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Abstract Cas9 is a metal-dependent nuclease that has revolutionized gene editing across diverse cells and organisms exhibiting varying ion uptake, metabolism, and concentrations. However, how divalent metals impact its catalytic function, and consequently its editing efficiency in different cells, remains unclear. Here, extensive molecular simulations, Markov State Models, biochemical and NMR experiments, demonstrate that divalent metals – Mg²⁺, Ca²⁺, and Co²⁺– promote activation of the catalytic HNH domain by binding within a dynamically forming divalent metal binding pocket (DBP) at the HNH-RuvC interface. Mutations in DBP residues disrupt HNH activation and impair the coupled catalytic activity of both nucleases, identifying this cryptic DBP as a key regulator of Cas9’s metal-dependent activity. The ionic strength thereby promotes Cas9’s conformational activation, while its catalytic activity is metal-specific. These findings are critical to improving the metal-dependent function of Cas9 and its use for genome editing in different cells and organisms. 

SUMMARY Evidence of seismic anisotropy is widespread within the Earth, including from individual crystals, rocks, borehole measurements, active-source seismic data, and global seismic data. The seismic anisotropy of a material determines how wave speeds vary as a function of propagation direction and polarization, and it is characterized by density and the elastic map, which relates strain and stress in the material. Associated with the elastic map is a symmetric $$6 \times 6$$ matrix, which therefore has 21 parameters. The 21-D space of elastic maps is vast and poses challenges for both theoretical analysis and typical inverse problems. Most estimation approaches using a given set of directional wave speed measurements assume a high-symmetry approximation, typically either in the form of isotropy (2 parameters), vertical transverse isotropy (radial anisotropy: 5 parameters), or horizontal transverse isotropy (azimuthal anisotropy: 6 parameters). We offer a general approach to explore the space of elastic maps by starting with a given elastic map $$\mathbf {T}$$. Using a combined minimization and projection procedure, we calculate the closest $$\Sigma$$-maps to $$\mathbf {T}$$, where $$\Sigma$$ is one of the eight elastic symmetry classes: isotropic, cubic, transverse isotropic, trigonal, tetragonal, orthorhombic, monoclinic and trivial. We apply this approach to 21-parameter elastic maps derived from laboratory measurements of minerals; the measurements include dependencies on pressure, temperature, and composition. We also examine global elasticity models derived from subduction flow modelling. Our approach offers a different perspective on seismic anisotropy and motivates new interpretations, such as for why elasticity varies as a function of pressure, temperature, and composition. The two primary advances of this study are (1) to provide visualization of elastic maps, including along specific pathways through the space of model parameters, and (2) to offer distinct options for reducing the complexity of a given elastic map by providing a higher-symmetry approximation or a lower-anisotropic version. This could contribute to improved imaging and interpretation of Earth structure and dynamics from seismic anisotropy. 

Background and Context.  Computing is considered a fundamental skill for civic engagement, self-expression, and employment opportunity. Despite this, there exist significant equity gaps in post-secondary computing enrollment and retention. Specifically, in the California State University (CSU) system, which serves close to half a million undergraduate students, students identifying as Hispanic/Latino make up a smaller percentage of CS majors than expected from the state’s overall population; and, once enrolled, tend to leave the CS major at higher rates than other students. Purpose.  We report on the impacts of a curricular intervention aimed at strengthening the sense of belonging of Hispanic/Latino students in computing, with the eventual goal of improving retention in computing majors for those students. Methods.  Working in an alliance of six universities within the CSU (five of which are designated as Hispanic-Serving Institutions), we have incorporated socially responsible computing across early CS courses. We aim for alignment between our curriculum and students’ communal goal orientations, and for coursework that attends to students’ interests, values, and cultural assets. Over a two-year-long study, we collected survey data to learn about the impact of our curricular intervention on students’ sense of belonging and perceived learning and agency. Findings.  We found that students generally reported high communal goal orientations and, at the campuseswithoutcompetitive enrollment policies, our intervention had a significant positive impact on students’ senses of belonging. This effect was observed between control and treatment terms as well as within treatment terms. We also note that Hispanic/Latino students were more likely than other students to report that non-curricular factors like work and family obligations interfered with their learning, and appeared to experience slightly stronger benefits from the intervention. Implications.  Our data suggest positive outcomes for integrating socially responsible computing into early CS courses, especially for Hispanic/Latino students at certain Primarily Undergraduate Institutions (PUIs). Unlike much prior research, we found that conducting studies outside of Primarily White Institutions (PWIs) can provide new insights into the impact of curricular interventions on student experience and retention. Our varying results by campus suggest that factors such as campus population, acceptance rate, and departmental enrollment policies ought to also be taken into account in studies that aim to broaden participation in computing. Would results from prior research on recruitment and retention of Hispanic/Latino students or other underrepresented students look different if such studies were replicated at institutions with different demographics and enrollment policies? 

Socially Responsible Computing (SRC) education entails the infusion of Computer Science (CS) education with interwoven attention to ethical, social, and political issues to position students to reflect and take action individually and collaboratively to create a more just world. Our approach to SRC supports students to explore computing design/development in early CS courses with a communal goal orientation (in contrast to agentic/individualized), shown to improve achievement and retention for students with identities that are minoritized in CS. Grounded in our own experiences as co-developers and implementers of this pedagogical transformation and as co-facilitators of a Faculty Learning Community (FLC) across six minority-serving institutions in California, we share how we use an iterative design and implementation process modeled from social design experimentation as research and development method. Initial results are presented as a set of promising practices for incorporating SRC into introductory CS courses: 1) choose the domain mindfully; 2) design for synergy with technical material; 3) scaffold for inclusivity; 4) structure with a framework; 5) avoid othering SRC elements; and 6) reuse and build on existing resources. We share how these promising practices guide our efforts; how they can address challenges and concerns for new and continuing SRC implementers; and the ways in which we have and will continue to test and co-design this approach.