Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.35 ng/g luciferase protein expression in the urothelium and lamina propria regions. The relatively higher molecular weight polymer (83 kDa) did not induce morphologic changes or inflammatory responses in the bladder. This approach of altering polymer molecular weight for prolonging gene transfer residence time and deeper penetration through the BPB could be the basis for the design of future gene therapies for bladder diseases

Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis

Chemoresistance is one of the barriers for the development of bladder cancer treatments. Previously, we showed that glycoprotein-130 (GP130) is overexpressed in chemoresistant bladder cancer cells and that knocking down GP130 expression reduced cell viability. In our current work, we showed that down-regulation of GP130 sensitized bladder cancer cells to cisplatin-based chemotherapy by activating DNA repair signaling. We performed immunohistochemistry and demonstrated a positive correlation between the levels of Ku70, an initiator of canonical non-homologous end joining repair (c-NHEJ) and suppressor of apoptosis, and GP130 in human bladder cancer specimens. GP130 knockdown by SC144, a small molecule inhibitor, in combination with cisplatin, increased the number of DNA lesions, specifically DNA double-stranded breaks, with a subsequent increase in apoptosis and reduced cell viability. Furthermore, GP130 inhibition attenuated Ku70 expression in bladder and breast cancer cells as well as in transformed kidney cells. In addition, we fabricated a novel polymer-lipid hybrid delivery system to facilitate GP130 siRNA delivery that had a similar efficiency when compared with Lipofectamine, but induced less toxicity

Decentralized Estimation over Orthogonal Multiple-access Fading Channels in Wireless Sensor Networks - Optimal and Suboptimal Estimators

Optimal and suboptimal decentralized estimators in wireless sensor networks (WSNs) over orthogonal multiple-access fading channels are studied in this paper. Considering multiple-bit quantization before digital transmission, we develop maximum likelihood estimators (MLEs) with both known and unknown channel state information (CSI). When training symbols are available, we derive a MLE that is a special case of the MLE with unknown CSI. It implicitly uses the training symbols to estimate the channel coefficients and exploits the estimated CSI in an optimal way. To reduce the computational complexity, we propose suboptimal estimators. These estimators exploit both signal and data level redundant information to improve the estimation performance. The proposed MLEs reduce to traditional fusion based or diversity based estimators when communications or observations are perfect. By introducing a general message function, the proposed estimators can be applied when various analog or digital transmission schemes are used. The simulations show that the estimators using digital communications with multiple-bit quantization outperform the estimator using analog-and-forwarding transmission in fading channels. When considering the total bandwidth and energy constraints, the MLE using multiple-bit quantization is superior to that using binary quantization at medium and high observation signal-to-noise ratio levels

Cartan subalgebras and the UCT problem, II

We show that outer approximately represenbtable actions of a finite cyclic group on UCT Kirchberg algebras satisfy a certain quasi-freeness type property if the corresponding crossed products satisfy the UCT and absorb a suitable UHF algebra tensorially. More concretely, we prove that for such an action there exists an inverse semigroup of homogeneous partial isometries that generates the ambient C*-algebra and whose idempotent semilattice generates a Cartan subalgebra. We prove a similar result for actions of finite cyclic groups with the Rokhlin property on UCT Kirchberg algebras absorbing a suitable UHF algebra. These results rely on a new construction of Cartan subalgebras in certain inductive limits of Cartan pairs. We also provide a characterisation of the UCT problem in terms of finite order automorphisms, Cartan subalgebras and inverse semigroups of partial isometries of the Cuntz algebra $\mathcal{O}_2$. This generalizes earlier work of the authors.Comment: minor revisions; final version, accepted for publication in Math. Ann.; 26 page

Nord Pool Ontology to Enhance Electricity Markets Simulation in MASCEM

This paper proposes the use of ontologies to enable information and knowledge exchange, to test different electricity market models and to allow players from different systems to interact in common market environments. Multi-agent based software is particularly well fitted to analyse dynamic and adaptive systems with complex interactions among its constituents, such as the complex and dynamic electricity markets. The main drivers are the markets’ restructuring and evolution into regional and continental scales, along with the constant changes brought by the increasing necessity for an adequate integration of renewable energy sources. An ontology to represent the concepts related to the Nord Pool Elspot market is proposed. It is validated through a case study considering the simulation of Elspot market. Results show that heterogeneous agents are able to effectively participate in the simulation by using the proposed ontologies to support their communications with the Nord Pool market operator.This work has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 641794 (project DREAM-GO) and from FEDER Funds through COMPETE program and from National Funds through FCT under the project UID/EEA/00760/2013.info:eu-repo/semantics/publishedVersio

Proposal for a multilevel university cybermetric analysis model

The final publication is available at Springer via http://dx.doi.org/10.1007/s11192-012-0868-5Universities’ online seats have gradually become complex systems of dynamic information where all their institutions and services are linked and potentially accessible. These online seats now constitute a central node around which universities construct and document their main activities and services. This information can be quantitative measured by cybermetric techniques in order to design university web rankings, taking the university as a global reference unit. However, previous research into web subunits shows that it is possible to carry out systemic web analyses, which open up the possibility of carrying out studies which address university diversity, necessary for both describing the university in greater detail and for establishing comparable ranking units. To address this issue, a multilevel university cybermetric analysis model is proposed, based on parts (core and satellite), levels (institutional and external) and sublevels (contour and internal), providing a deeper analysis of institutions. Finally the model is integrated into another which is independent of the technique used, and applied by analysing Harvard University as an example of use.Orduña Malea, E.; Ontalba Ruipérez, JA. (2013). Proposal for a multilevel university cybermetric analysis model. Scientometrics. 95(3):863-884. doi:10.1007/s11192-012-0868-5S863884953Acosta Márquez, T., Igartua Perosanz, J.J. & Gómez Isla, J. (2009). Páginas web de las universidades españolas. Enred: revista digital de la Universidad de Salamanca, 5 [online; discontinued].Aguillo, I. F. (1998). Hacia un concepto documental de sede web. El Profesional de la Información, 7(1–2), 45–46.Aguillo, I. F. (2009). Measuring the institutions’ footprint in the web. 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Journal of the American Society for Information Science and Technology, 55(14), 1216–1227.Buenadicha, M., Chamorro, A., Miranda, F. J., & González, O. R. (2001). A new web assessment index: Spanish Universities Analysis. Internet Research, 11(3), 226–234.Castells, M. (2001). La galaxia Internet. Barcelona: Plaza y Janés.Chu, H., He, S., & Thelwall, M. (2002). Library and Information Science Schools in Canada and USA: a Webometric perspective. Journal of Education for Library and Information Science, 43(2), 110–125.Crowston, K., & Williams, M. (2000). Reproduced and Emergent Genres of Communication on the World Wide Web. The Information Society: an International Journal, 16(3), 201–215.Goldfarb, A. (2006). The (teaching) role of universities in the diffusion of the Internet. International Journal of Industrial Organization, 24(2), 203–225.Ingwersen, P. (1998). The calculation of web impact factors. Journal of Documentation, 54(2), 236–243.Katz, R. N. (2008a). The tower and the cloud: Higher education in the age of cloud computing. USA: Educause.Katz, R. N. (2008b). The gathering cloud: is this the end of the middle. In R. N. Katz (Ed.), The tower and the cloud: Higher education in the age of cloud computing (p. 2008). USA: Educause.Li, X. (2005). National and international university departmental Web site interlinking: a webometric analysis. [Unpublished doctoral dissertation]. Wolverhampton, UK: University of Wolverhampton.Li, X., Thelwall, M., Musgrove, P., & Wilkinson, D. (2003). The relationship between the links/Web Impact Factors of computer science departments in UK and their RAE (Research Assessment Exercise) ranking in 2001. Scientometrics, 57(2), 239–255.Middleton, I., McConnell, M., & Davidson, G. (1999). Presenting a model for the structure and content of a University World Wide Web site. Journal of Information Science, 25(3), 217–219.Orduña-Malea, E. (2012). 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Use of news articles and announcements on official websites of universities. Turkish Online Journal of Educational Technology, 10(2), 287–296

Enhanced switching stability in Ta 2 O 5 resistive RAM by fluorine doping

The effect of fluorine doping on the switching stability of Ta2O5 resistive random access memory devices is investigated. It shows that the dopant serves to increase the memory window and improve the stability of the resistive states due to the neutralization of oxygen vacancies. The ability to alter the current in the low resistance state with set current compliance coupled with large memory window makes multilevel cell switching more favorable. The devices have set and reset voltages of <1V with improved stability due to the fluorine doping. Density functional modelling shows that the incorporation of fluorine dopant atoms at the two-fold O vacancy site in the oxide network removes the defect state in the mid bandgap, lowering the overall density of defects capable of forming conductive filaments. This reduces the probability of forming alternative conducting paths and hence improves the current stability in the low resistance states. The doped devices exhibit more stable resistive states in both dc and pulsed set and reset cycles. The retention failure time is estimated to be a minimum of 2 years for F-doped devices measured by temperature accelerated and stress voltage accelerated retention failure methods

Rate equation modelling of erbium luminescence dynamics in erbium-doped silicon-rich-silicon-oxide

Erbium doped silicon-rich silica offers broad band and very efficient excitation of erbium photoluminescence (PL) due to a sensitization effect attributed to silicon nanocrystals (Si-nc), which grow during thermal treatment. PL decay lifetime measurements of sensitised Er3+ ions are usually reported to be stretched or multi exponential, very different to those that are directly excited, which usually show a single exponential decay component. In this paper, we report on SiO2 thin films doped with Si-nc's and erbium. Time resolved PL measurements reveal two distinct 1.54 μm Er decay components; a fast microsecond component, and a relatively long lifetime component (10 ms). We also study the structural properties of these samples through TEM measurements, and reveal the formation of Er clusters. We propose that these Er clusters are responsible for the fast μs decay component, and we develop rate equation models that reproduce the experimental transient observations, and can explain some of the reported transient behaviour in previously published literature

Activation of EGFR/ERBB2 via Pathways Involving ERK1/2, P38 MAPK, AKT and FOXO Enhances Recovery of Diabetic Hearts from Ischemia-Reperfusion Injury

This study characterized the effects of diabetes and/or ischemia on epidermal growth factor receptor, EGFR, and/or erbB2 signaling pathways on cardiac function. Isolated heart perfusion model of global ischemia was used to study the effect of chronic inhibition or acute activation of EGFR/erbB2 signaling on cardiac function in a rat model of type-1 diabetes. Induction of diabetes with streptozotocin impaired recovery of cardiac function (cardiac contractility and hemodynamics) following 40 minutes of global ischemia in isolated hearts. Chronic treatment with AG825 or AG1478, selective inhibitors of erbB2 and EGFR respectively, did not affect hyperglycemia but led to an exacerbation whereas acute administration of the EGFR ligand, epidermal growth factor (EGF), led to an improvement in cardiac recovery in diabetic hearts. Diabetes led to attenuated dimerization and phosphorylation of cardiac erbB2 and EGFR receptors that was associated with reduced signaling via extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 mitogen activated protein (MAP) kinase and AKT (protein kinase B). Ischemia was also associated with reduced cardiac signaling via these molecules whereas EGF-treatment opposed diabetes and/or ischemia induced changes in ERK1/2, p38 MAP kinase, and AKT-FOXO signaling. Losartan treatment improved cardiac function in diabetes but also impaired EGFR phosphorylation in diabetic heart. Co-administration of EGF rescued Losartan-mediated reduction in EGFR phosphorylation and significantly improved cardiac recovery more than with either agent alone. EGFR/erbB2 signaling is an important cardiac survival pathway whose activation, particularly in diabetes, ischemia or following treatment with drugs that inhibit this cascade, significantly improves cardiac function. These findings may have clinical relevance particularly in the treatment of diabetes-induced cardiac dysfunction