Machine learning-guided directed evolution for protein engineering

Machine learning (ML)-guided directed evolution is a new paradigm for biological design that enables optimization of complex functions. ML methods use data to predict how sequence maps to function without requiring a detailed model of the underlying physics or biological pathways. To demonstrate ML-guided directed evolution, we introduce the steps required to build ML sequence-function models and use them to guide engineering, making recommendations at each stage. This review covers basic concepts relevant to using ML for protein engineering as well as the current literature and applications of this new engineering paradigm. ML methods accelerate directed evolution by learning from information contained in all measured variants and using that information to select sequences that are likely to be improved. We then provide two case studies that demonstrate the ML-guided directed evolution process. We also look to future opportunities where ML will enable discovery of new protein functions and uncover the relationship between protein sequence and function.Comment: Made significant revisions to focus on aspects most relevant to applying machine learning to speed up directed evolutio

Spectroscopic studies on the liquid phase dynamics and interactions of acetonitrile

Spectroscopic studies on the liquid phase dynamics and Interactions of acetonitrile. Microwave and far-infrared spectra were used to study the angular motion of CH(_3)CN molecules in the pure liquid and in the non-polar solvents carbon tetrachloride, benzene and n-heptane. The spectral data were analysed to give information on the static angular structure of the liquid and the rates of reorlentational motion of the CH(_3)CN molecules. The use of these two experimental techniques enabled the short and long time parts of the angular motion to be studied together using Fourier transform analysis of the combined microwave/far-Infrared spectrum. Band moment analysis was performed on the microwave/far-infrared band In order to obtain Information on Intermolecular torques. Gordon's sum rule was applied to the spectra In an attempt to estimate what proportion of the band is due to the presence of collision Induced dipoles In the CH(_3)CN molecules. The reorientational relaxation rates and static angular correlation factors obtained from the microwave/far-infrared spectra were compared with literature data on similar solutions obtained by depolarised light scattering experiments. The model for reorientational motion developed by Evans on the Mori formalism was fitted to the experimental spectrum of the pure liquid and the results discussed in terms of the parameters of the model. The V(_1) vibrational band of CH(_3)CN was analysed when the molecule was subject to hydrogen bonding' Interactions with methanol. An attempt was made to elucidate the processes which cause the vibrational band to be broadened in these solutions. The vibrational line shapes were analysed using the Kubo line shape theory for the rapid modulation limit

Visiting Nurse Services of Newport and Bristol County: Increasing Program Awareness for the Help at Home Program

We came up with the idea of using a cost analysis to clearly demonstrate the advantage of home care vs. hospitalization. John Hopkins Bay view Medical Center conducted a study within their geriatrics unit to test their Hospital At Home program against typical on-site care at the hospital. The study was held over the course of 30 days involving hundreds of patients across three cities and the results were staggering. Not only was at home care 32% cheaper ($5,081 versus$7,480) but also overall customer satisfaction was significantly higher

Discriminating single-photon states unambiguously in high dimensions

The ability to uniquely identify a quantum state is integral to quantum science, but for non-orthogonal states, quantum mechanics precludes deterministic, error-free discrimination. However, using the non-deterministic protocol of unambiguous state discrimination (USD) enables error-free differentiation of states, at the cost of a lower frequency of success. We discriminate experimentally between non-orthogonal, high-dimensional states encoded in single photons; our results range from dimension $d=2$ to $d=14$. We quantify the performance of our method by comparing the total measured error rate to the theoretical rate predicted by minimum-error state discrimination. For the chosen states, we find a lower error rate by more than one standard deviation for dimensions up to $d=12$. This method will find immediate application in high-dimensional implementations of quantum information protocols, such as quantum cryptography.Comment: 4 pages + 3 pages supplementary, 4 figure

Polarisation structuring of broadband light

Spatial structuring of the intensity, phase and polarisation of light is useful in a wide variety of modern applications, from microscopy to optical communications. This shaping is most commonly achieved using liquid crystal spatial light modulators (LC-SLMs). However, the inherent chromatic dispersion of LC-SLMs when used as diffractive elements presents a challenge to the extension of such techniques from monochromatic to broadband light. In this work we demonstrate a method of generating broadband vector beams with dynamically tunable intensity, phase and polarisation over a bandwidth of 100 nm. We use our system to generate radially and azimuthally polarised vector vortex beams carrying orbital angular momentum, and beams whose polarisation states span the majority of the Poincaré sphere. We characterise these broadband vector beams using spatially and spectrally resolved Stokes measurements, and detail the technical and fundamental limitations of our technique, including beam generation fidelity and efficiency. The broadband vector beam shaper that we demonstrate here may find use in applications such as ultrafast beam shaping and white light microscopy

Polarisation structuring of broadband light

Spatial structuring of the intensity, phase and polarisation of light is useful in a wide variety of modern applications, from microscopy to optical communications. This shaping is most commonly achieved using liquid crystal spatial light modulators (LC-SLMs). However, the inherent chromatic dispersion of LC-SLMs when used as diffractive elements presents a challenge to the extension of such techniques from monochromatic to broadband light. In this work we demonstrate a method of generating broadband vector beams with dynamically tunable intensity, phase and polarisation over a bandwidth of 100 nm. We use our system to generate radially and azimuthally polarised vector vortex beams carrying orbital angular momentum, and beams whose polarisation states span the majority of the Poincaré sphere. We characterise these broadband vector beams using spatially and spectrally resolved Stokes measurements, and detail the technical and fundamental limitations of our technique, including beam generation fidelity and efficiency. The broadband vector beam shaper that we demonstrate here may find use in applications such as ultrafast beam shaping and white light microscopy