The impact of long-term botulinum toxin injections on symptom severity in patients with spasmodic dysphonia

Injection of botulinum toxin (BT) into the muscles of the larynx is an effective treatment for the symptoms of spasmodic dysphonia (SD). To date, however, there have been no studies that have used blinded raters to assess the efficacy of BT injections on overall symptom severity in a cohort of SD patients followed over a prolonged period. In this study, 102 subjects with SD were treated with serial BT injections for up to 2 years. Voice recordings were obtained at several time points during treatment and were played to a panel of expert and novice listeners who rated them based on overall symptom severity in a single-blind fashion. Subjects demonstrated significant improvement over baseline at all time points. In addition, patients showed a sustained responsiveness to therapy over time. These results provide support for the efficacy of serial BT injections for SD and suggest that successful treatment may depend, in part, on patients' early recognition of returning symptoms.     

Review of fluorescence anisotropy decay analysis by frequency-domain fluorescence spectroscopy

This didactic paper summarizes the mathematical expressions needed for analysis of fluorescence anisotropy decays from polarized frequency-domain fluorescence data. The observed values are the phase angle difference between the polarized components of the emission and the modulated anisotropy, which is the ratio of the polarized and amplitude-modulated components of the emission. This procedure requires a separate measurement of the intensity decay of the total emission. The expressions are suitable for any number of exponential components in both the intensity decay and the anisotropy decay. The formalism is generalized for global analysis of anisotropy decays measured at different excitation wavelengths and for different intensity decay times as the result of quenching. Additionally, we describe the expressions required for associated anisotropy decays, that is, anisotropy decays where each correlation time is associated with a decay time present in the anisotropy decay. And finally, we present expressions appropriate for distributions of correlation times. This article should serve as a reference for researchers using frequency-domain fluorometry.     

Distance distributions and dynamics of a zinc finger peptide from fluorescence resonance energy transfer measurements

Time-resolved fluorescence resonance energy transfer (FRET) measurements were used to measure distance distributions and intramolecular dynamics (site-to-site diffusion) of a 28-residue single-domain zinc finger peptide in the absence and presence of zinc ion. Energy transfer was measured between TRP₁₄ and a N-terminal DNS group. As expected, the TRP-to-DNS distance distribution for zinc-bound peptide is shorter and narrower (R _av=11.2 Å,hw=2.8 Å) than the metal-free peptide (R _av=20.1 Å,hw=14.5 Å). The degree of mutual donor-to-acceptor diffusion (D) was also determined for these distributions. For zinc-bound peptide there is no detectible diffusion (D0.2 Ų/ns), whereas for metal-free peptide a considerable amount of motion is occurring between the donor and the acceptor (D=12 Ų/ns). These results indicate that the zinc-bound peptide folds into a unique, well-defined conformation, whereas the metal-free conformation is flexible and rapidly changing. The absence of detectible mutual site-to-site diffusion between the donor and the acceptor in the metal-bound zinc finger peptide indicates that intramolecular motion is essentially frozen out, on the FRET time scale, as a consequence of zinc coordination.Dedicated to the memory of Barbara D. Wells.     

Solving the Kadanoff-Baym equations for inhomogeneous systems: application to atoms and molecules

We implement time propagation of the nonequilibrium Green function for atoms and molecules by solving the Kadanoff-Baym equations within a conserving self-energy approximation. We here demonstrate the usefulness of time propagation for calculating spectral functions and for describing the correlated electron dynamics in a nonperturbative electric field. We also demonstrate the use of time propagation as a method for calculating charge-neutral excitation energies, equivalent to highly advanced solutions of the Bethe-Salpeter equation.     

On the Positivity of the Coefficients of a Certain Polynomial Defined by Two Positive Definite Matrices

It is shown that the polynomialp(t) = Tr[(A+tB)^m]has positive coefficients when m = 6 and A and B are any two 3-by-3 complex Hermitian positive definite matrices. This case is the first that is not covered by prior, general results. This problem arises from a conjecture raised by Bessis, Moussa, and Villani in connection with a long-standing problem in theoretical physics. The full conjecture, as shown recently by Lieb and Seiringer, is equivalent to p(t) having positive coefficients for any m and any two n-by-n positive definite matrices. We show that, generally, the question in the real case reduces to that of singular A and B, and this is a key part of our proof.     

Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells

Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive.     

Successive coordination of palladium(II)-ions and terpyridine-ligands to a pyridyl-terminated self-assembled monolayer on gold

The deposition of palladium on a novel, reversibly protonatable, pyridyl-terminated self-assembled monolayer on gold substrates has been studied by X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS spectroscopy) and time of flight-secondary ion mass spectrometry (ToF-SIMS). For this purpose, 12-(pyridin-4-yl)dodecane-1-thiol, consisting of a surface-active head group, an unfunctionalized hydrocarbon backbone and a terminal pyridyl group, has been synthesized and deposited on gold surfaces. Coordination of Pd(II) ions to the pyridyl group was examined. Furthermore, a reversible protonation/deprotonation cycle has been applied, and the relation between protonation and the amount of complexed palladium was studied. Investigation of the SAM by angle-resolved NEXAFS spectroscopy revealed the aliphatic backbone to be preferentially upright oriented with the aromatic head group being not preferentially oriented. The palladium layer was further coordinated with a CF₃-labeled terpyridine ligand in order to prove the accessibility of the Pd(II) ions to further complexation and the platform useful for deposition of further layers toward a multi-layered system.     

Detection of laser induced dielectric breakdown in water using a laser doppler vibrometer

This study is focused on exploring the feasibility of an all-optic surface scanning method in determining the size and position of a submerged, laser generated, optoacoustic (OA) source. The optoacoustic effect in this case was generated when the absorption of a short electromagnetic pulse in matter caused a dielectric breakdown, a plasma emission flash and a subsequent acoustic wave. In the experiment, a laser pulse with λ = 1064 nm and 12 ns pulse length was aimed at a volume of deionized water. When the laser beam was focused by a f = 16 mm lens, a single dielectric breakdown spot occurred. When a f = 40 mm was used several breakdowns in a row were induced. The breakdowns were photographed using a double shutter camera. The acoustic wave generated by the dielectric breakdowns were detected at a point on the water surface using a laser Doppler vibrometer (LDV). First, the LDV signal was used to calculate the speed of sound with an accuracy of 10 m/s. Secondly, the location and length of the dielectric breakdown was calculated with an accuracy of 1 mm. The calculated position matched the breakdown location recorded by a camera. The results show that it is possible to use LDV surface measurements from a single spot to determine both the position and length of the OA source as well as the speed of sound in the medium. Furthermore, the LDV measurements also show a secondary peak that originates from the OA source. To unravel the origin and properties of this interesting feature, further investigations are necessary