cpmg

We present an experimental study of the coherence properties of a single heavy-hole spin qubit formed in one quantum dot of a gated GaAs/AlGaAs double quantum dot device. We use a modified spin-readout latching technique in which the second quantum dot serves both as an auxiliary element for a fast spin-dependent readout within a 200 ns time window and as a register for storing the spin-state information. To manipulate the single-spin qubit, we apply sequences of microwave bursts of various amplitudes and durations to make Rabi, Ramsey, Hahn-echo, and CPMG measurements...

Chronic kidney disease (CKD) is the end point of a number of systemic chronic diseases. The prevalence of CKD is increasing worldwide and recent epidemiological studies are showing the high prevalence of renal failure in CKD patients using complementary and alternative medicines (CAMs). Clinicians believe that biochemical profiles of CKD patients using CAM (referred here to as CAM-CKD) may be different compared to those on standard clinical treatment and should be managed differently. The present study aims to explore the potential of the NMR-based metabolomics approach to reveal the serum metabolic disparity between CKD and CAM-CKD patients with respect to normal control (NC) subjects and if the differential metabolic patterns can provide rationale for the efficacy and safety of standard and/or alternative therapies...

Slow conformational changes are often directly linked to protein function. It is however less clear how such processes may perturb the overall folding stability of a protein. We previously found that the stabilizing double mutant L49I/I57V in the small protein chymotrypsin inhibitor 2 from barley led to distributed increased nanosecond and faster dynamics. Here we asked what effects the L49I and I57V substitutions, either individually or together, have on the slow conformational dynamics of CI2. We used 15 N CPMG spin relaxation dispersion experiments to measure the kinetics, thermodynamics and structural changes associated with slow conformational change in CI2...

14-3-3σ protein is one of the seven isoforms from the highly conserved eukaryotic 14-3-3 protein family. Downregulation of 14-3-3σ expression has been observed in various tumors. TRIM25 is responsible for the proteolytic degradation of 14-3-3σ, in which abrogation of TRIM25 suppressed tumor growth through 14-3-3σ upregulation. However, to date, the exact 14-3-3σ interacting residues of TRIM25 have yet to be resolved. Thus, this study attempts to identify the peptide binding sequence of TRIM25 on 14-3-3σ via both bioinformatics and biophysical techniques...

Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme responsible for the regulation of key human oncoproteins and tumor suppressors including Mdm2 and p53, respectively. Unlike other members of the USP family of proteases, the isolated catalytic domain of USP7 adopts an enzymatically inactive conformation that has been well characterized using X-ray crystallography. The catalytic domain also samples an active conformation, which has only been captured upon USP7 substrate-binding. Here, we utilized CPMG NMR relaxation dispersion studies to observe the dynamic motions of USP7 in solution...

The evolutionary role of conformational exchange in the emergence and preservation of function within structural homologs remains elusive. While protein engineering has revealed the importance of flexibility in function, productive modulation of atomic-scale dynamics has only been achieved on a finite number of distinct folds. Allosteric control of unique members within dynamically diverse structural families requires a better appreciation of exchange phenomena. Here, we examined the functional and structural role of conformational exchange within eosinophil-associated ribonucleases...

Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited to study the dynamics of biomolecules in solution. Most NMR studies exploit the spins of proton, carbon and nitrogen isotopes, as these atoms are highly abundant in proteins and nucleic acids. As an alternative and complementary approach, fluorine atoms can be introduced into biomolecules at specific sites of interest. These labels can then be used as sensitive probes for biomolecular structure, dynamics or interactions. Here, we address if the replacement of tryptophan with 5-fluorotryptophan residues has an effect on the overall dynamics of proteins and if the introduced fluorine probe is able to accurately report on global exchange processes...

In order to improve the efficiency of Soxhlet extraction and oven drying, low-field nuclear magnetic resonance (LF-NMR) technology was used to detect fat and moisture contents in pork. The transverse relaxation time (T2 ) distribution curves were constructed by Carr-Purcell-Meiboom-Gill (CPMG) experiments. In addition, the optimal conditions of adding MnCl2 aqueous solution was explored to separate water and fat signal peaks. Finally, the reliability of this method for the determination of fat and moisture contents in pork was verified...

The porosity of differently wetted carbonaceous material with disordered mesoporosity was investigated using low-field 1 H NMR relaxometry. Spin-spin relaxation (relaxation time T 2 ) was measured using the CPMG pulse sequence. We present a non-linear optimization method for the conversion of relaxation curves to the distribution of relaxation times by using non-specialized software. Our procedure consists of searching for the number of components, relaxation times, and their amplitudes, related to different types of hydrogen nuclei in the sample wetted with different amounts of water (different water-to-carbon ratio)...

NMR spectroscopy is an inherently insensitive technique with respect to the amount of observable signal. A common element in all NMR spectra is random thermal noise that is often characterized by a signal-to-noise ratio (SNR). SNR can be generically improved experimentally with repetitive signal averaging or during post-processing with apodization; the former of which often results in long experimental times and the latter results in the loss of spectral resolution. Denoising techniques can instead be used during post-processing to enhance SNR without compromising resolution...

Given the central role of conformational dynamics in protein function, it is essential to characterize the time scales and structures associated with these transitions. High pressure (HP) perturbation favors transitions to excited states because they typically occupy a smaller molar volume, thus facilitating characterization of conformational dynamics. Repeat proteins, with their straightforward architecture, provide good models for probing the sequence dependence of protein conformational dynamics. Investigations of chemical exchange by 15 N CPMG relaxation dispersion analysis revealed that introduction of a cavity via substitution of isoleucine 7 by alanine in the N-terminal capping motif of the pp32 leucine-rich repeat protein leads to pressure-dependent conformational exchange detected on the 500 μs-2 ms CPMG time scale...

Degenerate spin-systems consisting of magnetically equivalent nuclear spins, such as a 1 H3 spin-system in selectively 13 CH3 -labeled proteins, present considerable challenges for the design of Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiments to characterize chemical exchange on the micro-to-millisecond time-scale. Several approaches have been previously proposed for the elimination of deleterious artifacts observed in methyl 1 H CPMG relaxation dispersion profiles obtained for (13 C)1 H3 groups...

BACKGROUND: We previously showed that metabolomics predicts relapse in early breast cancer (eBC) patients, unselected by age. This study aims to identify a "metabolic signature" that differentiates eBC from advanced breast cancer (aBC) patients, and to investigate its potential prognostic role in an elderly population. METHODS: Serum samples from elderly breast cancer (BC) patients enrolled in 3 onco-geriatric trials, were retrospectively analyzed via proton nuclear magnetic resonance (1H NMR) spectroscopy...

Calgranulin C performs antimicrobial activity in the human immune response by sequestering Zn(II). This biological function is afforded with the aid of two structurally distinct Ca(II)-binding EF hand motifs, wherein one of which bears an unusual amino acid sequence. Here, we utilize solution state NMR relaxation measurements to investigate the mechanism of Ca(II)-modulated enhancement of Zn(II) sequestration by calgranulin C. Using C13 /N15 CPMG dispersion experiments we have measured pH-dependent major and minor state populations exchanging on micro-to-millisecond timescale...

Earlier diagnosis of non-alcoholic fatty liver disease (NAFLD) is important to prevent disease progression. Recently, a low-cost portable MR system was been developed as a point-of-care screening tool for in vivo liver fat quantification. However, subcutaneous fat may confound the liver fat quantification, particularly in the NAFLD population. In this work, we propose a novel RF coil design composed of a set of "saturation" coils sandwiching a main coil to improve human liver fat quantification. By comparison with conventional MRI, we demonstrate the capability and effectiveness of the novel RF coil design in phantom experiments as well as in vivo liver scans...

Human thymidylate synthase (hTS) is essential for DNA replication and therefore a therapeutic target for cancer. Effective targeting requires knowledge of the mechanism(s) of regulation of this 72 kDa homodimeric enzyme. Here, we investigate the mechanism of binding cooperativity of the nucleotide substrate. We have employed exquisitely sensitive methyl-based CPMG and CEST NMR experiments enabling us to identify residues undergoing bifurcated linear 3-state exchange, including concerted switching between active and inactive conformations in the apo enzyme...

Since recovery time of the RF coil is long at low field MRI, the rising and the ring-down times of the square pulse are also long, which means the applied sinc pulse can easily be distorted from the changing amplitude. However, both the rising time and ring-down time can be calculated using Q-factor. Using this information, an RF square pulse were compensated by appending two square pulses before and after the RF pulse. The durations of these RF square pulses were calculated using the Q-factor. Since the amplitude of the sinc pulse changes continuously, a series of square pulses were applied to apply sinc pulse to the coil...

The rise of antimicrobial resistance remains one of the greatest global health threats facing humanity. Furthermore, the development of novel antibiotics has all but ground to a halt due to a collision of intersectional pressures. Herein we determine the antimicrobial efficacy for 14 structurally related supramolecular self-associating amphiphiles against clinically relevant Gram-positive methicillin resistant Staphylococcus aureus and Gram-negative Escherichia coli . We establish the ability of these agents to selectively target phospholipid membranes of differing compositions, through a combination of computational host:guest complex formation simulations, synthetic vesicle lysis, adhesion and membrane fluidity experiments, alongside our novel 1 H NMR CPMG nanodisc coordination assays, to verify a potential mode of action for this class of compounds and enable the production of evermore effective next-generation antimicrobial agents...

Magnetic resonance imaging (MRI) has become one of the most important medical imaging techniques in the clinic due to its high degree of soft tissue resolution and no radiation damage, and it plays an important role in the early diagnosis and treatment of tumors. This article mainly studies the analysis of no-reflow in patients with acute ST-segment elevation myocardial infarction after PCI and the effect of coronary nicorandil on CoO nanoparticles combined with MRI. In this paper, the synthesized water-soluble nanoparticles are dispersed in a 2% xanthan gum or agarose solution...

PURPOSE: We develop and test a parallel transmit (pTx) pulse design framework to mitigate transmit field inhomogeneity with control of local specific absorption rate (SAR) in 2D rapid acquisition with relaxation enhancement (RARE) imaging at 7T. METHODS: We design large flip angle RF pulses with explicit local SAR constraints by numerical simulation of the Bloch equations. Parallel computation and analytical expressions for the Jacobian and the Hessian matrices are employed to reduce pulse design time...