No Tradeoff between Coherence and Sub-Poissonianity for Heisenberg-Limited Lasers.

The Heisenberg limit to laser coherence C-the number of photons in the maximally populated mode of the laser beam-is the fourth power of the number of excitations inside the laser. We generalize the previous proof of this upper bound scaling by dropping the requirement that the beam photon statistics be Poissonian (i.e., Mandel's Q=0). We then show that the relation between C and sub-Poissonianity (Q<0) is win-win, not a tradeoff. For both regular (non-Markovian) pumping with semiunitary gain (which allows Q→-1), and random (Markovian) pumping with optimized gain, C is maximized when Q is minimized.

Entanglement-free Heisenberg-limited phase estimation.

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/square root N-known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N (ref. 3). It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N < or = 6 (refs 6-15), but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.

How many bits does it take to track an open quantum system?

A D-dimensional Markovian open quantum system will undergo quantum jumps between pure states, if we can monitor the bath to which it is coupled with sufficient precision. In general, these jumps, plus the between-jump evolution, create a trajectory which passes through infinitely many different pure states. Here we show that, for any ergodic master equation, one can expect to find an adaptive monitoring scheme on the bath that can confine the system state to jumping between only K states, for some K ≥ (D - 1)(2) + 1. For D = 2 we explicitly construct a two-state ensemble for any ergodic master equation, showing that one bit is always sufficient to track a qubit.

Quantum optical waveform conversion.

Proposals for long-distance quantum communication rely on the entanglement of matter-based quantum nodes through optical communications channels, but the entangling light pulses have poor temporal behavior in current experiments. Here we show that nonlinear mixing of a quantum light pulse with a spectrally tailored classical field can compress the quantum pulse by more than a factor of 100 and flexibly reshape its temporal waveform while preserving all quantum properties, including entanglement. Our scheme paves the way for quantum communication at the full data rate of optical telecommunications.

Adaptive optical phase estimation using time-symmetric quantum smoothing.

Quantum parameter estimation has many applications, from gravitational wave detection to quantum key distribution. The most commonly used technique for this type of estimation is quantum filtering, using only past observations. We present the first experimental demonstration of quantum smoothing, a time-symmetric technique that uses past and future observations, for quantum parameter estimation. We consider both adaptive and nonadaptive quantum smoothing, and show that both are better than their filtered counterparts. For the problem of estimating a stochastically varying phase shift on a coherent beam, our theory predicts that adaptive quantum smoothing (the best scheme) gives an estimate with a mean-square error up to 2sqrt[2] times smaller than nonadaptive filtering (the standard quantum limit). The experimentally measured improvement is 2.24+/-0.14.

Mixed state discrimination using optimal control.

We present theory and experiment for the task of discriminating two nonorthogonal states, given multiple copies. We implement several local measurement schemes, on both pure states and states mixed by depolarizing noise. We find that schemes which are optimal (or have optimal scaling) without noise perform worse with noise than simply repeating the optimal single-copy measurement. Applying optimal control theory, we derive the globally optimal local measurement strategy, which outperforms all other local schemes, and experimentally implement it for various levels of noise.

A model for measurement of the states in a coupled-dot qubit.

We propose a quantum trajectory analysis of a scheme to measure the states of a coupled-dot device (qubit) where there is a fluctuating energy gap Δ between the two states. The system consists of the qubit and a readout dot coupled to source and drain leads. The tunnel rate through the detector is conditioned by the occupation number of the nearer quantum dot (target) of the qubit and therefore probes the states of the qubit. We derive a Lindblad-form master equation to calculate the unconditional evolution of the qubit and a conditional stochastic master equation calculating the conditional evolution for different tunneling rates. The results show the effects of various device parameters and provide the optimum selection and combination of the system structure.

Molecular and cellular events in alcohol-induced muscle disease.

Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms.

Enhancement by tamoxifen of the membrane antioxidant action of the yeast membrane sterol ergosterol: relevance to the antiyeast and anticancer action of tamoxifen.

The anticancer drug tamoxifen inhibits lipid peroxidation in ox-brain phospholipid liposomes, and is a good antiyeast agent, with clinical potential. We now report that the ergosterol-containing lipid fraction derived from yeast microsomal membranes (and the ergosterol separated from it) inhibited lipid peroxidation when introduced into ox-brain phospholipid liposomes. Inhibition of lipid peroxidation by the lipid fraction was greatly enhanced when yeast cell growth was inhibited with tamoxifen prior to lipid extraction. The ability of tamoxifen to enhance the membrane antioxidant ability of ergosterol is expressed in terms of a tamoxifen enhancement coefficient. Enhancement by tamoxifen of the membrane antioxidant action of ergosterol is discussed in relation to the antifungal and anticancer actions of tamoxifen.

The structural mimicry of membrane sterols by tamoxifen: evidence from cholesterol coefficients and molecular-modelling for its action as a membrane anti-oxidant and an anti-cancer agent.

The anti-cancer drug tamoxifen is a potent inhibitor of lipid peroxidation induced by Fe(III)-ascorbate in ox-brain phospholipid liposomes. Similar anti-oxidant effects, but with varying potencies, are also shown by 4-hydroxy-tamoxifen, cholesterol, ergosterol and 17-beta-oestradiol. We now describe a computer-graphic fitting technique that demonstrates a structural similarity between the five compounds. In addition, we have quantified the differences (relative to cholesterol) between the anti-oxidant activities of the compounds in terms of a novel expression referred to here as the cholesterol coefficient (Cc) Finally, we discuss how the inhibitory effect of tamoxifen on lipid peroxidation may result from a membrane stabilization that is associated with a decrease in membrane fluidity. This action may be related to the anti-proliferative effect exerted by tamoxifen on cancer and fungal cells.

Tamoxifen: new membrane-mediated mechanisms of action and therapeutic advances.

Tamoxifen protects membranes and lipoprotein particles against oxidative damage. This antioxidant action is likely to contribute to the observed cardioprotective action of tamoxifen and supports the use of this compound in treating and even preventing breast cancer. Membrane-mediated mechanisms of tamoxifen action, through a putative modulation of membrane fluidity, are likely to play an important role in its anticancer action and its ability to reverse multidrug resistance, and could also lead to clinical uses as an anti-Candida and anti-viral agent. In this review, Helen Wiseman discusses the interaction of tamoxifen with membranes and lipoprotein particles, and considers the possible clinical implications.

Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action.

Vitamin D is a membrane antioxidant: thus Vitamin D3 (cholecalciferol) and its active metabolite 1,25-dihydroxycholecalciferol and also Vitamin D2 (ergocalciferol) and 7-dehydrocholesterol (pro-Vitamin D3) all inhibited iron-dependent liposomal lipid peroxidation. Cholecalciferol, 1,25-dihydroxycholecalciferol and ergocalciferol were all of similar effectiveness as inhibitors of lipid peroxidation but were less effective than 7-dehydrocholesterol; this was a better inhibitor of lipid peroxidation than cholesterol, though not ergosterol. The structural basis for the antioxidant ability of these Vitamin D compounds is considered in terms of their molecular relationship to cholesterol and ergosterol. Furthermore, the antioxidant ability of Vitamin D is compared to that of the anticancer drug tamoxifen and its 4-hydroxy metabolite (structural mimics of cholesterol) and discussed in relation to the anticancer action of this vitamin.

Tamoxifen and related compounds protect against lipid peroxidation in isolated nuclei: relevance to the potential anticarcinogenic benefits of breast cancer prevention and therapy with tamoxifen?

Tamoxifen, 4-hydroxytamoxifen, nafoxidine, 17 beta-oestradiol and ICI 164,384 were all found to protect rat liver nuclei against Fe(III)-ascorbate dependent lipid peroxidation. The order of effectiveness of these compounds was 4-hydroxytamoxifen > 17 beta-oestradiol > nafoxidine > tamoxifen > ICI 164,384. This protection by tamoxifen against the formation of the genotoxic reactive-intermediates and products of lipid peroxidation in the nuclear membrane could be important in the prevention of nuclear DNA damage and thus carcinogenesis. This possible anticarcinogenic benefit of tamoxifen treatment could be important in long-term therapy with tamoxifen (and future derivatives) and in its proposed use in the prevention of breast cancer.

Carcinogenic antioxidants. Diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol.

The synthetic oestrogens diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol are known to be carcinogenic, yet they all exert antioxidant properties in vitro in that they are good inhibitors of iron ion-dependent lipid peroxidation. In rat liver microsomes incubated with Fe(III)-ascorbate or Fe(III)-ADP/NADPH and also in ox-brain phospholipid liposomes incubated with Fe(III)-ascorbate; the overall order of effectiveness of the compounds tested as inhibitors of lipid peroxidation was diethylstilboestrol > hexoestrol > 17 alpha-ethynyloestradiol > 4-hydroxytamoxifen > 17 beta-oestradiol > tamoxifen. Compounds acting as antioxidants towards lipids may also exert pro-oxidant effects towards other molecules such as DNA and thus must never be assumed to be safe for human use.

Tamoxifen and related compounds decrease membrane fluidity in liposomes. Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions?

Tamoxifen and related compounds decrease membrane fluidity in ox-brain phospholipid liposomes: their order of effectiveness is, 4-hydroxytamoxifen > 17 beta-oestradiol > tamoxifen > cis-tamoxifen > N-desmethyltamoxifen > cholesterol. A good positive correlation was demonstrated between the decrease in membrane fluidity by these compounds and their antioxidant ability as inhibitors of liposomal and microsomal lipid peroxidation (correlation coefficient, r = 0.99, P < 0.001, in both cases). The ability of tamoxifen to decrease membrane fluidity is suggested to be the mechanism of its antioxidant action and is discussed in relation to its anticancer and cardioprotective actions.

Tamoxifen decreases drug efflux from liposomes: relevance to its ability to reverse multidrug resistance in cancer cells?

Tamoxifen decreased the efflux of the fluorescent marker drug, chloroquine, from phosphatidylcholine liposomes. Tamoxifen is a known structural-mimic of cholesterol, which were both found to be similarly effective in preventing drug release from liposomes. This ability of tamoxifen and cholesterol to decrease drug efflux in a concentration-dependent manner is likely to arise from their known ability to decrease membrane fluidity both in liposomes and also in cancer cells. The possible importance of the ability of tamoxifen to inhibit drug efflux from liposomes in relation to its ability to reverse multidrug resistance in cancer patients caused by the efflux of cytotoxic therapeutic agents, is discussed.

Nitric oxide and oxygen radicals: a question of balance.

The production of superoxide and nitric oxide individually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neurodegenerative disease, ischaemia-reperfusion and cancer. These ideas are discussed in this short overview and placed in the context of the current and future status of therapies which could modulate the balance between nitric oxide and superoxide.

Mechanism of inhibition of lipid peroxidation by tamoxifen and 4-hydroxytamoxifen introduced into liposomes. Similarity to cholesterol and ergosterol.

The anticancer drug tamoxifen when introduced into phospholipid liposomes during their preparation inhibited Fe(III)-ascorbate induced lipid peroxidation to a greater extent than similarly introduced cholesterol. Ergosterol was equipotent with tamoxifen, but much less effective than 4-hydroxytamoxifen. Possible mechanisms underlying these effects are discussed in relation to structural mimicry of the sterols by these triphenylethylene drugs as membrane stabilizers against lipid peroxidation.

The antioxidant action of tamoxifen and its metabolites. Inhibition of lipid peroxidation.

The anti-oestrogen drug tamoxifen is an inhibitor of lipid peroxidation in rat liver microsomes and in phospholipid liposomes. Its cis isomer and N-desmethyl form are weaker inhibitors, but 4-hydroxytamoxifen is much more powerful. It is possible that the antioxidant property of tamoxifen might contribute to its biological actions.