A mixed reality telepresence system for collaborative space operation

This paper presents a Mixed Reality system that results from the integration of a telepresence system and an application to improve collaborative space exploration. The system combines free viewpoint video with immersive projection technology to support non-verbal communication, including eye gaze, inter-personal distance and facial expression. Importantly, these can be interpreted together as people move around the simulation, maintaining natural social distance. The application is a simulation of Mars, within which the collaborators must come to agreement over, for example, where the Rover should land and go. The first contribution is the creation of a Mixed Reality system supporting contextualization of non-verbal communication. Tw technological contributions are prototyping a technique to subtract a person from a background that may contain physical objects and/or moving images, and a light weight texturing method for multi-view rendering which provides balance in terms of visual and temporal quality. A practical contribution is the demonstration of pragmatic approaches to sharing space between display systems of distinct levels of immersion. A research tool contribution is a system that allows comparison of conventional authored and video based reconstructed avatars, within an environment that encourages exploration and social interaction. Aspects of system quality, including the communication of facial expression and end-to-end latency are reported

Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches

Smart Nanoparticles as Advanced Anti-Akt Kinase Delivery Systems for Pancreatic Cancer Therapy

Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site, and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry, and subcellular localization was determined by confocal microscopy, which showed a lysosomal localization of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-κB signaling pathway, and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt

Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using singlemolecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function

Combination light-based therapies to treat pancreatic cancer: A proof of concept

Pancreatic ductal adenocarcinoma remains one of the worst types of cancers mainly due to its late diagnosis, lack of effective therapies for advance disease and high chemoresistance. Novel therapeutic options that could improve patient quality of life and overall survival are therefore imperative. In this study, we describe the use of an original strategy based on photochemical internalisation (PCI) technology for pancreatic cancer treatment. Subcellular localisation of the photosensitiser meso-tetraphenylporphine-disulfonate (TPPS2a) was performed in PANC-1 cells, showing its preferential accumulation in lysosomes. Treatments with increasing concentrations of the ribosome-inactivating protein saporin or TPPS2a alone were compared with PCI-saporin. Metabolic activity and cell viability of PANC-1 cells were determined 96h post-illumination by MTT and trypan blue assays, respectively. Our results show that PCI using the photosensitiser TPPS2a, synergistically enhances the cytotoxic effects of saporin in PANC-1 cells and could offer more effective treatment options for pancreatic cancer

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Direct determination of the solar neutrino fluxes from solar neutrino data

We determine the solar neutrino fluxes from a global analysis of the solar and terrestrial neutrino data in the framework of three-neutrino mixing. Using a Bayesian approach we reconstruct the posterior probability distribution function for the eight normalization parameters of the solar neutrino fluxes plus the relevant masses and mixing, with and without imposing the luminosity constraint. This is done by means of a Markov Chain Monte Carlo employing the Metropolis-Hastings algorithm. We also describe how these results can be applied to test the predictions of the Standard Solar Models. Our results show that, at present, both models with low and high metallicity can describe the data with good statistical agreement.Comment: 24 pages, 1 table, 7 figures. Acknowledgments correcte

Mass hierarchy, 2-3 mixing and CP-phase with Huge Atmospheric Neutrino Detectors

We explore the physics potential of multi-megaton scale ice or water Cherenkov detectors with low ($\sim 1$ GeV) threshold. Using some proposed characteristics of the PINGU detector setup we compute the distributions of events versus neutrino energy $E_\nu$ and zenith angle $\theta_z$, and study their dependence on yet unknown neutrino parameters. The $(E_\nu - \theta_z)$ regions are identified where the distributions have the highest sensitivity to the neutrino mass hierarchy, to the deviation of the 2-3 mixing from the maximal one and to the CP-phase. We evaluate significance of the measurements of the neutrino parameters and explore dependence of this significance on the accuracy of reconstruction of the neutrino energy and direction. The effect of degeneracy of the parameters on the sensitivities is also discussed. We estimate the characteristics of future detectors (energy and angle resolution, volume, etc.) required for establishing the neutrino mass hierarchy with high confidence level. We find that the hierarchy can be identified at $3\sigma$ -- $10\sigma$ level (depending on the reconstruction accuracies) after 5 years of PINGU operation.Comment: 39 pages, 21 figures. Description of Fig.3 correcte