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Abstract: Great effort has been invested in increasing STEM achievement among students, but feelings of low status among underrepresented or otherwise vulnerable students may be creating additional challenges. The present study assessed how perceptions of social status within the classroom—termed subjective social status—aligned with objective course performance and differed by sex, first-generation status, work status, and race/ethnicity among 713 students enrolled across three introductory statistics classes. Findings indicated that final exam score was moderately related to ratings of subjective social status, suggesting that factors besides objective course performance may influence classroom subjective social status. When asked to explain how they evaluated their standing in the course, students reported five main themes, including both academic achievement with respect to exam scores and their understanding of course content. When examining differences by status-based identities in subjective social status, we found that female and first-generation students had lower subjective social status compared to their male and continuing-generation peers, although results were less robust for first-generation status. Likewise, working students reported lower subjective social status relative to non-working students, despite showing no difference in final exam score. In contrast, although Asian/Asian American students outperformed Latine students, there were no differences in reports of subjective social status between Asian/Asian American, Latine, and white students. Taken together, results suggest that factors beyond course performance may relate to students’ subjective social status, and subjective social status may contribute to disparities in academic performance, especially by sex and work status.

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1-4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

Substrates engineered to undergo a 1,4-C-H insertion to yield benzocyclobutenes resulted in a novel elimination reaction to yield ortho-quinone dimethide (o-QDM) intermediates that undergo Diels-Alder or hetero-Diels-Alder cycloadditions. The analogous benzylic acetals or ethers avoid the C-H insertion pathway completely and, after hydride transfer, undergo a de-aromatizing elimination reaction to o-QDM at ambient temperature. The resulting dienes undergo a variety of cycloaddition reactions with high diastereo- and regio-selectivity. This is one of the few examples of catalytic generation of o-QDM without the intermediacy of a benzocyclobutene and represents one of the mildest, ambient temperature processes to access these useful intermediates. This proposed mechanism is supported by DFT calculations. Moreover, the methodology was applied to the synthesis of (±)-isolariciresinol in 41% overall yield.

Prior research has shown negative relations between math anxiety and math performance. We posit that one potential pathway through which math anxiety influences performance of math equivalencies is through help seeking behavior during learning. Here, we examine whether middle school students' behavior, specifically the frequency of hint requests, within educational technologies mediates the association between math anxiety and performance of math equivalence. Students completed a pretest measuring their performance of math equivalence and math anxiety prior to the intervention, and a posttest measuring their performance of math equivalence. We examine mediation in two online math learning technologies: From Here to There (FH2T) and ASSISTments. In both FH2T and ASSISTments, students can request hints that provide just-in-time support during problem solving. We examined whether the frequency of hint requests mediates the effects of math anxiety on performance in both conditions. Using multi-group mediation analyses, we found that math anxiety was not a predictor of hint usage in either condition when controlling for pretest performance. Further, we found that students with lower performance at the pretest used more hints in the problem set condition, and using more hints was associated with lower performance of math equivalence at the posttest. This relation was not significant in the FH2T condition, suggesting a fundamental difference in hint usage between the two technologies. These findings have implications for designing educational technologies that simultaneously promote math performance and productive help seeking behaviors in middle school students.

Polysubstituted allenes are useful synthetic intermediates in many applications, offering structural complexity, modularity, and their axial chirality in further transformations. While acyl and alkoxy-substituted allenes are known, there are currently few examples of allenes containing both functionalities and no reports of geminally substituted acyl/alkoxy allenes being isolated and characterized. Herein, we report the synthesis of tetrasubstituted allenes featuring a novel geminal acyl/alkoxy substitution. These unique "push-pull" allenes are bench-stable and exhibit interesting reactivity in several applications.

We developed an interactive online textbook that interleaves R programming activities with text as a way to facilitate students' understanding of statistical ideas while minimizing the cognitive and emotional burden of learning programming. In this exploratory study, we characterize the attitudes and experiences of 672 undergraduate students as they used our online textbook as part of a 10-week introductory course in statistics. Students expressed negative attitudes and concerns related to R at the beginning of the course, but most developed more positive attitudes after engaging with course materials, regardless of demographic characteristics or prior programming experience. Analysis of a subgroup of students revealed that change in attitudes toward R may be linked to students' patterns of engagement over time and students' perceptions of the learning environment.

Panowamycins are a group of isochroman-based natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium-catalyzed C-H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond-forming step. The syntheses are completed without the use of protecting groups and feature a late-stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co-workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM-135, and veramycin F.

Intramolecular C-H insertions with donor/donor dirhodium carbenes provide a concise and highly stereoselective method to set two contiguous stereocenters in a single step. Herein, we report the insertion of donor/donor carbenes into stereogenic carbon centers allowing access to trisubstituted benzodihydrofurans in a single step. This study illuminates, for the first time, the stereochemical impact on the carbene center and delineates the structural factors that enable control over both stereogenic centers. Sterically bulky, highly activated C-H insertion centers exhibit high substrate control yielding a single diastereomer and a single enantiomer of product regardless of the catalyst used. Less bulky, less activated C-H insertion centers exhibit catalyst control over the diastereomeric ratio (dr), where a single enantiomer of each diastereomer is observed with high selectivity. A combination of experimental studies and DFT calculations was used to elucidate the origin of these results. First, hydride transfer from the stereogenic insertion site proceeds with high stereoselectivity to the carbene center, thus determining the absolute configuration of the product. Second, the short lived zwitterionic intermediate can diaster-eoselectively ring-close by a hitherto unreported SE2 mechanism that is either controlled by the substrate or the catalyst. These results demonstrate that donor/donor carbenes undergo uniquely stereoselective reactions that originate from a stepwise reaction mechanism, in contrast to the analogous concerted reactions of carbenes with one or more electron-withdrawing groups attached.

The metal-binding capabilities of the spiropyran family of molecular switches have been explored for several purposes from sensing to optical circuits. Metal-selective sensing has been of great interest for applications ranging from environmental assays to industrial quality control, but sensitive metal detection for field-based assays has been elusive. In this work, we demonstrate colorimetric copper sensing at low micromolar levels. Dimethylamine-functionalized spiropyran (SP1) was synthesized and its metal-sensing properties were investigated using UV-vis spectrophotometry. The formation of a metal complex between SP1 and Cu2+ was associated with a color change that can be observed by the naked eye as low as ≈6 μM and the limit of detection was found to be 0.11 μM via UV-vis spectrometry. Colorimetric data showed linearity of response in a physiologically relevant range (0-20 μM Cu2+) with high selectivity for Cu2+ ions over biologically and environmentally relevant metals such as Na+, K+, Mn2+, Ca2+, Zn2+, Co2+, Mg2+, Ni2+, Fe3+, Cd2+, and Pb2+. Since the color change accompanying SP1-Cu2+ complex formation could be detected at low micromolar concentrations, SP1 could be viable for field testing of trace Cu2+ ions.

Donor/donor carbenes are relatively new in the field of carbene chemistry; although applications in C-H and X-H insertion reactions are few in number, they demonstrate exquisite chemo- and stereo-selectivity. Recent reports have shown that C-H, N-H, B-H, O-H, S-H, Si-H, Ge-H, Sn-H and P-H insertion reactions are feasible with a variety of transition metal catalysts, both inter- and intramolecularly. Furthermore, high degrees of diastereo- and enantioselectivity have been observed in several cases. Methods typically involve the formation of a diazo-based carbene precursor, but procedures using diazo-free metal carbenes have been developed with significant success. This Minireview covers transition-metal catalyzed insertion reactions with donor/donor and donor carbenes, providing context for future developments in this emerging field.