Three-Dimensional Trapping of Individual Rydberg Atoms in Ponderomotive Bottle Beam Traps.

We demonstrate three-dimensional trapping of individual Rydberg atoms in holographic optical bottle beam traps. Starting with cold, ground-state ^{87}Rb atoms held in standard optical tweezers, we excite them to nS_{1/2}, nP_{1/2}, or nD_{3/2} Rydberg states and transfer them to a hollow trap at 850 nm. For principal quantum numbers 60≤n≤90, the measured trapping time coincides with the Rydberg state lifetime in a 300 K environment. We show that these traps are compatible with quantum information and simulation tasks by performing single qubit microwave Rabi flopping, as well as by measuring the interaction-induced, coherent spin-exchange dynamics between two trapped Rydberg atoms separated by 40 µm. These results will find applications in the realization of high-fidelity quantum simulations and quantum logic operations with Rydberg atoms.

Demonstration of a strong Rydberg blockade in three-atom systems with anisotropic interactions.

We study the Rydberg blockade in a system of three atoms arranged in different two-dimensional geometries (linear and triangular configurations). In the strong blockade regime, we observe high-contrast, coherent collective oscillations of the single excitation probability and an almost perfect van der Waals blockade. Our data are consistent with a total population in doubly and triply excited states below 2%. In the partial blockade regime, we directly observe the anisotropy of the van der Waals interactions between |nD> Rydberg states in the triangular configuration. A simple model that only uses independently measured two-body van der Waals interactions fully reproduces the dynamics of the system without any adjustable parameter. These results are extremely promising for scalable quantum information processing and quantum simulation with neutral atoms.

Direct measurement of the van der Waals interaction between two Rydberg atoms.

We report the direct measurement of the van der Waals interaction between two isolated, single Rydberg atoms separated by a controlled distance of a few micrometers. Working in a regime where the single-atom Rabi frequency for excitation to the Rydberg state is comparable to the interaction, we observe partial Rydberg blockade, whereby the time-dependent populations of the various two-atom states exhibit coherent oscillations with several frequencies. Quantitative comparison of the data with a simple model based on the optical Bloch equations allows us to extract the van der Waals energy, and observe its characteristic C6/R6 dependence. The measured C6 coefficients agree well with ab initio calculations, and we observe their dramatic increase with the principal quantum number n of the Rydberg state.

Realization of a distributed Bragg reflector for propagating guided matter waves.

We report on the experimental study of a Bragg reflector for guided, propagating Bose-Einstein condensates. A one-dimensional attractive optical lattice of finite length created by red-detuned laser beams selectively reflects some velocity components of the incident matter wave packet. We find quantitative agreement between the experimental data and one-dimensional numerical simulations and show that the Gaussian envelope of the optical lattice has a major influence on the properties of the reflector. In particular, it gives rise to multiple reflections of the wave packet between two symmetric locations where Bragg reflection occurs. Our results are a further step towards integrated atom-optics setups for quasi-cw matter waves.

Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo.

The gag membrane protein gP85gag, encoded by Moloney murine leukemia virus (M-MLV), was identified as a target molecule recognized by Moloney murine sarcoma virus--M-MLV (M-MSV--M-MLV)-specific cytolytic T lymphocyte (CTL) clones. Target cells infected with Ab-X-MLV, an M-MLV-derived mutant virus not encoding gP85gag, were not lysed by the CTL clones. The same CTL clones were shown previously to induce the destruction of M-MLV-induced tumor cells in the peritoneal cavity. We have now characterized CTL-resistant antigen-loss tumor cell variants that have lost the surface antigen, but which retain transcriptionally silent M-MLV genomes. A cloned antigen-loss variant that reverted in vitro to the CTL-susceptible phenotype reexpressed M-MLV genomes that had undergone an insertion event in the region of the viral DNA coding for the gag membrane protein. Intravenous injection of virus-specific CTL clones inhibited tumor formation in mice injected subcutaneously with M-MSV--M-MLV.

Mesoscopic ensembles of polar bosons in triple-well potentials.

Mesoscopic dipolar Bose gases in triple-well potentials offer a minimal system for the analysis of the nonlocal character of the dipolar interaction. We show that this nonlocal character may be clearly revealed by a variety of possible ground-state phases. In addition, an appropriate control of short-range and dipolar interactions may lead to novel scenarios for the dynamics of polar bosons in lattices, including the dynamical creation of mesoscopic quantum superpositions, which may be employed in the design of Heisenberg-limited atom interferometers.

Two-frequency acousto-optic modulator driver to improve the beam pointing stability during intensity ramps.

We report on a scheme to improve the pointing stability of the first order beam diffracted by an acousto-optic modulator (AOM). Due to thermal effects inside the crystal, the angular position of the beam can change by as much as 1 mrad when the radio-frequency power in the AOM is reduced to decrease the first order beam intensity. This is done, for example, to perform forced evaporative cooling in ultracold atom experiments using far-off-resonant optical traps. We solve this problem by driving the AOM with two radio frequencies f(1) and f(2). The power of f(2) is adjusted relative to the power of f(1) to keep the total power constant. Using this, the beam displacement is decreased by a factor of 20. The method is simple to implement in existing experimental setups, without any modification of the optics.

Evaluation of dose equivalent by the electronic personal dosemeter for neutron 'Saphydose-N' at different workplaces of nuclear facilities.

This paper presents the results of measurements made with the electronic personal neutron Saphydose-N during the four campaigns of the European contract EVIDOS (EValuation of Individual DOSimetry in mixed neutron and photon radiation fields). These measurements were performed at Institute for Radiological Protection and Nuclear Safety (IRSN) in France (C0), at the Krümmel Nuclear Power Plant in Germany (C1), at the VENUS Research Reactor and the Belgonucléaire fuel processing plant in Belgium (C2) and at the Ringhals Nuclear Power Plant in Sweden (C3). The results for Saphydose-N are compared with reference values for dose equivalent.

Workplace characterisation in case of rail transport of radioactive materials.

IRSN has been asked by SNCF (French Railways) to carry out measurements in order to establish the values of ambient dose equivalents H*(10) in the vicinity of shipments of radioactive materials to assess the external exposure to ionising radiation to which employees may be subjected during the carriage of radioactive goods. Detailed dosimetric characterisations of the wagons have been made and the external exposure at different stages of the work that is done by the employees have been measured in terms of H*(10). For the study presented in this paper, and corresponding to a used fuel shipment composed of UO2 and UO2-PuO2, it has been observed that the photon and neutron doses are very similar. In addition, the order of magnitude of the total dose integrated by an employee who would carry out 100 times the series of essential operational tasks, has been found to be approximately 250 microSv. This value is compared with those observed for other previously investigated shipments involving the exposure to photon fields only.

Gender aspects in chronic myeloid leukemia: long-term results from randomized studies.

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.

Performance of the electronic personal dosemeter for neutron 'Saphydose-N' at different workplaces of nuclear facilities.

This paper mainly aims at presenting the measurements and the results obtained with the electronic personal neutron dosemeter Saphydose-N at different facilities. Three campaigns were led in the frame of the European contract EVIDOS ('Evaluation of Individual Dosimetry in Mixed Neutron and Photon Radiation Fields'). The first one consisted in the measurements at the IRSN French research laboratory in reference neutron fields generated by a thermal facility (SIGMA), radionuclide ISO sources ((241)AmBe; (252)Cf; (252)Cf(D(2)O)\Cd) and a realistic spectrum (CANEL/T400). The second one was performed at the Krümmel Nuclear Power Plant (Germany) close to the boiling water reactor and to a spent fuel transport cask. The third one was realised at Mol (Belgium), at the VENUS Research Reactor and at Belgonucléaire, a fuel processing factory.

Electronic neutron personal dosemeters: their performance in mixed radiation fields in nuclear power plants.

This work describes spectral distributions of neutrons obtained as function of energy and direction at four workplace fields at the Krümmel reactor in Germany. Values of personal dose equivalent H(p)(10) and effective dose E are determined for different directions of a person's orientation in these fields and readings of personal neutron dosemeters--especially electronic dosemeters--are discussed with respect to H(p)(10) and E.

Evaluation of individual monitoring in mixed neutron/photon fields: mid-term results from the EVIDOS project.

EVIDOS is an EC sponsored project that aims at an evaluation and improvement of radiation protection dosimetry in mixed neutron/photon fields. This is performed through spectrometric and dosimetric investigations during different measurement campaigns in representative workplaces of the nuclear industry. The performance of routine and, in particular, novel personal dosemeters and survey instruments is tested in selected workplace fields. Reference values for the dose equivalent quantities, H(*)(10) and H(p)(10) and the effective dose E, are determined using different spectrometers that provide the energy distribution of the neutron fluence and using newly developed devices that determine the energy and directional distribution of the neutron fluence. The EVIDOS project has passed the mid-term, and three measurement campaigns have been performed. This paper will give an overview and some new results from the third campaign that was held in Mol (Belgium), around the research reactor VENUS and in the MOX producing plant of Belgonucléaire.

Molecular secrets of bacterial type III effector proteins.

Most Gram-negative phytopathogenic bacteria are thought to inject effector proteins into the plant cell via a type III secretion system that is essential for pathogenicity. Plant targets and the mode of action of type III effector proteins, which include avirulence (Avr) proteins, are largely unknown. However, recent findings have shed light on the molecular mechanisms of Avr action. Here, we focus on two classes of Avr proteins (the AvrBs3 and AvrRxv/YopJ families) that have been suggested to act as transcription factors and proteases, respectively.

Improvement of molecular monitoring of residual disease in leukemias by bedside RNA stabilization.

The sensitivity of assays designed to monitor minimal residual disease (MRD) by RT-PCR in leukemia depend on quality and quantity of RNA derived from peripheral blood (PB) and bone marrow (BM) leukocytes. Shipment of material may lead to RNA degradation resulting in a loss of sensitivity and, potentially, false negative results. Furthermore, degradation may lead to inaccurate estimates of MRD in positive specimens. We sought to determine feasibility and efficacy of a novel blood collection and processing system which is based on integrated RNA stabilization at the time of phlebotomy (PAXgene Blood RNA Kit) by comparison with standard methods of RNA extraction (cesium chloride gradient ultracentrifugation and RNeasy Mini Kit) using unstabilized EDTA anticoagulated PB. In 26 patients with chronic myelogenous leukemia (CML) on therapy, PB was processed after a storage time at room temperature of 2 and 72 h according to these protocols. BCR-ABL, total ABL and glucose-6-phosphate dehydrogenase (G6PD) mRNA transcripts of PB samples were quantified as a measure for response to therapy and RNA integrity. RNA yield expressed as the ratio of ABL transcripts after a storage time of 72 h/ABL transcripts after a storage time of 2 h at room temperature was significantly higher with the stabilizing method (median 0.40) compared to the RNeasy method using unstabilized PB (median 0.13, P = 0.01). Furthermore, ratios BCR-ABL/ABL after 72 vs 2 h still correlated well using the PAXgene method (r = 0.99, P < 0.0001) in contrast to the standard method which did not (r = 0.65, P = 0.03). Even investigation of complete cytogenetic responders with very low tumor burden showed a good correlation of ratios BCR-ABL/ABL compared to the reference method. Comparable results were achieved using G6PD transcripts as standard. We conclude that the new PAXgene stabilization method could improve RNA quality and the comparability of molecular monitoring within and between multicenter trials.

Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha.

The degree of tumor load reduction as measured by cytogenetic response is an important prognostic factor for chronic myelogenous leukemia (CML) patients on therapy. We sought to determine whether BCR-ABL transcript levels can predict chromosomal response. Residual disease was evaluated in 120 CML patients in chronic phase (CP) treated with the selective tyrosine kinase inhibitor imatinib after resistance or intolerance to interferon alpha (IFN). Median time of therapy was 401 days (range 111-704). BCR-ABL and total ABL transcripts were measured in 486 peripheral blood (PB) specimens with a real time RT-PCR approach using fluorescent-labeled hybridization probes (LightCycler technology) and results were expressed as the ratio BCR-ABL/ABL. Cytogenetic response was determined in 3-monthly intervals: From 101 evaluable patients, 42 achieved a complete (CR, 0% Philadelphia chromosome (Ph)- positive metaphases), 18 a partial (PR, 1-34% Ph+), 13 a minor (MR, 35-94% Ph+), and 26 no response (NR, >94% Ph+). All PB samples were RT-PCR positive. The proportion of Ph+ metaphases and simultaneous BCR-ABL/ABL ratios correlated with r = 0.74, P < 0.0001. In order to investigate whether early molecular analysis may predict cytogenetic response, quantitative RT-PCR data obtained after 1 and 2 months of therapy were compared with cytogenetic response at 6 months. BCR-ABL/ABL ratios after 1 month were not predictive, but results after 2 months correlated with the consecutive cytogenetic response (P = 0.0008). The probability for a major cytogenetic response was significantly higher in patients with a BCR-ABL/ABL ratio <20% after 2 months of imatinib therapy. We conclude that: (1) quantitative determination of residual disease with real time RT-PCR is a reliable and sensitive method to monitor CML patients on imatinib therapy; (2) BCR-ABL/ABL ratios correlate well with cytogenetic response; (3) in IFN-pretreated patients all complete responders to imatinib have evidence of residual disease with the limited follow-up available; and (4) cytogenetic response at 6 months of therapy in CP patients is predictable with real time RT-PCR at 2 months.

Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission.

A significant proportion of chronic myeloid leukemia (CML) patients achieve a major cytogenetic remission (MCR) to imatinib therapy after failing interferon (IFN) alpha-based protocols. We sought to determine levels of residual disease in patients with MCR using various molecular methods and to establish a relation between residual BCR-ABL transcript levels and rate of relapse in complete cytogenetic remission (CCR). Response was measured by conventional cytogenetic analysis, hypermetaphase and interphase fluorescence in situ hybridization (HM-FISH, IP-FISH) of bone marrow (BM) cells, qualitative nested and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts. We investigated 323 peripheral blood (PB) and BM samples from 48 CML patients who achieved a complete (Ph+ 0%; n=41) or partial (Ph+ 1-34%; n=7) cytogenetic remission after 3-20 months of imatinib therapy. Prior to imatinib, 35 patients were in chronic phase (CP), eight in accelerated phase (AP), four in myeloid and one in lymphoid blast crisis. HM-FISH results correlated with ratios BCR-ABL/ABL in PB and BM. In patients with CCR, residual disease was detectable by HM-FISH (31%), IP-FISH (18%), and RT-PCR (100%). During follow-up, BCR-ABL became undetectable in two patients (one CP, one AP) by both nested and quantitative RT-PCR. CCR is ongoing in 30 evaluable patients, 11 patients have relapsed. At the time of best response, median ratios BCR-ABL/ABL were 2.1% (range 0.82-7.8) in patients with subsequent relapse and 0.075% (range 0-3.9) in patients with ongoing remission (P=0.0011). All 16 CP patients, who achieved ratios BCR-ABL/ABL <0.1% as best molecular response are in continuous remission, while 6/13 patients (46%) with ratios >/=0.1% have relapsed (P=0.0036). We conclude that: (i) in patients with CCR to imatinib, HM-FISH and RT-PCR usually reveal residual BCR-ABL+ cells; (ii) RT-PCR results derived from PB and BM are comparable in CP CML; and (iii) low levels of residual disease with ratios BCR-ABL/ABL &<0.1% are associated with continuous remission.

Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy.

Selective inhibition of the BCR-ABL tyrosine kinase by imatinib (STI571, Glivec/Gleevec) is a promising new therapeutic strategy in patients with chronic myelogenous leukemia (CML). Despite significant hematologic and cytogenetic responses, resistance occurs, particularly in patients with advanced disease. We sought to determine the underlying mechanisms. Sixty-six patients with CML in myeloid blast crisis (n = 33), lymphoid blast crisis (n = 2), accelerated phase (n = 16), chronic phase (n = 13), and BCR-ABL-positive acute lymphoblastic leukemia (n = 2) resistant to imatinib were investigated. Median duration of imatinib therapy was 148 days (range 6-882). Patients were evaluated for genomic amplification of BCR-ABL, overexpression of BCR-ABL transcripts, clonal karyotypic evolution, and mutations of the imatinib binding site in the BCR-ABL tyrosine kinase domain. Results were as follows: (1) Median levels of BCR-ABL transcripts, were not significantly changed at the time of resistance but 7/55 patients showed a >10-fold increase in BCR-ABL levels; (2) genomic amplification of BCR-ABL was found in 2/32 patients evaluated by fluorescence in situ hybridization; (3) additional chromosomal aberrations were observed in 19/36 patients; (4) point mutations of the ABL tyrosine kinase domain resulting in reactivation of the BCR-ABL tyrosine kinase were detected in 23/66 patients. In conclusion, although the heterogeneous development of imatinib resistance is challenging, the fact that BCR-ABL is active in many resistant patients suggests that the chimeric oncoprotein remains a good therapeutic target. However, patients with clonal evolution are more likely to have BCR-ABL-independent mechanisms of resistance. The observations warrant trials combining imatinib with other agents.

Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.

Simulations of the mean chord length of a multi-element TEPC irradiated by monoenergetic neutrons.

In recent years IRSN has developed tissue-equivalent proportional counters (TEPCs) for neutron monitoring. A detector with a multi-element geometry was studied for personal dosimetry purposes. The determination of the personal dose equivalent using a multi-element TEPC requires to calculate the mean chord length of the charged particles in the counter gas. This paper presents the results of the simulations using the MCNPX code and explains the influence of the gas parameters on the mean chord length and the consequences on the dose equivalent response.