Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge

Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens perspectives for dengue vaccine development.

A control and automation system for wave basins

This paper presents the new active absorption wave basin, named Hydrodynamic Calibrator (HC), constructed at the University of São Paulo (USP), in the Laboratory facilities of the Numerical Offshore Tank (TPN). The square (14 m 14 m) tank is able to generate and absorb waves from 0.5 Hz to 2.0 Hz, by means of 148 active hinged flap wave makers. An independent mechanical system drives each flap by means of a 1HP servo-motor and a ball-screw based transmission system. A customized ultrasonic wave probe is installed in each flap, and is responsible for measuring wave elevation in the flap. A complex automation architecture was implemented, with three Programmable Logic Computers (PLCs), and a low-level software is responsible for all the interlocks and maintenance functions of the tank. Furthermore, all the control algorithms for the generation and absorption are implemented using higher level software (MATLAB /Simulink block diagrams). These algorithms calculate the motions of the wave makers both to generate and absorb the required wave field by taking into account the layout of the flaps and the limits of wave generation. The experimental transfer function that relates the flap amplitude to the wave elevation amplitude is used for the calculation of the motion of each flap. This paper describes the main features of the tank, followed by a detailed presentation of the whole automation system. It includes the measuring devices, signal conditioning, PLC and network architecture, real-time and synchronizing software and motor control loop. Finally, a validation of the whole automation system is presented, by means of the experimental analysis of the transfer function of the waves generated and the calculation of all the delays introduced by the automation system.

Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects

Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N = 9), dementia with Lewy bodies (DLB; N = 3), Alzheimer's disease (N = 3), progressive supranuclear palsy (N = 2) as well as elderly normal control subjects (N = 4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

Play the game or get played? Researchers’ strategies around R&D policies

This chapter focuses on possible effects of current R&D policies in the scientific work, exploring some of the dilemmas they cause to researchers. In a transnational scale, R&D policies embrace performance-based research funding systems, calling for a growing accountability and a more useful and published research. Often justified by the importance of knowledge in public policies or as part of the new managerialism regime, these trends emphasize performativity on research. In this scenario, how researchers receive and interpret R&D policies is influenced according to their values and interests? Do they play the game or do they get played by it? These questions rely on a conceptual framework that conceives the research as a political scene, where researchers and R&D policies meet. Moreover, researchers’ strategies are perceived as political, considering that it is in the context of the practices that policy is interpreted and reinvented. The chapter presents an empirical study conducted in Portugal, which will be taken as an example of what Waitere et al (2011) already named as “choosing whether to resist or reinforce” R&D policies. In fact, the study revealed a strategic calculation made by researchers and the coexistence of convergent and divergent strategies concerning R&D policies. I will argue that the tensions in this strategic game are both a reflex and generator of the dilemmas of scientific work today and a sign of the complexity of public policies.

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.

State-of-the-art in integrated vehicle health management

Cranfield University in collaboration with The Boeing Company have set up a Centre of Excellence in IVHM on the University?s technology park. Sponsored by the East of England Development Agency (EEDA), the Centre carries out pre-competitive research and development of IVHM technologies for the benefit of industrial partners. In addition, the dedicated facilities and university staff provide an unparalleled educational environment for learning and applying IVHM technologies. Boeing is actively involved in the creation and work of the Centre through its enterprise-wide Phantom Works technology organization. This paper will describe the organisation and operation of the Centre and will illustrate its activities by describing a research project being carried out in the Centre. This project is a demonstration of an end to end IVHM system beginning with cost/benefit analysis and extending to maintenance, logistics and operations decision support.

Túl a kritikus ponton…- Logisztikai képességek Magyarországon (Beyond the critical point … – Logistics capabilities at Hungarian firms)

A szerző kutatási célja, hogy megvizsgálja, vajon a hazai vállalatok mai gyakorlatában a fejlettebb logisztikai képességek együtt járnak-e magasabb teljesítménnyel. Az elemzés a Budapesti Corvinus Egyetem Vállalat-gazdaságtan Intézete mellett működő Versenyképesség Kutató Központ vállalati versenyképességet vizsgáló kérdőíves felmérés immár 4. fordulójának adatbázisát használja, melyet 2009 folyamán összesen 300 vállalat vezetőinek megkérdezésével hoztak létre. Ennek az adatbázisnak a felhasználásával a cikk két kérdésre keresi a választ. A szerző egyrészt megvizsgálja, vajon a mintában kimutatható-e egy fejlettebb logisztikai képességekkel rendelkező vállalatcsoport. Másrészt arra is kíváncsi, vajon ezek a fejlettebb logisztikai képességek együtt járnak-e a vállalatok magasabb teljesítményével. A 2009-es adatok elemzése igazolta, hogy logisztikai képességekben két szignifikánsan eltérő fejlettségű vállalatcsoport létét. Az eredményekből az is kiolvasható, hogy a magasabb logisztikai képességek a mintában együtt jártak a magasabb működési teljesítménnyel is. _________________ The overall objective of the paper is to investigate the relationship between logistics capabilities and company’s performance. Empirical analysis is carried out based on an extensive questionnaire developed and conducted at the Competitive Research Center at the Corvinus University of Budapest in 2009. Using this database the author had two separate research questions: Can she detect companies in their sample with significantly different logistics capabilities. If yes, does more developed logistics lead to higher level performance at the company level? After carrying out their empirical analysis they could state, that they could prove the existence of two clusters, one with less and another with more developed logistics capabilities. They also were able to show that firms with more developed logistics can achieve significantly higher operational performance and can be characterized with a more developed customer orientation.

Üzleti kapcsolatok beágyazottsága a magyar gazdaságban (Heaviness of the Hungarian business relationships)

A cikk a hazai ellátási láncok alapegységének, az üzleti kapcsolatoknak a beágyazottságát vizsgálja. A vállalatok közötti üzleti kapcsolatok sokféle jellemzője közül kiemelt jelentőségű azok stabilitása, ami közvetlenül függ a kapcsolatok beágyazottságának fokától. Az üzleti kapcsolat beágyazottságára hatást gyakorol az együttműködő felek közötti kötelékek három típusa (Håkansson – Snehota [szerk.], 1995): a megrendelő-beszállító közötti (i) tevékenység, (ii) szociális és (iii) erőforrás-kötelékek erőssége, intenzitása. A szerzők kutatásának hipotézise szerint e kötelékek erősségét, és ezen keresztül a kapcsolat beágyazottságának mértékét befolyásolja az, hogy milyen a felek közötti csere tárgyát képező termék- és szolgáltatáscsomag komplexitása. Tanulmányuk a Budapesti Corvinus Egyetem Versenyképesség Kutató Központjának „Kis- és középvállalatok beszállítói pozíciói” című kutatási programja (2007–2008) keretében készült kérdőíves felmérés kiemelt eredményeit mutatja be. Az elemzés magában foglalja az üzleti kapcsolatok számára releváns különböző köteléktípusok jellemzőinek bemutatását, a csere tárgyát meghatározó vevői elváráscsomagok, illetve azok leképeződéseként kialakuló tipikus termék- és szolgáltatáscsomagok ismertetését, végül annak bemutatását, hogy azok miképpen hatnak az üzleti kapcsolatok beágyazottságára. ________________ The focal question of this research is how heavy Hungarian business relationships are, and what specific characteristics this relationships have. Business relationship heaviness is one of the most important relationship features because substantially influences the stability of the relationship itself. The authors argue that the level of buyer-supplier relationship heaviness is determined by activity ties, social bonds and resource links (Håkansson – Snehota ed., 1995) and influenced by the complexity of the exchange object relevant for a specific relationship. The paper presents the results of an online survey carried out among Hungarian companies at the Competitive Research Centre of the Corvinus University of Budapest. The authors’ analysis examines the effect of the exchanged product and service package on relational ties and relationship heaviness.

Coupled symplectic maps as models for subdiffusive processes in disordered Hamiltonian lattices

Acknowledgements One of us (T. B.) acknowledges many interesting discussions on coupled maps with Professor C. Tsallis. We are also grateful to the anonymous referees for their constructive feedback that helped us improve the manuscript and to the HPCS Laboratory of the TEI of Western Greece for providing the computer facilities where all our simulations were performed. C. G. A. was partially supported by the “EPSRC EP/I032606/1” grant of the University of Aberdeen. This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) - Research Funding Program: THALES - Investing in knowledge society through the European Social Fund.

Coupled symplectic maps as models for subdiffusive processes in disordered Hamiltonian lattices

Acknowledgements One of us (T. B.) acknowledges many interesting discussions on coupled maps with Professor C. Tsallis. We are also grateful to the anonymous referees for their constructive feedback that helped us improve the manuscript and to the HPCS Laboratory of the TEI of Western Greece for providing the computer facilities where all our simulations were performed. C. G. A. was partially supported by the “EPSRC EP/I032606/1” grant of the University of Aberdeen. This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) - Research Funding Program: THALES - Investing in knowledge society through the European Social Fund.

Wnt signaling in the heart fields : variations on a common theme

The work was financially supported by the European Community in the framework of the ITN CardioNet registered under number GA289600. SH acknowledges research-funding support from the British Heart Foundation. The authors would like to thank Dr Jan Ruijter for discussion and critically reading the manuscript.

Biological fluorination from the sea : discovery of a SAM-dependent nucleophilic fluorinating enzyme from the marine-derived bacterium Streptomyces xinghaiensis NRRL B24674

We thank Prof. David O’Hagan and Dr Qingzhi Zhang (University of St Andrews, UK) for their helpful discussion and for providing the synthetic 50 -FDA sample. This work is supported by National Natural Science Foundation of China (No. 81503086), a starting funding (No. 20140520) from Tianjin University of Science & Technology, a research funding of “1000 Talents Plan” of Tianjin (to LM) and Foundation of Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education and Tianjin Key Lab of Industrial Microbiology (No. 2015IM106)

Differences in the prevalence of ankylosing spondylitis in primary and secondary care : only one-third of patients are managed in rheumatology

Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: G.T.J. and G.J.M. have received research funding from Pfizer and AbbVie. L.E.D. conducted the analysis while funded by an Medical Research Council PhD studentship

Estimating the effect of state-level gun purchasing policy on county-level firearm suicide mortality

Thesis (Master's)--University of Washington, 2016-08

Muscle Dysmorphia: Current Insights

Since 1997, there has been increasing research focused on Muscle Dysmorphia, a condition underpinned by people’s beliefs they have insufficient muscularity, in both the Western and non-western medical and scientific communities. Much of this empirical interest has surveyed nonclinical samples, and there is limited understanding of people with the condition beyond knowledge about their characteristics. Much existing knowledge about people with the condition is unsurprising and inherent in the definition of the disorder, such as dissatisfaction with muscularity and adherence to muscle-building activities. Only recently have investigators started to explore questions beyond these limited tautological findings that may give rise to substantial knowledge advances, such as the examination of masculine and feminine norms. There is limited understanding of additional topics such as etiology, prevalence, nosology, prognosis, and treatment. Further, the evidence is largely based on a small number of unstandardized case reports and descriptive studies (involving small samples), largely confined to Western (North American, British, and Australian) males. Although much research has been undertaken since the term Muscle Dysmorphia entered the psychiatric lexicon in 1997, there remains tremendous scope for knowledge advancement. A primary task in the short term is for investigators to examine the extent that the condition exists among well-defined populations to help determine the justification for research funding relative to other public health issues. A greater variety of research questions and designs may contribute to a broader and more robust knowledge base than currently exists. Future work will help clinicians assist a group of people whose quality of life and health is placed at risk by their muscular preoccupation.