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As environmental conservation and sustainability gain prominence globally, modern timber structures are receiving increased focus. Nonetheless, the combustible nature of timber raises significant fire safety concerns. This review explores the recent advancements in fire safety engineering for timber structures, emphasizing both contemporary high-rise buildings and historical timber constructions. It covers topics like inherently safer design principles, fire risk prediction, and evacuation methodologies. The review emphasizes the criticality of selecting suitable materials, structural design, firefighting systems, and advanced sensor technologies for early fire detection. Additionally, we analyze and compares various evacuation strategies, offering insights into the challenges and future directions for fire safety in modern timber structures. [ABSTRACT FROM AUTHOR]

In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense). We grew these native and invasive species with similar morphology with the addition of N and P under elevated CO2 in open-top chambers. The addition of N alone increased the relative growth rate (RGR) by 5.4% in invasive species, and its combination with P addition or elevated CO2 significantly increased the RGR of invasive species by 7.5 or 8.1%, respectively, and to a level higher than that of native species (by 14.4%, P  < 0.01). Combined N + P addition under elevated CO2 decreased the amount of defence-related compounds in the leaf, including lipids (by 17.7%) and total structural carbohydrates (by 29.0%), whereas it increased the growth-related compounds in the leaf, including proteins (by 75.7%), minerals (by 9.6%) and total non-structural carbohydrates (by 8.5%). The increased concentrations of growth-related compounds were possibly associated with the increase in ribulose 1,5-bisphosphate carboxylase oxygenase content and mineral nutrition (magnesium, iron and calcium), all of which were higher in the invasive species than in the native species. These results suggest that rising atmospheric CO2 concentration and N deposition combined with nutrient enrichment will increase the growth of invasive species more than that of native species. Our result also suggests that invasive species respond more readily to produce growth-related compounds under an increased soil nutrient availability and elevated CO2. [ABSTRACT FROM AUTHOR]

In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense). We grew these native and invasive species with similar morphology with the addition of N and P under elevated CO2 in open-top chambers. The addition of N alone increased the relative growth rate (RGR) by 5.4% in invasive species, and its combination with P addition or elevated CO2 significantly increased the RGR of invasive species by 7.5 or 8.1%, respectively, and to a level higher than that of native species (by 14.4%, P  < 0.01). Combined N + P addition under elevated CO2 decreased the amount of defence-related compounds in the leaf, including lipids (by 17.7%) and total structural carbohydrates (by 29.0%), whereas it increased the growth-related compounds in the leaf, including proteins (by 75.7%), minerals (by 9.6%) and total non-structural carbohydrates (by 8.5%). The increased concentrations of growth-related compounds were possibly associated with the increase in ribulose 1,5-bisphosphate carboxylase oxygenase content and mineral nutrition (magnesium, iron and calcium), all of which were higher in the invasive species than in the native species. These results suggest that rising atmospheric CO2 concentration and N deposition combined with nutrient enrichment will increase the growth of invasive species more than that of native species. Our result also suggests that invasive species respond more readily to produce growth-related compounds under an increased soil nutrient availability and elevated CO2. [ABSTRACT FROM AUTHOR]

Respiratory Syncytial Virus (RSV) causes severe respiratory infections and concomitant disease resulting in significant morbidity and mortality in infants, elderly, and immunocompromised adults. Vaccines, monoclonal antibodies, and small molecule antivirals are now either available, or in development, to prevent and treat RSV infections. Although, rodent and non-rodent preclinical animal models have been used to evaluate these emerging agents there is still a need to improve our understanding of the pharmacokinetic (PK)-pharmacodynamic (PD) relationships, within and between animal models to enable better design of human challenge studies and clinical trials. Herein, we report a PKPD evaluation of MRK-1, a novel small molecule non-nucleoside inhibitor of the RSV L polymerase protein, in the semi-permissive cotton rat and African green monkey models of RSV infection. These studies demonstrate a strong relationship between in vitro activity, in vivo drug exposure, and pharmacodynamic efficacy as well as revealing limitations of the cotton rat RSV model. Additionally, we report unexpected horizontal transmission of human RSV between co-housed African green monkeys, as well as a lack of drug specific resistant mutant generation. Taken together these studies further our understanding of these semi-permissive animal models and offer the potential for expansion of their preclinical utility in evaluating novel RSV therapeutic agents., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MPC, EM, XZ, WR, AL, JH are current employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. JB, DB are former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA at the time the study was conducted., (Copyright © 2024. Published by Elsevier Ltd.)

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t ½ ) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t ½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 study was performed to evaluate the pharmacokinetics and safety of islatravir in plasma and the pharmacokinetics of islatravir-TP in peripheral blood mononuclear cells after administration of a single oral dose of islatravir 30 mg. Eligible participants were healthy adult males without HIV infection between the ages of 18 and 65 years. Fourteen participants were enrolled. The median time to maximum plasma islatravir concentration was 1 hour. Plasma islatravir concentrations decreased in a biphasic manner, with a t ½ of 73 hours. The t ½ (percentage geometric coefficient of variation) of islatravir-TP in peripheral blood mononuclear cells through 6 weeks (~1008 hours) after dosing was 8.1 days or 195 hours (25.6%). Islatravir was generally well tolerated with no drug-related adverse events observed. Islatravir-TP has a long intracellular t ½ , supporting further clinical investigation of islatravir administered at an extended dosing interval., Competing Interests: X.Z., W.A., R.V., S.A.S., M.I., and R.P.M. are current or former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock and/or options in Merck & Co., Inc., Rahway, NJ, USA. W.A. was an employee of Merck & Co., Inc., Rahway, NJ, USA, at the time the study was conducted. W.K.K. has no conflicts to report.

In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense). We grew these native and invasive species with similar morphology with the addition of N and P under elevated CO2 in open-top chambers. The addition of N alone increased the relative growth rate (RGR) by 5.4% in invasive species, and its combination with P addition or elevated CO2 significantly increased the RGR of invasive species by 7.5 or 8.1%, respectively, and to a level higher than that of native species (by 14.4%, P < 0.01). Combined N + P addition under elevated CO2 decreased the amount of defence-related compounds in the leaf, including lipids (by 17.7%) and total structural carbohydrates (by 29.0%), whereas it increased the growth-related compounds in the leaf, including proteins (by 75.7%), minerals (by 9.6%) and total non-structural carbohydrates (by 8.5%). The increased concentrations of growth-related compounds were possibly associated with the increase in ribulose 1,5-bisphosphate carboxylase oxygenase content and mineral nutrition (magnesium, iron and calcium), all of which were higher in the invasive species than in the native species. These results suggest that rising atmospheric CO2 concentration and N deposition combined with nutrient enrichment will increase the growth of invasive species more than that of native species. Our result also suggests that invasive species respond more readily to produce growth-related compounds under an increased soil nutrient availability and elevated CO2., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)