Acidosis of the tumor microenvironment is typical of a malignant phenotype, particularly in hypoxic tumors. All cells express multiple isoforms of carbonic anhydrase (CA), enzymes catalyzing the reversible hydration of carbon dioxide into bicarbonate and protons. Tumor cells express membrane-bound CAIX and CAXII that are controlled via the hypoxia-inducible factor (HIF). Despite the recognition that tumor expression of HIF-1alpha and CAIX correlates with poor patient survival, the role of CAIX and CAXII in tumor growth is not fully resolved. To understand the advantage that tumor cells derive from expression of both CAIX and CAXII, we set up experiments to either force or invalidate the expression of these enzymes. In hypoxic LS174Tr tumor cells expressing either one or both CA isoforms, we show that (a) in response to a "CO(2) load," both CAs contribute to extracellular acidification and (b) both contribute to maintain a more alkaline resting intracellular pH (pH(i)), an action that preserves ATP levels and cell survival in a range of acidic outside pH (6.0-6.8) and low bicarbonate medium. In vivo experiments show that ca9 silencing alone leads to a 40% reduction in xenograft tumor volume with up-regulation of ca12 mRNA levels, whereas invalidation of both CAIX and CAXII gives an impressive 85% reduction. Thus, hypoxia-induced CAIX and CAXII are major tumor prosurvival pH(i)-regulating enzymes, and their combined targeting shows that they hold potential as anticancer targets.
We present a microscopic calculation of spontaneous photon emission by twisted (paraxial) electrons propagating through inhomogeneous, axisymmetric magnetic fields. We construct exact electron states that incorporate transverse mode structure and wavefront curvature by combining the Foldy-Wouthuysen transformation with a geometric framework based on Lewis-Ermakov invariants and metaplectic transformations. We show that the evolution of such structured states corresponds to an open path in the space of quadratic forms, giving rise to a geometric contribution to the emission amplitude that cannot be eliminated by gauge choice or adiabatic arguments. The inverse radius of curvature of the electron wavefront emerges as an effective geometric field that enables radiation even in regions where the external magnetic field vanishes locally. This mechanism generalizes Landau-level radiation to nonasymptotic, structured electron states and establishes a direct connection between noncyclic geometric evolution and photon emission.
Chiara Badiali, Rafael Almeida, Bernardo Malaca
et al.
We introduce a plasma wakefield acceleration scheme capable of boosting initially subrelativistic particles to relativistic velocities within millimeter-scale distances. A subluminal light pulse drives a wake whose velocity is continuously matched to the beam speed through a tailored plasma density, thereby extending the dephasing length. We develop a theoretical model that is generalizable across particle mass, initial velocity, and the particular accelerating bucket being used, and we verify its accuracy with particle-in-cell simulations using laser drivers with energies in the Joule range.
We present a closed-form analytic solution for the propagation of an arbitrary charged scalar state in a non-uniform magnetic field. The dynamics are governed by classical beam optics parameters (Courant-Snyder parameters), the Twiss functions, and phase advance, revealing a direct map between quantum evolution and its classical counterpart. The solution decomposes into three components, exhibiting a complex rotation dependent on the sign of the orbital angular momentum (OAM) projection, alongside an intrinsic distortion from interference governed by a generalized Gouy phase. For a relevant Glaser-type magnetic field and a half-blocked twisted electron, we demonstrate that asymmetry reveals interference-driven dynamics beyond rigid rotation. Our fully relativistic framework provides a practical tool for predicting beam behavior in particle accelerators and electron microscopes.
In plasma wakefield accelerators, the structure of the blowout sheath is vital for the blowout radius and the electromagnetic field distribution inside the blowout. Previous theories assume artificial distribution functions for the sheath, which are either inaccurate or require prior knowledge of parameters. In this study, we develop an adiabatic sheath model based on force balancing, which leads to a self-consistent form of the sheath distribution. This model gives a better estimate of the blowout channel balancing radius than previous models.
German Rojas-Lorenzo, Jesus Rubayo-Soneira, Maykel Marquez-Mijares
et al.
The angular distribution function of multiple scattering experienced by 855 MeV electrons passing through an amorphous silicon plate and an oriented silicon crystal has been studied by means of relativistic molecular dynamics simulations using two types of the potentials that describe electron-atom interaction. The differences in the angular distributions of the beam particles in both media are analysed. The results obtained are compared to the experimental data and to the results of Monte Carlo simulations.