Confinement Effects on the Kinetics and Thermodynamics of Protein Dimerization

In the cell, protein complexes form relying on specific interactions between their monomers. Excluded volume effects due to molecular crowding would lead to correlations between molecules even without specific interactions. What is the interplay of these effects in the crowded cellular environment? We study dimerization of a model homodimer both when the mondimers are free or tethered to each other. We consider a structured environment: Two monomers first diffuse into a cavity of size $L$ and then fold and bind within the cavity. The folding and binding are simulated using molecular dynamics based on a simplified topology based model. The {\it confinement} in the cell is described by an effective molecular concentration $C \sim L^{-3}$. A two-state coupled folding and binding behavior is found. We show the maximal rate of dimerization occurred at an effective molecular concentration $C^{op}\simeq 1m$M which is a relevant cellular concentration. In contrast, for tethered chains the rate keeps at a plateau when $CC^{op}$. For both the free and tethered cases, the simulated variation of the rate of dimerization and thermodynamic stability with effective molecular concentration agrees well with experimental observations. In addition, a theoretical argument for the effects of confinement on dimerization is also made

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

Spin swap gate in the presence of qubit inhomogeneity in a double quantum dot

We study theoretically the effects of qubit inhomogeneity on the quantum logic gate of qubit swap, which is an integral part of the operations of a quantum computer. Our focus here is to construct a robust pulse sequence for swap operation in the simultaneous presence of Zeeman inhomogeneity for quantum dot trapped electron spins and the finite-time ramp-up of exchange coupling in a double dot. We first present a geometric explanation of spin swap operation, mapping the two-qubit operation onto a single-qubit rotation. We then show that in this geometric picture a square-pulse-sequence can be easily designed to perform swap in the presence of Zeeman inhomogeneity. Finally, we investigate how finite ramp-up times for the exchange coupling $J$ negatively affect the performance of the swap gate sequence, and show how to correct the problems numerically.Comment: published versio

Dimensional Crossover in the Effective Second Harmonic Generation of Films of Random Dielectrics

The effective nonlinear response of films of random composites consisting of a binary composite with nonlinear particles randomly embedded in a linear host is theoretically and numerically studied. A theoretical expression for the effective second harmonic generation susceptibility, incorporating the thickness of the film, is obtained by combining a modified effective-medium approximation with the general expression for the effective second harmonic generation susceptibility in a composite. The validity of the thoretical results is tested against results obtained by numerical simulations on random resistor networks. Numerical results are found to be well described by our theory. The result implies that the effective-medium approximation provides a convenient way for the estimation of the nonlinear response in films of random dielectrics.Comment: 9 pages, 2 figures; accepted for publication in Phys. Rev.

Large Magnetoresistance Ratio in Ferromagnetic Single-Electron Transistors in the Strong Tunneling Regime

We study transport through a ferromagnetic single-electron transistor. The resistance is represented as a path integral, so that systems where the tunnel resistances are smaller than the quantum resistance can be investigated. Beyond the low order sequential tunneling and co-tunneling regimes, a large magnetoresistance ratio at sufficiently low temperatures is found. In the opposite limit, when the thermal energy is larger than the charging energy, the magnetoresistance ratio is only slightly enhanced.Comment: updated versio

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease