Simple Combined Model for Nonlinear Excitations in DNA

We propose a new simple model for DNA denaturation bases on the pendulum model of Englander\cite{A1} and the microscopic model of Peyrard {\it et al.},\cite{A3} so called "combined model". The main parameters of our model are: the coupling constant $k$ along each strand, the mean stretching $y^\ast$ of the hydrogen bonds, the ratio of the damping constant and driven force $\gamma/F$. We show that both the length $L$ of unpaired bases and the velocity $v$ of kinks depend on not only the coupling constant $k$ but also the temperature $T$. Our results are in good agreement with previous works.Comment: 6 pages, 10 figures, submitted to Phys. Rev.

Superdirective Arrays with Finite-Length Dipoles: Modeling and New Perspectives

Dense arrays can facilitate the integration of multiple antennas into finite volumes. In addition to the compact size, sub-wavelength spacing enables superdirectivity for endfire operation, a phenomenon that has been mainly studied for isotropic and infinitesimal radiators. In this work, we focus on linear dipoles of arbitrary yet finite length. Specifically, we first introduce an array model that accounts for the sinusoidal current distribution (SCD) on very thin dipoles. Based on the SCD, the loss resistance of each dipole antenna is precisely determined. Capitalizing on the derived model, we next investigate the maximum achievable rate under a fixed power constraint. The optimal design entails conjugate power matching along with maximizing the array gain. Our theoretical analysis is corroborated by the method of moments under the thin-wire approximation, as well as by full-wave simulations. Numerical results showcase that a super-gain is attainable with high radiation efficiency when the dipole antennas are not too short and thin.Comment: To appear in 2022 IEEE GLOBECO

The assessment report of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services on pollinators, pollination and food production

The thematic assessment of pollinators, pollination and food production carried out under the auspices of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services aims to assess animal pollination as a regulating ecosystem service underpinning food production in the context of its contribution to nature’s gifts to people and supporting a good quality of life. To achieve this, it focuses on the role of native and managed pollinators, the status and trends of pollinators and pollinator-plant networks and pollination, drivers of change, impacts on human well-being, food production in response to pollination declines and deficits and the effectiveness of responses

Summary for policymakers of the thematic assessment on pollinators, pollination and food production

The thematic assessment of pollinators, pollination and food production carried out under the auspices of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services aims to assess animal pollination as a regulating ecosystem service underpinning food production in the context of its contribution to nature’s gifts to people and supporting a good quality of life. To achieve this, it focuses on the role of native and managed pollinators, the status and trends of pollinators and pollinator-plant networks and pollination, drivers of change, impacts on human well-being, food production in response to pollination declines and deficits and the effectiveness of responses. The chapters and their executive summaries of this assessment are available as document IPBES/4/INF/1/Rev.2 (www.ipbes.net). The present document is a summary for policymakers of the information presented in these chapters

A global-scale expert assessment of drivers and risks associated with pollinator decline.

Pollinator decline has attracted global attention and substantial efforts are underway to respond through national pollinator strategies and action plans. These policy responses require clarity on what is driving pollinator decline and what risks it generates for society in different parts of the world. Using a formal expert elicitation process, we evaluated the relative regional and global importance of eight drivers of pollinator decline and ten consequent risks to human well-being. Our results indicate that global policy responses should focus on reducing pressure from changes in land cover and configuration, land management and pesticides, as these were considered very important drivers in most regions. We quantify how the importance of drivers and risks from pollinator decline, differ among regions. For example, losing access to managed pollinators was considered a serious risk only for people in North America, whereas yield instability in pollinator-dependent crops was classed as a serious or high risk in four regions but only a moderate risk in Europe and North America. Overall, perceived risks were substantially higher in the Global South. Despite extensive research on pollinator decline, our analysis reveals considerable scientific uncertainty about what this means for human society.University of Reading’s Building Outstanding Impact Support Programm

A screen for regulators of survival of motor neuron protein levels

The motor neuron disease spinal muscular atrophy (SMA) results from mutations that lead to low levels of the ubiquitously expressed protein survival of motor neuron (SMN). An ever-increasing collection of data suggests that therapeutics that elevate SMN may be effective in treating SMA. We executed an image-based screen of annotated chemical libraries and discovered several classes of compounds that were able to increase cellular SMN. Among the most important was the RTK–PI3K–AKT–GSK-3 signaling cascade. Chemical inhibitors of glycogen synthase kinase 3 (GSK-3) and short hairpin RNAs (shRNAs) directed against this target elevated SMN levels primarily by stabilizing the protein. It was particularly notable that GSK-3 chemical inhibitors were also effective in motor neurons, not only in elevating SMN levels, but also in blocking the death that was produced when SMN was acutely reduced by an SMN-specific shRNA. Thus, we have established a screen capable of detecting drug-like compounds that correct the main phenotypic change underlying SMA.Stem Cell and Regenerative Biolog

Survival and Growth of Yeast without Telomere Capping by Cdc13 in the Absence of Sgs1, Exo1, and Rad9

Maintenance of telomere capping is absolutely essential to the survival of eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively. Here we identify, for the first time, three genetic modifications that allow budding yeast cells to survive without telomere capping by Cdc13. We found that simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response (DDR) proteins, is sufficient to allow cell division in the absence of Cdc13. Quantitative amplification of ssDNA (QAOS) was used to show that the RecQ helicase Sgs1 plays an important role in the resection of uncapped telomeres, especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped telomeres and together with deletion of RAD9 permits cell survival without CDC13. Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Δ sgs1Δ exo1Δ strains can maintain linear chromosomes despite the absence of telomere capping by Cdc13. However, with continued passage, the telomeres of such strains eventually become short and are maintained by recombination-based mechanisms. Remarkably, cdc13Δ rad9Δ sgs1Δ exo1Δ strains, lacking any Cdc13 gene product, are viable and can grow indefinitely. Our work has uncovered a critical role for RecQ helicases in limiting the division of cells with uncapped telomeres, and this may provide one explanation for increased tumorigenesis in human diseases associated with mutations of RecQ helicases. Our results reveal the plasticity of the telomere cap and indicate that the essential role of telomere capping is to counteract specific aspects of the DDR

Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy

Multiscale scenarios for nature futures

Targets for human development are increasingly connected with targets for nature, however, existing scenarios do not explicitly address this relationship. Here, we outline a strategy to generate scenarios centred on our relationship with nature to inform decision-making at multiple scales