Cavity-Enhanced Ultrafast Transient Absorption Spectroscopy

We present a new technique using a frequency comb laser and optical cavities for performing ultrafast transient absorption spectroscopy with improved sensitivity. Resonantly enhancing the probe pulses, we demonstrate a sensitivity of $\Delta$OD = 1 \times 10^{-9}/\sqrt{\mbox{Hz}} for averaging times as long as 30 s per delay point ($\Delta$OD$_{min} = 2 \times 10^{-10}$). Resonantly enhancing the pump pulses allows us to produce a high excitation fraction at high repetition-rate, so that signals can be recorded from samples with optical densities as low as OD $\approx 10^{-8}$, or column densities $< 10^{10}$ molecules/cm$^2$. This high sensitivity enables new directions for ultrafast spectroscopy

Microbial revolt:Redefining biolab tools and practices for more-than-human care ecologies

Recent work in HCI has called for deeper ethical considerations when engaging with more-than-human organisms in design. In this paper, we introduce Microbial Revolt, a provocative method to support reflection on the perspectives of organisms involved in HCI and design practice. By asking participants to consider the reality of a chosen organism in feral and lab environments and to redesign lab tools in order to account for their “non-participation”, we identified the manifestation of key epistemic differences between approaches to care and ecologies in typical design and biology research - as well as the potential for design and HCI to creatively redefine power dynamics in the lab. Further interviews revealed specific challenges and opportunities that designers and HCI researchers face in adapting practices to lab standards, and lab equipment to their practices, calling for a redefinition of tools, spaces and guidance to accommodate phenomenological perspectives and multiple modes of interaction with living organisms

Microbial predictors of healing and short-term effect of debridement on the microbiome of chronic wounds.

Chronic wounds represent a large and growing disease burden. Infection and biofilm formation are two of the leading impediments of wound healing, suggesting an important role for the microbiome of these wounds. Debridement is a common and effective treatment for chronic wounds. We analyzed the bacterial content of the wound surface from 20 outpatients with chronic wounds before and immediately after debridement, as well as healthy skin. Given the large variation observed among different wounds, we introduce a Bayesian statistical method that models patient-to-patient variability and identify several genera that were significantly enriched in wounds vs. healthy skin. We found no difference between the microbiome of the original wound surface and that exposed by a single episode of sharp debridement, suggesting that this debridement did not directly alter the wound microbiome. However, we found that aerobes and especially facultative anaerobes were significantly associated with wounds that did not heal within 6 months. The facultative anaerobic genus Enterobacter was significantly associated with lack of healing. The results suggest that an abundance of facultative anaerobes is a negative prognostic factor in the chronic wound microbiome, possibly due to the increased robustness of such communities to different metabolic environments

Evaluation of marker density for population stratification adjustment and of a family-informed phenotype imputation method for single variant and variant-set tests of association

Whole exome sequencing (WES) data cover only 1% of the genome and is designed to capture variants in coding regions of genes. When associating genetic variations with an outcome, there are multiple issues that could affect the association test results. This dissertation will explore two of these issues: population stratification and missing data. Population stratification may cause spurious association in analysis using WES data, an issue also encountered in genome-wide association studies (GWAS) using genotyping array data. Population stratification adjustments have been well studied with array-based genotypes but need to be evaluated in the context of WES genotypes where a smaller portion of the genome is covered. Secondly, sample size is a major component of statistical power, which can be reduced by missingness in phenotypic data. While some phenotypes are hard to collect due to cost and loss to follow-up, correlated phenotypes that are easily collected and are complete can be leveraged in tests of association. First, we compare the performance of GWAS and WES markers for population stratification adjustments in tests of association. We evaluate two established approaches: principal components (PCs) and mixed effects models. Our results illustrate that WES markers are sufficient to correct for population stratification. Next, we develop a family-informed phenotype imputation method that incorporates information contained in family structure and correlated phenotypes. Our method has higher imputation accuracy than methods that do not use family members and can help improve power while achieving the correct type-I error rate. Finally, we extend the family-informed phenotype imputation method to variant-set tests. Single variant tests do not have enough power to identify rare variants with small effect sizes. Variant-set association tests have been proven to be a powerful alternative approach to detect associations with rare variants. We derive a theoretical statistical power approximation for both burden tests and Sequence Kernel Association Test (SKAT) and investigate situations where our imputation approach can improve power in association tests.2020-11-07T00:00:00

Cavity-enhanced Ultrafast Transient Absorption Spectroscopy

We introduce cavity enhanced ultrafast transient absorption spectroscopy, which employs frequency combs and high-finesse optical cavities. % The schematic of apparatus is shown in Figure 1. Sub-100 fs pulses with a repetition rate of 90 MHz are generated by a home-built Ytterbium fiber laser. The amplified light has a power up to 10 W, which is used to pump an optical parametric oscillator, followed by second-harmonic generation(SHG) that converts the wavelength from near-IR to visible. A pump comb at 530 nm is separately generated by SHG. Both pump and probe combs are coupled into high-finesse cavities. Compared to the conventional transient absorption spectroscopy method, the detection sensitivity can be improved by a factor of $\left(\frac{\mathcal{F}}{\pi} \right)^2 \sim 10^5$, where $\mathcal{F}$ is the finesse of cavity. This ultrasensitive technology enables the direct all-optical dynamics study in molecular beams. We will apply the cavity enhanced ultrafast transient absorption spectroscopy to investigate the dynamics of visible chromophores and then extend the wavelength to mid-IR to study vibrational dynamics of small hydrogen-bonded clusters. %\begin{wrapfigure}{I}{1\textwidth} % \centering % \includegraphics[width = 0.7\textwidth]{CETAS_details.eps} %\caption{Schematic of cavity enhanced ultrafast transient absorption spectroscopy apparatus. An amplified fiber laser frequency comb is converted to visible light and pump and probe combs are coupled to high-finesse optical resonators. Transmission of the probe light is measured.} %\end{wrapfigure