Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma

The pathophysiology of allergic asthma is driven by T-helper 2 (Th2) immune responses following aeroallergen inhalation. The mechanisms that initiate, potentiate and regulate airways allergy are incompletely characterized. We have previously shown that Hedgehog (Hh) signaling to T-cells, via downstream Gli transcription factors, enhances T-cell conversion to a Th2 phenotype. Here, we show for the first time that Gli-dependent transcription is activated in T-cells in vivo during murine allergic airways disease (AAD) a model for the immunopathology of asthma; and that genetic repression of Gli signaling in Tcells decreases the differentiation and/or recruitment of Th2 cells to the lung. We report that T-cells are not the only cells capable of expressing activated Gli during AAD. A substantial proportion of eosinophils and lung epithelial cells, both central mediators of the immunopathology of asthma, are also able to undergo Hh/Gli signaling. Finally, we show that Shh increases Il4 expression in eosinophils. We therefore propose that Hh signaling during AAD is complex, involving multiple cell types, signaling in an auto- or paracrine fashion. Improved understanding of the role of this major morphogenetic pathway in asthma may give rise to new drug targets for this chronic condition

Generation of spin-motion entanglement in a trapped ion using long-wavelength radiation

Applying a magnetic-field gradient to a trapped ion allows long-wavelength radiation to produce a mechanical force on the ion's motion when internal transitions are driven. We demonstrate such a coupling using a single trapped Yb+171 ion and use it to produce entanglement between the spin and motional state, an essential step toward using such a field gradient to implement multiqubit operations

Ground-state cooling of a trapped ion Using long-wavelength radiation

We demonstrate ground-state cooling of a trapped ion using radio-frequency (rf) radiation. This is a powerful tool for the implementation of quantum operations, where rf or microwave radiation instead of lasers is used for motional quantum state engineering. We measure a mean phonon number of n¯=0.13(4) after sideband cooling, corresponding to a ground-state occupation probability of 88(7)%. After preparing in the vibrational ground state, we demonstrate motional state engineering by driving Rabi oscillations between the |n=0⟩ and |n=1⟩ Fock states. We also use the ability to ground-state cool to accurately measure the motional heating rate and report a reduction by almost 2 orders of magnitude compared with our previously measured result, which we attribute to carefully eliminating sources of electrical noise in the system

Development of a Novel Multipenicillin Assay and Assessment of the Impact of Analyte Degradation: Lessons for Scavenged Sampling in Antimicrobial Pharmacokinetic Study Design

Penicillins are widely used to treat infections in children, however the evidence is continuing to evolve in defining optimal dosing. Modern paediatric pharmacokinetic study protocols frequently favour opportunistic, “scavenged” sampling. This study aimed to develop a small volume single assay for five major penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modelling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultra-high performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data, the impact of drug degradation on inferences made during pharmacokinetic modelling was evaluated. All evaluated penicillins indicated good stability at room temperature (23 ± 2°C) over 1 hour remaining in the range of 98-103% of the original concentration. More rapid analyte degradation had already occurred after 4 hours with stability ranging from 68% to 99%. Stability over longer periods declined: degradation of up to 60% was observed with delayed sample processing of up to 24 hours. Modelling showed that analyte degradation can lead to a 30% and 28% bias in clearance and volume of distribution, respectively, and falsely show nonlinearity in clearance. Five common penicillins can now be measured in a single low volume blood sample. Beta-lactam chemical instability in plasma can cause misleading pharmacokinetic modelling results, which could impact upon model-based dosing recommendations and the forthcoming era of beta-lactam therapeutic drug monitoring

Efficient preparation and detection of microwave dressed-state qubits and qutrits with trapped ions

We demonstrate a method for preparing and detecting all eigenstates of a three-level microwave dressed system with a single trapped ion. The method significantly reduces the experimental complexity of gate operations with dressed-state qubits, as well as allowing all three of the dressed states to be prepared and detected, thereby providing access to a qutrit that is well protected from magnetic field noise. In addition, we demonstrate individual addressing of the clock transitions in two ions using a strong static magnetic field gradient, showing that our method can be used to prepare and detect microwave dressed states in a string of ions when performing multi-ion quantum operations with microwave and radio frequency fields. The individual addressability of clock transitions could also allow for the control of pairwise interaction strengths between arbitrary ions in a string using lasers

Factors influencing online flight ticket purchasing

In spite of the rapid growth in Internet purchasing of products and services in Korea, the buying rate of online flight ticketing remains low. This research investigates the factors that influence online ticket purchasing through a survey of Internet consumers to determine the relationships between convenience, willingness to purchase and trust. From these, the present satisfaction levels can be assessed and future upgrades and requirements can be planned. It is also necessary to determine the background factors that influence Internet-using consumers who visit websites, with a view to simplifying procedures and encouraging repeat visits to the sites

Architects of time: Labouring on digital futures

Drawing on critical analyses of the internet inspired by Gilles Deleuze and the Marxist autonomia movement, this paper suggests a way of understanding the impact of the internet and digital culture on identity and social forms through a consideration of the relationship between controls exercised through the internet, new subjectivities constituted through its use and new labour practices enabled by it. Following Castells, we can see that the distinction between user, consumer and producer is becoming blurred and free labour is being provided by users to corporations. The relationship between digital technologies and sense of community, through their relationship to the future, is considered for its dangers and potentials. It is proposed that the internet may be a useful tool for highlighting and enabling social connections if certain dangers can be traversed. Notably, current remedies for the lack of trust on the internet are questioned with an alternative, drawing on Zygmunt Bauman and Georg Simmel, proposed which is built on community through a vision of a ‘shared network’