Optical read out and feedback cooling of a nanostring optomechanical cavity

Optical measurement of the motion of a 940 kHz mechanical resonance of a silicon nitride nanostring resonator is demonstrated with a read out noise imprecision reaching 37 dB below that of the resonator's zero-point fluctuations. Via intensity modulation of the optical probe laser, radiation pressure feedback is used to cool and damp the mechanical mode from an initial room temperature occupancy of $\bar{n}_{b} = 6.5 \times 10^6$ ($T_{b}=295$K) down to a phonon occupation of $\langle n \rangle = 66 \pm 10$, representing a mode temperature of $T_{m} \approx 3$mK. The five decades of cooling is enabled by the system's large single-photon cooperativity $(C_{1} = 4)$ and high quantum efficiency of optical motion detection ($\eta_{t} = 0.27$).Comment: 13 pages, 13 figure

The Taiwanese-American Occultation Survey: The Multi-Telescope Robotic Observatory

The Taiwanese-American Occultation Survey (TAOS) operates four fully automatic telescopes to search for occultations of stars by Kuiper Belt Objects. It is a versatile facility that is also useful for the study of initial optical GRB afterglows. This paper provides a detailed description of the TAOS multi-telescope system, control software, and high-speed imaging.Comment: 11 pages, 11 figure

Efficient use of single molecule time traces to resolve kinetic rates, models and uncertainties

Single molecule time traces reveal the time evolution of unsynchronized kinetic systems. Especially single molecule F\"orster resonance energy transfer (smFRET) provides access to enzymatically important timescales, combined with molecular distance resolution and minimal interference with the sample. Yet the kinetic analysis of smFRET time traces is complicated by experimental shortcomings - such as photo-bleaching and noise. Here we recapitulate the fundamental limits of single molecule fluorescence that render the classic, dwell-time based kinetic analysis unsuitable. In contrast, our Single Molecule Analysis of Complex Kinetic Sequences (SMACKS) considers every data point and combines the information of many short traces in one global kinetic rate model. We demonstrate the potential of SMACKS by resolving the small kinetic effects caused by different ionic strengths in the chaperone protein Hsp90. These results show an unexpected interrelation between conformational dynamics and ATPase activity in Hsp90.Comment: 17 pages, 6 figure

Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta.

Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer's, Parkinson's, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (Aβ) protein of Alzheimer's disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce Aβ cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to Aβ fibers, they do not reduce fiber formation of Aβ. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of Aβ from oligomers to fibers. DOI:http://dx.doi.org/10.7554/eLife.00857.001

Resiliency Assessment and Enhancement of Intrinsic Fingerprinting

Intrinsic fingerprinting is a class of digital forensic technology that can detect traces left in digital multimedia data in order to reveal data processing history and determine data integrity. Many existing intrinsic fingerprinting schemes have implicitly assumed favorable operating conditions whose validity may become uncertain in reality. In order to establish intrinsic fingerprinting as a credible approach to digital multimedia authentication, it is important to understand and enhance its resiliency under unfavorable scenarios. This dissertation addresses various resiliency aspects that can appear in a broad range of intrinsic fingerprints. The first aspect concerns intrinsic fingerprints that are designed to identify a particular component in the processing chain. Such fingerprints are potentially subject to changes due to input content variations and/or post-processing, and it is desirable to ensure their identifiability in such situations. Taking an image-based intrinsic fingerprinting technique for source camera model identification as a representative example, our investigations reveal that the fingerprints have a substantial dependency on image content. Such dependency limits the achievable identification accuracy, which is penalized by a mismatch between training and testing image content. To mitigate such a mismatch, we propose schemes to incorporate image content into training image selection and significantly improve the identification performance. We also consider the effect of post-processing against intrinsic fingerprinting, and study source camera identification based on imaging noise extracted from low-bit-rate compressed videos. While such compression reduces the fingerprint quality, we exploit different compression levels within the same video to achieve more efficient and accurate identification. The second aspect of resiliency addresses anti-forensics, namely, adversarial actions that intentionally manipulate intrinsic fingerprints. We investigate the cost-effectiveness of anti-forensic operations that counteract color interpolation identification. Our analysis pinpoints the inherent vulnerabilities of color interpolation identification, and motivates countermeasures and refined anti-forensic strategies. We also study the anti-forensics of an emerging space-time localization technique for digital recordings based on electrical network frequency analysis. Detection schemes against anti-forensic operations are devised under a mathematical framework. For both problems, game-theoretic approaches are employed to characterize the interplay between forensic analysts and adversaries and to derive optimal strategies. The third aspect regards the resilient and robust representation of intrinsic fingerprints for multiple forensic identification tasks. We propose to use the empirical frequency response as a generic type of intrinsic fingerprint that can facilitate the identification of various linear and shift-invariant (LSI) and non-LSI operations

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

The Taiwanese-American Occultation Survey Project Stellar Variability. II. Detection of 15 Variable Stars

The Taiwanese-American Occultation Survey (TAOS) project has collected more than a billion photometric measurements since 2005 January. These sky survey data—covering timescales from a fraction of a second to a few hundred days—are a useful source to study stellar variability. A total of 167 star fields, mostly along the ecliptic plane, have been selected for photometric monitoring with the TAOS telescopes. This paper presents our initial analysis of a search for periodic variable stars from the time-series TAOS data on one particular TAOS field, No. 151 (R.A. = 17^(h)30^(m)6^(s).7, decl. = 27°17'30", J2000), which had been observed over 47 epochs in 2005. A total of 81 candidate variables are identified in the 3 deg^2 field, with magnitudes in the range 8 < R < 16. On the basis of the periodicity and shape of the light curves, 29 variables, 15 of which were previously unknown, are classified as RR Lyrae, Cepheid, δ Scuti, SX Phonencis, semi-regular, and eclipsing binaries

The TAOS Project Stellar Variability II. Detection of 15 Variable Stars

The Taiwanese-American Occultation Survey (TAOS) project has collected more than a billion photometric measurements since 2005 January. These sky survey data-covering timescales from a fraction of a second to a few hundred days-are a useful source to study stellar variability. A total of 167 star fields, mostly along the ecliptic plane, have been selected for photometric monitoring with the TAOS telescopes. This paper presents our initial analysis of a search for periodic variable stars from the time-series TAOS data on one particular TAOS field, No. 151 (RA = 17^{\rm h}30^{\rm m}6\fs67, Dec = 27\degr17\arcmin 30\arcsec, J2000), which had been observed over 47 epochs in 2005. A total of 81 candidate variables are identified in the 3 square degree field, with magnitudes in the range 8 < R < 16. On the basis of the periodicity and shape of the lightcurves, 29 variables, 15 of which were previously unknown, are classified as RR Lyrae, Cepheid, delta Scuti, SX Phonencis, semi-regular and eclipsing binaries.Comment: 20 pages, 6 figures, accepted in The Astronomical Journa

Optical coupling to nanoscale optomechanical cavities for near quantum-limited motion transduction

A significant challenge in the development of chip-scale cavity-optomechanical devices as testbeds for quantum experiments and classical metrology lies in the coupling of light from nanoscale optical mode volumes to conventional optical components such as lenses and fibers. In this work we demonstrate a high-efficiency, single-sided fiber-optic coupling platform for optomechanical cavities. By utilizing an adiabatic waveguide taper to transform a single optical mode between a photonic crystal zipper cavity and a permanently mounted fiber, we achieve a collection efficiency for intracavity photons of 52% at the cavity resonance wavelength of λ ≈ 1538 nm. An optical balanced homodyne measurement of the displacement fluctuations of the fundamental in-plane mechanical resonance at 3.3 MHz reveals that the imprecision noise floor lies a factor of 2.8 above the standard quantum limit (SQL) for continuous position measurement, with a predicted total added noise of 1.4 phonons at the optimal probe power. The combination of extremely low measurement noise and robust fiber alignment presents significant progress towards single-phonon sensitivity for these sorts of integrated micro-optomechanical cavities