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Abstract: A legacy of radioactive waste has accumulated since the late 1940s and safe containment of long lived, highly radioactive waste is crucial for the future of nuclear power. A geological disposal facility (GDF) is the preferred method for the safe disposal of radioactive wastes; a multifaceted approach, using both engineered and natural barriers, to maximise the time between the breakdown of barriers and the final interaction with the environment and subsequently people. Clay is likely form an integral part of the engineered barrier system (EBS) surrounding the waste canisters in many proposed GDFs for heat generating radioactive wastes. The clay selected for this purpose would need to have the necessary physical and chemical properties to protect the waste container against corrosion and also to limit the release of radionuclides from the waste after container failure. Clays have a number of advantageous properties, such as high sorption capacity for radionuclides, small pore structure restricting microbial activity, and stability over geological time scales. Substitution of cations (Fe2+/3+, Mg2+, Al3+) into octahedral and tetrahedral (Al3+ and Si4+) sheets give a net negative charge on the clay layers giving interlayer spaces in-between; hydrated cations balance the negative charge within the interlayer space and cause the clay to swell filling surrounding gaps/cracks, avoiding advective flow, stabilizing the canister, and making diffusion the predominant transport mechanism within the barrier. A number of challenges such as heat (from the high level wastes 160 °C), with small changes being resisted further by divalent interlayer cations. gamma irradiation was shown to generate charge defects within the clay, increasing surface potential and activating redox properties (Fe); alpha irradiation showed localised amorphisation of the clay structure with long range order maintained. Maximising the ability of the clay barrier to withstand the challenges expected in the GDF environment would allow for the strengthening of public opinion and a faster, smaller (footprint), cheaper and safer GDF for high level, heat generating, radioactive wastes to be produced.

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Abstract: UNC-6 (UNCoordinated-6) was the first member of the netrin family to be discovered in Caenorhabditis elegans. With homology to human netrin-1 it is a key signaling molecule involved in directing axon migration in nematodes. Similar to netrin-1, UNC-6 interacts with multiple receptors (UNC-5 and UNC-40 specifically) to guide axon migration in development. As a result of the distinct evolutionary path of UNC-6 compared to vertebrate netrins, we decided to employ an integrated approach to study its solution behavior and compare it to the high-resolution structure we previously published on vertebrate netrins. Dynamic light scattering and analytical ultracentrifugation on UNC-6 (with and without its C-domain) solubilized in a low-ionic strength buffer suggested that UNC-6 forms high-order oligomers. An increase in the buffer ionic strength resulted in a more homogeneous preparation of UNC-6, that was used for subsequent solution X-ray scattering experiments. Our biophysical analysis of UNC-6 ΔC solubilized in a high-ionic strength buffer suggested that it maintains a similar head-to-stalk arrangement as netrins -1 and -4. This phenomenon is thought to play a role in the signaling behavior of UNC-6 and its ability to move throughout the extracellular matrix.

Open Access

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Abstract: It is well-known that the Dengue fever virus undergoes a distinct morphological transition from topologically smooth particles to ‘bumpy’ particle on increasing the temperature from that of the mosquito carrier (28 °C) to that of the human host (37 °C). This virus also possesses pH-sensitive surface domains that undergo conformational changes during infection which facilitates exit from the endosomes. Herein we take a bio-inspired approach to design synthetic Dengue virus-mimicking nanoparticles to target triple-negative (TN) breast cancer cells that overexpress SR-B1 scavenger receptors. Thus, sterile pH-responsive methacrylic ABC triblock copolymer vesicles were prepared in aqueous solution via polymerization-induced self-assembly. Microphase separation between two enthalpically-incompatible hydrophobic membrane-forming blocks produced a well-defined framboidal morphology, with surface globules of ∼28 nm diameter protruding from the membrane. The hydrophilic stabilizer block comprises 97% hydroxyl-functionalized chains and 3% phosphorylcholine-functionalized chains, with the latter being critical for selective intracellular uptake. These framboidal vesicles remain intact at neutral pH but become swollen and cationic at pH 5–6 because the tertiary amine residues in the hydrophobic C block become protonated. We demonstrate that such nanoparticles enable selective targeting of TN breast cancer cells. This is because such malignant cells overexpress SR-B1 receptors for naturally-occurring phospholipids and hence take up the phosphorylcholine-decorated framboidal vesicles preferentially. In contrast, negligible cell uptake is observed over the same time period for both human dermal fibroblasts and normal breast cancer cells that minimally express the SR-B1 receptor. Moreover, we show that genetic material within such pH-responsive framboidal vesicles can be efficiently delivered to the cell nuclei while maintaining high cell viability.

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Abstract: The HLA‐A*02:01‐restricted decapeptide EAAGIGILTV, derived from Melanoma Antigen Recognized by T‐cells‐1 (MART‐1) protein, represents one of the best‐studied tumor associated T‐cell epitopes, but clinical results targeting this peptide have been disappointing. This limitation may reflect the dominance of the nonapeptide, AAGIGILTV, at the melanoma cell surface. The decapeptide and nonapeptides are presented in distinct conformations by HLA‐A*02:01 and TCRs from clinically relevant T‐cell clones recognize the nonapeptide poorly. Here, we studied the MEL5 TCR that potently recognizes the nonapeptide. The structure of the MEL5‐HLA‐A*02:01‐AAGIGILTV complex revealed an induced fit mechanism of antigen recognition involving altered peptide‐MHC anchoring. This ‘flexing’ at the TCR‐peptide‐MHC interface to accommodate the peptide antigen explains previously‐observed incongruences in this well‐studied system and has important implications for future therapeutic approaches. Finally, this study expands upon the mechanisms by which molecular plasticity can influence antigen recognition by T‐cells.

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Abstract: Ageing mechanisms in Li‐ion batteries are dependent on the operational temperature but the detailed mechanisms on what processes that takes place at what temperature is still lacking. The electrochemical performance and capacity fading of the common cell chemistry LiNi1/3Mn1/3Co1/3O2 (NMC)/Li4Ti5O12 (LTO) pouch cells is studied at the temperatures: −10 °C, 30 °C and 55 °C. The full cells are cycled with the moderate upper cut‐off potential: 4.3 V vs. Li+/Li. The electrode interfaces are characterized post‐mortem using photoelectron spectroscopy techniques (SOXPES, HAXPES, XANES). Stable cycling at 30 °C is explained by electrolyte reduction forming a stabilizing interphase, thereby preventing further degradation. This initial reaction, between LTO and the electrolyte, seems to be beneficial for the NMC‐LTO full cell. At 55 °C, continuous electrolyte reduction and capacity fading is observed. It leads to formation of a thicker surface layer of organic‐species on the LTO surface than at 30 °C, contributing to an increased voltage hysteresis. At −10 °C, large cell‐resistances are observed, caused by poor electrolyte conductivity in combination with a relatively thicker and LixPFy‐rich surface layer on LTO, which all limit the capacity. ‘Slippage’ with a reduced voltage window showing the loss of active Li+ was observed using XRD.