Oriented Internal Electrostatic Fields Cooperatively Promote Ground- and Excited-State Reactivity: A Case Study in Photochemical CO2 Capture

Oriented electrostatic fields can exert catalytic effects upon both the kinetics and the thermodynamics of chemical reactions; however, the vast majority of studies thus far have focused upon ground-state chemistry and rarely consider any more than a single class of reaction. In the present study, we first use density functional theory (DFT) calculations to clarify the mechanism of CO2 storage via photochemical carboxylation of o-alkylphenyl ketones, originally proposed by Murakami et al. (J. Am. Chem. Soc.2015, 137, 14063); we then demonstrate that oriented internal electrostatic fields arising from remote charged functional groups (CFGs) can selectively and cooperatively promote both ground- and excited-state chemical reactivity at all points along the revised mechanism, in a manner otherwise difficult to access via classical substituent effects. What is particularly striking is that electrostatic field effects upon key photochemical transitions are predictably enhanced in increasingly polar solvents, thus overcoming a central limitation of the electrostatic catalysis paradigm. We explain these observations, which should be readily extendable to the ground state.We acknowledge financial support from the Australian Research Council (ARC) Centre of Excellence for Electromaterials Science (CE140100012, FL170100041), an ARC Laureate Fellowship (to M.L.C.), and generous supercomputing time from the National Computational Infrastructure. M.T.B. acknowledges an Australian Government Research Training Program Scholarship and Dean’s Merit Scholarship in Science. We also wish to thank Vincent Doan for helpful discussions

Establishing the Japan-Store House of Animal Radiobiology Experiments (J-SHARE), a large-scale necropsy and histopathology archive providing international access to important radiobiology data

Purpose: Projects evaluating the effects of radiation, within the National Institutes of Quantum and Radiological Science and Technology (QST), National Institute of Radiological Sciences (NIRS), have focused on risk analyses for life shortening and cancer prevalence using laboratory animals. Genetic and epigenetic alterations in radiation-induced tumors have been also analyzed, with the aim of better understanding mechanisms of radiation carcinogenesis. As well as the economic and practical limitations of repeating such large-scale experiments, ethical considerations make it vital that we store and share the pathological data and samples of the animal experiments for future use. We are now constructing such an archive called the Japan-Storehouse of Animal Radiobiology Experiments (J-SHARE). Methods: J-SHARE records include information such as detailed experimental protocols, necropsy records and photographs of organs at necropsy. For each animal organs and tumor tissues are dissected, and parts are stored as frozen samples at -80 ˚C. Samples fixed with formalin are also embedded in paraffin blocks for histopathological analyses. Digital copies of stained tissues are being systematically saved using a virtual slide system linked to original records by barcodes. Embedded and frozen tissues are available for molecular analysis. Conclusion: Similar archive systems for radiation biology have been also under construction in the USA and Europe, the Northwestern University Radiation Archive (NURA), and STORE at the BfS, respectively. The J-SHARE will be linked with the sister-archives and made available for collaborative research to institutions and universities all over the world

A multi-layer integral model for locally-heated thin film flow

Based on an approach used to model environmental flows such as rivers and estuaries, we develop a new multi-layered model for thin liquid film flow on a locally-heated inclined plane. The film is segmented into layers of equal thickness with the velocity and temperature of each governed by a momentum and energy equation integrated across each layer individually. Matching conditions applied between the layers ensure the continuity of down-plane velocity, temperature, stress and heat flux. Variation in surface tension of the liquid with temperature is considered so that local heating induces a surface shear stress which leads to variation in the film height profile (the Marangoni effect). Moderate inertia and heat convection effects are also included. In the absence of Marangoni effects, when the film height is uniform, we test the accuracy of the model by comparing it against a solution of the full heat equation using finite differences. The multi-layer model offers significant improvements over that of a single layer. Notably, with a sufficient number of layers, the solution does not exhibit local regions of negative temperature often predicted using a single-layer model. With Marangoni effects included the film height varies however we find heat convection can mitigate this variation by reducing the surface temperature gradient and hence the surface shear stress. Numerical results corresponding to the flow of water on a vertical plane show that very thin films are dominated by the Marangoni shear stress which can be sufficiently strong to overcome gravity leading to a recirculation in the velocity field. This effect reduces with increasing film thickness and the recirculation eventually disappears. In this case heating is confined entirely to the interior of the film leading to a uniform height profile

Calorie restriction alters the mechanisms of radiation-induced mouse thymic lymphomagenesis

Calorie restriction (CR) suppresses not only spontaneous but also chemical- and radiation-induced carcinogenesis. Our previous study revealed that the cancer-preventive effect of CR is tissue dependent and that CR does not effectively prevent the development of thymic lymphoma (TL). We investigated the association between CR and the genomic alterations of resulting TLs to clarify the underlying resistance mechanism. TLs were obtained from previous and new experiments, in which B6C3F1 mice were exposed to radiation at 1 week of age and fed with a CR or standard (non-CR) diet from 7 weeks throughout their lifetimes. All available TLs were used for analysis of genomic DNA. In contrast to the TLs of the non-CR group, those of the CR group displayed suppression of copy-neutral loss of heterozygosity (LOH) involving relevant tumor suppressor genes (Cdkn2a, Ikzf1, Trp53, Pten), an event regarded as cell division–associated. However, CR did not affect interstitial deletions of those genes, which were observed in both groups. In addition, CR affected the mechanism of Ikzf1 inactivation in TLs: the non-CR group exhibited copy-neutral LOH with duplicated inactive alleles, whereas the CR group showed expression of dominant-negative isoforms accompanying a point mutation or an intragenic deletion. These results suggest that, even though CR reduces cell division–related genomic rearrangements by suppressing cell proliferation, tumors arise via diverse carcinogenic pathways including inactivation of tumor suppressors via interstitial deletions and other mutations. These findings provide a molecular basis for improved prevention strategies that overcome the CR resistance of lymphomagenesis

Technology and the dis-placing of learning in educational futures

Common visions of online education entail radically re-configuring the experience of learning: a technological displacement from the spatial order of classrooms into the more diffuse arena of digital networks. One assumption seems to be that the very spatial order of classrooms creates an undesirably rigid sense of place for schooling, one that is depressingly impervious to change; and that the attendant solution is to escape the realm of the ‘physical’ altogether – into an online realm more supportive of collaboration and free of face-the-front conventions. In the present paper we seek to challenge this oppositional view. We consider several ways in which digital technology can restructure the traditional spaces of educational practice, and identify design dynamics that may be neglected in the wake of ‘virtualisation’. Discussion first highlights two theoretical perspectives that will inform many such designs: namely, situativity and sociality in learning. Three examples are then provided of how digital technology can intersect with learning space design to create novel interpersonal frameworks for learning and to destabilise conventional senses of ‘place’ in those settings. The examples concern, respectively, the organisation of collaborative, expository, and community-based social structures for learning. Those examples represent an illustrative counterpoint to models of online schooling and illustrate a potentially productive synergy between the opportunities afforded by digital technologies, the desires of those who wish to dis-place learning online, and a well-established interest in learning space design

Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion

Runx2 is a metastatic transcription factor (TF) increasingly expressed during prostate cancer (PCa) progression. Using PCa cells conditionally expressing Runx2, we previously identified Runx2-regulated genes with known roles in epithelial–mesenchymal transition, invasiveness, angiogenesis, extracellular matrix proteolysis and osteolysis. To map Runx2-occupied regions (R2ORs) in PCa cells, we first analyzed regions predicted to bind Runx2 based on the expression data, and found that recruitment to sites upstream of the KLK2 and CSF2 genes was cyclical over time. Genome-wide ChIP-seq analysis at a time of maximum occupancy at these sites revealed 1603 high-confidence R2ORs, enriched with cognate motifs for RUNX, GATA and ETS TFs. The R2ORs were distributed with little regard to annotated transcription start sites (TSSs), mainly in introns and intergenic regions. Runx2-upregulated genes, however, displayed enrichment for R2ORs within 40 kb of their TSSs. The main annotated functions enriched in 98 Runx2-upregulated genes with nearby R2ORs were related to invasiveness and membrane trafficking/secretion. Indeed, using SDS–PAGE, mass spectrometry and western analyses, we show that Runx2 enhances secretion of several proteins, including fatty acid synthase and metastasis-associated laminins. Thus, combined analysis of Runx2's transcriptome and genomic occupancy in PCa cells lead to defining its novel role in regulating protein secretion

Research into land atmosphere interactions supports the Sustainable Development agenda

Greenhouse gas emissions and land use change - from deforestation, forest degradation and agricultural intensification - are contributing to climate change and biodiversity loss. Important landbased strategies such as planting trees or growing bioenergy crops (with carbon capture and storage) are needed to achieve the goals of the Paris Climate Agreement and to enhance biodiversity. The integrated Land Ecosystems Atmospheric Processes Study (iLEAPS) is an international knowledge-exchange and capacity-building network, specialising in ecosystems and their role in controlling the exchange of water, energy and chemical compounds between the land surface and the atmosphere. We outline priority directions for land-atmosphere interaction research and its contribution to the sustainable development agenda

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting