Poly(ethylene glycol) (PEG) is a highly investigated polymer for the covalent modification of biological macromolecules and surfaces for many pharmaceutical and biotechnical applications. In the ...modification of biological macromolecules, peptides and proteins are of extreme importance. Reasons for PEGylation (i.e. the covalent attachment of PEG) of peptides and proteins are numerous and include shielding of antigenic and immunogenic epitopes, shielding receptor-mediated uptake by the reticuloendothelial system (RES), and preventing recognition and degradation by proteolytic enzymes. PEG conjugation also increases the apparent size of the polypeptide, thus reducing the renal filtration and altering biodistribution. An important aspect of PEGylation is the incorporation of various PEG functional groups that are used to attach the PEG to the peptide or protein. In this paper, we review PEG chemistry and methods of preparation with a particular focus on new (second-generation) PEG derivatives, reversible conjugation and PEG structures.
Poly(ethylene glycol) (PEG) is a highly investigated polymer for the covalent modification of biological macromolecules and surfaces for many pharmaceutical and biotechnical applications. In the ...modification of biological macromolecules, peptides and proteins are of extreme importance. Reasons for PEGylation (i.e. the covalent attachment of PEG) of peptides and proteins are numerous and include shielding of antigenic and immunogenic epitopes, shielding receptor-mediated uptake by the reticuloendothelial system (RES), and preventing recognition and degradation by proteolytic enzymes. PEG conjugation also increases the apparent size of the polypeptide, thus reducing the renal filtration and altering biodistribution. An important aspect of PEGylation is the incorporation of various PEG functional groups that are used to attach the PEG to the peptide or protein. In this paper, we review PEG chemistry and methods of preparation with a particular focus on new (second-generation) PEG derivatives, reversible conjugation and PEG structures.
The 'hot Jupiters' that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from ...which they were born, or by an alternative mechanism such as planet-planet scattering. The hot Jupiters closest to their parent stars, at orbital distances of only ∼0.02 astronomical units, have strong tidal interactions, and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory. Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10 MJup), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 106, as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.
Pine Island Glacier, a major outlet of the West Antarctic Ice Sheet, has been undergoing rapid thinning and retreat for the past two decades. We demonstrate, using glacial-geological and ...geochronological data, that Pine Island Glacier (PIG) also experienced rapid thinning during the early Holocene, around 8000 years ago. Cosmogenic 10Be concentrations in glacially transported rocks show that this thinning was sustained for decades to centuries at an average rate of more than 100 centimeters per year, which is comparable with contemporary thinning rates. The most likely mechanism was a reduction in ice shelf buttressing. Our findings reveal that PIG has experienced rapid thinning at least once in the past and that, once set in motion, rapid ice sheet changes in this region can persist for centuries.
SARS-CoV-2 has spread across the world, causing high mortality and unprecedented restrictions on social and economic activity. Policymakers are assessing how best to navigate through the ongoing ...epidemic, with computational models being used to predict the spread of infection and assess the impact of public health measures. Here, we present OpenABM-Covid19: an agent-based simulation of the epidemic including detailed age-stratification and realistic social networks. By default the model is parameterised to UK demographics and calibrated to the UK epidemic, however, it can easily be re-parameterised for other countries. OpenABM-Covid19 can evaluate non-pharmaceutical interventions, including both manual and digital contact tracing, and vaccination programmes. It can simulate a population of 1 million people in seconds per day, allowing parameter sweeps and formal statistical model-based inference. The code is open-source and has been developed by teams both inside and outside academia, with an emphasis on formal testing, documentation, modularity and transparency. A key feature of OpenABM-Covid19 are its Python and R interfaces, which has allowed scientists and policymakers to simulate dynamic packages of interventions and help compare options to suppress the COVID-19 epidemic.
Summary
Most alpha‐gliadin genes of the Gli‐D2 locus on the D genome of hexaploid bread wheat (Triticum aestivum) encode for proteins with epitopes that can trigger coeliac disease (CD), and several ...contain a 33‐mer peptide with six partly overlapping copies of three epitopes, which is regarded as a remarkably potent T‐cell stimulator. To increase genetic diversity in the D genome, synthetic hexaploid wheat lines are being made by hybridising accessions of Triticum turgidum (AB genome) and Aegilops tauschii (the progenitor of the D genome). The diversity of alpha‐gliadins in A. tauschii has not been studied extensively. We analysed the alpha‐gliadin transcriptome of 51 A. tauschii accessions representative of the diversity in A. tauschii. We extracted RNA from developing seeds and performed 454 amplicon sequencing of the first part of the alpha‐gliadin genes. The expression profile of allelic variants of the alpha‐gliadins was different between accessions, and also between accessions of the Western and Eastern clades of A. tauschii. Generally, both clades expressed many allelic variants not found in bread wheat. In contrast to earlier studies, we detected the 33‐mer peptide in some A. tauschii accessions, indicating that it was introduced along with the D genome into bread wheat. In these accessions, transcripts with the 33‐mer peptide were present at lower frequencies than in bread wheat varieties. In most A. tauschii accessions, however, the alpha‐gliadins do not contain the epitope, and this may be exploited, through synthetic hexaploid wheats, to breed bread wheat varieties with fewer or no coeliac disease epitopes.
Significance Statement
We sequenced the expressed alpha‐gliadins in grains of Aegilops tauschii across its range. Some accessions contained the 33‐mer peptide with six overlapping coeliac disease epitopes, indicating that this was introduced into bread wheat from A. tauschii. We also found a large variation in the occurrence of coeliac disease epitopes, including accessions with small numbers of epitopes, suitable as basis for breeding bread wheat varieties with fewer or no coeliac disease epitopes.
Background Despite concerns about the longevity of total shoulder arthroplasty (TSA) in young patients, it remains an attractive option because of the absence of superior options. Methods A ...systematic review was performed using searches of PubMed, Embase, and Cochrane databases. English-language studies were identified with search terms “total shoulder arthroplasty” (title/abstract) or “shoulder replacement” (title/abstract) and “young” (title/abstract) or “under 65 years of age” (title/abstract). Duplicate studies, studies not reporting outcomes, and those using a humeral resurfacing technique were excluded. Outcomes of interest included pain, range of motion, patient-reported outcome scores, patient satisfaction, radiographic changes, complication and revision rates, and implant survival. Results Six studies met inclusion criteria. Significant improvements in pain, range of motion, and patient-reported outcomes were found across all studies that reported these measures. At an average of 9.4 years, 17.4% underwent revision and 54% had glenoid lucency. Whereas glenoid loosening is the most common reason for revision (52%), overall implant survivorship was reported at 60% to 80% at 10- to 20-year follow-up. Outcome measures including the Constant, American Shoulder and Elbow Surgeons, and Simple Shoulder Test scores were reported, with generally satisfactory but not excellent results between 3 and 10 years from surgery. Conclusions Although there is concern with periprosthetic radiolucency and glenoid loosening in the young patient (<65 years) undergoing TSA, overall low revision rates and high implant survivorship are reported in the current literature. Whereas the patient-reported outcomes are inferior to those of the overall TSA population, there is significant improvement from baseline levels in young patients with glenohumeral arthritis.
Four ferritic alloys based on the composition Fe–14Cr–3W–0.4Ti (nominal wt%) were developed with a predominant dispersion of either oxide particles or nano-size Y-, Ti-, O-rich clusters, or ...nanoclusters (NC). Tensile specimens machined from the alloys were tested at room temperature and at temperatures ranging from ∼360
°C to 800
°C in air using a strain rate of 10
−3
s
−1. The results showed that the high-temperature strength of the NC strengthened alloys was significantly better than that of the oxide strengthened alloys. The room temperature yield strengths of the two alloys containing the NC were 1469
MPa and 1261
MPa while the yield strengths of the two oxide dispersion alloys were 819
MPa (Y–Ti-oxides) and 583
MPa (Ti-oxides). However, the ductility of the oxide strengthened alloys was better than that of the NC strengthened alloys.
Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island ...impacted the station. Measurements made included non-methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monoxide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a 4 h enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. A wind direction change lead to a dramatic reduction in BB tracers and a drop in the dominant particle mode to 50 nm. The dominant mode increased in size to 80 nm over 5 h in calm sunny conditions, accompanied by an increase in ozone. Due to an enhancement in BC but not CO during particle growth, the presence of BB emissions during this period could not be confirmed. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 ± 8 %), higher during the particle growth period (77 ± 4 %) and higher still (104 ± 3 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000 and 5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6–34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed (ΔO3 / ΔCO 0.001–0.074). A short-lived increase in NMOCs by a factor of 10 corresponded with a large CO enhancement, an increase of the NMOC / CO emission ratio (ER) by a factor of 2–4 and a halving of the BC / CO ratio. Rainfall on Robbins Island was observed by radar during this period which likely resulted in a lower fire combustion efficiency, and higher emission of compounds associated with smouldering. This highlights the importance of relatively minor meteorological events on BB emission ratios. Emission factors (EFs) were derived for a range of trace gases, some never before reported for Australian fires, (including hydrogen, phenol and toluene) using the carbon mass balance method. This provides a unique set of EFs for Australian coastal heathland fires. Methyl halide EFs were higher than EFs reported from other studies in Australia and the Northern Hemisphere which is likely due to high halogen content in vegetation on Robbins Island. This work demonstrates the substantial impact that BB plumes can have on the composition of marine air, and the significant changes that can occur as the plume interacts with terrestrial, aged urban and marine emission sources.
We report the discovery of the transiting giant planet WASP-17b, the least-dense planet currently known. It is 1.6 Saturn masses but 1.5-2 Jupiter radii, giving a density of 6-14 per cent that of ...Jupiter. WASP-17b is in a 3.7-day orbit around a sub-solar metallicity, V = 11.6, F6 star. Preliminary detection of the Rossiter-McLaughlin effect suggests that WASP-17b is in a retrograde orbit (lambda ~ -150 deg), indicative of a violent history involving planet-planet or planet-star scattering. WASP-17b's bloated radius could be due to tidal heating resulting from recent or ongoing tidal circularisation of an eccentric orbit, such as the highly eccentric orbits that typically result from scattering interactions. It will thus be important to determine more precisely the current orbital eccentricity by further high-precision radial velocity measurements or by timing the secondary eclipse, both to reduce the uncertainty on the planet's radius and to test tidal-heating models. Owing to its low surface gravity, WASP-17b's atmosphere has the largest scale height of any known planet, making it a good target for transmission spectroscopy.
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