Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Measures on Banach Manifolds and Supersymmetric Quantum Field Theory

We show how to construct measures on Banach manifolds associated to supersymmetric quantum field theories. These measures are mathematically well-defined objects inspired by the formal path integrals appearing in the physics literature on quantum field theory. We give three concrete examples of our construction. The first example is a family $\mu_P^{s,t}$ of measures on a space of functions on the two-torus, parametrized by a polynomial $P$ (the Wess-Zumino-Landau-Ginzburg model). The second is a family \mu_\cG^{s,t} of measures on a space \cG of maps from $\P^1$ to a Lie group (the Wess-Zumino-Novikov-Witten model). Finally we study a family $\mu_{M,G}^{s,t}$ of measures on the product of a space of connection s on the trivial principal bundle with structure group $G$ on a three-dimensional manifold $M$ with a space of \fg-valued three-forms on $M.$ We show that these measures are positive, and that the measures \mu_\cG^{s,t} are Borel probability measures. As an application we show that formulas arising from expectations in the measures \mu_\cG^{s,1} reproduce formulas discovered by Frenkel and Zhu in the theory of vertex operator algebras. We conjecture that a similar computation for the measures $\mu_{M,SU(2)}^{s,t},$ where $M$ is a homology three-sphere, will yield the Casson invariant of $M.$Comment: Minor correction

Adaptive hypermedia driven serious game design and cognitive style in school settings: an exploratory study

The potential value of adaptive hypermedia and game based learning to education and training has long been recognised, numerous studies have been undertaken in both those areas investigating its potential to improve learner performance. In particular research has indicated that tailoring content to match the prior knowledge of the user has the power to increase the effectiveness of learning systems. Recent studies have begun to indicate that Adaptive Hypermedia Learning Systems (AHLS) based on cognitive styles have the power to improve learner performance. Recent examples of research exploring avenues for effectively incorporating serious games into AHLS indicated that integrating serious games into a personalized learning environment has the potential educational benefits of combining a personalized delivery with increased learner motivation. The exploratory study presented in this paper here developed an Adaptive Hypermedia Driven Serious Game (AHDSG) based around Pask’s Holist-Serialist dimension of cognitive style. A prototype AHDSG was designed and developed to teach students about Sutton Hoo and archaeological methods. Sixty-six secondary school students participated in this study. Overall the findings of this study show that there was an improvement in performance among all participants. Although the participants that used the system which adapted to their preferred cognitive style achieved a higher mean gain score, the difference was not significant

Understanding mechanisms of asphaltene adsorption from organic solvent on mica

The adsorption process of asphaltene onto molecularly smooth mica surfaces from toluene solutions of various concentrations (0.01-1 wt %) was studied using a surface forces apparatus (SFA). Adsorption of asphaltenes onto mica was found to be highly dependent on adsorption time and asphaltene concentration of the solution. The adsorption of asphaltenes led to an attractive bridging force between the mica surfaces in asphaltene solution. The adsorption process was identified as being controlled by the diffusion of asphaltenes from the bulk solution to the mica surface with a diffusion coefficient on the order of 10-10 m2/s at room temperature, depending on the asphaltene bulk concentration. This diffusion coefficient corresponds to a hydrodynamic molecular radius of approximately 0.5 nm, indicating that asphaltene diffuses to mica surfaces as individual molecules at very low concentration (e.g., 0.01 wt %). Atomic force microscopy images of the adsorbed asphaltenes on mica support the results of the SFA force measurements. The results from the SFA force measurements provide valuable insights into the molecular interactions (e.g., steric repulsion and bridging attraction as a function of distance) of asphaltenes in organic media and hence their roles in crude oil and bitumen production

Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

PLCγ03B3 binds Spry1 and Spry2. Overexpression of Spry decreased PLCγ03B3 activity and IP3 and DAG production, whereas Spry-deficient cells yielded more IP3. Spry overexpression inhibited T-cell receptor signaling and Spry1 null T-cells hyperproliferated with TCR ligation. Through action of PLCγ03B3, Spry may influence signaling through multiple receptors

Demand-Orientated Power Production from Biogas: Modeling and Simulations under Swedish Conditions

The total share of intermittent renewable electricity is increasing, intensifying the need for power balancing in future electricity systems. Demand-orientated combined heat and power (CHP) production from biogas has potential for this purpose. An agricultural biogas plant, using cattle manure and sugar beet for biogas and CHP production, was analyzed here. The model Dynamic Biogas plant Model (DyBiM) was developed and connected to the Anaerobic Digestion Model No. 1 (ADM1). Flexible scenarios were simulated and compared against a reference scenario with continuous production, to evaluate the technical requirements and economic implications of demand-orientated production. The study was set in Swedish conditions regarding electricity and heat price, and the flexibility approaches assessed were increased CHP and gas storage capacity and feeding management. The results showed that larger gas storage capacity was needed for demand-orientated CHP production but that feeding management reduced the storage requirement because of fast biogas production response to feeding. Income from electricity increased by 10%, applying simple electricity production strategies to a doubled CHP capacity. However, as a result of the currently low Swedish diurnal electricity price variation and lack of subsidies for demand-orientated electricity production, the increase in income was too low to cover the investment costs. Nevertheless, DyBiM proved to be a useful modeling tool for assessing the economic outcome of different flexibility scenarios for demand-orientated CHP production

Analytical protocols for separation and electron microscopy of nanoparticles interacting with bacterial cells

An important step toward understanding interactions between nanoparticles (NPs) and bacteria is the ability to directly observe NPs interacting with bacterial cells. NPbacteria mixtures typical in nanomedicine, however, are not yet amendable for direct imaging in solution. Instead, evidence of NPcell interactions must be preserved in derivative (usually dried) samples to be subsequently revealed in high-resolution images, e.g., via scanning electron microscopy (SEM). Here, this concept is realized for a mixed suspension of model NPs and Staphylococcus aureus bacteria. First, protocols for analyzing the relative colloidal stabilities of NPs and bacteria are developed and validated based on systematic centrifugation and comparison of colony forming unit (CFU) counting and optical density (OD) measurements. Rate-dependence of centrifugation efficiency for each component suggests differential sedimentation at a specific predicted rate as an effective method for removing free NPs after co-incubation; the remaining fraction comprises bacteria with any associated NPs and can be examined, e.g., by SEM, for evidence of NPbacteria interactions. These analytical protocols, validated by systematic control experiments and high-resolution SEM imaging, should be generally applicable for investigating NPbacteria interactions.financial support from the following sources: grant SFRH/BPD/47693/2008 from the Portuguese Foundation for Science and Technology (FCT); FCT Strategic Project PEst-OE/EQB/LA0023/2013; project “BioHealth Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, cofunded by the Programa Operacional Regional do Norte (ON.2−O Novo Norte), QREN, FEDER; project “Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB”, ref. FCOMP-01-0124-FEDER- 027462