Phase Locking Of A 2.5 THz Quantum Cascade Laser To A Microwave Reference Using THz Schottky Mixer

The frequency of a 2.5 THz QCL are stabilized to sub-hertz accuracy by phase-locking to a stable 100 MHz microwave reference, using a 2.3–3.2 THz room temperature Schottky diode based harmonic mixer. The down-converted phase locked beat note is stable over a long term test

Dual Beneficial Effects of (-)-Epigallocatechin-3-Gallate on Levodopa Methylation and Hippocampal Neurodegeneration: In Vitro and In Vivo Studies

A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration

Measurement of 222Rn dissolved in water at the Sudbury Neutrino Observatory

The technique used at the Sudbury Neutrino Observatory (SNO) to measure the concentration of 222Rn in water is described. Water from the SNO detector is passed through a vacuum degasser (in the light water system) or a membrane contact degasser (in the heavy water system) where dissolved gases, including radon, are liberated. The degasser is connected to a vacuum system which collects the radon on a cold trap and removes most other gases, such as water vapor and nitrogen. After roughly 0.5 tonnes of H2O or 6 tonnes of D2O have been sampled, the accumulated radon is transferred to a Lucas cell. The cell is mounted on a photomultiplier tube which detects the alpha particles from the decay of 222Rn and its daughters. The overall degassing and concentration efficiency is about 38% and the single-alpha counting efficiency is approximately 75%. The sensitivity of the radon assay system for D2O is equivalent to ~3 E(-15) g U/g water. The radon concentration in both the H2O and D2O is sufficiently low that the rate of background events from U-chain elements is a small fraction of the interaction rate of solar neutrinos by the neutral current reaction.Comment: 14 pages, 6 figures; v2 has very minor change

Cancer genomics and biology 2015 - Meeting report

published_or_final_versio

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as $\alpha_1$-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create $\textit{conserpin}$, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.BTP is a Medical Research Council Career Development Fellow. AAN and JJH are supported by the Wellcome Trust (grant number WT 095195). SM acknowledges fellowship support from the Australian Research Council (FT100100960). NAB is an Australian Research Council Future Fellow (110100223). GIW is an Australian Research Council Discovery Outstanding Researcher Award Fellow (DP140100087). AMB is a National Health and Medical Research Senior Research Fellow (1022688). JCW is an NHMRC Senior Principal Research fellow and also acknowledges the support of an ARC Federation Fellowship. We thank the Australian Synchrotron for beam-time and technical assistance. This work was supported by the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au). We acknowledge the Monash Protein Production Unit and Monash Macromolecular Crystallization Facilit

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics

A Wide-angle Multi-Octave Broadband Waveplate Based on Field Transformation Approach

J.Z. acknowledge the support from the National Nature Science Foundation of China (61571218, 61571216, 61301017, 61371034, 61101011), and the Ph.D. Programs Foundation of Ministry of Education of China (20120091110032, 20110091120052). Y. H. acknowledge the support from the UK EPSRC under the QUEST Programme Grant (EP/I034548/1)