bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Interaction Determinants of CAPN1 Inhibition by CAST4 from Bovines Using Molecular Modeling Techniques
Authors: Chai Han-Ha , Lim Dajeong , Jung Eunkyoung , Choi Bong-Hwan , Cho Yong-Min
Published: September 2014

HCV-induced CAPN activation and its effects on virus-infected cells in a host-immune system have been studied recently. It has been shown that the HCV-nonstructural 5A protein acts as both an inducer and a substrate for host CAPN protease; it participates in suppressing the TNF-α-induced apoptosis response and downstream IFN-induced antiviral processes. However, little is known regarding the disturbance of antiviral responses generated by bovine CAPN activation by BVDV, which is a surrogate model of HCV and is one of the most destructive diseases leading to great economic losses in cattle herds worldwide. This is also thought to be associated with the effects of either small CAPN inhibitors or the natural inhibitor CAST. They mainly bind to the binding site of CAPN substrate proteins and competitively inhibit the binding of the enzyme substrates to possibly defend against the two viruses (HCV and BVDV) for anti-viral immunity. To devise a new stratagem to discover lead candidates for an anti-BVDV drug, we first attempted to understand the bovine CAPN-CAST interaction sites and the interaction constraints of local binding architectures, were well reflected in the geometry between the pharmacophore features and its shape constraints identified using our modeled bovine CAPN1/CAST4 complex structures. We propose a computer-aided molecular design of an anti-BVDV drug as a mimetic CAST inhibitor to develop a rule-based screening function for adjusting the puzzle of relationship between bovine CAPN1 and the BVDV nonstructural proteins from all of the data obtained in the study.
Three Novel Lanthanide Metal-Organic Frameworks (Ln-MOFs) Constructed by Unsymmetrical Aromatic Dicarboxylatic Tectonics: Synthesis, Crystal Structures and Luminescent Properties
Authors: Wu Ya-Pan , Li Dong-Sheng , Xia Wei , Guo Sha-Sha , Dong Wen-Wen
Published: September 2014

Three novel Ln(III)-based coordination polymers, {[Ln2 (2,4-bpda)3 (H2O)x]·yH2O}n (Ln = La (III) (1), x = 2, y = 0, Ce (III) (2), Pr (III) (3), x = 4, y = 1) (2,4-H2bpda = benzophenone-2,4-dicarboxylic acid) have been prepared via a solvothermal method and characterized by elemental analysis, IR, and single-crystal X-ray diffraction techniques. Complex 1 exhibits a 3D complicated framework with a new 2-nodal (3,7)-connected (42·5) (44·51·66·8) topology. Complexes 2 and 3 are isomorphous, and feature a 3D 4-connected (65·8)-CdSO4 network. Moreover, solid-state properties such as thermal stabilities and luminescent properties of 1 and 2 were also investigated. Complex 1 crystallized in a monoclinic space group P21/c with a = 14.800 (3), b = 14.500 (3), c = 18.800 (4) Å, β = 91.00 (3), V = 4033.9 (14) Å3 and Z = 4. Complex 2 crystallized in a monoclinic space group Cc with a = 13.5432 (4), b = 12.9981 (4), c = 25.7567 (11) Å, β = 104.028 (4), V = 1374.16 (7) Å3 and Z = 4.
Cyclin-Dependent Kinase Inhibitors as Marketed Anticancer Drugs: Where Are We Now? A Short Survey
Authors: Mariaule Gaëlle , Belmont Philippe
Published: September 2014

In the early 2000s, the anticancer drug imatinib (Glivec®) appeared on the market, exhibiting a new mode of action by selective kinase inhibition. Consequently, kinases became a validated therapeutic target, paving the way for further developments. Although these kinases have been thoroughly studied, none of the compounds commercialized since then target cyclin-dependent kinases (CDKs). Following a recent and detailed review on the subject by Galons et al., we concentrate our attention on an updated list of compounds under clinical evaluation (phase I/II/III) and discuss their mode of action as ATP-competitive inhibitors. CDK inhibition profiles and clinical development stages are reported for the 14 compounds under clinical evaluation. Also, tentative progress for forthcoming potential ATP non-competitive inhibitors and allosteric inhibitors are briefly described, along with their limitations.
Intrinsic Fabry-Perot Interferometeric Sensor Based on Microfiber Created by Chemical Etching
Authors: Wang Ruohui , Qiao Xueguang
Published: September 2014

An intrinsic Fabry-Perot interferometeric sensor based on a microfiber has been demonstrated. The micro-size suspended core is created by chemical etching a photonics crystal fiber, of which the cladding has a micrometer-spaced, hexagonal array of air holes. The sensing head is fabricated by chemical etching a short section of photonics crystal fiber spliced with a single mode fiber. The temperature sensing characteristic of the interferometer has also been demonstrated and a sensitivity 14.3 pm/°C is obtained.
Reliable Adaptive Data Aggregation Route Strategy for a Trade-off between Energy and Lifetime in WSNs
Authors: Guo Wenzhong , Hong Wei , Zhang Bin , Chen Yuzhong , Xiong Naixue
Published: September 2014

Mobile security is one of the most fundamental problems in Wireless Sensor Networks (WSNs). The data transmission path will be compromised for some disabled nodes. To construct a secure and reliable network, designing an adaptive route strategy which optimizes energy consumption and network lifetime of the aggregation cost is of great importance. In this paper, we address the reliable data aggregation route problem for WSNs. Firstly, to ensure nodes work properly, we propose a data aggregation route algorithm which improves the energy efficiency in the WSN. The construction process achieved through discrete particle swarm optimization (DPSO) saves node energy costs. Then, to balance the network load and establish a reliable network, an adaptive route algorithm with the minimal energy and the maximum lifetime is proposed. Since it is a non-linear constrained multi-objective optimization problem, in this paper we propose a DPSO with the multi-objective fitness function combined with the phenotype sharing function and penalty function to find available routes. Experimental results show that compared with other tree routing algorithms our algorithm can effectively reduce energy consumption and trade off energy consumption and network lifetime.
Coping with a Self-Induced Shock: The Heterarchic Organization of the London Olympic Games 2012
Authors: Grabher Gernot , Thiel Joachim
Published: September 2014

This paper starts from the assumption of a structural analogy between mega-events and large-scale disasters. Both imply forceful interruptions of everyday routines, and both involve imperatives for imminent action. Similar to the immovable deadline of an opening ceremony, a looming natural disaster triggers a complex set of precautions and preparations to cope with the inescapable forthcoming shock. In the case of mega-events, of course, this shock is self-induced. In fact, cities fiercely compete to host mega-events. In the face of the daunting challenges of hosting a mega-event—the immovable timeframe, the rigorous standards set by regulatory bodies, and the exceptional public visibility—the authorities and organizations in charge traditionally have resorted to strategies of a strict adaptation to the conditions imposed on them. Aligning all available resources and capabilities to match the foreseeable demands, however, undermines the adaptability to cope with unpredictable perturbations. This paper seeks to explore the strategies and practices to attain adaptability during the preparation, staging and implementation of legacy plans of a mega-event with an evidentially noteworthy record: the London Olympic Games 2012. The paper seeks to demonstrate that the project ecology in charge managed to enhance adaptability by implementing three key features of heterarchy: ambiguity, redundancy and loose coupling. By leveraging the principles of heterarchy, the project ecology was able to draw lessons from previous mega-events and both to anticipate and respond to unforeseen challenges.
Socioeconomic Position and Low Birth Weight: Evaluating Multiple and Alternative Measures Across Race in Michigan
Authors: Taylor Cedric , Sarathchandra Dilshani
Published: September 2014

In health research, socioeconomic position (SEP) is used to measure the context of social inequality. Studies on low birth weight (LBW) that attempt to capture social inequality have generally used single measures of SEP or have employed conventional SEP measures, such as income and education, without regard to how other indicators could influence findings. This study investigates the association between SEP and LBW across blacks and whites using multiple and alternative indicators of SEP. We use a stratified random sample of 13,513 postpartum mothers, obtained from the Michigan Pregnancy Risk Assessment Monitoring System (2000–2006), and evaluate four SEP measures across race: maternal education, Medicaid before pregnancy, Women, Infants and Children (WIC) enrollment during pregnancy and paternal acknowledgment. Results indicate that associations between SEP and LBW vary depending on the SEP measure used and the racial subpopulation under consideration. To explain and reduce social inequalities in LBW, a more differentiated approach that does not assume equivalence among SEP measures and across racial/ethnic groups should be employed.
Comparative Multi-Criteria Assessment of Climate Policies and Sustainable Development Strategies in Cameroon: Towards a GIS Decision-Support Tool for the Design of an Optimal REDD+ Strategy
Authors: Kehbila Anderson , Alemagi Dieudonne , Minang Peter
Published: September 2014

Cameroon is committed to reducing emissions from deforestation and forest degradation plus conservation, sustainable management of forests and enhancement of carbon stocks (REDD+). To achieve this goal, the government has introduced a series of policy reforms and formulated a number of key strategic planning documents to advance the REDD+ readiness process in Cameroon. This paper assesses the extent to which major cross-sectoral policies support or impede the development and implementation of an optimal REDD+ strategy in Cameroon from a comparative multi-criteria perspective. Study results reveal that a majority of the policy instruments reviewed appeared to be less prescriptive in terms of any tangible REDD+ strategy, as they do not have provisions for tangible measures to reduce deforestation and forest degradation. Given the lack of adequate flexibility, prompt review and responsiveness of these cross-sectoral policies to adapt themselves to new realities and respond to a changing environment, this paper introduces a GIS-REDD+ decision support system (GIS-REDD+DSS) that is necessary to support the adaptive element of an adaptive REDD+ strategy in Cameroon. The GIS-REDD+DSS, an electronic REDD+agri intermediary hub, serves the following purpose: (1) host a database of locally-relevant climate information, improved input technologies, best practices as well as land use and forest cover geo-spatial maps; (2) host a virtual economic tool that performs economic valuations (costs and benefits) and financial analysis of REDD+agri projects to aid investment decision-making; and (3) host an electronic marketplace to mediate any-to-any transactions among REDD+agri project developers, service providers, input suppliers, private and institutional investors and buyers (wholesalers and retailers), thereby creating value in two ways: aggregation and matching. This decision support tool, we argue, is a fundamental prerequisite for “policy and REDD+ safeguard integration” innovation that allows new scientific findings to be integrated into REDD+ strategies in a short period of time.
Water Resource Vulnerability Characteristics by District’s Population Size in a Changing Climate Using Subjective and Objective Weights
Authors: Chung Eun-Sung , Won Kwangjae , Kim Yeonjoo , Lee Hosun
Published: September 2014

The goal of this study is to derive water resource vulnerability characteristics for South Korea according to individual district populations in a changing climate. The definition of water resource vulnerability in this study consists of potential flood damage and potential water scarcity. To quantify these vulnerabilities, key factors, or indicators affecting vulnerability, are integrated with a technique for order of preference by similarity to ideal solution (TOPSIS), which is a multi-criteria decision-making approach to determine the optimal alternative by considering both the best and worst solutions. The weight for each indicator is determined based on both the Delphi technique and Shannon’s entropy, which are employed to reduce the uncertainty in the process of determining the weights. The Delphi technique reflects expert opinions, and Shannon’s entropy reflects the uncertainty of the performance data. Under A1B climate change scenarios, medium-sized districts (200,000–300,000 inhabitants) are the most vulnerable regarding potential flood damage; the largest districts (exceeding 500,000 inhabitants) are found to be the most vulnerable with respect to potential water scarcity. This result indicates that the local governments of cities or districts with more than 200,000 inhabitants should implement better preventative measures for water resources. In addition, the Delphi and entropy methods show the same rankings for flood vulnerability; however, these approaches produce slightly different rankings regarding water scarcity vulnerability. Therefore, it is suggested that rankings from not only subjective but also objective weights should be considered in making a final decision to implement specific adaptive measures to climate change.
Biofuels for a Greener Economy? Insights from Jatropha Production in Northeastern Ethiopia
Authors: Portner Brigitte , Ehrensperger Albrecht , Nezir Zufan , Breu Thomas , Hurni Hans
Published: September 2014

Many observers view Jatropha as a miracle plant that grows in harsh environments, halts land degradation and provides seeds for fuel production. This makes it particularly attractive for use in Ethiopia, where poverty levels are high and the degradation of agricultural land is widespread. In this article, we investigate the potentials and limitations of a government-initiated Jatropha project for smallholders in northeastern Ethiopia from a green economy perspective. Data are based on a 2009 household survey and interviews with key informants, as well as on a 2012 follow-up round of interviews with key informants. We conclude that the project has not contributed to a greener economy so far, but has the potential to do so in the future. To maximize Jatropha’s potential, interventions must focus mainly on smallholders and pay more attention to the entire biofuel value chain.
Sustainable Fashion Supply Chain: Lessons from H&M
Authors: Shen Bin
Published: September 2014

Sustainability is significantly important for fashion business due to consumers’ increasing awareness of environment. When a fashion company aims to promote sustainability, the main linkage is to develop a sustainable supply chain. This paper contributes to current knowledge of sustainable supply chain in the textile and clothing industry. We first depict the structure of sustainable fashion supply chain including eco-material preparation, sustainable manufacturing, green distribution, green retailing, and ethical consumers based on the extant literature. We study the case of the Swedish fast fashion company, H&M, which has constructed its sustainable supply chain in developing eco-materials, providing safety training, monitoring sustainable manufacturing, reducing carbon emission in distribution, and promoting eco-fashion. Moreover, based on the secondary data and analysis, we learn the lessons of H&M’s sustainable fashion supply chain from the country perspective: (1) the H&M’s sourcing managers may be more likely to select suppliers in the countries with lower degrees of human wellbeing; (2) the H&M’s supply chain manager may set a higher level of inventory in a country with a higher human wellbeing; and (3) the H&M CEO may consider the degrees of human wellbeing and economic wellbeing, instead of environmental wellbeing when launching the online shopping channel in a specific country.
Zebrafish as a Model for Developmental Neurotoxicity Assessment: The Application of the Zebrafish in Defining the Effects of Arsenic, Methylmercury, or Lead on Early Neurodevelopment
Authors: Lee Jinyoung , Freeman Jennifer
Published: September 2014

Developmental exposure to neurotoxic chemicals presents significant health concerns because of the vulnerability of the developing central nervous system (CNS) and the immature brain barrier. To date, a short list of chemicals including some metals have been identified as known developmental neurotoxicants; however, there are still numerous chemicals that remain to be evaluated for their potential developmental neurotoxicity (DNT). To facilitate evaluation of chemicals for DNT, the zebrafish vertebrate model system has emerged as a promising tool. The zebrafish possesses a number of strengths as a test species in DNT studies including an abundance of embryos developing ex utero presenting ease in chemical dosing and microscopic assessment at all early developmental stages. Additionally, rapid neurodevelopment via conserved molecular pathways supports the likelihood of recapitulating neurotoxic effects observed in other vertebrates. In this review, we describe the biological relevance of zebrafish as a complementary model for assessment of DNT. We then focus on a metalloid and two metals that are known developmental neurotoxicants (arsenic, methylmercury, and lead). We summarize studies in humans and traditional vertebrate models and then detail studies defining the toxicity of these substances using the zebrafish to support application of this model system in DNT studies.
Downregulation and Mutation of a Cadherin Gene Associated with Cry1Ac Resistance in the Asian Corn Borer, Ostrinia furnacalis (Guenée)
Authors: Jin Tingting , Chang Xue , Gatehouse Angharad , Wang Zhenying , Edwards Martin , He Kanglai
Published: September 2014

Development of resistance in target pests is a major threat to long-term use of transgenic crops expressing Bacillus thuringiensis (Bt) Cry toxins. To manage and/or delay the evolution of resistance in target insects through the implementation of effective strategies, it is essential to understand the basis of resistance. One of the most important mechanisms of insect resistance to Bt crops is the alteration of the interactions between Cry toxins and their receptors in the midgut. A Cry1Ac-selected strain of Asian corn borer (ACB), Ostrinia furnacalis, a key pest of maize in China, evolved three mutant alleles of a cadherin-like protein (OfCAD) (MPR-r1, MPR-r2 and MPR-r3), which mapped within the toxin-binding region (TBR). Each of the three mutant alleles possessed two or three amino acid substitutions in this region, especially Thr1457→Ser. In highly resistant larvae (ACB-Ac200), MPR-r2 had a 26-amino acid residue deletion in the TBR, which resulted in reduced binding of Cry1Ac compared to the MPR from the susceptible strain, suggesting that the number of amino acid deletions influences the level of resistance. Furthermore, downregulation of OfCAD gene (ofcad) transcription was observed in the Cry1Ac resistant strain, ACB-Ac24, suggesting that Cry1Ac resistance in ACB is associated with the downregulation of the transcript levels of the cadherin-like protein gene. The OfCAD identified from ACB exhibited a high degree of similarity to other members of the cadherin super-family in lepidopteran species.
Global scaling for semi-quantitative analysis in FP-CIT SPECT
Authors: Lange C. , Ulrich G. , Amthauer H. , Brenner W. , Kupitz D. , Apostolova I. , Buchert R.
Published: September 2014

Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semiquantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. Patients, methods: 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurode- generative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. Results: The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. Conclusion: We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.
MODELING THE SAILING RISK OF ROPAX SHIPS WITH BAYESIAN NETWORK
Authors: Zeng Qingcheng , Yang Luyan , Zhang Qian
Published: September 2014

In this paper, a methodology based on Bayesian Network (BN) was proposed to deal with the difficulty of risk analysis in RoPax transport. Based on data collection and expert survey, BN model for RoPax sailing risk analysis was constructed first. Then the Expectation Maximization (EM) algorithm for parameter learning and Evidence Prepropagation Importance Sampling (EPIS) algorithm for reasoning were designed. Finally, a sensitivity analysis was conducted. To validate the model algorithms, a case study on the RoPax system of Bohai gulf in China was provided. Results indicate that the BN model can effectively address the problem of data deficiency and mutual dependency of incidents in risk analysis. It can also model the development process of unexpected hazards and provide decision support for risk mitigation.
Spectral-Domain and Swept-Source OCT Imaging of Asteroid Hyalosis: A Case Report
Authors: Alasil Tarek , Adhi Mehreen , Liu Jonathan J. , Fujimoto James G. , Duker Jay S. , Baumal Caroline R.
Published: September 2014

A 72-year-old man with diabetes was referred to the retina clinic for diabetic retinopathy. Detailed funduscopic examination of the left eye was limited by prominent asteroid hyalosis. Spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) were utilized to examine the vitreous, vitreoretinal interface, and the morphology of the retina. Asteroid hyalosis induced artifacts of the OCT images, which resolved when the appropriate imaging protocols were applied. SS-OCT may show superior diagnostic and preoperative capabilities when compared to SD-OCT in the settings of asteroid hyalosis-induced media opacity.

[
Ophthalmic Surg Lasers Imaging Retina
. 2014;45:459–461.]
«Descendientes de los primeros». Las probanzas de méritos y servicios y la genealogía cacical. Audiencia de Charcas, 1574-1719
Authors: Carolina Jurado M.
Published: September 2014

El presente artículo propone abordar las probanzas de méritos y servicios de renombrados linajes cacicales de Charcas colonial, a partir de una imagen problematizadora que dé cuenta del modo en que se desarrollaba la escritura del documento legal, dirigiendo la mirada al actuar de los notarios, procuradores y asesores legales, como piezas clave en la adecuación y transmisión de su contenido. La lectura comparativa de distintas probanzas de méritos revela la emulación de un modelo arquetípico de liderazgo, en los intersticios del formulismo hispano. Se aspira así a proporcionar reflexiones sobre el uso de las probanzas de méritos para el conocimiento del pasado prehispánico y colonial.
Los indios americanos en las escenas líricas europeas: de los hermanos Purcell (1695) a Carl Heinrich Graun (1755)
Authors: Núñez Ronchi Ana
Published: September 2014

Se ha querido interpretar las primeras óperas de tema americano (Purcell, Vivaldi, Rameau y Graun) como una expresión dramático-musical de la llamada Leyenda Negra, contrapuesta a una producción teatral áurea española que, inversamente, sí habría dejado espacio a la dimensión histórico-crítica. Ello nos parece injusto e inexacto: en primer lugar, la comedia áurea no escenifica la dimensión crítica que se ha pretendido atribuirle; en segundo lugar, el teatro lírico europeo, si bien exalta al indio americano, no devalúa sistemáticamente a los conquistadores españoles; finalmente, la noción misma de «Leyenda Negra» debe ser problematizada.
De la «Patria Grande» a la «Madre Patria»: Manuel Ugarte y el hispanoamericanismo español (1900-1930)
Authors: Andrés García Manuel
Published: September 2014

El objetivo de este artículo es la revisión de una figura capital en el antiimperialismo latinoamericano, Manuel Baldomero Ugarte, a través de sus colaboraciones con el hispanoamericanismo de comienzos del XX. Partiendo de un análisis sobre la marginación sufrida por el intelectual y su obra durante décadas, centraremos el trabajo en sus aportes a tres de las principales revistas hispanoamericanistas de la época –La Rábida, Unión Ibero-Americana y Cultura Hispanoamericana– a fin de observar los puntos de confluencia entre este movimiento y el erudito argentino.
Factors Determining the Price of Umra Package among Travel Agencies in Kano Metropolis
Authors: Kuka Musa Gambo Kasuwar
Published: September 2014

The incessant complaints by civil society organizations and the general public in Nigeria against exploitative charges by tour operators and travel agencies on hapless Hajj and Umrah pilgrims call for careful examination. Previously, some of these unscrupulous tour operators have hidden under the excuse of the high cost of visas to charge exorbitant fees. However, with the recent clarification from the Saudi Arabian Embassy in Nigeria that both Hajj and Umrah visas are free, it is clear that some travel agencies have been exploiting Nigerian pilgrims. This chapter is conducted in order to address this issue. Consequently, the chapter attempts to provide relevant insights on Islamic tourism in Nigeria with specific emphasis on the reasons behind the high cost and variations in the prices of Umra packages among travel agencies in Kano State of Nigeria. It is an exploratory study that uses a qualitative approach through in-depth interviews with senior officers of selected travel agencies in Kano. Findings from the study reveal that Umra pilgrims in Kano pay higher and different fares. It has also been established that there are variations in Umra prices due to some direct and indirect factors that determine Umra package fares. Consequently, it is recommended that there is a need for the National Hajj Commission of Nigeria (NAHCON) to properly regulate Umra pilgrimage like that of Hajj and to embark on an aggressive enlightenment campaign to educate potential and present Umra pilgrims on the necessary factors that affect the price of a typical Umra package and how they can identify a registered travel agency from a quack one so as to protect themselves against undue exploitation.
Knowledge Discovery and Data Mining Applications in the Healthcare Industry
Authors: Barazandeh Iman , Gholamian Mohammad Reza
Published: September 2014

The healthcare industry is one of the most attractive domains to realize the actionable knowledge discovery objectives. This chapter studies recent researches on knowledge discovery and data mining applications in the healthcare industry and proposes a new classification of these applications. Studies show that knowledge discovery and data mining applications in the healthcare industry can be classified to three major classes, namely patient view, market view, and system view. Patient view includes papers that performed pure data mining on healthcare industry data. Market view includes papers that saw the patients as customers. System view includes papers that developed a decision support system. The goal of this classification is identifying research opportunities and gaps for researchers interested in this context.
TRIF Signaling Drives Homeostatic Intestinal Epithelial Antimicrobial Peptide Expression
Authors: Stockinger Silvia , Duerr Claudia U. , Fulde Marcus , Dolowschiak Tamas , Pott Johanna , Yang Ines , Eibach Daniel , Bäckhed Fredrik , Akira Shizuo , Suerbaum Sebastian , Brugman Martijn , Hornef Mathias W.
Published: September 2014

Recent results indicate a significant contribution of innate immune signaling to maintain mucosal homeostasis, but the precise underlying signal transduction pathways are ill-defined. By comparative analysis of intestinal epithelial cells isolated from conventionally raised and germ-free mice, as well as animals deficient in the adaptor molecules MyD88 and TRIF, the TLR3 and TLR4, as well as the type I and III IFN receptors, we demonstrate significant TLR-mediated signaling under homeostatic conditions. Surprisingly, homeostatic expression of Reg3γ and Paneth cell enteric antimicrobial peptides critically relied on TRIF and, in part, TLR3 but was independent of IFN receptor signaling. Reduced antimicrobial peptide expression was associated with significantly lower numbers of Paneth cells and a reduced Paneth cell maturation and differentiation factor expression in TRIF mutant compared with wild-type epithelium. This phenotype was not transferred to TRIF-sufficient germ-free animals during cohousing. Low antimicrobial peptide expression in TRIF-deficient mice caused reduced immediate killing of orally administered bacteria but was not associated with significant alterations in the overall composition of the enteric microbiota. The phenotype was rapidly restored in a TRIF-independent fashion after transient epithelial damage. Our results identify TRIF signaling as a truly homeostatic pathway to maintain intestinal epithelial barrier function revealing fundamental differences in the innate immune signaling between mucosal homeostasis and tissue repair.
TLR2-Dependent Activation of β-Catenin Pathway in Dendritic Cells Induces Regulatory Responses and Attenuates Autoimmune Inflammation
Authors: Manoharan Indumathi , Hong Yuan , Suryawanshi Amol , Angus-Hill Melinda L. , Sun Zuoming , Mellor Andrew L. , Munn David H. , Manicassamy Santhakumar
Published: September 2014

Dendritic cells (DCs) sense microbes via multiple innate receptors. Signals from different innate receptors are coordinated and integrated by DCs to generate specific innate and adaptive immune responses against pathogens. Previously, we have shown that two pathogen recognition receptors, TLR2 and dectin-1, which recognize the same microbial stimulus (zymosan) on DCs, induce mutually antagonistic regulatory or inflammatory responses, respectively. How diametric signals from these two receptors are coordinated in DCs to regulate or incite immunity is not known. In this study, we show that TLR2 signaling via AKT activates the β-catenin/T cell factor 4 pathway in DCs and programs them to drive T regulatory cell differentiation. Activation of β-catenin/T cell factor 4 was critical to induce regulatory molecules IL-10 (Il-10) and vitamin A metabolizing enzyme retinaldehyde dehydrogenase 2 (Aldh1a2) and to suppress proinflammatory cytokines. Deletion of β-catenin in DCs programmed them to drive Th17/Th1 cell differentiation in response to zymosan. Consistent with these findings, activation of the β-catenin pathway in DCs suppressed chronic inflammation and protected mice from Th17/Th1-mediated autoimmune neuroinflammation. Thus, activation of β-catenin in DCs via the TLR2 receptor is a novel mechanism in DCs that regulates autoimmune inflammation.
Eosinophil-Derived IL-10 Supports Chronic Nematode Infection
Authors: Huang Lu , Gebreselassie Nebiat G. , Gagliardo Lucille F. , Ruyechan Maura C. , Lee Nancy A. , Lee James J. , Appleton Judith A.
Published: September 2014

Eosinophilia is a feature of the host immune response that distinguishes parasitic worms from other pathogens, yet a discrete function for eosinophils in worm infection has been elusive. The aim of this study was to clarify the mechanism(s) underlying the striking and unexpected observation that eosinophils protect intracellular, muscle-stage Trichinella spiralis larvae against NO-mediated killing. Our findings indicate that eosinophils are specifically recruited to sites of infection at the earliest stage of muscle infection, consistent with a local response to injury. Early recruitment is essential for larval survival. By producing IL-10 at the initiation of infection, eosinophils expand IL-10+ myeloid dendritic cells and CD4+ IL-10+ T lymphocytes that inhibit inducible NO synthase (iNOS) expression and protect intracellular larvae. The results document a novel immunoregulatory function of eosinophils in helminth infection, in which eosinophil-derived IL-10 drives immune responses that eventually limit local NO production. In this way, the parasite co-opts an immune response in a way that enhances its own survival.
The SLMTA programme: Transforming the laboratory landscape in developing countries
Authors: Yao Katy , Maruta Talkmore , Luman Elizabeth T. , Nkengasong John N.
Published: September 2014

Background: Efficient and reliable laboratory services are essential to effective and well-functioning health systems. Laboratory managers play a critical role in ensuring the quality and timeliness of these services. However, few laboratory management programmes focus on the competencies required for the daily operations of a laboratory in resource-limited settings. This report provides a detailed description of an innovative laboratory management training tool called Strengthening Laboratory Management Toward Accreditation (SLMTA) and highlights some challenges, achievements and lessons learned during the first five years of implementation (2009–2013) in developing countries.Programme: SLMTA is a competency-based programme that uses a series of short courses and work-based learning projects to effect immediate and measurable laboratory improvement, while empowering laboratory managers to implement practical quality management systems to ensure better patient care. A SLMTA training programme spans from 12 to 18 months; after each workshop, participants implement improvement projects supported by regular supervisory visits or on-site mentoring. In order to assess strengths, weaknesses and progress made by the laboratory, audits are conducted using the World Health Organization’s Regional Office for Africa (WHO AFRO) Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist, which is based on International Organization for Standardization (ISO) 15189 requirements. These internal audits are conducted at the beginning and end of the SLMTA training programme.Conclusion: Within five years, SLMTA had been implemented in 617 laboratories in 47 countries, transforming the laboratory landscape in developing countries. To our knowledge, SLMTA is the first programme that makes an explicit connection between the performance of specific management behaviours and routines and ISO 15189 requirements. Because of this close relationship, SLMTA is uniquely positioned to help laboratories seek accreditation to ISO 15189.
Community-physician-based versus hospital-based antenatal care: A comparison of patient satisfaction
Authors: Phaladi-Digamela Mauwane R.
Published: September 2014

Background: Strategies to meet the healthcare needs of pregnant women are made available throughout antenatal, intra-partum and post-natal periods. These strategies are aimed at reducing perinatal and maternal mortality amongst women who access and utilise healthcare at an early stage. Late visits with irregular antenatal attendance result in failure to adequately use antenatal interventions.Objectives: This study intended to compare and describe the level of patient satisfaction with antenatal care between two groups of women who received free antenatal care from community private physicians and public midwives.Methods: A quantitative comparative descriptive design with a Likert-scale measure was used. Sixty women, half from each group, participated in the study. Structured questionnaires with closed-ended response options were used to obtain data.Results: The midwives’ group was less satisfied with antenatal care than the physicians’ group, with the former citing long waiting times as contributing to their dissatisfaction with antenatal care.Conclusion: Addressing long waiting times improves satisfaction with antenatal care. Daily antenatal visits, rather than visits on a specific day, may reduce long waiting times as women’s visits are spread over all clinic days. Satisfaction with antenatal care has implications for access to healthcare, resulting in positive pregnancy outcomes. Agtergrond: Strategieё om in die gesondheidsorgbehoeftes van swanger vroue te voorsien, word dwarsdeur die voorgeboorte, intra-partum en nageboorte periodes beskikbaar gestel. Hierdie strategieё beoog om die perinatale en moederlike sterfstesyfers te verlaag onder vroue wie reeds op ’n vroeë stadium gesondheidsorg benut. Onreёlmatige en laat voorgeboortebesoeke lei daartoe dat voorgeboorte ingrypings nie voldoende benut word nie.Doelwitte: Hierdie studie het beoog om twee groepe vroue se vlak van tevredenheid met die gratis voorgeboortesorg wat hul by privaat praktisyns uit die gemeenskap en vroedvroue uit die openbare sektor ontvang het, te vergelyk en beskryf.Metode: ’n Kwantitatiewe vergelykende beskrywende ontwerp met ’n Likert-skaal is gebruik. Sestig vroue, die helfte van elke groep, het aan die studie deelgeneem. Gestruktureerde vraelyste met geslote-vrae opsies is gebruik om die data te verkry.Resultate: Die praktisyns se groep was meer tevrede met die voorgeboortesorg as die vroedvroue se groep, veral ten opsigte van wagtye.Gevolgtrekkings: Deur die probleem van wagtye aan te spreek, kan die tevredenheid met voorgeboortesorg verhoog word. Daaglikse voorgeboortesorgbesoeke, eerder as besoeke op spesifieke dae, kan lang wagtye verminder aangesien besoeke dan oor al die kliniekdae versprei word. Tevredenheid met voorgeboortesorg hou implikasies in vir toegang tot gesondheidsorg, wat positiewe swangerskapsuitkomste tot gevolg het.
Prevalence of select vector-borne disease agents in owned dogs of Ghana
Authors: Clarke Lorelei L. , Ballweber Lora R. , Allen Kelly , Little Susan E. , Lappin Michael R.
Published: September 2014

Ticks, sera and ethylenediaminetetraacetic acid (EDTA) blood were collected from dogs evaluated at the Amakom Veterinary Clinic in Kumasi, Ghana. Sera were evaluated for Dirofilaria immitis antigen and antibodies against Borrelia burgdorferi, Anaplasma phagocytophilum and Ehrlichia canis. Conventional polymerase chain reaction assays designed to amplify the deoxyribonucleic acid (DNA) ofEhrlichia spp. or Anaplasma spp. or Neorickettsia spp. or Wolbachia spp., Babesia spp., Rickettsia spp., Hepatozoon spp., Bartonella spp. and the haemoplasmas were performed on DNA extracted from EDTA blood and all positive amplicons were sequenced. This small survey shows that the following vector-borne pathogens are present in urban Ghanian dogs: Ehrlichia canis, Hepatozoon canis,Dirofilaria immitis and Anaplasma platys. Bartonella henselae was isolated from ticks but not from the dogs.
Antigenic characterisation of lyssaviruses in South Africa
Authors: Ngoepe Ernest , Fehlner-Gardiner Christine , Wandeler Alex , Sabeta Claude
Published: September 2014

There are at least six Lyssavirus species that have been isolated in Africa, which include classical rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus. In this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in South Africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. A total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen by direct fluorescent antibody test, were subjected to antigenic differentiation. The lyssaviruses were differentiated into two species, namely rabies virus (99.5%) and Mokola virus (0.5%). Furthermore, rabies virus was further delineated into two common rabies biotypes in South Africa: canid and mongoose. Initially, it was found that the canid rabies biotype had two reactivity patterns; differential staining was observed with just one monoclonal antibody. This difference was likely to have been an artefact related to sample quality, as passage in cell culture restored staining. Mongoose rabies viruses were more heterogeneous, with seven antigenic reactivity patterns detected. Although Mokola viruses were identified in this study, prevalence and reservoir host species are yet to be established. These data demonstrate the usefulness of monoclonal antibody typing panels in lyssavirus surveillance with reference to emergence of new species or spread of rabies biotypes to new geographic zones.
Lifting Divisors on a Generic Chain of Loops
Authors: Cartwright Dustin , Jensen David , Payne Sam
Published: September 2014

Let C be a curve over a complete valued field having an infinite residue field and whose skeleton is a chain of loops with generic edge lengths. We prove that any divisor on the chain of loops that is rational over the value group lifts to a divisor of the same rank on C, confirming a conjecture of Cools, Draisma, Robeva, and the third author.
The symplectic topology of some rational homology balls
Authors: Lekili Yankı , Maydanskiy Maksim
Published: September 2014

We study the symplectic topology of some finite algebraic quotients of the

A_n

Milnor fibre which are diffeomorphic to the rational homology balls that appear in Fintushel and Stern’s rational blowdown construction. We prove that these affine surfaces have no closed exact Lagrangian submanifolds by using the already available and deep understanding of the Fukaya category of the

A_n

Milnor fibre coming from homological mirror symmetry. On the other hand, we find Floer theoretically essential monotone Lagrangian tori, finitely covered by the monotone tori which we study in the

A_n

Milnor fibre. We conclude that these affine surfaces have non-vanishing symplectic cohomology.
From Schanuel’s Conjecture to Shapiro’s Conjecture
Authors: D'Aquino Paola , Macintyre Angus , Terzo Giuseppina
Published: September 2014

In this paper we prove Shapiro’s 1958 Conjecture on exponential polynomials, assuming Schanuel’s Conjecture.
On the geometry of horospheres
Authors: Aquino Cicero Pedro , Fernandes de Lima Henrique
Published: September 2014

The aim of this paper is to investigate Bernstein-type properties of horospheres of the hyperbolic space

\mathbb H^{n+1}

. Our approach is based on the use of appropriate generalized maximum principles in order to obtain new characterization results of such horospheres. Furthermore, by supposing a linear dependence between support functions naturally attached to a hypersurface, we also establish a classification theorem concerning horospheres and hyperbolic cylinders of

\mathbb H^{n+1}

.
Embedding functors and their arithmetic properties
Authors: Lee Ting-Yu
Published: September 2014

In this article, we focus on how to embed a torus

\mathrm{T}

into a reductive group

\mathrm{G}

with respect to a given root datum

\Psi

over a scheme

\mathrm{S}

. This problem is also related to embedding an étale algebra with involution into a central simple algebra with involution (cf. [PR10]). We approach this problem by defining the embedding functor, which is representable and is a left homogeneous space over

\mathrm{S}

under the automorphism group of

\mathrm{G}

. In order to fix a connected component of the embedding functor, we define an orientation

u

of

\Psi

with respect to

\mathrm{G}

. We show that the oriented embedding functor is also representable and is a homogeneous space under the adjoint action of

\mathrm{G}

. Over a local field, the orientation

u

and the Tits index of

\mathrm{G}

determine the existence of an embedding of

\mathrm{T}

into

\mathrm{G}

with respect to the given root datum

\Psi

. We also use the techniques developed in Borovoi’s paper [Bo99] to prove that the local-global principle holds for oriented embedding functors in certain cases. Actually, the Brauer–Manin obstruction is the only obstruction to the local-global principle for the oriented embedding functor. Finally, we apply the results on oriented embedding functors to give an alternative proof of Prasad and Rapinchuk’s Theorem, and to improve Theorem 7.3 in [PR10].
Variability of the mixed phase in the Arctic with a focus on the Svalbard region: a study based on spaceborne active remote sensing
Authors: Mioche G. , Jourdan O. , Ceccaldi M. , Delanoë J.
Published: September 2014

Abstract. The Arctic region is known to be very sensitive to climate change. Clouds and in particular mixed phase clouds (MPC) remain one of the greatest sources of uncertainties in the modeling of the Arctic response to climate change due to an inaccurate representation of their variability and their quantification. In this study, we present a characterization of the vertical, spatial and seasonal variability of Arctic clouds and MPC over the whole Arctic region based on satellite active remote sensing observations. MPC properties in the region of Svalbard archipelago (78° N, 15° E) are also investigated. The occurrence frequency of clouds and MPC are determined from CALIPSO/CLOUDSAT measurements processed with the DARDAR retrieval algorithm which allows for a reliable cloud thermodynamic phase classification (warm liquid, supercooled liquid, ice, mixing of ice and supercooled liquid). Significant differences are observed between MPC variability over the whole Arctic region and over the Svalbard region. Results show that MPC are ubiquitous all along the year, with a minimum occurrence of 30% in winter and 50% during the rest of the year, in average over the whole Arctic. Over the Svalbard region, MPC occurrence is more constant with time with larger values (55%) compared to the average observed in the Arctic. MPC are especially located at low altitudes, below 3000 m, where their frequency of occurrence reaches 90%, in particular during winter, spring and autumn. Moreover, results highlight that MPC statistically prevail over sea. The temporal and spatial distribution of MPC over the Svalbard region seems to be linked to the contribution of moister air and warmer water from the North Atlantic Ocean which contribute to the initiation of the liquid water phase. Over the whole Arctic, and particularly in western regions, the increase of MPC occurrence from spring to autumn could be connected to the sea ice melting. During this period, the open water transports a part of the warm water from the Svalbard region to the rest of the Arctic region. This facilitates the vertical transfer of moisture and thus the persistence of the liquid phase. A particular attention is also paid on the measurements uncertainties and how they could affect our results.