Limit on the Temporal Variation of the Fine-Structure Constant Using Atomic Dysprosium

Over a period of eight months, we have monitored transition frequencies between nearly degenerate, opposite-parity levels in two isotopes of atomic dysprosium (Dy). These transition frequencies are highly sensitive to temporal variation of the fine-structure constant ($\alpha$) due to relativistic corrections of large and opposite sign for the opposite-parity levels. In this unique system, in contrast to atomic-clock comparisons, the difference of the electronic energies of the opposite-parity levels can be monitored directly utilizing a radio-frequency (rf) electric-dipole transition between them. Our measurements show that the frequency variation of the 3.1-MHz transition in $^{163}$Dy and the 235-MHz transition in $^{162}$Dy are 9.0$\pm$6.7 Hz/yr and -0.6$\pm$6.5 Hz/yr, respectively. These results provide a value for the rate of fractional variation of $\alpha$ of $(-2.7\pm2.6)\times 10^{-15}$ yr$^{-1}$ (1 $\sigma$) without any assumptions on the constancy of other fundamental constants, indicating absence of significant variation at the present level of sensitivity.Comment: 4 pages, 2 figure

Broadband Phase-Noise Suppression in a Yb-Fiber Frequency Comb

We report a simple technique to suppress high frequency phase noise of a Yb-based fiber optical frequency comb using an active intensity noise servo. Out-of-loop measurements of the phase noise using an optical heterodyne beat with a continuous wave (cw) laser show suppression of phase noise by \geq7 dB out to Fourier frequencies of 100 kHz with a unity-gain crossing of -700 kHz. These results are enabled by the strong correlation between the intensity and phase noise of the laser. Detailed measurements of intensity and phase noise spectra, as well as transfer functions, reveal that the dominant phase and intensity noise contribution above -100 kHz is due to amplified spontaneous emission (ASE) or other quantum noise sources.Comment: 4 pages, 3 figure

All-optical atomic magnetometers based on nonlinear magneto-optical rotation with amplitude modulated light

We demonstrate a magnetometric technique based on nonlinear magneto-optical rotation using amplitude modulated light. The magnetometers can be operated in either open-loop (typical nonlinear magneto-optical rotation with amplitude-modulated light) or closed-loop (self-oscillating) modes. The latter mode is particularly well suited for conditions where the magnetic field is changing by large amounts over a relatively short timescale.Comment: 8 pages, 6 figures, Submitted to Proc. of SPIE, Proceedings of XIVth International School on Quantum Electronics, Sunny Beach, Bulgaria 200

The 2.3 GHz continuum survey of the GEM project

We present a partial-sky survey of the radio continuum at 2.3 GHz within the scope of the Galactic Emission Mapping (GEM) project, an observational program conceived and developed to reveal the large-scale properties of Galactic synchrotron radiation through a set of self-consistent surveys of the radio continuum between 408 MHz and 10 GHz. The GEM experiment uses a portable and double-shielded 5.5-m radiotelescope in altazimuthal configuration to map 60-degree-wide declination bands from different observational sites by circularly scanning the sky at zenithal angles of 30 deg from a constantly rotating platform. The observations were accomplished with a total power receiver, whose front-end High Electron Mobility Transistor (HEMT) amplifier was matched directly to a cylindrical horn at the prime focus of the parabolic reflector. The Moon was used to calibrate the antenna temperature scale and the preparation of the map required direct subtraction and destriping algorithms to remove ground contamination as the most significant source of systematic error. We used 484 hours of total intensity observations from two locations in Colombia and Brazil to yield 66% sky coverage from DEC = -51.73 deg to DEC = +34.78 deg. The zero-level uncertainty of the combined survey is 103 mK with a temperature scale error of 5% after direct correlation with the Rhodes/HartRAO survey at 2326 MHz on a T-T plot. The sky brightness distribution into regions of low and high emission in the GEM survey is consistent with the appearance of a transition region as seen in the Haslam 408 MHz and WMAP K-band surveys. Preliminary results also show that the temperature spectral index between 408 MHz and the 2.3 GHz band of the GEM survey has a weak spatial correlation with these regions; but it steepens significantly from high to low emission regions with respect to the WMAP K-band survey.Comment: 20 pages, 21 figures, 6 tables. Extensively revised and enlarged version accepted for publication in Astronomy & Astrophysics. Smaller figure

Comparison of GPS analysis strategies for high-accuracy vertical land motion

Tide gauges measure sea level changes relative to land. To separate absolute changes in sea level from vertical land movements tide gauges are often co-located with Continuous GPS (CGPS). In order to achieve an accuracy of better than 1 mm/yr, as required for sea level studies in the global change context, vertical land motion needs to be determined with the same accuracy. This is an ambitious goal for CGPS and needs a carefully designed analysis strategy. We have compared the independent results from six different analysis centres, using three different GPS processing softwares and a number of different analysis strategies. Based on the comparison, we discuss the achieved accuracy and the quality of the different strategies. The data analysed are from the CGPS network of the European Sea Level Service and cover the time window from the beginning of 2000 until the end of 2003. The comparison reveals large differences in the day-to-day variations of the coordinate time series and also in the seasonal cycle contained in these. The trends show systematic differences, depending on software and strategy used. To a large extent, the latter deviations can be explained by differences in the realisation of the reference frame, while some parts may be due to other, as yet, unidentified contributions. The results suggest that the reference frame and its relation to the center of mass of the Earth system may be the main limitation in achieving the accuracy goal for the secular velocity of vertical land motion.Peer ReviewedPostprint (published version

The Ability to Generate Senescent Progeny as a Mechanism Underlying Breast Cancer Cell Heterogeneity

Background Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. Methodology/Principal Findings A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21Cip1 correlated with senescence in these cell lines. p21Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. Conclusions/Significance Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential. © 2010 Mumcuoglu et al

Amplified Loci on Chromosomes 8 and 17 Predict Early Relapse in ER-Positive Breast Cancers

Adjuvant hormonal therapy is administered to all early stage ER+ breast cancers, and has led to significantly improved survival. Unfortunately, a subset of ER+ breast cancers suffer early relapse despite hormonal therapy. To identify molecular markers associated with early relapse in ER+ breast cancer, an outlier analysis method was applied to a published gene expression dataset of 268 ER+ early-stage breast cancers treated with tamoxifen alone. Increased expression of sets of genes that clustered in chromosomal locations consistent with the presence of amplicons at 8q24.3, 8p11.2, 17q12 (HER2 locus) and 17q21.33-q25.1 were each found to be independent markers for early disease recurrence. Distant metastasis free survival (DMFS) after 10 years for cases with any amplicon (DMFS  = 56.1%, 95% CI  = 48.3–63.9%) was significantly lower (P  = 0.0016) than cases without any of the amplicons (DMFS  = 87%, 95% CI  = 76.3% –97.7%). The association between presence of chromosomal amplifications in these regions and poor outcome in ER+ breast cancers was independent of histologic grade and was confirmed in independent clinical datasets. A separate validation using a FISH-based assay to detect the amplicons at 8q24.3, 8p11.2, and 17q21.33-q25.1 in a set of 36 early stage ER+/HER2- breast cancers treated with tamoxifen suggests that the presence of these amplicons are indeed predictive of early recurrence. We conclude that these amplicons may serve as prognostic markers of early relapse in ER+ breast cancer, and may identify novel therapeutic targets for poor prognosis ER+ breast cancers

Membrane Fusion and Cell Entry of XMRV Are pH-Independent and Modulated by the Envelope Glycoprotein's Cytoplasmic Tail

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that was originally identified from human prostate cancer patients and subsequently linked to chronic fatigue syndrome. Recent studies showed that XMRV is a recombinant mouse retrovirus; hence, its association with human diseases has become questionable. Here, we demonstrated that XMRV envelope (Env)-mediated pseudoviral infection is not blocked by lysosomotropic agents and cellular protease inhibitors, suggesting that XMRV entry is not pH-dependent. The full length XMRV Env was unable to induce syncytia formation and cell-cell fusion, even in cells overexpressing the viral receptor, XPR1. However, truncation of the C-terminal 21 or 33 amino acid residues in the cytoplasmic tail (CT) of XMRV Env induced substantial membrane fusion, not only in the permissive 293 cells but also in the nonpermissive CHO cells that lack a functional XPR1 receptor. The increased fusion activities of these truncations correlated with their enhanced SU shedding into culture media, suggesting conformational changes in the ectodomain of XMRV Env. Noticeably, further truncation of the CT of XMRV Env proximal to the membrane-spanning domain severely impaired the Env fusogenicity, as well as dramatically decreased the Env incorporations into MoMLV oncoretroviral and HIV-1 lentiviral vectors resulting in greatly reduced viral transductions. Collectively, our studies reveal that XMRV entry does not require a low pH or low pH-dependent host proteases, and that the cytoplasmic tail of XMRV Env critically modulates membrane fusion and cell entry. Our data also imply that additional cellular factors besides XPR1 are likely to be involved in XMRV entry

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS