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Using a Game to Engage Stakeholders in Extreme Event Attribution Science

International Journal of Disaster risk Science 2016年第4期7卷 353-365页

作者： Hannah r.Parker rosalind J.Cornforth Pablo Suarez Myles r.Allen emily Boyd rachel James richard G.Jones Friederike E.L.Otto Peter Walton Department of Meteorology University of Reading Walker Institute University of Reading red Cross red Crescent Climate Centre Pardee Center for the Study of the Longer-range Future Boston University Environmental Change Institute University of Oxford Atmospheric Oceanic and Planetary PhysicsUniversity of Oxford Department of Geography and Environmental Science University of Reading Present Address:Lund University Centre for Sustainability Studies Met Office Hadley Centre School of Geography and the Environment University of Oxford

The impacts of weather and climate-related disasters are increasing,and climate change can exacerbate many *** communicating climate risk and integrating science into policy requires scientists and stakeholders to work *** dialogue between scientists and policymakers can be challenging given the inherently multidimensional nature of the issues at stake when managing climate *** on the growing use of serious games to create dialogue between stakeholders,we present a new game for policymakers called Climate Attribution Under Loss and Damage:risking,Observing,Negotiating(CAULDrON).CAULDrON aims to communicate understanding of the science attributing extreme events to climate change in a memorable and compelling way,and create space for dialogue around policy decisions addressing changing risks and loss and damage from climate *** describe the process of developing CAULDrON,and draw on observations of players and their feedback to demonstrate its potential to facilitate the interpretation of probabilistic climate information and the understanding of its relevance to informing *** looking to engage with stakeholders can learn valuable lessons in adopting similar innovative *** suitability of games depends on the policy context but,if used appropriately,experiential learning can drive coproduced understanding and meaningful dialogue.

关键词： Climate change Extreme event attribution Loss and damage policy Participatory games Probabilistic event attribution(PEA) risk management

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The insect-killing bacterium Photorhabdus luminescens has the lowest mutation rate among bacteria

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Marine Life Science & Technology 2021年第1期3卷 20-27页

作者： Jiao Pan emily Williams Way Sung Michael Lynch Hongan Long Institute of Evolution and Marine Biodiversity KLMMEOcean University of ChinaQingdao 266003China Center for Mechanisms of Evolution The Biodesign InstituteArizona State UniversityTempeAZ 85281USA Department of Bioinformatics and Genomics University of North CarolinaCharlotteNC 28223USA

Mutation is a primary source of genetic variation that is used to power *** studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for *** a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens *** mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T *** has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other *** fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.

关键词： Neutral evolution Mutation accumulation Mutation spectrum Drift-barrier hypothesis Lower-limit of mutation rate

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Structure, Diversity, and Evolution of a New Family of Soluble Carotenoid-Binding Proteins in Cyanobacteria

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Molecular Plant 2016年第10期9卷 1379-1394页

作者： Matthew r. Melnicki ryan L. Leverenz Markus Sutter rocio Lopez-lgual Adjele Wilson emily G. Pawlowski Francois Perreau Diana Kirilovsky Cheryl A. Kerfeld Department of Plant and Microbial Biology University of California Berkeley CA 94720 USA Physical Biosciences Division Lawrence Berkeley National Laboratory Berkeley CA 94720 USA MSU-DOE Plant research Laboratory Department of Biochemistry and Molecular Biology Michigan State University East Lansing MI 48824 USA Institute for Integrative Biology of the Cell (I2BC) CEA CNRS Universite Paris-Sud Universite Paris-Saclay 91198 Gif-sur-Yvette France Commissariat & I'Energie Atomique (CEA) Institut de Biologie et Technologies de Saclay (iBiTec-S) 91191 Gif-sur-Yvette France INrA Institut Jean-Pierre Bourgin UMR 1318 ERL CNRS 3559 Saclay Plant Sciences RD10 78026 Versailles France Unite Plasticite du Genome Bacterien Departement Genomes et Genetique Institut Pasteur CNRS Unite Mixte de Recherche 3525 75015 Paris France

Using a phylogenomic approach, we have identified and subciassified a new family of carotenoid-binding proteins. These proteins have sequence homology to the N-terminal domain （NTD） of the Orange Carotenoid Protein （OCP）, and are referred to as Helical Carotenoid Proteins （HCPs）. These proteins comprise at least nine distinct ciades and are found in diverse organisms, frequently as multiple paralogs representing the distinct ciades. These seem to be out-paralogs maintained from ancient duplications associated with subfunctionalization. All of the HCPs share conservation of the residues for carotenoid binding, and we confirm that carotenoid binding is a fundamental property of HCPso We solved two crystal structures of the Nostoc sp. PCC 7120 HCP1 protein, each binding a different carotenoid, suggesting that the proteins flexibly bind a range of carotenoids. Based on a comprehensive phylogenetic analysis, we propose that one of the HCP subtypes is likely the evolutionary ancestor of the NTD of the OCP, which arose following a domain fusion evenS. However, we predict that the majority of HCPs have functions distinct from the NTD of the OCP. Our results demonstrate that the HCPs are a new family of functionally diverse carotenoid-binding proteins found among ecophysiologically diverse cyanobacteria.

关键词： carotenoids cyanobacteria phylogenomics protein structure photoprotection molecular evolution

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Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

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International Journal of Oral Science 2018年第4期10卷 212-222页

作者： r.Nicole Howie Samuel Herberg emily Durham Zachary Grey Grace Bennfors Mohammed Elsalanty Amanda C.Larue William D.Hill James J.Cray Oral Health Sciences Medical University of South CarolinaCharlestonSCUSA Biomedical Engineering Case Western Reserve UniversityClevelandOHUSA Cellular Biology and Anatomy Augusta UniversityAugustaGAUSA Oral Biology Augusta UniversityAugustaGAUSA Orthopaedic Surgery Augusta UniversityAugustaGAUSA Pathology and Laboratory Medicine Medical University of South CarolinaCharlestonSCUSA Institute for regenerative and reparative Medicine Augusta UniversityAugustaGAUSA research Service of the ralph H Johnson VA Medical Center CharlestonSCUSA Charlie Norwood VA Medical Center AugustaGAUSA Department of regenerative Medicine and Cellular Biology CharlestonSCUSA Wake Forest Institute for regenerative Medicine Wake Forest School of MedicineWinston-SalemNCUSA Division of Anatomy College of MedicineOhio State UniversityColumbusOHUSA

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSrIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSrIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSrI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSrI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSrI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

关键词： Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

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Estimating the Level of Asymptomatic COVID-19 Infections in Northern Ireland in 2020

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Open Journal of Modelling and Simulation 2022年第2期10卷 190-218页

作者： Peter A. Hall Gabor Kiss Tilman Kuhn Salissou Moutari Ellen Patterson emily Smith Mathematical Sciences research Centre School of Mathematics & Physics Queen’s University Belfast Belfast UK School of Biological Sciences Queen’s University Belfast Belfast UK Heidelberg Institute of Global Health (HIGH) Heidelberg University Hospital Heidelberg Germany

The identification and understanding of COVID-19 potential routes of transmission are fundamental to informing policies and strategies to successfully control the outbreak. Various studies highlighted asymptomatic infections as one of the silent drivers of the epidemic. An accurate estimation of the asymptomatic cases and the understanding of their contribution to the spread of the disease could enhance the effectiveness of current control strategies, mainly based on the symptom onset, to curb transmission. We investigate the dynamics of the COVID-19 epidemic in Northern Ireland during the period 1st March 25th to December 2020 to estimate the proportion of the asymptomatic infections in the country. We extended our previous model to include the stage of the asymptomatic infection, and we implement the corresponding deterministic model using a publicly available dataset. We partition the data into 11 sets over the period of study and fit the model parameters on the consecutive intervals using the cumulative number of confirmed positive cases for each interval. Moreover, we assess numerically the impacts of uncertainty in testing and we provide estimates of the reproduction numbers using the fitted parameters. We found that the proportion of asymptomatically infectious subpopulations, in Northern Ireland during the period of study, ranged between 5% and 25% of exposed individuals. Also, the estimate of the basic reproduction number, r0, is 3.3089. The lower and upper estimates for herd immunity are (0.6181, 0.7243) suggesting that around 70% of the population of Northern Ireland should acquire immunity via infection or vaccination, which is in line with estimates reported in other studies.

关键词： Pandemic Epidemic SArS-CoV-2 COVID-19 Compartmental Model SEIAr Model Basic reproduction Number Effective reproduction Number Parameter Estimates Fitted Model Testing Uncertainty Asymptomatic Infection Northern Ireland

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Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

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Bone research 2015年第1期3卷 40-45页

作者： Douglas J DiGirolamo Vandana Singhal Xiaoli Chang Se-Jin Lee emily L Germain-Lee Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Bone & Osteogenesis Imperfecta Department Kennedy Krieger Institute Department of Molecular Biology and Genetics Johns Hopkins University School of Medicine Department of Pediatrics Johns Hopkins University School of Medicine

Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVr2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVr2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

关键词： bone Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

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The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: III Pharmacological Studies

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Neuroscience & Medicine 2011年第3期2卷 397-409页

作者： Peter K. Panegyres emily r. Atkins 不详

Pharmacological studies reveal APP and Aβ have interactions with glutamate and calcium, cytokines, copper/zinc chelators, secretases and presenilins, nicotinic receptors, acetycholinesterase, neurotrophins, non-steroidal anti-inflame-matory drugs, monoclonal antibodies to Aβ, protease inhibitors, oestrogen, homocysteine, immediate early genes such as c-fos or c-jun and cholesterol. These functional and pharmacological observations highlight the need for greater understanding of APP and Aβ in brain function and have implications for clinical trials.

关键词： Amyloid Precursor Protein APP Genes Dementia Alzheimer’s Disease

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Towards precision medicine:advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy

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Cancer Communications 2019年第1期39卷 113-121页

作者： Chang Zeng emily Kunce Stroup Zhou Zhang Brian C-HChiu Wei Zhang Driskill Graduate Program in Life Sciences Northwestern University Feinberg School of MedicineChicagoIL 60611USA Department of Preventive Medicine Northwestern University Feinberg School of Medicine680 N.Lake Shore Dr.Suite 1400ChicagoIL 60611USA Department of Public Health Sciences University of ChicagoChicagoIL 60637USA The robert H.Lurie Comprehensive Cancer Center Northwestern University Feinberg School of MedicineChicagoIL 60611USA Institute of Precision Medicine Jining Medical UniversityJining 272067ShandongP.R.China.

robust and clinically convenient biomarkers for cancer diagnosis,early detection,and prognosis have great potential to improve patient survival and are the key to precision *** advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived *** are now able to monitor the dynamics of tumorigenesis in new dimensions,such as using circulating cell-free DNA(cfDNA)and tumor DNA(ctDNA).Mutation-based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra-and inter-tumoral heterogeneity as well as technical *** contrast,epigenetic analysis of patient-derived cfDNA is a promising alternative,especially for early detection and disease surveillance,because epigenetic modifications are tissue-specific and reflect the dynamic process of cancer ***,cfDNA-based epigenetic assays are emerging to be a highly sensitive,minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer *** major obstacle for applying epigenetic analysis of cfDNA,however,has been the lack of enabling techniques with high sensitivity and technical *** this review,we summarized the advances in epigenome-wide profiling of 5-hydroxymethyl-cytosine(5hmC)in cfDNA,focusing on the detection approaches and potential role as biomarkers in different cancer types.

关键词： Liquid biopsy Cell-free DNA Epigenetics Cancer biomarker 5-Hydroxymethylcytosine

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Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

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Journal of Genetics and Genomics 2022年第7期49卷 654-665页

作者： Elisabetta Morini Dadi Gao emily M.Logan Monica Salani Aram J.Krauson Anil Chekuri Yei-Tsung Chen Ashok ragavendran Probir Chakravarty Serkan Erdin Alexei Stortchevoi Jesper Q.Svejstrup Michael E.Talkowski Susan A.Slaugenhaupt Center for Genomic Medicine Massachusetts General Hospital Research InstituteBostonMAUSA Department of Neurology Massachusetts General Hospital Research Institute and Harvard Medical SchoolBostonMAUSA Program in Medical and Population Genetics and Stanley Center for Psychiatric research Broad Institute of Harvard and MITCambridgeMAUSA Department of Life Sciences and Institute of Genome Sciences National Yang Ming Chiao Tung UniversityTaiwanChina Bioinformatics and Biostatistics The Francis Crick InstituteLondonUK Mechanisms of Transcription Laboratory The Francis Crick InstituteLondonUK Department of Cellular and Molecular Medicine Panum InstituteUniversity of CopenhagenCopenhagenDenmark

Familial dysautonomia(FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1(ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse(Elp1) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.

关键词： ELP1 Elongator Transcriptional elongation Familial dysautonomia Neurodevelopmental disease

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Highly efficient GaAs solar cells by limiting light emission angle

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Light(Science & Applications) 2013年第1期2卷 236-241页

作者： emily D Kosten Jackson H Atwater James Parsons Albert Polman Harry A Atwater Thomas J.Watson Laboratories of Applied Physics California Institute of TechnologyPasadenaCA 91125 USA Center for Nanophotonics FOM-Institute AMOLFScience Park 1041098XG AmsterdamThe Netherlands

In a conventional flat plate solar cell under direct sunlight,light is received from the solar disk,but is re-emitted *** isotropic emission corresponds to a significant entropy increase in the solar cell,with a corresponding drop in ***,using a detailed balance model,we show that limiting the emission angle of a high-quality GaAs solar cell is a feasible route to achieving power conversion efficiencies above 38%with a single *** highest efficiencies are predicted for a thin,light trapping cell with an ideal back reflector,though the scheme is robust to a non-ideal back *** with a conventional planar cell geometry illustrates that limiting emission angle in a light trapping geometry not only allows for much thinner cells,but also for significantly higher overall efficiencies with an excellent rear ***,we present ray-tracing and detailed balance analysis of two angular coupler designs,show that significant efficiency improvements are possible with these couplers,and demonstrate initial fabrication of one coupler design.

关键词： detailed balance GaAs solar cell light trapping photovoltaics two photon lithography

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