The current state of biomarker research for Friedreich's ataxia: a report from the 2018 FARA biomarker meeting

The 2018 FARA Biomarker Meeting highlighted the current state of development of biomarkers for Friedreich's ataxia. A mass spectroscopy assay to sensitively measure mature frataxin (reduction of which is the root cause of disease) is being developed. Biomarkers to monitor neurological disease progression include imaging, electrophysiological measures and measures of nerve function, which may be measured either in serum and/or through imaging-based technologies. Potential pharmacodynamic biomarkers include metabolic and protein biomarkers and markers of nerve damage. Cardiac imaging and serum biomarkers may reflect cardiac disease progression. Considerable progress has been made in the development of biomarkers for various contexts of use, but further work is needed in terms of larger longitudinal multisite studies, and identification of novel biomarkers for additional use cases

Maximizing Neumann fundamental tones of triangles

We prove sharp isoperimetric inequalities for Neumann eigenvalues of the Laplacian on triangular domains. The first nonzero Neumann eigenvalue is shown to be maximal for the equilateral triangle among all triangles of given perimeter, and hence among all triangles of given area. Similar results are proved for the harmonic and arithmetic means of the first two nonzero eigenvalues

Observation of diffractive orbits in the spectrum of excited NO in a magnetic field

We investigate the experimental spectra of excited NO molecules in the diamagnetic regime and develop a quantitative semiclassical framework to account for the results. We show the dynamics can be interpreted in terms of classical orbits provided that in addition to the geometric orbits, diffractive effects are appropriately taken into account. We also show how individual orbits can be extracted from the experimental signal and use this procedure to reveal the first experimental manifestation of inelastic diffractive orbits.Comment: 4 fig

Influence of diffraction on the spectrum and wavefunctions of an open system

In this paper, we demonstrate the existence and significance of diffractive orbits in an open microwave billiard, both experimentally and theoretically. Orbits that diffract off of a sharp edge of the system are found to have a strong influence on the transmission spectrum of the system, especially in the regime where there are no stable classical orbits. On resonance, the wavefunctions are influenced by both classical and diffractive orbits. Off resonance, the wavefunctions are determined by the constructive interference of multiple transient, nonperiodic orbits. Experimental, numerical, and semiclassical results are presented.Comment: 27 pages, 29 figures, and 3 tables. Submitted to Physical Review E. A copy with higher resolution figures is available at http://monsoon.harvard.edu/~hersch/papers.htm

Psychological Benefits 2 and 4 weeks After a Single Treatment with Near Infrared Light to the Forehead: A Pilot Study of 10 Patients with Major Depression and Anxiety

Background: Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects. Methods: We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. Results: At 2-weeks post treatment 6 of 10 patients had a remission (a score ≤ 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR "on" relative to NIR "off" when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects. Conclusion: This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated. Trial registration: ClinicalTrials.gov Identifier: NCT0096145

Scattering Theory of Kondo Mirages and Observation of Single Kondo Atom Phase Shift

We explain the origin of the Kondo mirage seen in recent quantum corral Scanning Tunneling Microscope (STM) experiments with a scattering theory of electrons on the surfaces of metals. Our theory combined with experimental data provides the first direct observation of a single Kondo atom phase shift. The Kondo mirage at the empty focus of an elliptical quantum corral is shown to arise from multiple electron bounces off the walls of the corral in a manner analagous to the formation of a real image in optics. We demonstrate our theory with direct quantitive comparision to experimental data.Comment: 13 pages; significant clarifications of metho

On the lowest eigenvalue of Laplace operators with mixed boundary conditions

In this paper we consider a Robin-type Laplace operator on bounded domains. We study the dependence of its lowest eigenvalue on the boundary conditions and its asymptotic behavior in shrinking and expanding domains. For convex domains we establish two-sided estimates on the lowest eigenvalues in terms of the inradius and of the boundary conditions

Mesoscopic scattering in the half-plane: squeezing conductance through a small hole

We model the 2-probe conductance of a quantum point contact (QPC), in linear response. If the QPC is highly non-adiabatic or near to scatterers in the open reservoir regions, then the usual distinction between leads and reservoirs breaks down and a technique based on scattering theory in the full two-dimensional half-plane is more appropriate. Therefore we relate conductance to the transmission cross section for incident plane waves. This is equivalent to the usual Landauer formula using a radial partial-wave basis. We derive the result that an arbitrarily small (tunneling) QPC can reach a p-wave channel conductance of 2e^2/h when coupled to a suitable reflector. If two or more resonances coincide the total conductance can even exceed this. This relates to recent mesoscopic experiments in open geometries. We also discuss reciprocity of conductance, and the possibility of its breakdown in a proposed QPC for atom waves.Comment: 8 pages, 3 figures, REVTeX. Revised version (shortened), accepted for publication in PR

Diffraction and boundary conditions in semi-classical open billiards

The conductance through open quantum dots or quantum billiards shows fluctuations, that can be explained as interference between waves following different paths between the leads of the billiard. We examine such systems by the use of a semi-classical Green's functions. In this paper we examine how the choice of boundary conditions at the lead mouths affect the diffraction. We derive a new formula for the S-matrix element. Finally we compare semi-classical simulations to quantum mechanical ones, and show that this new formula yield superior results.Comment: 7 pages, 4 figure

Application of a 3-CCD color camera for colorimetric and densitometric measurements

Video cameras have been used in the graphic arts industry primarily for quality inspection applications where one is interested only in the macro or large scale appearance defects of the print i.e. acceptable/not acceptable. CCD video cameras also have the potential for use in on-press color-type measurements. The advantages of such measurements are numerous, most notably the ability to accurately determine what has been measured. However, despite the advantages current CCD cameras are not designed to measure colors directly. One of the major drawbacks to the use of standard 3-CCD cameras for such measurements is that the spectral response of the cameras differ from standard densitometric or colorimetric responses. Additionally, the dynamic range of the CCD camera is not suitable to accurately measure the densities attainable in high quality sheet-fed printing. This paper discusses techniques which have been used, and results obtained, in an attempt to acquire both densitometric and colorimetric measurements from a standard 8-bit 3-CCD camera for use in newspaper printin