Pulse detonation assembly and hybrid engine

A pulse detonation (PD) assembly includes a number of PD chambers adapted to expel respective detonation product streams and a number of barriers disposed between respective pairs of PD chambers. The barriers define, at least in part, a number of sectors that contain at least one PD chamber. A hybrid engine includes a number of PD chambers and barriers. The hybrid engine further includes a turbine assembly having at least one turbine stage, being in flow communication with the PD chambers and being configured to be at least partially driven by the detonation product streams. A segmented hybrid engine includes a number of PD chambers and segments configured to receive and direct the detonation product streams from respective PD chambers. The segmented hybrid engine further includes a turbine assembly configured to be at least partially driven by the detonation product streams

Pulse detonation engines and components thereof

A pulse detonation engine comprises a primary air inlet; a primary air plenum located in fluid communication with the primary air inlet; a secondary air inlet; a secondary air plenum located in fluid communication with the secondary air inlet, wherein the secondary air plenum is substantially isolated from the primary air plenum; a pulse detonation combustor comprising a pulse detonation chamber, wherein the pulse detonation chamber is located downstream of and in fluid communication with the primary air plenum; a coaxial liner surrounding the pulse detonation combustor defining a cooling plenum, wherein the cooling plenum is in fluid communication with the secondary air plenum; an axial turbine assembly located downstream of and in fluid communication with the pulse detonation combustor and the cooling plenum; and a housing encasing the primary air plenum, the secondary air plenum, the pulse detonation combustor, the coaxial liner, and the axial turbine assembly

Light thresholds for seagrasses of the GBRWHA: a synthesis and guiding document

[Extract]. Key Findings. This synthesis contains light thresholds for seagrass species in the Great Barrier Reef World Heritage Area (GBRWHA). The thresholds can be applied to ensure protection of seagrasses from activities that impact water quality and the light environment over the short-term, such as coastal and port developments. Thresholds for long-term maintenance of seagrasses are also proposed. •The synthesis provides clear and consistent guidance on light thresholds to apply in managing potential water quality impacts to seagrass. •All available information on biological light thresholds was tabulated and conservative management thresholds were identified to ensure seagrass protection. •Acute management thresholds are suited to compliance guidelines for managing short-term impacts and these and are the focus of this synthesis. Long-term thresholds are suited to the setting of water quality guidelines for catchment management. •The synthesis identified key areas where further information is required, including: ◦species for which almost no information on light thresholds exists; ◦location and population-specific thresholds particularly for the most at-risk species; ◦definitions of desired state to underpin the development of long-term light guidelines to meet them; ◦the effect of spectral quality on light thresholds; and, consideration of cumulative impacts (temperature, nutrients, sedimentary conditions) on acute and long-term light thresholds. •Light management thresholds for acute impacts are presented for twelve species. Colonising species are the most sensitive to light reduction (i.e. lowest thresholds) and have the shortest time to impact while larger, persistent species have higher light thresholds and a longer time to impact. •The recommended acute management thresholds are ready for application, as the conservative approach (higher light threshold, shortest time to impact) for species with low confidence should ensure protection to seagrass meadows at risk from acute light stress

Improved earthquake response via simulation and integrated space- and ground-based technologies: the TREMOR proposal

Earthquakes occurring around the world each year cause thousands of deaths, millions of dollars in damage to infrastructure, and incalculable human suffering. In recent years, satellite technology has been a significant boon to response efforts following an earthquake and its after-effects by providing mobile communications between response teams and remote sensing of damaged areas to disaster management organizations. In 2007, an international team of students and professionals assembled during the International Space University’s Summer Session Program in Beijing, China to examine how satellite and ground-based technology could be better integrated to provide an optimised response in the event of an earthquake. The resulting Technology Resources for Earthquake MOnitoring and Response (TREMOR) proposal describes an integrative prototype response system that will implement mobile satellite communication hubs providing telephone and data links between response teams, onsite telemedicine consultation for emergency first-responders, and satellite navigation systems that will locate and track emergency vehicles and guide search-and-rescue crews. A prototype earthquake simulation system is also proposed, integrating historical data, earthquake precursor data, and local geomatics and infrastructure information to predict the damage that could occur in the event of an earthquake. The backbone of these proposals is a comprehensive education and training program to help individuals, communities and governments prepare in advance. The TREMOR team recommends the coordination of these efforts through a centralised, non-governmental organization

Pineapple Lectin AcmJRL Binds SARS-CoV-2 Spike Protein in a Carbohydrate-Dependent Fashion

The highly glycosylated spike protein of SARS-CoV-2 is essential for infection and constitutes a prime target for antiviral agents and vaccines. The pineapple-derived jacalin-related lectin AcmJRL is present in the medication bromelain in significant quantities and has previously been described to bind mannosides. Here, we performed a large ligand screening of AcmJRL by glycan array analysis, quantified the interaction with carbohydrates and validated high-mannose glycans as preferred ligands. Because the SARS-CoV-2 spike protein was previously reported to carry a high proportion of high-mannose N-glycans, we tested the binding of AcmJRL to the recombinantly produced extraviral domain of spike protein. We could demonstrate that AcmJRL binds the spike protein with a low-micromolar KD in a carbohydrate-dependent fashion

The Future of Global Water Stress: An Integrated Assessment

We assess the ability of global water systems, resolved at 282 large river basins or Assessment Sub Regions (ASRs), to the meet water requirements over the coming decades under integrated projections of socioeconomic growth and climate change. We employ a Water Resource System (WRS) component embedded within the MIT Integrated Global System Model (IGSM) framework in a suite of simulations that consider a range of climate policies and regional hydroclimatic changes through the middle of this century. We find that for many developing nations water-demand increases due to population growth and economic activity have a much stronger effect on water stress than climate change. By 2050, economic growth and population change alone can lead to an additional 1.8 billion people living in regions with at least moderate water stress. Of this additional 1.8 billion people, 80% are found in developing countries. Uncertain regional climate change can play a secondary role to either exacerbate or dampen the increase in water stress due to socioeconomic growth. The strongest climate impacts on relative changes in water stress are seen over many areas in Africa, but strong impacts also occur over Europe, Southeast Asia and North America. The combined effects of socioeconomic growth and uncertain climate change lead to a 1.0 to 1.3 billion increase of the world's 2050 projected population living in regions with overly exploited water conditions— where total potential water requirements will consistently exceed surface-water supply. Under the context of the WRS model framework, this would imply that adaptive measures would be taken to meet these surface-water shortfalls and would include: water-use efficiency, reduced and/or redirected consumption, recurrent periods of water emergencies or curtailments, groundwater depletion, additional inter-basin transfers, and overdraw from flow intended to maintain environmental requirements.We assess the ability of global water systems, resolved at 282 large river basins or Assessment Sub Regions (ASRs), to the meet water requirements over the coming decades under integrated projections of socioeconomic growth and climate change. We employ a Water Resource System (WRS) component embedded within the MIT Integrated Global System Model (IGSM) framework in a suite of simulations that consider a range of climate policies and regional hydroclimatic changes through the middle of this century. We find that for many developing nations water-demand increases due to population growth and economic activity have a much stronger effect on water stress than climate change. By 2050, economic growth and population change alone can lead to an additional 1.8 billion people living in regions with at least moderate water stress. Of this additional 1.8 billion people, 80% are found in developing countries. Uncertain regional climate change can play a secondary role to either exacerbate or dampen the increase in water stress due to socioeconomic growth. The strongest climate impacts on relative changes in water stress are seen over many areas in Africa, but strong impacts also occur over Europe, Southeast Asia and North America. The combined effects of socioeconomic growth and uncertain climate change lead to a 1.0 to 1.3 billion increase of the world's 2050 projected population living in regions with overly exploited water conditions— where total potential water requirements will consistently exceed surface-water supply. Under the context of the WRS model framework, this would imply that adaptive measures would be taken to meet these surface-water shortfalls and would include: water-use efficiency, reduced and/or redirected consumption, recurrent periods of water emergencies or curtailments, groundwater depletion, additional inter-basin transfers, and overdraw from flow intended to maintain environmental requirements

An Unbiased Lipid Phenotyping Approach To Study the Genetic Determinants of Lipids and Their Association with Coronary Heart Disease Risk Factors.

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4-51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

The authors would like to thank Michael Inouye for his helpful comments on an earlier version of the manuscript.Peer reviewe

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

Funder: PfizerFunder: NovartisFunder: National Institute for Health ResearchFunder: MerckBackgroundGenetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.MethodsWe characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.ResultsWe identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.ConclusionsOur findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy