization temperatures at different heating rates in rheological oscillatory temperature-sweep experiments were determined for different corn-starch/glycerol/clay formulations. The influences of the different formulation variables on the gelatinization processes and on the gel properties are analyzed. Some hypotheses postulating how the different intermolecular interactions present in the composites are responsible for these effects are discussed.
Necessidade de implantar programa nacional de seguranca do paciente no Brasil
Authors: Capucho Helaine Carneiro , Cassiani Silvia Helena De Bortoli
Published: January 2014

O objetivo do estudo foi suscitar reflexão acerca da necessidade de se criar um sistema nacional de notificações sobre incidentes como base para um programa de segurança do paciente. Incidentes em saúde acarretam danos aos pacientes e oneram o sistema de saúde. Embora tenha lançado recentemente um programa de avaliação da qualidade nas instituições de saúde, o Ministério da Saúde, Brasil, ainda não possui um programa que avalie sistematicamente os resultados negativos da assistência. Discute-se a necessidade de se implementar programa brasileiro de segurança do paciente, a fim de promover a cultura pela segurança do paciente e da qualidade em saúde no Sistema Único de Saúde.
Antivirais incorporados no Brasil para hepatite B cronica: analise de custo-efetividade
Authors: Oliveira Gustavo Laine Araujo de , Almeida Alessandra Maciel , Silva Anderson Lourenco da , Brandao Cristina Mariano Ruas , Andrade Eli Iola Gurgel , Cherchiglia Mariangela Leal , Acurcio Francisco de Assis
Published: January 2014

OBJETIVO Avaliar o custo-efetividade de diferentes tratamentos medicamentosos para hepatite B crônica entre pacientes adultos. MÉTODOS Utilizando modelo de Markov, construiu-se coorte hipotética de 40 anos para pacientes HBeAg-positivo ou HBeAg-negativo. Foram comparados os usos de adefovir, entecavir, tenofovir e lamivudina (com terapia de resgate em caso de resistência viral) para tratamento de pacientes adultos com hepatite B crônica, virgens de tratamento, com elevados níveis de alanina aminotransferase, sem evidência de cirrose e sem coinfecção por HIV. Valores para custo e efeito foram obtidos da literatura. A medida do efeito foi expressa em anos de vida ganhos (AVG). Taxa de desconto de 5% foi aplicada. Análise de sensibilidade univariada foi conduzida para avaliar incertezas do modelo. RESULTADOS O tratamento inicial com entecavir ou tenofovir apresentou melhores resultados clínicos. As menores razões custo-efetividade foram de entecavir para pacientes HBeAg-positivo (R$ 4.010,84/AVG) e lamivudina para pacientes HBeAg-negativo (R$ 6.205,08/AVG). Para pacientes HBeAg-negativo, a razão custo-efetividade incremental de entecavir (R$ 14.101,05/AVG) está abaixo do limiar recomendado pela Organização Mundial da Saúde. Análise de sensibilidade mostrou que variação nos custos dos medicamentos pode tornar tenofovir alternativa custo-efetiva tanto para pacientes HBeAg-positivo quanto para HBeAg-negativo. CONCLUSÕES Entecavir é alternativa recomendada para iniciar o tratamento de pacientes com hepatite B crônica no Brasil. Contudo, se houver redução no custo de tenofovir, esta pode se tornar alternativa mais custo-efetiva.
Identity Fusion and Status of the Evaluator as Moderators of Self-Enhancement and Self-Verification at the Group Level of Self-Description
Authors: Besta Tomasz , Kaźmierczak Maria , Błażek Magdalena
Published: January 2014

We examined the influence of identity fusion and status of evaluator on willingness to fight for one’s group after group-descriptive or not group-descriptive feedback. The valence of evaluative information was varied as well: feedback either support negative group-stereotype (negative but descriptive condition) or contradict negative group-stereotype (positive but not descriptive condition). In two studies (N=208 & N=119) we partially replicated previous findings on self-verification. Individuals fused with one’s group were more prone than non fused to fight for group members after receiving, challenging, not group-describing feedback, but only when evaluator’s status was high. When the evaluator’ status was low, fused participants (vs. non fused) engaged in self-enhancement strategies: that is they endorse radical behavior after negative, even if group-describing, feedback. We discuss the importance of identity fusion and evaluator’s status for determining when self-enhancement and self-verification will and will not be evoke.
Repetitive thought as a moderator of the impact of control deprivation on emotional and cognitive functioning
Authors: Jarmakowski-Kostrzanowski Tomasz
Published: January 2014

The present research explores the role of repetitive thought (RT) in developing control deprivation deficits. The two main RT theories lead to diverging predictions. The response style theory suggests that RT in reaction to distress leads to negative effects in terms of emotional and cognitive functioning. However, the theory of Marin and Tesser and its elaboration by Watkins, suggest that the effects of RT depend on its form and that individuals who are not depression-prone usually adopt the constructive form of RT that leads to positive effects. To test which of these predictions is true for control deprivation situation, two experimental studies were conducted. Participants after control deprivation were induced RT or distraction, followed by the measurement of their emotional and cognitive functioning. The results suggest that repetitive thought reduces both emotional and cognitive helplessness deficits and has no effect in no control deprivation condition. This supports the theory of Martin and Tesser and its elaboration by Watkins.
Dynamic Compression Plate Versus Intramedullary Interlocking Nail for Managemaent of Humeral Shaft Fractures
Authors: Chaudhary Pashupati , Karn Navin Kumar , Shrestha Bikram Prasad , Khanal Guru Prasad , Paneru Shivraj , Kalawar Rosan Prasad Sah
Published: January 2014

Introduction: With the dramatic success of intramedullary fixation for fractures of the femur and tibia, there was speculation that Intramedullary Interlocking Nails might be more appropriate for humeral shaft fractures in comparison to Dynamic Compression Plates. There are very few studies comparing these two methods of fixation in shaft of humerus fractures and virtually no study in this part of world. The aim of the study was to compare these fixation methods in terms of duration of operating time, amount of blood loss, rate of infection, pain at the fracture site, time to achieve union, functional outcome(DASH score) and complications of surgery. Methods: This was randamised control trial in which all patients with fractures of shaft of humerus that met the criteria for operative interventions ( intramedullary interlocking nailing and dynamic compression plating) presenting to the department of Orthopaedics BPKIHS during the study period and giving informed consent were included in the study. The patients were randomized using Excel random number generation technique into two groups. N Group: Cases treated with intramedullary interlocking nail and P Group: Cases treated with dynamic compression plate. Results: Most of the patients were right handed. The operating time for nailing was 100±11.24 minutess in comparision to 90.25± 15.6 minutes for humerus plating. The mean blood loss in nail group was 148.75 ±36.70 while in plate group blood loss was 205±45.60. Post operative hospital stay was similar in both groups with mean stay of 4.5 days.The peroperative radial nerve palsy was 4% in nailing group as compared to 2% in plating group. Radiologically four cortices union was only 50% in nailing group while it was 80% in plating group at 24 weeks post operatively. Dash score gradually improved in both nail and plate group but Dash score was significantly higher in plating group at 6,12,18 and 24 weeks follow up. Conclusion: Dynamic compression plating is better for fracture shaft of humerus. Plate osteosynthesis remains the gold standard of fixation for humeral shaft fractures. DOI: http://dx.doi.org/10.3126/noaj.v3i2.9513 NOAJ July-December 2013, Vol 3, Issue 2, 10-13
Detection of Adolescent Idiopathic Scoliosis among Nepalese Children Through the School Screening Program
Authors: Pokharel Rohit Kumar , Lakhey Rajesh Bahadur , Kafle Dinesh , Shah Lakahn Lall
Published: January 2014

Introduction: Idiopathic Adolescent Scoliosis (IAS) is the commonest type of scoliosis without any known cause. There has been studies in different countries and population on IAS; and its prevalence rate varies for different population. There has been no reported study done in Nepal on prevalence of adolescent idiopathic scoliosis (AIS). The aim of this study was to detect and evaluate the prevalence of idiopathic adolescent scoliosis in school children in different parts of Nepal. Methods: This was a descriptive cross sectional study conducted at five schools from different geographical parts of Nepal, from January 2010 to December 2010. Scoliosis screening was done in 5 schools from different geographical locations of Nepal. Children (from grade 6 to 10; age more than 10 years) with positive Adam’s forward bending test and scoliometer angle of 5 degrees or more were subjected for radiographic evaluation of the spine. The criterion for the diagnosis of scoliosis was detection of Cobb’s angle of more than 10 degrees. Evaluation of scoliosis according to the age, gender, ethnic group, spinal region and magnitude of curve was done. Results: Out of 1094 children screened, 31 (2.83%) were referred for radiological evaluation; and 12 of them had lateral spinal curvature of more than 10 degrees. Hence the prevalence of scoliosis was 1.09%. The girl to boy ratio of distribution of scoliosis was 3:1 for larger curves of more than 20 degrees. Maximum number of scoliosis cases was seen in girls of 13 years, and the right sided thoracic scoliosis was most common. There is no ethnic predominance of scoliosis. Conclusion: Prevalence of idiopathic scoliosis among school children who need treatment in Nepal is low; however, school screening program has its epidemiological value. DOI: http://dx.doi.org/10.3126/noaj.v3i2.9514   NOAJ July-December 2013, Vol 3, Issue 2, 14-19
Evaluating the Relationship between Pay and Research Productivity: Panel Data Evidence from Ontario Universities
Authors: Sen Anindya , Ariizumi Hideki , DeSousa Natasha
Published: January 2014

Exploiting data made available by the 1996 Ontario Public Sector Salary Disclosure Act, we construct a unique panel data set containing individual salaries of tenured and tenure-track economics professors from 16 universities in Ontario between 1996 and 2006 to evaluate the relationship between academic performance and salary. Our estimates suggest that universities reward research productivity, as a top journal publication is significantly associated with a roughly 1 percent–3 percent increase in annual salary. We interpret our results as empirical evidence of the potential importance of research productivity in determining publicly funded salaries of academics.
Development and characterization of 25 EST‐SSR markers in Pinus sylvestris var. mongolica (Pinaceae)
Authors: Fang Pan , Niu Shihui , Yuan Huwei , Li Zhexin , Zhang Yuncheng , Yuan Lu , Li Wei
Published: January 2014

• Premise of the study: A set of novel expressed sequence tag (EST) microsatellite markers was developed in Pinus sylvestris var. mongolica to promote further genetic studies in this species.

• Methods and Results: One hundred seventy‐five EST–simple sequence repeat (SSR) primers were designed and synthesized for 31,653 isotigs based on P. tabuliformis EST sequences. The primer pairs were used to identify 25 polymorphic loci in 48 individuals. The number of alleles ranged from two to eight with observed and expected heterozygosity values of 0.0435 to 0.8125 and 0.0430 to 0.7820, respectively.

• Conclusions: These new polymorphic EST‐SSR markers will be useful for assessing genetic diversity, molecular breeding and genetic improvement, and conservation of P. sylvestris var. mongolica.
Model-Driven Approaches to Service Composition
Authors: Dumez C. , Bakhouya M. , Gaber J. , Wack M.
Published: January 2014

Companies are now making their know-how and information available over the network using Web services. Business-to-Business collaboration through Web service interaction is now a necessary step to better satisfy user requests. The act of combining Web services to achieve a common goal - also known as Web service composition - is a complex issue that should be addressed. Many programming languages were developed to realize interaction between services, such as XLANG, WSFL, and BPEL. However, these languages are meant for the implementation and execution rather than providing a visual representation of the composition. In the past few years, the research community has been trying to tackle this issue by proposing model-driven approaches with the main objective to reduce development time. Some of these approaches are based on formal methods in order to describe, analyze, verify and validate the composition. In other words, applying these methods in design phase helps designers to show explicitly the behavior of Web services, to reason on the composition behavior and verify its properties. In this paper, the authors survey model-driven approaches for service composition. The focus is on surveying and classifying approaches that follow model-driven engineering principles for creating high-level models rather than programming concepts.
Best Practices for the Design and Development of Ethical Learning Video Games
Authors: McDaniel Rudy , Fiore Stephen M.
Published: January 2014

This article builds upon earlier research (McDaniel & Fiore, 2010) in which the authors presented case studies focused on the design and development of two original ethical learning video games. Through this case study and a review of relevant literature, the authors explored the content creation of, and theoretical rationale for, the design and development of ethics games. Both games were geared toward an undergraduate student audience as casual learning games to be completed in a few hours of gameplay. To update and expand this original work, the authors reviewed contemporary research on identity, cognition, and self in relation to video game environments as well as literature dealing more specifically with ethics and video games. From this literature base and their applied design experiences, the authors offer ten guidelines as best practices to follow for aspiring ethics game developers.
Responding to Hate Speech on Social Media
Authors: Pepper Molly B. , Leithauser Adriane , Loroz Peggy Sue , Steverson Brian
Published: January 2014

In the Spring of 2012, fans of the Gonzaga University basketball team used hate speech on social media site Twitter to express their frustration at losing a game to the Brigham Young University team. In response, the students in the Hate Studies in Business course started a student-led movement to “Take the Hate Out of Hoops.” The students applied their lessons in virtue ethics and leveraged the experiential structure of the course to create a positive response to a negative event. It was through the unique study of hate, the recognition that membership in a community implies responsibility for harms perpetuated by that community, and the action-oriented nature of this class that students were moved to respond to this instance of injustice. This paper describes the course, the incident of hate speech, the students’ response, and the lessons learned by the four instructors of the course.
Requirements for Personalized m-Commerce
Authors: Becker Laura , Pousttchi Key
Published: January 2014

Mobile devices are used to initiate shopping or enhance traditional shopping experiences. The integration of m-commerce with social networking sites enables marketers to provide really personalized offers to customers. The basis for that is an in-depth understanding of customers’ needs and expectations which can be analyzed on social networking sites due to their explicit and implicit presentation of the customers’ context and needs as well as due to their rising popularity. This study investigates the reasons for customers to use online social networks, using the example of Facebook. For that purpose, a structural equation model with formative constructs is developed and tested against data from young Facebook users. The authors’ results show that subjective norm might show no direct effect but, however, it has a large influence which occurs indirectly via perceived usefulness and perceived enjoyment. Additionally, the authors reveal that drivers for the usage intention of social networks show major differences between men and women.
Does a Good Fit between Mobile Work Support Functions and Mobile Sales-Force Worker Tasks Lead to Improved Work Performance?
Authors: Lembach Markus , Lane Michael
Published: January 2014

Mobile devices can improve the way sales-force work is conducted in information intensive industries such as the pharmaceutical industry. However, there is a lack of empirical research which has examined the extent to which a good fit between mobile work support functions and sales-force worker tasks and individual characteristics influences intention to use. Does a good fit translate into a perceived positive impact on sales-force worker performance? Drawing on TTF and TAM theories, an online survey was conducted with sales-force workers in the German division of a large pharmaceutical company. The findings indicate that location dependence and time criticality positively influence perceived usefulness of mobile work support functions and that this perceived fit positively influences intention to use and perceived performance impact of mobile work support functions. Furthermore, there are differences in the perceived usefulness of mobile work support functions across job roles, pharmaceutical business units and length of tenure.
Statistical Analysis based Hypothesis Testing Method in Biological Knowledge Discovery
Authors: Chowdhury Md. Naseef-Ur-Rahman , Paul Suvankar , Sultana Kazi Zakia
Published: January 2014

The correlation and interactions among different biological entities comprise the biological system. Although already revealed interactions contribute to the understanding of different existing systems, researchers face many questions everyday regarding inter-relationships among entities. Their queries have potential role in exploring new relations which may open up a new area of investigation. In this paper, we introduce a text mining based method for answering the biological queries in terms of statistical computation such that researchers can come up with new knowledge discovery. It facilitates user to submit their query in natural linguistic form which can be treated as hypothesis. Our proposed approach analyzes the hypothesis and measures the p-value of the hypothesis with respect to the existing literature. Based on the measured value, the system either accepts or rejects the hypothesis from statistical point of view. Moreover, even it does not find any direct relationship among the entities of the hypothesis, it presents a network to give an integral overview of all the entities through which the entities might be related. This is also congenial for the researchers to widen their view and thus think of new hypothesis for further investigation. It assists researcher to get a quantitative evaluation of their assumptions such that they can reach a logical conclusion and thus aids in relevant re-searches of biological knowledge discovery. The system also provides the researchers a graphical interactive interface to submit their hypothesis for assessment in a more convenient way.
Detecting super‐thin clouds with polarized sunlight
Authors: Sun Wenbo , Videen Gorden , Mishchenko Michael I.
Published: January 2014

We report a novel method for detecting cloud particles in the atmosphere. Solar radiation backscattered from clouds is studied with both satellite data and a radiative transfer model. A distinct feature is found in the angle of linear polarization of solar radiation that is backscattered from clouds. The dominant backscattered electric field from the clear‐sky Earth‐atmosphere system is nearly parallel to the Earth surface. However, when clouds are present, this electric field can rotate significantly away from the parallel direction. Model results demonstrate that this polarization feature can be used to detect super‐thin cirrus clouds having an optical depth of only ~0.06 and super‐thin liquid water clouds having an optical depth of only ~0.01. Such clouds are too thin to be sensed using any current passive satellite instruments.
Bone Erosion Is Associated With Reduction of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Rheumatoid Arthritis
Authors: Park Yune‐Jung , Kim Ji‐Young , Park Jeongmi , Choi Jin‐Jung , Kim Wan‐Uk , Cho Chul‐Soo
Published: January 2014

Objective

To identify factors influencing endothelial progenitor cell (EPC) counts in patients with rheumatoid arthritis (RA).

Methods

The number of circulating CD34+/vascular endothelial growth factor receptor 2–positive EPCs was measured in 126 RA patients and 46 non‐RA control patients. Endothelial function was assessed by brachial flow‐mediated dilation (FMD). Serum CXCL12 concentrations were determined using an enzyme‐linked immunosorbent assay. EPCs and FMD were measured at baseline and after 24 weeks of anti–tumor necrosis factor α (TNFα) therapy in 29 patients with active RA.

Results

The numbers of circulating EPCs were significantly lower in the RA patients than in the non‐RA controls. In multivariate analysis, older age, reduced levels of high‐density lipoprotein cholesterol, and higher bone erosion scores were independent risk factors for reduced EPC counts in RA patients. Serum CXCL12 levels correlated negatively with EPC counts, but positively with bone erosion scores. FMD was impaired in RA patients, and a decreased FMD in RA was closely associated with a higher bone erosion score and a reduced EPC count. In addition, EPC counts were restored by anti‐TNFα therapy, and this increase was paralleled by improvement in FMD. Interestingly, restoration of EPC counts was attenuated in patients with higher bone erosion scores than in those with lower scores, despite similar levels of improvement in disease activity.

Conclusion

The numbers of circulating EPCs in RA patients are reduced and are inversely correlated with serum levels of CXCL12. Reduced EPC counts are closely associated not only with bone erosion, but also with endothelial dysfunction.
Das neue Elefantenhaus im Zoo Zürich
Authors: Kübler Wolfram
Published: January 2014

Integriert in einen Landschaftspark soll das neue Elefantenhaus im Zoo Zürich nicht als technischer Zweckbau erscheinen. Das Schalentragwerk wurde mittels statischer Formfindung entwickelt. Die Holzkonstruktion besteht aus mehrlagigem Aufbau, damit die Materialeigenschaften Anisotropie sowie Festigkeits‐ und Steifigkeitsverhalten in Abhängigkeit vom Kraftfaserwinkel egalisiert werden und eine duktile und robuste Konstruktion entsteht. Obwohl die 271 geometrisch völlig unterschiedlichen und spitzwinkligen Oblichter mit bis zu 40 m2 Größe keine Regelmäßigkeit vermuten lassen, kann die Konstruktion auf zwei Regelschnitte reduziert werden.

The new elephant house at Zoo Zurich

Integrated into a landscape park the new elephant house at the zoo in Zurich should not appear as a technical and functional building. The shell structure was developed by means of static form‐finding. The timber structure consists of a multilayer composite structure, so that the material properties, anisotropy, strength and stiffness‐solubility behavior are leveled independent from the strength‐fiber angle and a ductile and sturdy construction is developed. Although the 271 geometrically completely different and acute‐angled skylights with up to 40 m2 size suggest any regularity, the construction can be reduced to two control sections.
Antibody performance in western blot applications is context‐dependent
Authors: Älgenäs Cajsa , Agaton Charlotta , Fagerberg Linn , Asplund Anna , Björling Lisa , Björling Erik , Kampf Caroline , Lundberg Emma , Nilsson Peter , Persson Anja , Wester Kenneth , Pontén Fredrik , Wernérus Henrik , Uhlén Mathias , Ottosson Takanen Jenny , Hober Sophia
Published: January 2014

An important concern for the use of antibodies in various applications, such as western blot (WB) or immunohistochemistry (IHC), is specificity. This calls for systematic validations using well‐designed conditions. Here, we have analyzed 13 000 antibodies using western blot with lysates from human cell lines, tissues, and plasma. Standardized stratification showed that 45% of the antibodies yielded supportive staining, and the rest either no staining (12%) or protein bands of wrong size (43%). A comparative study of WB and IHC showed that the performance of antibodies is application‐specific, although a correlation between no WB staining and weak IHC staining could be seen. To investigate the influence of protein abundance on the apparent specificity of the antibody, new WB analyses were performed for 1369 genes that gave unsupportive WBs in the initial screening using cell lysates with overexpressed full‐length proteins. Then, more than 82% of the antibodies yielded a specific band corresponding to the full‐length protein. Hence, the vast majority of the antibodies (90%) used in this study specifically recognize the target protein when present at sufficiently high levels. This demonstrates the context‐ and application‐dependence of antibody validation and emphasizes that caution is needed when annotating binding reagents as specific or cross‐reactive. WB is one of the most commonly used methods for validation of antibodies. Our data implicate that solely using one platform for antibody validation might give misleading information and therefore at least one additional method should be used to verify the achieved data.
Mechanistic Insights into the Pd‐Catalyzed Direct Amination of Allyl Alcohols: Evidence for an Outer‐Sphere Mechanism Involving a Palladium Hydride Intermediate
Authors: Sawadjoon Supaporn , Sjöberg Per J. R. , Orthaber Andreas , Matsson Olle , Samec Joseph S. M.
Published: January 2014

The mechanism of direct amination of allyl alcohol by a palladium triphenylphosphite complex has been explored. Labelling studies show that the reaction proceeds through a π‐allylpalladium intermediate. A second‐order dependence of reaction rate on allyl alcohol concentration was observed. Kinetic isotope effect studies and ESI‐MS studies are in agreement with a reaction proceeding through a palladium hydride intermediate in which both O–H bond and C–O bond cleavages are involved in rate‐determining steps. A stereochemical study supports an outer‐sphere nucleophilic attack of the π‐allylpalladium intermediate giving complete chiral transfer from starting material to product.
Synthesis of Water‐Soluble Red‐Emitting Thienyl–BODIPYs and Bovine Serum Albumin Labeling
Authors: Poirel Arnaud , Retailleau Pascal , De Nicola Antoinette , Ziessel Raymond
Published: January 2014

Thesynthesis of three red‐emitting and water‐soluble thienyl‐BODIPYs has beenachieved. The trimethyl(propargyl)ammonium group was chosen as a vector forwater solubility. One or two cationic arms were introduced either on the2‐position of the thienyl unit or on the 4‐position on the boron atom. Thesedyes have pronounced absorption around 600 nm and intense emission at 650 nmwith quantum yield of about 60% in water. Grafting of such BODIPYs via a flexible arm to BSA is veryefficient, allowing attachment of 1 to 30 labels in a controlled manner.  Very strong fluorescence (quantum yield 56%)without aggregation of the dye at a low loading ratio (1:5 BSA/label) in PBSbuffer is measured.
Identification of Low‐Molecular‐Weight Compounds Inhibiting Growth of Corynebacteria: Potential Lead Compounds for Antibiotics
Authors: Stark Jaime L. , Copeland Jennifer C. , Eletsky Alexander , Somerville Greg A. , Szyperski Thomas , Powers Robert
Published: January 2014

The bacterial genus Corynebacteria contains several pathogenic species that cause diseases such as diphtheria in humans and “cheesy gland” in goats and sheep. Thus, identifying new therapeutic targets to treat Corynebacteria infections is both medically and economically important. CG2496, a functionally uncharacterized protein from Corynebacterium glutamicum, was evaluated using an NMR ligand‐affinity screen. A total of 11 compounds from a library of 460 biologically active compounds were shown to selectively bind CG2496 in a highly conserved region of the protein. The best binder was identified to be methiothepin (KD=54±19 µM), an FDA‐approved serotonin receptor antagonist. Methiothepin was also shown to inhibit the growth of C. glutamicum, but not bacteria that lack CG2496 homologs. Our results suggest that CG2496 is a novel therapeutic target and methiothepin is a potential lead compound or structural scaffold for developing new antibiotics specifically targeting Corynebacteria.
Toward the Development of Dual‐Targeted Glyceraldehyde‐3‐phosphate Dehydrogenase/Trypanothione Reductase Inhibitors against Trypanosoma brucei and Trypanosoma cruzi
Authors: Belluti Federica , Uliassi Elisa , Veronesi Giacomo , Bergamini Christian , Kaiser Marcel , Brun Reto , Viola Angelo , Fato Romana , Michels Paul A. M. , Krauth‐Siegel R. Luise , Cavalli Andrea , Bolognesi Maria Laura
Published: January 2014

A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox–eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone–coumarin hybrids against glyceraldehyde‐3‐phosphate dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual‐target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2‐{[3‐(3‐dimethylaminopropoxy)‐2‐oxo‐2H‐chromen‐7‐yl]oxy}anthracene‐1,4‐dione (10) showed an IC50 value of 5.4 μM against TbGAPDH and a concomitant Ki value of 2.32 μM against TcTR. Notably, 2‐{4‐[6‐(2‐dimethylaminoethoxy)‐2‐oxo‐2H‐chromen‐3‐yl]phenoxy}anthracene‐1,4‐dione (compound 6) displayed a remarkable EC50 value for T. brucei parasites (0.026 μM) combined with a very low cytotoxicity toward mammalian L6 cells (7.95 μM). This promising low toxicity of compound 6 might be at least partially due to the fact that it does not interfere with human glutathione reductase.
Covalent Inhibition of the Lymphoid Tyrosine Phosphatase
Authors: Ahmed Vanessa F. , Bottini Nunzio , Barrios Amy M.
Published: January 2014

Covalent inhibitors of lymphoid tyrosine phosphatase (LYP) were identified from a screen of the NIH Molecular Libraries Small Molecules Repository (MLSMR). Both of the two lead compounds identified have phosphotyrosine‐mimetic benzoic acid moieties as well as electrophilic acrylonitrile groups. Inhibition kinetics of both compounds are consistent with covalent modification of the enzyme, with nanomolar KI and reciprocal millisecond kinact values, representing the best efficiency ratios (kinact/KI) among currently reported covalent LYP inhibitors. Covalent inhibitors can provide longer efficacy and better selectivity than more conventional noncovalent inhibitors, and these lead compounds are an important step toward the development of protein tyrosine phosphatase (PTP)‐targeted covalent therapeutic compounds.
Heart Failure Association of the European Society of Cardiology Specialist Heart Failure Curriculum
Authors: McDonagh Theresa A. , Gardner Roy S. , Lainscak Mitja , Nielsen Olav W. , Parissis John , Filippatos Gerasimos , Anker Stefan D.
Published: January 2014

It is well established that organized care of heart failure patients, including specialist management by cardiologists, improves patient outcomes. In response to this, other national training bodies (the UK and the USA) have developed heart failure subspecialty curricula within their Cardiology Training Curricula. In addition, European Society of Cardiology (ESC) subspecialty curricula exist for Interventional Cardiology and Heart Rhythm Management. The purpose of this heart failure curriculum is to provide a framework which can be used as a blueprint for training across Europe. This blueprint mirrors other ESC curricula. Each section has three components: the knowledge required, the skills which are necessary, and the professionalism (attitudes and behaviours) which should be attained. The programme is designed to last 2 years. The first year is devoted to the specialist heart failure module. The second year allows completion of the optional modules of advanced imaging, device therapy for implanters, cardiac transplantation, and mechanical circulatory support. The second year can also be devoted to continuation of specialist heart failure training and/or research for those not wishing to continue with the advanced modules.
Effect of increasing pump speed during exercise on peak oxygen uptake in heart failure patients supported with a continuous‐flow left ventricular assist device. A double‐blind randomized study
Authors: Jung Mette Holme , Hansen Peter Bo , Sander Kaare , Olsen Peter Skov , Rossing Kasper , Boesgaard Soeren , Russell Stuart D. , Gustafsson Finn
Published: January 2014

Aims

Continuous‐flow left ventricular assist device (CF‐LVAD) implantation is associated with improved quality of life, but the effect on exercise capacity is less well documented. It is uncertain whether a fixed CF‐LVAD pump speed, which allows for sufficient circulatory support at rest, remains adequate during exercise. The aim of this study was to evaluate the effects of fixed versus incremental pump speed on peak oxygen uptake (peak VO2) during a maximal exercise test.

Methods and results

In CF‐LVAD (HeartMate II) patients exercise testing measuring peak oxygen uptake (VO2) was performed on an ergometer bike twice in one day: once with fixed pump speed (testfix) and once with incremental pump speed (testinc). The order of testfix and testinc in each patient was determined by randomization. During testinc pump speed was increased from the baseline value by 400 rpm/2 min. Fourteen patients (aged 23–69 years) were included with a mean support duration of 465 ± 483 days. Baseline CF‐LVAD speed was 9357 ± 238 rpm and during testinc speed was increased by a mean of 1486 ± 775 rpm. Mean peak VO2 was significantly higher in testinc compared with testfix (15.4 ± 5.9 mL/kg/min vs. 14.1 ± 6.3 mL/kg/min; P = 0.012), corresponding to a 9.2% increase. All exercise tests (n = 28) were adequately performed with RER > 1.

Conclusion

Increasing pump speed during exercise augments peak VO2 in patients supported with CF‐LVADs. An automatic speed‐change function in future generations of CF‐LVADs might improve functional capacity.
Asymmetric Hydrovinylation and Hydrogenation with Metal Complexes of C3‐Symmetric Tris‐Binaphthyl Monophosphites
Authors: Carrilho Rui M. B. , Costa Gonçalo N. , Neves Ângela C. B. , Pereira Mariette M. , Grabulosa Arnald , Bayón J. Carles , Rocamora Mercè , Muller Guillermo
Published: January 2014

Neutral allyl–palladium complexes stabilised by bulky tris‐binaphthyl monophosphite ligands have been prepared and fully characterised in solution by NMR spectroscopy, which evidenced a dynamic equilibrium between two diastereomeric species. The new allyl–palladium phosphite complexes have been evaluated as catalytic precursors in the asymmetric hydrovinylation of styrene; they show moderate activity and good to excellent chemo‐ and enantioselectivity depending on the substituent at the ligand 2′‐binaphthyl position. Remarkably, the palladium complex bearing the ligand with an adamantyl ester substituent led to 92 % ee toward (R)‐3‐phenyl‐1‐butene, which suggests that the ester functionality might provide a secondary hemilabile interaction with the metal, thus favouring the enantioselectivity control. Rhodium(I) complexes formed in situ with the same ligands were further applied in the hydrogenation of dimethyl itaconate, but gave limited activity. The best enantioselectivity (62 %) was achieved with the same ligand that contained the adamantyl ester substituent.
Tripodal Bile Acid Architectures Based on a Triarylphosphine Oxide Core Obtained by Copper‐Catalysed [1,3]‐Dipolar Cycloaddition: Synthesis and Preliminary Aggregation Studies
Authors: Thota Bala N. S. , Savyasachi Aramballi J. , Lukashev Nikolay , Beletskaya Irina , Maitra Uday
Published: January 2014

We report the synthesis and aggregation behaviour of new water‐soluble, bile acid derived tripodal architectures based on a core derived from triphenylphosphine oxide. We employed the well‐established copper‐catalysed [1,3]‐dipolar cycloaddition (CuAAC) for the construction of these tripodal molecules. The aggregation behaviour of these molecules in aqueous media was studied by different analytical methods such as dye solubilisation, dynamic light scattering, NMR and AFM. These molecular architectures also offer an additional advantage in aiding understanding of the influence of the nature of the bile acid backbone and of the configuration at the steroid C‐3 position in these architectures; to the best of our knowledge this has not been reported in the literature. The unique gelation properties of the α‐derivatives were explained through molecular modelling studies and the mechanical behaviour of these gels was studied by rheology experiments.
Placebo Response in Binge Eating Disorder: A Pooled Analysis of 10 Clinical Trials from One Research Group
Authors: Blom Thomas J. , Mingione Carolyn J. , Guerdjikova Anna I. , Keck Paul E. , Welge Jeffrey A. , McElroy Susan L.
Published: January 2014

Objective

The aim of this study was to gain further understanding of placebo response in binge eating disorder.

Method

We pooled participant‐level data from 10 double‐blind, placebo‐controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes, change in mean weekly binge eating episodes and binge eating episodes per week.

Results

Of 234 participants receiving placebo, 89 (38%) were responders and 59 (26%) attained cessation. Placebo‐treated participants significantly reduced their binge eating. The mean (SD) binge eating episodes per week at baseline was 5.2 (3.2) and at endpoint was 2.2 (2.6). Lower baseline binge eating episode frequency and longer study participation were significantly associated with response and cessation.

Discussion

Less severe eating pathology at baseline was associated with higher placebo response and cessation rates. Future clinical trials may want to stipulate that participants exceed a threshold of illness severity, which may lead to better placebo and drug separation. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
On Mechanisms of Dynamic Nuclear Polarization in Solids
Authors: Thurber Kent R. , Tycko Robert
Published: January 2014

Dynamic nuclear polarization (DNP) can dramatically increase the signal in nuclear magnetic resonance (NMR) experiments by transferring spin polarization from electrons to nuclei. We discuss quantum mechanical descriptions of the “solid effect” and “cross effect” mechanisms of DNP that typically occur in solid state NMR at high magnetic field, both with and without magic angle spinning (MAS). We present several extensions of recent theoretical descriptions, including (i) treatments of solid effect DNP and cross effect DNP with MAS, in which two nuclei change spin states simultaneously and (ii) a treatment of solid effect DNP in a two‐spin system without MAS, in which the ratio of microwave field strength to hyperfine coupling strength can be arbitrary. We also briefly discuss factors that influence DNP efficiency in experiments, beyond the basic principles contained in simple quantum mechanical models.