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At least 271 records · Page 15

Transient histone deacetylase inhibition reveals cell type invariant and specific effects of chromatin decondensation on irradiation response

Radiation therapy plays a prominent role in breast cancer treatment, but the high doses of radiation damage both healthy and cancerous cells. Therefore, additional research is needed into combination therapies that could preferentially radiosensitize cancer cells compared to surrounding healthy tissue without causing deleterious side effects. Histone deacetylase inhibitor drugs (HDACis) have been tested as radiosensitizers in both basic research and clinical trials, but the long exposure time typically used in these treatments and the lack of matched healthy cell controls often leave aspects of their mechanism of action unclear. Here, we show that transient (2 h) trichostatin A (TSA) treatment of cancerous and non-tumorigenic breast epithelial cell lines increases immediate DNA damage and decreases long term cell viability in both cell types at high radiation doses. Transient TSA treatment also causes an increase in DNA damage signals after 5 Gy X-rays in other cancer and healthy cell types: A375 melanoma cells and BJ5-ta fibroblasts. This suggests that chromatin decompaction acts to increase cellular vulnerability to initial DNA damage from high doses of radiation in a cell type independent manner that does not rely on changes to DNA repair pathways caused by longer TSA treatment. However, responses to lower doses of radiation and long term survival are more cell type specific: only MCF7 cells experience an effect of TSA on DNA damage after 1 Gy X-ray radiation while MCF10a cells experience somewhat more evident cell viability effects of combined TSA and radiation treatment long term.

Li, Heng [Biochemistry & Cellular and Molecular Bi↗

Mind the crosscap: $τ$-scaling in non-orientable gravity and time-reversal-invariant systems

Spectral statistics of quantum chaotic systems are governed by random matrix universality. In many cases of interest, time-reversal symmetry selects the Gaussian Orthogonal Ensemble (GOE) as the relevant universality class. In holographic CFTs, this is mirrored by the presence of non-orientable geometries in the dual gravitational path integral. In this work, we analyze general properties of these matrix models and their gravitational counterparts. First, we develop a formalism to express the universal level statistics in the canonical ensemble for arbitrary spectral curves, leading to a topological expansion with finite radius of convergence in the late-time $τ$-scaling limit. Then, we focus on topological gravity and study topological recursion on the moduli space of non-orientable surfaces. We find that the Weil-Petersson volumes display non-analytic behaviour multiplying polynomials in the boundary lengths. The volumes give rise to wormholes with late-time divergences, in contrast with the orientable case, which is finite. We identify systematic cancellations among WP volumes implied by the consistency and finiteness of the $τ$-scaling limit. In particular, the cancellation of late-time divergences requires a nontrivial genus resummation. Working in the gravitational microcanonical ensemble, we derive and resum all orders of the topological expansion matching the GOE matrix model in the high-energy regime.

Chaotic Dynamics (nlin.CD)↗

Search for CPT and Lorentz invariance violation in the muon $g -2$ experiment at Fermilab

The Muon g-2 experiment at Fermilab (E989) aims to measure the anomalous magnetic moment of the muon, $a_{\mu}= (g-2)/2$, to a groundbreaking precision of $140$ ppb, obtaining a near four-fold increase in precision over the previous experiment, E821, at the Brookhaven National Laboratory (BNL). The value of $a_{\mu}$ from BNL currently differs from the Standard Model prediction by $\sim 3.7$ standard deviations, suggesting the potential for new physics and therefore, motivating a new experiment.Because the theory predicts this number with high precision, testing the g-factor through experiment provides a stringent test of the SM and can suggest physics beyond the Standard Model. The goal of the Fermilab Muon $g-2$ experiment is to increase the statistical precision by more than a factor of 20 and reduce systematic errors by a factor of 3. By measuring muon precession rate ($\omega_a$) in an external magnetic field, the anomalous magnetic moment will be calculated. This is an incredibly challenging experiment with a unique opportunity to provide new insight into nature. \\ The $g-2$ data also provides a great opportunity for setting the most stringent limits on some of the Standard Model Extension CPT Lorentz violating (LV) parameters in the muon sector. One of the CPT and Lorentz violating signatures that we can look for using $g-2$ data is a sidereal variation of $\omega_a(t)$. Extensive simulation studies confirm that the sensitivity regarding the sidereal varation roughly scales with $\omega_a$ uncertainty. Hence, the $g-2$ experiment at FNAL should be able to reach limits of $\sim 5\times10^{-25}$ GeV. Because the CPT and LV analyses are essentially studies of variations in $\omega_a$ as a function of time and charge, performing an $\omega_a$ analysis sets the stage for the CPT and LV measurement. This dissertation focuses on the methodology of a fully functioning framework and analyzing the Fermilab Muon $g - 2$ Run 2 data containing $\sim 11$ billion events above an energy threshold of $1.7$~GeV.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Data-Driven Operator Theoretic Methods for Phase Space Learning and Analysis

This paper uses data-driven operator theoretic approaches to explore the global phase space of a dynamical system. In this work, we defined conditions for discovering new invariant subspaces in the state space of a dynamical system starting from an invariant subspace based on the spectral properties of the Koopman operator. When the system evolution is known locally in several invariant subspaces in the state space of a dynamical system, a phase space stitching result is derived that yields the global Koopman operator. Additionally, in the case of equivariant systems, a phase space stitching result is developed to identify the global Koopman operator using the symmetry properties between the invariant subspaces of the dynamical system and time-series data from any one of the invariant subspaces. Finally, these results are extended to topologically conjugate dynamical systems; in particular, the relation between the Koopman tuple of topologically conjugate systems is established. The proposed results are demonstrated on several second-order nonlinear dynamical systems including a bistable toggle switch. Our method elucidates a strategy for designing discovery experiments: experiment execution can be done in many steps, and models from different invariant subspaces can be combined to approximate the global Koopman operator.

42 ENGINEERING↗

The kinetic origin of the fluid helicity—A symmetry in the kinetic phase space

Helicity, a topological degree that measures the winding and linking of vortex lines, is preserved by ideal (barotropic) fluid dynamics. In the context of the Hamiltonian description, the helicity is a Casimir invariant characterizing a foliation of the associated Poisson manifold. Casimir invariants are special invariants that depend on the Poisson bracket, not on the particular choice of the Hamiltonian. The total mass (or particle number) is another Casimir invariant, whose invariance guarantees the mass (particle) conservation (independent of any specific choice of the Hamiltonian). In a kinetic description (e.g., that of the Vlasov equation), the helicity is no longer an invariant (although the total mass remains a Casimir of the Vlasov’s Poisson algebra). The implication is that some “kinetic effect” can violate the constancy of the helicity. To elucidate how the helicity constraint emerges or submerges, we examine the fluid reduction of the Vlasov system; the fluid (macroscopic) system is a “sub-algebra” of the kinetic (microscopic) Vlasov system. In the Vlasov system, the helicity can be conserved if a special helicity symmetry condition holds. To put it another way, breaking helicity symmetry induces a change in the helicity. We delineate the geometrical meaning of helicity symmetry and show that for a special class of flows (the so-called epi-two-dimensional flows), the helicity symmetry is written as ∂γ = 0 for a coordinate γ of the configuration space.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

The Gauge Picture of Quantum Dynamics

Although local Hamiltonians exhibit local time dynamics, this locality is not explicit in the Schrödinger picture in the sense that the wavefunction amplitudes do not obey a local equation of motion. We show that geometric locality can be achieved explicitly in the equations of motion by "gauging" the global unitary invariance of quantum mechanics into a local gauge invariance. That is, expectation values $\langle \psi|A|\psi \rangle$ are invariant under a global unitary transformation acting on the wavefunction $|\psi\rangle \to U |\psi\rangle$ and operators $A \to U A U^\dagger$, and we show that it is possible to gauge this global invariance into a local gauge invariance. To do this, we replace the wavefunction with a collection of local wavefunctions $|\psi_J\rangle$, one for each patch of space $J$. The collection of spatial patches is chosen to cover the space; e.g. we could choose the patches to be single qubits or nearest-neighbor sites on a lattice. Local wavefunctions associated with neighboring pairs of spatial patches $I$ and $J$ are related to each other by dynamical unitary transformations $U_{IJ}$. The local wavefunctions are local in the sense that their dynamics are local. That is, the equations of motion for the local wavefunctions $|\psi_J\rangle$ and connections $U_{IJ}$ are explicitly local in space and only depend on nearby Hamiltonian terms. (The local wavefunctions are many-body wavefunctions and have the same Hilbert space dimension as the usual wavefunction.) We call this picture of quantum dynamics the gauge picture since it exhibits a local gauge invariance. The local dynamics of a single spatial patch is related to the interaction picture, where the interaction Hamiltonian consists of only nearby Hamiltonian terms. We can also generalize the explicit locality to include locality in local charge and energy densities.

Physics↗

Non-Semisimple TQFT's and BPS q -Series

We propose and in some cases prove a precise relation between 3-manifold invariants associated with quantum groups at roots of unity and at generic q. Both types of invariants are labeled by extra data which plays an important role in the proposed relation. Bridging the two sides - which until recently were developed independently, using very different methods - opens many new avenues. In one direction, it allows to study (and perhaps even to formulate) q-series invariants labeled by spin c structures in terms of non-semisimple invariants. In the opposite direction, it offers new insights and perspectives on various elements of non-semisimple TQFT's, bringing the latter into one unifying framework with other invariants of knots and 3-manifolds that recently found realization in quantum field theory and in string theory.

3-manifold invariants↗