Lunar Polar Coring Lander

Plans to build a lunar base are presently being studied with a number of considerations. One of the most important considerations is qualifying the presence of water on the Moon. The existence of water on the Moon implies that future lunar settlements may be able to use this resource to produce things such as drinking water and rocket fuel. Due to the very high cost of transporting these materials to the Moon, in situ production could save billions of dollars in operating costs of the lunar base. Scientists have suggested that the polar regions of the Moon may contain some amounts of water ice in the regolith. Six possible mission scenarios are suggested which would allow lunar polar soil samples to be collected for analysis. The options presented are: remote sensing satellite, two unmanned robotic lunar coring missions (one is a sample return and one is a data return only), two combined manned and robotic polar coring missions, and one fully manned core retrieval mission. One of the combined manned and robotic missions has been singled out for detailed analysis. This mission proposes sending at least three unmanned robotic landers to the lunar pole to take core samples as deep as 15 meters. Upon successful completion of the coring operations, a manned mission would be sent to retrieve the samples and perform extensive experiments of the polar region. Man's first step in returning to the Moon is recommended to investigate the issue of lunar polar water. The potential benefits of lunar water more than warrant sending either astronauts, robots or both to the Moon before any permanent facility is constructed

Rapid, cost-effective and scalable gmp-compliant simian adenovirus-vectored vaccine production for early-phase clinical trials using entirely disposable product-contact components

The Jenner Institute, University of Oxford, develops and produces a range of vaccines against emerging threats (such as Zika) and current global health challenges (including malaria, HIV and rabies). The Jenner Clinical Biomanufacturing Facility (CBF) manufactures multiple simian adenovirus-vectored vaccines for early phase clinical trials each year. Hitherto we have used shake flasks for upstream production and caesium chloride gradient ultracentrifugation for downstream purification. This process is robust and simple but also slow, human resource intensive and lacks scalability. Here we report the development of a novel process using a 2 x 3L single-use stirred tank bioreactor system (MilliporeSigma Mobius®), coupled to a tangential flow filtration (TFF) and anion exchange chromatography (AEX)-based downstream process. The process also includes particle lysis and nucleic acid digestion inside the bioreactor, as well as clarification of cells and debris using depth filters. As our test case, we used a novel simian adenovirus-vectored rabies vaccine (ChAdOx2 RabG), which we will manufacture to GMP standards in the coming year. Each process run yields \u3e5x1013 ChAdOx2 RabG virus particles (approximately 1000 human doses), with residual host cell DNA, host cell protein and nuclease levels suitable for clinical trial use. While similar processes have been previously reported for adenovirus manufacture, we will report a number of points of novelty. Firstly, we use single-use disposable product-contact components from beginning to end, greatly simplifying small-scale GMP manufacturing of multiple products. Secondly, we will report results of comparative testing with a range of modern ion exchange media (including resins, membrane adsorbers, monoliths and functionalized hydrogel formats). Thirdly, we will report the development and validation of novel quality control methods suitable for this process. The resulting process will allow the CBF to increase production yield and produce more vaccines that transfer more easily to larger facilities

Healthcare expenditure on Indigenous and non-Indigenous Australians at high risk of cardiovascular disease

Background: In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods: The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results: There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure ($932 per year P< 0.001) than other individuals. MBS expenditure was found to increase with being aged over 65 years ($128, p=0.013), being female ($472, p=0.003), lower baseline reported quality of life ($102 per 0.1 decrement of utility p=0.004) and a history of diabetes ($324, p=0.001), gout ($631, p=0.022), chronic obstructive pulmonary disease ($469, p=0.019) and established CVD whether receiving guideline-recommended treatment prior to the trial ($452, p=0.005) or not ($483, p=0.04). When controlling for all other characteristics, morbidly obese patients had lower MBS expenditure than other individuals (-$887, p=0.002). Conclusion: The findings suggest that for the majority of participants, once individuals are engaged with a primary care provider, factors other than whether they are Indigenous determine the level of Medicare expenditure for each person. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN 126080005833347

Feeding Preferences and the Nutritional Value of Tropical Algae for the Abalone Haliotis asinina

Understanding the feeding preferences of abalone (high-value marine herbivores) is integral to new species development in aquaculture because of the expected link between preference and performance. Performance relates directly to the nutritional value of algae – or any feedstock – which in turn is driven by the amino acid content and profile, and specifically the content of the limiting essential amino acids. However, the relationship between feeding preferences, consumption and amino acid content of algae have rarely been simultaneously investigated for abalone, and never for the emerging target species Haliotis asinina. Here we found that the tropical H. asinina had strong and consistent preferences for the red alga Hypnea pannosa and the green alga Ulva flexuosa, but no overarching relationship between protein content (sum of amino acids) and preference existed. For example, preferred Hypnea and Ulva had distinctly different protein contents (12.64 vs. 2.99 g 100 g−1) and the protein-rich Asparagopsis taxiformis (>15 g 100 g−1 of dry weight) was one of the least preferred algae. The limiting amino acid in all algae was methionine, followed by histidine or lysine. Furthermore we demonstrated that preferences can largely be removed using carrageenan as a binder for dried alga, most likely acting as a feeding attractant or stimulant. The apparent decoupling between feeding preference and algal nutritive values may be due to a trade off between nutritive values and grazing deterrence associated with physical and chemical properties

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Seaweeds as an alternative crop for the production of protein

The total global demand for protein from both humans and livestock will rise substantially into the future due to the combined increase in population and per capita consumption of animal protein. Currently, net protein is primarily produced by agricultural crops. However, the future production of agricultural crops is limited by a finite supply of arable land, fresh water and synthetic fertilisers. Alternative crops such as seaweeds have the potential to help meet the protein demand without applying additional stress on traditional agricultural resources. This thesis investigates the potential of seaweeds as an alternative crop for the production of protein. Chapter 1 provides a general introduction to the thesis. The chapter begins by introducing the current supply and future demand of protein globally, with a specific focus on the demands of mono-gastric livestock (poultry, swine and fish). This is followed by a summary of potential alternative protein sources that are currently being explored. Finally, seaweeds are introduced in the context of their potential as a biomass crop for the production of protein. Many seaweed species have considerable plasticity in nitrogen content, yet the relationship between nitrogen content, protein concentration, protein quality and growth rate are poorly understood. Therefore, in Chapter 2, the plasticity in protein content in the green seaweed Ulva ohnoi was investigated. This was done by assessing the quantitative and qualitative changes in protein in Ulva ohnoi and relating these to changes in internal nitrogen content and growth rate. To do this water nitrogen concentrations and water renewal rates were varied simultaneously to manipulating the supply of nitrogen to outdoor cultures of U. ohnoi. Both internal nitrogen content and growth rate varied substantially, and the quantitative and qualitative changes in total amino acids were described in the context of three internal nitrogen states; nitrogenlimited, metabolic, and luxury. The nitrogen-limited state was defined by increases in all amino acids with increasing nitrogen content and growth rates up until 1.2 % internal nitrogen. The metabolic nitrogen state was defined by increases in all amino acids with increasing internal nitrogen content up to 2.6 % with no increases in growth rate. Luxury state was defined by internal nitrogen contents above 2.6 % which occurred only when nitrogen availability was high but growth rates were reduced. In this luxury circumstance, excess nitrogen was accumulated as free amino acids, in two phases. The first phase is distinguished by a small increase in the majority of amino acids up to ≈ 3.3 % internal nitrogen, and the second by a large increase in glutamic acid/glutamine and arginine up to 4.2 % internal nitrogen. This chapter demonstrates that the relationship between internal nitrogen content and amino acid quality is dynamic but predictable, and could be used for holding seaweeds in a desired nitrogen state during culture. In Chapter 3, I assessed the relative importance of direct and indirect effects of salinity on protein in seaweed. Indirect effects, through altering growth rates, and direct effects, through altering the synthesis of specific amino acids and osmolytes, were examined in the context of the concentration and quality of protein in Ulva ohnoi. To do this, U. ohnoi was cultured under a range of salinities without nutrient limitation. Both the concentration and quality of protein varied across the salinity treatments. Protein concentration was strongly related to the growth rate of the seaweed and was highest in the slowest growing seaweed. In contrast, the quality of protein (individual amino acids as a proportion of total amino acid content) was strongly related to salinity for all amino acids, although this varied substantially amongst individual amino acids. Increases in salinity were positively correlated with the proportion of proline (46 % increase), tyrosine (36 % increase) and histidine (26 % increase), whereas there was a negative correlation with alanine (29 % decrease). The proportion of methionine, with strong links to the synthesis of the osmolyte dimethylsulphonioproprionate (DMSP), did not correlate linearly with salinity and instead was moderately higher at the optimal salinities for growth. This chapter demonstrates that salinity simultaneously affects the concentration and quality of protein in seaweed through both indirect and direct mechanisms, with growth rates playing the overarching role in determining the concentration of protein. During my investigations into the protein physiology and nutrition of seaweeds, it became evident that there were many inconsistencies and potential inaccuracies with the way protein concentrations are reported. Therefore, in Chapter 4, I assessed these issues on a broad scale by systematically analysing the literature to assess the way that people measure and report protein in seaweeds with the aim to provide an evidence-based conversion factor for nitrogen to protein that is specific to seaweeds. Almost 95 % of studies on seaweeds determined protein either by direct extraction procedures (42 % of all studies) or by applying an indirect nitrogen-to-protein conversion factor of 6.25 (52 % of all studies), with the latter the most widely used method in the last 6 years. Metaanalysis of the true protein content, defined as the sum of the proteomic amino acids, demonstrated that direct extraction procedures under-estimated protein content by 33 %, while the most commonly used indirect nitrogen-to-protein conversion factor of 6.25 overestimated protein content by 43 %. I then questioned whether a single nitrogen-toprotein conversion factor could be used for seaweeds and evaluated how robust this would be by analysing the variation in N-to-protein conversion factors for 103 species across 44 studies that span three taxonomic groups, multiple geographic regions and a range of nitrogen contents. This resulted in an overall median nitrogen-to-protein conversion factor of 4.97 and a mean nitrogen-to-protein conversion factor of 4.76. Based on these results I proposed that the value of 5 be adopted as the universal seaweed nitrogen-to-protein (SNP) conversion factor. This chapter highlighted that most of the quantitative data on the protein contents of seaweeds have been under- or overestimated and was in need of review in regards to the potential applications of seaweed protein. Therefore, in Chapter 5, seaweeds were quantitatively assessed as a protein source in livestock feeds using the dataset established in Chapter 4 as a platform to compare the quality and concentration of protein to traditional protein sources (soybean meal and fishmeal) and then benchmarking the seaweeds against the amino acid requirements of mono-gastric livestock (chicken, swine and fish). The quality of seaweed protein (% of essential amino acids in total amino acids) is similar to, if not better than, traditional protein sources. However, seaweeds without exception have substantially lower concentrations of essential amino acids, including methionine and lysine, than traditional protein sources (on a whole biomass basis, % dw). Correspondingly, seaweeds in their whole form contain insufficient protein, and specifically insufficient essential amino acids, to meet the requirements of most mono-gastric livestock. This chapter highlights that the protein from seaweeds must be concentrated or extracted, and these techniques are the most important goals for developing seaweeds as alternative source of protein for mono-gastric livestock. Therefore, in Chapter 6, I examined multiple techniques to isolate and concentrate protein in a seaweed, returning to the model organism the green seaweed Ulva ohnoi. The aim of this chapter was to compare the protein isolation and concentration efficiency of a mechanical-based method (as applied to leaves) to the solvent based method (as applied to seed crops). Protein isolate yields ranged from 12.28 ± 1.32 % to 21.57 ± 0.57 % and were higher using the methods established for leaves compared to those for seeds. Protein isolates from all treatment combinations were ~ 250 – 400 % higher in the concentration of protein and essential amino acids compared to the original whole biomass, reaching a maximum concentration of 56.04 ± 2.35 % and 27.56 ± 1.16 % for protein and total essential amino acids, respectively. In contrast, protein and essential amino acid concentrations were only ~ 30 – 50 % higher in protein concentrates compared to the original whole seaweed, reaching a maximum of 19.65 ± 0.21 % and 9.52 ± 0.11 % for protein and total essential amino acids, respectively. This chapter demonstrated that the methodologies used for the isolation of protein in leaves are more suited to seaweeds than those that are based on seed crops, which have traditionally been applied to seaweeds. This chapter also demonstrated that protein isolation methods are more suited to seaweeds with low concentrations of protein, such as Ulva ohnoi, compared to protein concentration methods. In summary, the research presented throughout this thesis establishes that seaweeds, irrespective of cultivation conditions and species, are not viable as a protein source for mono-gastric livestock in a whole form and will need to be processed post-harvest to concentrate their protein. Therefore, it is proposed that the most important strategy for developing seaweeds as a protein crop is the development of protein isolates and concentrates from seaweeds produced under intensive cultivation

Seaweed as a protein source for mono-gastric livestock

Background: Seaweeds are often cited as alternative protein sources for livestock due to their global distribution, nutritional profile and independence from terrestrial agricultural resources. Scope and approach: Here, we critically appraise the literature and quantitatively assess seaweeds as a protein source in livestock feeds by assembling a database of amino acid data for 121 seaweed species and comparing the quality and concentration of protein to 'traditional' protein sources (soybean meal and fishmeal) and then benchmarking the seaweeds against the amino acid requirements of mono gastric livestock (chicken, swine and fish). Key findings and conclusions: The quality of protein (% of essential amino acids in total amino acids) of many seaweeds is similar to, if not better than, traditional protein sources. However, seaweeds without exception have substantially lower concentrations of total essential amino acids, methionine and lysine (on a whole biomass basis, % dw) than traditional protein sources. Correspondingly, seaweeds contain an insufficient concentration of protein, and specifically insufficient essential amino acids, to meet the requirements of most mono-gastric livestock in the whole seaweed form. Consequently, the concentration or extraction of protein from seaweeds will be the most important goal in their development as an alternative source of protein for mono-gastric livestock

Seaweed as a protein source for mono-gastric livestock

Background: Seaweeds are often cited as alternative protein sources for livestock due to their global distribution, nutritional profile and independence from terrestrial agricultural resources. Scope and approach: Here, we critically appraise the literature and quantitatively assess seaweeds as a protein source in livestock feeds by assembling a database of amino acid data for 121 seaweed species and comparing the quality and concentration of protein to 'traditional' protein sources (soybean meal and fishmeal) and then benchmarking the seaweeds against the amino acid requirements of mono gastric livestock (chicken, swine and fish). Key findings and conclusions: The quality of protein (% of essential amino acids in total amino acids) of many seaweeds is similar to, if not better than, traditional protein sources. However, seaweeds without exception have substantially lower concentrations of total essential amino acids, methionine and lysine (on a whole biomass basis, % dw) than traditional protein sources. Correspondingly, seaweeds contain an insufficient concentration of protein, and specifically insufficient essential amino acids, to meet the requirements of most mono-gastric livestock in the whole seaweed form. Consequently, the concentration or extraction of protein from seaweeds will be the most important goal in their development as an alternative source of protein for mono-gastric livestock