Improved Limits for Violations of Local Position Invariance from Atomic Clock Comparisons.

We compare two optical clocks based on the ^{2}S_{1/2}(F=0)→^{2}D_{3/2}(F=2) electric quadrupole (E2) and the ^{2}S_{1/2}(F=0)→^{2}F_{7/2}(F=3) electric octupole (E3) transition of ^{171}Yb^{+} and measure the frequency ratio ν_{E3}/ν_{E2}=0.932829404530965376(32), improving upon previous measurements by an order of magnitude. Using two caesium fountain clocks, we find ν_{E3}=642121496772645.10(8) Hz, the most accurate determination of an optical transition frequency to date. Repeated measurements of both quantities over several years are analyzed for potential violations of local position invariance. We improve by factors of about 20 and 2 the limits for fractional temporal variations of the fine structure constant α to 1.0(1.1)×10^{-18}/yr and of the proton-to-electron mass ratio µ to -8(36)×10^{-18}/yr. Using the annual variation of the Sun's gravitational potential at Earth Φ, we improve limits for a potential coupling of both constants to gravity, (c^{2}/α)(dα/dΦ)=14(11)×10^{-9} and (c^{2}/µ)(dµ/dΦ)=7(45)×10^{-8}.

Dipole-Dipole Frequency Shifts in Multilevel Atoms.

Dipole-dipole interactions lead to frequency shifts that are expected to limit the performance of next-generation atomic clocks. In this work, we compute dipolar frequency shifts accounting for the intrinsic atomic multilevel structure in standard Ramsey spectroscopy. When interrogating the transitions featuring the smallest Clebsch-Gordan coefficients, we find that a simplified two-level treatment becomes inappropriate, even in the presence of large Zeeman shifts. For these cases, we show a net suppression of dipolar frequency shifts and the emergence of dominant nonclassical effects for experimentally relevant parameters. Our findings are pertinent to current generations of optical lattice and optical tweezer clocks, opening a way to further increase their current accuracy, and thus their potential to probe fundamental and many-body physics.

Coherent Suppression of Tensor Frequency Shifts through Magnetic Field Rotation.

We introduce a scheme to coherently suppress second-rank tensor frequency shifts in atomic clocks, relying on the continuous rotation of an external magnetic field during the free atomic state evolution in a Ramsey sequence. The method retrieves the unperturbed frequency within a single interrogation cycle and is readily applicable to various atomic clock systems. For the frequency shift due to the electric quadrupole interaction, we experimentally demonstrate suppression by more than two orders of magnitude for the ^{2}S_{1/2}→^{2}D_{3/2} transition of a single trapped ^{171}Yb^{+} ion. The scheme provides particular advantages in the case of the ^{171}Yb^{+} ^{2}S_{1/2}→^{2}F_{7/2} electric octupole (E3) transition. For an improved estimate of the residual quadrupole shift for this transition, we measure the excited state electric quadrupole moments Θ(^{2}D_{3/2})=1.95(1)ea_{0}^{2} and Θ(^{2}F_{7/2})=-0.0297(5)ea_{0}^{2} with e the elementary charge and a_{0} the Bohr radius, improving the measurement uncertainties by one order of magnitude.

Single-Ion Atomic Clock with 3×10(-18) Systematic Uncertainty.

We experimentally investigate an optical frequency standard based on the (2)S1/2(F=0)→(2)F7/2(F=3) electric octupole (E3) transition of a single trapped (171)Yb+ ion. For the spectroscopy of this strongly forbidden transition, we utilize a Ramsey-type excitation scheme that provides immunity to probe-induced frequency shifts. The cancellation of these shifts is controlled by interleaved single-pulse Rabi spectroscopy, which reduces the related relative frequency uncertainty to 1.1×10(-18). To determine the frequency shift due to thermal radiation emitted by the ion's environment, we measure the static scalar differential polarizability of the E3 transition as 0.888(16)×10(-40) J m(2)/V(2) and a dynamic correction η(300 K)=-0.0015(7). This reduces the uncertainty due to thermal radiation to 1.8×10(-18). The residual motion of the ion yields the largest contribution (2.1×10(-18)) to the total systematic relative uncertainty of the clock of 3.2×10(-18).

Evidence for superfluidity of ultracold fermions in an optical lattice.

The study of superfluid fermion pairs in a periodic potential has important ramifications for understanding superconductivity in crystalline materials. By using cold atomic gases, various models of condensed matter can be studied in a highly controllable environment. Weakly repulsive fermions in an optical lattice could undergo d-wave pairing at low temperatures, a possible mechanism for high temperature superconductivity in the copper oxides. The lattice potential could also strongly increase the critical temperature for s-wave superfluidity. Recent experimental advances in bulk atomic gases include the observation of fermion-pair condensates and high-temperature superfluidity. Experiments with fermions and bosonic bound pairs in optical lattices have been reported but have not yet addressed superfluid behaviour. Here we report the observation of distinct interference peaks when a condensate of fermionic atom pairs is released from an optical lattice, implying long-range order (a property of a superfluid). Conceptually, this means that s-wave pairing and coherence of fermion pairs have now been established in a lattice potential, in which the transport of atoms occurs by quantum mechanical tunnelling and not by simple propagation. These observations were made for interactions on both sides of a Feshbach resonance. For larger lattice depths, the coherence was lost in a reversible manner, possibly as a result of a transition from superfluid to insulator. Such strongly interacting fermions in an optical lattice can be used to study a new class of hamiltonians with interband and atom-molecule couplings.

Critical velocity for superfluid flow across the BEC-BCS crossover.

Critical velocities have been observed in an ultracold superfluid Fermi gas throughout the BEC-BCS crossover. A pronounced peak of the critical velocity at unitarity demonstrates that superfluidity is most robust for resonant atomic interactions. Critical velocities were determined from the abrupt onset of dissipation when the velocity of a moving one-dimensional optical lattice was varied. The dependence of the critical velocity on lattice depth and on the inhomogeneous density profile was studied.

Light scattering to determine the relative phase of two Bose-Einstein condensates.

We demonstrated an experimental technique based on stimulated light scattering to continuously sample the relative phase of two spatially separated Bose-Einstein condensates of atoms. The phase measurement process created a relative phase between two condensates with no initial phase relation, read out the phase, and monitored the phase evolution. This technique was used to realize interferometry between two trapped Bose-Einstein condensates without need for splitting or recombining the atom cloud.

NMDA receptor blockade rescues Clarke's and red nucleus neurons after spinal hemisection.

Hemisection of the adult rat spinal cord at T9 transects the ascending ipsilateral axons of Clarke's nucleus (CN) neurons and the descending contralateral axons of red nucleus (RN) neurons. Eight weeks following axotomy, 30% of CN neurons and 22% of RN neurons die. Since both nuclei receive glutamatergic input, we wished to examine the possibility that glutamatergic excitotoxicity contributes to axotomy-induced neuronal death in these nuclei. To test this we studied the effects of administration of the NMDA receptor antagonist MK-801 on cell survival after axotomy. When 1 mg/kg body weight MK-801 is administered subcutaneously every day for 1-8 weeks to hemisected rats, cell death is prevented. Treatment with 0.5 mg/kg body weight MK-801 over the same time periods results in only partial rescue of axotomized neurons. Paradoxically, when 1 mg/kg MK-801 administration is restricted to the first week of an 8 week survival period, cell death in both the RN and CN is greatly exaggerated over the cell loss found in saline-treated animals. Withdrawal of 1 mg/kg MK-801 after 1 week of administration induces the loss of 92% of CN neurons, which is 63% greater than that occurring after axotomy alone. If, however, 1 mg/kg MK-801 is withdrawn after 2 weeks post-axotomy in the RN and 3 weeks postaxotomy in CN, all axotomized neurons survive. This rescue is found at 6 months postsurgery, the longest survival period studied, and therefore appears to be permanent. These results suggest that glutamatergic afferent input contributes significantly to the death of axotomized red nucleus and Clarke's nucleus neurons via NMDA receptors located on these neurons.

Removal of dorsal root afferents prevents retrograde death of axotomized Clarke's nucleus neurons in the cat.

We investigated the effect of axotomy, deafferentation, and deafferentation plus axotomy on cell survival and cell size in Clarke's nucleus of the cat spinal cord. Hemisection of the adult spinal cord at T9 leads to retrograde cell death of 40% of the neurons in Clarke's nucleus at L3, as well as to a reduction in the mean soma size of the survivors. In contrast, deafferentation of Clarke's nucleus neurons by L1-S2 dorsal rhizotomy produces no cell loss and no shrinkage of the somata. These results indicate that dorsal root afferent input is not required for Clarke's nucleus cell survival. To test whether afferents may be required by the 60% of neurons that survive axotomy, we deafferented Clarke's nucleus prior to axotomy. Surprisingly, removal of primary afferents to Clarke's nucleus neurons prior to axotomy prevented the death of all neurons that would normally have died from axotomy. These results suggest that dorsal root afferent input is not required for Clarke's nucleus neuron survival after axotomy and may in fact be toxic to these axotomized neurons. This afferent toxicity is likely to be mediated through the dorsal root afferent neurotransmitter glutamate.

Upregulation of NMDARI mRNA induced by MK-801 is associated with massive death of axotomized motor neurones in adult rats.

Studies on the pathogenesis of human motor neurone disease have suffered from the absence of models of motor neurone degeneration in adult animals. Normally in adult rodents, transection of motor neurone axons results in only a modest degree of neuronal death. We reasoned that axotomy-induced motor neurone death might be enhanced by modulating glutamatergic transmission. By axotomizing the facial nerve in adult rats and then administering MK-801 for the first week of a 4-week or 8-week post-lesion survival period, we induced a 67% motor neurone loss by 8 weeks as compared with a 19% loss in controls. A possible explanation for the increased motor neurone loss after MK-801 treatment is that transient blockade of NMDA receptors may upregulate synthesis of NMDA receptor components. In order to test this idea, we employed quantitative in situ hybridization to determine the response of NMDAR1 mRNA to axotomy and axotomy + MK-801 treatment. Quantification of the percentage of area occupied by NMDAR1 silver grains per motor neurone somata indicated that axotomy alone did not provoke a change in NMDAR1 mRNA. However, axotomy and MK-801 combined treatment resulted in a highly significant upregulation of NMDAR1 mRNA when compared with controls or animals treated solely with axotomy. Our results suggest that motor neurone death in adult animals can be enhanced after axotomy in association with the upregulation of NMDA receptor mRNA. Thus, abnormalities in glutamate receptor signalling may lead to subacute motor neurone death in vivo. Furthermore these results indicate that transient treatment with MK-801 is a convenient method for enhancing the degree of motor neurone death after axotomy in adult animals.

An application framework for computer-aided patient positioning in radiation therapy.

The importance of exact patient positioning in radiation therapy increases with the ongoing improvements in irradiation planning and treatment. Therefore, new ways to overcome precision limitations of current positioning methods in fractionated treatment have to be found. The Department of Medical Physics at the German Cancer Research Centre (DKFZ) follows different video-based approaches to increase repositioning precision. In this context, the modular software framework FIVE (Fast Integrated Video-based Environment) has been designed and implemented. It is both hardware- and platform-independent and supports merging position data by integrating various computer-aided patient positioning methods. A highly precise optical tracking system and several subtraction imaging techniques have been realized as modules to supply basic video-based repositioning techniques. This paper describes the common framework architecture, the main software modules and their interfaces. An object-oriented software engineering process has been applied using the UML, C + + and the Qt library. The significance of the current framework prototype for the application in patient positioning as well as the extension to further application areas will be discussed. Particularly in experimental research, where special system adjustments are often necessary, the open design of the software allows problem-oriented extensions and adaptations.

15N- and 13C-NMR investigations of glucose oxidase from Aspergillus niger.

The apoprotein of glucose oxidase from Aspergillus niger was reconstituted with specifically 15N- and 13C-enriched FAD derivatives and investigated by 15N- and 13C-NMR spectroscopy. On the basis of the 15N-NMR results it is suggested that, in the oxidized state of glucose oxidase, hydrogen bonds are formed to the N(3) and N(5) positions of the isoalloxazine system. The hydrogen bond to N(3) is more pronounced than that to N(5) as compared with the respective hydrogen bonds formed between FMN and water. The resonance position of N(10) indicates a small decrease in sp2 hybridization compared to free flavin in water. Apparently the isoalloxazine ring is not planar at this position in glucose oxidase. Additional hydrogen bonds at the carbonyl groups of the oxidized enzyme-bound FAD were derived from the 13C-NMR results. A strong downfield shift observed for the C(4a) resonance may be ascribed in part to the decrease in sp2 hybridization at the N(10) position and to the polarization of the carbonyl groups at C(2) and C(4). The polarization of the isoalloxazine ring in glucose oxidase is more similar to FMN in water than to that of tetraacetyl-riboflavin in apolar solvents. In the reduced enzyme the N(1) position is anionic at pH 5.6. The pKa is shifted to lower pH values by at least 1 owing to the interaction of the FAD with the apoprotein. As in the oxidized state of the enzyme, a hydrogen bond is also formed at the N(3) position of the reduced flavin. The N(5) and N(10) resonances of the enzyme-bound reduced FAD indicate a decrease in the sp2 character of these atoms as compared with that of reduced FMN in aqueous solution. Some of the 15N- and 13C-resonance positions of the enzyme-bound reduced cofactor are markedly pH-dependent. The pH dependence of the N(5) and C(10a) resonances indicates a decrease in sp2 hybridization of the N(5) atom with increasing pH of the enzyme solution.

Medium-chain acyl CoA dehydrogenase: evidence for phosphorylation.

Mature medium chain acyl-CoA dehydrogenase isolated from pig kidney (pkMCADH) and originating from mitochondria carries a phosphate group as demonstrated by 31P-NMR-spectroscopy and chemical analysis. Two broad resonances at -6.3 and -8 ppm are observed and are assigned to the pyrophosphate group of the cofactor FAD. A third, narrow resonance at 4.65 ppm indicates the presence of a phosphomonoester residue. Chemical analysis of intact pkMCADH shows the presence of 3 +/- 0.3 phosphates, those of FAD and of an additional covalently attached phosphate. With recombinant, human wild type MCADH expressed in and purified from E. coli only the two FAD phosphates (2 +/- 0.35) are found. Similarly, pkMCADH which has been converted to the apoenzyme and reconstituted to holoenzyme also contains 2 +/- 0.4 phosphates. The covalently bound phosphate can be hydrolyzed by phosphatase and subsequently removed by dialysis. The phosphate group has no detectable effect on the catalytic activity of the MCADH measured with artificial and natural electron acceptors such as pig electron transferring flavoprotein. However, phosphorylation has a marked effect on protein solubility which is +5-fold lower for the dephosphorylated protein.

Quantum reflection from a solid surface at normal incidence.

We observed quantum reflection of ultracold atoms from the attractive potential of a solid surface. Extremely dilute Bose-Einstein condensates of 23Na, with peak density 10(11)-10(12) atoms/cm(3), confined in a weak gravitomagnetic trap were normally incident on a silicon surface. Reflection probabilities of up to 20% were observed for incident velocities of 1-8 mm/s. The velocity dependence agrees qualitatively with the prediction for quantum reflection from the attractive Casimir-Polder potential. Atoms confined in a harmonic trap divided in half by a solid surface exhibited extended lifetime due to quantum reflection from the surface, implying a reflection probability above 50%.

Dynamical instability of a doubly quantized vortex in a Bose-Einstein condensate.

Doubly quantized vortices were topologically imprinted in /F=1> 23Na condensates, and their time evolution was observed using a tomographic imaging technique. The decay into two singly quantized vortices was characterized and attributed to dynamical instability. The time scale of the splitting process was found to be longer at higher atom density.

Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients.

We determined the frequency of acute complications associated with insulin pump therapy in 161 insulin-dependent patients followed up for a total of 2,978 patient-months. Diabetes control improved substantively with pump therapy, but 42% of the patients experienced one or more acute complications while using insulin pumps. Infected infusion sites, ketoacidosis, and hypoglycemic coma occurred once in every 27, 78, and 175 patient-months, respectively. More patients experienced ketoacidosis after the onset of pump therapy than in an equivalent interval immediately before the onset of pump therapy. Ketoacidosis also occurred in more patients using pump therapy than in a comparison group of 165 patients receiving conventional insulin injections surveyed during an equivalent period. The frequency of hypoglycemic coma was not significantly changed by pump therapy.