Interference-free coherence dynamics of gas-phase molecules using spectral focusing

Spectral focusing using broadband femtosecond pulses to achieve highly selective measurements has been employed for numerous applications in spectroscopy and microspectroscopy. In this work we highlight the use of spectral focusing for selective excitation and detection of gas-phase species. Furthermore, we demonstrate that spectral focusing, coupled with time-resolved measurements based upon probe delay, allows the observation of interference-free coherence dynamics of multiple molecules and gas-phase temperature making this technique ideal for gas-phase measurements of reacting flows and combustion processes

Comparison of line-peak and line-scanning excitation in two-color laser-induced-fluorescence thermometry of OH

Two-line laser-induced-fluorescence (LIF) thermometry is commonly employed to generate instantaneous planar maps of temperature in unsteady flames. The use of line scanning to extract the ratio of integrated intensities is less common because it precludes instantaneous measurements. Recent advances in the energy output of high-speed, ultraviolet, optical parameter oscillators have made possible the rapid scanning of molecular rovibrational transitions and, hence, the potential to extract information on gas-phase temperatures. In the current study, two-line OH LIF thermometry is performed in a wellcalibrated reacting flow for the purpose of comparing the relative accuracy of various line-pair selections from the literature and quantifying the differences between peak-intensity and spectrally integrated line ratios. Investigated are the effects of collisional quenching, laser absorption, and the integration width for partial scanning of closely spaced lines on the measured temperatures. Data from excitation scans are compared with theoretical line shapes, and experimentally derived temperatures are compared with numerical predictions that were previously validated using coherent anti-Stokes–Raman scattering. Ratios of four pairs of transitions in the A2Σ+←X2Π (1,0) band of OH are collected in an atmospheric-pressure, near-adiabatic hydrogen-air flame over a wide range of equivalence ratios—from 0.4 to 1.4. It is observed that measured temperatures based on the ratio of Q1(14)/Q1(5) transition lines result in the best accuracy and that line scanning improves the measurement accuracy by as much as threefold at lowequivalence- ratio, low-temperature conditions. These results provide a comprehensive analysis of the procedures required to ensure accurate two-line LIF measurements in reacting flows over a wide range of conditions

High-Repetition-Rate Interferometric Rayleigh Scattering for Flow-Velocity Measurements

High-repetition-rate interferometric-Rayleigh-scattering (IRS) velocimetry is demonstrated for non-intrusive, high-speed flow-velocity measurements. High temporal resolution is obtained with a quasi-continuous burst-mode laser that is capable of operating at 10100 kHz, providing 10-ms bursts with pulse widths of 51000 ns and pulse energy >100 mJ at 532 nm. Coupled with a high-speed camera system, the IRS method is based on imaging the flow field through an etalon with 8-GHz free spectral range and capturing the Doppler shift of the Rayleigh-scattered light from the flow at multiple points having constructive interference. The seed-laser linewidth permits a laser linewidth of <150 MHz at 532 nm. The technique is demonstrated in a high-speed jet, and high-repetition-rate image sequences are shown

Dual-Pump Coherent Anti-Stokes Raman Scattering Temperature and CO2 Concentration Measurements

Measurements of temperature and CO2 concentration using dual-pump coherent anti-Stokes Raman scattering, (CARS) are described. The measurements were performed in laboratory flames,in a room-temperature gas cell, and on an engine test stand at the U.S. Air Force Research Laboratory, Wright-Patterson Air Force Base. A modeless dye laser, a single-mode Nd:YAG laser, and an unintensified back-illuminated charge-coupled device digital camera were used for these measurements. The CARS measurements were performed on a single-laser-shot basis. The standard deviations of the temperatures and CO2 mole fractions determined from single-shot dual-pump CARS spectra in steady laminar propane/air flames were approximately 2 and 10% of the mean values of approximately 2000 K and 0.10, respectively. The precision and accuracy of single-shot temperature measurements obtained from the nitrogen part of the dual-pump CARS system were investigated in detail in near-adiabatic hydrogen/air/CO2 flames. The precision of the CARS temperature measurements was found to be comparable to the best results reported in the literature for conventional two-laser, single-pump CARS. The application of dual-pump CARS for single-shot measurements in a swirl-stabilized combustor fueled with JP-8 was also demonstrated

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

Background: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for >= 20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms

Models, measurement and inference in epithelial tissue dynamics

The majority of solid tumours arise in epithelia and therefore much research effort has gone into investigating the growth, renewal and regulation of these tissues. Here we review different mathematical and computational approaches that have been used to model epithelia. We compare different models and describe future challenges that need to be overcome in order to fully exploit new data which present, for the first time, the real possibility for detailed model validation and comparison

Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(–9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(–6)), rs112290073 (OR = 1.85, P = 1.27×10(–5)), rs138895564 (OR = 2.16, P = 2.06×10(–5); among young cases, OR = 3.77, P = 8.41×10(–4)). In addition, we found that rs139852726 (P = 1.44×10(–3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(–7)) and lung cancer (P = 2.37×10(–5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism

BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry.

BRCA1 and BRCA2 (BRCA1/2) pathogenic sequence variants (PSVs) confer elevated risks of multiple cancers. However, most BRCA1/2 PSVs reports focus on European ancestry individuals. Knowledge of the PSV distribution in African descent individuals is poorly understood. We undertook a systematic review of the published literature and publicly available databases reporting BRCA1/2 PSVs also accessed the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) database to identify African or African descent individuals. Using these data, we inferred which of the BRCA PSVs were likely to be of African continental origin. Of the 43,817 BRCA1/2 PSV carriers in the CIMBA database, 469 (1%) were of African descent. Additional African descent individuals were identified in public databases (n = 291) and the literature (n = 601). We identified 164 unique BRCA1 and 173 unique BRCA2 PSVs in individuals of African ancestry. Of these, 83 BRCA1 and 91 BRCA2 PSVs are of likely or possible African origin. We observed numerous differences in the distribution of PSV type and function in African origin versus non-African origin PSVs. Research in populations of African ancestry with BRCA1/2 PSVs is needed to provide the information needed for clinical management and decision-making in African descent individuals worldwide