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A bstract Analog condensed matter systems present an exciting opportunity to simulate early Universe models in table-top experiments. We consider a recent proposal for an analog condensed matter experiment to simulate the relativistic quantum decay of the false vacuum. In the proposed experiment, two ultra-cold condensates are coupled via a time-varying radio-frequency field. The relative phase of the two condensates in this system is approximately described by a relativistic scalar field with a potential possessing a series of false and true vacuum local minima. If the system is set up in a false vacuum, it would then decay to a true vacuum via quantum mechanical tunnelling. Should such an experiment be realized, it would be possible to answer a number of open questions regarding non-perturbative phenomena in quantum field theory and early Universe cosmology. In this paper, we illustrate a possible obstruction: the time-varying coupling that is invoked to create a false vacuum for the long-wavelength modes of the condensate leads to a destabilization of shorter wavelength modes within the system via parametric resonance. We focus on an idealized setup in which the two condensates have identical properties and identical background densities. Describing the system by the coupled Gross-Pitaevskii equations (GPE), we use the machinery of Floquet theory to perform a linear stability analysis, calculating the wavenumber associated with the first instability band for a variety of experimental parameters. However, we demonstrate that, by tuning the frequency of the time-varying coupling, it may be possible to push the first instability band outside the validity of the GPE, where dissipative effects are expected to damp any instabilities. This provides a viable range of experimental parameters to perform analog experiments of false vacuum decay.

Inosine monophosphate dehydrogenase (IMPDH) mediates the first committed step in guanine nucleotide biosynthesis and plays important roles in cellular proliferation and the immune response. IMPDH reversibly polymerizes in cells and tissues in response to changes in metabolic demand. Self-assembly of metabolic enzymes is increasingly recognized as a general mechanism for regulating activity, typically by stabilizing specific conformations of an enzyme, but the regulatory role of IMPDH filaments has remained unclear. Here, we report a series of human IMPDH2 cryo-EM structures in both active and inactive conformations. The structures define the mechanism of filament assembly, and reveal how filament-dependent allosteric regulation of IMPDH2 makes the enzyme less sensitive to feedback inhibition, explaining why assembly occurs under physiological conditions that require expansion of guanine nucleotide pools. Tuning sensitivity to an allosteric inhibitor distinguishes IMPDH from other metabolic filaments, and highlights the diversity of regulatory outcomes that can emerge from self-assembly.

A bstract Metastable ‘false’ vacuum states are an important feature of the Standard Model of particle physics and many theories beyond it. Describing the dynamics of a phase transition out of a false vacuum via the nucleation of bubbles is essential for understanding the cosmology of vacuum decay and the full spectrum of observables. In this paper, we study vacuum decay by numerically evolving ensembles of field theories in 1+1 dimensions from a metastable state. We demonstrate that for an initial Bose-Einstein distribution of fluctuations, bubbles form with a Gaussian spread of center-of-mass velocities and that bubble nucleation events are preceded by an oscillon — a long-lived, time-dependent, pseudo-stable configuration of the field. Defining an effective temperature from the long-wavelength amplitude of fluctuations in the ensemble of simulations, we find good agreement between theoretical finite temperature predictions and empirical measurements of the decay rate, velocity distribution and critical bubble solution. We comment on the generalization of our results and the implications for cosmological observables.

The opioid epidemic remains a major public health issue in the U.S., with over 100,000 overdose deaths in 2022, many linked to synthetic opioids. Emergency medicine plays a vital role in managing opioid overdoses, which typically cause CNS depression and respiratory failure. However, atypical presentations are becoming more common, complicating diagnosis and treatment. This case report discusses a patient who developed focal neurologic deficits after an opioid overdose and was found to have radiographic findings suggestive of CHANTER syndrome. Cerebellar-Hippocampal-Basal Nuclei Transient Edema with Restricted Diffusion (CHANTER syndrome), first described in 2019, is marked by restricted diffusion and edema in the cerebellum, hippocampus, and basal ganglia. While most cases involve comatose patients requiring intensive care, the emergency department presentation is less understood. The differential diagnosis includes hypoxic-ischemic encephalopathy, posterior reversible encephalopathy syndrome, and heroin-associated spongiform leukoencephalopathy. Unlike ischemic infarcts, CHANTER syndrome can show significant improvement with aggressive management. Given the rise of opioid use, emergency physicians are likely to encounter more cases with similar presentations. MRI imaging should be considered in patients who do not recover as expected following an opioid overdose. Early identification of complications like CHANTER syndrome can lead to closer neurologic monitoring and neurosurgical intervention that may prevent decompensation or even death.

A bstract We investigate the nonlinear dynamics of cold atom systems that can in princi- ple serve as quantum simulators of false vacuum decay. The analog false vacuum manifests as a metastable vacuum state for the relative phase in a two-species Bose-Einstein con- densate (BEC), induced by a driven periodic coupling between the two species. In the appropriate low energy limit, the evolution of the relative phase is approximately governed by a relativistic wave equation exhibiting true and false vacuum configurations. In previous work, a linear stability analysis identified exponentially growing short-wavelength modes driven by the time-dependent coupling. These modes threaten to destabilize the analog false vacuum. Here, we employ numerical simulations of the coupled Gross-Pitaevski equa- tions (GPEs) to determine the non-linear evolution of these linearly unstable modes. We find that unless a physical mechanism modifies the GPE on short length scales, the analog false vacuum is indeed destabilized. We briefly discuss various physically expected correc- tions to the GPEs that may act to remove the exponentially unstable modes. To investigate the resulting dynamics in cases where such a removal mechanism exists, we implement a hard UV cutoff that excludes the unstable modes as a simple model for these corrections. We use this to study the range of phenomena arising from such a system. In particular, we show that by modulating the strength of the time-dependent coupling, it is possible to observe the crossover between a second and first order phase transition out of the false vacuum.

Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model. Our analyses suggest a lipid A-catalyzed, three-state mechanism for polymyxins: transient binding, membrane insertion, and super-stoichiometric cluster accumulation with a long residence time. Accumulation also occurs for brevicidine, another lipid A-targeting antibacterial molecule. Lipid A modifications that impart polymyxin resistance and a non-bactericidal polymyxin derivative exhibit binding that does not evolve into long-lived species. We propose that transient binding to lipid A permeabilizes the outer membrane and cluster accumulation enables the bactericidal activity of polymyxins. These findings could establish a blueprint for discovery of lipid A-targeting antibiotics and provide a generalizable approach to study interactions with the gram-negative outer membrane. Polymyxins are last-resort antibiotics targeting lipid A in the gram-negative outer membrane. Here, the authors use surface plasmon resonance-based kinetics to reveal a three-state mechanism governing superstoichiometric accumulation of polymyxins.

Electrical storm is defined as three or more sustained episodes of ventricular tachycardia, ventricular fibrillation, or appropriate cardioverter-defibrillator shocks during a 24-h period. These patients are notoriously difficult to manage. We present a case secondary to Chagas disease that was responsive to lidocaine. Although an uncommon presentation, given the large-scale population movement from South America, Chagas has an increased incidence and is an important diagnostic consideration in patients with new onset heart failure, arrhythmia, or electrical storm.

High-resolution protein structures are essential for understanding biological mechanisms and drug discovery. While cryoEM has revolutionized structure determination of large protein complexes, most disease-related proteins are small (<50 kDa) and challenging to resolve due to low signal-to-noise ratios and alignment difficulties. Current scaffold protein strategies increase target size but suffer from inherent flexibility, resulting in poorly resolved targets compared to scaffolds. We present an iteratively engineered molecular design transforming antibody fragments (Fabs) into conformationally Rigid Fabs that enable high-resolution structure determination of small proteins (~20 kDa). This design introduces strategic disulfide bonds, creating well-folded, rigidly constrained Fabs applicable across various species, frameworks, and chimeric constructs. Rigid Fabs enabled high-resolution cryoEM structures (2.3-2.5 Å) of two small proteins: Ang2 (26 kDa) and KRAS (21 kDa). Our disulfide-constrained Rigid Fab strategy provides a general approach for overcoming target size limitation of single-particle cryoEM. Small proteins (<50 kDa) are difficult to resolve by cryo-EM due to low signal-to-noise ratios and alignment challenges. Here, authors engineered conformationally rigid antibody fragments (Rigid Fabs) enabling high-resolution cryo-EM structures of small (~20 kDa) proteins like KRAS.

A bstract We study the nonlinear evolution of unstable flux compactifications, applying numerical relativity techniques to solve the Einstein equations in D dimensions coupled to a q -form field and positive cosmological constant. We show that initially homogeneous flux compactifications are unstable to dynamically forming warped compactifications. In some cases, we find that the warping process can serve as a toy-model of slow-roll inflation, while in other instances, we find solutions that eventually evolve to a singular state. Analogous to dynamical black hole horizons, we use the geometric properties of marginally trapped surfaces to characterize the lower dimensional vacua in the inhomogeneous and dynamical settings we consider. We find that lower-dimensional vacua with a lower expansion rate are dynamically favoured, and in some cases find spacetimes that undergo a period of accelerated expansion followed by contraction.

The best-characterized members of the plant-specific SIAMESE-RELATED (SMR) family of cyclin-dependent kinase inhibitors regulate the transition from the mitotic cell cycle to endoreplication, also known as endoreduplication, an altered version of the cell cycle in which DNA is replicated without cell division. Some other family members are implicated in cell cycle responses to biotic and abiotic stresses. However, the functions of most SMRs remain unknown, and the specific cyclindependent kinase complexes inhibited by SMRs are unclear. Here, we demonstrate that a diverse group of SMRs, including an SMR from the bryophyte Physcomitrella patens, can complement an Arabidopsis thaliana siamese (sim) mutant and that both Arabidopsis SIM and P. patens SMR can inhibit CDK activity in vitro. Furthermore, we show that Arabidopsis SIM can bind to and inhibit both CDKA;1 and CDKB1;1. Finally, we show that SMR2 acts to restrict cell proliferation during leaf growth in Arabidopsis and that SIM, SMR1/LGO, and SMR2 play overlapping roles in controlling the transition from cell division to endoreplication during leaf development. These results indicate that differences in SMR function in plant growth and development are primarily due to differences in transcriptional and posttranscriptional regulation, rather than to differences in fundamental biochemical function.