Optimal combination of signals from co-located gravitational wave interferometers for use in searches for a stochastic background

This article derives an optimal (i.e., unbiased, minimum variance) estimator for the pseudo-detector strain for a pair of co-located gravitational wave interferometers (such as the pair of LIGO interferometers at its Hanford Observatory), allowing for possible instrumental correlations between the two detectors. The technique is robust and does not involve any assumptions or approximations regarding the relative strength of gravitational wave signals in the detector pair with respect to other sources of correlated instrumental or environmental noise. An expression is given for the effective power spectral density of the combined noise in the pseudo-detector. This can then be introduced into the standard optimal Wiener filter used to cross-correlate detector data streams in order to obtain an optimal estimate of the stochastic gravitational wave background. In addition, a dual to the optimal estimate of strain is derived. This dual is constructed to contain no gravitational wave signature and can thus be used as on "off-source" measurement to test algorithms used in the "on-source" observation.Comment: 14 pages, 4 figures, submitted to Physical Review D Resubmitted after editing paper in response to referee comments. Removed appendices A, B and edited text accordingly. Improved legibility of figures. Corrected several references. Corrected reference to science run number (S1 vs. S2) in text and figure caption

Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

<p>Abstract</p> <p>Background</p> <p>Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.</p> <p>Results</p> <p>We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ΔH of -13 ± 2 kJ/mol and a ΔS of -0.04 ± 0.01 kJ/(K*mol). The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site.</p> <p>Conclusion</p> <p>We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the geometric relationship of arginine-tryptophan pairs, which often have significant roles in protein function. Using the unusual characteristics of the RTA system, we measured the still controversial thermodynamic changes of site-specific urea binding to a protein, results that are relevant to understanding the physical mechanisms of protein denaturation.</p

Stochastic Background Search Correlating ALLEGRO with LIGO Engineering Data

We describe the role of correlation measurements between the LIGO interferometer in Livingston, LA, and the ALLEGRO resonant bar detector in Baton Rouge, LA, in searches for a stochastic background of gravitational waves. Such measurements provide a valuable complement to correlations between interferometers at the two LIGO sites, since they are sensitive in a different, higher, frequency band. Additionally, the variable orientation of the ALLEGRO detector provides a means to distinguish gravitational wave correlations from correlated environmental noise. We describe the analysis underway to set a limit on the strength of a stochastic background at frequencies near 900 Hz using ALLEGRO data and data from LIGO's E7 Engineering Run.Comment: 8 pages, 2 encapsulated PostScript figures, uses IOP class files, submitted to the proceedings of the 7th Gravitational Wave Data Analysis Workshop (which will be published in Classical and Quantum Gravity

Progress on stochastic background search codes for LIGO

One of the types of signals for which the LIGO interferometric gravitational wave detectors will search is a stochastic background of gravitational radiation. We review the technique of searching for a background using the optimally-filtered cross-correlation statistic, and describe the state of plans to perform such cross-correlations between the two LIGO interferometers as well as between LIGO and other gravitational-wave detectors, in particular the preparation of software to perform such data analysis.Comment: 7 pages, 1 encapsulated PostScript figure, uses IOP class files, submitted to the proceedings of the 4th Amaldi meeting (which will be published in Classical and Quantum Gravity

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

Understanding the impetus for major systems change: A multiple case study of decisions and non-decisions to reconfigure emergency and urgent care services

Objective The optimal organisation of emergency and urgent care services (EUCS) is a perennial problem internationally. Similar to other countries, the Health Service Executive in Ireland pursued EUCS reconfiguration in response to quality and safety concerns, unsustainable costs and workforce issues. However, the implementation of reconfiguration has been inconsistent at a regional level. Our aim was to identify the factors that led to this inconsistency. Methods Using a multiple case study design, six case study regions represented full, partial and little/no reconfiguration at emergency departments (EDs). Data from documents and key stakeholder interviews were analysed using a framework approach with cross-case analysis. Results The impetus to reconfigure ED services was triggered by patient safety events, and to a lesser extent by having a region-specific plan and an obvious starting point for changes. However, the complexity of the next steps and political influence impeded reconfiguration in several regions. Implementation was more strategic in regions that reconfigured later, facilitated by clinical leadership and “lead-in time” to plan and sell changes. Conclusion While the global shift towards centralisation of EUCS is driven by universal challenges, decisions about when, where and how much to implement are influenced by local drivers including context, people and politics. This can contribute to a public perception of inequity and distrust in proposals for major systems change

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris

Objective: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. Methods: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). Results: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. Conclusions: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi