Synthetic ozone deposition and stomatal uptake at flux tower sites

We develop and evaluate a method to estimate O-3 deposition and stomatal O-3 uptake across networks of eddy covariance flux tower sites where O-3 concentrations and O-3 fluxes have not been measured. The method combines standard micrometeorological flux measurements, which constrain O-3 deposition velocity and stomatal conductance, with a gridded dataset of observed surface O-3 concentrations. Measurement errors are propagated through all calculations to quantify O-3 flux uncertainties. We evaluate the method at three sites with O(3 )flux measurements: Harvard Forest, Blodgett Forest, and Hyytiala Forest. The method reproduces 83 % or more of the variability in daily stomatal uptake at these sites with modest mean bias (21 % or less). At least 95 % of daily average values agree with measurements within a factor of 2 and, according to the error analysis, the residual differences from measured O-3 fluxes are consistent with the uncertainty in the underlying measurements. The product, called synthetic O-3 flux or SynFlux, includes 43 FLUXNET sites in the United States and 60 sites in Europe, totaling 926 site years of data. This dataset, which is now public, dramatically expands the number and types of sites where O-3 fluxes can be used for ecosystem impact studies and evaluation of air quality and climate models. Across these sites, the mean stomatal conductance and O-3 deposition velocity is 0.03-1.0 cm s(-1). The stomatal O-3 flux during the growing season (typically April-September) is 0.5-11.0 nmol O-3 m(-2) s(-1) with a mean of 4.5 nmol O(3 )m(-2) s(-1) and the largest fluxes generally occur where stomatal conductance is high, rather than where O-3 concentrations are high. The conductance differences across sites can be explained by atmospheric humidity, soil moisture, vegetation type, irrigation, and land management. These stomatal fluxes suggest that ambient O-3 degrades biomass production and CO2 sequestration by 20 %-24 % at crop sites, 6 %-29 % at deciduous broadleaf forests, and 4 %-20 % at evergreen needleleaf forests in the United States and Europe.Peer reviewe

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Versatile thiol-based reactions for micrometer- and nanometer-scale photopatterning of polymers and biomolecules

Thiol-based chemistry provides a mild and versatile tool for surface functionalization. In the present work, mercaptosilane films were patterned by utilizing UV-induced photo-oxidation of the thiol to yield sulfonate groups via contact and interferometric lithography (IL). These photo-generated sulfonic acid groups were used for selective immobilization of amino-functionalized molecules after activation with triphenylphosphine ditriflate (TPPDF). Moreover, protein-resistant poly(oligoethyleneglycolmethacrylate) (POEGMA) brushes were grown from the intact thiol groups by a surface-induced polymerization reaction. Exploiting both reactions it is possible to couple amino-labelled nitrilotriacetic acid (NH2-NTA) to sulfonate-functionalized regions, enabling the site-specific binding of green fluorescent protein (GFP) to regions defined lithographically, while exploiting the protein-resistant character of POEGMA brushes to prevent non-specific protein adsorption to previously masked areas. The outstanding reactivity of thiol groups paves the way towards novel strategies for the fabrication of complex protein nanopatterns beyond thiol–ene chemistry

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women’s empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and wome

Casimir Forces between Spherical Particles in a Critical Fluid and Conformal Invariance

Mesoscopic particles immersed in a critical fluid experience long-range Casimir forces due to critical fluctuations. Using field theoretical methods, we investigate the Casimir interaction between two spherical particles and between a single particle and a planar boundary of the fluid. We exploit the conformal symmetry at the critical point to map both cases onto a highly symmetric geometry where the fluid is bounded by two concentric spheres with radii R_- and R_+. In this geometry the singular part of the free energy F only depends upon the ratio R_-/R_+, and the stress tensor, which we use to calculate F, has a particularly simple form. Different boundary conditions (surface universality classes) are considered, which either break or preserve the order-parameter symmetry. We also consider profiles of thermodynamic densities in the presence of two spheres. Explicit results are presented for an ordinary critical point to leading order in epsilon=4-d and, in the case of preserved symmetry, for the Gaussian model in arbitrary spatial dimension d. Fundamental short-distance properties, such as profile behavior near a surface or the behavior if a sphere has a `small' radius, are discussed and verified. The relevance for colloidal solutions is pointed out.Comment: 37 pages, 2 postscript figures, REVTEX 3.0, published in Phys. Rev. B 51, 13717 (1995

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali

BACKGROUND:The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS/DESIGN: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. CONCLUSION: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04424511. Registered on 11 June 2020

Promoting gender, equity, human rights and ethnic equality in neglected tropical disease programmes.

Limited attention to tackling neglected tropical diseases (NTDs) through the lenses of gender, equity, ethnicity and human rights inadvertently undermines progress due to the exclusion of subgroups in populations living in conditions of vulnerability. Supporting national NTD programmes to make equity analysis part of their routine activities and revitalising intersectoral collaboration will be essential to achieve effective, sustainable service delivery with a person-centred approach. Gender, equity, human rights and ethnic equality for NTD programmes should therefore be incorporated in multisectoral engagements

PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer

Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell’s responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention

Measurement of the adhesion between single melamine-formaldehyde resin microparticles and a flat fabric surface using AFM

An understanding of the adhesion of microparticles, particularly microcapsules, containing a functional component to a fabric surface is crucial to an effective application of this component to the fibre. Fabric surface is very rough; hence, direct measurement of the adhesion of single microparticles to surfaces with a roughness greater than the particle diameter is difficult. In the study reported here, cotton films were generated by dissolving cotton powder in an organic solvent and their properties including surface roughness, thickness, contact angle and purity were characterised. The adhesive forces between single melamineformaldehyde (MF) resin microparticles and a cotton film under ambient conditions with a relative humidity of above 40% were measured using atomic force microscopy; they are considered to be dominated by capillary forces. It was found that there was little adhesion between a MF microparticle and a cotton film in an aqueous solution of sodium dodecylbenzene sulphonate as surfactant. Repulsion between them was observed, but it reduced with increase in the surfactant concentration and decrease in the pH of the solution. The repulsion contributions are thought to originate mainly from electrostatic repulsion. It is believed that the studies on the adhesion between single MF microparticles and a cotton film under ambient conditions or dispersed in surfactant solutions, are beneficial to the attempts to enhance the adhesion of microcapsules to fabric surfaces via a modification of their surface composition and morphology

Surface nanobubbles as a function of gas type

We experimentally investigate the nucleation of surface nanobubbles on PFDTS-coated silicon as a function of the specific gas dissolved in the water. In each case we restrict ourselves to equilibrium conditions ($c=100$, $T_{liquid} = T_{substrate}$). Not only is nanobubble nucleation a strong function of gas type, but there also exists an optimal system temperature of $\sim 35-40\mathrm{^oC}$ where nucleation is maximized, which is weakly dependent on gas type. We also find that contact angle is a function of nanobubble radius of curvature for all gas types investigated. Fitting this data allows us to describe a line tension which is dependent on the type of gas, indicating that the nanobubbles are sat on top of adsorbed gas molecules. The average line tension was $\tau \sim -0.8 \mathrm{nN}$