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At least 19 records

Novel structural features drive DNA binding properties of Cmr, a CRP family protein in TB complex mycobacteria

Mycobacterium tuberculosis (Mtb) encodes two CRP/FNR family transcription factors (TF) that contribute to virulence, Cmr (Rv1675c) and CRPMt (Rv3676). Prior studies identified distinct chromosomal binding profiles for each TF despite their recognizing overlapping DNA motifs. The present study shows that Cmr binding specificity is determined by discriminator nucleotides at motif positions 4 and 13. X-ray crystallography and targeted mutational analyses identified an arginine-rich loop that expands Cmr’s DNA interactions beyond the classical helixturn-helix contacts common to all CRP/FNR family members and facilitates binding to imperfect DNA sequences. Cmr binding to DNA results in a pronounced asymmetric bending of the DNA and its high level of cooperativity is consistent with DNAfacilitated dimerization. A unique N-terminal extension inserts between the DNA binding and dimerization domains, partially occluding the site where the canonical cAMP binding pocket is found. However, an unstructured region of this N-terminus may help modulate Cmr activity in response to cellular signals. Cmr’s multiple levels of DNA interaction likely enhance its ability to integrate diverse gene regulatory signals, while its novel structural features establish Cmr as an atypical CRP/FNR family member.

59 BASIC BIOLOGICAL SCIENCES↗

C-AAC Occupancy and Transition Out of CMR [Slides]

This in-depth evaluation was performed in order to gather information for a plan and time estimate of C-AAC space cleanout and handover to the CMR facility once programmatic operations are relocated to other facilities. C-AAC space ownership in CMR wings 1, 5, 7, and 9 have been identified down to the Team level (see subsequent slides and other supporting documentation). This plan assumes that C-AAC activities that support Pu sustainment efforts (Wings 1, 5, and 7) are relocated to PF-4 and RLUOB in mid/end FY24 and current projects in Wing 9 are completed by the end of FY24/mid FY25 (cessation of C-AAC programmatic operations in CMR). This plan assumes that no other programmatic activities are initiated in CMR (e.g. MOX fuel rods). Timing and order of cleanout of programmatic laboratory and office spaces in wings 1, 5, and 7 is dependent upon analytical chemistry operations being established and relocated to RLUOB and PF-4. Timing and order of cleanout of programmatic laboratory and office spaces in wing 9 is dependent upon completion of current projects (MR&R, Thermo Fisher drum, etc.). As C-AAC Teams move out of the CMR building and into other facilities, the spaces occupied by those teams are planned to be targeted for in depth cleanout in the order that teams and capabilities are relocated.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

MR Imaging of Patients with Cardiac Implantable Electronic Devices (CIEDs): Implementing a Program and Optimizing CMR

Purpose of review: How to implement a program for MRI in patients with conditional and non-conditional (“legacy”) CIED. How to optimize safety and image quality in CMR? What the radiologists need to know: device programming, pre- and post-MRI CIED parameters. Recent findings: New Center for Medicare and Medicaid Services (CMS) guidelines have opened MRI to many patients with nonconditional devices. Newer pulse sequences for cardiac MRI (CMR) in device patients, including modified cine, late gadolinium enhancement and T1 mapping sequences, have resulted in improved image quality in device patients. We present several cases of CMR in device patients, including imaging of leadless pacemakers subcutaneous ICDs. Imaging pitfalls/artifacts in CMR interpretation are also presented. Summary: An organized institutional workflow with an established protocol involving proper patient screening, device programming, scan monitoring, and pre- and post-ICD interrogation minimizes risk in patients with conditional and non-conditional CIEDs. Although rare, significant changes in lead performance, power-on/reset, inappropriate pacing or ICD discharges and battery voltage depletion should be documented. High-quality scans with accurate scar characterization in CIED patients require the use of wideband sequences. CMS has recently acknowledged MRI as a reasonable test necessary for the diagnosis and treatment of beneficiaries with implanted CIEDs, improving the financial prospects and encouraging future developments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Myocardial Imaging with CMR Parametric Mapping: Clinical Applications

Purpose of Review: Cardiovascular magnetic resonance (CMR) parametric mapping techniques enable the direct visualization and quantification of changes in myocardial T1, T2, T2* relaxation times and extracellular volume fraction. Recent updates on clinical applications of CMR parametric mapping techniques are reviewed in this article. Recent Findings: CMR parametric mapping techniques are useful in the evaluation of multiple conditions, including iron overload, amyloid infiltration, glycosphingolipid accumulation, myocardial edema, and fibrosis. An advantage of parametric mapping over conventional tissue characterization sequences is that these techniques are quantitative, allowing for standardization of measurements and assessment of longitudinal changes over time. Parametric mapping techniques are useful in clinical practice, including aiding in establishing a diagnosis, monitoring disease progression, evaluating response to therapy, and informing prognosis. Summary: This article provides a summary of the existing evidence for the clinical application of cardiac parametric mapping techniques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Criticality Safety Evaluation for Small Sample Preparation and Non-Destructive Assay (NDA) Operations in Wing 7 Basement of the CMR Facility

Nuclear Criticality Safety (NCS) has reviewed the fissionable material small sample preparation and NDA operations in Wing 7 Basement of the CMR Facility. This is a Level-1 evaluation conducted in accordance with NCS-AP-004 [Reference 1], formerly NCS-GUIDE-01, and the guidance set forth on use of the Standard Criticality Safety Requirements (SCSRs) [Reference 2]. As stated in Reference 2, the criticality safety evaluation consists of both the SCSR CSED and the SCSR Application CSED. The SCSR CSED is a Level-3 CSED [Reference 3]. This Level-1 CSED is the SCSR Application CSED. This SCSR Application (Level-1) evaluation does not derive controls, it simply applies controls derived from the SCSR CSED (Level-3) for the application of operations conducted here. The controls derived in the SCSR CSED (Level-3) were evaluated via the process described in Section 6.6.5 of SD-130 (also reproduced in Section 4.3.5 of NCS-AP-004 [Reference 1]) and were determined to not meet the requirements for consideration of elevation into the safety basis documentation for CMR. According to the guidance set forth on use of the SCSRs [Reference 2], the SCSR CSED (Level-3) is also applicable to the CMR Facility because the process and the normal and credible abnormal conditions in question are bounded by those that are described in the SCSR CSED. The controls derived in the SCSR CSED include allowances for solid materials and solution operations. Based on the operations conducted at this location, there are less-than-accountable (LTA) amounts of 233 U. Based on the evaluation documented herein, the normal and credible abnormal conditions that might arise during the execution of this process will remain subcritical with the following recommended controls.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Structural studies on the substitution of Ag, Na doped LCSMO CMR manganites

Synthesis and characterization of colossal magnetoresistance (CMR) materials has been a subject of scientific research due to the unique transport, magnetotransport, and magnetic properties. The single phase polycrystalline La{sub 0.7}Ca{sub 0.1}Sr{sub 0.1}M{sub 0.1}MnO{sub 3} (LCSMO) (M=Ag and Na) samples prepared using nitrate route method. The structural properties are studied at different dopants by X-ray diffraction. The surface morphology and elemental analysis of both samples were carried out by scanning electron microscopy (SEM) and energy dispersive X-ray technique (EDAX) respectively. The structural analysis shows that the LCSMO is crystallized in an orthorhombic perovskite structure belonging to Pnma space group. The crystal size of the sample is calculated using Scherrer formula. The SEM images show that the polycrystalline grains are observed to be near spherical shape and uniform in size. EDAX spectra taken from the surface of the synthesized powders show a nominal composition near the desired one for M=Na sample where as some vacancies are present in the A-site in the case of Ag substitution as will be discussed in this paper.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Evaluation of left ventricular mass on cadmium-zinc-telluride imaging: Validation against cardiac magnetic resonance

Background: Single-photon emission computed tomography has shown relevant limitations in the quantification of left ventricular (LV) mass. We sought to compare the estimates of LV mass on Cadmium-Zinc-Telluride (CZT) myocardial perfusion imaging (MPI) as compared to cardiac magnetic resonance (CMR). Methods and results: Twenty-five patients underwent MPI on a CZT camera and CMR on a 1.5 T scanner within 12 ± 3 weeks. LV mass was quantified on CZT images using two softwares: 4D-MSPECT (4DM) and Emory Cardiac Toolbox (ECTb). LV mass by CMR was quantified using MASS software (Medis, Leiden, The Netherlands). LV mass values obtained with 4DM and ECTb were highly reproducible [intraclass correlation coefficients .98 (95% CI .97-.99), and .98 (95% CI 0.97-.99), respectively]. The mean LVM mass values were 151 ± 44 g on CMR, 151 ± 43 g with 4DM (P = NS vs CMR), and 157 ± 42 g with ECTb (P < .001 vs CMR; P = .007 vs 4DM) CZT images. There was an excellent correlation between LV mass values between CMR and both 4DM (R{sup 2} = .95; P < .001) and ECTb (R{sup 2} = .98; P < .001) with narrow limits of agreement (− 13.6% to + 13.4% for 4DM, and − 5.6% to + 14.1% for ECTb). Conclusions: The evaluation of LV mass is feasible on CZT images, showing excellent agreement with CMR.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Colossal Magnetoresistance without Mixed Valence in a Layered Phosphide Crystal

Materials with strong magnetoresistive responses are the backbone of spintronic technology, magnetic sensors, and hard drives. Among them, manganese oxides with a mixed valence and a cubic perovskite structure stand out due to their colossal magnetoresistance (CMR). A double exchange interaction underlies the CMR in manganates, whereby charge transport is enhanced when the spins on neighboring Mn 3+ and Mn 4+ ions are parallel. Prior efforts to find different materials or mechanisms for CMR resulted in a much smaller effect. Here an enormous CMR at low temperatures in EuCd 2 P 2 without manganese, oxygen, mixed valence, or cubic perovskite structure is shown. EuCd 2 P 2 has a layered trigonal lattice and exhibits antiferromagnetic ordering at 11 K. The magnitude of CMR (10(4)%) in as-grown crystals of EuCd 2 P 2 rivals the magnitude in optimized thin films of manganates. In this work, the magnetization, transport, and synchrotron X-ray data suggest that strong magnetic fluctuations are responsible for this phenomenon. The realization of CMR at low temperatures without heterovalency leads to a new regime for materials and technologies related to antiferromagnetic spintronics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Evaluation of Hypertrophic Cardiomyopathy: Newer Echo and MRI Approaches

Purpose of Review: This review discusses the basic and evolving echocardiographic and cardiac magnetic resonance (CMR) approaches in the diagnosis and management of patients with hypertrophic cardiomyopathy (HCM). Recent Findings: Newer imaging technologies and techniques in both echocardiography and CMR have proved to add incremental value to our understanding of HCM. 3D reconstruction in echocardiography and CMR allows for more accurate morphological and volumetric assessment of the left ventricle. Echocardiographic and CMR-based left atrial assessment, including for its mechanical properties, has been shown to be correlated to outcomes and development of atrial fibrillation. Tissue characterization and scar burden quantification by late gadolinium enhancement on CMR has revolutionized our understanding of fibrotic processes in HCM and their contribution to disease severity and clinical outcomes. Summary: Cardiac imaging plays a crucial role in HCM patients. Using echocardiography and CMR as complementary modalities allows for improved diagnostics, optimization of treatment, and better prognostication.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Test–retest repeatability of myocardial oxidative metabolism and efficiency using standalone dynamic {sup 11}C-acetate PET and multimodality approaches in healthy controls

Background: Myocardial efficiency measured by {sup 11}C-acetate positron emission tomography (PET) has successfully been used in clinical research to quantify mechanoenergetic coupling. The objective of this study was to establish the repeatability of myocardial external efficiency (MEE) and work metabolic index (WMI) by non-invasive concepts. Methods and Results: Ten healthy volunteers (63 ± 4 years) were examined twice, one week apart, using {sup 11}C-acetate PET, cardiovascular magnetic resonance (CMR), and echocardiography. Myocardial oxygen consumption from PET was combined with stroke work data from CMR, echocardiography, or PET to obtain MEE and WMI for each modality. Repeatability was estimated as the coefficient of variation (CV) between test and retest. MEE{sub CMR}, MEE{sub Echo}, and MEE{sub PET} values were 21.9 ± 2.7%, 16.4 ± 3.7%, and 23.8 ± 4.9%, respectively, P < .001. WMI{sub CMR}, WMI{sub Echo}, and WMI{sub PET} values were 4.42 ± 0.90, 4.07 ± 0.63, and 4.58 ± 1.13 mmHg × mL/m{sup 2} × 10{sup 6}, respectively, P = .45. Repeatability for MEE{sub CMR} was superior compared with MEE{sub Echo} but did not differ significantly compared with MEE{sub PET} (6.3% vs 12.9% and 9.4%, P = .04 and .25). CV values for WMI{sub CMR}, WMI{sub Echo}, and WMI{sub PET} were 10.0%, 14.8%, and 12.0%, respectively, (P = .53). Conclusions: Non-invasive measurements of MEE using {sup 11}C-acetate PET are highly repeatable. A PET-only approach did not differ significantly from CMR/PET and might facilitate further clinical research due to lower costs and broader applicability.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of Machine Learning and Deep Learning for View Identification from Cardiac Magnetic Resonance Images

Background: Artificial intelligence is increasingly utilized to aid in the interpretation of cardiac magnetic resonance (CMR) studies. One of the first steps is the identification of the imaging plane depicted, which can be achieved by both deep learning (DL) and classical machine learning (ML) techniques without user input. We aimed to compare the accuracy of ML and DL for CMR view classification and to identify potential pitfalls during training and testing of the algorithms. Methods: To train our DL and ML algorithms, we first established datasets by retrospectively selecting 200 CMR cases. The models were trained using two different cohorts (passively and actively curated) and applied data augmentation to enhance training. Once trained, the models were validated on an external dataset, consisting of 20 cases acquired at another center. We then compared accuracy metrics and applied class activation mapping (CAM) to visualize DL model performance. Results: The DL and ML models trained with the passively-curated CMR cohort were 99.1% and 99.3% accurate on the validation set, respectively. However, when tested on the CMR cases with complex anatomy, both models performed poorly. After training and testing our models again on all 200 cases (active cohort), validation on the external dataset resulted in 95% and 90% accuracy, respectively. The CAM analysis depicted heat maps that demonstrated the importance of carefully curating the datasets to be used for training. Conclusions: Both DL and ML models can accurately classify CMR images, but DL outperformed ML when classifying images with complex heart anatomy.

artificial intelligence↗

RECONNECTION-DRIVEN DOUBLE LAYERS IN THE STRATIFIED PLASMA OF THE SOLAR TRANSITION REGION: SUPPLY OF HOT PLASMA INTO THE CORONA

A novel mechanism for the supply of hot plasma into the corona from the chromosphere is suggested here; the mechanism involves collisionless magnetic reconnection (CMR) in the transition region (TR) followed by double layer (DL) formation in the enhanced expansion of the chromospheric cold plasma mixed with CMR-heated hot electrons. It is well known that (i) the CMR produces energetic electrons and (ii) DLs naturally form in expanding dense plasmas containing a minor population of hot electrons. We apply these plasma physics facts to the dynamics of stratified plasma in the TR. In the TR where densities fall below ∼10{sup 16} m{sup −3}, all collisional mean-free paths, electron–ion, ion–neutral, and electron–neutral, become long enough to render plasma collisionless at kinetic scale lengths, making CMR and DL formation possible. The DLs accelerate the chromospheric cold ions to energies comparable to the energy of the hot electrons. When the upflowing energized ions neutralized by the escaping hot electrons thermalize, the resulting hot tenuous plasma supplies an energy flux ∼3 × 10{sup 5} erg cm{sup −2} s{sup −1} = 3 × 10{sup 2} J m{sup −2} s{sup −1} into the corona. The CMR–DL mechanism introduces sudden transitions in the TR as microstructures in both density and energy. The global transition in the TR could be a fractal structure containing such microscopic features. If not impossible, it is difficult to measure such microstructures, but it seems that the coronal heating begins in the nearly collisionless TR by CMR and DL formation.

79 ASTRONOMY AND ASTROPHYSICS↗

Positron Emission Tomography/Computed Tomography Assessment After Immunochemotherapy and Irradiation Using the Lugano Classification Criteria in the IELSG-26 Study of Primary Mediastinal B-Cell Lymphoma

Purpose: To assess the predictive value of {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for disease recurrence after immunochemotherapy (R-CHT) and mediastinal irradiation (RT), using the recently published criteria of the Lugano classification to predict outcomes for patients with primary mediastinal large B-cell lymphoma. Methods and Materials: Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT. According to the Lugano classification, a complete metabolic response (CMR) was defined by a Deauville score (DS) ≤3. Results: The CMR (DS1, -2, or -3) rate increased from 74% (65 patients) after R-CHT to 89% (78 patients) after consolidation RT. Among the 10 patients (11%) with persistently positive scans, the residual uptake after RT was slightly higher than the liver uptake in 6 patients (DS4; 7%) and markedly higher in 4 patients (DS5; 4%): these patients had a significantly poorer 5-year progression-free survival and overall survival. At a median follow-up of 60 months (range, 35-107 months), no patients with a CMR after RT have relapsed. Among the 10 patients who did not reach a CMR, 3 of the 4 patients (positive predictive value, 75%) with DS5 after RT had subsequent disease progression (within the RT volume in all cases) and died. All patients with DS4 had good outcomes without recurrence. Conclusions: All the patients obtaining a CMR defined as DS ≤3 remained progression-free at 5 years, confirming the excellent negative predictive value of the Lugano classification criteria in primary mediastinal large B-cell lymphoma patients. The few patients with DS4 also had an excellent outcome, suggesting that they do not necessarily require additional therapy, because the residual {sup 18}F-fluorodeoxyglucose uptake may not reflect persistent lymphoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Colossal terahertz magnetoresistance at room temperature in epitaxial La 0.7 Sr 0.3 MnO 3 nanocomposites and single-phase thin films

Colossal magnetoresistance (CMR) is demonstrated at terahertz (THz) frequencies by using terahertz time-domain magnetospectroscopy to examine vertically aligned nanocomposites (VANs) and planar thin films of La 0.7 Sr 0.3 MnO 3 . At the Curie temperature (room temperature), the THz conductivity of the VAN was dramatically enhanced by over 2 orders of magnitude under the application of a magnetic field with a non-Drude THz conductivity that increased with frequency. The direct current (dc) CMR of the VAN is controlled by extrinsic magnetotransport mechanisms such as spin-polarized tunneling between nanograins. In contrast, we find that THz CMR is dominated by intrinsic, intragrain transport: the mean free path was smaller than the nanocolumn size, and the planar thin-film exhibited similar THz CMR to the VAN. Surprisingly, the observed colossal THz magnetoresistance suggests that the magnetoresistance can be large for alternating current motion on nanometer length scales, even when the magnetoresistance is negligible on the macroscopic length scales probed by dc transport. This suggests that colossal magnetoresistance at THz frequencies may find use in nanoelectronics and in THz optical components controlled by magnetic fields. As a result, the VAN can be scaled in thickness while retaining a high structural quality and offers a larger THz CMR at room temperature than the planar film.

36 MATERIALS SCIENCE↗

Collapse of Jahn-Teller phonons in La 1−x Sr x MnO 3 with weak magnetoresistance

Perovskite manganites are quantum materials exhibiting competing interactions inducing colossal magnetoresistance (CMR). The prevailing theory of CMR highlights the essential role of electron-phonon coupling (EPC), but mounting evidence suggests the underlying mechanism is more complicated. Here, we investigate phonons and spin-phonon coupling in ferromagnetic CMR manganites La 1−x Sr x MnO 3 (x=0.2,0.3) with relatively small CMR associated with melting of the magnetic order above room temperature. High-resolution neutron scattering experiments combined with density functional theory (DFT) show that the low-temperature ferromagnetic phase is conventional: neutron scattering from phonons agrees with DFT predictions and magnons follow sinusoidal dispersions. Fluctuating magnetic moments and low-energy phonons remain conventional in the high-temperature paramagnetic phase, indicating the Mn and La/Sr sublattices are not strongly perturbed by melting of ferromagnetism. In contrast, the Jahn–Teller-active optical oxygen vibrations collapse entirely above the Curie temperature, despite low CMR in these compositions, with some of the lost spectral weight reappearing as quasielastic scattering. We attribute this highly anomalous behavior to giant EPC in the charge and/or orbital channel. It drives cooperative diffusive motion of quasistatic carrier-trapping oxygen sublattice distortions once ferromagnetism disappears. We hypothesize the magnitude of magnetoresistance correlates with the rate of diffusion rather than with the strength of Jahn–Teller EPC.

36 MATERIALS SCIENCE↗

Correlation matrix renormalization theory for correlated-electron materials with application to the crystalline phases of atomic hydrogen

Developing accurate and computationally efficient methods to calculate the electronic structure and total energy of correlated-electron materials has been a very challenging task in condensed matter physics and materials science. Recently, we have developed a correlation matrix renormalization (CMR) method which does not assume any empirical Coulomb interaction U parameters and does not have double counting problems in the ground-state total energy calculation. The CMR method has been demonstrated to be accurate in describing both the bonding and bond breaking behaviors of molecules. In this study, we extend the CMR method to the treatment of electron correlations in periodic solid systems. By using a linear hydrogen chain as a benchmark system, we show that the results from the CMR method compare very well with those obtained recently by accurate quantum Monte Carlo (QMC) calculations. We also study the equation of states of three-dimensional crystalline phases of atomic hydrogen. We show that the results from the CMR method agree much better with the available QMC data in comparison with those from density functional theory and Hartree-Fock calculations.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗