Quantum simulation. Coherent imaging spectroscopy of a quantum many-body spin system.

Quantum simulators, in which well-controlled quantum systems are used to reproduce the dynamics of less understood ones, have the potential to explore physics inaccessible to modeling with classical computers. However, checking the results of such simulations also becomes classically intractable as system sizes increase. Here, we introduce and implement a coherent imaging spectroscopic technique, akin to magnetic resonance imaging, to validate a quantum simulation. We use this method to determine the energy levels and interaction strengths of a fully connected quantum many-body system. Additionally, we directly measure the critical energy gap near a quantum phase transition. We expect this general technique to become a verification tool for quantum simulators once experiments advance beyond proof-of-principle demonstrations and exceed the resources of conventional computers.

Beat note stabilization of mode-locked lasers for quantum information processing.

We stabilize a chosen radio frequency beat note between two optical fields derived from the same mode-locked laser pulse train in order to coherently manipulate quantum information. This scheme does not require access or active stabilization of the laser repetition rate. We implement and characterize this external lock, in the context of two-photon stimulated Raman transitions between the hyperfine ground states of trapped 171Yb(+) quantum bits.

Order of magnitude smaller limit on the electric dipole moment of the electron.

The Standard Model of particle physics is known to be incomplete. Extensions to the Standard Model, such as weak-scale supersymmetry, posit the existence of new particles and interactions that are asymmetric under time reversal (T) and nearly always predict a small yet potentially measurable electron electric dipole moment (EDM), d(e), in the range of 10(-27) to 10(-30) e·cm. The EDM is an asymmetric charge distribution along the electron spin (S(→)) that is also asymmetric under T. Using the polar molecule thorium monoxide, we measured d(e) = (-2.1 ± 3.7stat ± 2.5syst) × 10(-29) e·cm. This corresponds to an upper limit of |d(e)| < 8.7 × 10(-29) e·cm with 90% confidence, an order of magnitude improvement in sensitivity relative to the previous best limit. Our result constrains T-violating physics at the TeV energy scale.

Emergence and frustration of magnetism with variable-range interactions in a quantum simulator.

Frustration, or the competition between interacting components of a network, is often responsible for the emergent complexity of many-body systems. For instance, frustrated magnetism is a hallmark of poorly understood systems such as quantum spin liquids, spin glasses, and spin ices, whose ground states can be massively degenerate and carry high degrees of quantum entanglement. Here, we engineer frustrated antiferromagnetic interactions between spins stored in a crystal of up to 16 trapped (171)Yb(+) atoms. We control the amount of frustration by continuously tuning the range of interaction and directly measure spin correlation functions and their coherent dynamics. This prototypical quantum simulation points the way toward a new probe of frustrated quantum magnetism and perhaps the design of new quantum materials.

Quantum catalysis of magnetic phase transitions in a quantum simulator.

We control quantum fluctuations to create the ground state magnetic phases of a classical Ising model with a tunable longitudinal magnetic field using a system of 6 to 10 atomic ion spins. Because of the long-range Ising interactions, the various ground state spin configurations are separated by multiple first-order phase transitions, which in our zero temperature system cannot be driven by thermal fluctuations. We instead use a transverse magnetic field as a quantum catalyst to observe the first steps of the complete fractal devil's staircase, which emerges in the thermodynamic limit and can be mapped to a large number of many-body and energy-optimization problems.

Ultrafast spin-motion entanglement and interferometry with a single atom.

We report entanglement of a single atom's hyperfine spin state with its motional state in a time scale of less than 3 ns. We engineer a short train of intense laser pulses to impart a spin-dependent momentum transfer of ± 2 hk. Using pairs of momentum kicks, we create an atomic interferometer and demonstrate collapse and revival of spin coherence as the motional wave packet is split and recombined. The revival after a pair of kicks occurs only when the second kick is delayed by an integer multiple of the harmonic trap period, a signature of entanglement and disentanglement of the spin with the motion. Such quantum control opens a new regime of ultrafast entanglement in atomic qubits.

Ultrafast gates for single atomic qubits.

We demonstrate single-qubit operations on a trapped atom hyperfine qubit using a single ultrafast pulse from a mode-locked laser. We shape the pulse from the laser and perform a π rotation of the qubit in less than 50 ps with a population transfer exceeding 99% and negligible effects from spontaneous emission or ac Stark shifts. The gate time is significantly shorter than the period of atomic motion in the trap (Ω(Rabi)/ν(trap)>10(4)), demonstrating that this interaction takes place deep within the strong excitation regime.

A historic photomicrograph of a parasite (Trichomonas vaginalis).

Knowing that Alfred Donné was the discoverer of an important human parasite, and finding that he was also a pioneer of photomicrography, it occurred to me that his parasite might well have become a subject of his photography. It was a simple matter to confirm that this was indeed the case. The parasite he discovered was Trichomonas vaginalis; and, in collaboration with Foucault, Donné made a photomicrograph showing several protozoan parasites lying among vaginal epithelial cells. His publication of an engraved image of the photomicrograph in 1845, was a landmark in the history of photography and microbiology.

Remembrance of past images of Trichinella.

The development of achromatic microscopy and the invention of photography were contemporaneous with the earliest investigations on trichinellosis. The former was more important than the latter to 19th century studies on Trichinella. A selection of images, diverse but not comprehensive, is presented to illustrate the early history of trichinellosis.

Effect of refrigeration on the antinematodal efficacy of ivermectin.

Several observations have suggested that the anthelmintic ivermectin can affect nematodes by non-oral entry into the nematode body. To investigate this possibility further, we refrigerated Caenorhabditis elegans at 5 C to prevent its locomotion and to block the pharyngeal pumping that is so prominent a feature of its feeding. Worms were exposed to ivermectin (1-25 microg/ml) at that temperature for 1 hr, after which the medium was replaced by unmedicated medium at room temperature. After 1 hr at room temperature the worms were examined and counted to determine the degree to which irreversible immobilization had occurred. The drug was significantly less effective at 5 C than at room temperature. This reduction in potency could be attributed to a general cold-induced decline in the rate of the biochemical processes involved in drug action. Alternatively, the reduction could be attributed to the cold-induced blockade of pharyngeal pumping, which would suggest that the efficacy of ivermectin is partially the result of oral intake of drug. The fact that antinematodal efficacy was not entirely abrogated and reached a significant level despite blockade of pharyngeal pumping supports the former interpretation and is in accord with earlier indications that ivermectin can enter by non-oral routes. This conclusion is further supported by the observation that ivermectin is active against the nonfeeding third-stage larva of Haemonchus contortus.

Optical billiards for atoms.

One of the central paradigms for classical and quantum chaos in conservative systems is the two-dimensional billiard in which particles are confined to a closed region in the plane, undergoing elastic collisions with the walls and free motion in between. We report the first realization of billiards using ultracold atoms bouncing off beams of light. These beams create the desired spatial pattern, forming an "optical billiard." We find excellent agreement between theory and our experimental demonstration of chaotic and stable motion in optical billiards, establishing a new testing ground for classical and quantum chaos.

Haemonchus contortus (Nematoda: Trichostrongylidae) is much more sensitive than Caenorhabditis elegans (Nematoda: Rhabditidae) to the ovicidal action of thiabendazole.

When eggs of the trichostrongylid nematode Haemonchus contortus were exposed to thiabendazole, the concentration required to prevent hatching in 90% of the eggs (MIC90) was found to be 0.1 microg/ml (using 1% dimethylsulfoxide [DMSO] as solvent). In contrast, eggs of the free-living rhabditid nematode Caenorhabditis elegans hatched at normal rates at a concentration 200 times higher, i.e., 20 microg/ml, and showed only a partial inhibitory effect at a concentration 1,200 times higher, i.e., 120 microg/ml (in 3% DMSO). Because solubility limitations precluded the testing of higher concentrations of thiabendazole, a more soluble derivative, 5-([1-methylethoxy]carbonylamino)-2-(4-thiazloyl)1H-++ +benzimidazolyliminoacetic acid N,N-diethylethanamine salt, was tested against C. elegans eggs. The MIC90 was found to be 400 microg/ml, and although the derivative was not tested against H. contortus eggs, this finding further suggests that C. elegans eggs have an exceptionally low degree of benzimidazole sensitivity.

Substance P dependence of endosomal fusion during bladder inflammation.

Urinary bladder instillation of ovalbumin into presensitized guinea pigs stimulates rapid development of local bladder inflammation. Substance P is an important mediator of this inflammatory response, as substance P antagonists largely reverse the process. Vacuolization of the subapical endosomal compartment of the transitional epithelial cells lining the bladder suggests that changes in endosomal trafficking and fusion are also part of the inflammatory response. To test directly for substance P mediation of changes in endosomal fusion, we reconstituted fusion of transitional cell endosomes in vitro using both cuvette-based and flow cytometry energy transfer assays. Bladders were loaded with fluorescent dyes by a hypotonic withdrawal protocol before endosomal isolation by gradient centrifugation. Endosomal fusion assayed by energy transfer during in vitro reconstitution was both cytosol and ATP dependent. Fusion was confirmed by the increase in vesicle size on electron micrographs of fused endosomal preparations compared with controls. In inflamed bladders, dye uptake was inhibited 20% and endosomal fusion was inhibited 50%. These changes are partly mediated by the neurokinin-1 (NK1) receptor (NK1R), as 4 mg/kg of CP-96,345, a highly selective NK1 antagonist, increased fusion in inflamed bladders but had no effect on control bladders. The receptor-mediated nature of this effect was demonstrated by the expression of substance P receptor mRNA in rat bladder lumen scrapings and by the detection of the NK1R message in guinea pig subapical endosomes by Western blot analysis. The NK1Rs were significantly upregulated following induction of an inflammatory response in the bladder. These results demonstrate that 1) in ovalbumin-induced inflammation in the guinea pig bladder, in vitro fusion of apical endosomes is inhibited, showing endocytotic processes are altered in inflammation; 2) pretreatment in vivo with an NK1R antagonist blocks this inhibition of in vitro fusion, demonstrating a role for NK1R in this process; and 3) the NK1R is present in higher amounts in apical endosomes of inflamed bladder, suggesting changes in translation or trafficking of the NK1R during the inflammatory process. This suggests that NK1R can change the fusion properties of membranes in which it resides.

Select de novo gene and protein expression during renal epithelial cell culture in rotating wall vessels is shear stress dependent.

The rotating wall vessel has gained popularity as a clinical cell culture tool to produce hormonal implants. It is desirable to understand the mechanisms by which the rotating wall vessel induces genetic changes, if we are to prolong the useful life of implants. During rotating wall vessel culture gravity is balanced by equal and opposite hydrodynamic forces including shear stress. The current study provides the first evidence that shear stress response elements, which modulate gene expression in endothelial cells, are also active in epithelial cells. Rotating wall culture of renal cells changes expression of select gene products including the giant glycoprotein scavenger receptors cubulin and megalin, the structural microvillar protein villin, and classic shear stress response genes ICAM, VCAM and MnSOD. Using a putative endothelial cell shear stress response element binding site as a decoy, we demonstrate the role of this sequence in the regulation of selected genes in epithelial cells. However, many of the changes observed in the rotating wall vessel are independent of this response element. It remains to define other genetic response elements modulated during rotating wall vessel culture, including the role of hemodynamics characterized by 3-dimensionality, low shear and turbulence, and cospatial relation of dissimilar cell types.

Myeloma light chains are ligands for cubilin (gp280).

Although myeloma light chains are known to undergo receptor-mediated endocytosis in the kidney, the molecular identity of the receptor has not been characterized. We examined the interaction between cubilin (gp280) and four species of light chains isolated from the urine of patients with multiple myeloma. Four lines of evidence identify cubilin, a giant glycoprotein receptor, which is restricted in distribution to endocytic scavenger pathways and which has potent effects on endosomal trafficking, as a potentially physiologically relevant binding site for light chains: 1) light chains coeluted during immunoaffinity purification of cubilin; 2) polyclonal antisera to cubilin but not control sera, displaced human light chain binding from rat renal brush-border membranes; 3) cubilin bound to multiple species of light chains during surface plasmon resonance; 4) anti-cubilin antiserum interfered with light chain endocytosis by visceral yolk sac epithelial cells. However, both binding of light chains to brush-border membranes and endocytosis of light chains by yolk sac epithelial cells were only partially inhibited by anticubilin antibodies, suggesting presence of additional or alternate binding sites for light chains. Excess light chain had a potent inhibitory effect on endosomal fusion in vitro. Binding showed dose and time-dependent saturability with low-affinity, high-capacity equilibrium binding parameters. These data demonstrate that cubilin plays a role in the endocytosis and trafficking of light chains in renal proximal tubule cells.

Membrane potential mediates H(+)-ATPase dependence of "degradative pathway" endosomal fusion.

In some epithelial cell lines, the uptake and degradation of proteins is so pronounced as to be regarded as a specialized function known as "degradative endocytosis." The endosomal pathways of the renal proximal tubule and the visceral yolk sac share highly specialized structures for "degradative endocytosis." These endosomal pathways also have a unique distribution of their H(+)-ATPase, predominantly in the subapical endosomal pathway. Previous studies provide only indirect evidence that H(+)-ATPases participate in endosomal fusion events: formation of vesicular intermediates between early and late endosomes is H(+)-ATPase dependent in baby hamster kidney cells, and H(+)-ATPase subunits bind fusion complex proteins in detergent extracts of fresh rat brain. To determine directly whether homotypic endosomal fusion is H(+)-ATPase dependent, we inhibited v-type H(+)-ATPase during flow cytometry and cuvette-based fusion assays reconstituting endosomal fusion in vitro. We report that homotypic fusion in subapical endosomes derived from rat renal cortex, and immortalized visceral yolk sac cells in culture, is inhibited by the v-type H(+)-ATPase specific inhibitor bafilomycin A1. Inhibition of fusion by H(+)-ATPase is mediated by the membrane potential as collapsing the pH gradient with nigericin had no effect on homotypic endosomal fusion, while collapsing the membrane potential with valinomycin inhibited endosomal fusion. Utilizing an in vitro reconstitution assay this data provides the first direct evidence for a role of v-type H(+)-ATPase in mammalian homotypic endosomal fusion.

Inhibitory effect of chlorpromazine on nematode eggs and larvae.

Chlorpromazine inhibited the hatching of eggs of the parasitic nematode Haemonchus contortus and the free-living nematode Caenorhabditis elegans. In both species, hatching occurred at a concentration of 100 microg/ml but was almost totally blocked at 400 microg/ml. In the case of C. elegans, the effect was shown to be reversible by removal of chlorpromazine after exposure of the eggs to the drug for 1 hr. Caenorhabditis elegans larvae that hatched in a chlorpromazine concentration of 100 microg/ml were killed, but those that hatched in a concentration of 6.25 microg/ml were not. Taken together with data published by others, these observations indicate that the first-stage larva of C. elegans is less sensitive to chlorpromazine than is the adult worm.

Enhanced ability of third-stage larvae of Haemonchus contortus to withstand drug exposure following chemically induced exsheathment.

Normal (ensheathed) and exsheathed third-stage larvae of Haemonchus contortus were exposed in vitro to various concentrations of levamisole or ivermectin. Exsheathment was induced by brief exposure to sodium hypochlorite. When observed approximately 2 min after immersion in levamisole at 0, 5, 10, and 100 micrograms/ml (3 trials), the mean percentage motility (to nearest whole number) of normal larvae was 84, 43, 37, and 15, respectively. However, the mean percent motility of exsheathed larvae was 77, 78, 79, and 72, respectively. When observed 55 min after immersion in levamisole at the same concentrations, the mean percent motility of normal larvae was 76, 4, 3, and 0, respectively, whereas that for exsheathed larvae was 72, 75, 68, and 0. When observed 45 min after initial exposure to ivermectin at 0, 8, 80, and 160 micrograms/ml, the mean percent motility of normal larvae was 87, 6, 3, and 3, respectively, whereas the mean percent motility of exsheathed larvae was 94, 75, 29, and 14, respectively. Thus, both drugs were effective against both kinds of larva; but the time and concentration required for efficacy were markedly affected by the presence or absence of a sheath or by unknown effects of the exsheathment process. For both levamisole and ivermectin, exsheathed larvae had a much greater ability than normal larvae to withstand drug exposure.