All-in-fiber SESAM based comb oscillator with an intra-cavity electro-optic modulator for coherent high bandwidth stabilization.

We demonstrate the stabilization of an all-in-fiber polarization maintaining semi-conductor saturable absorber mirror (SESAM) mode locked frequency comb oscillator with an intra-cavity waveguide electro-optic phase modulator (EOM) to a narrow linewidth HeNe laser over 46 hours. The high feedback bandwidth of the EOM allows a coherent optical lock with an in-loop integrated phase noise of 1.12 rad (integrated from 10 Hz to 3 MHz) from the carrier signal. No piezo fiber stretcher was required to guarantee long-term stabilization, preventing mechanical degradation of the optical fibers and enabling a long lifetime of the oscillator. As an application a hybrid stabilization scheme is presented, where a comb tooth is phase locked to a longitudinal mode of the large ring laser "G" located at the Geodatic Observatory Wettzell. The hybrid stabilization scheme describes the optical lock of the frequency comb to the G laser and the simultaneous compensation of the ring laser frequency drift by comparing the comb repetition rate against an active H-maser reference. In this context the ring laser reached a fractional Allan deviation of 5 · 10-16 at an integration time of 16384 s.

First Measurement of the Atomic Electric Dipole Moment of (225)Ra.

The radioactive radium-225 ((225)Ra) atom is a favorable case to search for a permanent electric dipole moment. Because of its strong nuclear octupole deformation and large atomic mass, (225)Ra is particularly sensitive to interactions in the nuclear medium that violate both time-reversal symmetry and parity. We have developed a cold-atom technique to study the spin precession of (225)Ra atoms held in an optical dipole trap, and demonstrated the principle of this method by completing the first measurement of its atomic electric dipole moment, reaching an upper limit of |d((225)Ra)|<5.0×10(-22) e cm (95% confidence).

Hippocampal structural and functional changes associated with electroconvulsive therapy response.

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.

Measurement of the hyperfine quenching rate of the clock transition in 171YB.

We report the first experimental determination of the hyperfine quenching rate of the 6s(2) (1)S(0)(F = 1/2) - 6s6p (3)P(0)(F = 1/2) transition in (171)Yb with nuclear spin I = 1/2. This rate determines the natural linewidth and the Rabi frequency of the clock transition of a Yb optical frequency standard. Our technique involves spectrally resolved fluorescence decay measurements of the lowest lying (3)P(0,1) levels of neutral Yb atoms embedded in a solid Ne matrix. The solid Ne provides a simple way to trap a large number of atoms as well as an efficient mechanism for populating (3)P(0). The decay rates in solid Ne are modified by medium effects including the index-of-refraction dependence. We find the (3)P(0) hyperfine quenching rate to be (4.42 ± 0.35) × 10(-2) s(-1) for free (171)Yb, which agrees with recent ab initio calculations.

An atomic clock with 10(-18) instability.

Atomic clocks have been instrumental in science and technology, leading to innovations such as global positioning, advanced communications, and tests of fundamental constant variation. Timekeeping precision at 1 part in 10(18) enables new timing applications in relativistic geodesy, enhanced Earth- and space-based navigation and telescopy, and new tests of physics beyond the standard model. Here, we describe the development and operation of two optical lattice clocks, both using spin-polarized, ultracold atomic ytterbium. A measurement comparing these systems demonstrates an unprecedented atomic clock instability of 1.6 × 10(-18) after only 7 hours of averaging.

[Effects of physical activity and physical training on the psychological status of older persons with and without cognitive impairment]. / Effekte körperlicher Aktivität und körperlichen Trainings auf den psychischen Status bei älteren Menschen mit und ohne kognitive Schädigung.

Fear of falling and depression in the elderly and among cognitively impaired people lead to restrictions in quality of life. Being more active is associated with improved mental health as documented in cross-sectional and longitudinal studies. This is especially true for depression. Such epidemiologic evidence is lacking in fear of falling. This review summarizes current evidence from epidemiological and randomized controlled trials (RCTs) and gives an outlook for future research perspectives. The majority of studies included in this review document a significant reduction of depression and fear of falling in older persons by physical training with less evidence in persons with cognitive impairment. With respect to intensity, duration, and amount of exercise, evidence-based recommendations were limited by the small number of high-quality comparative RCTs. High-intensity strength or endurance training was the most effective for reducing depression, while participation in Tai-Chi or multifactorial training programs was most effective to reduce fear of falling.

High-accuracy measurement of atomic polarizability in an optical lattice clock.

Presently, the Stark effect contributes the largest source of uncertainty in a ytterbium optical atomic clock through blackbody radiation. By employing an ultracold, trapped atomic ensemble and high stability optical clock, we characterize the quadratic Stark effect with unprecedented precision. We report the ytterbium optical clock's sensitivity to electric fields (such as blackbody radiation) as the differential static polarizability of the ground and excited clock levels α(clock) = 36.2612(7) kHz (kV/cm)(-2). The clock's uncertainty due to room temperature blackbody radiation is reduced by an order of magnitude to 3×10(-17).

Stretched-exponential behavior and random walks on diluted hypercubic lattices.

Diffusion on a diluted hypercube has been proposed as a model for glassy relaxation and is an example of the more general class of stochastic processes on graphs. In this article we determine numerically through large-scale simulations the eigenvalue spectra for this stochastic process and calculate explicitly the time evolution for the autocorrelation function and for the return probability, all at criticality, with hypercube dimensions N up to N=28. We show that at long times both relaxation functions can be described by stretched exponentials with exponent 1/3 and a characteristic relaxation time which grows exponentially with dimension N. The numerical eigenvalue spectra are consistent with analytic predictions for a generic sparse network model.

p-Wave cold collisions in an optical lattice clock.

We study ultracold collisions in fermionic ytterbium by precisely measuring the energy shifts they impart on the atoms' internal clock states. Exploiting Fermi statistics, we uncover p-wave collisions, in both weakly and strongly interacting regimes. With the higher density afforded by two-dimensional lattice confinement, we demonstrate that strong interactions can lead to a novel suppression of this collision shift. In addition to reducing the systematic errors of lattice clocks, this work has application to quantum information and quantum simulation with alkaline-earth atoms.

In vivo correlation of tumor blood volume and permeability with histologic and molecular angiogenic markers in gliomas.

BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo correlation of perfusion imaging parameters with angiogenic markers can help in better understanding the role of perfusion imaging as an imaging biomarker. The purpose of this study was to correlate PCT parameters such as CBV and PS with histologic and molecular angiogenic markers in gliomas. MATERIALS AND METHODS: Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression, tumor cellularity, and WHO grade of the image-guided biopsy specimens with the PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34, and VEGFR-2 and examined under a light microscope. These histologic and molecular angiogenic markers were correlated with perfusion parameters of the region of interest corresponding to the biopsy specimen. Pearson correlation coefficients and multiple regression analyses by using clustering methods were performed to assess these correlations. RESULTS: CBV showed a significant positive correlation with MVD (r = 0.596, P < .001), whereas PS showed a significant positive correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade. VEGFR-2 positive specimens showed higher PS and CBV; however, neither was statistically significant at the .05 level. CONCLUSIONS: CBV showed a significant positive correlation with MVD, whereas PS showed a significant positive correlation with MVCP, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels; hence, in vivo evaluation of these could be important in a better understanding of tumor angiogenesis.

Spin-1/2 optical lattice clock.

We experimentally investigate an optical clock based on ;{171}Yb (I = 1/2) atoms confined in an optical lattice. We have evaluated all known frequency shifts to the clock transition, including a density-dependent collision shift, with a fractional uncertainty of 3.4 x 10;{-16}, limited principally by uncertainty in the blackbody radiation Stark shift. We measured the absolute clock transition frequency relative to the NIST-F1 Cs fountain clock and find the frequency to be 518 295 836 590 865.2(0.7) Hz.

Probing interactions between ultracold fermions.

At ultracold temperatures, the Pauli exclusion principle suppresses collisions between identical fermions. This has motivated the development of atomic clocks with fermionic isotopes. However, by probing an optical clock transition with thousands of lattice-confined, ultracold fermionic strontium atoms, we observed density-dependent collisional frequency shifts. These collision effects were measured systematically and are supported by a theoretical description attributing them to inhomogeneities in the probe excitation process that render the atoms distinguishable. This work also yields insights for zeroing the clock density shift.

Optical lattice induced light shifts in an yb atomic clock.

We present an experimental study of the lattice-induced light shifts on the (1)S(0) --> (3)P(0) optical clock transition (nu(clock) approximately 518 THz) in neutral ytterbium. The "magic" frequency nu(magic) for the 174Yb isotope was determined to be 394 799 475(35) MHz, which leads to a first order light shift uncertainty of 0.38 Hz. We also investigated the hyperpolarizability shifts due to the nearby 6s6p(3)P(0) --> 6s8p(3)P(0), 6s8p(3)P(2), and 6s5f(3)F(2) two-photon resonances at 759.708, 754.23, and 764.95 nm, respectively. By measuring the corresponding clock transition shifts near these two-photon resonances, the hyperpolarizability shift was estimated to be 170(33) mHz for a linear polarized, 50 microK deep, lattice at the magic wavelength. These results indicate that the differential polarizability and hyperpolarizability frequency shift uncertainties in a Yb lattice clock could be held to well below 10(-17).

Sr lattice clock at 1 x 10(-16) fractional uncertainty by remote optical evaluation with a Ca clock.

Optical atomic clocks promise timekeeping at the highest precision and accuracy, owing to their high operating frequencies. Rigorous evaluations of these clocks require direct comparisons between them. We have realized a high-performance remote comparison of optical clocks over kilometer-scale urban distances, a key step for development, dissemination, and application of these optical standards. Through this remote comparison and a proper design of lattice-confined neutral atoms for clock operation, we evaluate the uncertainty of a strontium (Sr) optical lattice clock at the 1 x 10(-16) fractional level, surpassing the current best evaluations of cesium (Cs) primary standards. We also report on the observation of density-dependent effects in the spin-polarized fermionic sample and discuss the current limiting effect of blackbody radiation-induced frequency shifts.

Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response.

Sparc-null mice have been used as models to assess tumor-host immune cell interactions. However, it is not known if they have a competent immune system. In this study, the immune systems of Sparc wild-type and null mice were compared. Mice were assessed for differences in total body weight, spleen weight and spleen-to-body weight ratios. Spleens were compared with respect to morphology, and Sparc, Ki-67, MOMA-1 and IgM expression. Immune cells in blood, bone marrow and spleen were assessed by blood smears, automated blood panel, and flow cytometry. Additionally, the ability of Sparc-null mice to respond to immune challenge was evaluated using a footpad model. The morphological and immunohistochemical results indicated that Sparc-null spleens had more white pulp, hyperproliferative B cells in the germinal centers, and decreased marginal zones. Sparc-null spleens lacked normal Sparc expression in red and white pulp, marginal zones, endothelial and sinusoidal cells. By flow analysis, B cells were decreased and T cells were increased in the bone marrow. Finally, Sparc-null mice were unable to mount an immune response following footpad lipopolysaccharide challenge. These data confirm that Sparc-null mice have an impaired immune system.

Exploring molecular networks using MONET ontology

The description of the complex molecular network responsible for cell behavior requires new tools to integrate large quantities of experimental data in the design of biological information systems. These tools could be used in the characterization of these networks and in the formulation of relevant biological hypotheses. The building of an ontology is a crucial step because it integrates in a coherent framework the concepts necessary to accomplish such a task. We present MONET (molecular network), an extensible ontology and an architecture designed to facilitate the integration of data originating from different public databases in a single- and well-documented relational database, that is compatible with MONET formal definition. We also present an example of an application that can easily be implemented using these tools.

An integrated model for cellular analysis

We present the MOlecular NETwork (MONET) ontology as a model to integrate data from different networks that govern cell function. To achieve this, different existing ontologies were analyzed and an integrated ontology was built in a way to make it possible to share and reuse knowledge, support interoperability between systems, and also allow the formulation of hypotheses through inferences. By studying the cell as an entity of a myriad of elements and networks of interactions, we aim to offer a means to understand the large-scale characteristics responsible for the behavior of the cell and to enable new biological insights.

A model for the detection of clonality in marked hematopoietic stem cells.

The semirandom location of retroviral integration in the target cell genome introduces a marker in the form of a fusion sequence composed of a genomic and a proviral part that is unique for each transduced cell and its clonal progeny. High-sensitivity detection of these fusion sequences would allow the tracking of clonal contributions of individual, marked hematopoietic progenitor, and stem cells in vivo. Clone detection by Southern blot has helped to analyze models of oligoclonal repopulation but is limited in sensitivity and specificity. Inverse PCR (Nolta et al., Proc. Natl. Acad. Sci. USA 93: 2414-2419) can demonstrate the clonal identity by sequencing but does not permit simultaneous detection of multiple clones. In an efficiently transduced rhesus macaque model (Tisdale et al., Blood 92: 2681-2687; Wu et al., Mol. Ther. 1: 285-293) Kim et al. (Blood 96: 1-8) have identified more than 40 insertion sequences from marrow CFU by inverse PCR. However, no previous study has been able to directly analyze the number of clones active in vivo. Here we demonstrate that the application of a recently developed PCR technology allows the simultaneous visualization of multiple integration sites from small clonal contributions to hematopoietic cells. By combining solid-phase primer extension with ligation-mediated PCR, direct genomic sequencing of retroviral integration sites was obtained in murine bone marrow samples. Further development of this technology will allow analysis of the clonal composition of marked hematopoiesis in small and large animals as well as in human gene transfer.

Detection and direct genomic sequencing of multiple rare unknown flanking DNA in highly complex samples.

By identifying the sequence of retro- and lentiviral integration sites in peripheral blood leukocytes, the clonal composition and fate of genetically modified hematopoietic progenitor and stem cells could be mapped in vitro and in vivo. Previously available methods have been limited to the analysis of mono- or oligoclonal integration sites present in high copy numbers. Here, we perform characterization of multiple rare retroviral and lentiviral integration sites in highly complex DNA samples. The reliability of this method results from nontarget DNA removal via magnetic extension primer tag selection (EPTS) preceding solid-phase ligation-mediated PCR. EPTS/LM-PCR allowed the simultaneous direct genomic sequencing of multiple proviral LTR-flanking sequences of retro- and lentiviral vectors even if only 1 per 100 to 1000 cells contained the provirus. A primer walking "around" the integration locus demonstrated the adaptability of EPTS/LM-PCR to study unknown flanking DNA regions unrelated to proviruses. The technique is fast, inexpensive, and sensitive in minimal samples. It enables studies of retro- and lentiviral integration, viral vector tracking in gene therapy, insertional mutagenesis, transgene integration, and direct genomic sequencing that until now have been difficult or impossible to perform.

Video camera and light system for application in magnetic resonance scanners.

The direct observation and simultaneous recording of subject behavior, e.g. facial movements, during MR imaging is necessary for a variety of functional imaging studies involving phenomena such as emotions, humor, mood, etc. Such observation is also valuable for the monitoring of very ill or young patients. We describe a color video camera and light system which works within the functioning scanner. The camera acquires high resolution video sequences during conventional T(1)-weighted and functional T(2)*-weighted imaging. When fixed to the head coil artefacts during the MRI-acquisition were insignificant. The video allows observation of the face detailed enough to permit FACS scoring of facial expressions. We therefore propose that it can be applied for a wide variety of studies needing visual feedback of subject behavior.