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

From Monochrome to Technicolor: Simple Generic Approaches to Multicomponent Protein Nanopatterning Using Siloxanes with Photoremovable Protein-Resistant Protecting Groups.

We show that sequential protein deposition is possible by photodeprotection of films formed from a tetraethylene-glycol functionalized nitrophenylethoxycarbonyl-protected aminopropyltriethoxysilane (NPEOC-APTES). Exposure to near-UV irradiation removes the protein-resistant protecting group, and allows protein adsorption onto the resulting aminated surface. The protein resistance was tested using proteins with fluorescent labels and microspectroscopy of two-component structures formed by micro- and nanopatterning and deposition of yellow and green fluorescent proteins (YFP/GFP). Nonspecific adsorption onto regions where the protecting group remained intact was negligible. Multiple component patterns were also formed by near-field methods. Because reading and writing can be decoupled in a near-field microscope, it is possible to carry out sequential patterning steps at a single location involving different proteins. Up to four different proteins were formed into geometric patterns using near-field lithography. Interferometric lithography facilitates the organization of proteins over square cm areas. Two-component patterns consisting of 150 nm streptavidin dots formed within an orthogonal grid of bars of GFP at a period of ca. 500 nm could just be resolved by fluorescence microscopy

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

Design catalogue for eco-engineering of coastal artificial structures:a multifunctional approach for stakeholders and end-users

Coastal urbanisation, energy extraction, food production, shipping and transportation have led to the global proliferation of artificial structures within the coastal and marine environments (sensu “ocean sprawl”), with subsequent loss of natural habitats and biodiversity. To mitigate and compensate impacts of ocean sprawl, the practice of ecoengineering of artificial structures has been developed over the past decade. Eco-engineering aims to create sustainable ecosystems that integrate human society with the natural environment for the benefit of both. The science of eco-engineering has grown markedly, yet synthesis of research into a user-friendly and practitioner-focused format is lacking. Feedback from stakeholders has repeatedly stated that a “photo user guide” or “manual” covering the range of eco-engineering options available for artificial structures would be beneficial. However, a detailed and structured “user guide” for eco-engineering in coastal and marine environments is not yet possible; therefore we present an accessible review and catalogue of trialled eco-engineering options and a summary of guidance for a range of different structures tailored for stakeholders and end-users as the first step towards a structured manual. This work can thus serve as a potential template for future eco-engineering guides. Here we provide suggestions for potential eco-engineering designs to enhance biodiversity and ecosystem functioning and services of coastal artificial structures with the following structures covered: (1) rock revetment, breakwaters and groynes composed of armour stones or concrete units; (2) vertical and sloping seawalls; (3) over-water structures (i.e., piers) and associated support structures; and (4) tidal river walls

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

Peer expectations about outstanding competencies of men and women medical students

Men and women enrolled in a combined premedical-medical school programme were asked as they began their clinical training to rate their anticipated competence on sixteen criteria relevant to medical practice. Competence dimensions tapped scientific/technical skills, dedication/commitment, and interpersonal skills. Students then were asked to nominate one classmate whom they expected might be‘the best’in each area. Self-ratings revealed few differences among men and women. Peer nominations, however, revealed a preponderance of male nominees in ten competence areas. Women dominated nominations only in the category of sensitivity to patients. Patterns persisted when peer nominations were controlled for students’academic standing and self-ratings on parallel dimensions. The data suggest that medical school peer groups share expectations about competencies of men and women as physicians which are consistent with generalized sex stereotypes and career patterns of men and women physicians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74843/1/1467-9566.ep11340055.pd

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

Increased Production of the Soluble Tumor-Associated Antigens CA19-9, CA125, and CA15-3 in Rheumatoid Arthritis

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.3, may be increased in patients with RA, scleroderma, lupus, and SjÖgren's syndrome (SS). Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. We assessed levels of TAAs in the sera of RA patients and healthy subjects. Serum TAA levels were correlated with disease markers including serum rheumatoid factor (RF), C-reactive protein (CRP), and anti-CCP antibody levels, DAS28, age disease duration. TAAs including CEA, CA15-3, CA72-4, CA125, and CA19-9, and neuron-specific enolase (NSE) were assessed by immunoassay in the sera of 75 patients with RA and 50 age- and sex-matched healthy controls. Normal upper limits for these TAAs were 3.4 Μg/L, 25 kU/L, 6.9 kU/L, 35 kU/L, 34 kU/L, and 16.3 Μg/L, respectively. There were significantly more RA patients showing abnormally high levels of CA125 (10.8% versus 7.1%), CA19-9 (8.1% versus 0%), and CA15-3 (17.6% versus 14.3%) in comparison to controls ( P < 0.05). The mean absolute serum levels of CA125 (23.9 ± 1.8 versus 16.8 ± 2.2 kU/L) and CA19-9 (14.2 ± 1.2 versus 10.5 ± 1.6 kU/L) were also significantly higher in RA compared to controls ( P < 0.05). Among RA patients, serum CEA showed significant correlation with RF ( r = 0.270; P < 0.05). None of the assessed TAAs showed any correlation with CRP, anti-CCP, DAS28, age or disease duration. The concentration of some TAAs may be elevated in the sera of patients with established RA in comparison to healthy subjects. CEA, CA19-9, CA125, and CA15-3 contain carbohydrate motifs and thus they may be involved in synovitis-associated adhesive events. Furthermore, some TAAs, such as CEA, may also correlate with prognostic factors, such as serum RF levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73224/1/annals.1422.037.pd

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