138 research outputs found

    Activist 101 Activities for Pre-Service Teachers

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    This Teaching Note briefly describes three activities that can easily be integrated into any teacher education course

    An Experimental and Computational Investigation of n-Dodecane Ignition and Chemical Kinetics

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90619/1/AIAA-2011-90-831.pd

    Impact of highly basic solutions on sorption of Cs+ to subsurface sediments from the Hanford site, USA

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    The effect of caustic NaNO3 solutions on the sorption of 137Cs to a Hanford site micaceous subsurface sediment was investigated as a function of base exposure time (up to 168 d), temperature (10°C or 50°C), and NaOH concentration (0.1 mol/L to 3 mol/L). At 10°C and 0.1 M NaOH, the slow evolution of [Al]aq was in stark contrast to the rapid increase and subsequent loss of [Al]aq observed at 50°C (regardless of base concentration). Exposure to 0.1 M NaOH at 10°C for up to 168 d exhibited little if any measurable effect on sediment mineralogy, Cs+ sorption, or Cs+ selectivity; sorption was well described with a two-site ion exchange model modified to include enthalpy effects. At 50°C, dissolution of phyllosilicate minerals increased with [OH]. A zeolite (tetranatrolite; Na2Al2Si3O10·2H2O) precipitated in 0.1 M NaOH after about 7 days, while an unnamed mineral phase (Na14Al12Si13O51·6H2O) precipitated after 4 and 2 days of exposure to 1 M and 3 M NaOH solutions, respectively. Short-term (16 h) Cs+ sorption isotherms (10−9–10−2 mol/L) were measured on sediment after exposure to 0.1 M NaOH for 56, 112, and 168 days at 50°C. There was a trend toward slightly lower conditional equilibrium exchange constants (∆log NaCsKc ~ 0.25) over the entire range of surface coverage, and a slight loss of high affinity sites (15%) after 168 days of pretreatment with 0.1 M base solution. Cs+ sorption to sediment over longer times was also measured at 50°C in the presence of NaOH (0.1 M, 1 M, and 3MNaOH) at Cs+ concentrations selected to probe a range of adsorption densities. Model simulations of Cs+ sorption to the sediment in the presence of 0.1 M NaOH for 112 days slightly under-predicted sorption at the lower Cs+ adsorption densities. At the higher adsorption densities, model simulations under-predicted sorption by 57%. This under-prediction was surmised to be the result of tetranatrolite precipitation, and subsequent slow Na → Cs exchange. At higher OH concentrations, Cs+ sorption in the presence of base for 112 days was unexpectedly equal to, or greater than that expected for pristine sediment. The precipitation of secondary phases, coupled with the fairly unique mica distribution and quantity across all size-fractions in the Hanford sediment, appears to mitigate the impact of base dissolution on Cs+ sorption

    The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/1/epi13461_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/2/epi13461.pd

    Impact of highly basic solutions on sorption of Cs+ to subsurface sediments from the Hanford site, USA

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    The effect of caustic NaNO3 solutions on the sorption of 137Cs to a Hanford site micaceous subsurface sediment was investigated as a function of base exposure time (up to 168 d), temperature (10°C or 50°C), and NaOH concentration (0.1 mol/L to 3 mol/L). At 10°C and 0.1 M NaOH, the slow evolution of [Al]aq was in stark contrast to the rapid increase and subsequent loss of [Al]aq observed at 50°C (regardless of base concentration). Exposure to 0.1 M NaOH at 10°C for up to 168 d exhibited little if any measurable effect on sediment mineralogy, Cs+ sorption, or Cs+ selectivity; sorption was well described with a two-site ion exchange model modified to include enthalpy effects. At 50°C, dissolution of phyllosilicate minerals increased with [OH]. A zeolite (tetranatrolite; Na2Al2Si3O10·2H2O) precipitated in 0.1 M NaOH after about 7 days, while an unnamed mineral phase (Na14Al12Si13O51·6H2O) precipitated after 4 and 2 days of exposure to 1 M and 3 M NaOH solutions, respectively. Short-term (16 h) Cs+ sorption isotherms (10−9–10−2 mol/L) were measured on sediment after exposure to 0.1 M NaOH for 56, 112, and 168 days at 50°C. There was a trend toward slightly lower conditional equilibrium exchange constants (∆log NaCsKc ~ 0.25) over the entire range of surface coverage, and a slight loss of high affinity sites (15%) after 168 days of pretreatment with 0.1 M base solution. Cs+ sorption to sediment over longer times was also measured at 50°C in the presence of NaOH (0.1 M, 1 M, and 3MNaOH) at Cs+ concentrations selected to probe a range of adsorption densities. Model simulations of Cs+ sorption to the sediment in the presence of 0.1 M NaOH for 112 days slightly under-predicted sorption at the lower Cs+ adsorption densities. At the higher adsorption densities, model simulations under-predicted sorption by 57%. This under-prediction was surmised to be the result of tetranatrolite precipitation, and subsequent slow Na → Cs exchange. At higher OH concentrations, Cs+ sorption in the presence of base for 112 days was unexpectedly equal to, or greater than that expected for pristine sediment. The precipitation of secondary phases, coupled with the fairly unique mica distribution and quantity across all size-fractions in the Hanford sediment, appears to mitigate the impact of base dissolution on Cs+ sorption

    Development of a diesel surrogate for improved autoignition prediction: Methodology and detailed chemical kinetic modeling

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    While the surrogate fuel approach has been successfully applied to the simulation of the combustion behaviors of complex gasoline and jet fuels, its application to diesel fuels has been challenging. One of the main challenges derives from the large molecular size of the representative surrogate components necessary to simulate diesel blends, as the development of detailed chemical kinetic models and their validation becomes more complex. In this study, a new surrogate mixture that emulates the chemical and physical properties of a well-characterized diesel fuel is proposed. An optimization procedure was used to select surrogate components that can match both the physical and chemical properties of the target diesel fuel comprehensively. The surrogate fuel mixture composition was designed to have fuel properties (e.g., boiling point, cloud point, etc.) that enable its use in future diesel engine experiments. A detailed kinetic model for the surrogate fuel mixture was developed by combining well-validated sub-mechanisms of each surrogate component from Lawrence Livermore National Laboratory. The ability of the surrogate mixture and kinetic model to emulate ignition delay times was assessed by comparing the simulated results with measurements for the target diesel fuel. Comparison of the experimental and simulated ignition delay times shows that the current surrogate mixture and kinetic model well capture the autoignition response of the target diesel fuel at varying conditions of pressure, temperature, oxygen concentration, and fuel concentration. The current study is one of the first to demonstrate the efficacy of detailed chemical kinetics for diesel range fuels by assembling validated sub-mechanisms for palette compounds and successfully simulating the autoignition characteristics of a target diesel fuel. The experimental ignition delay times of diesel measured with a rapid compression machine, the surrogate mixture, and the kinetic model developed shall aid in progress of understanding diesel ignition under engine relevant conditions

    Biallelic inherited SCN8A variants, a rare cause of SCN8A‐related developmental and epileptic encephalopathy

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    ObjectiveMonoallelic de novo gain‐of‐function variants in the voltage‐gated sodium channel SCN8A are one of the recurrent causes of severe developmental and epileptic encephalopathy (DEE). In addition, a small number of de novo or inherited monoallelic loss‐of‐function variants have been found in patients with intellectual disability, autism spectrum disorder, or movement disorders. Inherited monoallelic variants causing either gain or loss‐of‐function are also associated with less severe conditions such as benign familial infantile seizures and isolated movement disorders. In all three categories, the affected individuals are heterozygous for a SCN8A variant in combination with a wild‐type allele. In the present study, we describe two unusual families with severely affected individuals who inherited biallelic variants of SCN8A.MethodsWe identified two families with biallelic SCN8A variants by diagnostic gene panel sequencing. Functional analysis of the variants was performed using voltage clamp recordings from transfected ND7/23 cells.ResultsWe identified three probands from two unrelated families with DEE due to biallelic SCN8A variants. Each parent of an affected individual carried a single heterozygous SCN8A variant and exhibited mild cognitive impairment without seizures. In both families, functional analysis demonstrated segregation of one allele with complete loss‐of‐function, and one allele with altered biophysical properties consistent with partial loss‐of‐function.SignificanceThese studies demonstrate that SCN8A DEE may, in rare cases, result from inheritance of two variants, both of which exhibit reduced channel activity. In these families, heterozygosity for the dominant variants results in less severe disease than biallelic inheritance of two variant alleles. The clinical consequences of variants with partial and complete loss of SCN8A function are variable and likely to be influenced by genetic background.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/1/epi16371_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/2/epi16371.pd

    The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria

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    The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes

    The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/1/epi14196.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/2/epi14196-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144249/3/epi14196_am.pd
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