First measurements of high frequency cross-spectra from a pair of large Michelson interferometers

Measurements are reported of the cross-correlation of spectra of differential position signals from the Fermilab Holometer, a pair of co-located 39 m long, high power Michelson interferometers with flat, broadband frequency response in the MHz range. The instrument obtains sensitivity to high frequency correlated signals far exceeding any previous measurement in a broad frequency band extending beyond the 3.8 MHz inverse light crossing time of the apparatus. The dominant but uncorrelated shot noise is averaged down over $2\times 10^8$ independent spectral measurements with 381 Hz frequency resolution to obtain $2.1\times 10^{-20} \ \mathrm{m}/\sqrt{\mathrm{Hz}}$ sensitivity to stationary signals. For signal bandwidths $\Delta f > 11$ kHz, the sensitivity to strain $h$ or shear power spectral density of classical or exotic origin surpasses a milestone $PSD_{\delta h} < t_p$ where $t_p= 5.39\times 10^{-44}/\mathrm{Hz}$ is the Planck time.Comment: 5 pages, 3 figure

The Use of Molecular Pathway Inhibitors in the Treatment of Osteosarcoma

Presently, the 5-year survival rate for metastatic osteosarcoma remains low despite advances in chemotherapeutics and neoadjuvant therapy. A majority of the morbidity and nearly all of the mortality in osteosarcoma rely not in the primary disease but in the metastatic disease. The pursuit of novel molecular therapies is attractive due to their targeted ability to combat metastasis. Unlike traditional chemotherapy agents, which work by targeting rapidly dividing cells, targeted therapies may spare normal cells and decrease the adverse effects of chemotherapy by targeting specific pathways. Here, we discuss key molecular pathways in osteosarcoma and their ability to be modulated for the goal of eradication of primary and metastatic disease. We focus specifically on the aldehyde dehydrogenase (ALDH), epidermal growth factor receptor (EGFR), and insulin-like growth factor-1 receptor (IGF-1R) pathways

Interferometric Constraints on Quantum Geometrical Shear Noise Correlations

Final measurements and analysis are reported from the first-generation Holometer, the first instrument capable of measuring correlated variations in space-time position at strain noise power spectral densities smaller than a Planck time. The apparatus consists of two co-located, but independent and isolated, 40 m power-recycled Michelson interferometers, whose outputs are cross-correlated to 25 MHz. The data are sensitive to correlations of differential position across the apparatus over a broad band of frequencies up to and exceeding the inverse light crossing time, 7.6 MHz. By measuring with Planck precision the correlation of position variations at spacelike separations, the Holometer searches for faint, irreducible correlated position noise backgrounds predicted by some models of quantum space-time geometry. The first-generation optical layout is sensitive to quantum geometrical noise correlations with shear symmetry---those that can be interpreted as a fundamental noncommutativity of space-time position in orthogonal directions. General experimental constraints are placed on parameters of a set of models of spatial shear noise correlations, with a sensitivity that exceeds the Planck-scale holographic information bound on position states by a large factor. This result significantly extends the upper limits placed on models of directional noncommutativity by currently operating gravitational wave observatories.Comment: Matches the journal accepted versio

High-throughput smFRET analysis of freely diffusing nucleic acid molecules and associated proteins

Single-molecule Förster resonance energy transfer (smFRET) is a powerful technique for nanometer-scale studies of single molecules. Solution-based smFRET, in particular, can be used to study equilibrium intra- and intermolecular conformations, binding/unbinding events and conformational changes under biologically relevant conditions without ensemble averaging. However, single-spot smFRET measurements in solution are slow. Here, we detail a high-throughput smFRET approach that extends the traditional single-spot confocal geometry to a multispot one. The excitation spots are optically conjugated to two custom silicon single photon avalanche diode (SPAD) arrays. Two-color excitation is implemented using a periodic acceptor excitation (PAX), allowing distinguishing between singly- and doubly-labeled molecules. We demonstrate the ability of this setup to rapidly and accurately determine FRET efficiencies and population stoichiometries by pooling the data collected independently from the multiple spots. We also show how the high throughput of this approach can be used o increase the temporal resolution of single-molecule FRET population characterization from minutes to seconds. Combined with microfluidics, this high-throughput approach will enable simple real-time kinetic studies as well as powerful molecular screening applications

ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import

Generation and Characterization of Anti-AA Amyloid-Specific Monoclonal Antibodies

AA amyloidosis results from the pathologic deposition in the kidneys and other organs of fibrils composed of N-terminal fragments of serum amyloid A protein (SAA). Given that there are only limited means to visualize these deposits, we have developed a series of mAbs, 2A4, 7D8, and 8G9, that bind specifically with nanomolar affinity to a carboxy-terminal epitope generated following proteolysis of SAA that yields the predominant component of AA amyloid deposits. Notably, these antibodies do not recognize native SAA, they retain their immunoreactivity when radiolabeled with I-125 and, after injection into AA amyloidotic mice, localize, as evidenced by autoradiography and micro-single photon emission computed tomography imaging, to histologically confirmed areas of amyloid deposition; namely, spleen, liver, and pancreas. The results of our in vitro and in vivo studies demonstrate the AA fibril-selectivity of mAbs 2A4, 7D8, and 8G9 and warrant further investigation into their role as novel diagnostic agents for patients with AA amyloidosis

MHz gravitational wave constraints with decameter Michelson interferometers

A new detector, the Fermilab Holometer, consists of separate yet identical 39-meter Michelson interferometers. Strain sensitivity achieved is better than 10[superscript -21]/√Hz between 1 to 13 MHz from a 130-h data set. This measurement exceeds the sensitivity and frequency range made from previous high frequency gravitational wave experiments by many orders of magnitude. Constraints are placed on a stochastic background at 382 Hz resolution. The 3σ upper limit on Ω[subscript GW], the gravitational wave energy density normalized to the closure density, ranges from 5.6×10[superscript 12] at 1 MHz to 8.4×10[superscript 15] at 13 MHz. Another result from the same data set is a search for nearby primordial black hole binaries (PBHB). There are no detectable monochromatic PBHBs in the mass range 0.83–3.5×10[superscript 21]  g between the Earth and the Moon. Projections for a chirp search with the same data set increase the mass range to 0.59-2.5×10[superscript 25]  g and distances out to Jupiter. This result presents a new method for placing limits on a poorly constrained mass range of primordial black holes. Additionally, solar system searches for PBHBs place limits on their contribution to the total dark matter fraction.United States. Dept. of Energy (Contract DE-AC02-07CH11359)United States. Dept. of Energy (Early Career Research Program FNAL FWP 11-03)Templeton FoundationNational Science Foundation (U.S.) (Grants PHY- 1205254 and DGE-1144082)National Aeronautics and Space Administration (Grant NNX09AR38G)Fermi Research AllianceUniversity of Chicago. Kavli Institute for Cosmological PhysicsUniversity of Chicago. Fermilab Strategic Collaborative InitiativesScience Support ConsortiumNational Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-0638477)Universities Research Association (U.S.). Visiting Scholars Progra