Development of ultrafast laser inscribed astrophotonic components

The rapid development of astronomical instrumentation has been aided by many innovative new photonic designs, which offer improvements in stability, precision, size and cost, scalability, etc. ─ the field of astrophotonics. A powerful technique enabling many of these astrophotonic devices, ultrafast laser inscription (ULI), creates highly localised and controlled refractive index modification, which guides the path of light in a very efficient manner. This thesis discusses three separate astrophotonic devices, each with a specific application, to demonstrate the versatility of ULI. Firstly, a reformatting device based on a photonic lantern and 3D ULI waveguide reformatting component, transforms a multimode telescope PSF to a diffraction-limited pseudo-slit. When used to feed a spectrograph, a significant reduction in modal noise ─ a limiting factor in high-resolution multimode fibre-fed spectrographs ─ is demonstrated, with the potential for improved near-infrared radial velocity observations. Secondly, a similar ULI reformatting device for an integral field unit, based on multicore fibre with affixed microlenses, may enable the direct imaging of exoplanets and characterisation of their atmospheres. Thirdly, a two-telescope K-band beam combiner based on ULI directional couplers with an achromatic 3dB splitting ratio is presented. Such a device will upgrade the stellar interferometry capabilities of the CHARA array

A systematic review of the use of an expertise-based randomised controlled trial design

Acknowledgements JAC held a Medical Research Council UK methodology (G1002292) fellowship, which supported this research. The Health Services Research Unit, Institute of Applied Health Sciences (University of Aberdeen), is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Views express are those of the authors and do not necessarily reflect the views of the funders.Peer reviewedPublisher PD

The Orphan G Protein-coupled Receptors GPR41 and GPR43 Are Activated by Propionate and Other Short Chain Carboxylic Acids

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31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Penetrators for in situ subsurface investigations of Europa

We present the scientific case for inclusion of penetrators into the Europan surface, and the candidate instruments which could significantly enhance the scientific return of the joint ESA/NASA Europa-Jupiter System Mission (EJSM). Moreover, a surface element would provide an exciting and inspirational mission highlight which would encourage public and political support for the mission. Whilst many of the EJSM science goals can be achieved from the proposed orbital platform, only surface elements can provide key exploration capabilities including direct chemical sampling and associated astrobiological material detection, and sensitive habitability determination. A targeted landing site of upwelled material could provide access to potential biological material originating from deep beneath the ice. Penetrators can also enable more capable geophysical investigations of Europa (and Ganymede) interior body structures, mineralogy, mechanical, magnetic, electrical and thermal properties. They would provide ground truth, not just for the orbital observations of Europa, but could also improve confidence of interpretation of observations of the other Jovian moons. Additionally, penetrators on both Europa and Ganymede, would allow valuable comparison of these worlds, and gather significant information relevant to future landed missions. The advocated low mass penetrators also offer a comparatively low cost method of achieving these important science goals. A payload of two penetrators is proposed to provide redundancy, and improve scientific return, including enhanced networked seismometer performance and diversity of sampled regions. We also describe the associated candidate instruments, penetrator system architecture, and technical challenges for such penetrators, and include their current status and future development plans

Accurate whole human genome sequencing using reversible terminator chemistry

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications