Modulating Calcium Signaling by Protein Design and Analysis of Calcium Binding Proteins

Transient change of cytosolic calcium level leads to physiological actions, which are modulated by the intracellular calcium stores, and gated by membrane calcium channels/pumps. To closely monitor calcium dynamics there is a pressing need to develop calcium sensors that are targeted to high calcium environment such as the ER/SR with relatively low binding affinity and fast kinetic properties to complement the current calcium indicator toolkits. In this dissertation, the development of fast red florescent calcium binding protein using the protein design is reported. The results show the calcium dependent fluorescence increase of mCherry mutant MCD1 (RapidER) and MCD15 (RapidER’) is able to monitor the ER calcium release in several cell lines responding to perturbations of extracellular calcium signaling. The specific targeting to the ER membrane was achieved by fusing the ryanodine receptor 1 transmembrane domains for the spatio-temporal calcium imaging. To understand the underlying mechanism of calcium binding induced fluorescence increase in the designed calcium sensor CatchER, the fluorescence lifetime of CatchER was determined in calcium free and bound forms using time resolved florescence spectroscopy. The results suggest that calcium binding inhibits the geminate quenching, resulting in a longer lifetime when the anionic form is indirectly excited at 395 nm. It is believed that such unique calcium-induced lifetime change can be applied to monitor calcium signaling in cell imaging. NMR spectroscopy was used to investigate the protein-protein/ligand interaction in this dissertation. The residual dipolar coupling and T1, T2, NOE dynamic study were carried out to understand the binding mode of CaM and the N-terminal intracellular loop of connexin 43. The results show that both N and C terminal domains of Ca2+-CaM contact with the peptide, leading to a partially unwound and bending central helix of CaM. The ligand binding induced conformational change was demonstrated by selectively labeled proteins including extracellular domain of calcium sensing receptor and the bacterial membrane protein SecA fragments C34 and N68

Quantum dense coding scheme via cavity decay

We investigate a secure scheme for implementing quantum dense coding via cavity decay and liner optics devices. Our scheme combines two distinct advantages: atomic qubit sevres as stationary bit and photonic qubit as flying bit, thus it is suitable for long distant quantum communication.Comment: 5 pages, 2 figure. A revised version, accept for publication in Journal of Modern Optc

Scheme for preparation of W state via cavity QED

In this paper, we presented a physical scheme to generate the multi-cavity maximally entangled W state via cavity QED. All the operations needed in this scheme are to modulate the interaction time only once.Comment: 8 pages, 1 figur

Scheme for sharing classical information via tripartite entangled states

We investigate schemes for quantum secret sharing and quantum dense coding via tripartite entangled states. We present a scheme for sharing classical information via entanglement swapping using two tripartite entangled GHZ states. In order to throw light upon the security affairs of the quantum dense coding protocol, we also suggest a secure quantum dense coding scheme via W state in analogy with the theory of sharing information among involved users.Comment: 4 pages, no figure. A complete rewrritten vession, accepted for publication in Chinese Physic

Generation of 3-Dimensional graph state with Josephson charge qubits

On the basis of generations of 1-dimensional and 2-dimensional graph states, we generate a 3-dimensional N3-qubit graph state based on the Josephson charge qubits. Since any two charge qubits can be selectively and effectively coupled by a common inductance, the controlled phase transform between any two-qubit can be performed. Accordingly, we can generate arbitrary multi-qubit graph states corresponding to arbitrary shape graph, which meet the expectations of various quantum information processing schemes. All the devices in the scheme are well within the current technology. It is a simple, scalable and feasible scheme for the generation of various graph states based on the Josephson charge qubits.Comment: 4 pages, 4 figure

Implementation of Grover search algorithm with Josephson charge qubits

A scheme of implementing the Grover search algorithm based on Josephson charge qubits has been proposed, which would be a key step to scale more complex quantum algorithms and very important for constructing a real quantum computer via Josephson charge qubits. The present scheme is simple but fairly efficient, and easily manipulated because any two-charge-qubit can be selectively and effectively coupled by a common inductance. More manipulations can be carried out before decoherence sets in. Our scheme can be realized within the current technology.Comment: 4 pages, 4 figure

Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery

The combination of calcipotriol with methotrexate can strengthen the topical therapy for psoriasis. The aim of the present study was to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with lipophilic calcipotriol and hydrophilic methotrexate as topical therapy. NLCs composed of Precirol ATO 5 with various amounts of squalene as the liquid lipid were prepared. The particle size, surface charge, molecular environment, drug permeation, and skin irritation of the carriers were assessed. Hyperproliferative skin was also used as a permeation barrier in this study. It was found that variations in the Precirol®/squalene ratio had profound effects on the physicochemical characteristics of the NLCs. The range of particle size of the NLC preparations was 270 to 320 nm, with vehicles containing a higher Precirol amount exhibiting a larger diameter. NLCs with a higher Precirol/squalene ratio also showed greater polarity in their molecular environment. Calcipotriol-loaded NLC systems provided drug fluxes of 0.62 to 1.08 μg/cm2/h, which were slightly higher or comparable to the 30% ethanol vehicle (control, 0.72 μg/cm2/h). The methotrexate amount permeating the skin was 2.4 to 4.4-times greater using NLCs compared to that with the control. Dual drug-loaded NLCs exhibited reduced skin permeation of calcipotriol but not methotrexate. The in vivo topical delivery examined by confocal laser scanning microscopy (CLSM) showed a good correlation with the in vitro results. These two drugs with extremely different polarities can successfully be combined in NLCs. Results suggest that NLCs may have the potential to serve as delivery carriers for antipsoriatic drugs because of enhanced drug permeation and limited skin irritation