PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes

Non-viral vector formulations comprise typically complexes of nucleic acids with cationic polymers or lipids. However, for in vivo applications cationic formulations suffer from problems of poor tissue penetration, non-specific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic formulations may provide a solution to these problems but they have not been developed to the same extent as cationic formulations due to difficulties of nucleic acid packaging and poor transfection efficiency. We have developed novel PEGylated, anionic nanocomplexes containing cationic targeting peptides that act as a bridge between PEGylated anionic liposomes and plasmid DNA. At optimized ratios, the components self-assemble into anionic nanocomplexes with a high packaging efficiency of plasmid DNA. Anionic PEGylated nanocomplexes were resistant to aggregation in serum and transfected cells with a far higher degree of receptor-targeted specificity than their homologous non-PEGylated anionic and cationic counterparts. Gadolinium-labeled, anionic nanoparticles, administered directly to the brain by convection-enhanced delivery displayed improved tissue penetration and dispersal as well as more widespread cellular transfection than cationic formulations. Anionic PEGylated nanocomplexes have widespread potential for in vivo gene therapy due to their targeted transfection efficiency and ability to penetrate tissues

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at √S=7 and 8 TeV in the ATLAS experiment

Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the H -> gamma gamma, ZZ*, WW*, Z gamma, b (b) over bar, tau tau and mu mu decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 fb(-1) at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is 1.18(-0.14)(+0.15). The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered

Towards improved monitoring of offshore carbon storage: A real-world field experiment detecting a controlled sub-seafloor CO2 release

Carbon capture and storage (CCS) is a key technology to reduce carbon dioxide (CO2) emissions from industrial processes in a feasible, substantial, and timely manner. For geological CO2 storage to be safe, reliable, and accepted by society, robust strategies for CO2 leakage detection, quantification and management are crucial. The STEMM-CCS (Strategies for Environmental Monitoring of Marine Carbon Capture and Storage) project aimed to provide techniques and understanding to enable and inform cost-effective monitoring of CCS sites in the marine environment. A controlled CO2 release experiment was carried out in the central North Sea, designed to mimic an unintended emission of CO2 from a subsurface CO2 storage site to the seafloor. A total of 675 kg of CO2 were released into the shallow sediments (∼3 m below seafloor), at flow rates between 6 and 143 kg/d. A combination of novel techniques, adapted versions of existing techniques, and well-proven standard techniques were used to detect, characterise and quantify gaseous and dissolved CO2 in the sediments and the overlying seawater. This paper provides an overview of this ambitious field experiment. We describe the preparatory work prior to the release experiment, the experimental layout and procedures, the methods tested, and summarise the main results and the lessons learnt