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www.AntarcticGlaciers.org was set up in 2012 to promote public understanding of glaciers and climate change. The website aims to connect researchers to the next generation, to focus on make science accessible and interesting, and to provide an easy-to-find resource for teachers, with relevant, engaging, original content, interesting visuals and teaching resources. This approach helps scientists connect with a large community; there are 250,000 GCSE Geography school students in the UK alone. AntarcticGlaciers.org is used as a teaching resource by numerous universities and schools worldwide, and is recommended explicitly to teachers by the UK Geographical Association, SCAR, the Quaternary Research Association, the Royal Geographical Society and the Geologists’ Association, among others. Resources from the website have been used in numerous school textbooks and MOOCs. Evaluation of user statistics shows that, to date, AntarcticGlaciers.org has received >3.2 million page views from >1.7 million visitors located across the globe. It has been well cited by diverse news outlets and scientific institutions including NASA, NSIDC, AGU, EGU and RealClimate.org. Google Analytics data shows that a substantial portion of the audience are engaged in the education sector. The website is the top or second hit in Google for a number of related search terms, and the majority of the traffic originates from organic searches. AntarcticGlaciers.org is supported by an unpaid Advisory Board comprising Higher Education professionals and practicing school teachers. The Advisory Board, in conjunction with focus groups and interviews held with teachers and teaching professional bodies, helps to guide website development. These interviews have revealed few appropriate teaching resources covering Antarctica for younger age groups (11-14 years). Resources that focused on quantitative data, introducing GIS and mapping, and that were clearly linked into the curriculum, were particularly sought after. Teachers indicated that existing content is often too hard and needs to be rewritten. Case studies, exciting multimedia visuals, interactive GIS and interesting student exercises are intensely desired. In current times, accessibility for learners at home is key priority. The limited attention spans of children means that large blocks of text do not work well and are best broken up with multimedia resources. Interactivity engages the learner and increases knowledge retention. Supporting teachers in teaching these topics, by developing engaging and exciting introductory content, is therefore a critical outreach goal. In this project, funded by the Antarctic Science Bursary, academic experts have worked with pedagogical consultants and ESRI educational consultants to develop a series of four ESRI StoryMap collections that cover: Introduction to Antarctica, Antarctic Wildlife, Antarctica and Climate Change, and People in Antarctica. These fully interactive StoryMaps include student mapping exercises, videos and interviews with experts, high quality photography and engaging imagery. They are tightly keyed into the national curriculum, and by working with educational experts, we have attempted to ensure that they are useful for teachers. Reviews by independent stakeholders at the final stage of the project will ensure that the StoryMaps will be effective in the classroom, especially in an online learning environment.

Genome-wide transcriptomic analyses in whole tissues reflect the aggregate gene expression in heterogeneous cell populations comprising resident and migratory cells, and they are unable to identify cell type–specific information. We used a computational method (population-specific expression analysis [PSEA]) to decompose gene expression in gingival tissues into cell type–specific signatures for 8 cell types (epithelial cells, fibroblasts, endothelial cells, neutrophils, monocytes/macrophages, plasma cells, T cells, and B cells). We used a gene expression data set generated using microarrays from 120 persons (310 tissue samples; 241 periodontitis affected and 69 healthy). Decomposition of the whole-tissue transcriptomes identified differentially expressed genes in each of the cell types, which mapped to biologically relevant pathways, including dysregulation of Th17 cell differentiation, AGE-RAGE signaling, and epithelial-mesenchymal transition in epithelial cells. We validated selected PSEA-predicted, differentially expressed genes in purified gingival epithelial cells and B cells from an unrelated cohort ( n = 15 persons), each of whom contributed with 1 periodontitis-affected and 1 healthy gingival tissue sample. Differential expression of these genes by quantitative reverse transcription polymerase chain reaction corroborated the PSEA predictions and pointed to dysregulation of biologically important pathways in periodontitis. Collectively, our results demonstrate the robustness of the PSEA in the decomposition of gingival tissue transcriptomes and its ability to identify differentially regulated transcripts in particular cellular constituents. These genes may serve as candidates for further investigation with respect to their roles in the pathogenesis of periodontitis.

A typical microgrid is consists of interconnected load with renewable, non-renewable distributed generation sources and energy storage devices to manage load demand. The utilization of solar renewable energy sources offers many advantages, such as decreasing environmental emissions and enhancing cost economy. The optimal design of the microgrid includes identifying the most suitable configuration from all possible configuration and choosing the suitable capacities of the storage devices and the energy sources. In this case study, the grid-connected microgrid is designing based on the minimum energy cost and net present cost. Therefore, the proposed microgrid shows more benefits with respect to technical and cost economy performances relative to base case system. A case study of NIT Durgapur system is presented to design and analyze utility grid-connected microgrid systems, including the two optional tariffs. Finally, the comparative analysis is also presented for the proposed microgrid system.

Supplemental material, sj-pdf-1-jdr-10.1177_0022034520979614 for Cell Type–Specific Decomposition of Gingival Tissue Transcriptomes by F. Momen-Heravi, R.A. Friedman, S. Albeshri, A. Sawle, M. Kebschull, A. Kuhn and P.N. Papapanou in Journal of Dental Research

Nowadays, the demand for renewable energy is increased for electrical power generation with conventional sources. Renewable energy resources are available free of cost, as pollution-free, and abundantly available in the environment. While designing renewable hybrid systems, there are so many challenges, such as the issue of continuous power supply to the load, storage issues, and sizing of the substation. All these issue are addressed in this chapter using the Hybrid Optimization Model for Electric Renewable software. An off-grid hybrid renewable energy system is proposed with photovoltaic (PV), wind turbine (WT), biomass, and backup protection unit to electrify the remote location where utility supply is not available. The off-grid hybrid system design location has great potential of solar irradiation 5.19 kWh/day, wind speed 4.51 m/s, and biomass resource production 0.13 tonnes/day. The off-grid hybrid system prefeasibility analysis is based on economic, technical, and emission parameters. In this chapter, six different configurations of the hybrid renewable system are considered to evaluate the feasibility and was found that PV/WT/biomass/generator/battery hybrid system is more optimal solution among all six configurations. This configuration has the lowest levelized cost of energy ($0.1914), less initial cost ($99,889.45), and operating cost ($3415) of the hybrid system. Among all off-grid system, PV/WT/biomass/generator/battery produces very less emission and a high renewable fraction of 86.5% as compared to other configurations.

Background: BCAT1 (Branched Chain Amino Transferase 1) has been shown to be upregulated in human IDH (isocitrate dehydrogenase) wild-type glioblastoma (GBM) and BCAT1 knockdown leads to reduced cell proliferation in vitro and in vivo1. Here we investigated the role of BCAT1 in human patient-derived glioblastoma cells and the corresponding orthotopically implanted xenografts to understand how upregulation of the enzyme leads to a more aggressive phenotype. Methods: The expression of BCAT1 was investigated in a panel of patient derived IDH wild-type glioblastoma cells and BCAT1 expression modulation was achieved using lentiviral expression of a doxycycline-inducible shRNA, to knockdown BCAT1 and expression of a BCAT1 cDNA to overexpress BCAT1. Effects of BCAT1 knockdown and overexpression were investigated in vitro in cell culture and in vivo, following intracranial implantation of mice with the relevant cells. Results: Variable levels of BCAT1 expression were identified in different patient-derived cell lines. RNA sequencing analysis of BCAT1 knockdown in BCAT1 expressing glioblastoma cells revealed that knockdown led to significant downregulation of HIF 1α (Hypoxia Inducible Factor 1α) and its targets, which was confirmed by Western Blot analysis of Carbonic Anhydrase IX (CAIX) and Hexokinase II (HKII) in cell and tumor lysates. The opposite was observed following BCAT1 overexpression. BCAT1 knockdown also led to higher DNA demethylation levels. Treatment with membrane permeant dimethyl-alpha ketoglutarate mimicked the effect of BCAT1 knockdown. These data suggest that decreased cell proliferation following BCAT1 knockdown in BCAT1 expressing cells is mediated by accumulation of alpha-ketoglutarate, a substrate of BCAT1. Cells that had no BCAT1 expression showed a similar growth profile and overexpression had no effect on proliferation, suggesting that these cells are not dependent on BCAT1 expression. Conclusion: We conclude that in a subtype of GBM characterized by upregulated BCAT1, BCAT1 expression results in lowered levels of alpha-ketoglutarate, leading to reduced prolyl hydroxylase activity and stabilization of HIF 1α and therefore a pseudo-hypoxic state, resulting in a transcriptome that favors a high proliferation rate. This makes BCAT1 a potential therapeutic target, for tumors that show BCAT1 upregulation.1. Tönjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med. 2013;19(7):901-908. doi:10.1038/nm.3217 Citation Format: Maria Fala, Susana Ros, Ashley Sawle, Kevin M. Brindle. Increased BCAT1 expression creates a pseudo-hypoxic environment that promotes cell proliferation in a subtype of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2179.

GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs. DNA topoisomerases help unwind DNA but occasionally get trapped, resulting in DNA-protein crosslinks (DPCs). DPCs damage DNA and threaten genomic integrity. Dokshin et al. find that GCNA protein family complements standard DPC processing machinery in resolving topoisomerase II DPCs to ensure heritable genome stability and germline immortality., National Institutes of Health (U.S.) (Grant P40 OD010440)

This paper presents a maximum power point tracking (MPPT) algorithm in a solar photovoltaic (SPV) system that requires fewer sensors, is easy to implement, and offers a good tracking efficiency and speed. Among various MPPT algorithms found in literature, the perturb and observe (P&O) algorithm is most popular as it required less complex circuitry and is easy to implement, but it suffers against fast-changing environmental conditions mostly in the case of partial shading conditions and requires two sensors, i.e., voltage and current. This paper presents the one sensor-based method based on the modified converter design which eliminates the effect of partial shading conditions as well as the fast-changing environmental condition. The presented MPPT algorithm was implemented and tested using an FPGA-based NI-sbRIO card interfaced with Labview software.

This paper presents the optimal hybrid power system design including various configurations of renewable energy generation. To decide the optimal configuration of parameters a new multi-objective function with six separate objectives of hybrid renewable system is presented using GA, PSO, BFPSO and TLBO optimization techniques. The different parameters namely technical (LPSP, Renewable factor), economical (COE, Penalty & Fuel consumption) and social (Job creation, HDI & PM) features are investigated as objectives simultaneously for optimal design of hybrid system. The design consideration of hybrid system using a novel PM factor, human health impacts are directly shown whereas pollutant emission is measured in the hybrid system design. Based on the minimum value of multi-objective function optimal values are decided for objective indices. For optimal configuration including various combinations of wind, PV, diesel generator, biomass and battery bank, separate cases from I to VI of hybrid system are tested. Performance of TLBO is found to be better than BFPSO, PSO and GA as per the analysis of results for individual cases. Also the case I found to be the most efficient solution among all cases.

PV and wind hybrid are found to be the most lucrative solution for the diminishing traditional energy sources. Whereas these alternatives sources of the energy have many remarkable rewards like cost of energy and feasibility etc. The attributes of these sources of being cost effective and stable are possible due to their complementary nature as compared to independent energy systems. Therefore, these systems have admirable capability to meet energy crisis up to some extent. The proposed work gives the idea about various configuration, control strategy, techno-economic analysis and social effect. The findings of comprehensive review will help for further improvements in hybrid system design and control with respect to practical system implementation. This paper also presents a case study of remote area Barwani, India and results are compared using Homer and PSO. The resulting analysis reveals that configurations of hybrid system are the most techno-economical feasible solution concerning COE, renewable fraction, maximum renewable penetration, levelized cost, operating cost, mean electrical efficiency, and emission amongst various hybrid system configurations using PSO as compared to HOMER.

Summary The optimal design of a hybrid system with different configurations including renewable generation is presented in this paper. A novel multi-objective function consisting of 6 different objectives of hybrid system is reported using GA, PSO, and TLBO to decide the optimal configurations of parameters. The technical (loss of power supply probability, renewable factor), economical (cost of energy, penalty and fuel consumption), and social (job creation, human development index, and particular matter) features are investigated as objectives simultaneously for optimal design of hybrid system. The different objective indices namely cost of energy, loss of power supply probability, particular matter, human development index, job creation, and renewable factor indices are considered. The newly invented particular matter factor for design consideration of hybrid system directly shows the human health impacts, while pollutant emission is measured in the hybrid system design. The optimum values of objective indices are decided on the basis of the minimum value of multi-objective function. The distinct cases from I to VI of hybrid system are examined for optimal configuration including different combinations of PV, wind, biomass, diesel generator, and battery bank. The resulting analysis of each case reveals that the performance of TLBO is better than PSO, and PSO is better than GA in all respect through new multi-objective function and found case I is more efficient solution.

This paper presents the optimal planning of PV-Wind-Biomass hybrid energy system, which includes back up power sources as battery bank and diesel generator. The cost of energy (COE) or electricity price is minimized as objective function using GA and PSO. The optimal configuration of hybrid system is obtained on the basis of minimum COE. The optimal solution is consists with high reliability, maximum value of renewable fraction, less emission and low penalty cost according to minimum COE. The reliability is computed on the basis of loss of power supply probability (LPSP), which is assumed 2% maximum in this case study. This paper aim's to present the techno-economic feasibility of pv-wind-biomass hybrid energy system (HES) for a case study of remote area of barwani district, India. The optimization results are presented for load following and cycle charging strategy and also compared the results using GA and PSO optimization techniques.

The Estrogen Receptor (ER) drives 75% of breast cancers. On activation, the ER recruits co-factors to form a transcriptionally active complex. These co-factors can modulate tumour growth, and understanding their roles can help to identify new therapeutic targets.Here, we present the discovery of an ER-ZMIZ1 interaction by quantitative proteomics, and validated by proximity ligation assay. We characterise ZMIZ1 function by demonstrating that targeting ZMIZ1 results in the reduction of ER transcriptional activity at estrogen response elements and a significant decrease in the proliferation of ER-positive cancer cell lines.To establish a role for the ER-ZMIZ1 interaction, we measured the transcriptional changes in the estrogen response post-ZMIZ1 knockdown using an RNA-seq time-course over 24 hours. GSEA analysis of the ZMIZ1-knockdown data identified a specific delay in the response of estradiol-induced cell-cycle genes.Integration of ENCODE data with our RNA-seq results identified ER and ZMIZ1 binding at the promoter of E2F2. We therefore propose that ER and ZMIZ1 co-regulate an important subset of cell cycle genes via a novel ER-ZMIZ1-E2F2 signalling axis.Finally, we show that high ZMIZ1 expression is predictive of worse patient outcome, ER and ZMIZ1 are co-expressed in breast cancer patients in TCGA, METABRIC, and the proteins are co-localised within the nuclei of tumours cell in patient biopsies.In conclusion, we establish that ZMIZ1 is a regulator of the estrogenic cell cycle response and provide evidence of the biological importance of the ER-ZMIZ1 interaction ER+ patient tumours, supporting potential clinical relevance.

The Estrogen Receptor (ER) drives 75% of breast cancers. On activation, the ER recruits specific co-factors to form a transcriptionally active complex. These co-factors can modulate tumour growth and understanding their roles can help to identify new therapeutic targets. We applied a quantitative proteomics method, qPLEX-RIME, to analyse the ER protein complex and characterise changes in protein-protein interactions on activation. Our analysis identified ZMIZ1 as novel co-factor within the ER chromatin-bound complex, extending its known role as a co-factor of the Androgen Receptor. We find further evidence for an ER–ZMIZ1 interaction by showing that both proteins are co-expressed in biopsy samples. We characterise ZMIZ1 function by showing that targeting ZMIZ1 results in the reduction of ER transcriptional activity and significantly reduces the proliferation of ER-positive cell lines. We validated these results genome-wide by RNA-seq and identified that targeting ZMIZ1 resulted in a specific reduction of estradiol-induced cell cycle genes. These results establish ZMIZ1 as a having a key role in the ability of the ER to activate key genes that drive the proliferation of breast cancer, and its biological importance in patient tumours.

The piRNA pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialised machinery that converts long single-stranded precursors into small RNAs of ~25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb-body and mitochondria. How these two sites communicate to achieve accurate substrate selection and efficient processing remains unclear. Here, we investigate a previously uncharacterized piRNA biogenesis factor, Daedalus (Daed), that is located on the outer mitochondrial membrane. Daed is essential for Zucchini-mediated piRNA production and for the correct localisation of the indispensable piRNA biogenesis factor, Armitage (Armi). We find that Gasz and Daed interact with each other and likely provide a mitochondrial “anchoring platform” to ensure that Armi is held in place, proximal to Zucchini, during piRNA processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb-bodies in a manner that depends upon Piwi and then moves to mitochondria to present precursors to the mitochondrial biogenesis machinery. These results represent a significant step in understanding a critical aspect of transposon silencing, namely how RNAs are chosen to instruct the piRNA machinery in the nature of its silencing targets.

SummaryGCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan/DVC-1 and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. We show that GCNA and Topoisomerase 2 (Top2) physically interact and colocalize on condensed chromosomes during mitosis, when Spartan is not present. We show thatC. elegans gcna-1mutants are sensitive to Top2 poison and accumulate mutations consistent with low fidelity repair of DNA damage, leading to loss of fitness and fertility over generations. We also demonstrate that mouse GCNA interacts with TOP2, andGcna-mutant mice exhibit abnormalities consistent with the inability to process DPCs, including chromatin condensation and crossover defects. Together, our findings provide evidence that GCNA maintains genomic integrity by processing Top2 DPCs in the germline and early embryo, where the genome is challenged with an increased DPC burden.

Ehlers–Danlos Syndrome (EDS) is a group of connective tissue disorders which are both heterogeneous and heritable. The condition is a result of collagen defects, which include genetic variations and collagen protein processing. Collagen is present in fibrous tissues, such as skin, tendons and ligaments, and is also found in cartilage, blood vessels, the cornea, bones and the gut, highlighting its importance and explaining the varied pathophysiology of collagen conditions. These disorders were classified into six major types based upon the genetic and diagnostic variability and pathophysiology which includes skin hyperextensibility, joint hypermobility and tissue friability, but this classification has recently been amended. Determining the type of EDS an individual suffers from is a multifaceted process which relies on clinical examination as well as multiple laboratory techniques. These include: collagen biochemistry; genetic sequencing of the collagen genes, light microscopy, electron microscopy and urinary cross-link analysis. Diagnosis is important to both identify EDS types, allowing management of the condition, and also to aid psychologically where sufferers can appear fit and healthy but in fact be suffering pain and remain undiagnosed. This chapter aims to give an overview of connective tissue disorders, specifically EDS, and to describe and discuss diagnosing EDS in an NHS diagnostic unit. Giving detail on the techniques involved and the interpretation of results obtained.

Here we report a novel nitridation technique for transforming niobium into hexagonal Nb2N which appears to be superconducting below 1K. The nitridation is achieved by high temperature annealing of Nb films grown on Si3N4/Si (100) substrate under high vacuum. The structural characterization directs the formation of a majority Nb2N phase while the morphology shows granular nature of the films. The temperature dependent resistance measurements reveal a wide metal-to-superconductor transition featuring two distinct transition regions. The region close to the normal state varies strongly with the film thickness, whereas, the second region in the vicinity of the superconducting state remains almost unaltered but exhibiting resistive tailing. The current-voltage characteristics also display wide transition embedded with intermediate resistive states originated by phase slip lines. The transition width in current and the number of resistive steps depend on film thickness and they both increase with decrease in thickness. The broadening in transition width is explained by progressive establishment of superconductivity through proximity coupled superconducting nano-grains while finite size effects and quantum fluctuation may lead to the resistive tailing. Finally, by comparing with Nb control samples, we emphasize that Nb2N offers unconventional superconductivity with promises in the field of phase slip based device applications.

Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury.\ud \ud Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors.\ud \ud Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies.\ud \ud Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Estrogen Receptor alpha (ERα) plays a major role in most breast cancers, and it is the target of endocrine therapies used in the clinic as standard of care for women with breast cancer expressing this receptor. The two methods ChIP-seq (chromatin immunoprecipitation coupled with deep sequencing) and RIME (Rapid Immunoprecipitation of Endogenous Proteins) have greatly improved our understanding of ERα function during breast cancer progression and in response to anti-estrogens. A critical component of both ChIP-seq and RIME protocols is the antibody that is used against the bait protein. To date, most of the ChIP-seq and RIME experiments for the study of ERα have been performed using the sc-543 antibody from Santa Cruz Biotechnology. However, this antibody has been discontinued, thereby severely impacting the study of ERα in normal physiology as well as diseases such as breast cancer and ovarian cancer. Here, we compare the sc-543 antibody with other commercially available antibodies, and we show that 06-935 (EMD Millipore) and ab3575 (Abcam) antibodies can successfully replace the sc-543 antibody for ChIP-seq and RIME experiments.