NRAP reduction rescues sarcomere defects in nebulin-related nemaline myopathy.

Nemaline myopathy (NM) is a rare neuromuscular disorder associated with congenital or childhood-onset of skeletal muscle weakness and hypotonia, which results in limited motor function. NM is a genetic disorder and mutations in 12 genes are known to contribute to autosomal dominant or recessive forms of the disease. Recessive mutations in nebulin (NEB) are the most common cause of NM affecting about 50% of patients. Because of the large size of the NEB gene and lack of mutational hot spots, developing therapies that can benefit a wide group of patients is challenging. Although there are several promising therapies under investigation, there is no cure for NM. Therefore, targeting disease modifiers that can stabilize or improve skeletal muscle function may represent alternative therapeutic strategies. Our studies have identified Nrap upregulation in nebulin deficiency that contributes to structural and functional deficits in NM. We show that genetic ablation of nrap in nebulin deficiency restored sarcomeric disorganization, reduced protein aggregates and improved skeletal muscle function in zebrafish. Our findings suggest that Nrap is a disease modifier that affects skeletal muscle structure and function in NM; thus, therapeutic targeting of Nrap in nebulin-related NM and related diseases may be beneficial for patients.

Past dynamics and future prediction of the impacts of land use cover change and climate change on landscape ecological risk across the Mongolian plateau.

Land use/land cover (LULC) change and climate change are interconnected factors that affect the ecological environment. However, there is a lack of quantification of the impacts of LULC change and climate change on landscape ecological risk under different shared socioeconomic pathways and representative concentration pathways (SSP-RCP) on the Mongolian Plateau (MP). To fill this knowledge gap and understand the current and future challenges facing the MP's land ecological system, we conducted an evaluation and prediction of the effects of LULC change and climate change on landscape ecological risk using the landscape loss index model and random forest method, considering eight SSP-RCP coupling scenarios. Firstly, we selected MCD12Q1 as the optimal LULC product for studying landscape changes on the MP, comparing it with four other LULC products. We analyzed the diverging patterns of LULC change over the past two decades and observed significant differences between Mongolia and Inner Mongolia. The latter experienced more intense and extensive LULC change during this period, despite similar climate changes. Secondly, we assessed changes in landscape ecological risk and identified the main drivers of these changes over the past two decades using a landscape index model and random forest method. The highest-risk zone has gradually expanded, with a 30% increase compared to 2001. Lastly, we investigated different characteristics of LULC change under different scenarios by examining future LULC products simulated by the FLUS model. We also simulated the dynamics of landscape ecological risks under these scenarios and proposed an adaptive development strategy to promote sustainable development in the MP. In terms of the impact of climate change on landscape ecological risk, we found that under the same SSP scenario, increasing RCP emission concentrations significantly increased the areas with high landscape ecological risk while decreasing areas with low risk. By integrating quantitative assessments and scenario-based modeling, our study provides valuable insights for informing sustainable land management and policy decisions in the region.

Consistent predictors of microbial community composition across spatial scales in grasslands reveal low context-dependency.

Environmental circumstances shaping soil microbial communities have been studied extensively. However, due to disparate study designs, it has been difficult to resolve whether a globally consistent set of predictors exists, or context-dependency prevails. Here, we used a network of 18 grassland sites (11 of those containing regional plant productivity gradients) to examine (i) if similar abiotic or biotic factors predict both large-scale (across sites) and regional-scale (within sites) patterns in bacterial and fungal community composition, and (ii) if microbial community composition differs consistently at two levels of regional plant productivity (low vs. high). Our results revealed that bacteria were associated with particular soil properties (such as base saturation) and both bacteria and fungi were associated with plant community composition across sites and within the majority of sites. Moreover, a discernible microbial community signal emerged, clearly distinguishing high and low-productivity soils across different grasslands independent of their location in the world. Hence, regional productivity differences may be typified by characteristic soil microbial communities across the grassland biome. These results could encourage future research aiming to predict the general effects of global changes on soil microbial community composition in grasslands and to discriminate fertile from infertile systems using generally applicable microbial indicators.

Tissue Clearing To Localize Microplastics via Three-Dimensional Imaging of Whole Organisms.

Understanding the biological impacts of plastic pollution requires an effective methodology to detect unlabeled microplastics in environmental samples. Detecting unlabeled microplastics in an organism generally requires a digestion protocol, which results in the loss of spatial information on the distribution of microplastic within the organism and could lead to the disappearance of the smaller plastics. Fluorescence microscopy allows visualization of ingested microplastics but many labeling strategies are nonspecific and label biomass, thus limiting our ability to distinguish internalized plastics. While prelabeled plastics can be used to avoid nonspecific labeling, this approach precludes the detection of environmental microplastics in organisms. Also, using prelabeled microplastics can affect the viability of the organism and impact plastic uptake. Thus, a method was developed that employs nonspecific labeling with a tissue-clearing technique. Briefly, unlabeled microplastics are stained with a fluorescent dye after ingestion by the organism. The tissue-clearing technique then removes tissue-bound dye while rendering the structurally intact organism transparent. The internalized plastics remain stained and can be visualized in the cleared tissue with fluorescence microscopy. The technique is demonstrated using polystyrene beads in living aquatic organismsTigriopus californicusandDaphnia magnaand by spiking a model vertebrate (Cephalochordata) with different microplastics.

Light grazing intensity enhances ecosystem services in semi-arid grasslands through plant trait associations.

Grasslands provide multiple ecosystem services (ESs) including provisioning, regulating, supporting, and cultural services that are largely affected by livestock grazing. Linking plant functional traits (PFTs) to ecosystem processes and functions has attracted extensive ecological research to explore the responses and inter-relations of ecosystem services to environmental and management changes. However, little information is available on the links between PFTs and ESs in most ecosystems. We conducted a grazing experiment to investigate the response of PFTs at different levels, including in plant organs (leaves and stems), individual plants, and the overall community in a typical steppe region of Inner Mongolia. Additionally, we examined the effect of animal grazing at four intensities (nil, light, moderate, and heavy) and explored the dynamic interconnections between PFTs and ecosystem services in grasslands. Our analysis revealed that the highest total ecosystem service and provisioning service were achieved under light- and moderate-grazing treatments, respectively. Heavy grazing also increased provisioning service but with a large decline in regulating and total ecosystem services. These changes in ESs were closely associated with grazing-induced variations in PFTs. Compared to no grazing, light grazing increased plant size-related functional traits, such as height, leaf length, leaf area, stem length, and the ratio of stem length to diameter. In contrast, heavy grazing decreased these PFTs. Provisioning and regulating services were determined by plant above-ground community function and structural properties, while supporting service was jointly affected by the below-ground community and soil properties. Our results indicate that light grazing should be recommended for the best total ESs, although moderate grazing may lead to high short-term economic benefits. Moreover, PFTs are powerful indicators for provisioning and regulating services. These findings provide a valuable reference for developing effective management practices to achieve targeted ESs using PFTs as indicators.

Deleting nebulin's C-terminus reveals its importance to sarcomeric structure and function and is sufficient to invoke nemaline myopathy.

Nebulin is a large skeletal muscle protein wound around the thin filaments, with its C-terminus embedded within the Z-disk and its N-terminus extending out toward the thin filament pointed end. While nebulin's C-terminus has been implicated in both sarcomeric structure and function as well as the development of nemaline myopathy, the contributions of this region remain largely unknown. Additionally, the C-terminus is reported to contribute to muscle hypertrophy via the IGF-1 growth pathway. To study the functions of nebulin's C-terminus, we generated a mouse model deleting the final two unique C-terminal domains, the serine-rich region (SRR) and the SH3 domain (NebΔ163-165). Homozygous NebΔ163-165 mice that survive past the neonatal stage exhibit a mild weight deficit. Characterization of these mice revealed that the truncation caused a moderate myopathy phenotype reminiscent of nemaline myopathy despite the majority of nebulin being localized properly in the thin filaments. This phenotype included muscle weight loss, changes in sarcomere structure, as well as a decrease in force production. Glutathione S-transferase (GST) pull-down experiments found novel binding partners with the SRR, several of which are associated with myopathies. While the C-terminus does not appear to be a limiting step in muscle growth, the IGF-1 growth pathway remained functional despite the deleted domains being proposed to be essential for IGF-1 mediated hypertrophy. The NebΔ163-165 mouse model emphasizes that nebulin's C-terminus is necessary for proper sarcomeric development and shows that its loss is sufficient to induce myopathy.

Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.

Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin's influence on thin filament structure and function. Here, we used small-angle X-ray diffraction and compared intact muscle deficient in nebulin (using a conditional nebulin-knockout, Neb cKO) with control (Ctrl) muscle. When muscles were activated, the spacing of the actin subunit repeat (27 Å) increased in both genotypes; when converted to thin filament stiffness, the obtained value was 30 pN/nm in Ctrl muscle and 10 pN/nm in Neb cKO muscle; that is, the thin filament was approximately threefold stiffer when nebulin was present. In contrast, the thick filament stiffness was not different between the genotypes. A significantly shorter left-handed (59 Å) thin filament helical pitch was found in passive and contracting Neb cKO muscles, as well as impaired tropomyosin and troponin movement. Additionally, a reduced myosin mass transfer toward the thin filament in contracting Neb cKO muscle was found, suggesting reduced cross-bridge interaction. We conclude that nebulin is critically important for physiological force levels, as it greatly stiffens the skeletal muscle thin filament and contributes to thin filament activation and cross-bridge recruitment.

Transcriptome-Wide Gene Expression Plasticity in Stipa grandis in Response to Grazing Intensity Differences.

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is a representative species for studying the grazing effect on typical steppe plants in the Inner Mongolia Plateau. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Here, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. As a result, a total of 2357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified in RNA-Seq and qRT-PCR analyses that indicated the modulation of the Calvin-Benson cycle and photorespiration metabolic pathways. The key gene expression profiles encoding various proteins (e.g., ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase, etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection and identifying important questions to address in future transcriptome studies.

The Compounding Effect of Race/Ethnicity and Disability Status on Children's Health and Health Care by Geography in the United States.

OBJECTIVE: The objective of this study was to examine the potential compounding effect of race/ethnicity, and disability status on children's health and health care, stratified by selected geographies. METHODS: We used the 2011/2012 NSCH and the 2012 Boston Survey of Children's Health for our compounded disparity analysis. We used VanderWheel and Knol method to first predict combined risk ratios of race/ethnicity and disability and then compared them with the observed combined risk ratios. RESULTS: We demonstrated that racial/ethnic minority children with disabilities experience additional disparities in health care access outcomes that are greater than the sum of the effects from either characteristic alone. Further, we demonstrate that disparities persist across all selected geographies irrespective of whether children lived in states or metropolitan cities with the best health care systems in the United States. CONCLUSIONS: Despite reform efforts, our study demonstrates that racial/ethnic minority children with disabilities experience a double burden. Given the deleterious compounded disparities, public health and social service programs at all geographical levels should prioritize identifying participants that face this and tailor programs to meet their needs.

Land use alters relationships of grassland productivity with plant and arthropod diversity in Inner Mongolian grassland.

The threats of land-use intensification to biodiversity have motivated considerable research directed toward understanding the relationship between biodiversity and ecosystem functioning (BEF). Functional diversity is deemed a better indicator than species diversity to clarify the BEF relationships. However, most tests of the BEF relationship have been conducted in highly controlled plant communities, with terrestrial animal communities largely unexplored. Additionally, most BEF studies examined the effects of biodiversity on ecosystem functions, with the effects of ecosystem functioning strength on biodiversity hardly considered. Based on a 6-yr grassland experiment in the typical steppe region of Inner Mongolia, we examined the variation of taxonomic diversity (TD) and functional diversity (FD) of both plant and arthropod communities, and their relations with grassland productivity, across three land management types (moderate grazing, mowing, and enclosure). We aimed to clarify the interrelations among plant FD, arthropod FD, grassland productivity, and soil factors. We found the following: (1) Grassland under mowing performed best in terms of sustaining a high TD and FD of plants and arthropods compared to that under grazing and enclosure. (2) The relationships between plant and arthropod diversity and productivity varied with management types. Plant TD and FD were negatively related, whereas arthropod FD was positively related with productivity under enclosure; plant FD, but not arthropod FD, was positively related with productivity under grazing; arthropod FD, but not plant FD, was negatively related with productivity under mowing. (3) Grassland productivity was positively interrelated with plant FD, but not plant TD; and was negatively interrelated with arthropod TD, but not arthropod FD across different management types. The respective positive vs. negative bidirectional relationships of productivity with plant diversity vs. arthropod diversity, were majorly a consequence of divergent grazing/mowing effects on plant vs. arthropod diversity. The results indicate that grazing increases plant diversity, but decreases arthropod diversity, whereas fall mowing provides a management strategy for conservation of both trophic levels. These results also provide new insights into the effects of land-use changes on biodiversity and ecosystem processes, and indicate the importance of incorporating the functional interrelations among different trophic groups in sustainable grassland management.

Plant production decreases whereas nutrients concentration increases in response to the decrease of mowing stubble height.

Mowing is a common practice in grassland management. It removes the majority of current year's aboveground plant biomass and thus substantial amounts of nutrients residing in plant tissues. The responses of plant aboveground biomass and nutrients to mowing stubble height is of great importance for developing sustainable mowing regimes, however, they are not well understood. We studied the effects of 4-year annual mowing at different height on plant aboveground biomass, plant N, P and N:P ratio, and soil nutrients in an Inner Mongolian steppe. Six stubble heights were set respectively at 14 cm (M14), 12 cm (M12), 10 cm (M10), 8 cm (M8), 6 cm (M6) and less than 0.3 cm (M0) height to ground surface. A no-mowing treatment (CK) was also included, making seven treatments. The results show that plant biomass production increased under light mowing (stubble height  > 12 cm) but decreased under heavy mowing (stubble height  < 6 cm), and the optimal stubble height for sustainable mowing was 6-12 cm. Plant N and P concentrations increased with mowing intensity (i.e. with the decrease of mowing stubble height). Plant N:P ratio decreased for some species, but no a directional change was detected in plant N:P ratio at the community level, nor in soil organic carbon and nutrient concentrations across the stubble height treatments. Our results indicate that plant biomass and N & P respond quickly to mowing height, whereas the response of soil chemical properties is insignificant over the 4-year period. To elucidate variation of species compensatory growth along mowing intensity gradient and the mutual feedback mechanism of soil-plant in mowing grassland, long-term study at permanent sites with changing stubble heights should be strengthened.

Intervertebral disc needle puncture injury can be repaired using a gelatin-poly (γ-glutamic acid) hydrogel: an in vitro bovine biomechanical validation.

PURPOSE: The subtle impairments of the disc due to anular punctures may have an immediate effect on the functional integrity due to the altered intradiscal pressure, hence the subsequent catabolic degradation. This study evaluates functional restoration of needle puncture injured intervertebral discs with a newly developed injectable hydrogel using the quantitative discomanometry (QD) test. The proposed hydrogel is composed of gelatin and poly (γ-glutamic acid) (γ-PGA) and crosslinked with 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC). METHODS: Thirty-six bovine motion segments were distributed into six groups. Needle puncture injured discs were created in all discs except for those in the first group (intact). The second group included injured discs that received no treatment (injury). The remaining four groups included injured discs repaired with injected hydrogels fabricated with different polymer solutions and EDC concentrations including: gelatin/γ-PGA solution crosslinked with the EDC solution at a 10:1 and 40:1 ratio to form the GP/E(10:1) and GP/E(40:1) groups, respectively, and gelatin and γ-PGA solution crosslinked with the EDC solution at a 10:1 ratio to form the G/E(10:1) or P/E(10:1) groups. The QD tests were performed to evaluate disc integrity of all six groups. RESULTS: Among all hydrogel repair groups, the GP/E(10:1) group was found to have the highest leakage and saturate pressure and was the only group comparable to the intact one. CONCLUSIONS: Restoration of disc integrity secondary to needle puncture injury can be achieved via the repair with the newly developed gelatin hydrogel incorporated with γ-PGA and EDC. These slides can be retrieved under Electronic Supplementary Material.

Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy.

Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly understood. To establish nebulin's functional roles in adult muscle, we studied a novel conditional nebulin KO (Neb cKO) mouse model in which nebulin deletion was driven by the muscle creatine kinase (MCK) promotor. Neb cKO mice are born with high nebulin levels in their skeletal muscles, but within weeks after birth nebulin expression rapidly falls to barely detectable levels Surprisingly, a large fraction of the mice survive to adulthood with low nebulin levels (<5% of control), contain nemaline rods and undergo fiber-type switching toward oxidative types. Nebulin deficiency causes a large deficit in specific force, and mechanistic studies provide evidence that a reduced fraction of force-generating cross-bridges and shortened thin filaments contribute to the force deficit. Muscles rich in glycolytic fibers upregulate proteolysis pathways (MuRF-1, Fbxo30/MUSA1, Gadd45a) and undergo hypotrophy with smaller cross-sectional areas (CSAs), worsening their force deficit. Muscles rich in oxidative fibers do not have smaller weights and can even have hypertrophy, offsetting their specific-force deficit. These studies reveal nebulin as critically important for force development and trophicity in adult muscle. The Neb cKO phenocopies important aspects of NEM (muscle weakness, oxidative fiber-type predominance, variable trophicity effects, nemaline rods) and will be highly useful to test therapeutic approaches to ameliorate muscle weakness.

Light transmission spectroscopy in real time: a high-resolution nanoparticle analysis instrument.

This paper describes light transmission spectroscopy (LTS), a technique for eliminating spectral noise and systematic effects in real-time spectroscopic measurements. In our work, we combine LTS with spectral inversion for the purpose of nanoparticle analysis. This work employs a wideband multi-wavelength light source and grating spectrometers coupled to CCD detectors. The light source ranges from 210 to 2000 nm, the wavelength-dependent light detection system ranges from 200 to 1100 nm with ≤1 nm resolution, and the nanoparticle diameters range from 1 to 3000 nm. The nanoparticles are suspended in pure water or water-based buffer solutions. For testing and calibration purposes, results are presented for nanoparticles composed of polystyrene and gold. Mie theory is used to model the total extinction cross section, and spectral inversion is employed to obtain quantitative particle size distributions, from which information on the size, shape, and number of nanoparticles can be derived. Discussed are the precision, accuracy, resolution, and sensitivity of our results. The LTS technique is quite versatile and can be applied to spectroscopic investigations where wideband, accurate, low-noise, real-time spectra are desired.

Deleting titin's I-band/A-band junction reveals critical roles for titin in biomechanical sensing and cardiac function.

Titin, the largest protein known, forms a giant filament in muscle where it spans the half sarcomere from Z disk to M band. Here we genetically targeted a stretch of 14 immunoglobulin-like and fibronectin type 3 domains that comprises the I-band/A-band (IA) junction and obtained a viable mouse model. Super-resolution optical microscopy (structured illumination microscopy, SIM) and electron microscopy were used to study the thick filament length and titin's molecular elasticity. SIM showed that the IA junction functionally belongs to the relatively stiff A-band region of titin. The stiffness of A-band titin was found to be high, relative to that of I-band titin (∼ 40-fold higher) but low, relative to that of the myosin-based thick filament (∼ 70-fold lower). Sarcomere stretch therefore results in movement of A-band titin with respect to the thick filament backbone, and this might constitute a novel length-sensing mechanism. Findings disproved that titin at the IA junction is crucial for thick filament length control, settling a long-standing hypothesis. SIM also showed that deleting the IA junction moves the attachment point of titin's spring region away from the Z disk, increasing the strain on titin's molecular spring elements. Functional studies from the cellular to ex vivo and in vivo left ventricular chamber levels showed that this causes diastolic dysfunction and other symptoms of heart failure with preserved ejection fraction (HFpEF). Thus, our work supports titin's important roles in diastolic function and disease of the heart.

Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin.

Thin filament length (TFL) is an important determinant of the force-sarcomere length (SL) relation of cardiac muscle. However, the various mechanisms that control TFL are not well understood. Here we tested the previously proposed hypothesis that the actin-binding protein nebulin contributes to TFL regulation in the heart by using a cardiac-specific nebulin cKO mouse model (αMHC Cre Neb cKO). Atrial myocytes were studied because nebulin expression has been reported to be most prominent in this cell type. TFL was measured in right and left atrial myocytes using deconvolution optical microscopy and staining for filamentous actin with phalloidin and for the thin filament pointed-end with an antibody to the capping protein Tropomodulin-1 (Tmod1). Results showed that TFLs in Neb cKO and littermate control mice were not different. Thus, deletion of nebulin in the heart does not alter TFL. However, TFL was found to be ~0.05µm longer in the right than in the left atrium and Tmod1 expression was increased in the right atrium. We also tested the hypothesis that the length of titin's spring region is a factor controlling TFL by studying the Rbm20(ΔRRM) mouse which expresses titins that are ~500kDa (heterozygous mice) and ~1000kDa (homozygous mice) longer than in control mice. Results revealed that TFL was not different in Rbm20(ΔRRM) mice. An unexpected finding in all genotypes studied was that TFL increased as sarcomeres were stretched (~0.1µm per 0.35µm of SL increase). This apparent increase in TFL reached a maximum at a SL of ~3.0µm where TFL was ~1.05µm. The SL dependence of TFL was independent of chemical fixation or the presence of cardiac myosin-binding protein C (cMyBP-C). In summary, we found that in cardiac myocytes TFL varies with SL in a manner that is independent of the size of titin or the presence of nebulin.

Exome sequencing reveals a nebulin nonsense mutation in a dog model of nemaline myopathy.

Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches.

Discovery of the imidazole-derived GPR40 agonist AM-3189.

As a follow-up to the GPR40 agonist AMG 837, which was evaluated in clinical trials for the treatment of type II diabetes, further optimization led to the discovery of AM-3189 (13k). AM-3189 is representative of a new class of compounds with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837.

A Theoretical Design Approach for Passive Shimming of a Magic-Angle-Spinning NMR Magnet.

This paper presents a passive shimming design approach for a magic-angle-spinning (MAS) NMR magnet. In order to achieve a 1.5-T magic-angle field in NMR samples, we created two independent orthogonal magnetic vector fields by two separate coils: the dipole and solenoid. These two coils create a combined 1.5-T magnetic field vector directed at the magic angle (54.74° from the spinning axis). Additionally, the stringent magnetic field homogeneity requirement of the MAS magnet is the same as that of a solenoidal NMR magnet. The challenge for the magic-angle passive shimming design is to correct both the dipole and solenoid magnetic field spherical harmonics with one set of iron pieces, the so-called ferromagnetic shimming. Furthermore, the magnetization of the iron pieces is produced by both the dipole and solenoid coils. In our design approach, a matrix of 2 mm by 5 mm iron pieces with different thicknesses was attached to a thin-walled tube, 90-mm diameter and 40-mm high. Two sets of spherical harmonic coefficients were calculated for both the dipole and solenoid coil windings. By using the multiple-objective linear programming optimization technique and coordinate transformations, we have designed a passive shimming set that can theoretically reduce 22 lower-order spherical harmonics and improve the homogeneity of our MAS NMR magnet.

High-Resolution Magnetic Field Mapping System With an NMR Probe.

This paper presents a high-resolution magnetic field mapping system in development that is capable of collecting spatial magnetic field data for NMR magnets. An NMR probe was designed and built with a resonant frequency of 5.73 MHz. The measured Q-factor of the NMR probe is ~191 with a half-power bandwidth in the range of 5.72-5.75 MHz. An RF continuous-wave technique with magnetic field modulation was utilized to detect the power dispersion of water molecules. The zero-crossing frequency of the NMR dispersion signal corresponds to the magnetic field at the center of the water sample. An embedded system was developed to sweep the frequency and record the reflected RF power simultaneously. A numerically controlled digital oscillator is able to provide a precise frequency step as small as 0.02 Hz, which is equivalent to 4.7 e-7 mT for hydrogen atoms. An RF preamplifier was built to supply up to 4 W of RF power to a bidirectional coupler. The coupler supplies RF power to the NMR probe and channels reflect the RF power back to the detection circuit, which detects the reflected RF power from the NMR probe during the frequency sweep. The homogeneity of an NMR magnet can be determined by magnetic field data.