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Mouse sensorimotor cortex reflects complex kinematic details during reaching and grasping
No full textCoordinated forelimb actions, such as reaching and grasping, rely on motor commands that span a spectrum from abstract target selection to detailed instantaneous muscle control. The sensorimotor cortex is central to controlling these complex movements, yet how the detailed command signals are distributed across its numerous subregions remains unclear. In particular, in mice, it is unknown if the primary motor (M1) and somatosensory (S1) cortices represent low-level joint angle details in addition to high-level signals like movement direction. Here, we combine high-quality markerless tracking and two-photon imaging during a reach-to-grasp task to quantify movement-related activity in the mouse forelimb M1 (M1-fl) and forelimb S1 (S1-fl). Linear decoding models reveal a strong representation of proximal and distal joint angles in both areas, and both areas support joint angle decoding with comparable fidelity. Despite shared low-level encoding, the time course of high-level target-specific information varied across areas. M1-fl exhibited early onset and sustained encoding of target-specific signals, while S1-fl was more transiently modulated around lift onset. These results reveal both shared and unique contributions of M1-fl and S1-fl to reaching and grasping, implicating a more distributed cortical circuit for mouse forelimb control than has been previously considered.</p
Lepton flavor violation: From muon decays to muon colliders
No full textWe investigate the unique potential of a high-energy muon collider to probe lepton-flavor-violating signals arising from physics beyond the Standard Model (SM). Low-energy, precision searches for charged lepton flavor violation (LFV) are projected to dramatically improve their sensitivity in the coming years and could provide the first evidence of new physics. We interpret the sensitivity of these searches in terms of a set of LFV operators in the SM effective field theory. The same operators are then probed at the TeV scale via new, high-energy processes only available at a high-energy muon collider, such as → or the scattering of a muon of an electroweak gauge boson into LFV final states. We find that, for most operators, a muon collider could confirm signals if they are seen at future low-energy experiments, whereas for certain flavor combinations it extends the reach to scales well beyond those accessible at lower energies. We also project the sensitivity of a muon collider to lepton-flavor-violating decays of the SM Higgs boson and demonstrate improved sensitivity to ℎ → and ℎ → by an order of magnitude compared to the High-Luminosity LHC. The importance of having multiple, complementary probes is illustrated by considering both various combinations of operators and relative sizes of flavor-violating transitions between generations under various assumptions for the flavor structure of new physics
Generation and Maintenance of Motor Neuron Identity Through the Intersection of HOX/PBX and Terminal Selector Functions
No full textAnimals rely on many different types of motor neurons to generate precise and flexible movements, but how these neuron subtypes are specified remains an open question. Here, we examine how the highly conserved family of developmental genes called Hox genes, together with their cofactors, help define distinct spatial motor neuron identities in the nervous system of the nematode Caenorhabditis elegans. We find that different Hox genes act in specific anteroposterior regions of the ventral nerve cord to either positively or negatively regulate motor neuron terminal identity genes. First, in anterior motor neurons, certain Hox genes work together with a cofactor called PBX and a neuron-type-specific regulator (UNC-3) to activate genes required for proper motor neuron function. Second, a posterior midbody Hox gene suppresses these genes in posterior midbody neurons, while a more posterior Hox gene activates a unique set of genes in lumbar motor neurons through a different mechanism. Third, we show that some Hox genes and PBX are needed not only during early development but also later in life to maintain motor neuron identity. Together, our findings reveal how combinations of Hox genes and cofactors generate and preserve motor neuron diversity across the anterior-posterior axis, providing insight into general principles of nervous system development
Design, Synthesis, and Characterization of Atomically Precise Graphene Nanoribbons via Bottom-Up Strategies
No full textGraphene nanoribbons represent a unique class of one-dimensional carbon nanomaterials whose electronic, optical, and magnetic properties are governed by atomic-scale structural parameters, including width, edge topology, length, and chemical composition. Unlike bulk graphene, which lacks an intrinsic band gap, GNRs exhibit tunable band gaps and emergent quantum phenomena arising from lateral quantum confinement and edge effects, rendering them promising candidates for next-generation nanoelectronic and optoelectronic devices. However, the realization of these properties in functional materials critically depends on synthetic approaches capable of delivering atomically precise structures with strict control over ribbon geometry and chemical uniformity. This dissertation focuses on the bottom-up synthesis of graphene nanoribbons as a strategy to overcome the limitations of conventional top-down fabrication methods, which often suffer from structural disorder, edge roughness, and poor reproducibility. Using our own Protecting Group Assisted Iterative Synthetic (PAIS) bottom-up approach enabled the programmed construction of GNRs from rationally designed molecular precursors, allowing precise control over ribbon width, edge structure, heteroatom incorporation, and length. Both solution-phase and surface-assisted synthetic methodologies are explored, with a delicate interplay between the two methods producing interesting scaffolds not previously reported in the literature. Through the development and optimization of these synthetic routes, this work demonstrates the preparation of atomically precise armchair graphene nanoribbons with well-defined widths and narrow band gaps, as well as structurally complex architectures incorporating heterojunctions, edge modulation, and functional substituents. Comprehensive structural and electronic characterization is carried out using a combination of spectroscopic, microscopic, and computational techniques, including nuclear magnetic resonance spectroscopy, mass spectrometry, scanning tunneling microscopy, and electronic structure calculations. These studies elucidate the relationships between molecular design, on-surface reaction pathways, and the resulting electronic and optoelectronic properties of the nanoribbons
Toward a Next-Generation Measurement of the Electron Electric Dipole Moment
No full textOver the past decades, measurements of the electron electric dipole moment (eEDM, de) have emerged as a powerful probe of physics beyond the Standard Model. The current best limit, |de| < 4.1×10−30 e·cm, set by the JILA EDM experiment, improves upon the previous ACME II result by a factor of two. This thesis presents the progress and developments of the ACME III experiment, which aims to further improve the sensitivity to de by an additional order of magnitude. Such an improvement will enable probes of new physics at the 10 TeV scale and beyond using a tabletop experiment. To achieve this target sensitivity, several major upgrades have been implemented in ACME III. These include engineering efforts to increase the molecular flux, extend the spin precession time, and improve the readout efficiency. In parallel, new engineering controls have been developed to mitigate known sources of systematic error. This thesis describes these upgrades in detail and documents the progress made toward understanding and controlling systematic effects
Molecular Dynamics of Potassium Channels: Ion Conduction and Activation
No full textPotassium (K+) ion channels are molecular machines in cells that catalyze the efficient transport of ions across the cell's low dielectric lipid bilayer. It is well understood that K+ ion channels are gated through several mechanisms, such as transmembrane potential, ligands, or mechanical force. In particular, the conserved inverted teepee structure of ion channels and the makings of the ion conducting pathway lend to a belief that structure and function are highly conserved among K+ channels. Thus, the approach in molecular dynamics (MD) simulation studies of K+ channels is to study simple channels containing conserved components to infer channel properties. Although the field of theoretical and computational models of K+ channels is rich, there are details that remain unresolved. For example, the microscopic mechanistic details of how ions cross the ion conduction pathway, as well as the molecular details of the activation mechanism of voltage-gated K+ channels are yet to be fully understood. Thus, the work presented in this dissertation details an increased understanding of the multi-ion conduction mechanism of K+ channels, revealed from MD simulations of a given force field. We show that small changes, on the order of kBT, to the key microscopic interactions that occur at the ion conduction pathway affect its occupancy. Then, we show how the occupancy is affected by the details of the force field and importantly the magnitude of the transmembrane potential. Next, we formulate an approach to estimate the K+ channel conductance at small physiologically-relevant transmembrane potentials using Green-Kubo linear response theory. Then, we formulate an expanded Markov State Model (MSM) and transition path theory (TPT) framework that addresses the challenges in representing the dynamics of systems with indefinite number of reaction pathways, such as ion channels. Using this expanded MSM/TPT framework, we gain new insight into the mechanistic details of the multi-ion conduction mechanism of K+ channels. Lastly, we provide insight into the voltage-dependent activation mechanism of a voltage-activated K+ ion channel
Linking Genetic Variants to Complex Traits with Single-cell Genomics and RNA Modification
No full textGenome-wide association studies have extensive success on identifying genetic variants associated with complex traits and diseases. However, the underlying molecular mechanisms are mostly unknown. Though many efforts on linking variants to functions have been through functional fine-mapping, colocation of expression QTLs with GWAS, etc., there are limitations in each approach. We aimed to fill the gaps by taking two emerging directions in the field - single-cell genomics and RNA modification. For the first of direction, we profiled single-cell multiomics on lung lymphocytes and integrated them with GWAS to identify asthma risk genes and their cell-type specific functions. We were able to identify distinct transcriptomes for lungs by cell type, but the differences in chromatin accessibility were subtle. We further identified open chromatin regions (OCRs) in each lung immune cell type and showed their unique contributions to asthma heritability beyond commonly used OCRs in blood immune cells. Using the lung OCRs and previously fine-mapped variants for COA and AOA, we identified 43 cis-regulatory elements (CREs) likely contributing to asthma risk. We also mapped target genes of 34 of these CREs and found they collectively showed evidence of being disease causing, based on gene functions. We highlighted two genes, CCR4 and LRRC32 with their supporting variants that show enhancer activity in specific lung immune cell types. Lastly, we built cell-type level gene regulatory networks (GRNs), which shed light on the regulation of gene expression in disease through several asthma risk genes that are TFs. Our results demonstrate the utility of single-cell multiomics in interpretating GWAS risk loci. For the second direction, we investigated the role of one type of mRNA modification – N6-adenosine (m6A) in human genetics. We curated m6A peaks from various cell lines and tissues and systematically assessed their contribution to the heritability of a wide range of complex traits and diseases. Overall, we observed broad enrichment of m6A peaks in trait heritability. To identify putative causal variants with potential m6A-mediated roles, we leveraged m6A peaks to annotate published fine-mapped data. The resulting high-confident SNPs in m6A peaks were mostly non-coding and their likely downstream effects were on RNA processing. Lastly, we leveraged published m6A-QTL datasets to nominate risk genes for immune-related traits. We discovered 4 to 13 genes per trait, and they together were strongly enriched for type I interferon signaling. All these results together thus supported mediating roles of m6A to diverse traits and diseases
Paul Tillich and the university
No full textThe purpose of this inquiry is to state Paul Tillich's position on the nature and function of the university, to draw out those portions of his thought with relevance to a theory of the institution, and to integrate Tillich's earlier and later views on issues of importance to the university. The purpose is not to argue for the truth of Tillich's position per se, nor for the relative merit of a “mediating” position on the university vis-à-vis others. Rather, the goal is to develop what might accurately be called a Tillichian view of the university, in his own terms and consistent with his overall system
“Can You Be Both Democrat and ‘Conspiracy Theorist’?”: Partisan Identity Dynamics in the 9/11 Truth Movement
No full textExisting scholarship often treats conspiracy theories (CTs) either as mere reflections of partisan alignment (correspondence thesis) or as separate, passive belief systems that are co-opted by parties (independence thesis). This study argues for a more nuanced, dialectical view. Specifically, this thesis explores the complex relationship between partisan identity and CT endorsement within the 9/11 Truth movement, centering on how activists navigate their dual identification as both CT believers and political partisans. Through 15 in-depth, semi-structured interviews conducted with members and leaders of 9/11 Truth movement mostly affiliated with the Democratic Party, this thesis uncovers how CT endorsement among this community functions as a distinct activist identity that both reinforces and destabilizes conventional partisan attachments. Participants frame their involvement in the 9/11 Truth movement not simply as opposition to the official explanation, but as an extension of broader anti-war, transparency, and democratic ideals. These activists view their CT advocacy as a promotive, reformative stance in pursuit of social justice and civic engagement, challenging media and institutional representations that often stigmatize them as merely ‘conspiracy theorists.’ The thesis documents how the historical party-movement alliance between anti-war activism and the Democratic Party unraveled, especially as Democratic leaders and liberal media proved unreceptive to CT narratives and continued support for military interventions. This breakdown prompts cognitive dissonance among activists, leading some to realign with Republican or third-party candidates who are perceived as more open to alternative, “deviant” narratives and anti-establishment discourse—though this shift seldom translates into full partisan conversion. This thesis highlights the active role of CTs as social forces: they catalyze new forms of civic engagement and foster solidarity among marginalized, stigmatized groups. Rather than stabilizing partisan boundaries, CTs are seen to disrupt and reshape political identities, pushing activists to critique exclusionary practices and hegemonic discourse in both political and epistemic domains. This thesis also calls for a multidirectional, interpretive approach, such as utilizing grounded theory and qualitative interviews, to foreground the lived experiences and identity negotiations of activists navigating ambiguous, politically non-mainstream CTs. This approach moves beyond static models and emphasizes the dynamic, dialectical interplay between CT endorsement, party politics, and social movement activism in the U.S. context
Conformational ensembles of the magnesium channel CorA reveal structural basis for channel gating
No full textIn prokaryotes, CorA is the primary influx pathway for magnesium, a critical divalent cation in cellular physiology and biochemistry. Mechanistic studies show that homopentameric CorA is regulated through an intracellular [Mg2+]-dependent negative feedback loop, involving the asymmetric participation of individual subunits. To understand the connection between asymmetry and activation, we used single-particle cryo-EM to solve sixteen structures of nanodisc-reconstituted CorA. We utilized conformation-specific synthetic antibodies to stabilize subtle but significant conformational differences in the cryo-EM structures. Our results demonstrate that CorA exists as a set of conformational ensembles, where population size inversely correlates with intracellular Mg2+ concentration. These ensembles include channels with a variety of pore conformations, both constricted and dilated, suggesting a spectrum of active CorA functional states. The ensembles connect asymmetric structural transitions in the cytoplasmic domain with conformational changes in the permeation pathway via an electrostatic network, ultimately controlling channel-gating events. We believe that these results establish a framework for understanding magnesium homeostasis in prokaryotic systems.</p