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  1. Abstract Background

    Double-strand break repair (DSBR) is a highly regulated process involving dozens of proteins acting in a defined order to repair a DNA lesion that is fatal for any living cell. Model organisms such asSaccharomyces cerevisiaehave been used to study the mechanisms underlying DSBR, including factors influencing its efficiency such as the presence of distinct combinations of microsatellites and endonucleases, mainly by bulk analysis of millions of cells undergoing repair of a broken chromosome. Here, we use a microfluidic device to demonstrate in yeast that DSBR may be studied at a single-cell level in a time-resolved manner, on a large number of independent lineages undergoing repair.

    Results

    We used engineeredS. cerevisiaecells in which GFP is expressed following the successful repair of a DSB induced by Cas9 or Cpf1 endonucleases, and different genetic backgrounds were screened to detect key events leading to the DSBR efficiency. Per condition, the progenies of 80–150 individual cells were analyzed over 24 h. The observed DSBR dynamics, which revealed heterogeneity of individual cell fates and their contributions to global repair efficacy, was confronted with a coupled differential equation model to obtain repair process rates. Good agreement was found between the mathematical model and experimental results at differentmore »scales, and quantitative comparisons of the different experimental conditions with image analysis of cell shape enabled the identification of three types of DSB repair events previously not recognized: high-efficacy error-free, low-efficacy error-free, and low-efficacy error-prone repair.

    Conclusions

    Our analysis paves the way to a significant advance in understanding the complex molecular mechanism of DSB repair, with potential implications beyond yeast cell biology. This multiscale and multidisciplinary approach more generally allows unique insights into the relation between in vivo microscopic processes within each cell and their impact on the population dynamics, which were inaccessible by previous approaches using molecular genetics tools alone.

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  2. Abstract Flux-rope-based magnetohydrodynamic modeling of coronal mass ejections (CMEs) is a promising tool for prediction of the CME arrival time and magnetic field at Earth. In this work, we introduce a constant-turn flux rope model and use it to simulate the 2012 July 12 16:48 CME in the inner heliosphere. We constrain the initial parameters of this CME using the graduated cylindrical shell (GCS) model and the reconnected flux in post-eruption arcades. We correctly reproduce all the magnetic field components of the CME at Earth, with an arrival time error of approximately 1 hr. We further estimate the average subjective uncertainties in the GCS fittings by comparing the GCS parameters of 56 CMEs reported in multiple studies and catalogs. We determined that the GCS estimates of the CME latitude, longitude, tilt, and speed have average uncertainties of 5.°74, 11.°23, 24.°71, and 11.4%, respectively. Using these, we have created 77 ensemble members for the 2012 July 12 CME. We found that 55% of our ensemble members correctly reproduce the sign of the magnetic field components at Earth. We also determined that the uncertainties in GCS fitting can widen the CME arrival time prediction window to about 12 hr for the 2012more »July 12 CME. On investigating the forecast accuracy introduced by the uncertainties in individual GCS parameters, we conclude that the half-angle and aspect ratio have little impact on the predicted magnetic field of the 2012 July 12 CME, whereas the uncertainties in longitude and tilt can introduce relatively large spread in the magnetic field predicted at Earth.« less
    Free, publicly-accessible full text available July 1, 2023
  3. Zou, Di (Ed.)
    Professional development has been identified as an effective way to increase college STEM instructors’ use of research-based instructional strategies (RBIS) known to benefit student learning and persistence in STEM. Yet only a few studies relate professional development experiences to later teaching behaviors of higher education instructors. This study of 361 undergraduate mathematics instructors, all of whom participated in multi-day, discipline-based workshops on teaching held in 2010–2019, examined the relationship between such participation and later use of RBIS. We found that instructors’ RBIS attitudes, knowledge, and skills strengthened after participating in professional development, and their self-reported use of RBIS became more frequent in the first year after the workshop. Applying the Theory of Planned Behavior as a conceptual framework, we used a structural equation model to test whether this theory could explain the roles of workshop participation and other personal, professional and contextual factors in fostering RBIS use. Findings indicated that, along with workshop participation, prior RBIS experience, class size, and course coordination affected RBIS use. That is, both targeted professional development and elements of the local context for implementation were important in supporting instructors’ uptake of RBIS—but, remarkably, both immediate and longer-term outcomes of professional development did not depend onmore »other individual or institutional characteristics. In this study, the large sample size, longitudinal measurement approach, and consistency of the form and quality of professional development make it possible to distinguish the importance of multiple possible influences on instructors’ uptake of RBIS. We discuss implications for professional development and for institutional structures that support instructors as they apply what they learned, and we offer suggestions for the use of theory in future research on this topic.« less
    Free, publicly-accessible full text available April 15, 2023
  4. Faculty professional development is an important lever for change in supporting instructors to adopt research-based instructional strategies that engage students intellectually, foster learning-supportive attitudes and habits of mind, and strengthen their persistence in mathematics. Yet the literature contains few well-rationalized models for faculty development in higher education. We describe the rationale and design for a model for discipline-based faculty development to support instructional change, and we detail our implementation of this model as applied to intensive workshops on inquiry-based learning (IBL) in college mathematics. These workshops seek to foster post-secondary mathematics instructors’ adoption of IBL, to help them adapt inquiry approaches for their classrooms, and ultimately to increase student learning and persistence in science and mathematics. Based on observed faculty needs, four strands of activity help instructors develop a mental model for an IBL classroom, adapt that model to their teaching context, develop facilitation and task-design skills, and plan an IBL mathematics course. Evaluation data from surveys and observations illustrate participant responses to the workshop and its components. The model has been robust across 15 years of workshops implemented by three generations of workshop leaders and its features make it adaptive, strategic, and practical for other faculty developers.
    Free, publicly-accessible full text available April 1, 2023
  5. ABSTRACT The 21 cm transition from neutral hydrogen promises to be the best observational probe of the epoch of reionization (EoR). The main difficulty in measuring the 21 cm signal is the presence of bright foregrounds that require very accurate interferometric calibration. Closure quantities may circumvent the calibration requirements but may be, however, affected by direction-dependent effects, particularly antenna primary beam responses. This work investigates the impact of antenna primary beams affected by mutual coupling on the closure phase and its power spectrum. Our simulations show that primary beams affected by mutual coupling lead to a leakage of foreground power into the EoR window, which can be up to ∼104 times higher than the case where no mutual coupling is considered. This leakage is, however, essentially confined at k < 0.3 h Mpc−1 for triads that include 29 m baselines. The leakage magnitude is more pronounced when bright foregrounds appear in the antenna sidelobes, as expected. Finally, we find that triads that include mutual coupling beams different from each other have power spectra similar to triads that include the same type of mutual coupling beam, indicating that beam-to-beam variation within triads (or visibility pairs) is not the major source of foreground leakage in the EoR window.
    Free, publicly-accessible full text available March 29, 2023
  6. Abstract The internal architecture of chambered ammonoid conchs profoundly increased in complexity through geologic time, but the adaptive value of these structures is disputed. Specifically, these cephalopods developed fractal-like folds along the edges of their internal divider walls (septa). Traditionally, functional explanations for septal complexity have largely focused on biomechanical stress resistance. However, the impact of these structures on buoyancy manipulation deserves fresh scrutiny. We propose increased septal complexity conveyed comparable shifts in fluid retention capacity within each chamber. We test this interpretation by measuring the liquid retained by septa, and within entire chambers, in several 3D-printed cephalopod shell archetypes, treated with (and without) biomimetic hydrophilic coatings. Results show that surface tension regulates water retention capacity in the chambers, which positively scales with septal complexity and membrane capillarity, and negatively scales with size. A greater capacity for liquid retention in ammonoids may have improved buoyancy regulation, or compensated for mass changes during life. Increased liquid retention in our experiments demonstrate an increase in areas of greater surface tension potential, supporting improved chamber refilling. These findings support interpretations that ammonoids with complex sutures may have had more active buoyancy regulation compared to other groups of ectocochleate cephalopods. Overall, the relationship betweenmore »septal complexity and liquid retention capacity through surface tension presents a robust yet simple functional explanation for the mechanisms driving this global biotic pattern.« less
  7. Observations are widely used in research and evaluation to characterize teaching and learning activities. Because conducting observations is typically resource intensive, it is important that inferences from observation data are made confidently. While attention focuses on interrater reliability, the reliability of a single-class measure over the course of a semester receives less attention. We examined the use and limitations of observation for evaluating teaching practices, and how many observations are needed during a typical course to make confident inferences about teaching practices. We conducted two studies based on generalizability theory to calculate reliabilities given class-to-class variation in teaching over a semester. Eleven observations of class periods over the length of a semester were needed to achieve a reliable measure, many more than the one to four class periods typically observed in the literature. Findings suggest practitioners may need to devote more resources than anticipated to achieve reliable measures and comparisons.
  8. Abstract

    Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC),N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. Nonemore »of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.

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  9. Abstract Many scientists use coronal hole (CH) detections to infer open magnetic flux. Detection techniques differ in the areas that they assign as open, and may obtain different values for the open magnetic flux. We characterize the uncertainties of these methods, by applying six different detection methods to deduce the area and open flux of a near-disk center CH observed on 2010 September 19, and applying a single method to five different EUV filtergrams for this CH. Open flux was calculated using five different magnetic maps. The standard deviation (interpreted as the uncertainty) in the open flux estimate for this CH ≈ 26%. However, including the variability of different magnetic data sources, this uncertainty almost doubles to 45%. We use two of the methods to characterize the area and open flux for all CHs in this time period. We find that the open flux is greatly underestimated compared to values inferred from in situ measurements (by 2.2–4 times). We also test our detection techniques on simulated emission images from a thermodynamic MHD model of the solar corona. We find that the methods overestimate the area and open flux in the simulated CH, but the average error in the flux ismore »only about 7%. The full-Sun detections on the simulated corona underestimate the model open flux, but by factors well below what is needed to account for the missing flux in the observations. Under-detection of open flux in coronal holes likely contributes to the recognized deficit in solar open flux, but is unlikely to resolve it.« less