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Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

Plasmodium falciparum requires a two-host system, moving between Anopheles mosquito and humans, to complete its life cycle. To overcome such dynamic growth conditions its histones undergo various post-translational modifications to regulate gene expression. The P. falciparum Bromodomain Protein 1 (PfBDP1) has been shown to interact with acetylated lysine modifications on histone H3 to regulate the expression of invasion-related genes. Here, we investigated the ability of the PfBDP1 bromodomain to interact with acetyllsyine modifications on additional core and variant histones. A crystal structure of the PfBDP1 bromodomain (PfBDP1-BRD) reveals it contains the conserved bromodomain fold, but our comparative analysis between the PfBDP1-BRD and human bromodomain families indicates it has a unique binding mechanism. Solution NMR spectroscopy and ITC binding assays carried out with acetylated histone ligands demonstrate that it preferentially recognizes tetra-acetylated histone H4, and we detected weaker interactions with multi-acetylated H2A.Z in addition to the previously reported interactions with acetylated histone H3. Our findings indicate PfBDP1 may play additional roles in the P. falciparum life cycle, and the distinctive features of its bromodomain binding pocket could be leveraged for the development of new therapeutic agents to help overcome the continuously evolving resistance of P. falciparum against currently available drugs.

BackgroundDistribution of long-lasting insecticidal bed nets (LLINs) is one of the main control strategies for malaria. Improving malaria prevention programmes requires understanding usage patterns in households receiving LLINs, but there are limits to what standard cross-sectional surveys of self-reported LLIN use can provide. This study was designed to assess the performance of an accelerometer-based approach for measuring a range of LLIN use behaviours as a proof of concept for more granular LLIN-use monitoring over longer time periods.MethodsThis study was carried out under controlled conditions from May to July 2018 in Liverpool, UK. A single accelerometer was affixed to the side panel of an LLIN and participants carried out five LLIN use behaviours: (1) unfurling a net; (2) entering an unfurled net; (3) lying still as if sleeping; (4) exiting from under a net; and, (5) folding up a net. The randomForest package in R, a supervised non-linear classification algorithm, was used to train models on 20-s epochs of tagged accelerometer data. Models were compared in a validation dataset using overall accuracy, sensitivity and specificity, receiver operating curves and the area under the curve (AUC).ResultsThe five-category model had overall accuracy of 82.9% in the validation dataset, a sensitivity of 0.681 for entering a net, 0.632 for exiting, 0.733 for net down, and 0.800 for net up. A simplified four-category model, combining entering/exiting a net into one category had accuracy of 94.8%, and increased sensitivity for net down (0.756) and net up (0.829). A further simplified three-category model, identifying sleeping, net up, and a combined net down/enter/exit category had accuracy of 96.2% (483/502), with an AUC of 0.997 for net down and 0.987 for net up. Models for detecting entering/exiting by adults were significantly more accurate than for children (87.8% vs 70.0%; p

Abstract Background Efforts to evaluate the residual efficacy of new indoor residual spraying (IRS) formulations have identified limitations with the industry standard laboratory sprayer, the Potter Spray Tower (PT). Calibrating the PT can be time-consuming, and the dosing of surfaces may not be as accurate or uniform as previously assumed. Methods To address these limitations, the Micron Horizontal Track Sprayer with Spray Cabinet (TS) was developed to provide higher efficiency, ease of operation and deposition uniformity equal to or better than the PT. A series of studies were performed using a fluorescent tracer and three IRS formulations (Actellic® 300CS, K-Othrine WG250 and Suspend PolyZone) sprayed onto surfaces using either the PT or the TS. Results Deposition volumes could be accurately calibrated for both spray systems. However, the uniformity of spray deposits was higher for the TS compared to the PT. Less than 12% of the volume sprayed using the PT reaches the target surface, with the remaining 88% unaccounted for, presumably vented out of the fume hood or coating the internal surfaces of the tower. In contrast, the TS deposits most of the spray on the floor of the spray chamber, with the rest contained therein. The total sprayed surface area in one run of the TS is 1.2 m2, and the operational zone for spray target placement is 0.7 m2, meaning that 58% of the applied volume deposits onto the targets. The TS can treat multiple surfaces (18 standard 15 × 15 cm tiles) in a single application, whereas the PT treats one surface at a time and a maximum area of around 0.0225 m2. An assessment of the time taken to perform spraying, including the setup, calibration and cleaning, showed that the cost of application using the TS was around 25–35 × less per tile sprayed. Standard operating procedures (SOPs) for calibration and use of both the Potter Tower and Track Sprayer have been developed. Conclusions Overall, the TS represents a significant improvement over the PT in terms of the efficiency and accuracy of IRS formulation applications onto test substrates and offers a useful additional tool for researchers and manufacturers wanting to screen new active ingredients or evaluate the efficacy of IRS or other sprayable formulations for insect control. Graphical Abstract

Abstract The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory.

Abstract Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

The COVID-19 pandemic--coupled with ongoing prominent injustice related to race, poverty, healthcare, and education--has highlighted the interlocking and reinforcing nature of systemic oppression. Now more than ever, facilitators of experiential learning are galvanized to explore and deepen their understanding of systemic change and to enhance their teaching of justice concepts, perspectives, and skills. Advancing social justice was a part of the original vision for service-learning (Stanton et al., 1999). However, scholars have long identified the ways in which service-learning can perpetuate inequitable social hierarchies, be miseducative in teaching simplistic understandings of solutions to social problems, and not equip students to participate in social movements for justice (Eby, 1998; Mitchell and Latta, 2020). By incorporating critical pedagogy, action, and reflection in and beyond the classroom, "critical service-learning" seeks to increase understanding of oppression, redistribute power, and find solutions to social issues through community-campus partnerships (Mitchell, 2008; Santiago-Ortiz, 2019). However, many service-learning practitioners report uncertainty about how to take concrete steps to align their courses with justice orientated techniques and pedagogy. In order to address this need, students, staff, and faculty in Duke Service-Learning began creating a tool to support the implementation of critical pedagogy and justice in service-learning courses in 2016 (Stith et al., 2018). For the past 8 months an expanded group has worked to update that original tool. The resulting tool organizes course design choices into five themes: reckoning with systems, authentic relationships, redistribution of power, equitable classrooms & cognitive justice, and social change skills. The resulting tool generates concrete, actionable questions for service-learning and experiential learning to interrogate how their pedagogy and practices incorporate social, economic, environmental, and racial justice. Our article summarizes the advances in our understanding and of the literature on implementing justice aligned experiential education and links to the current version of our tool. Further, our article will summarize lessons learned from conversations with practitioners who use and reflect on the implications of the tool for their own pedagogy. We will also reflect on holding the tensions in balancing the various aspects of course designs and our commitments to anti-oppressive practices. Finally, we will reflect on further implications for service-learning and experiential education that the process of creating this tool has surfaced.

The purposes of this study were to assess the effects of fractions intervention for students who are at risk for poor outcomes and to examine whether a component that combines self-regulated learning with growth-mindset instruction (SR-GM) provides added value for improving outcomes. At-risk students (N = 84) were randomly assigned to three conditions: fractions intervention, fractions intervention with embedded SR-GM, and a control group. Intervention was conducted three times per week for 35 min per session for 13 weeks. Multilevel models indicated both fractions intervention conditions produced strong effects, with no added value for SR-GM. Posttest fractions achievement gaps for both intervention conditions held steady, narrowed, or closed, whereas the control group's gaps remained sizeable or grew. Results suggest that intervention can address challenging mathematics standards for at-risk learners and that SR-GM instruction may not be necessary in the context of strong intervention. [For the corresponding grantee submission, see ED604271.]

Instruments for assessing secondary students' conceptual understanding of core concepts in biology are needed by educational practitioners and researchers alike. Most instruments available for secondary biology (years 9 to 12) focus only on highly specific biological concepts instead of multiple core concepts. This study describes the development of a 25-item instrument designed to fill this gap, the High School Biology Concept Inventory (HS-BCI). The HS-BCI not only assesses student knowledge of key biological concepts but also alternative conceptions. Using Rasch theory, the initial instrument was constructed from a pool of 61 instrument items using test results from 1015 students. The final 25-item instrument was validated with 1955 students. The results provide reliability and validity evidence for the HS-BCI. The findings suggest that it can be utilized to assess both conceptual knowledge and alternative conceptions.

Christian higher education uniquely marries neoplantation academia with the practice of religious jawboning, using persuasion rather than the exertion of vehement enforcement, to engage Black faculty of faith in upholding white supremacy ideology. These institutions can and do use faith as a tool of oppression through their policies and practice, reinforcing the domination of whites and the subordination of people of Color as the divine order of God. This was the reality and experience of two Black women faculty during their time at one of these institutions. Using Black Liberation Theology as a framework, duoethnographies detail how a racialized hierarchy was embedded into the fabric of a faith-based university and describe the institutional expectation for Black faculty to subscribe to a system that supported their own physical and mental demise in exchange for spiritual redemption. More than just a cautionary tale of religious academic spaces, implications include the need for faith-based institutions to come to terms with and reconceptualize their commitment to racial diversity and the authors' ability to reclaim their faith as an act of resistance, despite the attempted lure to participate in their own spiritual murder.

Children in urban environments tend to have limited exposure to environmental education programs for many reasons. This paper describes the development of a short-session after-school program, created to introduce children in an inner-city school to the concept of urban ecology. In this program, we met with a class of 20 fifth graders once a week for four weeks and evaluated students' perceptions of nature with a pre-post-intervention activity that asked students to draw a picture describing "nature." Researchers evaluated the drawings together. The results indicated an increase in the instances of animals and insects in drawings with fewer anthropic influences, such as people, buildings, and vehicles. Overall, the program achieved its goal of exposing urban children to the ecology all around them.