Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast.

Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3-5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10-1000µM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established.

Measurement of the Spin-Dipolar Part of the Tensor Polarizability of

We report on the measurement of the contribution of the magnetic-dipole hyperfine interaction to the tensor polarizaility of the electronic ground state in ^{87}Rb. This contribution was isolated by measuring the differential shift of the clock transition frequency in ^{87}Rb atoms that were optically trapped in the focus of an intense CO_{2} laser beam. By comparing to previous tensor polarizability measurements in ^{87}Rb, the contribution of the interaction with the nuclear electric-quadrupole moment was isolated as well. Our measurement will enable better estimation of blackbody shifts in Rb atomic clocks. The methods reported here are applicable for future spectroscopic studies of atoms and molecules under strong quasistatic fields.

Precision and accuracy of clinical quantification of myocardial blood flow by dynamic PET: A technical perspective.

A number of exciting advances in PET/CT technology and improvements in methodology have recently converged to enhance the feasibility of routine clinical quantification of myocardial blood flow and flow reserve. Recent promising clinical results are pointing toward an important role for myocardial blood flow in the care of patients. Absolute blood flow quantification can be a powerful clinical tool, but its utility will depend on maintaining precision and accuracy in the face of numerous potential sources of methodological errors. Here we review recent data and highlight the impact of PET instrumentation, image reconstruction, and quantification methods, and we emphasize (82)Rb cardiac PET which currently has the widest clinical application. It will be apparent that more data are needed, particularly in relation to newer PET technologies, as well as clinical standardization of PET protocols and methods. We provide recommendations for the methodological factors considered here. At present, myocardial flow reserve appears to be remarkably robust to various methodological errors; however, with greater attention to and more detailed understanding of these sources of error, the clinical benefits of stress-only blood flow measurement may eventually be more fully realized.

A 3D experiment that provides isotropic homonuclear correlations of half-integer quadrupolar nuclei.

Two 3D experiments, capable of producing enhanced resolution two-spin double-quantum (DQ) homonuclear correlations for half-integer quadrupolar nuclei, are described. The first uses a split-t1 MQMAS sequence followed by a sandwiched oR(3) symmetry-based dipolar recoupling sequence to directly excite DQ coherences. In this case an isotropic single-quantum (SQ) coherence starts the homonuclear DQ excitation. In the second experiment a single strong pulse is used to create triple quantum (TQ) coherence followed by a further single pulse conversion to zero-order before a non-sandwiched oR(3) DQ sequence. The first experiment is demonstrated using (87)Rb in RbNO3, with three Rb sites in a ∼5ppm range, and the second to (11)B in caesium triborate, CsB3O5, with two three-coordinated sites separated by ∼2ppm and one four-coordinated boron site. In both cases, all sites are clearly resolved and their connections observed. The second experiment has higher sensitivity and a good signal to noise is obtained in a reasonable time despite the long T1 relaxation time of (11)B in this material.

Evaluation of in vivo detection properties of 22Na, 65Zn, 86Rb, 109Cd and 137Cs in plant tissues using real-time radioisotope imaging system.

In plant research, radioisotope imaging provides useful information about physiological activities in various tissues and elemental transport between plant organs. To expand the usage of imaging techniques, a new system was developed to visualize beta particles, x-rays and gamma-rays emitted from plant bodies. This real-time radioisotope imaging system (RRIS) visualizes radioactivity after conversion into light with a CsI(Tl) scintillator plate. Herein, the RRIS detection properties of the gamma-ray emitters (22)Na, (65)Zn, (86)Rb, (109)Cd and (137)Cs were evaluated in comparison with those of radioluminography (RLG) using an imaging plate. The lower quantitative detection limit (Bq mm(-2)) during a 15 min period ranged from 0.1 to 4, depending on the nuclide, similar to that of RLG. When the quantitative ability to detect radiation from various Arabidopsis tissues was analyzed, the quantitative capability in silique and the thick internode tended to be low. In an EGS5 simulation, beta particles were the greatest contributors to RRIS imaging of (22)Na, (86)Rb and (137)Cs, and low-energy x-rays contributed significantly to (65)Zn and (109)Cd detection. Thus, both self-absorption and air space between the sample and scintillator surface could impair quantitative RRIS imaging. Despite these issues, RRIS is suggested for quantitative time-course measurements of radionuclide motion within plants.

Molecular motions involved in Na-K-Cl cotransporter-mediated ion transport and transporter activation revealed by internal cross-linking between transmembrane domains 10 and 11/12.

We examined the relationship between transmembrane domain (TM) 10 and TM11/12 in NKCC1, testing homology models based on the structure of AdiC in the same transporter superfamily. We hypothesized that introduced cysteine pairs would be close enough for disulfide formation and would alter transport function: indeed, evidence for cross-link formation with low micromolar concentrations of copper phenanthroline or iodine was found in 3 of 8 initially tested pairs and in 1 of 26 additionally tested pairs. Inhibition of transport was observed with copper phenanthroline and iodine treatment of P676C/A734C and I677C/A734C, consistent with the proximity of these residues and with movement of TM10 during the occlusion step of ion transport. We also found Cu(2+) inhibition of the single-cysteine mutant A675C, suggesting that this residue and Met(382) of TM3 are involved in a Cu(2+)-binding site. Surprisingly, cross-linking of P676C/I730C was found to prevent rapid deactivation of the transporter while not affecting the dephosphorylation rate, thus uncoupling the phosphorylation and activation steps. Consistent with this, (a) cross-linking of P676C/I730C was dependent on activation state, and (b) mutants lacking the phosphoregulatory domain could still be activated by cross-linking. These results suggest a model of NKCC activation that involves movement of TM12 relative to TM10, which is likely tied to movement of the large C terminus, a process somehow triggered by phosphorylation of the regulatory domain in the N terminus.

Automatic detection of left and right ventricles from CTA enables efficient alignment of anatomy with myocardial perfusion data.

BACKGROUND: Accurate alignment between cardiac CT angiographic studies (CTA) and nuclear perfusion images is crucial for improved diagnosis of coronary artery disease. This study evaluated in an animal model the accuracy of a CTA fully automated biventricular segmentation algorithm, a necessary step for automatic and thus efficient PET/CT alignment. METHODS AND RESULTS: Twelve pigs with acute infarcts were imaged using Rb-82 PET and 64-slice CTA. Post-mortem myocardium mass measurements were obtained. Endocardial and epicardial myocardial boundaries were manually and automatically detected on the CTA and both segmentations used to perform PET/CT alignment. To assess the segmentation performance, image-based myocardial masses were compared to experimental data; the hand-traced profiles were used as a reference standard to assess the global and slice-by-slice robustness of the automated algorithm in extracting myocardium, LV, and RV. Mean distances between the automated and the manual 3D segmented surfaces were computed. Finally, differences in rotations and translations between the manual and automatic surfaces were estimated post-PET/CT alignment. The largest, smallest, and median distances between interactive and automatic surfaces averaged 1.2 ± 2.1, 0.2 ± 1.6, and 0.7 ± 1.9 mm. The average angular and translational differences in CT/PET alignments were 0.4°, -0.6°, and -2.3° about x, y, and z axes, and 1.8, -2.1, and 2.0 mm in x, y, and z directions. CONCLUSIONS: Our automatic myocardial boundary detection algorithm creates surfaces from CTA that are similar in accuracy and provide similar alignments with PET as those obtained from interactive tracing. Specific difficulties in a reliable segmentation of the apex and base regions will require further improvements in the automated technique.

Reduction in ¹8F-fluorodeoxyglucose uptake on serial cardiac positron emission tomography is associated with improved left ventricular ejection fraction in patients with cardiac sarcoidosis.

BACKGROUND: Cardiac positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) has been used to diagnose and monitor cardiac sarcoidosis (CS). It is not known whether a reduction in myocardial inflammation, as measured by FDG uptake, is associated with improvement in LV ejection fraction (EF). METHODS: For 23 patients with CS followed by a total of 90 serial PET exams (median 4 per patient), two physicians blinded to EF quantified the maximum of standardized uptake value (SUV) and volume of inflamed tissue above two distinct thresholds to assess the intensity and extent of FDG uptake on each study. Using gated (82)Rubidium rest myocardial perfusion images, EF was measured blinded to all clinical and FDG data. To account for clustering and differences in scan frequency, a longitudinal mixed effects model was used to evaluate the relationship between FDG uptake and changes in EF on interval scans. RESULTS: Among 23 patients with serial PET exams (mean age 49, 74% male, mean baseline EF 43% ± 13%), the median time between the first and last scan was 2.0 years. Overall, 91% were treated with corticosteroids, 78% with ACE/ARB, 83% with beta-blockers, and 83% had ICDs. Longitudinal regression demonstrated a significant inverse linear relationship between maximum SUV and EF with an expected increase in EF of 7.9% per SUV reduction of 10 g·mL(-1) (P = .008). Likewise, in an analysis based on volume, there was an increase in EF of 2.1% per 100 cm(3) decrease in volume of inflamed tissue using a threshold of 2.7 g·mL(-1) (P = .028) and an increase in EF of 3.8% per 100 cm(3) decrease (P = .022) using a SUV threshold of 4.1 g·mL(-1). CONCLUSIONS: In a longitudinal cohort of CS patients, a reduction in the intensity and extent of myocardial inflammation on FDG PET is associated with improvement in EF. These data suggest serial PET scanning may help guide titration of immunosuppressive therapy to improve or prevent heart failure in CS.

Characterizing the normal range of myocardial blood flow with 8²rubidium and ¹³N-ammonia PET imaging.

BACKGROUND: Diagnosis of coronary disease and microvascular dysfunction may be improved by comparing myocardial perfusion scans with a database defining the lower limit of normal myocardial blood flow and flow reserve (MFR). To maximize disease detection sensitivity, a small normal range is desirable. Both (13)N-ammonia and (82)Rb tracers are used to quantify blood flow and MFR using positron emission tomography (PET). The goal of this study was to investigate the trade-off between noise and accuracy in both (82)Rb and (13)N-ammonia normal databases formed using a net retention model. METHODS: Fourteen subjects with <5% risk of CAD underwent rest and stress (82)Rb and (13)N-ammonia dynamic PET imaging in a randomized order within 2 weeks. Myocardial blood flow was quantified using a one-compartment model for (82)Rb, and a two-compartment model for (13)N-ammonia. A simplified model was used to estimate tracer retention, with tracer-specific net extraction functions derived to obtain flow estimates. RESULTS: Normal variability of retention reserve was equivalent for both tracers (±15% globally, ±16% regionally) and was lower in comparison to compartment model results (P < .05). The two-compartment model for (13)N-ammonia had the smallest normal range of global blood flow resulting in a lower limit of normal MFR = 2.2 (mean - 2 SD). CONCLUSION: These results suggest that the retention model may have higher sensitivity for detection and localization of abnormal flow and MFR using (82)Rb and (13)N-ammonia, whereas the (13)N-ammonia two-compartment model has higher precision for absolute flow quantification.

Incremental diagnostic benefit of resolution recovery software in patients with equivocal myocardial perfusion single-photon emission computed tomography (SPECT).

BACKGROUND: Though myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is an established diagnostic method, equivocal studies are commonly encountered. New software has been introduced that incorporates resolution recovery (RR) and noise regulation into the reconstruction algorithm and has been used to facilitate "half-dose" and "half-time" studies. Its utility with "full-time, full-dose" acquisition has not been well studied. OBJECTIVE: We sought to understand the potential benefit of incorporating RR software in equivocal SPECT studies. METHODS: Patients with full-time, full-dose SPECT MPI were reviewed and those with equivocal results, who subsequently underwent cardiac Rb-82 positron emission tomography (PET) scan were identified. Image reconstruction was performed with iterative reconstruction (IR), attenuation correction (IR + AC), and RR software (IR + AC + RR). Images were anonymized and read blindly by consensus of two experienced readers. All images were qualitatively assessed and semi-quantitatively graded using summed stress and summed rest scores. RESULTS: 45 patients were included (28 males, age = 59.6 ± 9.9 years) and the diagnostic accuracy of each of the reconstruction algorithms (IR, IR + AC, IR + AC + RR) was compared to Rb-82 PET. Agreement of clinical diagnosis of each SPECT reconstruction with Rb-PET showed incremental improvement. The agreement with PET for IR + AC + RR (κ = 0.66, CI 0.454-0.875) is significantly better than for IR (κ = 0.22, CI 0.0-0.450, P = .005) and for IR + AC (κ = 0.32, CI 0.077-0.563, P = .03). Also, IR + AC + RR improved the clinical diagnosis in 14 cases and with overall improvement of reclassification proportion of 23.5% compared to IR (P = .01). Using PET as a reference standard, ROC curves were created for IR + AC + RR, IR + AC, and IR which showed incremental value of the area under the curve of IR + AC + RR (AUC: 0.87; CI 0.76-0.98) over IR + AC (AUC: 0.75; CI 0.61-0.89, P = .078), and over IR (AUC 0.68; CI 0.52-0.84, P = .025). CONCLUSION: The addition of RR may help in the diagnosis of patients with equivocal SPECT MPI without the need for additional testing. Further prospective studies are needed to define the role of this new software.

Mechanism for selectivity-inactivation coupling in KcsA potassium channels.

Structures of the prokaryotic K(+) channel, KcsA, highlight the role of the selectivity filter carbonyls from the GYG signature sequence in determining a highly selective pore, but channels displaying this sequence vary widely in their cation selectivity. Furthermore, variable selectivity can be found within the same channel during a process called C-type inactivation. We investigated the mechanism for changes in selectivity associated with inactivation in a model K(+) channel, KcsA. We found that E71A, a noninactivating KcsA mutant in which a hydrogen-bond behind the selectivity filter is disrupted, also displays decreased K(+) selectivity. In E71A channels, Na(+) permeates at higher rates as seen with and flux measurements and analysis of intracellular Na(+) block. Crystal structures of E71A reveal that the selectivity filter no longer assumes the "collapsed," presumed inactivated, conformation in low K(+), but a "flipped" conformation, that is also observed in high K(+), high Na(+), and even Na(+) only conditions. The data reveal the importance of the E71-D80 interaction in both favoring inactivation and maintaining high K(+) selectivity. We propose a molecular mechanism by which inactivation and K(+) selectivity are linked, a mechanism that may also be at work in other channels containing the canonical GYG signature sequence.

High efficiency coherent optical memory with warm rubidium vapour.

By harnessing aspects of quantum mechanics, communication and information processing could be radically transformed. Promising forms of quantum information technology include optical quantum cryptographic systems and computing using photons for quantum logic operations. As with current information processing systems, some form of memory will be required. Quantum repeaters, which are required for long distance quantum key distribution, require quantum optical memory as do deterministic logic gates for optical quantum computing. Here, we present results from a coherent optical memory based on warm rubidium vapour and show 87% efficient recall of light pulses, the highest efficiency measured to date for any coherent optical memory suitable for quantum information applications. We also show storage and recall of up to 20 pulses from our system. These results show that simple warm atomic vapour systems have clear potential as a platform for quantum memory.

Nonlinear magneto-optical rotation in the presence of a radio-frequency field.

We report measurements of nonlinear magneto-optical rotation (NMOR) for the D2 line of 87Rb atoms in an antirelaxation-coated vapor cell in the presence of a radio-frequency (rf) field. The experimental NMOR signals as a function of rf field frequency for various rf field powers are compared to a theoretical model based on the density-matrix formalism. The comparison between experiment and theory enables understanding of the ground-state atomic spin polarization dynamics, illustrated using plots of the probability distribution of the atomic angular momentum.

Superluminal propagation of pulsed pseudo-thermal light in atomic vapor.

We report an experimental demonstration of slow and superluminal propagation of pseudo-thermal (chaotic) light in the Λ-type system of the 5S(1/2)-5P(1/2) transition of (87)Rb atom. The slowed propagation of pulsed pseudo-thermal light was demonstrated in an electromagnetically-induced transparency medium while the superluminal propagation was demonstrated with the enhanced absorption scheme where the coupling field takes the form of a standing wave.We have also demonstrated that the photon number statistics of the pseudo-thermal light is preserved for both the subluminal and superluminal cases.

High efficient loading of two atoms into a microscopic optical trap by dynamically reshaping the trap with a spatial light modulator.

We demonstrated trapping two neutral (87)Rb atoms in a two site optical ring lattice generated by reflecting a single laser beam from a computer controlled spatial light modulator directly. The ring lattice was transformed into a Gaussian trap by dynamically displaying the holograms animation movie on the modulator. The trapped atoms follow the evolution of traps and move into the same microscopic dipole trap at the end. The detected success rate of this manipulation is larger than 90%. Under imposing the near resonance light, we observed strong light-induce collision between two atoms.

Basics and principles of radiopharmaceuticals for PET/CT.

The presented review provides general background on PET radiopharmaceuticals for oncological applications. Special emphasis is put on radiopharmacological, radiochemical and regulatory aspects. This review is not meant to give details on all different PET tracers in depth but to provide insights into the general principles coming along with their preparation and use. The PET tracer plays a pivotal role because it provides the basis both for image quality and clinical interpretation. It is composed of the radionuclide (signaller) and the molecular vehicle which determines the (bio-)chemical properties (e.g. binding characteristics, metabolism, elimination rate).

Transformation of electromagnetically induced transparency into enhanced absorption with a standing-wave coupling field in an Rb vapor cell.

We present the transformation of electromagnetically induced transparency (EIT) into narrow enhanced absorption with an on-resonant standing-wave coupling field in the 5S(1/2)-5P(1/2) transition of the Lambda-type system of (87)Rb atoms. When a coupling laser field was changed from a travelling-wave to a standing-wave that was made by adding a counter-propagating L(C) laser, the transmittance spectrum of the L(P) laser transformed the typical EIT into dramatically enhanced absorption, and a Bragg reflection signal was generated by the periodic modulation of atomic absorption. The reflected probe laser corresponding to a Bragg reflection was measured to be approximately 11.5% of the power of the incident probe laser. We analyzed the enhanced absorption signal and Bragg reflection spectrum as a function of the power and frequency detuning of the coupling laser.

Transport of Bose-Einstein condensate in QUIC trap and separation of trapping spin states.

We have studied the locomotion track of (87)Rb Bose-Einstein condensate during decompressing the trap into the center of the glass cell in a quadrupole-Ioffe configuration trap. In order to change the position of the BEC, the current in the quadrupole coils is reduced while the current in the Ioffe coil keeps constant. Because of the strongly reduced trap frequencies of the moved trap, the BEC considerably sags down due to the gravity. Thus an inflexion point exists in the process of moving BEC. When rubidium atoms go over the inflexion point, they cannot keep in balance under the gravity and the force provided by a magnetic field, and flow downward and towards Ioffe coil. By utilizing this effect, the trapped atoms with the spin state |F = 2,mF = 1>, which are left over in the BEC, can be separated from the BEC of |F = 2,mF = 2> state.