Revealing the Velocity Uncertainties of a Levitated Particle in the Quantum Ground State.

We demonstrate time-of-flight measurements for an ultracold levitated nanoparticle and reveal its velocity for the translational motion brought to the quantum ground state. We discover that the velocity distributions obtained with repeated release-and-recapture measurements are significantly broadened via librational motions of the nanoparticle. Under feedback cooling on all the librational motions, we recover the velocity distributions in reasonable agreement with an expectation from the occupation number, with approximately twice the width of the quantum limit. The strong impact of librational motions on the translational motions is understood as a result of the deviation between the libration center and the center of mass, induced by the asymmetry of the nanoparticle. Our results elucidate the importance of the control over librational motions and establish the basis for exploring quantum mechanical properties of levitated nanoparticles in terms of their velocity.

Ultracold Dipolar Molecules Composed of Strongly Magnetic Atoms.

In a combined experimental and theoretical effort, we demonstrate a novel type of dipolar system made of ultracold bosonic dipolar molecules with large magnetic dipole moments. Our dipolar molecules are formed in weakly bound Feshbach molecular states from a sample of strongly magnetic bosonic erbium atoms. We show that the ultracold magnetic molecules can carry very large dipole moments and we demonstrate how to create and characterize them, and how to change their orientation. Finally, we confirm that the relaxation rates of molecules in a quasi-two-dimensional geometry can be reduced by using the anisotropy of the dipole-dipole interaction and that this reduction follows a universal dipolar behavior.

Reaching Fermi degeneracy via universal dipolar scattering.

We report on the creation of a degenerate dipolar Fermi gas of erbium atoms. We force evaporative cooling in a fully spin-polarized sample down to temperatures as low as 0.2 times the Fermi temperature. The strong magnetic dipole-dipole interaction enables elastic collisions between identical fermions even in the zero-energy limit. The measured elastic scattering cross section agrees well with the predictions from the dipolar scattering theory, which follow a universal scaling law depending only on the dipole moment and on the atomic mass. Our approach to quantum degeneracy proceeds with very high cooling efficiency and provides large atomic densities, and it may be extended to various dipolar systems.

Anisotropic relaxation dynamics in a dipolar Fermi gas driven out of equilibrium.

We report on the observation of a large anisotropy in the rethermalization dynamics of an ultracold dipolar Fermi gas driven out of equilibrium. Our system consists of an ultracold sample of strongly magnetic 167Er fermions, spin polarized in the lowest Zeeman sublevel. In this system, elastic collisions arise purely from universal dipolar scattering. Based on cross-dimensional rethermalization experiments, we observe a strong anisotropy of the scattering, which manifests itself in a large angular dependence of the thermal relaxation dynamics. Our result is in good agreement with recent theoretical predictions. Furthermore, we measure the rethermalization rate as a function of temperature for different angles and find that the suppression of collisions by Pauli blocking is not influenced by the dipole orientation.

Bose-Einstein condensation of erbium.

We report on the achievement of Bose-Einstein condensation of erbium atoms and on the observation of magnetic Feshbach resonances at low magnetic fields. By means of evaporative cooling in an optical dipole trap, we produce pure condensates of 168Er, containing up to 7×10(4) atoms. Feshbach spectroscopy reveals an extraordinary rich loss spectrum with six loss resonances already in a narrow magnetic-field range up to 3 G. Finally, we demonstrate the application of a low-field Feshbach resonance to produce a tunable dipolar Bose-Einstein condensate and we observe its characteristic d-wave collapse.

Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG 9809.

BACKGROUND: CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), and dose intensification is a potential strategy for improving therapeutic results. We conducted a phase III trial to determine whether dose-dense strategy involving interval shortening of CHOP (CHOP-14) is superior to CHOP-21. PATIENTS AND METHODS: A total of 323 previously untreated patients (aged 15-69 years) with stages II-IV aggressive NHL were randomized. The primary end point was progression-free survival (PFS). RESULTS: Treatment compliance was comparable in both study arms. At 7-year follow-up, no substantial differences were observed in PFS and overall survival (OS) between CHOP-21 (n = 161) and CHOP-14 (n = 162) arms. Median PFS was 2.8 and 2.6 years with CHOP-21 and CHOP-14, respectively (one-sided log-rank P = 0.79). Eight-year OS and PFS rates were 56% and 42% [95% confidence interval (CI) 47% to 64% and 34% to 49%], respectively, with CHOP-21 and 55% and 38% (95% CI 47% to 63% and 31% to 46%), respectively, with CHOP-14. Subgroup analyses showed no remarkable differences in PFS or OS for patients stratified as per the International Prognostic Index or by age. CONCLUSION: Dose-intensification strategy involving interval shortening of CHOP did not prolong PFS in advanced, aggressive NHL.

Narrow-linewidth light source for a coherent Raman transfer of ultracold molecules.

We describe a tunable two-color CW light source sufficient for realizing a coherent Raman transfer between two molecular states that are more than 0.5 eV (120 THz) apart. The simultaneous frequency stabilization of 901 nm and 655 nm light was achieved by locking diode lasers to a single ultralow expansion cavity with dual wavelengths coating. By utilizing offset-locking and optical phase-locked loop (OPLL), we ensured a large mode-hop free tuning range (> 2 GHz). The obtained short term linewidth (<10 Hz) and the linear drift of frequency (65 mHz/s) were both sufficient to eliminate the influence of laser linewidths on the efficiency of coherent Raman transition.

Lack of antibodies against the antigen domain 2 epitope of cytomegalovirus (CMV) glycoprotein B is associated with CMV disease after renal transplantation in recipients having the same glycoprotein H serotypes as their donors.

Cytomegalovirus (CMV) reinfection of seropositive individuals has been associated with adverse outcomes in organ transplantation and is a frequent cause of congenital infection. Previously we demonstrated that mismatching of CMV glycoprotein H (gH) serotypes was associated with CMV disease after renal transplantation. Because the antigen domain 2 (AD2) epitope of glycoprotein B (gB) is conserved among CMV isolates and is one of the known targets of neutralizing antibodies, in this study we investigated whether antibodies against the epitope contribute to protection from CMV reinfection in renal transplantation, irrespective of gH serological matching. For this purpose, the gB and gH serology and clinical outcomes were analyzed retrospectively for 77 transplant recipients in the donor positive/recipient positive setting, who were managed by preemptive strategy. We found that there was a good negative correlation between the numbers of antigenemia-positive cells and the levels of antibodies against gB AD2 in the CMV-gH antibody matched group, but not in the CMV-gH antibody mismatched group. None of the recipients with antibodies against both gB AD2 and strain-specific epitopes of gH have experienced CMV disease during 6 month after transplantation, while 28% of those who lacked either/both antibody response needed preemptive therapy. Because the outcome was statistically significant, antibodies against gB AD2 can be a useful indicator to predict emergence of CMV disease for preemptive therapy, in addition to antibodies against the mismatched gH types.

Coherent transfer of photoassociated molecules into the rovibrational ground state.

We report on the direct conversion of laser-cooled 41K and 87Rb atoms into ultracold 41K87Rb molecules in the rovibrational ground state via photoassociation followed by stimulated Raman adiabatic passage. High-resolution spectroscopy based on the coherent transfer revealed the hyperfine structure of weakly bound molecules in an unexplored region. Our results show that a rovibrationally pure sample of ultracold ground-state molecules is achieved via the all-optical association of laser-cooled atoms, opening possibilities to coherently manipulate a wide variety of molecules.

Effect of DNA-damaging agents on isolated spleen cells and lung fibroblasts from the mouse mutant "wasted," a putative animal model for ataxia-telangiectasia.

Spleen cells from control and wasted (wst) mice, a putative animal model for the human genetic disease ataxia-telangiectasia, were tested for inhibition of replicative (semiconservative) DNA synthesis after treatments with bleomycin, gamma-irradiation, 4-nitroquinoline 1-oxide, and ultraviolet irradiation. The wasted cells were found to be more resistant than control cells to the first three treatments, but equally sensitive to ultraviolet light. Bleomycin-stimulated repair synthesis in spleen cells was also studied by the CsCl/bromodeoxyuridine method and found to be similar in cells from wasted and control animals. Similarly, no differences in sensitivity to killing by gamma-rays, as manifested by relative cloning efficiencies, were demonstrated between primary lung fibroblasts from mutant and control mice. We concluded that observed defects in DNA repair in wasted cells are not identical to those reported in human cells from ataxia-telangiectasia patients.

Extended Bose-Hubbard models with ultracold magnetic atoms.

The Hubbard model underlies our understanding of strongly correlated materials. Whereas its standard form only comprises interactions between particles at the same lattice site, extending it to encompass long-range interactions is predicted to profoundly alter the quantum behavior of the system. We realize the extended Bose-Hubbard model for an ultracold gas of strongly magnetic erbium atoms in a three-dimensional optical lattice. Controlling the orientation of the atomic dipoles, we reveal the anisotropic character of the onsite interaction and hopping dynamics and their influence on the superfluid-to-Mott insulator quantum phase transition. Moreover, we observe nearest-neighbor interactions, a genuine consequence of the long-range nature of dipolar interactions. Our results lay the groundwork for future studies of exotic many-body quantum phases.

Structure-specific inhibition of lysosomal cholesterol transport in macrophages by various steroids.

Cultured mouse peritoneal macrophages effectively take up and metabolize liposomes containing phosphatidylserine and cholesterol, resulting in massive accumulation of cholesteryl esters and triacylglycerols in their cytoplasm (Nishikawa, K., Arai, H. and Inoue, K. (1990) J. Biol. Chem. 265, 5226-5231). With this system, various steroid derivatives were assessed as to their ability to inhibit the cholesteryl ester formation from endocytosed cholesterol in macrophages. Among the steroids tested, one group of steroids having an oxo group at the C17 or C20 position, such as androstenedione, dehydroisoandrosterone, progesterone and pregnenolone, completely inhibited cholesteryl ester formation at 10 microM. Another group of steroids having a hydroxy group at the C17 position, such as testosterone and androstenediol, had a lesser effect; complete inhibition of cholesteryl ester formation was achieved with 100 microM or more. The mechanism underlying the inhibition by the former class of steroids was further studied. These steroids did not block the uptake or lysosomal hydrolysis of liposomes, nor esterification of fatty acyl chains into triacylglycerols. Moreover, dehydroisoandrosterone and pregnenolone, both of which possess a hydroxy group at the C3 position, had essentially no effect on 25-hydroxycholesterol-stimulated esterification of endogenous cellular cholesterol. On the other hand, androstenedione and progesterone, which possess an oxo group at the C3 position, had a mild inhibitory effect on the esterification of endogenous cholesterol. Upon incubation with a steroid having an oxo group at the C17 or C20 position, free cholesterol taken up by macrophages was accumulated in phagolysosomes, as judged from cytochemical study with filipin-cholesterol staining. These results indicate that a series of structurally-related steroids characterized by the presence of an oxo group at the C17 or C20 position inhibit cholesteryl ester formation in macrophages through blocking the intracellular transport of endocytosed cholesterol from lysosomes to endoplasmic reticulum.

Side-chain structure is critical for the transport of sterols from lysosomes to cytoplasm.

Macrophages take up and metabolize negatively charged liposomes containing free cholesterol efficiently, resulting in a massive accumulation of cholesteryl esters and triacylglycerols in their cytoplasm (Nishikawa, K., Arai, H. and Inoue, K. (1990) J. Biol. Chem. 265, 5226-5231). This system was used to assess the effects of structural variation of sterol on the intracellular transport and the metabolism of endocytosed sterols by the cells. Liposomes containing phytosterols with an extra one (campesterol) or two (beta-sitosterol, stigmasterol, fucosterol) carbons at the C-24 position of the cholesterol side-chain were endocytosed as efficiently as those containing cholesterol without exhibiting any apparent toxicity on the cells. Esterification of endocyotosed phytosterols was, however, extremely low; campesterol esterification was only 20% that of cholesterol and either beta-sitosterol or stigmasterol was not esterified appreciably. A morphological study showed that the endocytosed phytosterols were accumulated in the phagolysosomes of the cells. Blocking of esterification of endocytosed cholesterol by an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor did not lead to cholesterol accumulation in the phagolysosomes. These data suggest that accumulation of endocytosed phytosterols in phagolysosomes is not a consequence of the inability of the cell to esterify sterols in the endoplasmic reticulum. In the light of these observations, we conclude that cultured macrophages can discriminate between sterols that differ only by a methyl or ethyl group at the C-24 position at their lysosomal compartment.

Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A2.

OBJECTIVES: The study was undertaken to develop a coronary microvascular spasm model in pigs by repeated epicardial coronary artery endothelial injury. BACKGROUND: The pathophysiologic mechanisms responsible for coronary microvascular spasm remain unclear, in large part because a suitable animal model has yet to be found. METHODS: Balloon endothelial denudation was done just distal to the site of an implanted Doppler flowmeter in the left anterior descending coronary artery (LAD) every two weeks for a total of four times. Changes in LAD blood flow by intracoronary administration of vasoactive agents were assessed before each denudation. RESULTS: In the epicardial LAD endothelial denudation pigs, decreases in LAD blood flow caused by acetylcholine were augmented. Before denudation, it was - 15 +/- 4%, and at week 8 (i.e., two weeks after the fourth denudation) it was -100% (i.e., zero flow [p < 0.01]). The LAD flow changes in response to 5-hydroxytryptamine (5-HT) changed from an increase to a decrease, accompanied by medial thickening of microvessels in the LAD perfusion area. These flow responses were observed without significant changes in LAD diameter. In contrast, the LAD blood flow responses to acetylcholine and 5-HT did not change throughout the experiment in pigs given aspirin and a thromboxane A2 (TXA2) synthase inhibitor orally. CONCLUSIONS: This microvascular spasm model indicates that hypersensitivity to vasoactive substances in the microvascular beds as well as microvascular remodeling are brought about partly through TXA2. This model should be useful for examining the pathophysiology and treatment of microvascular angina.

Morphological and functional changes in coronary vessel evoked by repeated endothelial injury in pigs.

OBJECTIVE: We examined the morphological changes induced by repeated endothelial denudation in coronary artery (CA), as well as functional changes in the endothelium-dependent and smooth muscle responses to various vasoactive agents during the process of intimal thickening. METHODS: We observed vascular responses in denuded and non-denuded portions of pig CA while being fed a normal diet (n = 11, N group) or 2% cholesterol diet (n = 25, C group) to intracoronary acetylcholine (ACh), 5-hydroxytryptamine (5-HT), substance P (SP), and isosorbide dinitrate (ISDN) with and without the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v.) over a period of 8 weeks. Balloon endothelial denudation of the left anterior descending CA was carried out every 2 weeks. RESULTS: In N group, maximum vasoconstriction was obtained with ACh 2 weeks after the first denudation [26 +/- 5% vs. 1 +/- 1% pre-denudation, p < 0.05]. L-NAME did not affect ACh-induced CA diameter changes. Thereafter, the response to ACh was attenuated by repeated denudation in N groups. However, the degree of 5-HT-induced CA narrowing at the denuded portion increased from 7 +/- 4% (0 week) to 88 +/- 8% (8 weeks) (p < 0.05). The changes resulted in severe myocardial ischaemia, and suggested that endothelium-dependent vasodilation was progressively attenuated while hyperreactivity of vascular smooth muscle simultaneously increased. Vasodilation induced by SP was attenuated somewhat, but ISDN-induced vasodilation was preserved. Although mild hypercholesterolaemia was induced in C group, the vascular responses to these vasoactive agents did not differ from those of N group. CONCLUSIONS: Repeated CA endothelial injury and regeneration induce the change of morphology and vascular reactivity in the denuded portion regardless of atherogenic diet. This study strongly suggests that intimal thickening caused by repeated endothelial injury and regeneration induces specific vascular responses to vasoactive agents. Moreover, it is also suggested that during the progression of intimal thickening, increased vascular smooth muscle contraction and decreased endothelium-dependent dilation appear in a stimulus-dependent manner, often leading to severe coronary vasoconstriction accompanied with definitive ECG ST change.

Emergence of Chaotic Scattering in Ultracold Er and Dy.

We show that for ultracold magnetic lanthanide atoms chaotic scattering emerges due to a combination of anisotropic interaction potentials and Zeeman coupling under an external magnetic field. This scattering is studied in a collaborative experimental and theoretical effort for both dysprosium and erbium. We present extensive atom-loss measurements of their dense magnetic Feshbach-resonance spectra, analyze their statistical properties, and compare to predictions from a random-matrix-theory-inspired model. Furthermore, theoretical coupled-channels simulations of the anisotropic molecular Hamiltonian at zero magnetic field show that weakly bound, near threshold diatomic levels form overlapping, uncoupled chaotic series that when combined are randomly distributed. The Zeeman interaction shifts and couples these levels, leading to a Feshbach spectrum of zero-energy bound states with nearest-neighbor spacings that changes from randomly to chaotically distributed for increasing magnetic field. Finally, we show that the extreme temperature sensitivity of a small, but sizable fraction of the resonances in the Dy and Er atom-loss spectra is due to resonant nonzero partial-wave collisions. Our threshold analysis for these resonances indicates a large collision-energy dependence of the three-body recombination rate.

Inhibition of cholesteryl ester formation in macrophages by azole antimycotics.

Cultured macrophages take up and metabolize cholesterol-containing liposomes, resulting in massive accumulation of cholesteryl esters in the cells. Using this system, the effects of azole antimycotics on cholesteryl ester formation were studied. Incubation of mouse peritoneal macrophages with ketoconazole, miconazole, or econazole (0.1-10 microM) resulted in concentration-dependent inhibition of cholesteryl ester synthesis from endocytosed cholesterol. IC50 values (concentration resulting in 50% inhibition) were 1.4 +/- 0.1 microM, 4.1 +/- 0.2 microM, and 3.6 +/- 0.2 microM for ketoconazole, miconazole, and econazole, respectively. Complete inhibition was observed with 10 microM ketoconazole, and miconazole and econazole, each at 10 microM, caused 70 and 75% inhibition, respectively, of cholesteryl ester synthesis. The mechanism underlying the inhibition by ketoconazole was further studied. Ketoconazole did not appreciably block the uptake of liposomes or formation of triacylglycerol up to 10 microM. Interestingly, ketoconazole suppressed only 30% of 25-hydroxycholesterol-induced endogenous cholesterol esterification under conditions where esterification of endocytosed cholesterol was completely inhibited. Cytochemical studies with filipin-cholesterol staining revealed that ketoconazole induced massive accumulation of endocytosed cholesterol in macrophage phagolysosomes. These results indicate that ketoconazole inhibits cholesteryl ester formation in macrophages by blocking the intracellular transport of endocytosed cholesterol from lysosomes to the endoplasmic reticulum.

General synthetic route to chiral flexible biphenylphosphine ligands: the use of a chiral additive enables the preparation and observation of metal complexes incorporating the enantiopure form.

[figure: see text] The enantio- and diastereomerically pure metal complex of a chirally flexible BIPHEP ligand is obtained through enantiomer-selective coordination of a BIPHEP-Ru complex with enantiopure 3,3'-dimethyldiaminobinaphthyl, DM-DBN, followed by epimerization of the remaining BIPHEP-Ru enantiomer to complex with DM-DABN. Thus, an efficient and general synthetic route to a variety of substituted BIPHEP ligands from biphenol and observation of the enantiomerically pure BIPHEP ligands in their Ru(II) complexes are described.

SA channel mediates superoxide production in HUVECs.

Superoxide production in response to cyclic stretch (1 Hz, 20% in length) was investigated in human umbilical vein endothelial cells (HUVECs). The basal production of superoxide without stretch increased gradually, while the production of superoxide with stretch increased significantly as compared to that without stretch and it became significant 80 min after the onset of cyclic stretch (P<0.05, n=8-14). The superoxide production increased in a stretch-dependent manner and became significant when stretch was more than 10% (p<0.05, n=11-16). To investigate the involvement of SA channel, we added Gd3+ or EGTA in the reaction solution and examined the stretch-induced superoxide production. In cells stretched in the presence of 20 microM Gd3+, the stretch-induced superoxide production was significantly inhibited (at 120 min, p<0.05, n=8-18). The cyclic stretch-induced superoxide production was also significantly inhibited by the removal of extracellular Ca2+ with 5 mM EGTA (at 120 min, p<0.05, n=8-18). Neither the application of Gd3+ nor the removal of extracellular Ca2+ significantly changed the basal production of superoxide. These data suggest that the stretch-induced superoxide production increases in time- and stretch-dependent manner and that the stretch-induced superoxide production in HUVECs is regulated by Ca2+ influx through SA channels.

Occurrence of clostridia in glass bottled foods.

Forty-one marketed samples of imported and domestic glass bottled foods were tested for clostridia contamination. It was detected in nine (22%) samples. Clostridia were isolated from fish sauce (Nam pla, Nuoc-mam), dressing, mustard, hot and sour soup mix (Tom Yum), mysids boiled down in soy, and salmon flakes. The origin of all clostridia positive samples was Asia. Clostridium botulinum and C. perfringens were not detected. The frequency of occurrence was higher by enrichment broth culture detection methods than by agar plate or pouch methods. These findings suggest that the number of bacteria in most of these clostridia positive food samples is very low, and the use of enrichment methods for detection of clostridia is essential.