Abstract As scientific projects and labs benefit from increasingly interdisciplinary expertise, students and trainees find themselves navigating a myriad of academic spaces, each with its own workplace culture and demographics. A clear example is the interdisciplinary field of optics and biological microscopy which bridges biology, physics and engineering. While Biology PhDs are now >50% women, men in physics and engineering fields still significantly outnumber women, resulting in an imbalance of gender representation among microscopists and other ‘tool innovators’ in the interdisciplinary field of biological microscopy and biomedical optics. In addition to the cultural and cognitive whiplash that results from disparate representation between fields such as Biology, Engineering, and Physics, indifference from institutional leaders to implement equity‐focused initiatives further contributes to cultures of exclusion, rather than belonging, for women. Here we elaborate on the motivation, structure, and outcomes of building a specific affinity‐based bootcamp as an intervention to create an inclusive, welcoming learning environment for women in optics. Considering the presence of nonbinary, trans and other gender minoritised scientists, we recognise that women are not the only gender group underrepresented in biological microscopy and biomedical optics; still, we focus our attention on women in this specific intervention to improve gender parity in biological microscopy and biomedical optics. We hope that these strategies exemplify concrete paths forward for increasing belonging in interdisciplinary fields, a key step towards improving and diversifying graduate education.
Dengue virus (DENV) is a mosquito-borne disease that poses a public health threat to sub/tropical areas worldwide. Vaccination drives require differential diagnosis of serotype-specific DENV exposure to reduce severe dengue risks, yet state-of-the-art DENV serology relies upon short-lived serotype-specific IgM or labor intensive neutralization assays. The need for high-throughput differential diagnosis is met with our multiSero platform (Byrum et al.), a screening technique capable of detecting 48 antigen-antibody pairs simultaneously, demonstrating utility for population-wide screening. Through machine-vision techniques, we quantify and classify antibody-response signals with high sensitivity to develop automated analysis pipelines capable of diagnosing serotype-specific DENV exposure.
Much work has been done to characterize the reasoning of students as they solve mathematics-intensive problems and characterizing differences in expert and novice problem solving. In this work, we characterize the problem-solving strategies in a classroom setting of "transitioning novices," students who have completed an introductory physics course and have learned some problem-solving strategies, but are far from expertlike in their reasoning. We find that students mostly use intermediate strategies that reflect an understanding of specific relationships between quantities, such as analyzing the units of an expression, to reason about mathematical expressions. Few students use more sophisticated strategies like checking limits, which require students to run mental simulations to predict how a system will behave as different physical variables are changed. The teaching of more advanced strategies like limit checking will require careful scaffolding of the cognitive complexity, as students generally do not succeed when simply told to check limits. This is supported by the findings of Lin and Singh [Phys. Rev. Phys. Educ. Res. 7, 020104 (2011)] that careful scaffolding is needed to help students solve more complex problems. In this particular group, students were able to successfully analyze the dimensions of an expression and compute component forces and torques to check if their answer made sense. Our results show that there is a need to recognize and teach these intermediary strategies to enable more novice students to check their answers and encourage students to become more expertlike.Received 20 August 2020Accepted 19 October 2020DOI:https://doi.org/10.1103/PhysRevPhysEducRes.16.020134Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasScientific reasoning & problem solvingPhysics Education Research
In a previous study, we found that students' incoming preparation in physics—crudely measured by concept inventory prescores and math SAT or ACT scores—explains 34% of the variation in Physics 1 final exam scores at Stanford University. In this study, we sought to understand the large variation in exam scores not explained by these measures of incoming preparation. Why are some students’ successful in physics 1 independent of their preparation? To answer this question, we interviewed 34 students with particularly low concept inventory prescores and math SAT/ACT scores about their experiences in the course. We unexpectedly found a set of common practices and attitudes. We found that students’ use of instructional resources had relatively little impact on course performance, while student characteristics, student attitudes, and students’ interactions outside the classroom all had a more substantial impact on course performance. These results offer some guidance as to how instructors might help all students succeed in introductory physics courses.
A multiplexed enzyme-linked immunosorbent assay (ELISA) that simultaneously measures antibody binding to multiple antigens can extend the impact of serosurveillance studies, particularly if the assay approaches the simplicity, robustness, and accuracy of a conventional single-antigen ELISA. Here, we report on the development of multiSero, an open-source multiplex ELISA platform for measuring antibody responses to viral infection. Our assay consists of three parts: (1) an ELISA against an array of proteins in a 96-well format; (2) automated imaging of each well of the ELISA array using an open-source plate reader; and (3) automated measurement of optical densities for each protein within the array using an open-source analysis pipeline. We validated the platform by comparing antibody binding to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigens in 217 human sera samples, showing high sensitivity (0.978), specificity (0.977), positive predictive value (0.978), and negative predictive value (0.977) for classifying seropositivity, a high correlation of multiSero determined antibody titers with commercially available SARS-CoV-2 antibody tests, and antigen-specific changes in antibody titer dynamics upon vaccination. The open-source format and accessibility of our multiSero platform can contribute to the adoption of multiplexed ELISA arrays for serosurveillance studies, for SARS-CoV-2 and other pathogens of significance.
Raman optical spectroscopy promises label-free bacterial detection, identification, and antibiotic susceptibility testing in a single step. However, achieving clinically relevant speeds and accuracies remains challenging due to weak Raman signal from bacterial cells and numerous bacterial species and phenotypes. Here we generate an extensive dataset of bacterial Raman spectra and apply deep learning approaches to accurately identify 30 common bacterial pathogens. Even on low signal-to-noise spectra, we achieve average isolate-level accuracies exceeding 82% and antibiotic treatment identification accuracies of 97.0±0.3%. We also show that this approach distinguishes between methicillin-resistant and -susceptible isolates of Staphylococcus aureus (MRSA and MSSA) with 89±0.1% accuracy. We validate our results on clinical isolates from 50 patients. Using just 10 bacterial spectra from each patient isolate, we achieve treatment identification accuracies of 99.7%. Our approach has potential for culture-free pathogen identification and antibiotic susceptibility testing, and could be readily extended for diagnostics on blood, urine, and sputum.
Abstract The flexibility of tethered molecules, such as those bound to biological membranes, is an important property that can influence molecular height, mobility, and accessibility. However, quantifying the flexibility of surface-tethered biomolecules in aqueous environments has been difficult due to a lack of experimental tools. Here we introduce SurFlex microscopy, a method based on fluorescence anisotropy that exploits the relationship between the conformational dynamics of a tethered molecule and the rotational diffusion of an attached fluorophore to extract information about molecular flexibility. By analyzing the polarization state of photons emitted after polarized excitation, we quantify apparent molecular flexibilities that include effects of tethering, self-interactions and buffer conditions. We first demonstrate the capabilities of SurFlex microscopy by measuring the flexibility of bilayer-tethered single-stranded DNA (ssDNA) of different lengths and nucleotide sequences. We find that sequence significantly impacts ssDNA flexibility, consistent with theoretical estimates, with weak intramolecular interactions in random sequences leading to higher apparent stiffness. Interestingly, we show that a pathological DNA sequence linked to Huntington’s disease exhibits unusual flexibility despite intramolecular interactions. We next extend SurFlex microscopy to live cells by measuring surface glycoprotein flexibility on red blood cells using fluorescent lectins. We show that trypsinization decreases glycan fluctuations, demonstrating that modifications to the cell surface can alter the flexibility of remaining surface molecules. SurFlex microscopy provides a new tool for quantifying molecular flexibility that can be used to study the role of tethered surface molecules in fundamental biological processes. Significance statement Biomolecules immobilized on one end play crucial roles in diverse cellular processes, from cell-cell signaling through surface receptors to the formation of DNA secondary structures. However, measuring biomolecular flexibility on surfaces has remained challenging. Here we present SurFlex microscopy, a technique that uses fluorescence anisotropy to quantify the flexibility of surface-anchored molecules. By analyzing the rotational dynamics of fluorophores attached to the ends of fluctuating biomolecules, SurFlex microscopy can be used to quantify persistence length. We demonstrate its capabilities by measuring sequence-dependent flexibility of DNA and crowding-dependent changes in glycan flexibility on native cell surfaces. This method opens new avenues for understanding how biomolecular flexibility influences key biological processes, such as those at cell surfaces during cell-cell contact formation and subsequent signaling.
Abstract Reflecting on one’s solution is widely recognized as an important part of the problem-solving process, though the cognitive processes underlying this action are not well understood. In previous work, we identified certain strategies students used while reflecting on a solution but found that strategies most often used by experts were not often used by students and were often used incorrectly. In this paper, we present the results of a study that more carefully examines why this could be the case. We conducted think-aloud interviews with students from a variety of physics backgrounds and asked them to check the answer to a particular static equilibrium problem (there were two different problems, but each student saw only one). We found that students’ strategy use varied both by problem features and level of experience. We found students’ epistemological framing to be more stable across problem-difficulty but still correlated with experience. We further noticed more frequent shifting of epistemological frames among intermediate students. Altogether, the results point to an epistemological transition from solution reflection as an algorithmic procedure to be performed using whatever strategy is most useful, to a conceptual procedure more aligned with sense-making as students gain more experience with physics. This will be useful for instructors when thinking about the best ways to encourage novice students to engage in meaningful solution reflection or mathematical sense-making more broadly.
