Squeezing and entanglement in a Bose-Einstein condensate.

Entanglement, a key feature of quantum mechanics, is a resource that allows the improvement of precision measurements beyond the conventional bound attainable by classical means. This results in the standard quantum limit, which is reached in today's best available sensors of various quantities such as time and position. Many of these sensors are interferometers in which the standard quantum limit can be overcome by using quantum-entangled states (in particular spin squeezed states) at the two input ports. Bose-Einstein condensates of ultracold atoms are considered good candidates to provide such states involving a large number of particles. Here we demonstrate spin squeezed states suitable for atomic interferometry by splitting a condensate into a few parts using a lattice potential. Site-resolved detection of the atoms allows the measurement of the atom number difference and relative phase, which are conjugate variables. The observed fluctuations imply entanglement between the particles, a resource that would allow a precision gain of 3.8 dB over the standard quantum limit for interferometric measurements.

X-ray and cis-diamminedichloroplatinum(II) cross-resistance in human tumor cell lines.

Clinical studies have suggested a close correlation between cis-diamminedichloroplatinum(II) (cisplatin) and radiation resistance. To determine whether this cross-resistance is due to an inherent cellular resistance to both agents, ten early passage human tumor cell lines were examined for their radiation and cisplatin sensitivity in vitro. Previous studies have suggested that these early passage tumor cell lines retain many of their in vivo characteristics and are therefore good models for tumor cells in vivo. Radioresistance was strongly associated with cisplatin resistance in these cell lines. Four of the cell lines examined were radioresistant, having Dos greater than 2.0 Gy. These four lines were also resistant to cisplatin, with the dose reducing survival to 10% greater than 1.29 microM. The remaining six cell lines had Dos ranging from 1.07 to 1.57 Gy of X-ray and doses reducing survival to 10% of less than 0.83 microM cisplatin. Because early passage human tumor cell lines were used, resistance or sensitivity to radiation and cisplatin most likely developed in vivo and was not due to selection in vitro. These results indicate that cross-resistance between cisplatin and radiation in vivo is probably due primarily to an inherent cellular resistance to these agents and not necessarily to the tumor microenvironment in situ.

Expression of recombinant human granulocyte colony-stimulating factor in CHO dhfr- cells: new insights into the in vitro amplification expression system.

The in vitro amplification method for heterologous gene expression in mammalian cells is based on the stable transfection of cells with long, linear DNA molecules having several copies of complete expression units, coding for the gene of interest, linked to one terminal unit, coding for the selectable marker. DNA concatenamers containing additional expression units can also be prepared: we exploited this feature by co-polymerizing expression units coding for granulocyte colony-stimulating factor (G-CSF) with cassettes for dihydrofolate reductase (DHFR) and for neomycin (Nm) resistance, as selectable markers. We were thus able to obtain high level production of G-CSF in chinese hamster ovary (CHO) dhfr- cells by combining in vitro amplification to just one step of in vivo amplification. This approach required a considerably shorter time than the classical, stepwise amplification by methotrexate.

Saliva as a medium for investigating intra- and interindividual differences in sex hormone levels in premenopausal women.

Repeated measurement of ovarian steroids in saliva could provide an advantage in studies estimating long-term sex steroid exposure in premenopausal women, by reducing the measurement error associated with collection of serum or urine samples. We previously reported on characteristics of ultrasensitive RIAs adapted for extraction-free measurement of estradiol (E2) and progesterone (PG) in saliva. The purpose of the present study was to evaluate the consistency of E2 and PG levels in saliva in the same women across menstrual cycles, and to compare this with the variation observed between women. We also evaluated the effect of altering the number of consecutive daily samples considered and the method for locating a particular cycle day in relation to ovulation (day 0). Study participants included 12 healthy women who provided daily saliva samples for two consecutive, ovulatory menstrual cycles. A single midluteal serum sample was collected 7-8 days after detection of a luteinizing hormone (LH) peak in urine. We plotted individual cycle profiles and computed intraclass correlation coefficients (ICC) for various definitions of peak and cumulative daily hormone level. For peak PG, determined as the maximal running 3-day mean, ICC was 0.68. For cumulative PG, based on 8 consecutive cycle days (+2 to +9), ICCs were 0.72-0.76 when reverse dating LH peak or rise in salivary PG determined day 0. For E2, ICCs ranged from 0.74 to 0.79 by various dating methods for the 5 preovulatory days (-4-0), and from 0.85 to 0.92 for the 15 days about the center of the cycle (-6 to +8). With exclusion of just the first 5 days of the cycle, the ICC for E2 was 0.91. For both E2 and PG, selection of 5 or 7 days for the estimation of the midluteal mean level provided separation of within and between subject variance that was comparable with a LH-timed serum sample. These results indicate that daily saliva samples can be combined to clarify the interindividual differences in E2 and PG levels in premenopausal women, and that these interindividual differences may be greater than previously imagined.

Faster repair of DNA double-strand breaks in radioresistant human tumor cells.

To investigate the molecular basis of radiation resistance in human tumor cells, the induction and repair of radiation-induced DNA single- and double-strand breaks was determined by DNA elution analysis in two normal human cell lines and 12 early-passage human tumor cell lines of varying radiosensitivities. The radiosensitivities (D0) of the cell lines ranged from 1 to 2.9 Gy. Inherent cellular radiosensitivity was found to directly correlate with the rate at which the DNA double-strand breaks were repaired. Radioresistant cell lines repaired approximately 90% of their radiation-induced DNA double-strand breaks within 1 hr of irradiation while more radiosensitive cell lines required 2-4 hr to repair the same fraction of damage. Radioresistant cell lines also had lower initial DNA double-strand break frequencies. DNA single-strand break induction and repair was not found to be an important factor in the radiation response of human tumor and normal cell lines. Therefore, the rate at which DNA double strand breaks are repaired is a critical factor underlying radioresistance in human tumor cell lines.

Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma.

We have identified and characterized two different subclasses of binding site for the novel peptido-leukotriene (LT) antagonist, [3H]ICI 198,615, in membranes from human lung parenchyma using a receptor-ligand assay. This novel compound is representative of a new class of LT receptor antagonists and it has been demonstrated to be several orders of magnitude more potent and selective than most other LT antagonists described to date. The binding of [3H]ICI 198,615 is rapid, specific and saturable. Equilibrium was reached within 5-10 min. Non linear fitting of dissociation time courses has revealed the presence of two different components (K(off)1 = 8.3 +/- 6.8 x 10(-4) sec-1 and K(off)2 = 0.79 +/- 1.66 x 10(-3) sec-1) of the kinetic curves, suggesting heterogeneity of the binding sites. Computer analysis of equilibrium binding data obtained at 25 degrees results in a model with two classes of binding sites, a high affinity-low capacity class with Kd1 = 0.024 +/- 0.014 nM and Bmax1 = 0.015 +/- 0.004 pmol/mg protein and a low affinity-high capacity class with Kd2 = 6326 +/- 3859 nM and Bmax2 = 473 +/- 383 pmol/mg protein. In competition studies, LTD4 was also found to interact with two classes of binding site (Kd1 = 0.016 +/- 0.008 nM and Kd2 = 15195 +/- 8965 nM). On the contrary, LTE4 and LTC4 were found to interact with a homogeneous class of sites only with Kd = 7466 +/- 4629 nM and Kd = 428 +/- 73 nM, respectively. Furthermore, we have evaluated the effect of a number of LT antagonists on the binding of [3H]ICI 198,615. Ro 24-5913 (Kd = 3.0 +/- 2.1 nM), FPL55712 (Kd = 4945 +/- 2868 nM), LY171883 (Kd = 19628 +/- 12365 nM), SKF 104353 (Kd = 74.2 +/- 46 nM) and its enantiomer SKF 104373 (Kd = 13627 +/- 6813 nM) were found to interact with a single class of binding sites. The present studies indicate a heterogeneity of binding sites for ICI 198,615 in membranes from human lung parenchyma and that ICI 198,615 is a very potent and selective antagonist of LTD4 receptors in this tissue.

Josephson effects in dilute bose-einstein condensates

We propose an experiment that would demonstrate the dc and ac Josephson effects in two weakly linked Bose-Einstein condensates. We consider a time-dependent barrier, moving adiabatically across the trapping potential. The phase dynamics are governed by a "driven-pendulum" equation, as in current-driven superconducting Josephson junctions. At a critical velocity of the barrier (proportional to the critical tunneling current), there is a sharp transition between the dc and ac regimes. The signature is a sudden jump of a large fraction of the relative condensate population. Analytical results are compared with a numerical integration of the Gross-Pitaevskii equation, in an experimentally realistic situation.

Recovery from sublethal and potentially lethal damage in an X-ray-sensitive CHO cell.

It has been suggested that DNA strand breaks are the molecular lesions responsible for radiation-induced lethality and that their repair is the basis for the recovery of irradiated cells from sublethal and potentially lethal damage. EM9 is a Chinese hamster ovary cell line that is hypersensitive to killing by X rays and has been reported to have a defect in the rate of rejoining of DNA single-strand breaks. To establish the importance of DNA strand-break repair in cellular recovery from sublethal and potentially lethal X-ray damage, those two parameters, recovery from sublethal and potentially lethal damage, were studied in EM9 cells as well as in EM9's parental repair-proficient strain, AA8. As previously reported, EM9 is the more radiosensitive cell line, having a D0 of 0.98 Gy compared to a D0 of 1.56 Gy for AA8 cells. DNA alkaline elution studies suggest that EM9 cells repair DNA single-strand breaks at a slower rate than AA8 cells. Neutral elution analysis suggests that EM9 cells also repair DNA double-strand breaks more slowly than AA8 cells. All of these data are consistent with the hypothesis that DNA strand-break ligation is defective in EM9 cells and that this defect accounts for increased radiosensitivity. The kinetics and magnitude of recovery from sublethal and potentially lethal damage, however, were similar for both EM9 and AA8 cells. Six-hour recovery ratios for sublethal damage repair were found to be 2.47 for AA8 cells and 1.31 for EM9 cells. Twenty-four-hour recovery ratios for potentially lethal damage repair were 3.2 for AA8 and 3.3 for EM9 cells. Both measurements were made at approximately equitoxic doses. Thus, the defect in EM9 cells that confers radiosensitivity and affects DNA strand-break rejoining does not affect sublethal damage repair or potentially lethal damage repair.

2-[(Aminopropyl)amino] ethanethiol-mediated reductions in 60Co gamma-ray and fission-spectrum neutron-induced chromosome damage in V79 cells.

The radioprotector 2-[aminopropyl)amino] ethanethiol (WR1065), which has been reported to reduce the cytotoxic and mutagenic effects of low LET radiation, was investigated for its ability to protect against low LET (60Co gamma ray) and high LET (fission-spectrum neutron)-induced chromosome damage in V79 cells. Cells were irradiated in G2 phase in the presence or absence of 4 mM WR1065 and were harvested and analyzed 2 h later for chromatid-type aberrations. Irradiation of G2-phase V79 cells in the presence of WR1065 resulted in a 30 to 50% reduction in the frequency of gamma-ray and neutron-induced chromatid-type breaks and exchanges. The effects were found only after exposures of greater than 200 cGy gamma-ray or 50 cGy neutron irradiation. The radioprotector was effective at reducing neutron-induced aberrations after exposures at dose rates of both 10 and 43 cGy/min. Thus the radioprotector WR1065 is an effective anti-clastogenic agent in V79 cells, protecting against both 60Co gamma-ray and fission-spectrum neutron-induced aberrations, when present during irradiation.

Decrease in rat brain calcitonin binding sites and adenylyl-cyclase activity during ageing.

In order to investigate the effects of ageing on the cerebral receptors for calcitonin (CT), we used an in vitro autoradiographic method to study the distribution of the binding sites for eel CT (eCT) in young and old rat brain. The inhibitory action of eCT on adenylyl-cyclase (AC) activity upon isolated brain cell membranes was also evaluated. The results show area-specific reduction of binding particularly in the hypothalamus and pons medulla of the old rat. The inhibitory action of eCT on AC activity was significantly reduced in the same areas, whereas in the striatum and mesencephalon no changes were observed. The parallel decrease of binding of eCT and of the inhibitory action of eCT on AC in ageing may represent a functional decline of neuronal activities during ageing.

Hawking radiation in sonic black holes.

I present a microscopic description of Hawking radiation in sonic black holes. A one-dimensional Fermi-degenerate liquid squeezed by a smooth barrier forms a transonic flow, a sonic analog of a black hole. The quantum treatment of the noninteracting case establishes a close relationship between sonic Hawking radiation and quantum tunneling through the barrier. Quasiparticle excitations appear at the barrier and are then radiated with a thermal distribution in exact agreement with Hawking's formula. The signature of the radiation can be found in the dynamic structure factor, which can be measured in a scattering experiment. The possibility for experimental verification of this new transport phenomenon for ultracold atoms is discussed.

Observation of dipole-dipole interaction in a degenerate quantum gas.

We have investigated the expansion of a Bose-Einstein condensate of strongly magnetic chromium atoms. The long-range and anisotropic magnetic dipole-dipole interaction leads to an anisotropic deformation of the expanding chromium condensate which depends on the orientation of the atomic dipole moments. Our measurements are consistent with the theory of dipolar quantum gases and show that a chromium condensate is an excellent model system to study dipolar interactions in such gases.

Rotons in gaseous Bose-Einstein condensates irradiated by a laser.

A gaseous Bose-Einstein condensate irradiated by a far off-resonance laser has long-range interatomic correlations caused by laser-induced dipole-dipole interactions. These correlations, which are tunable via the laser intensity and frequency, can produce a "roton" minimum in the excitation spectrum--behavior reminiscent of the strongly correlated superfluid liquid He II.

Correlation between leukotriene D4-induced contraction and cytosolic calcium elevation: a quantitative and simultaneous evaluation in smooth muscle.

The role of Ca++ as an intracellular messenger in leukotriene (LT)D4-induced muscle contraction was investigated by measuring force development and elevation in cytosolic Ca++ concentration simultaneously in strips of guinea pig ileal longitudinal muscle loaded with the fluorescent calcium indicator Fura 2. Upon addition of LTD4, a simultaneous increase in tension and cytosolic calcium concentration, [Ca++]i, was observed. Cumulative applications of LTD4 induced concentration-dependent increases in both muscle tension and [Ca++]i, being the half-maximal effect reached at approximately 6 to 9 nM. A statistically significant positive correlation (r = 0.993, P < .001) exists between the two parameters examined. Removal of calcium in the bathing solution, accompanied by addition of 7.5 mM EGTA, completely prevented any increase in either calcium levels or force development, thus indicating a role for Ca++ influx, rather than a release from intracellular stores. All of the LTD4 antagonists tested were able to counteract the effect of the leukotriene on both [Ca++]i and tension increase. However, although LY171883 shifted both of the LTD4 curves to the right in a parallel fashion, FPL 55712 and ICI 198,615 behaved as non-competitive antagonists in reversing the effect of LTD4 on [Ca++]i and tension. Thus, these results strongly suggest that changes in muscle tension induced by LTD4 are attributable to changes in cytosolic free Ca++ concentrations in guinea pig ileum.

Density modulations of Bose-Einstein condensates via laser-induced interactions.

We show that the dipole-dipole interatomic forces induced by an off-resonant running laser beam can lead to a self-bound pencil-shaped Bose condensate, even if the laser beam is a plane wave. For an appropriate laser intensity the ground state has a quasi-one-dimensional density modulation-a Bose-Einstein "supersolid."

Effects of prostaglandins and PAF on the contractility of the bovine ciliary muscle.

The present study has investigated the effect of prostaglandins and PAF on the contractility of the bovine ciliary muscle, a tissue involved in the control of aqueous outflow. The results show that the prostaglandins tested (PGI2, its stable analogue Iloprost, PGE2, PGE1, and PGF2 alpha) as well as PAF, were able to contract the ciliary muscle, although with different potencies and efficacies. PGI2 and Iloprost displayed parallel dose-effect curves with upper plateaus that did not differ significantly; however, PGI2 was slightly more potent than Iloprost. This is at variance with what is observed at the level of the platelet prostacyclin receptor. PGF2 alpha was equipotent with the PGEs tested, with a maximal effect not different from either PGI2 or PGEs. PAF was the most efficacious of the compounds tested.

Superoxide anion is generated from cellular metabolites by solar radiation and its components.

Several endogenous cellular constituents were tested for their ability to produce superoxide anion (O2-) from ground-state molecular oxygen upon irradiation by solar radiation. The pyridine cofactors NADPH and NADH, riboflavin, and the nucleosides 2-thiouracil and 4-thiouridine were found to sensitize the transmission of photon energy from solar radiation and monochromatic radiation (290, 334, 365, and 405 nm) to oxygen, resulting in O2- formation, as detected by superoxide dismutase-inhibitable cytochrome c reduction. Quantum yields for the production of O2- indicate that NADPH is the most efficient and riboflavin the least efficient of the compounds tested. These data indicate that endogenous compounds may participate in the production of O2- by solar radiation and imply that O2- may play a role in sunlight-induced erythema and dermal carcinogenesis.

Internalization and down-regulation of the prostacyclin receptor in human platelets.

The internalization of [3H]iloprost, a prostacyclin analogue, was studied in human platelets by binding studies. After incubation with [3H]iloprost at 37 degrees C, addition of unlabelled ligand at either 37 degrees C or 4 degrees C caused dissociation of 74% and 52% of the bound ligand respectively, suggesting that a portion had been internalized. The percentage of [3H]iloprost bound at equilibrium to the surface (evaluated by acid treatment) at either 37 degrees C or 4 degrees C was markedly different (80% versus 25%). Internalization was dependent on time and on the ligand nature and concentration. Energy-depleting agents (dinitrophenol and 2-deoxyglucose) completely inhibited internalization, whereas probenecid (inhibitor of organic anion transporters) did not affect it significantly. Subcellular fractionation indicated that, at 4 degrees C or in the absence of ligand, most of the receptor was present in membrane fractions (pellet at 27000 or 105000 g), whereas, when platelets were preincubated at 37 degrees C with iloprost, the receptor was found mainly in the cytosolic fraction. In platelets preincubated with iloprost at 4 degrees C, two classes of binding sites were present, whereas after preincubation at 37 degrees C only the lower-affinity sites were detected. After exposure to the agonist, iloprost-induced inhibition of platelet aggregation and activation of adenylate cyclase and cAMP production were significantly lower. Taken together, these data demonstrate that human platelets can internalize a high-affinity binding site for iloprost, presumably the prostacyclin receptor.