Overlapping two standing waves in a microcavity for a multi-atom photon interface.

We develop a light-matter interface enabling strong and uniform coupling between a chain of cold atoms and photons of an optical cavity. This interface is a fiber Fabry-Perot cavity, doubly resonant for both the wavelength of the atomic transition and for a geometrically commensurate red-detuned intracavity trapping lattice. Fulfilling the condition of a strong and uniform atom-photon coupling requires optimization of the spatial overlap between the two standing waves in the cavity. In a strong-coupling cavity, where the mode waists and Rayleigh range are small, we derive the expression of the optimal trapping wavelength, taking into account the Gouy phase. The main parameter controlling the overlap of the standing waves is the relative phase shift at the reflection on the cavity mirrors between the two wavelengths, for which we derive the optimal value. We have built a microcavity optimized according to these results, employing custom-made mirrors with engineered reflection phase for both wavelengths. We present a method to measure with high precision the relative phase shift at reflection, which allows us to determine the spatial overlap of the two modes in this cavity.

Mapping optical standing-waves of an open-access Fabry-Perot cavity with a tapered fiber.

We describe a method to map the standing-wave pattern inside an open-access Fabry-Perot optical cavity with sub-wavelength resolution by perturbing it with a commercially available tapered fiber. The method is applied to a fiber Fabry-Perot microcavity. We demonstrate its use in determining the relative position of the antinodes at two different wavelengths. In addition, we use the tapered optical fiber as a point-like source, allowing precise positioning of a microscope objective with respect to the cavity mode.

Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress.

H11 kinase/Hsp22 (Hsp22) is a small heat shock protein, which, when overexpressed cardiac specifically in transgenic (TG) mice, induces stable left ventricular (LV) hypertrophy. Hsp22 also increases oxidative phosphorylation and mitochondrial reactive oxygen species (ROS) production, mechanisms mediating LV hypertrophy, senescence and reduced lifespan. Therefore, we investigated whether ROS production mediates LV hypertrophy, senescence and reduced life span in Hsp22 TG mice. Survival curves revealed that TG mice had a 48% reduction in their mean life span compared to wild type (WT) mice. This was associated with a significant increase in senescence markers, such as p16, p19 mRNA levels as well as the percentage of ß-galactosidase positive cells and telomerase activity. Oxidized (GSSG)/reduced (GSH) glutathione ratio, an indicator of oxidative stress, and ROS production from 3 major cellular sources was measured in cardiac tissue. Hearts from TG mice exhibited a decrease in GSH/GSSG ratio together with increased ROS production from all sources. To study the role of ROS, mice were treated with the antioxidant Tempol from weaning to their sacrifice. Chronic Tempol treatment abolished oxidative stress and overproduction of ROS, and reduced myocardial hypertrophy and Akt phosphorylation in TG mice. Tempol also significantly extended life span and prevented aging markers in TG mice. Taken together these results show that overexpression of Hsp22 increases oxidative stress responsible for the induction of hypertrophy and senescence and ultimately reduction in life span.

Dual-wavelength fiber Fabry-Perot cavities with engineered birefringence.

We present a method to engineer the frequency splitting of polarization eigenmodes in fiber Fabry-Perot (FFP) cavities. Using specific patterns of multiple CO2 laser pulses, we machine paraboloidal micromirrors with controlled elliptical shape in a large range of radii of curvature. This method is versatile and can be used to produce cavities with maximized or near-zero polarization mode splitting. In addition, we realize dual-wavelength FFP cavities with finesse exceeding 40 000 at 780 nm and at 1559 nm in the telecom range. We provide direct evidence that the birefringent frequency splitting in FFP cavities is governed only by the geometrical shape of the mirrors, and that the astigmatism of the cavity modes needs to be taken into account for specific cavities.

Millimeter-long fiber Fabry-Perot cavities.

We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5 mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

CORM-3, a water soluble CO-releasing molecule, uncouples mitochondrial respiration via interaction with the phosphate carrier.

Carbon monoxide is continuously produced in small quantities in tissues and is an important signaling mediator in mammalian cells. We previously demonstrated that CO delivered to isolated rat heart mitochondria using a water-soluble CO-releasing molecule (CORM-3) is able to uncouple mitochondrial respiration. The aim of this study was to explore more in depth the mechanism(s) of this uncoupling effect. We found that acceleration of mitochondrial O2 consumption and decrease in membrane potential induced by CORM-3 were associated with an increase in mitochondrial swelling. This effect was independent of the opening of the mitochondrial transition pore as cyclosporine A was unable to prevent it. Interestingly, removal of phosphate from the incubation medium suppressed the effects mediated by CORM-3. Blockade of the dicarboxylate carrier, which exchanges dicarboxylate for phosphate, decreased the effects induced by CORM-3 while direct inhibition of the phosphate carrier with N-ethylmaleimide completely abolished the effects of CORM-3. In addition, CORM-3 was able to enhance the transport of phosphate into mitochondria as evidenced by changes in mitochondrial phosphate concentration and mitochondrial swelling that evaluates the activity of the phosphate carrier in de-energized conditions. These results indicate that CORM-3 activates the phosphate carrier leading to an increase in phosphate and proton transport inside mitochondria, both of which could contribute to the non-classical uncoupling effect mediated by CORM-3. The dicarboxylate carrier amplifies this effect by increasing intra-mitochondrial phosphate concentration.

Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aß25-35 peptide-injected mice, a nontransgenic Alzheimer's disease model.

Alzheimer's disease (AD), the most prevalent dementia in the elderly, is characterized by progressive synaptic and neuronal loss. Mitochondrial dysfunctions have been consistently reported as an early event in AD and appear before Aß deposition and memory decline. In order to define a new neuroprotectant strategy in AD targeting mitochondrial alterations, we develop tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine (ANAVEX2-73, AE37), a mixed muscarinic receptor ligand and a sigma-1 receptor (σ1R) agonist. We previously reported that ANAVEX2-73 shows anti-amnesic and neuroprotective activities in mice injected intracerebroventricular (ICV) with oligomeric amyloid-ß25-35 peptide (Aß25-35). The σ1R is present at mitochondria-associated endoplasmic reticulum (ER) membranes, where it acts as a sensor/modulator of ER stress responses and local Ca(2+) exchanges with the mitochondria. We therefore evaluated the effect of ANAVEX2-73 and PRE-084, a reference σ1R agonist, on preservation of mitochondrial integrity in Aß25-35-injected mice. In isolated mitochondria from hippocampus preparations of Aß25-35 injected animals, we measured respiration rates, complex activities, lipid peroxidation, Bax/Bcl-2 ratios and cytochrome c release into the cytosol. Five days after Aß25-35 injection, mitochondrial respiration in mouse hippocampus was altered. ANAVEX2-73 (0.01-1 mg/kg IP) restored normal respiration and PRE-084 (0.5-1 mg/kg IP) increased respiration rates. Both compounds prevented Aß25-35-induced increases in lipid peroxidation levels, Bax/Bcl-2 ratio and cytochrome c release into the cytosol, all indicators of increased toxicity. ANAVEX2-73 and PRE-084 efficiently prevented the mitochondrial respiratory dysfunction and resulting oxidative stress and apoptosis. The σ1R, targeted selectively or non-selectively, therefore appears as a valuable target for protection against mitochondrial damages in AD.

Cardiac H11 kinase/Hsp22 stimulates oxidative phosphorylation and modulates mitochondrial reactive oxygen species production: Involvement of a nitric oxide-dependent mechanism.

H11 kinase/Hsp22 (Hsp22), a small heat shock protein upregulated by ischemia/reperfusion, provides cardioprotection equal to ischemic preconditioning (IPC) through a nitric oxide (NO)-dependent mechanism. A main target of NO-mediated preconditioning is the mitochondria, where NO reduces O2 consumption and reactive oxygen species (ROS) production during ischemia. Therefore, we tested the hypothesis that Hsp22 overexpression modulates mitochondrial function through an NO-sensitive mechanism. In cardiac mitochondria isolated from transgenic (TG) mice with cardiac-specific overexpression of Hsp22, mitochondrial basal, ADP-dependent, and uncoupled O2 consumption was increased in the presence of either glucidic or lipidic substrates. This was associated with a decrease in the maximal capabilities of complexes I and III to generate superoxide anion in combination with an inhibition of superoxide anion production by the reverse electron flow. NO synthase expression and NO production were increased in mitochondria from TG mice. Hsp22-induced increase in O2 consumption was abolished either by pretreatment of TG mice with the NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) or in isolated mitochondria by the NO scavenger phenyltetramethylimidazoline-1-oxyl-3-oxide. L-NAME pretreatment also restored the reverse electron flow. After anoxia, mitochondria from TG mice showed a reduction in both oxidative phosphorylation and H2O2 production, an effect partially reversed by L-NAME. Taken together, these results demonstrate that Hsp22 overexpression increases the capacity of mitochondria to produce NO, which stimulates oxidative phosphorylation in normoxia and decreases oxidative phosphorylation and reactive oxygen species production after anoxia. Such characteristics replicate those conferred by IPC, thereby placing Hsp22 as a potential tool for prophylactic protection of mitochondrial function during ischemia.

Cavity-based single atom preparation and high-fidelity hyperfine state readout.

We prepare and detect the hyperfine state of a single 87Rb atom coupled to a fiber-based high-finesse cavity on an atom chip. The atom is extracted from a Bose-Einstein condensate and trapped at the maximum of the cavity field, resulting in a reproducibly strong atom-cavity coupling. We use the cavity reflection and transmission signal to infer the atomic hyperfine state with a fidelity exceeding 99.92% in a readout time of 100 µs. The atom is still trapped after detection.

Enhanced and reduced atom number fluctuations in a BEC splitter.

We measure atom number statistics after splitting a gas of ultracold 87Rb atoms in a purely magnetic double-well potential created on an atom chip. Well below the critical temperature for Bose-Einstein condensation Tc, we observe reduced fluctuations down to -4.9 dB below the atom shot noise level. Fluctuations rise to more than +3.8 dB close to Tc, before reaching the shot noise level for higher temperatures. We use two-mode and classical field simulations to model these results. This allows us to confirm that the supershot noise fluctuations directly originate from quantum statistics.

Magnetic microchip traps and single-atom detection.

Microchip traps provide a promising approach to quantum information processing and communication (QIPC) with neutral atoms: strong and complex potentials can be produced for acting on the qubit atoms, and the potentials can be scaled to higher qubit numbers by virtue of the microfabrication process. We describe experimental results that are relevant to use in QIPC, such as the transport of Bose-Einstein-condensed atomic ensembles along the chip surface with the help of a magnetic conveyor belt. The second part of the paper is devoted to single-atom detection on the chip.