Complex Polysaccharide-Based Nanocomposites for Oral Insulin Delivery

Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca2+-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400–600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions

Sheet metal plate design: a structured approach to product optimization in the presence of technological constraints

Geometrical optimization of structural components is a topic of high interest for engineers involved with design activities mainly related to mass reduction. The study described in these pages focuses on the optimization of plates subjected to bending for which stiffness is obtained by a pattern of ribs. Although stiffening by means of ribs is a well-known and old technique, the design of ribs for maximum stiffness is often based on practice and experience. Classical optimization methods such as topological, topographical and parametric optimization fail to give an efficient design with a reasonable programming effort, especially when dealing with many and complex constraints. These constraints are both technical and technological. A most promising technique to obtain optimal rib patterns was to define a set of feasible rib trajectories and then to select the subset with the most efficient combinations. The result is not unique and a method to select the optimal patterns is required. In fact, the stiffening effect increases with increasing rib length, but at a greater cost. A trade-off must be found between structural performance and cost: The tools to guide this selection process is the main objective of the paper, with particular attention in evaluating the stiffening due to the presence of beads on the plate with a close link with the production system and possible technological constraints which can occur during manufacturing processes, such as minimum rib distance or the presence of discontinuities or the presence of holes or other elements on the plate. A special tool with enforced rib cross section is considered, and optimal rib deployment has to be found. Numerical examples attached show the methodology and obtainable results. \ua9 2011 Springer-Verlag London Limited

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Do ResearchGate Scores create ghost academic reputations?

[EN] The academic social network site ResearchGate (RG) has its own indicator, RG Score, for its members. The high profile nature of the site means that the RG Score may be used for recruitment, promotion and other tasks for which researchers are evaluated. In response, this study investigates whether it is reasonable to employ the RG Score as evidence of scholarly reputation. For this, three different author samples were investigated. An outlier sample includes 104 authors with high values. A Nobel sample comprises 73 Nobel winners from Medicine and Physiology, Chemistry, Physics and Economics (from 1975 to 2015). A longitudinal sample includes weekly data on 4 authors with different RG Scores. The results suggest that high RG Scores are built primarily from activity related to asking and answering questions in the site. In particular, it seems impossible to get a high RG Score solely through publications. Within RG it is possible to distinguish between (passive) academics that interact little in the site and active platform users, who can get high RG Scores through engaging with others inside the site (questions, answers, social networks with influential researchers). Thus, RG Scores should not be mistaken for academic reputation indicators.Alberto Martin-Martin enjoys a four-year doctoral fellowship (FPU2013/05863) granted by the Ministerio de Educacion, Cultura, y Deporte (Spain). Enrique Orduna-Malea holds a postdoctoral fellowship (PAID-10-14), from the Polytechnic University of Valencia (Spain).Orduña Malea, E.; Martín-Martín, A.; Thelwall, M.; Delgado-López-Cózar, E. (2017). Do ResearchGate Scores create ghost academic reputations?. Scientometrics. 112(1):443-460. https://doi.org/10.1007/s11192-017-2396-9S4434601121Bosman, J. & Kramer, B. (2016). Innovations in scholarly communication—data of the global 2015–2016 survey. Available at: http://zenodo.org/record/49583 #. Accessed December 11, 2016.González-Díaz, C., Iglesias-García, M., & Codina, L. (2015). Presencia de las universidades españolas en las redes sociales digitales científicas: Caso de los estudios de comunicación. El profesional de la información, 24(5), 1699–2407.Goodwin, S., Jeng, W., & He, D. (2014). Changing communication on ResearchGate through interface updates. Proceedings of the American Society for Information Science and Technology, 51(1), 1–4.Hicks, D., Wouters, P., Waltman, L., de Rijcke, S., & Rafols, I. (2015). The Leiden Manifesto for research metrics. Nature, 520(7548), 429–431.Hoffmann, C. P., Lutz, C., & Meckel, M. (2015). A relational altmetric? Network centrality on ResearchGate as an indicator of scientific impact. Journal of the Association for Information Science and Technology, 67(4), 765–775.Jiménez-Contreras, E., de Moya Anegón, F., & Delgado López-Cózar, E. (2003). The evolution of research activity in Spain: The impact of the National Commission for the Evaluation of Research Activity (CNEAI). Research Policy, 32(1), 123–142.Jordan, K. (2014a). Academics’ awareness, perceptions and uses of social networking sites: Analysis of a social networking sites survey dataset (December 3, 2014). Available at: http://dx.doi.org/10.2139/ssrn.2507318 . Accessed December 11, 2016.Jordan, K. (2014b). Academics and their online networks: Exploring the role of academic social networking sites. First Monday, 19(11). Available at: http://dx.doi.org/10.5210/fm.v19i11.4937 . Accessed December 11, 2016.Jordan, K. (2015). Exploring the ResearchGate score as an academic metric: reflections and implications for practice. Quantifying and Analysing Scholarly Communication on the Web (ASCW’15), 30 June 2015, Oxford. Available at: http://ascw.know-center.tugraz.at/wp-content/uploads/2015/06/ASCW15_jordan_response_kraker-lex.pdf . Accessed December 11, 2016.Kadriu, A. (2013). Discovering value in academic social networks: A case study in ResearchGate. Proceedings of the ITI 2013—35th Int. Conf. on Information Technology Interfaces Information Technology Interfaces, pp. 57–62.Kraker, P. & Lex, E. (2015). A critical look at the ResearchGate score as a measure of scientific reputation. Proceedings of the Quantifying and Analysing Scholarly Communication on the Web workshop (ASCW’15), Web Science conference 2015. Available at: http://ascw.know-center.tugraz.at/wp-content/uploads/2016/02/ASCW15_kraker-lex-a-critical-look-at-the-researchgate-score_v1-1.pdf . Accessed December 11, 2016.Li, L., He, D., Jeng, W., Goodwin, S. & Zhang, C. (2015). Answer quality characteristics and prediction on an academic Q&A Site: A case study on ResearchGate. Proceedings of the 24th International Conference on World Wide Web Companion, pp. 1453–1458.Martín-Martín, A., Orduna-Malea, E., Ayllón, J. M. & Delgado López-Cózar, E. (2016). The counting house: measuring those who count. Presence of Bibliometrics, Scientometrics, Informetrics, Webometrics and Altmetrics in the Google Scholar Citations, ResearcherID, ResearchGate, Mendeley & Twitter. Available at: https://arxiv.org/abs/1602.02412 . Accessed December 11, 2016.Martín-Martín, A., Orduna-Malea, E. & Delgado López-Cózar, E. (2016). The role of ego in academic profile services: Comparing Google Scholar, ResearchGate, Mendeley, and ResearcherID. Researchgate, Mendeley, and Researcherid. The LSE Impact of Social Sciences blog. Available at: http://blogs.lse.ac.uk/impactofsocialsciences/2016/03/04/academic-profile-services-many-mirrors-and-faces-for-a-single-ego . Accessed December 11, 2016.Matthews, D. (2016). Do academic social networks share academics’ interests?. Times Higher Education. Available at: https://www.timeshighereducation.com/features/do-academic-social-networks-share-academics-interests . Accessed December 11, 2016.Memon, A. R. (2016). ResearchGate is no longer reliable: leniency towards ghost journals may decrease its impact on the scientific community. Journal of the Pakistan Medical Association, 66(12), 1643–1647.Mikki, S., Zygmuntowska, M., Gjesdal, Ø. L. & Al Ruwehy, H. A. (2015). Digital presence of norwegian scholars on academic network sites-where and who are they?. Plos One 10(11). Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142709 . Accessed December 11, 2016.Nicholas, D., Clark, D., & Herman, E. (2016). ResearchGate: Reputation uncovered. Learned Publishing, 29(3), 173–182.Orduna-Malea, E., Martín-Martín, A., & Delgado López-Cózar, E. (2016). The next bibliometrics: ALMetrics (Author Level Metrics) and the multiple faces of author impact. El profesional de la información, 25(3), 485–496.Ortega, Jose L. (2015). Relationship between altmetric and bibliometric indicators across academic social sites: The case of CSIC’s members. Journal of informetrics, 9(1), 39–49.Ortega, Jose L. (2016). Social network sites for scientists. Cambridge: Chandos.Ovadia, S. (2014). ResearchGate and Academia. edu: Academic social networks. Behavioral & Social Sciences Librarian, 33(3), 165–169.Thelwall, M., & Kousha, K. (2015). ResearchGate: Disseminating, communicating, and measuring Scholarship? Journal of the Association for Information Science and Technology, 66(5), 876–889.Thelwall, M. & Kousha, K. (2017). ResearchGate articles: Age, discipline, audience size and impact. Journal of the Association for Information Science and Technology, 68(2), 468–479.Van Noorden, R. (2014). Online collaboration: Scientists and the social network. Nature, 512(7513), 126–129.Wilsdon, J., Allen, L., Belfiore, E., Campbell, P., Curry, S., Hill, S. et al. (2015). The Metric Tide: Independent Review of the Role of Metrics in Research Assessment and Management. HEFCE. Available at: http://doi.org/10.13140/RG.2.1.4929.1363 . Accessed December 11, 2016

A Search for MeV to TeV Neutrinos from Fast Radio Bursts with IceCube

We present two searches for IceCube neutrino events coincident with 28 fast radio bursts (FRBs) and 1 repeating FRB. The first improves on a previous IceCube analysis - searching for spatial and temporal correlation of events with FRBs at energies greater than roughly 50 GeV - by increasing the effective area by an order of magnitude. The second is a search for temporal correlation of MeV neutrino events with FRBs. No significant correlation is found in either search; therefore, we set upper limits on the time-integrated neutrino flux emitted by FRBs for a range of emission timescales less than one day. These are the first limits on FRB neutrino emission at the MeV scale, and the limits set at higher energies are an order-of-magnitude improvement over those set by any neutrino telescope

Efficient propagation of systematic uncertainties from calibration to analysis with the SnowStorm method in IceCube

Efficient treatment of systematic uncertainties that depend on a large number of nuisance parameters is a persistent difficulty in particle physics and astrophysics experiments. Where low-level effects are not amenable to simple parameterization or re-weighting, analyses often rely on discrete simulation sets to quantify the effects of nuisance parameters on key analysis observables. Such methods may become computationally untenable for analyses requiring high statistics Monte Carlo with a large number of nuisance degrees of freedom, especially in cases where these degrees of freedom parameterize the shape of a continuous distribution. In this paper we present a method for treating systematic uncertainties in a computationally efficient and comprehensive manner using a single simulation set with multiple and continuously varied nuisance parameters. This method is demonstrated for the case of the depth-dependent effective dust distribution within the IceCube Neutrino Telescope

Combined sensitivity to the neutrino mass ordering with JUNO, the IceCube Upgrade, and PINGU

The ordering of the neutrino mass eigenstates is one of the fundamental open questions in neutrino physics. While current-generation neutrino oscillation experiments are able to produce moderate indications on this ordering, upcoming experiments of the next generation aim to provide conclusive evidence. In this paper we study the combined performance of the two future multi-purpose neutrino oscillation experiments JUNO and the IceCube Upgrade, which employ two very distinct and complementary routes toward the neutrino mass ordering. The approach pursued by the 20 kt medium-baseline reactor neutrino experiment JUNO consists of a careful investigation of the energy spectrum of oscillated νe produced by ten nuclear reactor cores. The IceCube Upgrade, on the other hand, which consists of seven additional densely instrumented strings deployed in the center of IceCube DeepCore, will observe large numbers of atmospheric neutrinos that have undergone oscillations affected by Earth matter. In a joint fit with both approaches, tension occurs between their preferred mass-squared differences Δm312=m32-m12 within the wrong mass ordering. In the case of JUNO and the IceCube Upgrade, this allows to exclude the wrong ordering at >5σ on a timescale of 3-7 years - even under circumstances that are unfavorable to the experiments' individual sensitivities. For PINGU, a 26-string detector array designed as a potential low-energy extension to IceCube, the inverted ordering could be excluded within 1.5 years (3 years for the normal ordering) in a joint analysis

Search for sources of astrophysical neutrinos using seven years of icecube cascade events

Low-background searches for astrophysical neutrino sources anywhere in the sky can be performed using cascade events induced by neutrinos of all flavors interacting in IceCube with energies as low as ∼1 TeV. Previously we showed that, even with just two years of data, the resulting sensitivity to sources in the southern sky is competitive with IceCube and ANTARES analyses using muon tracks induced by charge current muon neutrino interactions - especially if the neutrino emission follows a soft energy spectrum or originates from an extended angular region. Here, we extend that work by adding five more years of data, significantly improving the cascade angular resolution, and including tests for point-like or diffuse Galactic emission to which this data set is particularly well suited. For many of the signal candidates considered, this analysis is the most sensitive of any experiment to date. No significant clustering was observed, and thus many of the resulting constraints are the most stringent to date. In this paper we will describe the improvements introduced in this analysis and discuss our results in the context of other recent work in neutrino astronomy

Design and performance of the first IceAct demonstrator at the South Pole

In this paper we describe the first results of IceAct, a compact imaging air-Cherenkov telescope operating in coincidence with the IceCube Neutrino Observatory (IceCube) at the geographic South Pole. An array of IceAct telescopes (referred to as the IceAct project) is under consideration as part of the IceCube-Gen2 extension to IceCube. Surface detectors in general will be a powerful tool in IceCube-Gen2 for distinguishing astrophysical neutrinos from the dominant backgrounds of cosmic-ray induced atmospheric muons and neutrinos: the IceTop array is already in place as part of IceCube, but has a high energy threshold. Although the duty cycle will be lower for the IceAct telescopes than the present IceTop tanks, the IceAct telescopes may prove to be more effective at lowering the detection threshold for air showers. Additionally, small imaging air-Cherenkov telescopes in combination with IceTop, the deep IceCube detector or other future detector systems might improve measurements of the composition of the cosmic ray energy spectrum. In this paper we present measurements of a first 7-pixel imaging air Cherenkov telescope demonstrator, proving the capability of this technology to measure air showers at the South Pole in coincidence with IceTop and the deep IceCube detector