8,771 research outputs found

    Efficacy of photochemical internalisation using disulfonated chlorin and porphyrin photosensitisers: An in vitro study in 2D and 3D prostate cancer models

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    This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2a and TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS2a and TPCS2a were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer

    Probing strongly coupled anisotropic plasma

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    We calculate the static potential, the drag force and the jet quenching parameter in strongly coupled anisotropic N=4 super Yang-Mills plasma. We find that the jet quenching is in general enhanced in presence of anisotropy compared to the isotropic case and that its value depends strongly on the direction of the moving quark and the direction along which the momentum broadening occurs. The jet quenching is strongly enhanced for a quark moving along the anisotropic direction and momentum broadening happens along the transverse one. The parameter gets lower for a quark moving along the transverse direction and the momentum broadening considered along the anisotropic one. Finally, a weaker enhancement is observed when the quark moves in the transverse plane and the broadening occurs on the same plane. The drag force for quark motion parallel to the anisotropy is always enhanced. For motion in the transverse space the drag force is enhanced compared to the isotropic case only for quarks having velocity above a critical value. Below this critical value the force is decreased. Moreover, the drag force along the anisotropic direction is always stronger than the force in the transverse space. The diffusion time follows exactly the inverse relations of the drag forces. The static potential is decreased and stronger decrease observed for quark-antiquark pair aligned along the anisotropic direction than the transverse one. We finally comment on our results and elaborate on their similarities and differences with the weakly coupled plasmas.Comment: 1+44 pages, 18 Figures; Added results on static force; Added references; version published in JHE

    The Mannose Receptor Mediates Dengue Virus Infection of Macrophages

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    Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell–produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection

    Multidimensional cluster states using a single spin-photon interface coupled strongly to an intrinsic nuclear register

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    Photonic cluster states are a powerful resource for measurement-based quantum computing and loss-tolerant quantum communication. Proposals to generate multi-dimensional lattice cluster states have identified coupled spin-photon interfaces, spin-ancilla systems, and optical feedback mechanisms as potential schemes. Following these, we propose the generation of multi-dimensional lattice cluster states using a single, efficient spin-photon interface coupled strongly to a nuclear register. Our scheme makes use of the contact hyperfine interaction to enable universal quantum gates between the interface spin and a local nuclear register and funnels the resulting entanglement to photons via the spin-photon interface. Among several quantum emitters, we identify the silicon-29 vacancy centre in diamond, coupled to a nanophotonic structure, as possessing the right combination of optical quality and spin coherence for this scheme. We show numerically that using this system a 2x5-sized cluster state with a lower-bound fidelity of 0.5 and repetition rate of 65 kHz is achievable under currently realised experimental performances and with feasible technical overhead. Realistic gate improvements put 100-photon cluster states within experimental reach

    Can transplanting enhance mobile marine invertebrates in ecologically engineered rock pools?

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    © 2018 Elsevier Ltd The field of eco-engineering has burgeoned in recent years in response to the proliferation of artificial structures. Adding water-retaining features to seawalls has been successful in increasing biodiversity relative to the surrounding structure. Artificial rock pools may not, however, completely mimic natural rock pools. Here, we compared natural colonisation, through dispersal and recruitment, of intertidal mobile species to water-retaining flowerpots on seawalls with that into rock pools. This represents the more usual ‘passive’ approach to eco-engineering where features are built to enhance biodiversity and are allowed to colonise naturally, as opposed to seeding or transplanting organisms to features. While flowerpots supported some mobile species not found on the seawall, other species common on natural shores did not recruit to flowerpots. Thus, in a second experiment we tested the effectiveness of an ‘active’ approach through transplanting mobile organisms to flowerpots to expedite the colonisation process. For the species examined, however, most individuals did not stay in the flowerpots for more than 24 h after being transplanted. Further understanding of the processes (e.g. dispersal distances, recruitment) influencing colonisation of eco-engineered habitats is needed to effectively inform management of marine infrastructure, particularly for projects targeted at restoration rather than enhancement

    Autophagy in dental tissues: a double-edged sword

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    Biotechnology and Biological Sciences Research Council [BB/L02392X/1]SCI(E)PubMedEDITORIAL [email protected]

    Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

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    This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don't support the previous finding of association between hereditary breast cancer and shorter TL
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