Accurate phase detection in time-domain heterodyne SFG spectroscopy.

Heterodyne detection is a ubiquitous tool in spectroscopy for the simultaneous detection of intensity and phase of light. However, the need for phase stability hinders the application of heterodyne detection to electronic spectroscopy. We present an interferometric design for a phase-sensitive electronic sum frequency generation (e-SFG) spectrometer in the time domain with lock-in detection. Our method of continuous phase modulation of one arm of the interferometer affords direct measurement of the phase between SFG and local oscillator fields. Errors in the path length difference caused by drifts in the optics are corrected, offering unprecedented stability. This spectrometer has the added advantage of collinear fundamental beams. The capabilities of the spectrometer are demonstrated with proof-of-principle experiments with GaAs e-SFG spectra, where we see significantly improved signal to noise ratio, spectral accuracy, and lineshapes.

Probing the predissociated levels of the S1 state of acetylene via H-atom fluorescence and photofragment fluorescence action spectroscopy.

We report two new experimental schemes to obtain rotationally resolved high-resolution spectra of predissociated S1 acetylene levels in the 47 000-47 300 cm-1 energy region (∼1200 cm-1 above the predissociation threshold). The two new detection schemes are compared to several other detection schemes (employed at similar laser power, molecular beam temperature, and number of signal averages) that have been used in our laboratory to study predissociated S1 acetylene levels, both in terms of the signal-to-noise ratio (S/N) of the resultant spectra and experimental simplicity. In the first method, H-atoms from the predissociated S1 acetylene levels are probed by two-photon laser-induced fluorescence (LIF). The H-atoms are pumped to the 3d level by the two-photon resonance transition at 205.14 nm. The resulting 3d-2p fluorescence (654.5 nm) is collected by a photomultiplier. The S/N of the H-atom fluorescence action spectrum is consistently better by ∼3× than that of the more widely used H-atom resonance-enhanced multiphoton ionization (REMPI) detection. Laser alignment is also considerably easier in H-atom fluorescence detection than H-atom REMPI detection due to the larger number-density of molecules that can be used in fluorescence vs. REMPI detection schemes. In the second method, fluorescence from electronically excited C2 and C2H photofragments of S1 acetylene is detected. In contrast to the H-atom detection schemes, the detected C2 and C2H photofragments are produced by the same UV laser as is used for the à - X ̃ acetylene excitation. As a result, laser alignment is greatly simplified for the photofragment fluorescence detection scheme, compared to both H-atom detection schemes. Using the photofragment fluorescence detection method, we are able to obtain action spectra of predissociated S1 acetylene levels with S/N ∼2× better than the HCCH REMPI detection and ∼10× better than H-atom and HCCH LIF detection schemes.

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.