Observation of Small Cluster Formation in Concentrated Monoclonal Antibody Solutions and Its Implications to Solution Viscosity

AbstractMonoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions

Eukaryotic virus composition can predict the efficiency of carbon export in the global ocean

海洋ウイルスの種組成と炭素の鉛直輸送の相関を確認 --ウイルスによる地球環境の制御を示唆. 京都大学プレスリリース. 2021-01-15.The biological carbon pump, in which carbon fixed by photosynthesis is exported to the deep ocean through sinking, is a major process in Earth's carbon cycle. The proportion of primary production that is exported is termed the carbon export efficiency (CEE). Based on in-lab or regional scale observations, viruses were previously suggested to affect the CEE (i.e., viral “shunt” and “shuttle”). In this study, we tested associations between viral community composition and CEE measured at a global scale. A regression model based on relative abundance of viral marker genes explained 67% of the variation in CEE. Viruses with high importance in the model were predicted to infect ecologically important hosts. These results are consistent with the view that the viral shunt and shuttle functions at a large scale and further imply that viruses likely act in this process in a way dependent on their hosts and ecosystem dynamics

Self-Management Support Using a Digital Health System Compared With Usual Care for Chronic Obstructive Pulmonary Disease:Randomized Controlled Trial

BACKGROUND: We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE' sElf-management anD support proGrammE) in improving quality of life and clinical outcomes. METHODS: We compared daily use of EDGE with usual care for 12 months. The primary outcome was COPD-specific health status measured with the St George's Respiratory Questionnaire for COPD (SGRQ-C). RESULTS: A total of 166 patients were randomized (110 EDGE, 56 usual care). All patients were included in an intention to treat analysis. The estimated difference in SGRQ-C at 12 months (EDGE-usual care) was -1.7 with a 95% CI of -6.6 to 3.2 (P=.49). The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care. Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03). The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively. CONCLUSIONS: The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention. However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK)

Crop Updates 2006 - Cereals

This session covers twenty nine papers from different authors: PLENARY 1. The 2005 wheat streak mosaic virus epidemic in New South Wales and the threat posed to the Western Australian wheat industry, Roger Jones and Nichole Burges, Department of Agriculture SOUTH COAST AGRONOMY 2. South coast wheat variety trial results and best options for 2006, Mohammad Amjad, Ben Curtis and Wal Anderson, Department of Agriculture 3. Dual purpose winter wheats to improve productivity, Mohammad Amjad and Ben Curtis, Department of Agriculture 4. South coast large-scale premium wheat variety trials, Mohammad Amjad and Ben Curtis, Department of Agriculture 5. Optimal input packages for noodle wheat in Dalwallinu – Liebe practice for profit trial, Darren Chitty, Agritech Crop Research and Brianna Peake, Liebe Group 6. In-crop risk management using yield prophet®, Harm van Rees1, Cherie Reilly1, James Hunt1, Dean Holzworth2, Zvi Hochman2; 1Birchip Cropping Group, Victoria; 2CSIRO, Toowoomba, Qld 7. Yield Prophet® 2005 – On-line yield forecasting, James Hunt1, Harm van Rees1, Zvi Hochman2,Allan Peake2, Neal Dalgliesh2, Dean Holzworth2, Stephen van Rees1, Trudy McCann1 and Peter Carberry2; 1Birchip Cropping Group, Victoria; 2CSIRO, Toowoomba, Qld 8. Performance of oaten hay varieties in Western Australian environments, Raj Malik and Kellie Winfield, Department of Agriculture 9. Performance of dwarf potential milling varieties in Western Australian environments, Kellie Winfield and Raj Malik, Department of Agriculture 10. Agronomic responses of new wheat varieties in the Southern agricultural region of WA, Brenda Shackley and Judith Devenish, Department of Agriculture 11. Responses of new wheat varieties to management factors in the central agricultural region of Western Australia, Darshan Sharma, Steve Penny and Wal Anderson,Department of Agriculture 12. Sowing time on wheat yield, quality and $ - Northern agricultural region, Christine Zaicou-Kunesch, Department of Agriculture NUTRITION 13.The most effective method of applying phosphorus, copper and zinc to no-till crops, Mike Bolland and Ross Brennan, Department of Agriculture 14. Uptake of K from the soil profile by wheat, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 15. Reducing nitrogen fertiliser risks, Jeremy Lemon, Department of Agriculture 16. Yield Prophet® and canopy management, Harm van Rees1, Zvi Hochman2, Perry Poulton2, Nick Poole3, Brooke Thompson4, James Hunt1; 1Birchip Cropping Group, Victoria; 2CSIRO, Toowoomba, Qld; 3Foundation for Arable Research, New Zealand; 4Cropfacts, Victoria 17. Producing profits with phosphorus, Stephen Loss, CSBP Ltd, WA 18. Potassium response in cereal cropping within the medium rainfall central wheatbelt, Jeff Russell1, Angie Roe2 and James Eyres2, Department of Agriculture1, Farm Focus Consultants, Northam2 19. Matching nitrogen supply to wheat demand in the high rainfall cropping zone, Narelle Simpson, Ron McTaggart, Wal Anderson, Lionel Martin and Dave Allen, Department of Agriculture DISEASES 20. Comparative study of commercial wheat cultivars and differential lines (with known Pm resistance genes) to powdery mildew response, Hossein Golzar, Manisha Shankar and Robert Loughman, Department of Agriculture 21. On farm research to investigate fungicide applications to minimise leaf disease impacts in wheat – part II, Jeff Russell1, Angie Roe2and James Eyres2, Department of Agriculture1, and Farm Focus Consultants, Northam2 22. Disease resistance update for wheat varieties in WA, Manisha Shankar, John Majewski, Donna Foster, Hossein Golzar, Jamie Piotrowski, Nicole Harry and Rob Loughman, Department of Agriculture 23. Effect of time of stripe rust inoculum arrival on variety response in wheat, Manisha Shankar, John Majewski and Rob Loughman, Department of Agriculture 24. Fungicide seed dressing management of loose smut in Baudin barley, Geoff Thomas and Kith Jayasena, Department of Agriculture PESTS 25. How to avoid insect contamination in cereal grain at harvest, Svetlana Micic, Paul Matson and Tony Dore, Department of Agriculture ABIOTIC 26. Environment – is it as important as variety in sprouting tolerance? Thomas (Ben) Biddulph1, Dr Daryl Mares1, Dr Julie Plummer1 and Dr Tim Setter2, School of Plant Biology, University of Western Australia1 and Department of Agriculture2 27. Frost or fiction, Garren Knell, Steve Curtin and Wade Longmuir, ConsultAg Pty Ltd, WA 28. High moisture wheat harvesting in Esperance 2005, Nigel Metz, South East Premium Wheat Growers Association (SEPWA) Projects Coordinator, Esperance, WA SOILS 28. Hardpan penetration ability of wheat roots, Tina Botwright Acuña and Len Wade, School of Plant Biology, University of Western Australia MARKETS 29. Crop shaping to meet predicted market demands for wheat in the 21st Century, Cindy Mills and Peter Stone,Australian Wheat Board, Melbourn

Crop Updates 2005 - Cereals

This session covers thirty six papers from different authors: WHEAT AGRONOMY 1. Optimum sowing time of new wheat varieties in Western Australia, Darshan Sharma, Brenda Shackley, Mohammad Amjad, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 2. Wheat varieties updated in ‘Flowering Calculator’: A model predicting flowering time, B. Shackley, D. Tennant, D. Sharma and C.M. Zaicou-Kunesch, Department of Agriculture 3. Plant populations for wheat varieties, Christine M. Zaicou-Kunesch, Wal Anderson, Darshan Sharma, Brenda Shackley and Mohammad Amjad, Department of Agriculture 4. New wheat cultivars response to fertiliser nitrogen in four major agricultural regions of Western Australia, Mohammad Amjad, Wal Anderson, Brenda Shackley, Darshan Sharma and Christine Zaicou-Kunesch, Department of Agriculture 5. Agronomic package for EGA Eagle Rock, Steve Penny, Department of Agriculture 6. Field evaluation of eastern and western wheats in large-scale farmer’s trials, Mohammad Amjad, Ben Curtis and Veronika Reck, Department of Agriculture 7. New wheat varieties for a changing environment, Richard Richards, CSIRO Plant Industry; Canberra 8. Farmers can profitably minimise exposure to frost! Garren Knell, Steve Curtin and David Sermon, ConsultAg 9. National Variety Trials, Alan Bedggood, Australian Crops Accreditation System; Horsham 10. Preharvest-sprouting tolerance of wheat in the field, T.B. Biddulph1, T.L. Setter2, J.A. Plummer1 and D.J. Mares3; 1Plant Biology; FNAS, University of Western Australia; 2Department of Agriculture, 3School of Agriculture and Wine, University of Adelaide 11. Waterlogging induces high concentration of Mn and Al in wheat genotypes in acidic soils, H. Khabaz-Saberi, T. Setter, I. Waters and G. McDonald, Department of Agriculture 12. Agronomic responses of new wheat varieties in the Northern Agricultural Region, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 13. Agronomic responses of new wheat varieties in the Central Agricultural Region of WA, Darshan Sharma, Steve Penny and Wal Anderson, Department of Agriculture 14. EGA Eagle Rock tolerance to metribuzin and its mixtures, Harmohinder Dhammu, David Nicholson and Chris Roberts, Department of Agriculture 15. Herbicide tolerance of new bread wheats, Harmohinder Dhammu1 and David Nicholson2, Department of Agriculture NUTRITION 16. The impact of fertiliser placement, timing and rates on nitrogen-use efficiency, Stephen Loss, CSBP Ltd 17. Cereals deficient in potassium are most susceptible to some leaf diseases, Ross Brennan and Kith Jayasena, Department of Agriculture 18. Responses of cereal yields to potassium fertiliser type, placement and timing, Eddy Pol, CSBP Limited 19. Sulphate of Potash, the potash of choice at seeding, Simon Teakle, United Farmers Co-operative 20. Essential disease management for successful barley production, K. Jayasena, R. Loughman, C. Beard, B. Paynter, K. Tanaka, G. Poulish and A. Smith, Department of Agriculture 21. Genotypic differences in potassium efficiency of wheat, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 22. Genotypic differences in potassium efficiency of barley, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 23. Investigating timing of nitrogen application in wheat, Darshan Sharma and Lionel Martin, Department of Agriculture, and Muresk Institute of Agriculture, Curtin University of Technology 24. Nutrient timing requirements for increased crop yields in the high rainfall cropping zone, Narelle Hill, Ron McTaggart, Dr Wal Anderson and Ray Tugwell, Department of Agriculture DISEASES 25. Integrate strategies to manage stripe rust risk, Geoff Thomas, Robert Loughman, Ciara Beard, Kith Jayasena and Manisha Shankar, Department of Agriculture 26. Effect of primary inoculum level of stripe rust on variety response in wheat, Manisha Shankar, John Majewski and Robert Loughman, Department of Agriculture 27. Disease resistance update for wheat varieties in WA, M. Shankar, J.M. Majewski, D. Foster, H. Golzar, J. Piotrowski and R. Loughman, Department of Agriculture 28. Big droplets for wheat fungicides, Rob Grima, Agronomist, Elders 29. On farm research to investigate fungicide applications to minimise leaf disease impacts in wheat, Jeff Russell and Angie Roe, Department of Agriculture, and Farm Focus Consultants PESTS 30. Rotations for nematode management, Vivien A. Vanstone, Sean J. Kelly, Helen F. Hunter and Mena C. Gilchrist, Department of Agriculture 31. Investigation into the adaqyacy of sealed farm silos in Western Australia to control phosphine-resistant Rhyzopertha dominica, C.R. Newman, Department of Agriculture 32.Insect contamination of cereal grain at harvest, Svetlana Micic and Phil Michael, Department of Agriculture 33. Phosure – Extending the life of phosphine, Gabrielle Coupland and Ern Kostas, Co-operative Bulk Handling SOIL 34. Optimum combinations of ripping depth and tine spacing for increasing wheat yield, Mohammed Hamza and Wal Anderson, Department of Agriculture 35. Hardpan penetration ability of wheat roots, Tina Botwright Acuña and Len Wade, School of Plant Biology, University of Western Australia MARKETS 36. Latin America: An emerging agricultural powerhouse, Ingrid Richardson, Food and Agribusiness Research, Rabobank; Sydne

Enteric Pathogens in Stored Drinking Water and on Caregiver's Hands in Tanzanian Households with and without Reported Cases of Child Diarrhea.

Diarrhea is one of the leading causes of mortality in young children. Diarrheal pathogens are transmitted via the fecal-oral route, and for children the majority of this transmission is thought to occur within the home. However, very few studies have documented enteric pathogens within households of low-income countries. The presence of molecular markers for three enteric viruses (enterovirus, adenovirus, and rotavirus), seven Escherichia coli virulence genes (ECVG), and human-specific Bacteroidales was assessed in hand rinses and household stored drinking water in Bagamoyo, Tanzania. Using a matched case-control study design, we examined the relationship between contamination of hands and water with these markers and child diarrhea. We found that the presence of ECVG in household stored water was associated with a significant decrease in the odds of a child within the home having diarrhea (OR = 0.51; 95% confidence interval 0.27-0.93). We also evaluated water management and hygiene behaviors. Recent hand contact with water or food was positively associated with detection of enteric pathogen markers on hands, as was relatively lower volumes of water reportedly used for daily hand washing. Enteropathogen markers in stored drinking water were more likely found among households in which the markers were also detected on hands, as well as in households with unimproved water supply and sanitation infrastructure. The prevalence of enteric pathogen genes and the human-specific Bacteroidales fecal marker in stored water and on hands suggests extensive environmental contamination within homes both with and without reported child diarrhea. Better stored water quality among households with diarrhea indicates caregivers with sick children may be more likely to ensure safe drinking water in the home. Interventions to increase the quantity of water available for hand washing, and to improve food hygiene, may reduce exposure to enteric pathogens in the domestic environment

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Erratum:Towards a muon collider

LPT

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure