Gamma-herpesvirus latency requires T cell evasion during episome maintenance.

The gamma-herpesviruses persist as latent episomes in a dynamic lymphocyte pool. Their consequent need to express a viral episome maintenance protein presents a potential immune target. The glycine-alanine repeat of the Epstein-Barr virus episome maintenance protein, EBNA-1, limits EBNA-1 epitope presentation to CD8(+) T lymphocytes (CTLs). However, CTL recognition occurs in vitro, so the significance of such evasion for viral fitness is unclear. We used the murine gamma-herpesvirus-68 (MHV-68) to define the in vivo contribution of cis-acting CTL evasion to host colonisation. Although the ORF73 episome maintenance protein of MHV-68 lacks a glycine-alanine repeat, it was equivalent to EBNA-1 in conferring limited presentation on linked epitopes. This was associated with reduced protein synthesis and reduced protein degradation. We bypassed the cis-acting evasion of ORF73 by using an internal ribosome entry site to express in trans-a CTL target from the same mRNA. This led to a severe, MHC class I-restricted and CTL-dependent reduction in viral latency. Thus, despite MHV-68 encoding at least two trans-acting CTL evasion proteins, cis-acting evasion during episome maintenance was essential for normal host colonisation

On the behavior of titanium within thermal barrier coatings and its influence on residual stress within the TGO

This research focuses on analysing the interaction between three commercially used diffusion coatings and a nickel based superalloy CMSX-4. The coatings applied are alumide, Pt-alumide and Pt-modifed γ/γ′. The research has two main themes, firstly diffusion and secondly oxidation. Results of quantitative EPMA show that titanium diffusion towards the surface varies between coatings, and has a strong correlation with the use of platinum within coatings. The concentrations of Ti within Pt-aluminide coatings after 100 hours oxidation in air at 1100°C were found to be twice as high as those within the plain aluminised CMSX-4 samples. Furthermore uphill diffusion of Ti was observed to occur within Pt-modifed γ/γ′ after the same exposure. In order to examine the effect of platinum additions on the diffusive behavior of titanium, first principle calculations using the density functional theory implementation CASTEP have been performed. In an ordered lattice structure, diffusion of a solute species must occur via the presence of defects, either anti-site (NiAl) or vacancy (VNi). Moreover clustering of these defects leads to increased opportunities for solute diffusion and hence increased diffusion rates within that structure. We have shown that the use of Pt strengthens defect formation and defect clustering within the Ni3Al L12 phase. By increasing the amount of defect clusters Ti can diffuse more freely from the substrate through the coating to the surface

A Quantum Random Walk Search Algorithm

Quantum random walks on graphs have been shown to display many interesting properties, including exponentially fast hitting times when compared with their classical counterparts. However, it is still unclear how to use these novel properties to gain an algorithmic speed-up over classical algorithms. In this paper, we present a quantum search algorithm based on the quantum random walk architecture that provides such a speed-up. It will be shown that this algorithm performs an oracle search on a database of $N$ items with $O(\sqrt{N})$ calls to the oracle, yielding a speed-up similar to other quantum search algorithms. It appears that the quantum random walk formulation has considerable flexibility, presenting interesting opportunities for development of other, possibly novel quantum algorithms.Comment: 13 pages, 3 figure

Effects of Noisy Oracle on Search Algorithm Complexity

Grover's algorithm provides a quadratic speed-up over classical algorithms for unstructured database or library searches. This paper examines the robustness of Grover's search algorithm to a random phase error in the oracle and analyzes the complexity of the search process as a function of the scaling of the oracle error with database or library size. Both the discrete- and continuous-time implementations of the search algorithm are investigated. It is shown that unless the oracle phase error scales as O(N^(-1/4)), neither the discrete- nor the continuous-time implementation of Grover's algorithm is scalably robust to this error in the absence of error correction.Comment: 16 pages, 4 figures, submitted to Phys. Rev.

The Anatomy of Sartorius Muscle and its Implications for Sarcoma Radiotherapy

Purpose: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume

Discovery of pyrazolopyrimidines that selectively inhibit CSF-1R kinase by iterative design, synthesis and screening against glioblastoma cells

We are grateful to Medical Research Scotland (PHD-1046-2016) for funding and a joint Cancer Research UK (A28596) and The Brain Tumour Charity award (GN-000676) to N. O. C. T. V. thanks EU Horizon 2020 research and innovation programme under the Marie Skls PHD-1046-2016Medical Research Scotland A28596Cancer Research UK GN-000676Brain Tumour Charity award 749299European Union (EU)MS

Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity, and Inflammation in Adult Females

We previously observed greater ozone-induced lung function decrements in obese than non-obese women. Animal models suggest that obesity enhances ozone-induced airway reactivity and inflammation. In a controlled exposure study, we compared the acute effect of randomized 0.4ppm ozone and air exposures (2 h with intermittent light exercise) in obese (N = 20) (30<BMI<40Kg/m2) vs. non-obese (N = 20) (BMI<25Kg/m2) non-smoking 18–35 year old women. We measured spirometry and bronchial reactivity to inhaled methacholine (3h post-exposure). Inflammation and obesity markers were assessed in the blood (pre, 4h post, and 20h post exposures) and induced-sputum (4h post-exposures and on 24h pre-exposure training day, no exercise): measures of C reactive protein (CRP) (blood only), leptin (blood only), adiponectin, interleukins IL-6, IL-1b, and IL-8, and tumor necrosis factor alpha, and sputum cell differential cell counts. The pre- to post-exposure decrease in forced vital capacity after ozone (adjusted for the change after air exposure) was significantly greater in the obese group (12.5+/-7.5 vs. 8.0+/-5.8%, p<0.05). Post ozone exposure, 6 obese and 6 non-obese subjects responded to methacholine at ≤ 10mg/ml (the maximum dose); the degree of hyperresponsiveness was similar for the two groups. Both BMI groups showed similar and significant ozone-induced increases in sputum neutrophils. Plasma IL-6 was increased by exercise (4 hr post air exposure vs. pre) only in the obese but returned to pre-air exposure levels at 20hr post-exposure. Plasma IL-6 was significantly increased at 4hr post ozone exposure in both groups and returned to pre-exposure levels by 20h post-exposure. These results confirm our previous findings of greater post-ozone spirometric decrements in obese young women. However, acute ozone-induced airway reactivity to methacholine and airway inflammation did not differ by obesity at the exposure and exercise levels used

Citizen participation in news

The process of producing news has changed significantly due to the advent of the Web, which has enabled the increasing involvement of citizens in news production. This trend has been given many names, including participatory journalism, produsage, and crowd-sourced journalism, but these terms are ambiguous and have been applied inconsistently, making comparison of news systems difficult. In particular, it is problematic to distinguish the levels of citizen involvement, and therefore the extent to which news production has genuinely been opened up. In this paper we perform an analysis of 32 online news systems, comparing them in terms of how much power they give to citizens at each stage of the news production process. Our analysis reveals a diverse landscape of news systems and shows that they defy simplistic categorisation, but it also provides the means to compare different approaches in a systematic and meaningful way. We combine this with four case studies of individual stories to explore the ways that news stories can move and evolve across this landscape. Our conclusions are that online news systems are complex and interdependent, and that most do not involve citizens to the extent that the terms used to describe them imply