689 research outputs found
Site-specific incorporation of phosphotyrosine using an expanded genetic code.
Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination
Optimization of a solid-state electron spin qubit using gate set tomography
State of the art qubit systems are reaching the gate fidelities required for scalable quantum computation architectures. Further improvements in the fidelity of quantum gates demands characterization and benchmarking protocols that are efficient, reliable and extremely accurate. Ideally, a benchmarking protocol should also provide information on how to rectify residual errors. Gate set tomography (GST) is one such protocol designed to give detailed characterization of as-built qubits. We implemented GST on a high-fidelity electron-spin qubit confined by a single 31P atom in 28Si. The results reveal systematic errors that a randomized benchmarking analysis could measure but not identify, whereas GST indicated the need for improved calibration of the length of the control pulses. After introducing this modification, we measured a new benchmark average gate fidelity of , an improvement on the previous value of . Furthermore, GST revealed high levels of non-Markovian noise in the system, which will need to be understood and addressed when the qubit is used within a fault-tolerant quantum computation scheme
Individualizing therapy β in search of approaches to maximize the benefit of drug treatment (II)
Adjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20(th )century, when several different drugs were administered on the basis of individual plasma concentration measurements. Genetic control of drug metabolism was well established by the 1960s, and pharmakokinetic-based individualized therapy was in use by 1973
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Reversible Control of Magnetic Interactions by Electric Field in a Single Phase Material
Intrinsic magnetoelectric coupling describes the interaction between magnetic
and electric polarization through an inherent microscopic mechanism in a single
phase material. This phenomenon has the potential to control the magnetic state
of a material with an electric field, an enticing prospect for device
engineering. We demonstrate 'giant' magnetoelectric cross-field control in a
single phase rare earth titanate film. In bulk form, EuTiO3 is
antiferromagnetic. However, both anti and ferromagnetic interactions coexist
between different nearest neighbor europium ions. In thin epitaxial films,
strain can be used to alter the relative strength of the magnetic exchange
constants. Here, we not only show that moderate biaxial compression
precipitates local magnetic competition, but also demonstrate that the
application of an electric field at this strain state, switches the magnetic
ground state. Using first principles density functional theory, we resolve the
underlying microscopic mechanism resulting in the EuTiO3 G-type magnetic
structure and illustrate how it is responsible for the 'giant' cross-field
magnetoelectric effect
Proton magnetic spectroscopy agreed better with magnetic resonance image to lateralization of epileptogenic zone than with surface electroencephalography
Modelling credit spreads with time volatility, skewness, and kurtosis
This paper seeks to identify the macroeconomic and financial factors that drive credit spreads on bond indices in the US credit market. To overcome the idiosyncratic nature of credit spread data reflected in time varying volatility, skewness and thick tails, it proposes asymmetric GARCH models with alternative probability density functions. The results show that credit spread changes are mainly explained by the interest rate and interest rate volatility, the slope of the yield curve, stock market returns and volatility, the state of liquidity in the corporate bond market and, a heretofore overlooked variable, the foreign exchange rate. They also confirm that the asymmetric GARCH models and Student-t distributions are systematically superior to the conventional GARCH model and the normal distribution in in-sample and out-of-sample testing
PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]
BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1Β°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3Β°C (95% CI: 0.1β0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one
Yes, I Am Ready Now: Differential Effects of Paced versus Unpaced Mating on Anxiety and Central Oxytocin Release in Female Rats
Sexual activity and partner intimacy results in several positive consequences in the context of stress-coping, both in males and females, such as reduced state anxiety in male rats after successful mating. However, in female rats, mating is a rewarding experience only when the estrous female is able to control sexual interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex-steroid priming required for female mating is anxiolytic; subsequent sexual activity under paced mating conditions did not disrupt this anxiolytic priming effect, whereas mating under unpaced conditions increased anxiety-related behavior. In primed females, the release of the neuropeptide oxytocin (OT) within the hypothalamic paraventricular nucleus was found to be elevated and to further increase during paced, but not unpaced mating. Central administration of an OT receptor antagonist partly prevented priming/mating-induced anxiolysis indicating the involvement of brain OT in the anxiolysis triggered by priming and/or sexual activity
Trichomonas Transmembrane Cyclases Result from Massive Gene Duplication and Concomitant Development of Pseudogenes
Trichomonas vaginalis is the only medically important protist (single-cell eukaryote) that is sexually transmitted. The βΌ160-Mb Trichomonas genome contains more predicted protein-encoding genes (βΌ60,000) than the human genome. To begin to understand why there are so many copies of some genes, we chose here to study a large family of genes encoding unique transmembrane cyclases. Our most important results include the following. More than 100 transmembrane cyclase genes do not result from chromosomal duplications, because for the most part only the coding regions of the genes, rather than flanking sequences, are duplicated. Almost half of the transmembrane cyclase genes are pseudogenes, and these pseudogenes are polymorphic among laboratory strains of Trichomonas. Messenger RNAs for numerous transmembrane cyclases are expressed simultaneously, and representative cyclase domains have adenylyl cyclase activity. In summary, the large family of Trichomonas genes encoding transmembrane adenylyl cyclases results from massive gene duplication and concomitant development of pseudogenes
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