Evaluation of warfarin resistance using transcription activator-like effector nucleases-mediated vitamin K epoxide reductase knockout HEK293 cells

Single nucleotide polymorphisms in the vitamin K epoxide reductase (VKOR) gene have been successfully used for warfarin dosage prediction. However, warfarin resistance studies of naturally occurring VKOR mutants do not correlate with their clinical phenotype. This discrepancy presumably arises because the in vitro VKOR activity assay is performed under artificial conditions using the non-physiological reductant dithiothreitol

Persistent Current From the Competition Between Zeeman Coupling and Spin-Orbit Interaction

Applying the non-adiabatic Aharonov-Anandan phase approach to a mesoscopic ring with non-interacting many electrons in the presence of the spin-orbit interaction, Zeeman coupling and magnetic flux, we show that the time-reversal symmetry breaking due to Zeeman coupling is intrinsically different from that due to magnetic flux. We find that the direction of the persistent currents induced by the Zeeman coupling changes periodically with the particle number, while the magnetic flux determines the direction of the induced currents by its sign alone.Comment: 5 pages, ReVTeX, including 3 figures on request,Submitted to Phys.Rev.Let

Grounded theory research: A design framework for novice researchers

Background: Grounded theory is a well-known methodology employed in many research studies. Qualitative andquantitative data generation techniques can be used in a grounded theory study. Grounded theory sets out to discoveror construct theory from data, systematically obtained and analysed using comparative analysis. While grounded theoryis inherently flexible, it is a complex methodology. Thus, novice researchers strive to understand the discourse and thepractical application of grounded theory concepts and processes.Objective: The aim of this article is to provide a contemporary research framework suitable to inform a grounded theorystudy.Result: This article provides an overview of grounded theory illustrated through a graphic representation of the processesand methods employed in conducting research using this methodology. The framework is presented as a diagrammaticrepresentation of a research design and acts as a visual guide for the novice grounded theory researcher.Discussion: As grounded theory is not a linear process, the framework illustrates the interplay between the essentialgrounded theory methods and iterative and comparative actions involved. Each of the essential methods and processes thatunderpin grounded theory are defined in this article.Conclusion: Rather than an engagement in philosophical discussion or a debate of the different genres that can be used ingrounded theory, this article illustrates how a framework for a research study design can be used to guide and inform thenovice nurse researcher undertaking a study using grounded theory. Research findings and recommendations can contributeto policy or knowledge development, service provision and can reform thinking to initiate change in the substantive area ofinquiry

The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis

Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36) demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes

High-capacity quantum secure direct communication based on quantum hyperdense coding with hyperentanglement

We present a quantum hyperdense coding protocol with hyperentanglement in polarization and spatial-mode degrees of freedom of photons first and then give the details for a quantum secure direct communication (QSDC) protocol based on this quantum hyperdense coding protocol. This QSDC protocol has the advantage of having a higher capacity than the quantum communication protocols with a qubit system. Compared with the QSDC protocol based on superdense coding with $d$-dimensional systems, this QSDC protocol is more feasible as the preparation of a high-dimension quantum system is more difficult than that of a two-level quantum system at present.Comment: 5 pages, 2 figur

Time-Dependent Partition-Free Approach in Resonant Tunneling Systems

An extended Keldysh formalism, well suited to properly take into account the initial correlations, is used in order to deal with the time-dependent current response of a resonant tunneling system. We use a \textit{partition-free} approach by Cini in which the whole system is in equilibrium before an external bias is switched on. No fictitious partitions are used. Besides the steady-state responses one can also calculate physical dynamical responses. In the noninteracting case we clarify under what circumstances a steady-state current develops and compare our result with the one obtained in the partitioned scheme. We prove a Theorem of asymptotic Equivalence between the two schemes for arbitrary time-dependent disturbances. We also show that the steady-state current is independent of the history of the external perturbation (Memory Loss Theorem). In the so called wide-band limit an analytic result for the time-dependent current is obtained. In the interacting case we propose an exact non-equilibrium Green function approach based on Time Dependent Density Functional Theory. The equations are no more difficult than an ordinary Mean Field treatment. We show how the scattering-state scheme by Lang follows from our formulation. An exact formula for the steady-state current of an arbitrary interacting resonant tunneling system is obtained. As an example the time-dependent current response is calculated in the Random Phase Approximation.Comment: final version, 18 pages, 9 figure

In vivo study of the bioavailability and metabolic profile of (poly)phenols after sous-vide artichoke consumption

Artichokes are a rich source of (poly)phenols, mainly caffeoylquinic acids, but little is known about their bioavailability from this source. This study investigated the absorption, metabolism and excretion of (poly)phenols after sous-vide artichoke consumption (5776 µmol of (poly)phenols) by healthy volunteers. Seventy-six (poly)phenol metabolites were identified by UHPLC-MS/MS using authentic standards, including acyl-quinic acids plus C6–C3, C6–C1, C6–C2, C6–C1–N, C6–C0 metabolites, and their phase-II conjugates. The major metabolites were 3ʹ-methoxy-4ʹ-hydroxycinnamic acid, 3ʹ-methoxycinnamic acid-4ʹ-sulfate, and 4ʹ-hydroxycinnamic acid-3ʹ-sulfate, which appeared early in plasma (Tmax 6 h). The 24 h urinary recovery averaged 8.9% (molar basis) of the (poly)phenols consumed. Hepatic beta-oxidation of 3ʹ,4ʹ-dihydroxycinnamic acid and methylated conjugates occurred, but was limited (<0.04%). 3ʹ-Methylation exceeded 4ʹ-methylation and interindividual variability was high, especially for gut microbial metabolites (up to 168-fold)

Clinical applications of magnetic resonance imaging based functional and structural connectivity

Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pathological processes and treatments as well as prognostic biomarkers. These tools have the real potential to inform patient-specific treatment strategies. Nevertheless, a realistic appraisal of clinical utility is needed that balances the growing excitement and interest in the field with important limitations associated with these techniques. Quality of the raw data, minutiae of the processing methodology, and the statistical models applied can all impact on the results and their interpretation. A lack of standardization in data acquisition and processing has also resulted in issues with reproducibility. This limitation has had a direct impact on the reliability of these tools and ultimately, confidence in their clinical use. Advances in MRI technology and computational power as well as automation and standardization of processing methods, including machine learning approaches, may help address some of these issues and make these tools more reliable in clinical use. In this review, we will highlight the current clinical uses of MRI connectomics in the diagnosis and treatment of neurological disorders; balancing emerging applications and technologies with limitations of connectivity analytic approaches to present an encompassing and appropriate perspective