[NiFeSe]-hydrogenase chemistry.

The development of technology for the inexpensive generation of the renewable energy vector H2 through water splitting is of immediate economic, ecological, and humanitarian interest. Recent interest in hydrogenases has been fueled by their exceptionally high catalytic rates for H2 production at a marginal overpotential, which is presently only matched by the nonscalable noble metal platinum. The mechanistic understanding of hydrogenase function guides the design of synthetic catalysts, and selection of a suitable hydrogenase enables direct applications in electro- and photocatalysis. [FeFe]-hydrogenases display excellent H2 evolution activity, but they are irreversibly damaged upon exposure to O2, which currently prevents their use in full water splitting systems. O2-tolerant [NiFe]-hydrogenases are known, but they are typically strongly biased toward H2 oxidation, while H2 production by [NiFe]-hydrogenases is often product (H2) inhibited. [NiFeSe]-hydrogenases are a subclass of [NiFe]-hydrogenases with a selenocysteine residue coordinated to the active site nickel center in place of a cysteine. They exhibit a combination of unique properties that are highly advantageous for applications in water splitting compared with other hydrogenases. They display a high H2 evolution rate with marginal inhibition by H2 and tolerance to O2. [NiFeSe]-hydrogenases are therefore one of the most active molecular H2 evolution catalysts applicable in water splitting. Herein, we summarize our recent progress in exploring the unique chemistry of [NiFeSe]-hydrogenases through biomimetic model chemistry and the chemistry with [NiFeSe]-hydrogenases in semiartificial photosynthetic systems. We gain perspective from the structural, spectroscopic, and electrochemical properties of the [NiFeSe]-hydrogenases and compare them with the chemistry of synthetic models of this hydrogenase active site. Our synthetic models give insight into the effects on the electronic properties and reactivity of the active site upon the introduction of selenium. We have utilized the exceptional properties of the [NiFeSe]-hydrogenase from Desulfomicrobium baculatum in a number of photocatalytic H2 production schemes, which are benchmark systems in terms of single site activity, tolerance toward O2, and in vitro water splitting with biological molecules. Each system comprises a light-harvesting component, which allows for light-driven electron transfer to the hydrogenase in order for it to catalyze H2 production. A system with [NiFeSe]-hydrogenase on a dye-sensitized TiO2 nanoparticle gives an enzyme-semiconductor hybrid for visible light-driven generation of H2 with an enzyme-based turnover frequency of 50 s(-1). A stable and inexpensive polymeric carbon nitride as a photosensitizer in combination with the [NiFeSe]-hydrogenase shows good activity for more than 2 days. Light-driven H2 evolution with the enzyme and an organic dye under high O2 levels demonstrates the excellent robustness and feasibility of water splitting with a hydrogenase-based scheme. This has led, most recently, to the development of a light-driven full water splitting system with a [NiFeSe]-hydrogenase wired to the water oxidation enzyme photosystem II in a photoelectrochemical cell. In contrast to the other systems, this photoelectrochemical system does not rely on a sacrificial electron donor and allowed us to establish the long sought after light-driven water splitting with an isolated hydrogenase.We acknowledge support by the Christian Doppler Research Association (Austrian Federal Ministry of Science, Research and Economy and National Foundation for Research, Technology and Development), the OMV Group, the EPSRC (EP/H00338X/2) and a Marie Curie fellowship to C.C. (GAN 624997).This is the accepted manuscript. It is currently embargoed pending publication

Solar hydrogen production using carbon quantum dots and a molecular nickel catalyst.

Carbon quantum dots (CQDs) are established as excellent photosensitizers in combination with a molecular catalyst for solar light driven hydrogen production in aqueous solution. The inexpensive CQDs can be prepared by straightforward thermolysis of citric acid in a simple one-pot, multigram synthesis and are therefore scalable. The CQDs produced reducing equivalents under solar irradiation in a homogeneous photocatalytic system with a Ni-bis(diphosphine) catalyst, giving an activity of 398 μmolH2 (gCQD)(-1) h(-1) and a "per Ni catalyst" turnover frequency of 41 h(-1). The CQDs displayed activity in the visible region beyond λ > 455 nm and maintained their full photocatalytic activity for at least 1 day under full solar spectrum irradiation. A high quantum efficiency of 1.4% was recorded for the noble- and toxic-metal free photocatalytic system. Thus, CQDs are shown to be a highly sustainable light-absorbing material for photocatalytic schemes, which are not limited by cost, toxicity, or lack of scalability. The photocatalytic hybrid system was limited by the lifetime of the molecular catalyst, and intriguingly, no photocatalytic activity was observed using the CQDs and 3d transition metal salts or platinum precursors. This observation highlights the advantage of using a molecular catalyst over commonly used heterogeneous catalysts in this photocatalytic system.This work was supported by an Oppenheimer PhD scholarship (to B.C.M.M.), a Poynton PhD scholarship (to G.A.M.H.), a Marie Curie postdoctoral fellowship (GAN 624997 to C.C.), an EPSRC Career Acceleration Fellowship (EP/H00338X/2 to E.R.), the Christian Doppler Research Association (Austrian Federal Ministry of Science, Research, and Economy and the National Foundation for Research, Technology and Development), and the OMV Group.This is the final version of the article. It first appeared from ACS via http://dx.doi.org/10.1021/jacs.5b01650

Solar-Driven Reduction of Aqueous Protons Coupled to Selective Alcohol Oxidation with a Carbon Nitride-Molecular Ni Catalyst System.

Solar water-splitting represents an important strategy toward production of the storable and renewable fuel hydrogen. The water oxidation half-reaction typically proceeds with poor efficiency and produces the unprofitable and often damaging product, O2. Herein, we demonstrate an alternative approach and couple solar H2 generation with value-added organic substrate oxidation. Solar irradiation of a cyanamide surface-functionalized melon-type carbon nitride ((NCN)CNx) and a molecular nickel(II) bis(diphosphine) H2-evolution catalyst (NiP) enabled the production of H2 with concomitant selective oxidation of benzylic alcohols to aldehydes in high yield under purely aqueous conditions, at room temperature and ambient pressure. This one-pot system maintained its activity over 24 h, generating products in 1:1 stoichiometry, separated in the gas and solution phases. The (NCN)CNx-NiP system showed an activity of 763 μmol (g CNx)(-1) h(-1) toward H2 and aldehyde production, a Ni-based turnover frequency of 76 h(-1), and an external quantum efficiency of 15% (λ = 360 ± 10 nm). This precious metal-free and nontoxic photocatalytic system displays better performance than an analogous system containing platinum instead of NiP. Transient absorption spectroscopy revealed that the photoactivity of (NCN)CNx is due to efficient substrate oxidation of the material, which outweighs possible charge recombination compared to the nonfunctionalized melon-type carbon nitride. Photoexcited (NCN)CNx in the presence of an organic substrate can accumulate ultralong-lived "trapped electrons", which allow for fuel generation in the dark. The artificial photosynthetic system thereby catalyzes a closed redox cycle showing 100% atom economy and generates two value-added products, a solar chemical, and solar fuel.This work was supported by the Christian Doppler Research Association (Austrian Federal Ministry of Science, Research, and Economy and the National Foundation for Research, Technology and Development) and the OMV Group (to E.R.), an Oppenheimer PhD scholarship (to B.C.M.M.), a Marie Curie Postdoctoral Fellowship (GAN 624997 to C.A.C.), a FRQNT Postdoctoral Fellowship (to R.G.), and an ERC Starting Grant (B. V. L., Grant No. 639233).This is the final version of the article. It first appeared from American Chemical Society via http://dx.doi.org/10.1021/jacs.6b0432

Willow short-rotation production systems in Canada and Northern United States: A review

Willow short rotation coppice (SRC) systems are becoming an attractive practice because they are a sustainable system fulfilling multiple ecological objectives with significant environmental benefits. A sustainable supply of bioenergy feedstock can be produced by willow on marginal land using well-adapted or tolerant cultivars. Across Canada and northern U.S.A., there are millions of hectares of available degraded land that have the potential for willow SRC biomass production, with a C sequestration potential capable of offsetting appreciable amount of anthropogenic green-house gas emissions. A fundamental question concerning 1 sustainable SRC willow yields was whether long-term soil productivity is maintained within a multi-rotation SRC system, given the rapid growth rate and associated nutrient exports offsite when harvesting the willow biomass after repeated short rotations. Based on early results from the first willow SRC rotation, it was found willow systems are relatively low nutrient-demanding, with minimal nutrient output other than in harvested biomass. The overall aim of this manuscript is to summarize the literature and present findings and data from ongoing research trials across Canada and northern U.S.A. examining willow SRC system establishment and viability. The research areas of interest presented here are the crop production of willow SRC systems, above- and below-ground biomass dynamics and the C budget, comprehensive soil-willow system nutrient budget, and soil nutrient amendments (via fertilization) in willow SRC systems. Areas of existing research gaps were also identified for the Canadian context

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Disrupting colonial discourses in the Geography curriculum during the introduction of British Values policy in schools

The main purpose of this article is to expose and disrupt discourses dominating global development in an English school geography textbook chapter. The study was prompted by a teacher’s encounter with cultural difference in a geography lesson in South Korea. I investigate the issues raised through the lens of a new curriculum policy in English schools called ‘Promoting Fundamental British Values’ which forms part of England’s education-securitisation agenda, a topic of international attention. Following contextualisation across research fields and in recent curriculum and assessment policy reform, I bring together theoretical perspectives from curriculum studies and Continental philosophy that do not usually speak to each other, to construct a new analytical approach. I identify three key themes, each informed by colonial logic: ‘development’, ‘numerical indicators’ and ‘learning to divide the world’. The inquiry appears to expose a tension between the knowledge of the textbook chapter and the purported aims of the British Values curriculum policy, but further investigation reveals the two to be connected through common colonial values. The findings are relevant to teachers, publishers, textbook authors, policy makers and curriculum researchers. I recommend a refreshed curriculum agenda with the politics of knowledge and ethical global relations at its centre

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations