Myc-binding Protein Orthologue Interacts with AKAP240 In the Central Pair Apparatus of the \u3cem\u3eChlamydomonas\u3c/em\u3e Flagella

Background Flagella and cilia are fine thread-like organelles protruding from cells that harbour them. The typical ‘9 + 2’ cilia confer motility on these cells. Although the mechanistic details of motility remain elusive, the dynein-driven motility is regulated by various kinases and phosphatases. A-kinase anchoring proteins (AKAPs) are scaffolds that bind to a variety of such proteins. Usually, they are known to possess a dedicated domain that in vitro interacts with the regulatory subunits (RI and RII) present in the cAMP-dependent protein kinase (PKA) holoenzyme. These subunits conventionally harbour contiguous stretches of a.a. residues that reveal the presence of the Dimerization Docking (D/D) domain, Catalytic interface domain and cAMP-Binding domain. The Chlamydomonas reinhardtii flagella harbour two AKAPs; viz., the radial spoke AKAP97 or RSP3 and the central pair AKAP240. Both these were identified on the basis of their RII-binding property. Interestingly, AKAP97 binds in vivo to two RII-like proteins (RSP7 and RSP11) that contain only the D/D domain. Results We found a Chlamydomonas Flagellar Associated Protein (FAP174) orthologous to MYCBP-1, a protein that binds to organellar AKAPs and Myc onco-protein. An in silico analysis shows that the N-terminus of FAP174 is similar to those RII domain-containing proteins that have binding affinities to AKAPs. Binding of FAP174 was tested with the AKAP97/RSP3 using in vitro pull down assays; however, this binding was rather poor with AKAP97/RSP3. Antibodies were generated against FAP174 and the cellular localization was studied using Western blotting and immunoflourescence in wild type and various flagella mutants. We show that FAP174 localises to the central pair of the axoneme. Using overlay assays we show that FAP174 binds AKAP240 previously identified in the C2 portion of the central pair apparatus. Conclusion It appears that the flagella of Chlamydomonas reinhardtii contain proteins that bind to AKAPs and except for the D/D domain, lack the conventional a.a. stretches of PKA regulatory subunits (RSP7 and RSP11). We add FAP174 to this growing list

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub

Background AU Coronavirus Disease 2019 (COVID-19) continues to cause :significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). Methods and findings The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. Conclusions COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year

Impact of SARS-CoV-2 vaccination of children ages 5–11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021–March 2022: A multi-model study

Background: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5–11 years on COVID-19 burden and resilience against variant strains. Methods: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5–11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. Findings: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5–11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880–0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834–0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797–1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. Interpretation: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5–11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Funding: Various (see acknowledgments)

Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty

Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Enhancement of Jet Mixing using Stepped Tandem Tabs

Mixing characteristics of jet emerging from a subsonic nozzle exit has been experimented and the results are compared with uncontrolled jet and controlled jet configurations. The mixing enhancement was achieved using a passive method of jet control in which tandem tabs arrangement with rectangular cross section are fixed at the nozzle exit. Two Tab configurations, the Tandem tab (TT) and Stepped Tandem Tab (STT) are used to enhance the mixing characteristics of the jet, the aspect ratio (length /width) of the tabs was 1.67 offering a blockage ratio of 9.55% to the nozzle exit. The blockage ratio of TT and STT configurations are maintained to be equal so that the mixing characteristics can be compared. The axial and radial jet spread are compared for nozzle exit Mach numbers of 0.6, 0.8 and 1.0. The TT controlled jet offered a potential core reduction of 63%, 78% and 82% for Mach numbers 0.6, 0.8 and 1.0 respectively. The STT controlled jet offered a potential core reduction of 89%, 90% and 85% for Mach numbers 0.6, 0.8 and 1.0 respectively. The radial spread of uncontrolled jet, controlled jet with TT and STT are plotted at several X/D locations and found that the controlled jets have more jet spread in both radial directions. A simulation is conducted for jets with exit Mach number 0.8 and the results are validated with the experimental findings. Based on the preliminary experimentation and computation, the STT controlled jet achieved better jet mixing through more potential core reduction and radial spread characteristics as compared to the TT configuration and base nozzle

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Not AvailableCurrently, energy security, sustainable development and wellbeing are the energy policy drivers throughout the world. India has made significant progress, far more rapidly in the past 2 years, increasing the installed capacity of sustainable energy, and potentially this upward drift is anticipated to persist. The innovation in new and advanced technologies, aggressive energy policies, action, and planning activities has enabled India to resolve the barriers of commercial production of sustainable energy. The domestic production and use of renewable energy, such as offgrid power sources, i.e., solar power, wind power, small hydropower, biofuels and bioenergy from new biomass will help to reduce the fossil fuel use and its imports from other countries. Sustainable economic and industrial growth also requires safe and sustainable energy resources. The use of sustainable energy will help in strengthening low carbon energy in India and providing a clean environment through reduction of pollutants and greenhouse gas emissions. Prospective attention to financial and development needs by the use of sustainable energy will also improve the living standards of society with equity and economic sustainability. There is a strong need to extensively adopt and use sustainable energy technologies to supply off-grid power, especially in the areas with difficulty in accessing the central grid power, such as un-electrified villages, remote areas, and hilly terrains. Finally, these sustainable energy sources offer massive benefits and can contribute significantly to ensuring a secure energy future for India.Not Availabl

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Not AvailableAir quality (AQ) and greenhouse gas (GHG) emission management are the key drivers related to sustainability goal around the world today because most of the aforementioned issues are attributable to fossil fuels burning. Biofuels are the clean, alternative fuels that are derived from biomass-based resources. It addresses efficient management of air pollution problems and the collective goal of climate change mitigation. Recent times have witnessed accelerated growth in biofuel production worldwide. The Government of India has been very keen on promoting manufacture and blending of ethanol derived from sugarcane molasses, and biodiesel from non-edible and waste oils for mixing with diesel. India’s biofuel policy (2003), dealing with bio-ethanol and biodiesel, sights to channelize biofuels into the energy and transport sector to address energy security and improvement in the living standard of rural areas. Biofuels as an alternative energy source can help to lessen the dependency on imported fossil fuel oil, achieve sustainability goal and several other societal requirements.Not Availabl