Swarthmore College

Federal administrative agencies have been having a rough time in the Supreme Court, with environmental regulations a particular recent target. And on June 28, 2024, the Court struck an even more significant blow to administrative agencies and the regulations they have promulgated in Loper Bright v. Raimondo and Relentless v. Department of Commerce.

Cochlear implants (CI) are a highly successful neural prosthesis that can restore hearing in individuals with sensorineural hearing loss. However, the extent of hearing restoration varies widely. Two major factors likely contribute to poor performance: (1) the distances between electrodes and surviving spiral ganglion neurons and (2) the density of those neurons. Reprogramming the CI at a poor electrode-neuron interface, using focused tripolar stimulation or remapping the electrodes, would benefit from understanding the cause of the poor interface. We used a cochlear model with simplified geometry and neuronal composition to investigate how the interface affects stimulation thresholds. We then inverted the model to infer electrode distance and neuronal density from monopolar and tripolar threshold values obtained behaviorally. We validated this inverted model for known scenarios of electrode distance and neuronal density. Finally, we assessed the model using data from 18 CI users whose electrode distances were measured from CT imaging. The inverted model accurately inferred electrode distance and neuronal density for known scenarios. It also reliably reproduced behavioral monopolar and tripolar threshold profiles for CI users, with mean prediction errors within 1 dB for 17/18 subjects. Fits of electrode distance were more variable; accuracy depended on the assumed value of temporal bone resistivity. Twelve subjects had minimum distance error (0.31 mm) using low resistivity (70 Ω-cm) while the others had better fits (0.30 mm) with higher resistivity (250 Ω-cm). This inverted model shows promise as a simple, practical tool to better assess and understand the electrode-neuron interface.

For aquatic and semi-aquatic vertebrates like amphibians, it is possible to estimate excreted hormone levels using non-invasive methods such as waterborne and salivary sampling. These techniques allow monitoring of endocrine activity over varying, repeated and simultaneous integration periods while minimizing handling-related stress that can ‘contaminate’ hormone estimates, including estimates of baseline glucocorticoids. Here we have validated the extraction and quantification of three steroid hormones (corticosterone, CORT; 17-b estradiol, E2; testosterone, TST) in Couch’s spadefoots (Scaphiopus couchii)—a desert-adapted anuran of special interest for physiology, evolution and conservation—using non-invasive waterborne and minimally invasive salivary hormone methods. We combined extraction and enzyme immunoassay methods to conduct conventional technical validations of parallelism, recovery and time-course. Next, we carried out biological validations by testing the correlation between excreted and circulating concentrations and conducting pharmacological challenges. We found that all three hormones can be precisely estimated from 60-min water baths, exhibit robust parallelism, and have high recoveries. Further, we demonstrated that secretory responses to pharmacological challenges can be detected in waterborne CORT in male and female frogs; in TST and E2 in male frogs, but not consistently for TST or E2 in female frogs. Lastly, plasma hormone concentrations were consistently correlated with their waterborne complements for CORT (both sexes), as well as TST and E2 in males (but not females). Plasma CORT was also positively correlated with salivary CORT. Together, our findings suggest that sampling waterborne and salivary hormones offers a minimally invasive method that field endocrinologists and conservation physiologists can use to obtain biologically informative endocrine estimates from desert-adapted amphibians.

MagNetUS is a network of scientists and research groups that coordinates and advocates for fundamental magnetized plasma research in the USA. Its primary goal is to bring together a broad community of researchers and the experimental and numerical tools they use in order to facilitate the sharing of ideas, resources and common tasks. Discussed here are the motivation and goals for this network and details of its formation, history and structure. An overview of associated experimental facilities and numerical projects is provided, along with examples of scientific topics investigated therein. Finally, a vision for the future of the organization is given.

Member state participation is essential in global governance, affording international organizations (IOs) legitimacy and translating member state preferences into institutional attention. We contend that institutional leadership positions bolster states’ authority via “proxy representation,” in which states are grouped together and indirectly represented by one leader. We argue that by serving as proxy group leaders, even relatively weak states can obtain greater influence in IOs. We examine these expectations in the context of the IMF’s Executive Board, where wealthy states represent themselves directly while other states belong to multi-member constituencies in which leadership often rotates among members. Focusing on issues related to climate change discussions at the IMF—a key concern for Global South countries and an increasingly important issue in international finance—we examine the extent to which countries’ preferences over climate issues are expressed at IMF Board meetings. Using textual data based on 52,551 internal IMF documents from 1987-2017, we find evidence to support our theoretical expectations; states more effectively advance their preferences when they are proxy leaders — this finding holds robustly even for otherwise weak states. These results suggest that even in IOs with highly asymmetric decision-making, weaker states can gain voice through proxy representation. This has important and positive implications for IO legitimacy, as member state participation is integral to the livelihood of these institutions.

The apparent sizes of horizontal and vertical lines show an anisotropy known as the horizontal vertical illusion (HVI) wherein vertical lines appear to be longer than their horizontal counterparts. Whereas a typical HVI comparing vertical and horizontal lines in a plane produces a 5–10% illusion, a much larger-scale illusion (15–25%) is often found for large objects in the real world, and this has been related to differential angular exaggerations in perceived elevation (vertical) and azimuthal (horizontal) direction. Recently supine observers in virtual environments were found to show larger exaggerations in perceived azimuth than upright observers. Here, 48 participants were tested in both supine and upright postures in an outdoor environment while matching fairly small physical extents in the real world. They adjusted the magnitude of the horizontal extent to perceptually match fairly small vertical poles (0.7–1.3 m tall) that were either presented at the same viewing distance as the matching extent or in a different depth plane, so that size at a distance had to be compared. Supine observers viewed the scene, as though upright, through a large mirror mounted overhead at 45° that was adjusted to approximate their normal eye height. When the matcher extent was at a different distance than the pole, horizontal extent matches typically exceeded the actual pole height by about 15% or more, whether the viewer was upright or supine. The average overestimation was only about 10% when the matching extent was at the same distance. Despite the similarity in performance across different postures for spatial matching, supine observers gave much higher explicit estimates of azimuthal direction than upright observers. However, although the observation of exaggeration in perceived azimuth for supine observers was replicated in a second study with 24 additional participants using a mirror with a smaller (more normal) aspect ratio, the magnitude of the exaggeration seemed to be greatly reduced when the field of view of the apparatus had a more typical aspect ratio. This suggests that the unusually large exaggeration of azimuth found in a previous report with supine observers may have been caused by the unusually large aspect ratio of the viewing apparatus used.

The N-terminal ectodomain of the influenza A M2 protein is a target for universal influenza vaccine development and novel antiviral strategies. Despite the significance of this domain, it is poorly understood and most structural studies of the M2 protein have disregarded the N-terminal ectodomain in their analyses. Here, we report conformational properties and describe insights into the membrane topology of sites along the N-terminal ectodomain. Full-length M2 protein is embedded in lipid bilayer nanodiscs and studied using site-directed spin labeling electron paramagnetic resonance spectroscopy. Results are consistent with a turn in the middle of the ectodomain that changes in proximity to the membrane surface upon the addition of cholesterol or the antiviral drug rimantadine. Similarly to other domains of M2 protein, lineshape analysis suggests that the N-terminal ectodomain can adopt multiple conformations.

Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism. Organismal behavioral testing is needed to fill the gap, but mammalian studies are too time-consuming and cost-prohibitive for the early stages of drug discovery. Behavioral medium-throughput screening (MTS) in small organisms promises to address this need and complement in silico and in vitro HTS to improve the discovery of novel neuroactive compounds. Here, we used cheminformatics and MTS in the freshwater planarian Dugesia japonica–an invertebrate system used for neurotoxicant testing–to evaluate the extent to which complementary insight could be gained from the two data streams. In this pilot study, our goal was to classify 19 neuroactive compounds into their functional categories: antipsychotics, anxiolytics, and antidepressants. Drug classification was performed with the same computational methods, using either physicochemical descriptors or planarian behavioral profiling. As it was not obvious a priori which classification method was most suited to this task, we compared the performance of four classification approaches. We used principal coordinate analysis or uniform manifold approximation and projection, each coupled with linear discriminant analysis, and two types of machine learning models–artificial neural net ensembles and support vector machines. Classification based on physicochemical properties had comparable accuracy to classification based on planarian profiling, especially with the machine learning models that all had accuracies of 90–100%. Planarian behavioral MTS correctly identified drugs with multiple therapeutic uses, thus yielding additional information compared to cheminformatics. Given that planarian behavioral MTS is an inexpensive true 3R (refine, reduce, replace) alternative to vertebrate testing and requires zero a priori knowledge about a chemical, it is a promising experimental system to complement in silico cheminformatics to identify new drug candidates.

This study combines experimental techniques and mathematical modeling to investigate the dynamics of C. elegans body-wall muscle cells. Specifically, by conducting voltage clamp and mutant experiments, we identify key ion channels, particularly the L-type voltage-gated calcium channel (EGL-19) and potassium channels (SHK-1, SLO-2), which are crucial for generating action potentials. We develop Hodgkin-Huxley-based models for these channels and integrate them to capture the cells’ electrical activity. To ensure the model accurately reflects cellular responses under depolarizing currents, we develop a parallel simulation-based inference method for determining the model’s free parameters. This method performs rapid parallel sampling across high-dimensional parameter spaces, fitting the model to the responses of muscle cells to specific stimuli and yielding accurate parameter estimates. We validate our model by comparing its predictions against cellular responses to various current stimuli in experiments and show that our approach effectively determines suitable parameters for accurately modeling the dynamics in mutant cases. Additionally, we discover an optimal response frequency in body-wall muscle cells, which corresponds to a burst firing mode rather than regular firing mode. Our work provides the first experimentally constrained and biophysically detailed muscle cell model of C. elegans, and our analytical framework combined with robust and efficient parametric estimation method can be extended to model construction in other species.

It has been argued that the incidental and arbitrary use of gender markings for inanimate concepts in language may affect the conceptualization or semantics of those inanimate concepts. The present article sought to replicate the findings of a classic paper that made this argument. Konishi used the potency dimension of the semantic differential method as an implicit measure of perceived gender. He reported that words for inanimate concepts of masculine grammatical gender were rated as higher in potency than words for the same concepts that had feminine grammatical gender. Two preregistered replication studies are reported here. The first was a conceptual replication of Konishi’s study that was conducted with 240 bilingual native speakers of either German or Spanish. Included in the study was a follow-up with 120 monolingual native English speakers. This data was used to test whether the grammatical gender in the native languages of German and Spanish speakers affected their sense of the potency of common inanimate categories when tested in a second language (English) in which they were fluent and the nouns had no grammatical gender. A second version of the study was conducted in the native languages of Spanish and German speakers, as a closer attempt at a replication of Konishi’s original study. The results of both studies provided evidence against the grammatical-gender hypothesis. Bayesian tests of both studies strongly favored the null hypothesis that there were no grammatical gender effects on implicit measures of perceived potency.