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Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) possess low sequence complexity of amino acids and display non-globular tertiary structures. They can act as scaffolds, form regulatory hubs, or trigger biomolecular condensation to control diverse aspects of biology. Emerging evidence has recently implicated critical roles of IDPs and IDR-contained proteins in nuclear transcription and cytoplasmic post-transcriptional processes, among other molecular functions. We here summarize the concepts and organizing principles of IDPs. We then illustrate recent progress in understanding the roles of key IDPs in machineries that regulate transcriptional and post-transcriptional gene silencing (PTGS) in plants, aiming at highlighting new modes of action of IDPs in controlling biological processes.
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Proteínas Intrinsicamente Desordenadas , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Plantas/genética , Plantas/metabolismo , Inativação Gênica , Conformação ProteicaRESUMO
Solid-state defects are attractive platforms for quantum sensing and simulation, e.g., in exploring many-body physics and quantum hydrodynamics. However, many interesting properties can be revealed only upon changes in the density of defects, which instead is usually fixed in material systems. Increasing the interaction strength by creating denser defect ensembles also brings more decoherence. Ideally one would like to control the spin concentration at will while keeping fixed decoherence effects. Here, we show that by exploiting charge transport, we can take some steps in this direction, while at the same time characterizing charge transport and its capture by defects. By exploiting the cycling process of ionization and recombination of NV centers in diamond, we pump electrons from the valence band to the conduction band. These charges are then transported to modulate the spin concentration by changing the charge state of material defects. By developing a wide-field imaging setup integrated with a fast single photon detector array, we achieve a direct and efficient characterization of the charge redistribution process by measuring the complete spectrum of the spin bath with micrometer-scale spatial resolution. We demonstrate a two-fold concentration increase of the dominant spin defects while keeping the T2 of the NV center relatively unchanged, which also provides a potential experimental demonstration of the suppression of spin flip-flops via hyperfine interactions. Our work paves the way to studying many-body dynamics with temporally and spatially tunable interaction strengths in hybrid charge-spin systems.
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Intrinsically disordered proteins (IDPs) SAID1/2 are hypothetic dentin sialophosphoprotein-like proteins, but their true functions are unknown. Here, we identified SAID1/2 as negative regulators of SERRATE (SE), a core factor in miRNA biogenesis complex (microprocessor). Loss-of-function double mutants of said1; said2 caused pleiotropic developmental defects and thousands of differentially expressed genes that partially overlapped with those in se. said1; said2 also displayed increased assembly of microprocessor and elevated accumulation of microRNAs (miRNAs). Mechanistically, SAID1/2 promote pre-mRNA processing 4 kinase A-mediated phosphorylation of SE, causing its degradation in vivo. Unexpectedly, SAID1/2 have strong binding affinity to hairpin-structured pri-miRNAs and can sequester them from SE. Moreover, SAID1/2 directly inhibit pri-miRNA processing by microprocessor in vitro. Whereas SAID1/2 did not impact SE subcellular compartmentation, the proteins themselves exhibited liquid-liquid phase condensation that is nucleated on SE. Thus, we propose that SAID1/2 reduce miRNA production through hijacking pri-miRNAs to prevent microprocessor activity while promoting SE phosphorylation and its destabilization in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas Intrinsicamente Desordenadas , MicroRNAs , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a RNA/metabolismo , Processamento Pós-Transcricional do RNA , MicroRNAs/metabolismo , Ribonuclease III/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Certain non-Hermitian systems exhibit the skin effect, whereby the wave functions become exponentially localized at one edge of the system. Such exponential amplification of wavefunction has received significant attention due to its potential applications in, e.g., classical and quantum sensing. However, the opposite edge of the system, featured by exponentially suppressed wave functions, remains largely unexplored. Leveraging this phenomenon, we introduce a non-Hermitian cooling mechanism, which is fundamentally distinct from traditional refrigeration or laser cooling techniques. Notably, non-Hermiticity will not amplify thermal excitations, but rather redistribute them. Hence, thermal excitations can be cooled down at one edge of the system, and the cooling effect can be exponentially enhanced by the number of auxiliary modes, albeit with a lower bound that depends on the dissipative interaction with the environment. Non-Hermitian cooling does not rely on intricate properties such as exceptional points or nontrivial topology, and it can apply to a wide range of excitations.
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Living active collectives have evolved with remarkable self-patterning capabilities to adapt to the physical and biological constraints crucial for their growth and survival. However, the intricate process by which complex multicellular patterns emerge from a single founder cell remains elusive. In this study, we utilize an agent-based model, validated through single-cell microscopy imaging, to track the three-dimensional (3D) morphodynamics of cells within growing bacterial biofilms encased by agarose gels. The confined growth conditions give rise to a spatiotemporally heterogeneous stress landscape within the biofilm. In the core of the biofilm, where high hydrostatic and low shear stresses prevail, cell packing appears disordered. In contrast, near the gel-cell interface, a state of high shear stress and low hydrostatic stress emerges, driving nematic ordering, albeit with a time delay inherent to shear stress relaxation. Strikingly, we observe a robust spatiotemporal correlation between stress anisotropy and nematic ordering within these confined biofilms. This correlation suggests a mechanism whereby stress anisotropy plays a pivotal role in governing the spatial organization of cells. The reciprocity between stress anisotropy and cell ordering in confined biofilms opens new avenues for innovative 3D mechanically guided patterning techniques for living active collectives, which hold significant promise for a wide array of environmental and biomedical applications.
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Biofilmes , Estresse Mecânico , Anisotropia , Modelos BiológicosRESUMO
The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.
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Osteogênese , Fosfatidilinositol 3-Quinases , Ratos , Animais , Nanogéis , Osso e Ossos/diagnóstico por imagem , Hidrogéis/farmacologiaRESUMO
In this paper, the Cu and Ni accumulation and contamination levels in agricultural soils and wheat around a smelter in Jinchang City in northwest China were investigated with a combination of field investigations and indoor analytical tests, using a soil-wheat system as the study area. The average Cu and Ni contents in the soil were 119.50 mg kg-1 and 123.40 mg kg-1, respectively, both of which exceeded the local soil background values. The Cu and Ni contents in 46.15% o and 26.92% of sampling sites, respectively, exceeded the screening values for soil contamination risk in agricultural land in China. The average Cu content in different parts of wheat was in the order of roots (24.22 mg kg-1) > leaves (20.11 mg kg-1) > husks (5.51 mg kg-1) > grains (4.05 mg kg-1) > stalks (3.74 mg kg-1). Furthermore, the average Ni content ranked as leaves (24.64 mg kg-1) > roots (21.12 mg kg-1) > husks (6.95 mg kg-1) > stalks (1.75 mg kg-1) > grains (0.38 mg kg-1). The health risk evaluation showed that with average hazard index values of 0.88 for adults and 1.04 for children for Cu and Ni in wheat grain, wheat in this region is unlikely to pose a health risk to adults but may pose a lesser health risk to children. The Ni bio-concentration and translocation factors in the husk and leaves of wheat were greater than those of Cu and smaller than those of Cu in the other parts of wheat. The results of this study provide basic data for the remediation of heavy metal contamination in local agricultural soils.
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Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Solo , Triticum , Metais Pesados/análise , Agricultura , China , Medição de Risco , Poluentes do Solo/análise , Monitoramento Ambiental/métodosRESUMO
OBJECTIVES: To explore the clinical application of orbital fat fascia flap in the correction of sunken upper eyelid in Asian blepharoplasty based on anatomical and histological research. METHODS: Observe the histological structure of the orbital fat and its fascia vascularity through cadaver anatomy and histological sections of 10 cadavers. Based on the anatomical and histological characteristics of orbital fat, 36 patients with mild to moderate sunken upper eyelids were corrected by transposition of orbital fat fascia flap with preservation of fascia vascular pedicle. During the operation, the lateral part of the central cellulite of orbital fat was separated longitudinally and transferred to the sunken place to correct the sunken upper eyelid. RESULTS: Anatomy and histology show that the orbital fat was located between the anterior layer of the levator aponeurosis and the posterior layer of the orbital septum and was separated into fat lobules by many fibrous septa. The blood vessels move forward from back to front along the orbital fat interlobular septum, and the blood vessels in the capsule below the orbital fat are abundant. Clinical results showed that the shape of the sunken upper eyelid was significantly improved in 35 cases after correction with this method during the postoperative follow-up from 9 months to 18 months. The mean sunken depth improved from 6.2mm (±1.0 mm) preoperatively to 2.2mm (±0.9 mm) at the last follow-up with a statistical significance. And only 1 case had partial depression in the unilateral eyelid and received autologous granular fat transplantation with satisfactory postoperative results. CONCLUSION: The transposition of orbital fat fascia flap with longitudinal separation and preservation of fascia vascular pedicle can better correct the sunken upper eyelid during blepharoplasty, and the long-term effect is stable, which is worthy of clinical promotion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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RNA helicases (RHs) are a family of ubiquitous enzymes that alter RNA structures and remodel ribonucleoprotein complexes typically using energy from the hydrolysis of ATP. RHs are involved in various aspects of RNA processing and metabolism, exemplified by transcriptional regulation, pre-mRNA splicing, miRNA biogenesis, liquid-liquid phase separation, and rRNA biogenesis, among other molecular processes. Through these mechanisms, RHs contribute to vegetative and reproductive growth, as well as abiotic and biotic stress responses throughout the life cycle in plants. In this review, we systematically characterize RH-featured domains and signature motifs in Arabidopsis. We also summarize the functions and mechanisms of RHs in various biological processes in plants with a focus on DEAD-box and DEAH-box RNA helicases, aiming to present the latest understanding of RHs in plant biology.
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Proteínas de Arabidopsis , Arabidopsis , RNA Helicases DEAD-box/genética , Plantas/genética , Plantas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Splicing de RNARESUMO
The initialization of nuclear spin to its ground state is challenging due to its small energy scale compared with thermal energy, even at cryogenic temperature. In this Letter, we propose an optonuclear quadrupolar effect, whereby two-color optical photons can efficiently interact with nuclear spins. Leveraging such an optical interface, we demonstrate that nuclear magnons, the collective excitations of nuclear spin ensemble, can be cooled down optically. Under feasible experimental conditions, laser cooling can suppress the population and entropy of nuclear magnons by more than 2 orders of magnitude, which could facilitate the application of nuclear spins in quantum information science.
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The growing demands of remote detection and an increasing amount of training data make distributed machine learning under communication constraints a critical issue. This work provides a communication-efficient quantum algorithm that tackles two traditional machine learning problems, the least-square fitting and softmax regression problems, in the scenario where the dataset is distributed across two parties. Our quantum algorithm finds the model parameters with a communication complexity of O(log_{2}(N)/ε), where N is the number of data points and ε is the bound on parameter errors. Compared to classical and other quantum methods that achieve the same goal, our methods provide a communication advantage in the scaling with data volume. The core of our methods, the quantum bipartite correlator algorithm that estimates the correlation or the Hamming distance of two bit strings distributed across two parties, may be further applied to other information processing tasks.
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Solid-state spin defects, especially nuclear spins with potentially achievable long coherence times, are compelling candidates for quantum memories and sensors. However, their current performances are still limited by dephasing due to variations of their intrinsic quadrupole and hyperfine interactions. We propose an unbalanced echo to overcome this challenge by using a second spin to refocus variations of these interactions while preserving the quantum information stored in the nuclear spin free evolution. The unbalanced echo can be used to probe the temperature and strain distribution in materials. We develop first-principles methods to predict variations of these interactions and reveal their correlation over large temperature and strain ranges. Experiments performed in an ensemble of â¼10^{10} nuclear spins in diamond demonstrate a 20-fold dephasing time increase, limited by other noise sources. We further numerically show that our method can refocus even stronger noise variations than present in our experiments.
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In this work, we systematically study an immiscible binary system undergoing thermal/photo reversible reactions in theory. For the thermal reaction case, no dissipative structures can be formed and only uniform equilibrium states are observed but the dynamical evolution to these trivial states witnesses a new type of sophisticated phase amplification phenomenon-temporary phase separation (TPS). Linear analysis and light-scattering calculations confirm that TPS is predominated either by spinodal decomposition or nucleation and growth mechanism, or by both successively. For the photo reaction case, steady dissipative patterns exist and are maintained by the external energy input of lights. Linear analysis together with simulations reveals that the characteristic wavelength (ξ) of these structures shortens as the input energy density increases and they obey the relation of ln ξâ 1/Tb with Tb the effective temperature of lights. The TPS phenomenon and length-scale dependency of dissipative patterns observed in this simple binary system might have rich implications for the non-equilibrium thermodynamics of biological systems.
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OBJECTIVES: To explore the effect of surgery combined with platelet-rich plasma (PRP) in the correction of mild to moderate blepharoptosis. METHODS: A retrospective study was conducted on 36 patients with bilateral mild to moderate blepharoptosis from January 2021 to January 2023, which were corrected by surgery combined with local multi-point injection of PRP. The postoperative effect was observed, and the incidence of postoperative complications and patient satisfaction were calculated. RESULTS: Postoperative follow-up was 3 months to 2 years. Thirty-five cases of blepharoptosis were well corrected; 1 case (2.8%) had insufficient correction and was corrected by reoperation. There were no obvious complications such as incomplete closure, conjunctival prolapse, and exposed keratitis in 36 patients. All patients were satisfied. CONCLUSION: Surgery combined with PRP is effective in the correction of mild to moderate blepharoptosis with few complications and high satisfaction. As far as we know, this is the first time to apply PRP in the correction of blepharoptosis, which may provide a new idea for the clinical treatment of blepharoptosis and is worth popularizing.
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Blefaroplastia , Blefaroptose , Plasma Rico em Plaquetas , Humanos , Blefaroptose/cirurgia , Estudos Retrospectivos , Músculos Oculomotores/cirurgia , Resultado do TratamentoRESUMO
The development of highly sensitive and rapid biosensing tools targeted to the highly contagious virus SARS-CoV-2 is critical to tackling the COVID-19 pandemic. Quantum sensors can play an important role because of their superior sensitivity and fast improvements in recent years. Here we propose a molecular transducer designed for nitrogen-vacancy (NV) centers in nanodiamonds, translating the presence of SARS-CoV-2 RNA into an unambiguous magnetic noise signal that can be optically read out. We evaluate the performance of the hybrid sensor, including its sensitivity and false negative rate, and compare it to widespread diagnostic methods. The proposed method is fast and promises to reach a sensitivity down to a few hundreds of RNA copies with false negative rate less than 1%. The proposed hybrid sensor can be further implemented with different solid-state defects and substrates, generalized to diagnose other RNA viruses, and integrated with CRISPR technology.
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COVID-19 , Diamante , Humanos , Nitrogênio , Pandemias , RNA Viral , SARS-CoV-2RESUMO
This work is devoted to deriving the entropy of a single photon in a beam of light from first principles. Based on the quantum processes of light-matter interaction, we find that, if the light is not in equilibrium, there are two different ways, depending on whether the photon is being added or being removed from the light, of defining the single-photon entropy of this light. However, when the light is in equilibrium at temperature T, the two definitions are equivalent and the photon entropy of this light is hν/T. From first principles, we also re-derive the Jüttner velocity distribution showing that, even without interatomic collisions, two-level atoms will relax to the state satisfying the Maxwell-Jüttner velocity distribution when they are moving in blackbody radiation fields.
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The majority of the genome is transcribed to RNA in living organisms. RNA transcripts can form astonishing arrays of secondary and tertiary structures via Watson-Crick, Hoogsteen, or wobble base pairing. In vivo, RNA folding is not a simple thermodynamic event of minimizing free energy. Instead, the process is constrained by transcription, RNA-binding proteins, steric factors, and the microenvironment. RNA secondary structure (RSS) plays myriad roles in numerous biological processes, such as RNA processing, stability, transportation, and translation in prokaryotes and eukaryotes. Emerging evidence has also implicated RSS in RNA trafficking, liquid-liquid phase separation, and plant responses to environmental variations such as temperature and salinity. At molecular level, RSS is correlated with splicing, polyadenylation, protein synthesis, and miRNA biogenesis and functions. In this review, we summarize newly reported methods for probing RSS in vivo and functions and mechanisms of RSS in plant physiology.
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Processamento Pós-Transcricional do RNA , RNA , Pareamento de Bases , Biologia , Conformação de Ácido Nucleico , RNA/metabolismo , Splicing de RNA , RNA de Plantas/genética , RNA de Plantas/metabolismoRESUMO
Periodically driven (Floquet) quantum systems have recently been a focus of nonequilibrium physics by virtue of their rich dynamics. Time-periodic systems not only exhibit symmetries that resemble those in spatially periodic systems, but also display novel behavior that arises from symmetry breaking. Characterization of such dynamical symmetries is crucial, but often challenging due to limited driving strength and lack of an experimentally accessible characterization technique. Here, we show how to reveal dynamical symmetries, namely, parity, rotation, and particle-hole symmetries, by observing symmetry-induced Floquet selection rules. Notably, we exploit modulated driving to reach the strong light-matter coupling regime, and we introduce a protocol to experimentally extract the transition matrix elements between Floquet states from the system coherent evolution. By using nitrogen-vacancy centers in diamond as an experimental test bed, we execute our protocol to observe symmetry-protected dark states and dark bands, and coherent destruction of tunneling. Our work shows how one can exploit the quantum control toolkit to study dynamical symmetries that arise in the topological phases of strongly driven Floquet systems.
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Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Antagonistas de Estrogênios/síntese química , Antagonistas de Estrogênios/química , Receptor alfa de Estrogênio/metabolismo , Feminino , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/químicaRESUMO
Sensing the local environment through the motional response of small molecules lays the foundation of many fundamental technologies. The information on local viscosity, for example, is contained in the random rotational Brownian motions of molecules. However, detection of the motions is challenging for molecules with sub-nanometer scale or high motional rates. Here we propose and experimentally demonstrate a novel method of detecting fast rotational Brownian motions of small magnetic molecules. With electronic spins as sensors, we are able to detect changes in motional rates, which yield different noise spectra and therefore different relaxation signals of the sensors. As a proof-of-principle demonstration, we experimentally implemented this method to detect the motions of gadolinium (Gd) complex molecules with nitrogen-vacancy (NV) centers in nanodiamonds. With all-optical measurements of the NV centers' longitudinal relaxation, we distinguished binary solutions with varying viscosities. Our method paves a new way for detecting fast motions of sub-nanometer sized magnetic molecules with better spatial resolution than conventional optical methods. It also provides a new tool in designing better contrast agents in magnetic resonance imaging.