1,862 research outputs found

    Enabling Modular Autonomous Feedback-Loops in Materials Science through Hierarchical Experimental Laboratory Automation and Orchestration

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    Materials acceleration platforms (MAPs) operate on the paradigm of integrating combinatorial synthesis, high-throughput characterization, automatic analysis, and machine learning. Within a MAP, one or multiple autonomous feedback loops may aim to optimize materials for certain functional properties or to generate new insights. The scope of a given experiment campaign is defined by the range of experiment and analysis actions that are integrated into the experiment framework. Herein, the authors present a method for integrating many actions within a hierarchical experimental laboratory automation and orchestration (HELAO) framework. They demonstrate the capability of orchestrating distributed research instruments that can incorporate data from experiments, simulations, and databases. HELAO interfaces laboratory hardware and software distributed across several computers and operating systems for executing experiments, data analysis, provenance tracking, and autonomous planning. Parallelization is an effective approach for accelerating knowledge generation provided that multiple instruments can be effectively coordinated, which the authors demonstrate with parallel electrochemistry experiments orchestrated by HELAO. Efficient implementation of autonomous research strategies requires device sharing, asynchronous multithreading, and full integration of data management in experimental orchestration, which to the best of the authors’ knowledge, is demonstrated for the first time herein

    FOXO1 Modulates Osteoblast Differentiation

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    Forkhead box O1 (FOXO1) is upregulated during bone formation and in response to stimulation by bone morphogenetic proteins. Studies presented here examined the functional role of FOXO1 in a well defined culture system in which pre-osteoblastic cells undergo terminal differentiation in vitro. Mineralizing cultures of MC3T3-E1 cells were examined with or without FOXO1 knockdown by RNAi. Normal cells show the upregulation of FOXO1 and RUNX2 DNA binding activity, alkaline phosphatase activity, and mRNA levels of FOXO1, RUNX2, type 1 collagen, osteocalcin and MMP13 during formation of mineralizing nodules. In FOXO1 depleted cells each of these measurements was significantly reduced compared to values in control cells transfected with scrambled siRNA (P \u3c 0.05). Depletion of FOXO1 also reduced the number of mineralized nodules formed. Moreover, chromatin immunoprecipitation assays revealed a direct interaction of FOXO1 with the RUNX2 promoter. Overexpression of FOXO1 reduced the MC3T3-E1 cell number and the number of PCNA positive cells with little effect on apoptosis. These findings indicate that FOXO1 plays an important role in promoting osteoblast differentiation and suppressing proliferation in differentiating cells

    Improving HIV Pre Exposure Prophylaxis (PrEP) uptake and initiation: process evaluation and recommendation development from a national PrEP programme

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    HIV pre-exposure prophylaxis (PrEP) is key to HIV transmission elimination but implementation is challenging and under-researched. We undertook a process evaluation of the first 2years of a national PrEP program to explore barriers and facilitators to implementation and to develop recommendations to improve implementation, focusing on PrEP uptake and initiation. Stage 1 involved semi-structured telephone interviews and focus groups (September 2018-July 2019) with geographically and demographically diverse patients seeking/using/declining/stopping PrEP (n =39), sexual healthcare professionals (n =54), community-based organisation service users (n =9) and staff (n =15) across Scotland. We used deductive thematic analysis, to derive and then map key barriers and facilitators to priority areas that experts agreed would enhance uptake and initiation. In Stage 2, we used analytic tools from implementation science to systematically generate evidence-based, theoretically-informed recommendations to enhance uptake and initiation of PrEP. Barriers and facilitators were multi-levelled and interdependent. Barriers included the rapid pace of implementation without additional resource, and a lack of familiarity with PrEP prescribing. Facilitators included opportunities for acquisition of practice-based knowledge and normalisation of initiation activities. We refined our 68 'long-list' recommendations to 41 using expert input and the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria. Examples include: provision of PrEP in diverse settings to reach all in need; co-produced, culturally sensitive training resources for healthcare professionals, with focused content on non-daily dosing; meaningful collaborative working across all stakeholders. These evidence-based, theory informed recommendations provide a robust framework for optimising PrEP uptake and initiation in diverse settings to ensure PrEP reaches all who may benefit

    Improving HIV pre-exposure prophylaxis (PrEP) uptake and initiation: process evaluation and recommendation development from a national PrEP program

    Get PDF
    BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is key to HIV transmission elimination but implementation is challenging and under-researched. We undertook a process evaluation of the first 2 years of a national PrEP program to explore barriers and facilitators to implementation and to develop recommendations to improve implementation, focusing on PrEP uptake and initiation. METHODS: Stage 1 involved semi-structured telephone interviews and focus groups (September 2018–July 2019) with geographically and demographically diverse patients seeking/using/declining/stopping PrEP (n = 39), sexual healthcare professionals (n = 54), community-based organisation service users (n = 9) and staff (n = 15) across Scotland. We used deductive thematic analysis, to derive and then map key barriers and facilitators to priority areas that experts agreed would enhance uptake and initiation. In Stage 2, we used analytic tools from implementation science to systematically generate evidence-based, theoretically-informed recommendations to enhance uptake and initiation of PrEP. RESULTS: Barriers and facilitators were multi-levelled and interdependent. Barriers included the rapid pace of implementation without additional resource, and a lack of familiarity with PrEP prescribing. Facilitators included opportunities for acquisition of practice-based knowledge and normalisation of initiation activities. We refined our 68 ‘long-list’ recommendations to 41 using expert input and the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria. Examples include: provision of PrEP in diverse settings to reach all in need; co-produced, culturally sensitive training resources for healthcare professionals, with focused content on non-daily dosing; meaningful collaborative working across all stakeholders. CONCLUSIONS: These evidence-based, theory informed recommendations provide a robust framework for optimising PrEP uptake and initiation in diverse settings to ensure PrEP reaches all who may benefit

    Understanding and responding to remote mental health help-seeking by gay, bisexual and other men who have sex with men (GBMSM) in the U.K. and Republic of Ireland : a mixed-method study conducted in the context of COVID-19

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    Background: Gay, bisexual and other men who have sex with men (GBMSM) are at far greater risk of experiencing poor mental health (MH) than wider society. This disparity was exacerbated by additional unique to sexual minority status' COVID-19 stressors. Objective: This sequential, mixed-methods study examined remote MH help-seeking among GBMSM in the U.K. and Ireland during the first COVID-19 lockdown. Methods and Results: Quantitative survey data (n = 1368), analysed with logistic regression, suggested GBMSM experiencing moderate-to-severe anxiety and those with a past MH diagnosis were most likely to seek MH support. Thematic analysis of qualitative interview (n = 18) data identified multiple barriers and enablers to GBMSM seeking remote MH help, with the help primarily sought from GBMSM-facing organisations and generic online resources. Finally, the behaviour change wheel was used to generate theoretically informed recommendations to promote MH help-seeking among GBMSM in Scotland. Implications: We discuss how applying these recommendations in the short, medium and long term will begin to address GBMSM's MH needs, post COVID-19

    The Vehicle, Fall 2009

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    Table of Contents Poetry AliveRashelle McNairpage 3 Train of ThoughtsJeanette Saribekianpage 4 Biding the TideMarlee Lutzpage 5 Rotten HarvestJessyca Revillapage 15 Nostalgia ODJustine Fittonpage 16 Beyond WordsAshley Wrightpage 26 Don\u27tMelinda Knightpage 27 Happy HourStephen Garciapage 35 UntitledDaniel Paquinpage 37 Vibrant SensationsAshton Tembypage 38 Scarecrow Sally on a Saturday NightDaniel Davispage 45 The FarmAshley Wrightpage 49 Anything ButJustine Fittonpage 51 CrashDanielle Shirtinopage 53 Weathering SatisfactionRashelle McNairpage 54 SeminarDaniel Davispage 71 Nature\u27s Mood SwingsJeanette Saribekianpage 72 The PerformanceMelinda Knightpage 68 AmaterasuMarlee Lutzpage 82 Prose AirLauren Davidsonpage 6 The Twang of OrangesJ.T. Dawsonpage 18 ListenStephani Pescitellipage 29 The Rise and Fall of NickNickolas Alexanderpage 30 LossSimyona Deanovapage 39 Like DiamondsMark Rheaumepage 42 Moral FixationBryan Rolfsenpage 47 Reflections in College AlgebraNicole Reichertpage 52 LeashDaniel Paquinpage 56 I Lost My KeysJustine Fittonpage 75 A Third Grade EssayMark Rheaumepage 69 Be Careful, They BiteDaniel Davispage 84 Art Limb BurgAlycia Rockeycover AvesSamantha Flowerspage 14 Life-LuminescenceStephani Pescitellipage 25 MonopolyMegan Mathypage 28 Carousel NostalgiaAlycia Rockeypage 36 ShoesSarah Olsonpage 41 Waimea BayJarrod Taylorpage 50 Peacock Plumage Alycia Rockeypage 55 Building a HouseStephani Pescitellipage 70 ShellMegan Mathypage 74 From the VacationSamantha Flowerspage 73 Chicago CanopyAlycia Rockeypage 83 Features Editor\u27s NoteLindsey Durbinpage 1 LazarusDr. David Radavichpage 2 James K. Johnson Creative Writing Awardpage 88 Winning Entries (Poetry)Matthew J. Schumakepage 89 Winning Entry (Nonfiction)Jennifer O\u27Neilpage 92 Interview, 2009 Chapbook WinnerDaniel Davispage 95 Contributorspage 99https://thekeep.eiu.edu/vehicle/1090/thumbnail.jp

    The Vehicle, Fall 2009

    Get PDF
    Table of Contents Poetry AliveRashelle McNairpage 3 Train of ThoughtsJeanette Saribekianpage 4 Biding the TideMarlee Lutzpage 5 Rotten HarvestJessyca Revillapage 15 Nostalgia ODJustine Fittonpage 16 Beyond WordsAshley Wrightpage 26 Don\u27tMelinda Knightpage 27 Happy HourStephen Garciapage 35 UntitledDaniel Paquinpage 37 Vibrant SensationsAshton Tembypage 38 Scarecrow Sally on a Saturday NightDaniel Davispage 45 The FarmAshley Wrightpage 49 Anything ButJustine Fittonpage 51 CrashDanielle Shirtinopage 53 Weathering SatisfactionRashelle McNairpage 54 SeminarDaniel Davispage 71 Nature\u27s Mood SwingsJeanette Saribekianpage 72 The PerformanceMelinda Knightpage 68 AmaterasuMarlee Lutzpage 82 Prose AirLauren Davidsonpage 6 The Twang of OrangesJ.T. Dawsonpage 18 ListenStephani Pescitellipage 29 The Rise and Fall of NickNickolas Alexanderpage 30 LossSimyona Deanovapage 39 Like DiamondsMark Rheaumepage 42 Moral FixationBryan Rolfsenpage 47 Reflections in College AlgebraNicole Reichertpage 52 LeashDaniel Paquinpage 56 I Lost My KeysJustine Fittonpage 75 A Third Grade EssayMark Rheaumepage 69 Be Careful, They BiteDaniel Davispage 84 Art Limb BurgAlycia Rockeycover AvesSamantha Flowerspage 14 Life-LuminescenceStephani Pescitellipage 25 MonopolyMegan Mathypage 28 Carousel NostalgiaAlycia Rockeypage 36 ShoesSarah Olsonpage 41 Waimea BayJarrod Taylorpage 50 Peacock Plumage Alycia Rockeypage 55 Building a HouseStephani Pescitellipage 70 ShellMegan Mathypage 74 From the VacationSamantha Flowerspage 73 Chicago CanopyAlycia Rockeypage 83 Features Editor\u27s NoteLindsey Durbinpage 1 LazarusDr. David Radavichpage 2 James K. Johnson Creative Writing Awardpage 88 Winning Entries (Poetry)Matthew J. Schumakepage 89 Winning Entry (Nonfiction)Jennifer O\u27Neilpage 92 Interview, 2009 Chapbook WinnerDaniel Davispage 95 Contributorspage 99https://thekeep.eiu.edu/vehicle/1090/thumbnail.jp

    Incorporating New Technologies Into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework

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    Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency
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