Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease.

The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells. Dominant T cell receptor clonotypes overlap between organs and across recipients and their relative abundance correlates with protection efficacy. Thus, this study reveals donor regulatory T cell selection and adaptation mechanisms in target organs and highlights protective features of Treg to guide the development of improved graft-versus-host disease prevention strategies.

Time Dependence of Gel Formation in Lyotropic Nematic Liquid Crystals: From Hours to Weeks.

The combination of lyotropic liquid crystals (LLCs) and low-molecular-weight gelators (LMWGs) for the formation of lyotropic liquid crystal gels (LLC gels) leads to a versatile and complex material combining properties of both parent systems. We gelled the calamitic nematic NC phases of a binary and ternary system using the LMWG 3,5-bis-(5-hexylcarbamoyl-pentoxy)-benzoic acid hexyl ester (BHPB-6). This binary system consists of the surfactant N,N-dimethyl-N-ethyl-1-hexadecylammonium bromide (CDEAB) and water, whereas the ternary system consists of the surfactant N,N,N-trimethyl-N-tetradecylammonium bromide (C14TAB), the cosurfactant n-decanol, and water. Though containing similar surfactants, the gelled NC phases of the binary and ternary systems show differences in their visual and gel properties. The gelled NC phase of the binary system remains clear for several days after preparation, whereas the gelled NC phase of the ternary system turns turbid within 24 h. We investigated the time evolution of the gel strength with oscillation rheology measurements (a) within the first 24 h and (b) up to two weeks after gel formation. The shape of the fibers was investigated over different time scales with freeze fracture electron microscopy (FFEM). We demonstrate that despite their similarities, the two LLC gels also have distinct differences.

Reduced basis surrogates for quantum spin systems based on tensor networks.

Within the reduced basis methods approach, an effective low-dimensional subspace of a quantum many-body Hilbert space is constructed in order to investigate, e.g., the ground-state phase diagram. The basis of this subspace is built from solutions of snapshots, i.e., ground states corresponding to particular and well-chosen parameter values. Here, we show how a greedy strategy to assemble the reduced basis and thus to select the parameter points can be implemented based on matrix-product-state calculations. Once the reduced basis has been obtained, observables required for the computation of phase diagrams can be computed with a computational complexity independent of the underlying Hilbert space for any parameter value. We illustrate the efficiency and accuracy of this approach for different one-dimensional quantum spin-1 models, including anisotropic as well as biquadratic exchange interactions, leading to rich quantum phase diagrams.

Surrogate models for quantum spin systems based on reduced-order modeling.

We present a methodology to investigate phase diagrams of quantum models based on the principle of the reduced basis method (RBM). The RBM is built from a few ground-state snapshots, i.e., lowest eigenvectors of the full system Hamiltonian computed at well-chosen points in the parameter space of interest. We put forward a greedy strategy to assemble such a small-dimensional basis, i.e., to select where to spend the numerical effort needed for the snapshots. Once the RBM is assembled, physical observables required for mapping out the phase diagram (e.g., structure factors) can be computed for any parameter value with a modest computational complexity, considerably lower than the one associated to the underlying Hilbert space dimension. We benchmark the method in two test cases, a chain of excited Rydberg atoms and a geometrically frustrated antiferromagnetic two-dimensional lattice model, and illustrate the accuracy of the approach. In particular, we find that the ground-state manifold can be approximated to sufficient accuracy with a moderate number of basis functions, which increases very mildly when the number of microscopic constituents grows-in stark contrast to the exponential growth of the Hilbert space needed to describe each of the few snapshots. A combination of the presented RBM approach with other numerical techniques circumventing even the latter big cost, e.g., tensor network methods, is a tantalizing outlook of this work.

Quantum Chemistry Common Driver and Databases (QCDB) and Quantum Chemistry Engine (QCEngine): Automation and interoperability among computational chemistry programs.

Community efforts in the computational molecular sciences (CMS) are evolving toward modular, open, and interoperable interfaces that work with existing community codes to provide more functionality and composability than could be achieved with a single program. The Quantum Chemistry Common Driver and Databases (QCDB) project provides such capability through an application programming interface (API) that facilitates interoperability across multiple quantum chemistry software packages. In tandem with the Molecular Sciences Software Institute and their Quantum Chemistry Archive ecosystem, the unique functionalities of several CMS programs are integrated, including CFOUR, GAMESS, NWChem, OpenMM, Psi4, Qcore, TeraChem, and Turbomole, to provide common computational functions, i.e., energy, gradient, and Hessian computations as well as molecular properties such as atomic charges and vibrational frequency analysis. Both standard users and power users benefit from adopting these APIs as they lower the language barrier of input styles and enable a standard layout of variables and data. These designs allow end-to-end interoperable programming of complex computations and provide best practices options by default.

Autocalibrating segmented diffusion-weighted acquisitions.

PURPOSE: Segmented echo-planar imaging enables high-resolution diffusion-weighted imaging (DWI). However, phase differences between segments can lead to severe artifacts. This work investigates an algorithm to enable reconstruction of interleaved segmented acquisitions without the need of additional calibration or navigator measurements. METHODS: A parallel imaging algorithm is presented that jointly reconstructs all segments of one DWI frame maintaining their phase information. Therefore, the algorithm allows for an iterative improvement of the phase estimates included in the joint reconstruction. Given a limited number of interleaves, the initial-phase estimates can be calculated by a traditional parallel-imaging reconstruction, using the unweighted scan of the DWI measurement as a reference. RESULTS: Reconstruction of phantom data and g-factor simulations show substantial improvement (up to 93% reduction in root mean square error) compared with a generalized auto-calibrating partially parallel-acquisition reconstruction. In vivo experiments show robust reconstruction outcomes in critical imaging situations, including small numbers of receiver channels or low signal-to-noise ratio. CONCLUSION: An algorithm for the robust reconstruction of segmented DWI data is presented. The method requires neither navigator nor calibration measurements; therefore, it can be applied to existing DWI data sets.

Black-box inhomogeneous preconditioning for self-consistent field iterations in density functional theory.

We propose a new preconditioner based on the local density of states for computing the self-consistent problem in Kohn-Sham density functional theory. This preconditioner is inexpensive and able to cure the long-range charge sloshing known to hamper convergence in large, inhomogeneous systems such as clusters and surfaces. It is based on a parameter-free and physically motivated approximation to the independent-particle susceptibility operator, appropriate for both metals and insulators. It can be extended to semiconductors by using the macroscopic electronic dielectric constant as a parameter in the model. We test our preconditioner successfully on inhomogeneous systems containing metals, insulators, semiconductors and vacuum.

A posteriori error estimation for the non-self-consistent Kohn-Sham equations.

We address the problem of rigorously bounding the errors in the numerical solution of the Kohn-Sham equations due to (i) the finiteness of the basis set, (ii) the convergence thresholds in iterative procedures, and (iii) the propagation of rounding errors in floating-point arithmetic. In this contribution, we compute fully-guaranteed bounds on the solution of the non-self-consistent equations in the pseudopotential approximation in a plane-wave basis set. We demonstrate our methodology by providing band structure diagrams of silicon annotated with error bars indicating the combined error.

Salinity-independent dissipation of antibiotics from flooded tropical soil: a microcosm study.

River deltas are frequently facing salinity intrusion, thus challenging agricultural production in these areas. One adaption strategy to increasing salinity is shrimp production, which however, heavily relies on antibiotic usage. This study was performed to evaluate the effect of increasing salinity on the dissipation rates of antibiotics in tropical flooded soil systems. For this purpose, paddy top soil from a coastal Vietnamese delta was spiked with selected frequently used antibiotics (sulfadiazine, sulfamethazine, sulfamethoxazole, trimethoprim) and incubated with flood water of different salt concentrations (0, 10, 20 g L-1). Antibiotic concentrations were monitored in water and soil phases over a period of 112 days using liquid chromatography and tandem mass spectrometry. We found that sulfamethazine was the most persistent antibiotic in the flooded soil system (DT50 = 77 days), followed by sulfadiazine (DT50 = 53 days), trimethoprim (DT50 = 3 days) and sulfamethoxazole (DT50 = 1 days). With the exception of sulfamethoxazole, the apparent distribution coefficient increased significantly (p < 0.05) for all antibiotics in course of the incubation, which indicates an accumulation of antibiotics in soil. On a whole system basis, including soil and water into the assessment, there was no overall salinity effect on the dissipation rates of antibiotics, suggesting that common e-fate models remain valid under varying salinity.

Quantifying the error of the core-valence separation approximation.

For the calculation of core-excited states probed through X-ray absorption spectroscopy, the core-valence separation (CVS) scheme has become a vital tool. This approach allows us to target such states with high specificity, albeit introducing an error. We report the implementation of a post-processing step for CVS excitations obtained within the algebraic-diagrammatic construction scheme for the polarization propagator, which removes this error. Based on this, we provide a detailed analysis of the CVS scheme, identifying its accuracy to be dominated by an error balance between two neglected couplings, one between core and valence single excitations and the other between single and double core excitations. The selection of the basis set is shown to be vital for a proper description of both couplings, with tight polarizing functions being necessary for a good balance of errors. The CVS error is confirmed to be stable across multiple systems, with an element-specific spread for K-edge spectrum calculations of only about ±0.02 eV. A systematic lowering of the CVS error by 0.02 eV-0.03 eV is noted when considering excitations to extremely diffuse states, emulating ionization.

Toward quantum-chemical method development for arbitrary basis functions.

We present the design of a flexible quantum-chemical method development framework, which supports employing any type of basis function. This design has been implemented in the light-weight program package molsturm, yielding a basis-function-independent self-consistent field scheme. Versatile interfaces, making use of open standards like python, mediate the integration of molsturm with existing third-party packages. In this way, both rapid extension of the present set of methods for electronic structure calculations as well as adding new basis function types can be readily achieved. This makes molsturm well-suitable for testing novel approaches for discretising the electronic wave function and allows comparing them to existing methods using the same software stack. This is illustrated by two examples, an implementation of coupled-cluster doubles as well as a gradient-free geometry optimisation, where in both cases, arbitrary basis functions could be used. molsturm is open-sourced and can be obtained from http://molsturm.org.

Polarizable Embedding Combined with the Algebraic Diagrammatic Construction: Tackling Excited States in Biomolecular Systems.

We present a variant of the algebraic diagrammatic construction (ADC) scheme by combining ADC with the polarizable embedding (PE) model. The presented PE-ADC method is implemented through second and third order and is designed with the aim of performing accurate calculations of excited states in large molecular systems. Accuracy and large-scale applicability are demonstrated with three case studies, and we further analyze the importance of both state-specific and linear-response-type corrections to the excitation energies in the presence of the polarizable environment. We demonstrate how our combined method can be readily applied to study photoinduced biochemical processes as we model the charge-transfer (CT) excitation which is key to the photoprotection mechanism in the dodecin protein with PE-ADC(2). Through direct access to state-of-the-art excited state analysis, we find that the polarizable environment plays a decisive role by significantly increasing the CT character of the electronic excitation in dodecin. PE-ADC is thus suited to decipher photoinduced processes in complex, biomolecular systems at high precision and at reasonable computational cost.

Improving temporal resolution in fMRI using a 3D spiral acquisition and low rank plus sparse (L+S) reconstruction.

Rapid whole-brain dynamic Magnetic Resonance Imaging (MRI) is of particular interest in Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). Faster acquisitions with higher temporal sampling of the BOLD time-course provide several advantages including increased sensitivity in detecting functional activation, the possibility of filtering out physiological noise for improving temporal SNR, and freezing out head motion. Generally, faster acquisitions require undersampling of the data which results in aliasing artifacts in the object domain. A recently developed low-rank (L) plus sparse (S) matrix decomposition model (L+S) is one of the methods that has been introduced to reconstruct images from undersampled dynamic MRI data. The L+S approach assumes that the dynamic MRI data, represented as a space-time matrix M, is a linear superposition of L and S components, where L represents highly spatially and temporally correlated elements, such as the image background, while S captures dynamic information that is sparse in an appropriate transform domain. This suggests that L+S might be suited for undersampled task or slow event-related fMRI acquisitions because the periodic nature of the BOLD signal is sparse in the temporal Fourier transform domain and slowly varying low-rank brain background signals, such as physiological noise and drift, will be predominantly low-rank. In this work, as a proof of concept, we exploit the L+S method for accelerating block-design fMRI using a 3D stack of spirals (SoS) acquisition where undersampling is performed in the kz-t domain. We examined the feasibility of the L+S method to accurately separate temporally correlated brain background information in the L component while capturing periodic BOLD signals in the S component. We present results acquired in control human volunteers at 3T for both retrospective and prospectively acquired fMRI data for a visual activation block-design task. We show that a SoS fMRI acquisition with an acceleration of four and L+S reconstruction can achieve a brain coverage of 40 slices at 2mm isotropic resolution and 64 x 64 matrix size every 500ms.

Comparative T2 and T1ρ mapping of patellofemoral cartilage under in situ mechanical loading with prospective motion correction.

PURPOSE: To demonstrate improved T2 and T1ρ mapping of patellofemoral cartilage with in situ loading by means of prospective motion correction and to assess load-induced changes in healthy subjects. MATERIALS AND METHODS: Established T2 and T1ρ mapping sequences were augmented with prospective motion correction based on optical tracking. Protocols were optimized for robust imaging of the patellofemoral cartilage at a field strength of 3T. Subjects were positioned in the scanner with knee flexion and in situ loading of the patellofemoral joint was performed with a pneumatic loading device. In a pilot study on a cohort of 10 healthy subjects, load-induced T2 and T1ρ changes were evaluated through measurements with axial loads of 0/20/40 kg. RESULTS: With prospective motion correction and additional lipid saturation, motion artifacts in patellofemoral cartilage magnetic resonance imaging (MRI) with in situ loading could be notably decreased, as demonstrated for T2 mapping. The acquired relaxation maps suggested a T2 /T1ρ decrease in superficial cartilage and a T2 /T1ρ increase in deep cartilage under loading. However, in the quantitative group evaluation of the lateral patellar facet, only T1ρ in superficial cartilage was significantly changed by loading (P ≤ 0.05), while no significant T2 differences for the three loading conditions were observed (P ≥ 0.3). CONCLUSION: Prospective motion correction enables T2 and T1ρ mapping of patellofemoral cartilage with in situ loading and a comparison of the two contrasts in terms of their response to mechanical loading. T1ρ is a more sensitive marker for load-induced patellar cartilage changes than T2 . LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:452-460.

Segmented simultaneous multi-slice diffusion weighted imaging with generalized trajectories.

PURPOSE: The purpose of this work is to develop and evaluate a single framework for the use of Cartesian and non-Cartesian segmented trajectories for rapid and robust simultaneous multislice (SMS) diffusion weighted imaging (DWI) at 3 Telsa (T). METHODS: A generalized SMS approach with intrinsic phase navigation using Multiplexed Sensitivity Encoding (MUSE) was developed. Segmented blipped-controlled aliasing in parallel imaging echo planar imaging (EPI) and z-gradient modulated spiral trajectories were examined using SMS DWI scans at 3T with a 32-channel head coil. RESULTS: The generalized SMS MUSE reconstruction framework was successful in significantly reducing artifacts for all trajectories. A DWI brain volume with a 67.5-mm height, 1.5-mm isotropic resolution, and 90 diffusion weightings was obtained in a scan time of 6 minutes. CONCLUSION: The MUSE technique can be generalized to allow for reconstruction of both Cartesian and non-Cartesian segmented trajectories. Magn Reson Med 78:1476-1481, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Marker-based ballistocardiographic artifact correction improves spike identification in EEG-fMRI of focal epilepsy patients.

OBJECTIVES: Ballistocardiographic (BCG) artifacts resemble interictal epileptic discharges (IEDs) and can lead to incorrect IED identification in EEG-fMRI. This study investigates IEDs marked in EEGs corrected using information from a moiré phase tracking (MPT) marker. METHODS: EEG-fMRI from 18 patients was processed with conventional methods for BCG removal, while 9 patients used a MPT marker. IEDs were marked first without ECG information. In a second review, suspicious IEDs synchronous with the BCG were discarded. After each review, an event-related fMRI analysis was performed on the marked IEDs. RESULTS: No difference was found in the proportion of suspicious IEDs in the 2 patient groups. However, the distribution of IED timings was significantly related to the cardiac cycle in 11 of 18 patients recorded without MPT marker, but only 2 of 9 patients with marker. In patients recorded without marker, failing to discard suspicious IEDs led to more inaccurate fMRI maps and more distant activations. CONCLUSIONS: BCG artifact correction based on MPT recordings allowed a more straightforward identification of IEDs that did not require ECG information in the large majority of patients. SIGNIFICANCE: Marker-based ballistocardiographic artifact correction greatly facilitates the study of the generators of interictal discharges with EEG-fMRI.

Reverse retrospective motion correction.

PURPOSE: One potential barrier for using prospective motion correction (PMC) in the clinic is the unpredictable nature of a scan because of the direct interference with the imaging sequence. We demonstrate that a second set of "de-corrected" images can be reconstructed from a scan with PMC that show how images would have appeared without PMC enabled. THEORY AND METHODS: For three-dimensional scans, the effects of PMC can be undone by performing a retrospective reconstruction based on the inverse of the transformation matrix used for real time gradient feedback. Retrospective reconstruction is performed using a generalized SENSE approach with continuous head motion monitored using a single-marker optical camera system. RESULTS: Reverse retrospective reconstruction is demonstrated for phantom and in vivo scans using an magnetization-prepared rapid gradient echo (MPRAGE) sequence including parallel and Partial Fourier acceleration. CONCLUSION: Reverse retrospective reconstruction can almost perfectly undo the effects of prospective feedback, and thereby provide a second image data set with the effects of motion correction removed. In case of correct feedback, one can directly compare the quality of the corrected with that of the uncorrected scan. Additionally, because erroneous feedback during PMC may introduce artifacts, it is possible to eliminate artifacts in a corrupted scan by reversing the false gradient updates. Magn Reson Med 75:2341-2349, 2016. © 2015 Wiley Periodicals, Inc.

Quantitative framework for prospective motion correction evaluation.

PURPOSE: Establishing a framework to evaluate performances of prospective motion correction (PMC) MRI considering motion variability between MRI scans. METHODS: A framework was developed to obtain quantitative comparisons between different motion correction setups, considering that varying intrinsic motion patterns between acquisitions can induce bias. Intrinsic motion was considered by replaying in a phantom experiment the recorded motion trajectories from subjects. T1-weighted MRI on five volunteers and two different marker fixations (mouth guard and nose bridge fixations) were used to test the framework. Two metrics were investigated to quantify the improvement of the image quality with PMC. RESULTS: Motion patterns vary between subjects as well as between repeated scans within a subject. This variability can be approximated by replaying the motion in a distinct phantom experiment and used as a covariate in models comparing motion corrections. We show that considering the intrinsic motion alters the statistical significance in comparing marker fixations. As an example, two marker fixations, a mouth guard and a nose bridge, were evaluated in terms of their effectiveness for PMC. A mouth guard achieved better PMC performance. CONCLUSION: Intrinsic motion patterns can bias comparisons between PMC configurations and must be considered for robust evaluations. A framework for evaluating intrinsic motion patterns in PMC is presented.

Optical tracking with two markers for robust prospective motion correction for brain imaging.

OBJECTIVE: Prospective motion correction (PMC) during brain imaging using camera-based tracking of a skin-attached marker may suffer from problems including loss of marker visibility due to the coil and false correction due to non-rigid-body facial motion, such as frowning or squinting. A modified PMC system is introduced to mitigate these problems and increase the robustness of motion correction. MATERIALS AND METHODS: The method relies on simultaneously tracking two markers, each providing six degrees of freedom, that are placed on the forehead. This allows us to track head motion when one marker is obscured and detect skin movements to prevent false corrections. Experiments were performed to compare the performance of the two-marker motion correction technique to the previous single-marker approach. RESULTS: Experiments validate the theory developed for adaptive marker tracking and skin movement detection, and demonstrate improved image quality during obstruction of the line-of-sight of one marker when subjects squint or when subjects squint and move simultaneously. CONCLUSION: The proposed methods eliminate two common failure modes of PMC and substantially improve the robustness of PMC, and they can be applied to other optical tracking systems capable of tracking multiple markers. The methods presented can be adapted to the use of more than two markers.