A morpholino oligomer therapy regime that restores mitochondrial function and prevents mdx cardiomyopathy

Current clinical trials demonstrate Duchenne muscular dystrophy (DMD) patients receiving phosphorodiamidate morpholino oligomer (PMO) therapy exhibit improved ambulation and stable pulmonary function; however, cardiac abnormalities remain. Utilizing the same PMO chemistry as current clinical trials, we have identified a non-toxic PMO treatment regimen that restores metabolic activity and prevents DMD cardiomyopathy. We propose that a treatment regimen of this nature may have the potential to significantly improve morbidity and mortality from DMD by improving ambulation, stabilizing pulmonary function, and preventing the development of cardiomyopathy

Synchronized pulse control of decoherence

We present a new strategy for multipulse control over decoherence. When a two-level system interacts with a reservoir characterized by a specific frequency, we find that the decoherence is effectively suppressed by synchronizing the pulse-train application with the dynamical motion of the reservoir.Comment: 14 pages, 8 figure

Decoherence control in microwave cavities

We present a scheme able to protect the quantum states of a cavity mode against the decohering effects of photon loss. The scheme preserves quantum states with a definite parity, and improves previous proposals for decoherence control in cavities. It is implemented by sending single atoms, one by one, through the cavity. The atomic state gets first correlated to the photon number parity. The wrong parity results in an atom in the upper state. The atom in this state is then used to inject a photon in the mode via adiabatic transfer, correcting the field parity. By solving numerically the exact master equation of the system, we show that the protection of simple quantum states could be experimentally demonstrated using presently available experimental apparatus.Comment: 13 pages, RevTeX, 8 figure

Universal quantum interfaces

To observe or control a quantum system, one must interact with it via an interface. This letter exhibits simple universal quantum interfaces--quantum input/output ports consisting of a single two-state system or quantum bit that interacts with the system to be observed or controlled. It is shown that under very general conditions the ability to observe and control the quantum bit on its own implies the ability to observe and control the system itself. The interface can also be used as a quantum communication channel, and multiple quantum systems can be connected by interfaces to become an efficient universal quantum computer. Experimental realizations are proposed, and implications for controllability, observability, and quantum information processing are explored.Comment: 4 pages, 3 figures, RevTe

Non-Markovian homodyne-mediated feedback on a two-level atom: a quantum trajectory treatment

Quantum feedback can stabilize a two-level atom against decoherence (spontaneous emission), putting it into an arbitrary (specified) pure state. This requires perfect homodyne detection of the atomic emission, and instantaneous feedback. Inefficient detection was considered previously by two of us. Here we allow for a non-zero delay time $\tau$ in the feedback circuit. Because a two-level atom is a nonlinear optical system, an analytical solution is not possible. However, quantum trajectories allow a simple numerical simulation of the resulting non-Markovian process. We find the effect of the time delay to be qualitatively similar to that of inefficient detection. The solution of the non-Markovian quantum trajectory will not remain fixed, so that the time-averaged state will be mixed, not pure. In the case where one tries to stabilize the atom in the excited state, an approximate analytical solution to the quantum trajectory is possible. The result, that the purity ($P=2{\rm Tr}[\rho^{2}]-1$) of the average state is given by $P=1-4\gamma\tau$ (where $\gamma$ is the spontaneous emission rate) is found to agree very well with the numerical results.Comment: Changed content, Added references and Corrected typo

Fidelity and coordination of mitochondrial protein synthesis in health and disease

The evolutionary acquisition of mitochondria has given rise to the diversity of eukaryotic life. Mitochondria have retained their ancestral α-proteobacterial traits through the maintenance of double membranes and their own circular genome. Their genome varies in size from very large in plants to the smallest in animals and their parasites. The mitochondrial genome encodes essential genes for protein synthesis and has to coordinate its expression with the nuclear genome from which it sources most of the proteins required for mitochondrial biogenesis and function. The mitochondrial protein synthesis machinery is unique because it is encoded by both the nuclear and mitochondrial genomes thereby requiring tight regulation to produce the respiratory complexes that drive oxidative phosphorylation for energy production. The fidelity and coordination of mitochondrial protein synthesis are essential for ATP production. Here we compare and contrast the mitochondrial translation mechanisms in mammals and fungi to bacteria and reveal that their diverse regulation can have unusual impacts on the health and disease of these organisms. We highlight that in mammals the rate of protein synthesis is more important than the fidelity of translation, enabling coordinated biogenesis of the mitochondrial respiratory chain with respiratory chain proteins synthesised by cytoplasmic ribosomes. Changes in mitochondrial protein fidelity can trigger the activation of the diverse cellular signalling networks in fungi and mammals to combat dysfunction in energy conservation. The physiological consequences of altered fidelity of protein synthesis can range from liver regeneration to the onset and development of cardiomyopathy. (Figure presented.)

Impaired functional communication between the L-type calcium channel and mitochondria contributes to metabolic inhibition in the mdx heart

Duchenne muscular dystrophy is a fatal X-linked disease characterized by the absence of dystrophin. Approximately 20% of boys will die of dilated cardiomyopathy that is associated with cytoskeletal protein disarray, contractile dysfunction, and reduced energy production. However, the mechanisms for altered energy metabolism are not yet fully clarified. Calcium influx through the L-type Ca2+ channel is critical for maintaining cardiac excitation and contraction. The L-type Ca2+ channel also regulates mitochondrial function and metabolic activity via transmission of movement of the auxiliary beta subunit through intermediate filament proteins. Here, we find that activation of the L-type Ca2+ channel is unable to induce increases in mitochondrial membrane potential and metabolic activity in intact cardiac myocytes from the murine model of Duchenne muscular dystrophy (mdx) despite robust increases recorded in wt myocytes. Treatment of mdx mice with morpholino oligomers to induce exon skipping of dystrophin exon 23 (that results in functional dystrophin accumulation) or application of a peptide that resulted in block of voltage-dependent anion channel (VDAC) “rescued” mitochondrial membrane potential and metabolic activity in mdx myocytes. The mitochondrial VDAC coimmunoprecipitated with the L-type Ca2+ channel. We conclude that the absence of dystrophin in the mdx ventricular myocyte leads to impaired functional communication between the L-type Ca2+ channel and mitochondrial VDAC. This appears to contribute to metabolic inhibition. These findings provide new mechanistic and functional insight into cardiomyopathy associated with Duchenne muscular dystrophy

IMF Emission in the 14-N + nat-Ag, Au Reactions at E/A = 60-100 MeV

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Two-Particle Correlation Functions for the 200-MeV 3-He + Ag Reaction

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Noise-assisted preparation of entangled atoms

We discuss the generation of entangled states of two two-level atoms inside an optical cavity. The cavity mode is supposed to be coupled to a white noise with adjustable intensity. We describe how the entanglement between the atoms inside the cavity arise in such a situation. The entanglement is maximized for intermediate values of the noise intensity, while it is a monotonic function of the spontaneous rate. This resembles the phenomenon of stochastic resonance and sheds more light on the idea to exploit white noise in quantum information processing.Comment: 4 pages, 4 figure