Hamid R. Molavian

Dynamically induced frustration as a route to a quantum spin ice state in Tb2Ti2O7 via virtual crystal field excitations and quantum many-body effects.

The Tb2Ti2O7 pyrochlore magnetic material is attracting much attention for its spin liquid state, failing to develop long-range order down to 50 mK despite a Curie-Weiss temperature thetaCW approximately -14 K. In this Letter we reinvestigate the theoretical description of this material by considering a quantum model of independent tetrahedra to describe its low-temperature properties. The naturally tuned proximity of this system near a Néel to spin ice phase boundary allows for a resurgence of quantum fluctuation effects that lead to an important renormalization of its effective low-energy spin Hamiltonian. As a result, Tb2Ti2O7 is argued to be a quantum spin ice. We put forward an experimental test of this proposal using neutron scattering on a single crystal.

Fingerprint of Cell Metabolism in the Experimentally Observed Interstitial pH and pO2 in Solid Tumors

Understanding cancer cell metabolism and targeting associated pathways is a field of increasing interest. Helmlinger and colleagues measured average pH and pO(2) as functions of distance from a single blood vessel on the micrometer scale. We show that these results provide unique insight into cancer cell metabolism in vivo when combined with an appropriate mathematical model. We calculate pH as a function of distance from a single blood vessel and for a given metabolism while incorporating a single CO(2) buffer with effective diffusion constants. By assuming that cancer cell metabolism is dominated by respiration with a smaller component of glycolysis in the normoxic state, by more balanced respiration and glycolysis in the hypoxic state, and by glycolysis alone in the anoxic state, we are able to semiquantitatively derive the experimental results of Helmlinger and colleagues. We also apply our model to glycolysis-impaired metabolism and show that the low pH and high pO(2) observed in these tumors may be related to the substantial shift from a respiration-dominated metabolism to one in which glutaminolysis dominates. Based on this, we propose an in vivo experimental measurement of pH in a glycolysis-impaired tumor to validate the modeling results.

Understanding paramagnetic spin correlations in the spin-liquid pyrochlore Tb 2 Ti 2 O 7

Recent elastic and inelastic neutron scattering studies of the highly frustrated pyrochlore antiferromagnet

Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects

{\mathrm{Tb}}_{2}{\mathrm{Ti}}_{2}{\mathrm{O}}_{7}

The Synergetic Coupling among the Cellular Antioxidants Glutathione Peroxidase/Peroxiredoxin and Other Antioxidants and its Effect on the Concentration of H2O2

have shown some very intriguing features that cannot be modeled by the local

The spin liquid state of the Tb2Ti2O7 pyrochlore antiferromagnet: a puzzling state of affairs

〈111〉

High Concentrations of H2O2 Make Aerobic Glycolysis Energetically More Favorable for Cellular Respiration.

classical Ising model, naively expected to describe this system at low temperatures. By including single-ion excitations from the ground state doublet to higher crystal field levels, we successfully describe the elastic neutron scattering pattern and dispersion relations in

Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

{\mathrm{Tb}}_{2}{\mathrm{Ti}}_{2}{\mathrm{O}}_{7},

Proposal for a [111] magnetization plateau in the spin liquid state of Tb2Ti2O7

quantitatively consistent with experimental observations.

A microscale mathematical model for metabolic symbiosis: Investigating the effects of metabolic inhibition on ATP turnover in tumors

Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties.