Abstract The geometric phase, originating from cyclic and adiabatic evolutions in parameter space, is central to both quantum and classical systems. In optics, it enables polarization-based control of light and has been widely exploited in birefringent elements. Here we show that, through its interaction with optical valves, light can self-induce a localized geometric phase structure. Molecular reorientation forced by light intensity imprints a confined geometric phase with zero orbital angular momentum on the transmitted beam, revealed through interference. An amplitude equation derived from first principles captures the observed phase fields, with analytical, numerical, and experimental results in close agreement. This establishes a universal framework for light-driven geometric-phase localization, bridging fundamental optics with reconfigurable photonic applications.
Abstract Although urban segregation has been widely studied, how race- and class-based neighborhood differences affect everyday mobility is less understood and in need of consistent metrics. Such social dimensions of travel are not reflected in conventional spatial accessibility measures or theoretical models of intra-urban mobility, potentially omitting an important aspect of travel behavior. Using Census Block Group–level cellphone mobility data from the 498 largest U.S. cities, we examine how differences in social characteristics between neighborhoods are manifested in where people travel within their city. Specifically, we propose a novel time-equivalent measure that expresses how racial and income differences between neighborhoods are associated with reduced travel between them, allowing a quantitative comparison in and across cities. We find that racial differences demonstrate a stronger negative association with cross-neighborhood mobility than income differences—associated with reductions in travel equivalent to adding 17% versus 8% of average travel time. Our findings suggest that human mobility in American cities reflects not only by geographic proximity but also social affinity, with important implications for inequality and access to opportunity.
Abstract Ionotropic glutamate receptors AMPAR and NMDAR are central to synaptic transmission and key targets in neurological disease therapy. Here, we developed a de novo design pipeline combining a generative neural network, AlphaFold2 structural predictions, and molecular dynamics to create short, high-affinity, receptor-selective peptide modulators. The algorithm targets receptor hotspots, optimizing for minimal contact distance and high structural confidence, and avoids mode collapse through position-specific scoring matrix integration. In silico evaluation of top candidates exhibited strong binding affinity, low RMSD fluctuations, and stable hydrogen bonding. Selectivity tests confirmed minimal cross-binding between AMPAR- and NMDAR-specific peptides. Top candidates were synthesized and evaluated in in vitro experiments. In rat cortical and hippocampal cultures, peptides induced robust, concentration-dependent intracellular Ca2+ influx, abolished by extracellular calcium removal or selective antagonists (CNQX, MK-801), thus confirming the positive modulatory action of designed peptides. Cross-inhibition assays demonstrated strict receptor specificity. Although calcium responses were lower than those elicited by conventional ligands (AMPA and NMDA), functional modulation was confirmed. This integrated computational–experimental framework enables efficient development of receptor-specific peptide modulators and offers a promising strategy for therapeutic discovery.
Abstract Chronic inflammatory skin diseases are characterized by epithelial barrier dysfunction and immune dysregulation, yet the epithelial-intrinsic mechanisms that initiate inflammation remain poorly understood. TMEM79 is a dermatitis-associated transmembrane protein expressed in keratinocytes, but how its loss promotes skin disease remains unclear. Here, using keratinocyte-specific Tmem79 conditional knockout (cKO) mice and TMEM79-deficient human keratinocytes, we find that TMEM79 is required for proper epithelial differentiation and barrier formation, and that its loss induces keratinocyte stress and ferroptosis-associated lipid peroxidation. Longitudinal analysis of neonatal and early postnatal Tmem79-deficient skin revealed disrupted epidermal homeostasis and early type I IFN signaling preceding the later emergence of type 17 inflammation. Mechanistically, genetic ablation of Sting1, but not Mavs, ameliorated dermatitis and downstream type 17 inflammation, while IL-17A was required for subsequent epidermal hyperplasia. These findings establish STING-dependent signaling as an upstream driver of skin immune activation and pathology. Together, our findings link early-life epithelial stress to innate immune activation and suggest that targeting lipid peroxidation or STING signaling may help prevent inflammatory skin disease progression.
Abstract Public opinion of hate crimes may be malleable because these acts are understood through victims' varying social identities. We investigate whether violent attacks provoke different reactions when framed around victims' national rather than religious identities. We first document media coverage of hate crimes, showing that more than 20% of headlines about anti-Jewish hate crimes use nationalist frames, invoking Israel. We then analyze discourse surrounding a high-profile anti-Jewish attack and demonstrate the prominence of nationalist framing. In two survey experiments with U.S. adults, we show widespread aversion to religiously motivated violence, but greater ambivalence toward attacks motivated by nationalism. Specifically, opposition to physically violent attacks against Jews weakens when framed through the victim's support for Israel rather than their religious identification. Similarly, opposition to attacks on Muslims and Hindus declines when linked to Palestinian and Indian nationalism, respectively. While Americans display near-universal opposition to religious bigotry, nationalist frames erode public condemnation of identity-based violence.
