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  1. Article ; Online: TargetDB

    Stephane De Cesco / John B Davis / Paul E Brennan

    PLoS ONE, Vol 15, Iss 9, p e

    A target information aggregation tool and tractability predictor.

    2020  Volume 0232644

    Abstract: When trying to identify new potential therapeutic protein targets, access to data and knowledge is increasingly important. In a field where new resources and data sources become available every day, it is crucial to be able to take a step back and look ... ...

    Abstract When trying to identify new potential therapeutic protein targets, access to data and knowledge is increasingly important. In a field where new resources and data sources become available every day, it is crucial to be able to take a step back and look at the wider picture in order to identify potential drug targets. While this task is routinely performed by bespoke literature searches, it is often time-consuming and lacks uniformity when comparing multiple targets at one time. To address this challenge, we developed TargetDB, a tool that aggregates public information available on given target(s) (links to disease, safety, 3D structures, ligandability, novelty, etc.) and assembles it in an easy to read output ready for the researcher to analyze. In addition, we developed a target scoring system based on the desirable attributes of good therapeutic targets and machine learning classification system to categorize novel targets as having promising or challenging tractrability. In this manuscript, we present the methodology used to develop TargetDB as well as test cases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Economics Imperialism under the Impact of Psychology

    John B. Davis

    Œconomia, Vol 3, Iss 1, Pp 119-

    The Case of Behavioral Development Economics

    2013  Volume 138

    Abstract: Economics imperialism is broadly explained as economics having an impact on other disciplines. But how should economics imperialism be understood when it is in some sense the product of other disciplines having an impact on economics? The paper examines ... ...

    Abstract Economics imperialism is broadly explained as economics having an impact on other disciplines. But how should economics imperialism be understood when it is in some sense the product of other disciplines having an impact on economics? The paper examines psychology’s impact on economics in connection with the emergence of behavioral development economics, and then discusses the nature of behavioral development economics imperialism associated with development economists’ explanations of non-market dimensions of life in developing economies in behavioral economics terms. The paper argues that this new form of economics imperialism reflects economics’ selective appropriation from psychology of the Kahneman-Tversky heuristics and biases view of choice behavior and rejection of the Gigerenzer-ABC group fast and frugal heuristics view. This selective appropriation, however, causes behavioral development economics imperialism to also function as a social and cultural imperialism since its utility theory-based policy recommendations impose liberal society economic values on developing economy societies. Thus recent economics-plus-psychology imperialism might be said to function as social science imperialism under the leadership of economics.
    Keywords economics imperialism ; choice heuristics ; behavioral development economics ; Gigerenzer (Gerd) ; Kahneman (Daniel) ; Tversky (Amos) ; Social Sciences ; H
    Subject code 338 ; 336
    Language English
    Publishing date 2013-06-01T00:00:00Z
    Publisher Association Œconomia
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Gaps in Protection of Important Ocean Areas

    Natasha J. Gownaris / Christine M. Santora / John B. Davis / Ellen K. Pikitch

    Frontiers in Marine Science, Vol

    A Spatial Meta-Analysis of Ten Global Mapping Initiatives

    2019  Volume 6

    Abstract: To safeguard biodiversity effectively, marine protected areas (MPAs) should be sited using the best available science. There are numerous ongoing United Nations and non-governmental initiatives to map globally important marine areas. The criteria used by ...

    Abstract To safeguard biodiversity effectively, marine protected areas (MPAs) should be sited using the best available science. There are numerous ongoing United Nations and non-governmental initiatives to map globally important marine areas. The criteria used by these initiatives vary, resulting in contradictions in the areas identified as important. Our analysis is the first to overlay these initiatives, quantify consensus, and conduct gap analyses at the global scale. We found that 55% of the ocean has been identified as important by one or more initiatives, and that individual areas have been identified by as many as seven overlapping initiatives. Using our overlay map and data on current MPA coverage, we highlight gaps in protection of important areas of the ocean. We considered any area identified by two to four initiatives to be of moderate consensus. Over 14% of the ocean fell under this category and most of this area (88%) is not yet protected. The largest concentrations of medium-consensus areas without protection were found in the Caribbean Sea, Madagascar and the southern tip of Africa, the Mediterranean Sea, and the Coral Triangle. Areas of high consensus (identified by five to seven initiatives) were almost always within MPAs, but their no-take status was often unreported. We found that nearly every marine province and nearly every exclusive economic zone contained area that has been identified as important but is not yet protected. Much of the identified area lies within contiguous stretches of >100,000 km2; it is unrealistic to expect that all this area be protected. Nonetheless, our results on areas of consensus provide initial insight into opportunities for further ocean protection.
    Keywords areas beyond national jurisdiction ; Aichi Target 11 ; marine protected area ; overlay analysis ; hotspots ; representativeness ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
    Subject code 333
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages

    Juliane Obst / Hazel L. Hall-Roberts / Thomas B. Smith / Mira Kreuzer / Lorenza Magno / Elena Di Daniel / John B. Davis / Emma Mead

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 17

    Abstract: Abstract Human genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a ... ...

    Abstract Abstract Human genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A phenotypic high-content, high-throughput screen identifies inhibitors of NLRP3 inflammasome activation

    Sohaib Nizami / Val Millar / Kanisa Arunasalam / Tryfon Zarganes-Tzitzikas / David Brough / Gary Tresadern / Paul E. Brennan / John B. Davis / Daniel Ebner / Elena Di Daniel

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Abstract Inhibition of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome has recently emerged as a promising therapeutic target for several inflammatory diseases. After priming and activation by inflammation triggers, NLRP3 forms a ...

    Abstract Abstract Inhibition of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome has recently emerged as a promising therapeutic target for several inflammatory diseases. After priming and activation by inflammation triggers, NLRP3 forms a complex with apoptosis-associated speck-like protein containing a CARD domain (ASC) followed by formation of the active inflammasome. Identification of inhibitors of NLRP3 activation requires a well-validated primary high-throughput assay followed by the deployment of a screening cascade of assays enabling studies of structure–activity relationship, compound selectivity and efficacy in disease models. We optimized a NLRP3-dependent fluorescent tagged ASC speck formation assay in murine immortalized bone marrow-derived macrophages and utilized it to screen a compound library of 81,000 small molecules. Our high-content screening assay yielded robust assay metrics and identified a number of inhibitors of NLRP3-dependent ASC speck formation, including compounds targeting HSP90, JAK and IKK-β. Additional assays to investigate inflammasome priming or activation, NLRP3 downstream effectors such as caspase-1, IL-1β and pyroptosis form the basis of a screening cascade to identify NLRP3 inflammasome inhibitors in drug discovery programs.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Sohaib Nizami / Val Millar / Kanisa Arunasalam / Tryfon Zarganes-Tzitzikas / David Brough / Gary Tresadern / Paul E. Brennan / John B. Davis / Daniel Ebner / Elena Di Daniel

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    A phenotypic high-content, high-throughput screen identifies inhibitors of NLRP3 inflammasome activation

    2021  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A Geographic Model to Assess and Limit Cumulative Ecological Degradation from Marcellus Shale Exploitation in New York, USA

    John B. Davis / George R. Robinson

    Ecology and Society, Vol 17, Iss 2, p

    2012  Volume 25

    Abstract: When natural resources are exploited, environmental costs and economic benefits are often asymmetric. An example is apparent in the environmental impacts from fossil fuel extraction by hydraulic fracturing. So far, most scrutiny has been focused on water ...

    Abstract When natural resources are exploited, environmental costs and economic benefits are often asymmetric. An example is apparent in the environmental impacts from fossil fuel extraction by hydraulic fracturing. So far, most scrutiny has been focused on water quality in affected aquifers, with less attention paid to broader ecological impacts beyond individual drilling operations. Marcellus Shale methane exploitation in New York State, USA, has been delayed because of a regulatory moratorium, pending evaluation that has been directed primarily at localized impacts. We developed a GIS-based model, built on a hexagonal grid underlay nested within the U.S. Environmental Protection Agency's EMAP system, to examine potential cumulative ecological impacts. In a two-step process, we characterized > 19,000 hexagons, each sized to approximate the footprint of one drilling site (2.57 km²), using ecological attributes; we then developed a method for apportioning resource access that includes assessments of cumulative ecological costs. Over one-quarter of the hexagons were excluded as off-limits on the basis of six criteria: slope suitability, regulated wetland cover, protected-land cover, length of high-quality streams, mapped road density, and open water cover. Three additional criteria were applied to assess the estimated conservation vulnerability of the remaining sites: density of grassland birds (North American Breeding Bird Survey), percent core forest (Coastal Change Analysis Program), and total density of all state-mapped streams; these were determined and used in combination to rank the 14,000 potentially accessible sites. In a second step, an iterative process was used to distribute potential site access among all towns (sub-county governments) within the Marcellus Shale Formation. At each iteration, one site was selected per town, either randomly or in rank order of increasing vulnerability. Results were computed as percent cumulative impact versus the number of sites committed and compared to a most-conservative ...
    Keywords Core forest ; hexagon land-cover grid ; hydraulic fracturing ; Marcellus Shale formation ; natural resource sharing ; New York State ; sensitive species and ecosystems ; Biology (General) ; QH301-705.5 ; Ecology ; QH540-549.5
    Subject code 333
    Language English
    Publishing date 2012-06-01T00:00:00Z
    Publisher Resilience Alliance
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Economics and economic methodology in a core-periphery economic world

    John B. Davis

    Brazilian Journal of Political Economy, Vol 39, Iss 3, Pp 408-426

    Abstract: ABSTRACT This paper uses a core-periphery distinction to characterize contemporary economics, economic methodology, and also today’s world economy. First, it applies the distinction to the organization of contemporary economics through an examination of ... ...

    Abstract ABSTRACT This paper uses a core-periphery distinction to characterize contemporary economics, economic methodology, and also today’s world economy. First, it applies the distinction to the organization of contemporary economics through an examination of the problem of explaining economics’ relations to and boundaries with other disciplines. Second, it argues that economics’ core-periphery organization is replicated in a similar organization of the use and practice of contemporary economic methodology in economics. Third, it draws on the use of the core-periphery thinking in economics itself regarding the uneven development of the world economy to provide possible foundations for economics and economic methodology being organized in core-periphery terms. Fourth, the paper briefly discusses three potential countervailing forces operating on the development of contemporary economics that might work against its core-periphery organization.
    Keywords Core-periphery ; economics and other disciplines ; economic methodology ; uneven development ; specialization ; formal modeling ; empirical turn ; Economics as a science ; HB71-74
    Subject code 338 ; 330
    Language English
    Publisher Editora 34
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: A Geographic Model to Assess and Limit Cumulative Ecological Degradation from Marcellus Shale Exploitation in New York, USA

    George R. Robinson / John B. Davis

    Abstract: When natural resources are exploited, environmental costs and economic benefits are often asymmetric. An example is apparent in the environmental impacts from fossil fuel extraction by hydraulic fracturing. So far, most scrutiny has been focused on water ...

    Abstract When natural resources are exploited, environmental costs and economic benefits are often asymmetric. An example is apparent in the environmental impacts from fossil fuel extraction by hydraulic fracturing. So far, most scrutiny has been focused on water quality in affected aquifers, with less attention paid to broader ecological impacts beyond individual drilling operations. Marcellus Shale methane exploitation in New York State, USA, has been delayed because of a regulatory moratorium, pending evaluation that has been directed primarily at localized impacts. We developed a GIS-based model, built on a hexagonal grid underlay nested within the U.S. Environmental Protection Agency’s EMAP system, to examine potential cumulative ecological impacts. In a two-step process, we characterized > 19,000 hexagons, each sized to approximate the footprint of one drilling site (2.57 km²), using ecological attributes; we then developed a method for apportioning resource access that includes assessments of cumulative ecological costs. Over one-quarter of the hexagons were excluded as off-limits on the basis of six criteria: slope suitability, regulated wetland cover, protected-land cover, length of high-quality streams, mapped road density, and open water cover. Three additional criteria were applied to assess the estimated conservation vulnerability of the remaining sites: density of grassland birds (North American Breeding Bird Survey), percent core forest (Coastal Change Analysis Program), and total density of all state-mapped streams; these were determined and used in combination to rank the 14,000 potentially accessible sites. In a second step, an iterative process was used to distribute potential site access among all towns (sub-county governments) within the Marcellus Shale Formation. At each iteration, one site was selected per town, either randomly or in rank order of increasing vulnerability. Results were computed as percent cumulative impact versus the number of sites committed and compared to a most-conservative selection process (ranked by statewide conservation vulnerability). Random selection with proportional distribution by town resulted in larger cumulative ecological impacts, but rank-ordered selection by town was in many ways comparable to selection by statewide conservation vulnerability ranking. These outcomes allow for a political solution for managing resource access fairly, based on a balanced geographic distribution of economic benefits, coupled with an underlying scientific basis for assessing the ecological costs that are publicly shared.
    Language English
    Document type Article
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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