T-Cell Receptor Repertoire Analysis with Computational Tools—An Immunologist’s Perspective

Over the last few years, there has been a rapid expansion in the application of information technology to biological data. Particularly the field of immunology has seen great strides in recent years. The development of next-generation sequencing (NGS) and single-cell technologies also brought forth a revolution in the characterization of immune repertoires. T-cell receptor (TCR) repertoires carry comprehensive information on the history of an individual’s antigen exposure. They serve as correlates of host protection and tolerance, as well as biomarkers of immunological perturbation by natural infections, vaccines or immunotherapies. Their interrogation yields large amounts of data. This requires a suite of highly sophisticated bioinformatics tools to leverage the meaning and complexity of the large datasets. Many different tools and methods, specifically designed for various aspects of immunological research, have recently emerged. Thus, researchers are now confronted with the issue of having to choose the right kind of approach to analyze, visualize and ultimately solve their task at hand. In order to help immunologists to choose from the vastness of available tools for their data analysis, this review addresses and compares commonly used bioinformatics tools for TCR repertoire analysis and illustrates the advantages and limitations of these tools from an immunologist’s perspective

Determinisitic Writing and Control of the Dark Exciton Spin using Short Single Optical Pulses

We demonstrate that the quantum dot-confined dark exciton forms a long-lived integer spin solid state qubit which can be deterministically on-demand initiated in a pure state by one optical pulse. Moreover, we show that this qubit can be fully controlled using short optical pulses, which are several orders of magnitude shorter than the life and coherence times of the qubit. Our demonstrations do not require an externally applied magnetic field and they establish that the quantum dot-confined dark exciton forms an excellent solid state matter qubit with some advantages over the half-integer spin qubits such as the confined electron and hole, separately. Since quantum dots are semiconductor nanostructures that allow integration of electronic and photonic components, the dark exciton may have important implications on implementations of quantum technologies consisting of semiconductor qubits.Comment: Added two authors, minor edits to figure captions, expanded discussion of dark exciton eigenstate

Calculation of Raman optical activity spectra for vibrational analysis

By looking back on the history of Raman Optical Activity (ROA), the present article shows that the success of this analytical technique was for a long time hindered, paradoxically, by the deep level of detail and wealth of structural information it can provide. Basic principles of the underlying theory are discussed, to illustrate the technique's sensitivity due to its physical origins in the delicate response of molecular vibrations to electromagnetic properties. Following a short review of significant advances in the application of ROA by UK researchers, we dedicate two extensive sections to the technical and theoretical difficulties that were overcome to eventually provide predictive power to computational simulations in terms of ROA spectral calculation. In the last sections, we focus on a new modelling strategy that has been successful in coping with the dramatic impact of solvent effects on ROA analyses. This work emphasises the role of complementarity between experiment and theory for analysing the conformations and dynamics of biomolecules, so providing new perspectives for methodological improvements and molecular modelling development. For the latter, an example of a next-generation force-field for more accurate simulations and analysis of molecular behaviour is presented. By improving the accuracy of computational modelling, the analytical capabilities of ROA spectroscopy will be further developed so generating new insights into the complex behaviour of molecules

The Raman optical activity of β-D-xylose: where experiment and theory meet

Besides its applications in bioenergy and biosynthesis, β-D-xylose is a very simple monosaccharide that exhibits relatively high rigidity. As such, it provides the best basis to study the impact of different solvation shell radii on the computation of its Raman optical activity (ROA) spectrum. Indeed, this chiroptical spectroscopic technique provides exquisite sensitivity to stereochemistry, and benefits much from theoretical support for interpretation. Our simulation approach combines density functional theory (DFT) and molecular dynamics (MD) in order to efficiently account for the crucial hydration effects in the simulation of carbohydrates and their spectroscopic response predictions. Excellent agreement between the simulated spectrum and the experiment was obtained with a solvation radius of 10 Å. Vibrational bands have been resolved from the computed ROA data, and compared with previous results on different monosaccharides in order to identify specific structure–spectrum relationships and to investigate the effect of the solvation environment on the conformational dynamics of small sugars. From the comparison with ROA analytical results, a shortcoming of the classical force field used for the MD simulations has been identified and overcome, again highlighting the complementary role of experiment and theory in the structural characterisation of complex biomolecules. Indeed, due to unphysical puckering, a spurious ring conformation initially led to erroneous conformer ratios, which are used as weights for the averaging of the spectral average, and only by removing this contribution was near perfect comparison between theory and experiment achieved

Distinguishing epimers through raman optical activity

The Raman optical activity spectra of the epimers β-d-glucose and β-d-galactose, two monosaccharides of biological importance, have been calculated using molecular dynamics combined with a quantum mechanics/molecular mechanics approach. Good agreement between theoretical and experimental spectra is observed for both monosaccharides. Full band assignments have been carried out, which has not previously been possible for carbohydrate epimers. For the regions where the spectral features are opposite in sign, the differences in the vibrational modes have been noted and ascribed to the band sign changes

Classical and Quantum Dynamics in a Random Magnetic Field

Using the supersymmetry approach, we study spectral statistical properties of a two-dimensional quantum particle subject to a non-uniform magnetic field. We focus mainly on the problem of regularisation of the field theory. Our analysis begins with an investigation of the spectral properties of the purely classical evolution operator. We show that, although the kinetic equation is formally time-reversible, density relaxation is controlled by {\em irreversible} classical dynamics. In the case of a weak magnetic field, the effective kinetic operator corresponds to diffusion in the angle space, the diffusion constant being determined by the spectral resolution of the inhomogeneous magnetic field. Applying these results to the quantum problem, we demonstrate that the low-lying modes of the field theory are related to the eigenmodes of the irreversible classical dynamics, and the higher modes are separated from the zero mode by a gap associated with the lowest density relaxation rate. As a consequence, we find that the long-time properties of the system are characterised by universal Wigner-Dyson statistics. For a weak magnetic field, we obtain a description in terms of the quasi one-dimensional non-linear $\sigma$-model.Comment: 16 pages, RevTe

Isopycnic Phases and Structures in H2O/CO2/Ethoxylated Alcohol Surfactant Mixtures

Ternary mixtures of H2O and CO2 with ethoxylated alcohol (C(i)E(j)) surfactants can form three coexisting liquid phases at conditions where two of the phases have the same density (isopycnic phases). Isopycnic phase behavior has been observed for mixtures containing the surfactants C8E5, C10E6, and C12E6, but not for those mixtures containing either C4E1 or CgE3. Pressure-temperature (PT) projections for this isopycnic three-phase equilibrium were determined for H2O/CO2/C8E5 and H2O/CO2/C10E6 mixtures at temperatures from approximately 25 to 33 C and pressures between 90 and 350 bar. As a preliminary to measuring the microstructure in isopycnic three component mixtures, phase behavior and small angle neutron scattering (SANS) experiments were performed on mixtures of D2O/CO2/ n-hexaethyleneglycol monododecyl ether (C12E6) as a function of temperature (25-31 C), pressure (63.1-90.7 bar), and CO2 composition (0-3.9 wt%). Parameters extracted from model fits of the SANS spectra indicate that, while micellar structure remains essentially unchanged, critical concentration fluctuations increase as the phase boundary and plait point are approached

A retrospective comparison of waterbirth outcomes in two United States hospital settings

BackgroundWater immersion during labor is an effective comfort measure; however, outcomes for waterbirth in the hospital setting have not been well documented. Our objective was to report the outcomes from two nurse‐midwifery services that provide waterbirth within a tertiary care hospital setting in the United States.MethodsThis study is a retrospective, observational, matched comparison design. Data were collected from two large midwifery practices in tertiary care centers using information recorded at the time of birth for quality assurance purposes. Land birth cases were excluded if events would have precluded them from waterbirth (epidural, meconium stained fluid, chorioamnionitis, estimated gestational age  40). Neonatal outcomes included Apgar score and admission to the neonatal intensive care unit. Maternal outcomes included perineal lacerations and postpartum hemorrhage.ResultsA total of 397 waterbirths and 2025 land births were included in the analysis. There were no differences in outcomes between waterbirth and land birth for Apgar scores or neonatal intensive care admissions (1.8% vs 2.5%). Women in the waterbirth group were less likely to sustain a first‐ or second‐degree laceration. Postpartum hemorrhage rates were similar for both groups. Similar results were obtained using a land birth subset matched on insurance, hospital location, and parity using propensity scores.DiscussionIn this study, waterbirth was not associated with increased risk to neonates, extensive perineal lacerations, or postpartum hemorrhage. Fewer women in the waterbirth group sustained first‐ or second‐degree lacerations requiring sutures.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154290/1/birt12473.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154290/2/birt12473_am.pd