In this paper, we analyze the subjective inclusion experiences of visually impaired (VI) adult tennis players from an ableism-critical perspective. The primary focus of this research is the inclusive potential of blind tennis from the perspective of VI individuals. Episodic interviews were conducted to capture subjective perspectives. A qualitative text analysis revealed that the interviewees were confronted with multiple ability assumptions by sighted people in their everyday lives. Deficit notions on the performance of VI people included sports, work, and general activities. Participation in blind tennis helped the interviewees build a "competent identity" and acquire various skills useful for their everyday lives as participation in blind tennis was a pathway for competence in sports. Further research is needed to identify exclusion experiences from the perspective of disabled people to recognize the potential of different sports in reducing barriers to participation.

While it is known that associative memory is preferentially encoded by memory-eligible "primed" neurons, in vivo neural activity hierarchy has not been quantified and little is known about how such a hierarchy is established. Leveraging in vivo calcium imaging of hippocampal neurons on freely behaving mice, we developed the first method to quantify real-time neural activity hierarchy in the CA1 region. Neurons on the top of activity hierarchy are identified as primed neurons. In cilia knockout mice that exhibit severe learning deficits, the percentage of primed neurons is drastically reduced. We developed a simplified neural network model that incorporates simulations of linear and non-linear weighted components, modeling the synaptic ionic conductance of AMPA and NMDA receptors, respectively. We found that moderate non-linear to linear conductance ratios naturally leads a small fraction of neurons to be primed in the simulated neural network. Removal of the non-linear component eliminates the existing activity hierarchy and reinstate it to the network stochastically primes a new pool of neurons. Blockade of NMDA receptors by ketamine not only decreases general neuronal activity causing learning impairments, but also disrupts neural activity hierarchy. Additionally, ketamine-induced super-synchronized slow oscillation during anesthesia can be simulated if the non-linear NMDAR component is removed to flatten activity hierarchy. Together, this study develops a unique method to measure neural activity hierarchy and identifies NMDA receptors as a key factor that controls the hierarchy. It presents the first evidence suggesting that hierarchy disruption by NMDAR blockade causes dissociation and psychosis.

Hydroxymethanesulfonate (HMS) in fine aerosol particles has been reported at significant concentrations along with sulfate under extreme cold conditions (-35 °C) in Fairbanks, Alaska, a high latitude city. HMS, a component of S(IV) and an adduct of formaldehyde and sulfur dioxide, forms in liquid water. Previous studies may have overestimated HMS concentrations by grouping it with other S(IV) species. In this work, we further investigate HMS and the speciation of S(IV) through the Alaskan Layered Pollution and Chemical Analysis (ALPACA) intensive study in Fairbanks. We developed a method utilizing hydrogen peroxide to isolate HMS and found that approximately 50% of S(IV) is HMS for total suspended particulates and 70% for PM2.5. The remaining unidentified S(IV) species are closely linked to HMS during cold polluted periods, showing strong increases in concentration relative to sulfate with decreasing temperature, a weak dependence on particle water, and similar particle size distributions, suggesting a common aqueous formation process. A portion of the unidentified S(IV) may originate from additional aldehyde-S(IV) adducts that are unstable in the water-based chemical analysis process, but further chemical characterization is needed. These results show the importance of organic S(IV) species in extreme cold environments that promote unique aqueous chemistry in supercooled liquid particles.

The allosteric inhibition of insulin-like growth factor receptor 1 kinase (IGF1RK) is a potential strategy to overcome selectivity barriers for targeting receptor tyrosine kinases. We constructed structural models of a series of 12 indole-butyl-amine derivatives that have been reported as allosteric inhibitors of IGF1RK. We further studied the dynamics and interactions of each inhibitor in the allosteric pocket via all-atom explicit-solvent molecular dynamics (MD) simulations. We discovered that a bulky carbonyl substitution at the R1 indole ring is structurally unfavorable for inhibitor binding in the IGF1RK allosteric pocket. Moreover, we found that the most potent derivative (termed C11) acquires a distinct conformation: forming an allosteric pocket channel with better shape complementarity and interactions with the receptor. In addition to a hydrogen-bonding interaction with V1063, the cyano derivative C11 forms a stable hydrogen bond with M1156, which is responsible for its unique binding conformation in the allosteric pocket. Our findings show that the positioning of chemical substituents with different pharmacophore features at the R1 indole ring influences molecular interactions and binding conformations of indole-butyl-amine derivatives and, hence, dramatically affects their potencies. Our results provide a structural framework for the design of allosteric inhibitors with improved affinities and specificities against IGF1RK.

We consider the problem of simultaneously managing capacity, inventory and backorders in a multi-mode production environment modelled via Brownian motion. The presence of more than two production modes adds an additional level of complexity: not just when to change modes, but also which mode to change to. We show that, under the two assumptions that demand is the overriding source of variability in the process and that the cost to change from one production mode to another is proportional to the difference in the production capacities, a policy that moves stepwise among the modes minimizes the long-run average cost. Examples demonstrate that if either assumption is violated no policy that moves stepwise among the modes may be optimal. To focus on the complexity of identifying when to change modes and which mode to change to, we restrict our model to simple convex holding and backorder costs and linear processing costs and costs for rejecting demand and idling capacity. We adopt the economic average cost model that allows the manager to reject demand or idle capacity at any time. We demonstrate that under our two assumptions we may impose an ordering assumption on the relative value functions that dramatically simplifies the classic Hamilton-Jacobi-Bellman equations. We show that under the economic average cost model a production mode that is initially unattractive may later become attractive as new modes are added. Our arguments are essentially constructive and lead to a practical algorithm for finding an optimal policy.

This paper responds to the call made by mobilities scholars to deepen attention to imagination and imaginaries by proposing that oneiric experiences – nighttime dreams – be investigated as significant but under-examined artifacts of mobile cultures. Based on a long-term, ethnographically-informed study of the dreams of young adults in the US and grounded in both contemporary dream theory and the automobilities literature, I argue that dreams of car trouble serve to expose otherwise overlooked and taken-for-granted dimensions of waking-life automobility, automotive consciousness, and lifecourse transitions. Targeting two commonly seen themes within this subgenre of dreams – that of failed brakes and driving from the backseat – I argue that oneiric automobility draws on conceptual metaphors and waking-life automotive biographies. Such dreams, moreover, draw liberally from and comment on larger and often silenced dimensions of emerging automobility – the patterned processes and performances by which (usually young) adults habituate to their lives as drivers. Attention to the common experience of driving while dreaming, I argue, enhances efforts to theorize the multiple ontologies of mobile lifeways.

In chaos control, one usually seeks to stabilize the unstable periodic orbits (UPOs) that densely inhabit the attractors of many chaotic dynamical systems. These orbits collectively play a significant role in determining the dynamics and properties of chaotic systems and are said to form the skeleton of the associated attractors. While UPOs are insightful tools for analysis, they are naturally unstable and, as such, are difficult to find and computationally expensive to stabilize. An alternative to using UPOs is to approximate them using cupolets. Cupolets, a name derived from chaotic, unstable, periodic, orbit-lets, are a relatively new class of waveforms that represent highly accurate approximations to the UPOs of chaotic systems, but which are generated via a particular control scheme that applies tiny perturbations along Poincaré sections. Originally discovered in an application of secure chaotic communications, cupolets have since gone on to play pivotal roles in a number of theoretical and practical applications. These developments include using cupolets as wavelets for image compression, targeting in dynamical systems, a chaotic analog to quantum entanglement, an abstract reducibility classification, a basis for audio and video compression, and, most recently, their detection in a chaotic neuron model. This review will detail the historical development of cupolets, how they are generated, and their successful integration into theoretical and computational science and will also identify some unanswered questions and future directions for this work.

The ATPase family AAA+ domain containing 2 (ATAD2) protein and its paralog ATAD2B have a C-terminal bromodomain (BRD) that functions as a reader of acetylated lysine residues on histone proteins. Using a structure-function approach, we investigated the ability of the ATAD2/B BRDs to select acetylated lysine among multiple histone post-translational modifications. The ATAD2B BRD can bind acetylated histone ligands that also contain adjacent methylation or phosphorylation marks, while the presence of these modifications significantly weakened the acetyllysine binding activity of the ATAD2 BRD. Our structural studies provide mechanistic insights into how ATAD2/B BRD-binding pocket residues coordinate the acetyllysine group in the context of adjacent post-translational modifications. Furthermore, we investigated how sequence changes in amino acids of the histone ligands impact the recognition of an adjacent acetyllysine residue. Our study highlights how the interplay between multiple combinations of histone modifications influences the reader activity of the ATAD2/B BRDs, resulting in distinct binding modes.