Enhanced Resolution in Nanoscale NMR via Quantum Sensing with Pulses of Finite Duration

The nitrogen-vacancy (N-V) color center in diamond is an enormously important platform for the development of quantum sensors, including for single-spin and single-molecule NMR. Detection of weak single-spin signals is greatly enhanced by repeated sequences of microwave pulses; in these dynamicaldecoupling techniques, the key control parameters swept in the experiment are the time intervals, τ, between pulses. Here, we show that, in fact, the pulse duration tp offers a powerful additional control parameter. While a non-negligible tp was previously considered simply a source of experimental error, we elucidate here the underlying quantum dynamics: we identify a landscape of quantum-state crossings which are usually inactive (closed) but may be controllably activated (opened) by adjusting tp from zero. We identify these crossings with recently observed but unexpected dips (so-called spurious dips) seen in the quantum coherence of the N-V spin. With this new understanding, both the position and the strength of these sharp features may be accurately controlled; they coexist with the usual broader coherence dips of short-duration microwave pulses, but their sharpness allows for higher-resolution spectroscopy with quantum diamond sensors, or their analogs

Enhanced Resolution in Nanoscale NMR via Quantum Sensing with Pulses of Finite Duration

The nitrogen-vacancy (N-V) color center in diamond is an enormously important platform for the development of quantum sensors, including for single-spin and single-molecule NMR. Detection of weak single-spin signals is greatly enhanced by repeated sequences of microwave pulses; in these dynamicaldecoupling techniques, the key control parameters swept in the experiment are the time intervals, τ, between pulses. Here, we show that, in fact, the pulse duration tp offers a powerful additional control parameter. While a non-negligible tp was previously considered simply a source of experimental error, we elucidate here the underlying quantum dynamics: we identify a landscape of quantum-state crossings which are usually inactive (closed) but may be controllably activated (opened) by adjusting tp from zero. We identify these crossings with recently observed but unexpected dips (so-called spurious dips) seen in the quantum coherence of the N-V spin. With this new understanding, both the position and the strength of these sharp features may be accurately controlled; they coexist with the usual broader coherence dips of short-duration microwave pulses, but their sharpness allows for higher-resolution spectroscopy with quantum diamond sensors, or their analogs

Rapid covariance-based sampling of linear SPDE approximations in the multilevel Monte Carlo method

The efficient simulation of the mean value of a non-linear functional of the solution to a linear stochastic partial differential equation (SPDE) with additive Gaussian noise is considered. A Galerkin finite element method is employed along with an implicit Euler scheme to arrive at a fully discrete approximation of the mild solution to the equation. A scheme is presented to compute the covariance of this approximation, which allows for rapid sampling in a Monte Carlo method. This is then extended to a multilevel Monte Carlo method, for which a scheme to compute the cross-covariance between the approximations at different levels is presented. In contrast to traditional path-based methods it is not assumed that the Galerkin subspaces at these levels are nested. The computational complexities of the presented schemes are compared to traditional methods and simulations confirm that, under suitable assumptions, the costs of the new schemes are significantly lower.Comment: 18 pages, 5 figures; numerical simulations revised, implementation section added; To appear in Monte Carlo and Quasi-Monte Carlo Methods - MCQMC, Rennes, France, July 201

Functional interactions between polypyrimidine tract binding protein and PRI peptide ligand containing proteins.

Polypyrimidine tract binding protein (PTBP1) is a heterogeneous nuclear ribonucleoprotein (hnRNP) that plays roles in most stages of the life-cycle of pre-mRNA and mRNAs in the nucleus and cytoplasm. PTBP1 has four RNA binding domains of the RNA recognition motif (RRM) family, each of which can bind to pyrimidine motifs. In addition, RRM2 can interact via its dorsal surface with proteins containing short peptide ligands known as PTB RRM2 interacting (PRI) motifs, originally found in the protein Raver1. Here we review our recent progress in understanding the interactions of PTB with RNA and with various proteins containing PRI ligands.This work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/H004203/1 (to C.W.J.S.)]; the Wellcome Trust [grant number 092900 (to C.W.J.S.)]; the Boehringer Ingelheim Fond (to J.A.); the Medical Research Council [grant number MR/M026302/1 (to D.B.A. and D.E.V.P.)]; the Fundação de Amparo à Pesquisa do Estado de Minas Gerais [grant number MR/M026302/1 (to D.B.A. and D.E.V.P.)]; and the National Health and Medical Research Council CJ Martin Fellowship [grant number APP1072476 (to D.B.A.)]

The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium. Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels. Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites. Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium

Significance of Metastatic Lymph Node Ratio on Stimulated Thyroglobulin Levels in Papillary Thyroid Carcinoma after Prophylactic Unilateral Central Neck Dissection

Background: Prognostic significance of metastatic central lymph node ratio (CLNR) in papillary thyroid carcinoma (PTC) remains unknown. Because postsurgical detectable stimulated thyroglobulin (DsTg) after radioiodine ablation may imply persistent or recurrent disease, we evaluated the association between CLNR and rate of DsTg in patients with PTC who underwent unilateral prophylactic central neck dissection. Methods: To be eligible for analysis, the prophylactic central neck dissection specimen had to contain ≥3 central lymph nodes (CLNs) with ≥1 harboring metastasis. Of 129 specimens, 51 (39.5%) were eligible. CLNR was calculated as follows: (number of metastatic CLNs/number of CLNs retrieved) × 100. They were categorized into group 1 (CLNR 66.67%) (n = 22). Postablation sTg level was measured 6 months after radioiodine ablation. A multivariate analysis was conducted to identify factors for postablation DsTg. Results: Young age, palpable neck swelling, large tumor size, advanced tumor, node, metastasis system (TNM) stage, and large number of metastatic CLNs were significantly associated with high CLNR (Ppublished_or_final_versionSpringer Open Choice, 21 Feb 201

Colossal magnetocapacitance and scale-invariant dielectric response in phase-separated manganites

Thin films of strongly-correlated electron materials (SCEM) are often grown epitaxially on planar substrates and typically have anisotropic properties that are usually not captured by edge-mounted four-terminal electrical measurements, which are primarily sensitive to in-plane conduction paths. Accordingly, the correlated interactions in the out-of-plane (perpendicular) direction cannot be measured but only inferred. We address this shortcoming and show here an experimental technique in which the SCEM under study, in our case a 600 Angstrom-thick (La1-yPry)0.67Ca0.33MnO3 (LPCMO) film, serves as the base electrode in a metal-insulator-metal (MIM) trilayer capacitor structure. This unconventional arrangement allows for simultaneous determination of colossal magnetoresistance (CMR) associated with dc transport parallel to the film substrate and colossal magnetocapacitance (CMC) associated with ac transport in the perpendicular direction. We distinguish two distinct strain-related direction-dependent insulator-metal (IM) transitions and use Cole-Cole plots to establish a heretofore unobserved collapse of the dielectric response onto a universal scale-invariant power-law dependence over a large range of frequency, temperature and magnetic field.Comment: 32 pages, 4 figures, Supplementary section included, Submitted to Nature Physic

Central Coherence in Eating Disorders: A Synthesis of Studies Using the Rey Osterrieth Complex Figure Test

Background: Large variability in tests and differences in scoring systems used to study central coherence in eating disorders may lead to different interpretations, inconsistent findings and between study discrepancies. This study aimed to address inconsistencies by collating data from several studies from the same research group that used the Rey Osterrieth Complex Figure Test (Rey Figure) in order to produce norms to provide benchmark data for future studies. Method: Data was collated from 984 participants in total. Anorexia Nervosa, Bulimia Nervosa, recovered Anorexia Nervosa, unaffected family members and healthy controls were compared using the Rey Figure. Results: Poor global processing was observed across all current eating disorder sub-groups and in unaffected relatives. There was no difference in performance between recovered AN and HC groups. Conclusions: This is the largest dataset reported in the literature and supports previous studies implicating poor global processing across eating disorders using the Rey Figure. It provides robust normative data useful for future studies

A Potential Role for Drosophila Mucins in Development and Physiology

Vital vertebrate organs are protected from the external environment by a barrier that to a large extent consists of mucins. These proteins are characterized by poorly conserved repeated sequences that are rich in prolines and potentially glycosylated threonines and serines (PTS). We have now used the characteristics of the PTS repeat domain to identify Drosophila mucins in a simple bioinformatics approach. Searching the predicted protein database for proteins with at least 4 repeats and a high ST content, more than 30 mucin-like proteins were identified, ranging from 300–23000 amino acids in length. We find that Drosophila mucins are present at all stages of the fly life cycle, and that their transcripts localize to selective organs analogous to sites of vertebrate mucin expression. The results could allow for addressing basic questions about human mucin-related diseases in this model system. Additionally, many of the mucins are expressed in selective tissues during embryogenesis, thus revealing new potential functions for mucins as apical matrix components during organ morphogenesis