Fiber chirped pulse amplifier at 2.08 µm emitting 383-fs pulses at 10 nJ and 7 MHz.

An all-polarization maintaining (PM) fiber chirped pulse amplifier system at 2.08 µm based on thulium:holmium codoped gain fibers is reported. An inhouse built oscillator emits pulses at a repetition rate of 7 MHz with a spectral full width at half-maximum (FWHM) bandwidth of 23.5 nm at 2.8 mW average output power. The pulses are temporally stretched and subsequently amplified in a double-stage amplifier setup. The stretched pulses are compressed to 383 fs by use of a Martinez-style setup at an output pulse energy of 10.2 nJ. By neglecting temporal stretching, high peak powers in a single amplifier stage led to Raman soliton formation at 2.3 µm.

[DLys(6)]-luteinizing hormone releasing hormone-curcumin conjugate inhibits pancreatic cancer cell growth in vitro and in vivo.

Pancreatic ductal adenocarcinomas are invariably lethal, and developing effective treatments that have minimal side effects is a challenge. Previous studies from our laboratory have shown that conjugates of cell membrane disrupting lytic peptides and luteinizing hormone releasing hormone (LHRH) target and destroy human prostate and breast cancer cells in xenografts in the nude mouse model (Hansel et al., Mol Cell Endocrinol 2007;260-262:183-9; Hansel et al., Mol Cell Endocrinol 2007;269:26-33), which express LHRH receptors. The objectives of our study were to synthesize a bioconjugate of LHRH analog ([DLys(6)]-LHRH) and a dietary microchemical (curcumin) and test the hypothesis that [DLys(6)]-LHRH-curcumin targets and inhibits pancreatic cancer cell growth in vitro and in vivo. In in vitro studies, we determined by confocal microscopy, flow cytometry analysis and reverse transcriptase-polymerase chain reaction that MIAPaCa-2, Panc-1 and BxPC-3 pancreatic cancer cell lines express LHRH receptors. [DLys(6)]-LHRH-curcumin inhibited cell proliferation of pancreatic cancer cell lines and induced apoptotic cell death (p < 0.05). Apoptosis was induced by cleavage of polyadenosine-5'-diphosphate-ribose-polymerase and caspase-3. The activity of [DLys(6)]-LHRH-curcumin was equal to free curcumin at equimolar concentrations in vitro. Unlike curcumin itself, the [DLys(6)]-LHRH-curcumin conjugate is water soluble which allows its intravenous administration. In two in vivo studies, [DLys(6)]-LHRH-curcumin given intravenously caused a significant (p < 0.01) reduction in tumor weights and volumes, and free curcumin given by gavage at an equal dose failed to cause a significant reduction in tumor weights and volumes in the nude mouse pancreatic cancer model. [DLys(6)]-LHRH-curcumin treatment enhanced apoptosis compared to [DLys(6)]-LHRH and vehicle-treated controls in tumor tissue. In conclusion, [DLys(6)]-LHRH-curcumin may be useful in treating pancreatic cancer.

Trapped-ion antennae for the transmission of quantum information.

More than 100 years ago, Hertz succeeded in transmitting signals over a few metres to a receiving antenna using an electromagnetic oscillator, thus proving the electromagnetic theory developed by Maxwell. Since this seminal work, technology has developed, and various oscillators are now available at the quantum mechanical level. For quantized electromagnetic oscillations, atoms in cavities can be used to couple electric fields. However, a quantum mechanical link between two mechanical oscillators (such as cantilevers or the vibrational modes of trapped atoms or ions) has been rarely demonstrated and has been achieved only indirectly. Examples include the mechanical transport of atoms carrying quantum information or the use of spontaneously emitted photons. Here we achieve direct coupling between the motional dipoles of separately trapped ions over a distance of 54 micrometres, using the dipole-dipole interaction as a quantum mechanical transmission line. This interaction is small between single trapped ions, but the coupling is amplified by using additional trapped ions as antennae. With three ions in each well, the interaction is increased by a factor of seven compared to the single-ion case. This enhancement facilitates bridging of larger distances and relaxes the constraints on the miniaturization of trap electrodes. The system provides a building block for quantum computers and opportunities for coupling different types of quantum systems.

Absolute frequency measurement of the 40Ca+ 4s(2)S_(1/2)-3d(2)D_(5/2) clock transition.

We report on the first absolute transition frequency measurement at the 10;{-15} level with a single, laser-cooled 40Ca+ ion in a linear Paul trap. For this measurement, a frequency comb is referenced to the transportable Cs atomic fountain clock of LNE-SYRTE and is used to measure the 40Ca+ 4s ;{2}S_{1/2}-3d ;{2}D_{5/2} electric-quadrupole transition frequency. After the correction of systematic shifts, the clock transition frequency nu_{Ca;{+}}=411 042 129 776 393.2(1.0) Hz is obtained, which corresponds to a fractional uncertainty within a factor of 3 of the Cs standard. In addition, we determine the Landé g factor of the 3d;{2}D_{5/2} level to be g_{5/2}=1.200 334 0(3).

Realization of the quantum Toffoli gate with trapped ions.

Gates acting on more than two qubits are appealing as they can substitute complex sequences of two-qubit gates, thus promising faster execution and higher fidelity. One important multiqubit operation is the quantum Toffoli gate that performs a controlled NOT operation on a target qubit depending on the state of two control qubits. Here we present the first experimental realization of the quantum Toffoli gate in an ion trap quantum computer, achieving a mean gate fidelity of 71(3)%. Our implementation is particularly efficient as the relevant logic information is directly encoded in the motion of the ion string.

Realization of universal ion-trap quantum computation with decoherence-free qubits.

Any residual coupling of a quantum computer to the environment results in computational errors. Encoding quantum information in a so-called decoherence-free subspace provides means to avoid these errors. Despite tremendous progress in employing this technique to extend memory storage times by orders of magnitude, computation within such subspaces has been scarce. Here, we demonstrate the realization of a universal set of quantum gates acting on decoherence-free ion qubits. We combine these gates to realize the first controlled-NOT gate towards a decoherence-free, scalable quantum computer.

Process tomography of ion trap quantum gates.

A crucial building block for quantum information processing with trapped ions is a controlled-NOT quantum gate. In this Letter, two different sequences of laser pulses implementing such a gate operation are analyzed using quantum process tomography. Fidelities of up to 92.6(6)% are achieved for single-gate operations and up to 83.4(8)% for two concatenated gate operations. By process tomography we assess the performance of the gates for different experimental realizations and demonstrate the advantage of amplitude-shaped laser pulses over simple square pulses. We also investigate whether the performance of concatenated gates can be inferred from the analysis of the single gates.

Scalable multiparticle entanglement of trapped ions.

The generation, manipulation and fundamental understanding of entanglement lies at the very heart of quantum mechanics. Entangled particles are non-interacting but are described by a common wavefunction; consequently, individual particles are not independent of each other and their quantum properties are inextricably interwoven. The intriguing features of entanglement become particularly evident if the particles can be individually controlled and physically separated. However, both the experimental realization and characterization of entanglement become exceedingly difficult for systems with many particles. The main difficulty is to manipulate and detect the quantum state of individual particles as well as to control the interaction between them. So far, entanglement of four ions or five photons has been demonstrated experimentally. The creation of scalable multiparticle entanglement demands a non-exponential scaling of resources with particle number. Among the various kinds of entangled states, the 'W state' plays an important role as its entanglement is maximally persistent and robust even under particle loss. Such states are central as a resource in quantum information processing and multiparty quantum communication. Here we report the scalable and deterministic generation of four-, five-, six-, seven- and eight-particle entangled states of the W type with trapped ions. We obtain the maximum possible information on these states by performing full characterization via state tomography, using individual control and detection of the ions. A detailed analysis proves that the entanglement is genuine. The availability of such multiparticle entangled states, together with full information in the form of their density matrices, creates a test-bed for theoretical studies of multiparticle entanglement. Independently, 'Greenberger-Horne-Zeilinger' entangled states with up to six ions have been created and analysed in Boulder.

5-(3-Phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen: mechanistic studies on phototoxicity.

5-(3-Phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen are blockers of the lymphocyte potassium channel Kv1.3 with EC50 values < 10 nM and may be used as new potential immunosuppressive drugs. As reported for many furocoumarins, these compounds show phototoxic properties and react under UV radiation with different targets in the cell, e.g. DNA or proteins and lipids in membranes. The photoreactions with these targets were investigated and compared to the well-known derivatives psoralen, 5-methoxypsoralen, 8-methoxypsoralen and 4,5',8-trimethylpsoralen. Moreover, absorption properties and the capability to photoproduce singlet oxygen (1O2) and reactive oxygen species (ROS) were studied. It was found that 5-(3-phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen are similar or less phototoxic in vitro as 5-methoxypsoralen which is the furocoumarin with the weakest phototoxicity in vivo compared to psoralen, 8-methoxypsoralen and 4,5',8-trimethylpsoralen.

Photodynamic and photo-cross-linking potential of bergamottin.

Bergamottin (5-geranoxypsoralen) is a main component of bergamot and grapefruit oil. In order to investigate the photophysical and photochemical behaviour of bergamottin, absorption and fluorescence properties, production of singlet oxygen and superoxide radical anions and further cross-linking of DNA were studied. Strong photochemical reactions were not observed.

Bell states of atoms with ultralong lifetimes and their tomographic state analysis.

Arbitrary atomic Bell states with two trapped ions are generated in a deterministic and preprogrammed way. The resulting entanglement is quantitatively analyzed using various measures of entanglement. For this, we reconstruct the density matrix using single qubit rotations and subsequent measurements with near-unity detection efficiency. This procedure represents the basic building block for future process tomography of quantum computations. As a first application, the temporal decay of entanglement is investigated in detail. We observe ultralong lifetimes for the Bell states Psi(+/-), close to the fundamental limit set by the spontaneous emission from the metastable upper qubit level and longer than all reported values by 3 orders of magnitude.

Deterministic quantum teleportation with atoms.

Teleportation of a quantum state encompasses the complete transfer of information from one particle to another. The complete specification of the quantum state of a system generally requires an infinite amount of information, even for simple two-level systems (qubits). Moreover, the principles of quantum mechanics dictate that any measurement on a system immediately alters its state, while yielding at most one bit of information. The transfer of a state from one system to another (by performing measurements on the first and operations on the second) might therefore appear impossible. However, it has been shown that the entangling properties of quantum mechanics, in combination with classical communication, allow quantum-state teleportation to be performed. Teleportation using pairs of entangled photons has been demonstrated, but such techniques are probabilistic, requiring post-selection of measured photons. Here, we report deterministic quantum-state teleportation between a pair of trapped calcium ions. Following closely the original proposal, we create a highly entangled pair of ions and perform a complete Bell-state measurement involving one ion from this pair and a third source ion. State reconstruction conditioned on this measurement is then performed on the other half of the entangled pair. The measured fidelity is 75%, demonstrating unequivocally the quantum nature of the process.

3-Alkyl- and 3-aryl-7H-furo[3,2-g]chromen-7-ones as blockers of the voltage-gated potassium channel Kv1.3.

3-Alkyl- and 3-aryl-7H-furo[3,2-g]chromen-7-ones were synthesised and studied for their effects on voltage-gated K+ and Na+ channels of the neuroblastoma cell-line N1E-115 and K+ channels of L-929 mouse-fibroblasts, stably transfected with mKv1.3. All furocoumarins tested showed Kv channel blocking activities, the most potent one in a half-blocking concentration of 0.7 microM.

Evidence that lamprey GnRH-III does not release FSH selectively in cattle.

Experiments were performed to test the hypothesis that lamprey GnRH-III (lGnRH-III) selectively releases FSH. Primary cultures of bovine adenohypophyseal cells were treated with mammalian GnRH (mGnRH) and lGnRH-III (10(-9), 10(-8), 10(-7) and 10(-6) M) or control media in Experiment 1. All doses of mGnRH and the two highest doses of lGnRH-III stimulated (P < 0.001) a non-selective release of LH and FSH. In Experiments 2-4, Latin Square designs were utilized in vivo to examine whether physiological and hormonal milieu regulate putative selective effects of lGnRH-III. In Experiments 2 and 3, ovariectomized cows with basal levels of estradiol only (Experiment 2) or in combination with luteal phase levels of progester-one (Experiment 3) were injected with mGnRH and lGnRH-III (0.055, 0.11, 0.165 and 1.1 microg/kg body weight (BW) and saline. All doses of mGnRH released (P < 0.001) LH and FSH, but only the highest dose of lGnRH-III stimulated (P < 0.001) a non-selective release of both LH and FSH (Experiment 3). For Experiments 4A and 4B, intact, mid-luteal phase cows were injected with mGnRH and lGnRH-III (1.1 microg/kg BW; Experiment 4A), lGnRH-III (1.1 and 4.4 microg/kg BW; Experiment 4B) and saline. As before, mGnRH released (P < 0.001) both LH and FSH at all doses. In contrast, lGnRH-III at the highest dose released (P < 0.001) LH but not FSH. These findings suggest that lGnRH-III may act as a weak competitor for the mGnRH receptor and do not support the hypothesis that it selectively releases FSH in cattle.

The potential for improving the growth and development of cultured farm animal oocytes.

Previous predictions that the technologies for producing genetically engineered large animal embryos containing genes for faster growth rates, leaner carcasses, greater disease resistance and improved lactational performance would be available early in the twenty-first century have been, for the most part, realized. The animal industries have been slow to adopt these technological advances and it cannot be said that any of them are currently having great impact on animal agriculture worldwide. A major reason for this is the inefficiencies of the techniques for superovulation, ovum recovery, in vitro fertilization, nuclear transfer, cloning and embryo transfer. Although improvements in these techniques can be expected, the best hope for increasing the impact of embryo transfer technologies on the animal industries lies in developing ways to mature, harvest, store and fertilize in vitro the large numbers of primordial oocytes present in the ovaries of all farm animals. Although limited progress has been made in the culture of bovine primordial oocytes, it is clear that much more research is needed to achieve success in this important area.

Targeted destruction of normal and cancer cells through lutropin/choriogonadotropin receptors using Hecate-betaCG conjugate.

A recent approach to cancer treatment is destruction of malignant and non-malignant tumors by hormonally targeted lytic peptides. The presence of lutropin/choriogonadotropin (LH/CG) receptors has been confirmed in several cancer cells (e.g. breast, ovarian, and prostate). In a series of experiments conducted in vitro, we have used a conjugate of the 23-amino acid lytic peptide Hecate and a 15-amino acid segment of beta-chain of CG. To test the hypothesis that Hecate-betaCG selectively destroys porcine granulosa and luteal cells, and Leydig cancer cell line (BLT-1) possessing LH/CG receptors, the conjugate was added to culture media at different concentrations of 0.5 to 10 micro M. Spleen cells and late passage of granulosa cancer cell line (KK-1) not-possessing LH/CG receptors were used as controls. The toxicity of Hecate-betaCG conjugate was concentration-dependent in all cell types but different among various cells. The toxicity of the conjugate to treated cells was closely correlated with the number of LH/CG receptors per cell. At low concentration (1 micro M), Hecate-betaCG was more cytotoxic to cells bearing LH/CG receptors than to controls (p < 0.01). In contrast to cells possessing LH/CG receptors, cancer cell line KK-1 and spleen cells were sensitive only at concentration of 5 micro M (p < 0.001). We conclude that Hecate-betaCG selectively kills cells expressing LH/CG receptors; its toxicity is dependent on the number of binding sites for LH/CG.

Bose-Einstein condensation on a microelectronic chip.

Although Bose-Einstein condensates of ultracold atoms have been experimentally realizable for several years, their formation and manipulation still impose considerable technical challenges. An all-optical technique that enables faster production of Bose-Einstein condensates was recently reported. Here we demonstrate that the formation of a condensate can be greatly simplified using a microscopic magnetic trap on a chip. We achieve Bose-Einstein condensation inside the single vapour cell of a magneto-optical trap in as little as 700 ms-more than a factor of ten faster than typical experiments, and a factor of three faster than the all-optical technique. A coherent matter wave is emitted normal to the chip surface when the trapped atoms are released into free fall; alternatively, we couple the condensate into an 'atomic conveyor belt', which is used to transport the condensed cloud non-destructively over a macroscopic distance parallel to the chip surface. The possibility of manipulating laser-like coherent matter waves with such an integrated atom-optical system holds promise for applications in interferometry, holography, microscopy, atom lithography and quantum information processing.

Angular methoxy-substituted furo- and pyranoquinolinones as blockers of the voltage-gated potassium channel Kv1.3.

The voltage-gated potassium channel Kv1.3 constitutes an attractive target for immunosuppression because of its role in T-lymphocyte activation and its functionally restricted expression to lymphocytes. Blockade of Kv1.3 channels by margatoxin has previously been shown to prevent T-cell activation and attenuate immune responses in vivo. In the present study, several furo- and pyranoquinoline derivatives were synthesized and screened for their blocking activities of Kv1.3 channels, stably expressed in mice-fibroblasts L929. In addition the activities of the compounds on Kv currents of the neuroblastoma cell line N1E-115 were determined. The most potent compounds, the angular furoquinolinone 8-methoxy-2-(1'-methylethyl)-5-methyl-4,5-dihydrofuro[3,2-c]quinolin-4-one (8c) and the angular pyranoquinolinone 9-methoxy-2,2,6-trimethyl-2,6-dihydro-5H-pyrano[3,2-c]quinolin-5-one (9a), inhibited Kv1.3 channels with half-blocking concentrations of 5 and 10 microM, respectively, and displayed 8-fold (8c) and 2-fold (9a) selectivity over Kv currents of N1E-115 cells. Thus, compounds 8c and 9a might function as a template for the development of novel immunosuppressants.

Vilsmeier formylation of praziquantel: synthesis and application for polarographic assay.

A simple and sensitive method for the polarographic determination of praziquantel (1) after derivatization using Vilsmeier formylation is described. The polarographically active compound obtained by this procedure has been separated, identified and prepared using N,N-dimethylformamide and phosphorus oxychloride.

Magnetic conveyor belt for transporting and merging trapped atom clouds.

We demonstrate an integrated magnetic device which transports cold atoms near a surface with very high positioning accuracy. Time-dependent currents in a lithographic conductor pattern create a moving chain of potential wells; atoms are transported in these wells while remaining confined in all three dimensions. We achieve mean fluxes up to 10(6) s(-1) with a negligible heating rate. An extension of this device allows merging of atom clouds by unification of two Ioffe-Pritchard potentials. The unification, which we demonstrate experimentally, can be performed without loss of phase space density. This novel, all-magnetic atom manipulation offers exciting perspectives, such as trapped-atom interferometry.