NATO Code of Best Practice for C2 Assessment

This major revision to the Code of Best Practice (COBP) for C2 Assessment is the product of a NATO Research and Technology Organisation (RTO) sponsored Research Group (SAS-026). It represents over a decade of work by many of the best analysts from the NATO countries. A symposium (SAS-039) was hosted by the NATO Consultation Command Control Agency (NC3A) that provided the venue for a rigorous peer review of the code. This new version of the COBP for C2 assessment builds upon the initial version of the COBP produced by SAS-002. The earlier version focused on the analysis of ground forces at a tactical echelon in mid- to high-intensity conflicts. In developing this new version of the COBP, SAS-026 focused on a changed geopolitical context characterized by a shift from preoccupation with a war involving NATO and the Warsaw Pact to concern for a broad range of smaller military conflicts and Operations Other Than War (OOTW). This version also takes into account the impact of significantly improved information-related capabilities and their implications for reducing the fog and friction traditionally associated with conflict. Significantly reduced levels of fog and friction offer an opportunity for the military to develop new concepts of operations, new organizational forms, and new approaches to C2, as well as to the processes that support it. In addition, SAS-026 was cognizant that NATO operations are likely to include coalitions of the willing that might involve Partnership for Peace (PfP) nations, other partners outside of NATO, international organizations, and NGOs. Cost analyses continue to be excluded because they differ among NATO members, so no single approach would be appropriate. Advances in technology are expected to continue at an increasing rate and spur both sustaining and disruptive innovation in military organizations. It is to be expected that this COBP will need to be periodically revisited in light of these developments.https://digitalcommons.odu.edu/msve_books/1012/thumbnail.jp

Tools for quantifying isotopic niche space and dietary variation at the individual and population level

Ecologists are increasingly using stable isotope analysis to inform questions about variation in resource and habitat use from the individual to community level. In this study we investigate data sets from 2 California sea otter (Enhydra lutris nereis) populations to illustrate the advantages and potential pitfalls of applying various statistical and quantitative approaches to isotopic data. We have subdivided these tools, or metrics, into 3 categories: IsoSpace metrics, stable isotope mixing models, and DietSpace metrics. IsoSpace metrics are used to quantify the spatial attributes of isotopic data that are typically presented in bivariate (e.g., d 13 C versus d 15 N) 2-dimensional space. We review IsoSpace metrics currently in use and present a technique by which uncertainty can be included to calculate the convex hull area of consumers or prey, or both. We then apply a Bayesian-based mixing model to quantify the proportion of potential dietary sources to the diet of each sea otter population and compare this to observational foraging data. Finally, we assess individual dietary specialization by comparing a previously published technique, variance components analysis, to 2 novel DietSpace metrics that are based on mixing model output. As the use of stable isotope analysis in ecology continues to grow, the field will need a set of quantitative tools for assessing isotopic variance at the individual to community level. Along with recent advances in Bayesian-based mixing models, we hope that the IsoSpace and DietSpace metrics described here will provide another set of interpretive tools for ecologists

Making sense of social prescribing

This booklet provides advice and guidance on all things social prescribing

Ligand-induced conformational changes in a SMALP-encapsulated GPCR.

The adenosine 2A receptor (A2AR), a G-protein-coupled receptor (GPCR), was solubilised and purified encapsulated in styrene maleic acid lipid particles (SMALPs). The purified A2AR-SMALP was associated with phospholipids characteristic of the plasma membrane of Pichia pastoris, the host used for its expression, confirming that the A2AR-SMALP encapsulated native lipids. The fluorescence spectrum of the A2AR-SMALP showed a characteristic broad emission peak at 330 nm, produced by endogenous Trp residues. The inverse agonist ZM241385 caused 30% increase in fluorescence emission, unusually accompanied by a red-shift in the emission wavelength. The emission spectrum also showed sub-peaks at 321 nm, 335 nm and 350 nm, indicating that individual Trp inhabited different environments following ZM241385 addition. There was no effect of the agonist NECA on the A2AR-SMALP fluorescence spectrum. Substitution of two Trp residues by Tyr suggested that ZM241385 affected the environment and mobility of Trp2466.48 in TM6 and Trp2687.33 at the extracellular face of TM7, causing transition to a more hydrophobic environment. The fluorescent moiety IAEDANS was site-specifically introduced at the intracellular end of TM6 (residue 2316.33) to report on the dynamic cytoplasmic face of the A2AR. The inverse agonist ZM241385 caused a concentration-dependent increase in fluorescence emission as the IAEDANS moved to a more hydrophobic environment, consistent with closing the G-protein binding crevice. NECA generated only 30% of the effect of ZM241385. This study provides insight into the SMALP environment; encapsulation supported constitutive activity of the A2AR and ZM241385-induced conformational transitions but the agonist NECA generated only small effects

GPCR-styrene maleic acid lipid particles (GPCR-SMALPs):their nature and potential

G-protein-coupled receptors (GPCRs) form the largest class of membrane proteins and are an important target for therapeutic drugs. These receptors are highly dynamic proteins sampling a range of conformational states in order to fulfil their complex signalling roles. In order to fully understand GPCR signalling mechanisms it is necessary to extract the receptor protein out of the plasma membrane. Historically this has universally required detergents which inadvertently strip away the annulus of lipid in close association with the receptor and disrupt lateral pressure exerted by the bilayer. Detergent-solubilized GPCRs are very unstable which presents a serious hurdle to characterization by biophysical methods. A range of strategies have been developed to ameliorate the detrimental effect of removing the receptor from the membrane including amphipols and reconstitution into nanodics stabilized by membrane scaffolding proteins (MSPs) but they all require exposure to detergent. Poly(styrene-co-maleic acid) (SMA) incorporates into membranes and spontaneously forms nanoscale poly(styrene-co-maleic acid) lipid particles (SMALPs), effectively acting like a 'molecular pastry cutter' to 'solubilize' GPCRs in the complete absence of detergent at any stage and with preservation of the native annular lipid throughout the process. GPCR-SMALPs have similar pharmacological properties to membrane-bound receptor, exhibit enhanced stability compared with detergent-solubilized receptors and being non-proteinaceous in nature, are fully compatible with downstream biophysical analysis of the encapsulated GPCR

G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent

G-protein coupled receptors (GPCRs) constitute the largest class of membrane proteins and are a major drug target. A serious obstacle to studying GPCR structure/function characteristics is the requirement to extract the receptors from their native environment in the plasma membrane, coupled with the inherent instability of GPCRs in the detergents required for their solubilization. In the present study, we report the first solubilization and purification of a functional GPCR [human adenosine A2A receptor (A2AR)], in the total absence of detergent at any stage, by exploiting spontaneous encapsulation by styrene maleic acid (SMA) co-polymer direct from the membrane into a nanoscale SMA lipid particle (SMALP). Furthermore, the A2AR-SMALP, generated from yeast (Pichia pastoris) or mammalian cells, exhibited increased thermostability (∼5°C) compared with detergent [DDM (n-dodecyl-β-D-maltopyranoside)]-solubilized A2AR controls. The A2AR-SMALP was also stable when stored for prolonged periods at 4°C and was resistant to multiple freeze-thaw cycles, in marked contrast with the detergent-solubilized receptor. These properties establish the potential for using GPCR-SMALP in receptor-based drug discovery assays. Moreover, in contrast with nanodiscs stabilized by scaffold proteins, the non-proteinaceous nature of the SMA polymer allowed unobscured biophysical characterization of the embedded receptor. Consequently, CD spectroscopy was used to relate changes in secondary structure to loss of ligand binding ([3H]ZM241385) capability. SMALP-solubilization of GPCRs, retaining the annular lipid environment, will enable a wide range of therapeutic targets to be prepared in native-like state to aid drug discovery and understanding of GPCR molecular mechanisms

GPCRs in the round:SMA-like copolymers and SMALPs as a platform for investigating GPCRs

G-protein-coupled receptors (GPCRs) are the largest family of membrane proteins, regulate a plethora of physiological responses and are the therapeutic target for 30–40% of clinically-prescribed drugs. They are integral membrane proteins deeply embedded in the plasma membrane where they activate intracellular signalling via coupling to G-proteins and β-arrestin. GPCRs are in intimate association with the bilayer lipids and that lipid environment regulates the signalling functions of GPCRs. This complex lipid ‘landscape’ is both heterogeneous and dynamic. GPCR function is modulated by bulk membrane properties including membrane fluidity, microdomains, curvature, thickness and asymmetry but GPCRs are also regulated by specific lipid:GPCR binding, including cholesterol and anionic lipids. Understanding the molecular mechanisms whereby GPCR signalling is regulated by lipids is a very active area of research currently. A major advance in membrane protein research in recent years was the application of poly(styrene-co-maleic acid) (SMA) copolymers. These spontaneously generate SMA lipid particles (SMALPs) encapsulating membrane protein in a nano-scale disc of cell membrane, thereby removing the historical need for detergent and preserving lipid:GPCR interaction. The focus of this review is how GPCR-SMALPs are increasing our understanding of GPCR structure and function at the molecular level. Furthermore, an increasing number of ‘second generation’ SMA-like copolymers have been reported recently. These are reviewed from the context of increasing our understanding of GPCR molecular mechanisms. Moreover, their potential as a novel platform for downstream biophysical and structural analyses is assessed and looking ahead, the translational application of SMA-like copolymers to GPCR drug discovery programmes in the future is considered

Sheep Updates 2008 - part 2

This session covers eleven papers from different authors: The Sheep Room 1. Analgesia for Surgical Husbandry Procedures in Sheep and Other Livestock, Dr Meredith L. Sheil, Animal Ethics Pty Ltd, Associate Sydney University Faculty of Veterinary Science The Wool Enterprise 2. Unmulsed sheep - implications for chemical use, Di Evans & Brown Besier, Department of Agriculture and Food WA 3. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Growth rates, Tim Scanlon1, Andre Martinho de Almeida2, Johan Greeff1, Tanya Kilminster1, John Milton3, Chris Oldham1, Department of Agriculture and Food WA1, Instituto de Investigacao Cientifica Tropical, Lisbon, Portugal2, University of Western Australia3 4. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Carcass attributes, Tanya Kilminster1, Andre Martinho de Almeida2, Johan Greeff1, John Milton3, Chris Oldham1, Tim Scanlon1, Department of Agriculture and Food WA1, Instituto de Investigacao Cientifica Tropical, Lisbon, Portugal2, University of Western Australia3 The Beef Room 5. Benefits of matching animal requirements with pasture feed supply and animal supply market requirements, B.L. McIntyre, Department of Agriculture and Food Western Australia, 6. Optimal grazing for beef, Alison Wheatley, Beef farmer Winnejup, John Lucey, Department of Agriculture and Food, Western Australia 7. Grain Introduction in commercial cattle feedlots, Fiona Jones1,2, Nick Costa2, 1 Department of Agriculture and Food WA and 2 Murdoch University. Mixed Systems 8. Confinement feeding stock in mixed enterprises, John Milton, The University of Western Australia & Independent Lab Services The Sheep Enterprise 9. Making More than Sheep, Ed Riggall, Australian Wool Innovation and Meat & Livestock Australia 10. Sheep Cost of Production - the enemy is at the gate!, JRL (Bob) Hall, JRL Hall & Co 11. Australian lamb - high yielding good to eat, Robin Jacob1, Dave Pethick2, Dave Hopkins3 and Graham Gardner2, 1Department of Agrcultre and Food WA, 2Murdoch University, 3NSW Department of Primary Industrie

Potreba - temeljni parametar čovjekovih aktivnosti

Dosad zanemaren kompleksni fenomen potreba, kako u teorijskim, tako i u praktičnim razmatranjima, zahtjeva nužno promjenu. Jer potreba, predstavlja i početnu i završnu točku i proizvodnje i potrošnje. Relativno je prirodom neograničen i beskonačan broj potreba koji čovjek posjeduje. Razvojem proizvodnje i humanizacijom potrošnje on se geometrijskom progresijom povećava. Ne sagledavanje ovog fenomena u svoj svojoj kompleksnosti, važnosti i dinamičnosti uzrokuje višestruke gubitke čije dimenzije su u svim svojim granicama teško sagledive. Stoga se pred ekonomsku politiku (makro i mikro) postavlja staro-novi problem čije dubinsko sagledavanje je temeljna pretpostavka ostvarivanja željenih pravaca i dinamike razvoja

The life cycle of stars and their planets from the high energy perspective

One of the key research themes identified by the Astro2020 decadal survey is Worlds and Suns in Context. The Advanced X-ray Imaging Satellite (AXIS) is a proposed NASA APEX mission that will become the prime high-energy instrument for studying star-planet connections from birth to death. This work explores the major advances in this broad domain of research that will be enabled by the AXIS mission, through X-ray observations of stars in clusters spanning a broad range of ages, flaring M-dwarf stars known to host exoplanets, and young stars exhibiting accretion interactions with their protoplanetary disks. In addition, we explore the ability of AXIS to use planetary nebulae, white dwarfs, and the Solar System to constrain important physical processes from the microscopic (e.g., charge exchange) to the macroscopic (e.g., stellar wind interactions with the surrounding interstellar medium).Comment: This White Paper is part of a series commissioned for the AXIS Probe Concept Missio