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  1. Dolan, Erin L. (Ed.)
    Mindset interventions, which shift students’ beliefs about classroom experiences, have shown promise for promoting diversity in science, technology, engineering, and mathematics (STEM). Psychologists have emphasized the importance of customizing these interventions to specific courses, but there is not yet a protocol for doing so. We developed a protocol for creating customized “peer-modeled” mindset interventions that elicit advice from former students in videotaped interviews. In intervention activities, clips from these interviews, in which the former students’ stories model the changes in thinking about challenge and struggle that helped them succeed in a specific course, are provided to incoming life sciences students. Using this protocol, we developed a customized intervention for three sections of Introductory Biology I at a large university and tested it in a randomized controlled trial ( N = 917). The intervention shifted students’ attributions for struggle in the class away from a lack of potential to succeed and toward the need to develop a better approach to studying. The intervention also improved students’ approaches to studying and sense of belonging and had promising effects on performance and persistence in biology. Effects were pronounced among first-generation college students and underrepresented racial/ethnic minority students, who have been historically underrepresented inmore »the STEM fields.« less
    Free, publicly-accessible full text available December 1, 2023
  2. Base editors (BEs) are genome editing agents that install point mutations with high efficiency and specificity. Due to their reliance on uracil and inosine DNA damage intermediates (rather than double-strand DNA breaks, or DSBs), it has been hypothesized that BEs rely on more ubiquitous DNA repair pathways than DSB-reliant genome editing methods, which require processes that are only active during certain phases of the cell cycle. We report here the first systematic study of the cell cycle-dependence of base editing using cell synchronization experiments. We find that nickase-derived BEs (which introduce DNA backbone nicks opposite the uracil or inosine base) function independently of the cell cycle, while non-nicking BEs are highly dependent on S-phase (DNA synthesis phase). We found that synchronization in G1 (growth phase) during the process of cytosine base editing causes significant increases in C•G to A•T “byproduct” introduction rates, which can be leveraged to discover new strategies for precise C•G to A•T base editing. We observe that endogenous expression levels of DNA damage repair pathways are sufficient to process base editing intermediates into desired editing outcomes, and the process of base editing does not significantly perturb transcription levels. Overall, our study provides mechanistic data demonstrating the robustnessmore »of nickase-derived BEs for performing genome editing across the cell cycle.« less
    Free, publicly-accessible full text available July 14, 2023

    We present the first 2.5 yr of data from the MeerKAT Pulsar Timing Array (MPTA), part of MeerTime, a MeerKAT Large Survey Project. The MPTA aims to precisely measure pulse arrival times from an ensemble of 88 pulsars visible from the Southern hemisphere, with the goal of contributing to the search, detection, and study of nanohertz-frequency gravitational waves as part of the International Pulsar Timing Array. This project makes use of the MeerKAT telescope and operates with a typical observing cadence of 2 weeks using the L-band receiver that records data from 856 to 1712 MHz. We provide a comprehensive description of the observing system, software, and pipelines used and developed for the MeerTime project. The data products made available as part of this data release are from the 78 pulsars that had at least 30 observations between the start of the MeerTime programme in February 2019 and October 2021. These include both sub-banded and band-averaged arrival times and the initial timing ephemerides, noise models, and the frequency-dependent standard templates (portraits) used to derive pulse arrival times. After accounting for detected noise processes in the data, the frequency-averaged residuals of 67 of the pulsars achieved a root-mean-square residual precision of $\ltmore »1 \, \mu \rm {s}$. We also present a novel recovery of the clock correction waveform solely from pulsar timing residuals and an exploration into preliminary findings of interest to the international pulsar timing community. The arrival times, standards, and full Stokes parameter-calibrated pulsar timing archives are publicly available.

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    We present the polarization profiles of 22 pulsars in the globular cluster 47 Tucanae using observations from the MeerKAT radio telescope at UHF band (544–1088 MHz) and report precise values of dispersion measure (DM) and rotation measure (RM). We use these measurements to investigate the presence of turbulence in electron density and magnetic fields. The structure function of DM shows a break at ∼30 arcsec (∼0.6 pc at the distance of 47 Tucanae) that suggests the presence of turbulence in the gas in the cluster driven by the motion of wind-shedding stars. On the other hand, the structure function of RM does not show evidence of a break. This non-detection could be explained either by the limited number of pulsars or by the effects of the intervening gas in the Galaxy along the line of sight. Future pulsar discoveries in the cluster could help confirm the presence and localize the turbulence.

  5. The development of CRISPR-derived genome editing technologies has enabled the precise manipulation of DNA sequences within the human genome. In this review, we discuss the initial development and cellular mechanism of action of CRISPR nucleases and DNA base editors. We then describe factors that must be taken into consideration when developing these tools into therapeutic agents, including the potential for unintended and off-target edits when using these genome editing tools, and methods to characterize these types of edits. We finish by considering specific challenges associated with bringing a CRISPR-based therapy to the clinic: manufacturing, regulatory oversight and considerations for clinical trials that involve genome editing agents.
  6. Lockman, Jeffrey J. (Ed.)
    Beliefs play a central role in human development. For instance, a growth mindset—a belief about the malleability of intelligence—can shape how adolescents interpret and respond to academic difficulties and how they subsequently navigate the educational system. But do usually-adaptive beliefs have the same effects for adolescents regardless of the contexts they are in? Answering this question can reveal new insights into classic developmental questions about continuity and change. Here we present the Mindset×Context framework and we apply this model to the instructive case of growth mindset interventions. We show that teaching students a growth mindset is most effective in educational contexts that provide affordances for a growth mindset; that is, contexts that permit and encourage students to view ability as developable and to act on that belief. This evidence contradicts the “beliefs alone” hypothesis, which holds that teaching adolescents a growth mindset is enough and that students can profit from these beliefs in almost any context, even unsupportive ones. The Mindset×Context framework leads to the realization that in order to produce more widespread and lasting change, we must complement the belief-changing interventions that have been aimed at students with new interventions that guide teachers toward classroom policies and practices thatmore »allow students' growth mindset beliefs to take root and yield benefits.« less
  7. Existing tactile stimulation technologies powered by small actuators offer low-resolution stimuli compared to the enormous mechanoreceptor density of human skin. Arrays of soft pneumatic actuators initially show promise as small-resolution (1- to 3-mm diameter), highly conformable tactile display strategies yet ultimately fail because of their need for valves bulkier than the actuators themselves. In this paper, we demonstrate an array of individually addressable, soft fluidic actuators that operate without electromechanical valves. We achieve this by using microscale combustion and localized thermal flame quenching. Precisely, liquid metal electrodes produce sparks to ignite fuel lean methane–oxygen mixtures in a 5-mm diameter, 2-mm tall silicone cylinder. The exothermic reaction quickly pressurizes the cylinder, displacing a silicone membrane up to 6 mm in under 1 ms. This device has an estimated free-inflation instantaneous stroke power of 3 W. The maximum reported operational frequency of these cylinders is 1.2 kHz with average displacements of ∼100 µm. We demonstrate that, at these small scales, the wall-quenching flame behavior also allows operation of a 3 × 3 array of 3-mm diameter cylinders with 4-mm pitch. Though we primarily present our device as a tactile display technology, it is a platform microactuator technology with application beyond this one.

  8. Researchers often invoke the metaphor of a pipeline when studying participation in careers in science, technology, engineering, and mathematics (STEM), focusing on the important issue of students who “leak” from the pipeline, but largely ignoring students who persist in STEM. Using interview, survey, and institutional data over 6 years, we examined the experiences of 921 students who persisted in biomedical fields through college graduation and planned to pursue biomedical careers. Despite remaining in the biomedical pipeline, almost half of these students changed their career plans, which was almost twice the number of students who abandoned biomedical career paths altogether. Women changed plans more often and were more likely than men to change to a career requiring fewer years of post-graduate education. Results highlight the importance of studying within-pipeline patterns rather than focusing only on why students leave STEM fields.