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Stimulus-response habits benefit behavior by automatizing the selection of rewarding actions. However, this automaticity can come at the cost of reduced flexibility to adapt behavior when circumstances change. The goal-directed system is thought to counteract the habit system by providing the flexibility to pursue context-appropriate behaviors. The dichotomy between habitual action selection and flexible goal-directed behavior has recently been challenged by findings showing that rewards bias both action and goal selection. Here, we test whether reward reinforcement can give rise to habitual goal selection much as it gives rise to habitual action selection. We designed a rewarded, context-based perceptual discrimination task in which performance on one rule was reinforced. Using drift-diffusion models and psychometric analyses, we found that reward facilitates the initiation and execution of rules. Strikingly, we found that these biases persisted in a test phase in which rewards were no longer available. Although this facilitation is consistent with the habitual goal selection hypothesis, we did not find evidence that reward reinforcement reduced cognitive flexibility to implement alternative rules. Together, the findings suggest that reward creates a lasting impact on the selection and execution of goals but may not lead to the inflexibility characteristic of habits. Our findings demonstrate the role of the reward learning system in influencing how the goal-directed system selects and implements goals.

Research Question: A sizable portion of college students experience food and housing insecurity, which poses a roadblock to fully and successfully engaging in higher education. In light of these complex challenges, we ask: "How do Florida College System (FCS) institutions meet the basic needs of their students?" Methods: To answer the question at hand, we conducted an embedded single case study of the FCS. Between 2014 and 2019, researchers traveled to 21 Florida colleges on one or more occasions to speak with college presidents, administrators, faculty members, advisors, academic support staff, and students. In total, we gathered data from 1,379 people through 213 focus group sessions and 20 individual interviews. Results: From these data emerged evidence of the extensive services and support programs provided by FCS institutions, ranging from food and housing assistance to clothing, transportation, and childcare. Such initiatives aim to meet the chronic, daily needs of students and their families, as well as acute needs that arise out of local disasters and crises. Contributions: The findings of this study contribute to the literature on the mission of community colleges. While these support programs address needs traditionally considered non-academic, participants suggest that they are essential to fostering student success. By meeting students' physiological and safety needs, institutions can better accomplish their academic goals of remediation, transfer, vocational training, and contract education, particularly among students who have been traditionally excluded from higher education. The findings also highlight the importance of acknowledging the needs of students' families when providing support.

This study evaluated the efficacy of an 8-week (two sessions/week; 60 min/session) adapted soccer intervention on skill performance and retention in 30 adults (18 men and 12 women) ages 17-40 years with autism spectrum disorder, Down syndrome, and intellectual disability. Of these 30 participants, 18 completed a 1-month retention test. The program included behavior supports and adaptations for participants with varying levels of behavioral needs. Dribbling, kicking a moving ball, kicking a stationary ball, throw-ins, trapping, and a composite skill score were examined. Linear mixed-effect regression revealed a significant time main effect with improvements from pretest to posttest and pretest to retention for all skills. In addition, modest offline gains (i.e., posttest < retention) were observed for throw-ins, kicking a moving ball, and the composite skill score. A significant main effect of diagnosis was observed such that participants with autism spectrum disorder had better performance on kicking a moving ball than those with Down syndrome and intellectual disability. Finally, a significant main effect of level of function was observed. This program enabled adults with various disabilities to acquire fundamental soccer skills that may lead to meaningful participation in community soccer programs.

Brain tumors and genomics have a long-standing history given that glioblastoma was the first cancer studied by the cancer genome atlas. The numerous and continuous advances through the decades in sequencing technologies have aided in the advanced molecular characterization of brain tumors for diagnosis, prognosis, and treatment. Since the implementation of molecular biomarkers by the WHO CNS in 2016, the genomics of brain tumors has been integrated into diagnostic criteria. Long-read sequencing, also known as third generation sequencing, is an emerging technique that allows for the sequencing of longer DNA segments leading to improved detection of structural variants and epigenetics. These capabilities are opening a way for better characterization of brain tumors. Here, we present a comprehensive summary of the state of the art of third-generation sequencing in the application for brain tumor diagnosis, prognosis, and treatment. We discuss the advantages and potential new implementations of long-read sequencing into clinical paradigms for neuro-oncology patients.

The Recipe 4 Success preventive intervention targeted multiple factors critical to the health and well-being of toddlers living in poverty. This randomized controlled trial, which was embedded within Early Head Start home visits for 12 weeks, included 242 racially and ethnically diverse families (51% girls; toddler mean age = 2.58 years; data collected 2016-2019). Compared to parents in usual practice home visits, parents in Recipe 4 Success displayed greater sensitive scaffolding of toddlers' learning and more responsive food parenting practices (Cohen's d = 0.21-0.30). Toddlers in Recipe 4 Success exhibited greater self-regulation and had healthier eating habits (Cohen's d = |0.16-0.35|). Results highlight the value of Recipe 4 Success in promoting parent and toddler behavior change that could have life-long benefits.

BackgroundApproximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest given the first regulatory approval of a nanoCAR in multiple myeloma.MethodsWe humanized our previous nanobody framework regions, derived from llama, to generate a series of humanized anti-CD72 nanobodies. These nanobody binders were inserted into second-generation CD72 CAR-T cells and were evaluated against preclinical models of B cell acute lymphoblastic leukemia and B cell non-Hodgkin's lymphoma in vitro and in vivo. Humanized CD72 nanoCARs were compared with parental ("NbD4") CD72 nanoCARs and the clinically approved CD19-directed CAR-T construct tisangenlecleucel. RNA-sequencing, flow cytometry, and cytokine secretion profiling were used to determine differences between the different CAR constructs. We then used affinity maturation on the parental NbD4 construct to generate high affinity binders against CD72 to test if higher affinity to CD72 improved antitumor potency.ResultsToward clinical translation, here we humanize our previous nanobody framework regions, derived from llama, and surprisingly discover a clone ("H24") with enhanced potency against B-cell tumors, including patient-derived samples after CD19 CAR-T relapse. Potentially underpinning improved potency, H24 has moderately higher binding affinity to CD72 compared with a fully llama framework. However, further affinity maturation (KD

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture 'structural surfaceomics'. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 as a structurally defined, widely expressed AML-specific target. We develop and characterize recombinant antibodies to this protein conformation and show that chimeric antigen receptor T cells eliminate AML cells and patient-derived xenografts without notable toxicity toward normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen and demonstrate a tool kit for applying these strategies more broadly.

Course assessment is traditionally a one-way process, where instructors evaluate pupils' progress toward mastery. Done conscientiously, this sort of feedback can be effective but relies upon an individual student's ability to self-regulate, which is predicated upon their ability to manage their environment and incorporate evaluations into their work. Co-regulated learning is a relatively new idea, wherein students evaluate themselves and each other, which helps the learners not only improve their own work, but absorb the underlying rationale of the lessons as well. One underexplored area is whether a co-regulated environment in which the learners are also expected to evaluate the instructor can lead to better outcomes. The authors designed doctoral-level online courses with the explicit intent of using student feedback to improve the curricula, and this study demonstrates that incorporating those assessments seemed to markedly improve enrollees' ratings of course-design elements and their mastery of the subject matter.

Developing and exploring new tools to engage students in the learning process have been major foci of chemistry education research. Creative exercises are one such tool that has drawn increasing interest from researchers over the past decade. While studies have reported the impact of creative exercises on learning and types of student responses generated, how the students engage with these particular exercises has yet to be explored. This study seeks to fill this gap within the literature by exploring student approaches to the creative exercises, within the context of biochemistry, through semistructured, think-aloud interviews. Analysis of 10 participant interviews investigated how undergraduate biochemistry students actively and verbally engaged in creative exercises. Findings reveal the variation in how the participants approached the creative exercises as well as the role that the course modality played in shaping the student approaches.

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.

Florida Senate Bill 1720 drastically changed developmental education, beginning in fall 2014. This paper considers affected faculty members' perceptions and experiences with the passage and implementation of reform, according to focus group data provided by 294 participants at 21 Florida College System institutions between 2014 and 2019. We found that faculty members experienced feelings of powerlessness and meaninglessness--the two main components of policy alienation--related to the passage of SB 1720, with some reported opportunities for discretion and innovation at a local level. Despite feelings of alienation, faculty worked hard to facilitate student success through the changes.

Recent studies showed a considerable amount of individual variations in lesbian, gay, bisexual, and queer (LGBQ) college students' reporting of peer harassment experiences. This result is often interpreted as an indication that LGBQ students differ in their chance of experiencing peer harassment, but it may also reflect students' varying interpretations of peer behaviors. To examine this possibility, we analyzed data from in-depth interviews with 45 LGBQ students by using narrative construction as a theoretical framework. The analysis showed that LGBQ students constructed largely two types of narratives regarding heterosexual peers' behaviors, which we call stigma narratives and post-closet narratives. Those who told stigma narratives described heterosexual peers' behaviors critically and believed that those behaviors reflected the institutional oppression of LGBQ students. Those who told post-closet narratives did not see these types of peer behaviors as problematic and sometimes interpreted them as heterosexual peers' friendliness and an indication of inclusive campus climate. The results suggest that college assessments of peer harassment and campus climate require close attention to LGBQ students' efforts to construct coherent narratives.

When it comes to the creation of higher education policy, state legislators are challenged with addressing the diverse academic needs of college students enrolled across a spectrum of institutions. In this paper, we explore how 203 individuals at five rural-serving colleges in Florida engaged in state-wide developmental education (DE) reform using the theoretical framework of "situated cognition." Specifically, we ask whether the colleges implemented DE reform in unique ways that may have differed from their non-rural counterparts and what their rationale was for doing so. Our work indicates that institutional culture and capacity generated a combination of strengths and constraints in how reform played out in a rural context. In some ways, a rural-serving identity made colleges more flexible and better able to adjust their advising and curricular structures to comply with the mandates of SB 1720. But in other ways, rural-serving institutions lacked the resources necessary to adequately support students and campus personnel through this dramatic transition toward new ways of providing DE. In looking toward the passage and implementation of future education reform, we call upon policymakers to consider more deeply the design of policies to ensure they support rural and non-rural colleges alike.

The purpose of this literature review was to examine how language is used to describe and advance culturally-based pedagogy to critically reflect on the language employed in teacher education research. Our intent was to understand the terminology that has moved conversations of equity, diversity, and cultural ways of knowing to the center of urban education research and practice. Findings indicate the discourse of culturally-based pedagogy relies upon: (1) the exploration of the construct of culture, (2) the knowledge of the socio-historical context of specific terminology, and (3) a perspective that discourse is generative and dynamic.

Physics graduate teaching assistants (GTAs) are tasked with multifaceted teaching assignments, such as leading tutorials and inquiry-based laboratories, yet their professional development rarely includes opportunities to rehearse complex pedagogical skills or receive feedback on their teaching. In this study, physics GTAs practiced specific pedagogical skills during four sessions in a mixed-reality classroom simulator; here, we focus on GTAs' use of a specific questioning strategy called "Stretch-It." GTAs can apply Stretch-It by asking students to explain their logic (Explain Logic), either by explaining their work or providing evidence for their claim; or by asking students to take the content further (Follow-Up), either by applying it in an analogous situation or answering the initial question in another way. We found GTAs used all four types of Stretch-It subcategories during simulator sessions that incorporated facilitator feedback about their use of questioning. We also compared the use of Stretch-It questioning in the classroom for a pretraining semester cohort and the high-intensity simulator training cohort and found that the high-intensity cohort's average use of Explain Logic questions in the observation immediately following the Stretch-It rehearsal was meaningfully higher than the pretraining cohort's average use of Explain Logic. However, the high-intensity cohort's use of Explain Logic is unstable, and values fall back within the pretraining average in subsequent classroom observations. We did not find a significant difference between the cohorts' use of Follow-Up. We discuss the implications of our findings for science, technology, engineering, and medicine GTA professional development and the significance of providing feedback to GTAs about their teaching.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.

The myeloma surface proteome (surfaceome) determines tumor interaction with the microenvironment and serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to define the myeloma surfaceome at baseline, in drug resistance, and in response to acute drug treatment. We provide a scoring system for surface antigens and identify CCR10 as a promising target in this disease expressed widely on malignant plasma cells. We engineer proof-of-principle chimeric antigen receptor (CAR) T-cells targeting CCR10 using its natural ligand CCL27. In myeloma models we identify proteins that could serve as markers of resistance to bortezomib and lenalidomide, including CD53, CD10, EVI2B, and CD33. We find that acute lenalidomide treatment increases activity of MUC1-targeting CAR-T cells through antigen upregulation. Finally, we develop a miniaturized surface proteomic protocol for profiling primary plasma cell samples with low inputs. These approaches and datasets may contribute to the biological, therapeutic, and diagnostic understanding of myeloma.

A day, March 8, 2021, in sounds.

Objective: Community colleges have long made higher education more accessible to students from diverse academic backgrounds, particularly those who are academically underprepared and require remediation. In light of developmental education (DE) reform, our article answers the following questions: How do campus personnel articulate the unique mission of Florida's state colleges, formerly known as community colleges? Furthermore, how do they perceive the mandates of reform to have shaped their ability to carry out this mission? Method: This work is based on an embedded case study of 10 Florida College System institutions. Qualitative data were gathered between 2014 and 2018 from 544 college presidents, administrators, faculty, staff through 92 focus groups and 8 interviews. Results: Campus personnel strongly affirmed the mission of the Florida Colleges System as one of democratic equality. However, many were concerned that DE reform, namely Senate Bill 1720, prioritized efficiency over equality in the pursuit of cost savings. Specifically, participants expressed frustration that reforms accelerated DE coursework to an unmanageable pace and ignored the presence of a digital divide. Opinions of DE reform improved in the 4 years following implementation, but some concern persisted. Contributions: Our findings highlight the centrality of democratic equality to the community college mission for campus personnel. They also suggest that equality and efficiency need not always be opposing goals in education reform. Finally, they call into question social policy that universally promotes accelerated and computer-based courses without considering that some students may require accommodations.

Sexual minority youth (SMY) students who identify as lesbian, gay, bisexual, or transgender (LGBT+) often struggle with gender identity and sexual orientation (Craig, Austin, & McInroy, 2014). The inclusion of Gay-Straight Alliances (GSA) and Safe Zones have united students and facilitated cultural shifts in schools (Patterson, 2013). Gay-Straight Alliances build metaphorical bridges by connecting all students regardless of their beliefs and cultural differences. By creating an inclusive environment--meaning one that has established a Gay-Straight Alliance, creating Safe Zones for students, and enriching the curriculum with resiliency lessons--the overall social connectedness mean scores would likely increase, resulting in happier and more productive students. The main research question for this study was: How does social connectedness improve in a Texas high school that creates an inclusive learning environment? Over the course of the study, steps were taken to create an inclusive environment for all students. Results suggested the importance of social connectedness for individuals to their environment regardless of identifying as SMY. The benefit of creating an inclusive environment (GSA, established Safe Zones, and implemented resiliency curriculum) was justified.