Robust conversion of singlet spin order in coupled spin-1/2 pairs by adiabatically switched RF-fields

We propose a robust and highly efficient NMR technique to create singlet spin order from longitudinal spin magnetization in coupled spin-1/2 pairs and to perform backward conversion (singlet order)$\to$magnetization. In this method we exploit adiabatic switching of an RF-field in order to drive transitions between the singlet state and the $T_\pm$ triplet states of a spin pair under study. We demonstrate that the method works perfectly for both strongly and weakly coupled spin pairs, providing a conversion efficiency between the singlet spin order and magnetization, which is equal to the theoretical maximum. We anticipate that the proposed technique is useful for generating long-lived singlet order, for preserving spin hyperpolarization and for assessing singlet spin order in nearly equivalent spin pairs in specially designed molecules and in low-field NMR studies.Comment: 21 pages, 11 figure

Non-thermal nuclear magnetic resonance quantum computing using hyperpolarized Xenon

Current experiments in liquid-state nuclear magnetic resonance quantum computing are limited by low initial polarization. To address this problem, we have investigated the use of optical pumping techniques to enhance the polarization of a 2-qubit NMR quantum computer (13C and 1H in 13CHCl3). To efficiently use the increased polarization, we have generalized the procedure for effective pure state preparation. With this new, more flexible scheme, an effective pure state was prepared with polarization-enhancement of a factor of 10 compared to the thermal state. An implementation of Grover's quantum search algorithm was demonstrated using this new technique.Comment: 4 pages, 3 figures. Submitted for publicatio

Transfer of Parahydrogen Induced Polarization in Scalar Coupled Systems at Variable Magnetic Field

Para-Hydrogen Induced Polarization (PHIP) experiments were performed in coupled multispin systems at variable magnetic fields. We studied the magnetic field dependence of PHIP in styrene, which is the product of hydrogenation of phenylacetylene. At low magnetic fields where the spins are coupled strongly by scalar interaction efficient polarization transfer among the interacting protons takes place. The experimentally observed spectra are in good agreement with the simulation, which takes into account eight coupled spins. We also demonstrate effects of nuclear spin level anti-crossings on the PHIP pattern. It is shown that rapid passage through the level anti-crossing enables highly efficient polarization transfer between specific spin orders. In addition, we studied PHIP transfer to 13C and 19F hetero-nuclei. It is shown that hetero- nuclei can be efficiently polarized in a wide field range; in particular, for polarizing them it is not necessary to go to ultra-low fields, which provide their strong coupling to protons. The resulting polarization is of the multiplet type and gives strong enhancements of the individual NMR lines. In general, variation of the magnetic field gives the opportunity for manipulating PHIP patterns and transferring polarization to target spins of choice

Generating and sustaining long-lived spin states in 15N,15N′-azobenzene

Long-Lived spin States (LLSs) hold a great promise for sustaining non-thermal spin order and investigating various slow processes by Nuclear Magnetic Resonance (NMR) spectroscopy. Of special interest for such application are molecules containing nearly equivalent magnetic nuclei, which possess LLSs even at high magnetic fields. In this work, we report an LLS in trans-15N,15N′-azobenzene. The singlet state of the 15N spin pair exhibits a long-lived character. We solve the challenging problem of generating and detecting this LLS and further increase the LLS population by converting the much higher magnetization of protons into the 15N singlet spin order. As far as the longevity of this spin order is concerned, various schemes have been tested for sustaining the LLS. Lifetimes of 17 minutes have been achieved at 16.4 T, a value about 250 times longer than the longitudinal relaxation time of 15N in this magnetic field. We believe that such extended relaxation times, along with the photochromic properties of azobenzene, which changes conformation upon light irradiation and can be hyperpolarized by using parahydrogen, are promising for designing new experiments with photo-switchable long-lived hyperpolarization

Exploiting adiabatically switched RF-field for manipulating spin hyperpolarization induced by parahydrogen

A method for precise manipulation of non-thermal nuclear spin polarization by switching a RF-field is presented. The method harnesses adiabatic correlation of spin states in the rotating frame. A detailed theory behind the technique is outlined; examples of two-spin and three-spin systems prepared in a non- equilibrium state by Para-Hydrogen Induced Polarization (PHIP) are considered. We demonstrate that the method is suitable for converting the initial multiplet polarization of spins into net polarization: compensation of positive and negative lines in nuclear magnetic resonance spectra, which is detrimental when the spectral resolution is low, is avoided. Such a conversion is performed for real two-spin and three-spin systems polarized by means of PHIP. Potential applications of the presented technique are discussed for manipulating PHIP and its recent modification termed signal amplification by reversible exchange as well as for preparing and observing long-lived spin states

Splicing factor ESRP1 controls ER-positive breast cancer by altering metabolic pathways

The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels of ESRP1, but not ESRP2, are associated with poor prognosis in estrogen receptor positive (ER+) breast tumors. Knockdown of ESRP1 in endocrine-resistant breast cancer models decreases growth significantly and alters the EMT splicing signature, which we confirm using TCGA SpliceSeq data of ER+ BRCA tumors. However, these changes are not accompanied by the development of a mesenchymal phenotype or a change in key EMT-transcription factors. In tamoxifen-resistant cells, knockdown of ESRP1 affects lipid metabolism and oxidoreductase processes, resulting in the decreased expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH) at both the mRNA and protein levels. Furthermore, ESRP1 knockdown increases the basal respiration and spare respiration capacity. This study reports a novel role for ESRP1 that could form the basis for the prevention of tamoxifen resistance in ER+ breast cancer

Manipulating spin hyper-polarization by means of adiabatic switching of a spin-locking RF-field

We propose a technique for transferring the multiplet spin polarization (CIDNP or PHIP, or one created by any other method), which is the mutual entanglement of spins, into net hyper-polarization with respect to the direction of a high magnetic field by slowly (adiabatically) switching-off a strong external RF- field with a specially selected frequency. The net hyper-polarized molecules can then be used in NMR spectroscopy or imaging for strong signal enhancement

cis Versus trans-Azobenzene: Precise Determination of NMR Parameters and Analysis of Long-Lived States of 15N Spin Pairs

We provide a detailed evaluation of nuclear magnetic resonance (NMR) parameters of the cis- and trans-isomers of azobenzene (AB). For determining the NMR parameters, such as proton–proton and proton–nitrogen J-couplings and chemical shifts, we compared NMR spectra of three different isotopomers of AB: the doubly 15N labeled azobenzene, 15N,15N′-AB, and two partially deuterated AB isotopomers with a single 15N atom. For the total lineshape analysis of NMR spectra, we used the recently developed ANATOLIA software package. The determined NMR parameters allowed us to optimize experiments for investigating singlet long-lived spin states (LLSs) of 15N spin pairs and to measure LLS lifetimes in cis-AB and trans-AB. Magnetization-to-singlet-to-magnetization conversion has been performed using the SLIC and APSOC techniques, providing a degree of conversion up to 17 and 24% of the initial magnetization, respectively. Our approach is useful for optimizing the performance of experiments with singlet LLSs; such LLSs can be exploited for preserving spin hyperpolarization, for probing slow molecular dynamics, slow chemical processes and also slow transport processes

Dynamic nuclear polarization at high magnetic fields in liquids

High field dynamic nuclear polarization spectrometer for liquid samples have been constructed. ► The field dependence of the Overhauser DNP efficiency has been measured for the first time up to 9.2 T. ► High DNP enhancements for liquid samples have been observed at high magnetic fields. ► The enhancements have been compared with results from NMRD, MD and theoretical models. ► Coherent and relaxation effects within fast magnetic field changes have been analyzed

Higher bone resorption excretion in South Asian women vs. White Caucasians and increased bone loss with higher seasonal cycling of vitamin D: Results from the D-FINES cohort study

Few data exist on bone turnover in South Asian women and it is not well elucidated as to whether Western dwelling South Asian women have different bone resorption levels to that of women from European ethnic backgrounds. This study assessed bone resorption levels in UK dwelling South Asian and Caucasian women as well as evaluating whether seasonal variation in 25-hydroxyvitamin D [25(OH)D] is associated with bone resorption in either ethnic group. Data for seasonal measures of urinary N-telopeptide of collagen (uNTX) and serum 25(OH)D were analysed from n = 373 women (four groups; South Asian postmenopausal n = 44, South Asian premenopausal n = 50, Caucasian postmenopausal n = 144, Caucasian premenopausal n = 135) (mean (± SD) age 48 (14) years; age range 18–79 years) who participated in the longitudinal D-FINES (Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England) cohort study (2006–2007). A mixed between-within subjects ANOVA (n = 192) showed a between subjects effect of the four groups (P < 0.001) on uNTX concentration, but no significant main effect of season (P = 0.163). Bonferroni adjusted Post hoc tests (P ≤ 0.008) suggested that there was no significant difference between the postmenopausal Asian and premenopausal Asian groups. Season specific age-matched-pairs analyses showed that in winter (P = 0.04) and spring (P = 0.007), premenopausal Asian women had a 16 to 20 nmol BCE/mmol Cr higher uNTX than premenopausal Caucasian women. The (amplitude/mesor) ratio (i.e. seasonal change) for 25(OH)D was predictive of uNTX, with estimate (SD) = 0.213 (0.015) and 95% CI (0.182, 0.245; P < 0.001) in a non-linear mixed model (n = 154). This showed that individuals with a higher seasonal change in 25(OH)D, adjusted for overall 25(OH)D concentration, showed increased levels of uNTX. Although the effect size was smaller than for the amplitude/mesor ratio, the mesor for 25(OH)D concentration was also predictive of uNTX, with estimate (SD) = − 0.035 (0.004), and 95% CI (− 0.043, − 0.028; P < 0.001). This study demonstrates higher levels of uNTX in premenopausal South Asian women than would be expected for their age, being greater than same-age Caucasian women, and similar to postmenopausal Asian women. This highlights potentially higher than expected bone resorption levels in premenopausal South Asian women which, if not offset by concurrent increased bone formation, may have future clinical and public health implications which warrant further investigation. Individuals with a larger seasonal change in 25(OH)D concentration showed an increased bone resorption, an association which was larger than that of the 25(OH)D yearly average, suggesting it may be as important clinically to ensure a stable and steady 25(OH)D concentration, as well as one that is high enough to be optimal for bone health