Coherent optical transfer of Feshbach molecules to a lower vibrational state

Using the technique of stimulated Raman adiabatic passage (STIRAP) we have coherently transferred ultracold 87Rb2 Feshbach molecules into a more deeply bound vibrational quantum level. Our measurements indicate a high transfer efficiency of up to 87%. As the molecules are held in an optical lattice with not more than a single molecule per lattice site, inelastic collisions between the molecules are suppressed and we observe long molecular lifetimes of about 1 s. Using STIRAP we have created quantum superpositions of the two molecular states and tested their coherence interferometrically. These results represent an important step towards Bose-Einstein condensation (BEC) of molecules in the vibrational ground state.Comment: 4 pages, 5 figure

Cruising through molecular bound state manifolds with radio frequency

The emerging field of ultracold molecules with their rich internal structure is currently attracting a lot of interest. Various methods have been developed to produce ultracold molecules in pre-set quantum states. For future experiments it will be important to efficiently transfer these molecules from their initial quantum state to other quantum states of interest. Optical Raman schemes are excellent tools for transfer, but can be involved in terms of equipment, laser stabilization and finding the right transitions. Here we demonstrate a very general and simple way for transfer of molecules from one quantum state to a neighboring quantum state with better than 99% efficiency. The scheme is based on Zeeman tuning the molecular state to avoided level crossings where radio-frequency transitions can then be carried out. By repeating this process at different crossings, molecules can be successively transported through a large manifold of quantum states. As an important spin-off of our experiments, we demonstrate a high-precision spectroscopy method for investigating level crossings.Comment: 5 pages, 5 figures, submitted for publicatio

Phosphocholine – an agonist of metabotropic but not of ionotropic functions of alpha9-containing nicotinic acetylcholine receptors

We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha9 and alpha10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha9 subunits or heteromeric receptors containing alpha9 and alpha10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions

Conductance fluctuations in mesoscopic normal-metal/superconductor samples

We study the magnetoconductance fluctuations of mesoscopic normal-metal/superconductor (NS) samples consisting of a gold-wire in contact with a niobium film. The magnetic field strength is varied over a wide range, including values that are larger than the upper critical field B_c2 of niobium. In agreement with recent theoretical predictions we find that in the NS sample the rms of the conductance fluctuations (CF) is by a factor of 2.8 +/- 0.4 larger than in the high field regime where the entire system is driven normal conducting. Further characteristics of the CF are discussed.Comment: 4 pages, REVTEX, 3 eps-figures included. To be published in Phys. Rev. Lett.. Changes: one misplaced figure correcte

Fractal Conductance Fluctuations in Gold--Nanowires

A detailed analysis of magneto-conductance fluctuations of quasiballistic gold-nanowires of various lengths is presented. We find that the variance $=$ when analyzed for $\Delta B$ much smaller than the correlation field $B_c$ varies according to $<(\Delta G)^2>\propto \Delta B^{\gamma}$ with $\gamma < 2$ indicating that the graph of $G$ vs. $B$ is fractal. We attribute this behavior to the existence of long-lived states arising from chaotic trajectories trapped close to regular classical orbits. We find that $\gamma$ decreases with increasing length of the wires.Comment: 5 pages, Revtex with epsf, 4 Postscript figures, final version accepted as Phys. Rev. Let

The effect of CpG-ODN on antigen presenting cells of the foal

BACKGROUND: Cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) has been used successfully to induce immune responses against viral and intracellular organisms in mammals. The main objective of this study was to test the effect of CpG-ODN on antigen presenting cells of young foals. METHODS: Peripheral blood monocytes of foals (n = 7) were isolated in the first day of life and monthly thereafter up to 3 months of life. Adult horse (n = 7) monocytes were isolated and tested once for comparison. Isolated monocytes were stimulated with IL-4 and GM-CSF (to obtain dendritic cells, DC) or not stimulated (to obtain macrophages). Macrophages and DCs were stimulated for 14-16 hours with either CpG-ODN, LPS or not stimulated. The stimulated and non-stimulated cells were tested for cell surface markers (CD86 and MHC class II) using flow cytometry, mRNA expression of cytokines (IL-12, IFNalpha, IL-10) and TLR-9 using real time quantitative RT-PCR, and for the activation of the transcription factor NF-kappaB p65 using a chemiluminescence assay. RESULTS: The median fluorescence of the MHC class II molecule in non-stimulated foal macrophages and DCs at birth were 12.5 times and 11.2 times inferior, respectively, than adult horse cells (p = 0.009). That difference subsided at 3 months of life (p = 0.3). The expression of the CD86 co-stimulatory molecule was comparable in adult horse and foal macrophages and DCs, independent of treatment. CpG-ODN stimulation induced IL-12p40 (53 times) and IFNalpha (23 times) mRNA expression in CpG-ODN-treated adult horse DCs (p = 0.078), but not macrophages, in comparison to non-stimulated cells. In contrast, foal APCs did not respond to CpG-ODN stimulation with increased cytokine mRNA expression up to 3 months of age. TLR-9 mRNA expression and NF-kB activation (NF-kB p65) in foal DCs and macrophages were comparable (p \u3e 0.05) to adult horse cells. CONCLUSION: CpG-ODN treatment did not induce specific maturation and cytokine expression in foal macrophages and DCs. Nevertheless, adult horse DCs, but not macrophages, increased their expression of IL-12 and IFNalpha cytokines upon CpG-ODN stimulation. Importantly, foals presented an age-dependent limitation in the expression of MHC class II in macrophages and DCs, independent of treatment

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the ‘review & revise’ experience

Background: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription ‘review & revise’ which is a key strategy to minimise antibiotic overuse in hospitals. Methods: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study. Results: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions. Conclusions: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the ‘review & revise’ approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received

Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift

In humans, low serum carnosinase (CN1) activity protects patients with type 2 diabetes from diabetic nephropathy. We now characterized the interaction of thiol-containing compounds with CN1 cysteine residue at position 102, which is important for CN1 activity. Reduced glutathione (GSH), N-acetylcysteine and cysteine (3.2 \uc2\ub1 0.4, 2.0 \uc2\ub1 0.3, 1.6 \uc2\ub1 0.2 \uc2\ub5mol/mg/h/mM; p &lt;.05) lowered dose-dependently recombinant CN1 (rCN1) efficiency (5.2 \uc2\ub1 0.2 \uc2\ub5mol/mg/h/mM) and normalized increased CN1 activity renal tissue samples of diabetic mice. Inhibition was allosteric. Substitution of rCN1 cysteine residues at position 102 (Mut1C102S) and 229 (Mut2C229S) revealed that only cysteine-102 is influenced by cysteinylation. Molecular dynamic simulation confirmed a conformational rearrangement of negatively charged residues surrounding the zinc ions causing a partial shift of the carnosine ammonium head and resulting in a less effective pose of the substrate within the catalytic cavity and decreased activity. Cysteine-compounds influence the dynamic behaviour of CN1 and therefore present a promising option for the treatment of diabetes

Superconducting Proximity Effect and Universal Conductance Fluctuations

We examine universal conductance fluctuations (UCFs) in mesoscopic normal-superconducting-normal (N-S-N) structures using a numerical solution of the Bogoliubov - de Gennes equation. We discuss two cases depending on the presence (``open'' structure) or absence (``closed'' structure) of quasiparticle transmission. In contrast to N-S structures, where the onset of superconductivity increases fluctuations, we find that UCFs are suppressed by superconductivity for N-S-N structures. We demonstrate that the fluctuations in ``open'' and ``closed'' structures exhibit distinct responses to an applied magnetic field and to an imposed phase variation of the superconducting order parameter.Comment: (4 pages, 5 figures). Corrected typos in equations, added references, changed Fig. 5 and its discussions. Phys. Rev. B, accepted for publicatio