Reactions of biologically inspired hydride sources with B(C6F5)3

The combination of 1-benzyl-1,4-dihydropyridines with the strong Lewis acid, B(C6F5)3, generates a stable pyridinium borohydride species in high yields (94%) in as little as 10 min. This use of biologically inspired hydride sources further builds on the recent work of new hydride donors in the formation of borohydrides. When functionalizing the dihydropyridine with an amide or carboxylic acid moiety, a disproportionation reaction composed of a series of protonation/reduction steps is observed upon the addition of B(C6F5)3. As a result, one equivalent of dihydropyridine undergoes net hydrogenation, whereas the other is dehydrogenated yielding the pyridinium counterpart in a transfer hydrogenation-type mechanism

Enabling protein-hosted organocatalytic transformations

In this review, the development of organocatalytic artificial enzymes will be discussed. This area of protein engineering research has underlying importance, as it enhances the biocompatibility of organocatalysis for applications in chemical and synthetic biology research whilst expanding the catalytic repertoire of enzymes. The approaches towards the preparation of organocatalytic artificial enzymes, techniques used to improve their performance (selectivity and reactivity) as well as examples of their applications are presented. Challenges and opportunities are also discussed

Measurement of Cosmic-ray Muons and Muon-induced Neutrons in the Aberdeen Tunnel Underground Laboratory

We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be $I_{\mu} = (5.7 \pm 0.6) \times 10^{-6}$ cm$^{-2}$s$^{-1}$sr$^{-1}$. The yield of muon-induced neutrons in the liquid scintillator was determined to be $Y_{n} = (1.19 \pm 0.08 (stat) \pm 0.21 (syst)) \times 10^{-4}$ neutrons/($\mu\cdot$g$\cdot$cm$^{-2}$). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of $\left\langle E_{\mu} \right\rangle^{0.76 \pm 0.03}$ for liquid-scintillator targets.Comment: 14 pages, 17 figures, 3 table

Colorectal carcinoma in Hong Kong: epidemiology and genetic mutations.

The incidence of colorectal carcinoma is rising at an alarming pace in Asian urban societies such as Hong Kong. Detailed examination of the epidemiological pattern and genetic mutation of colorectal cancer in the Hong Kong Chinese population is overdue. We compared the reported age incidence of colorectal carcinoma in Hong Kong with that of Scotland and other countries. Hong Kong showed a much higher incidence of colorectal carcinoma among the young age groups. By comparison with other countries, this raised incidence among the young appeared to be related to southern Chinese societies. The recent dramatic rise in colorectal cancer in Hong Kong was largely attributable to an increase in the over 50 years age group, while the young incidence remained unchanged. We also defined the mutation spectrum of p53 and Ki-ras in 67 unselected cases by direct DNA sequencing. Interestingly, insertion/deletion mutations in p53 from colorectal carcinoma in Hong Kong showed a significantly higher frequency (17.2%) than the Scottish data (0%) and the world database (6.6%), although the overall frequency of p53 mutation (43%) in Hong Kong was similar to others. The high incidence of colorectal carcinoma in young people and the raised proportion of frameshift mutations in p53 encourage further search for a genetic basis for susceptibility to this disease in the Hong Kong Chinese population

Carbapenems as water soluble organocatalysts

Background: Identification of organocatalysts functioning in aqueous environments will provide methods for more sustainable chemical transformations and allow tandem reactions with biocatalysts, like enzymes. Here we examine three water-soluble carbapenem antibiotics (meropenem, doripenem, and ertapenem) as secondary amine organocatalysts in aqueous environments. Methods: The Michael addition of nitromethane to cinnamaldehyde was used as the model reaction. The reactions were monitored by 1H NMR, and the enantioselectivity was determined by chiral HPLC. Results: The effects of buffer components, pH, organic co-solvents and anchoring into a protein scaffold were investigated. Moderate yields of the Michael addition were obtained in buffer alone. The use of methanol as a co-solvent in a ratio of 1:1 increases the yield by 50%. Anchoring of the catalysts into a protein backbone reverses the enatioselectivity of the reaction. Conclusions: Despite only moderate yields and enantioselectivities being obtained, this study lays the foundations for future development of efficient organocatalysis in aqueous environments

Applying switchable Cas9 variants to in vivo gene editing for therapeutic applications

Progress in targeted gene editing by programmable endonucleases has paved the way for their use in gene therapy. Particularly, Cas9 is an endonuclease with high activity and flexibility, rendering it an attractive option for therapeutic applications in clinical settings. Many disease-causing mutations could potentially be corrected by this versatile new technology. In addition, recently developed switchable Cas9 variants, whose activity can be controlled by an external stimulus, provide an extra level of spatiotemporal control on gene editing and are particularly desirable for certain applications. Here, we discuss the considerations and difficulties for implementing Cas9 to in vivo gene therapy. We put particular emphasis on how switchable Cas9 variants may resolve some of these barriers and advance gene therapy in the clinical setting

Search for the Lepton-Number-Violating Decay Ξ−→pμ−μ−\Xi^- \to p \mu^- \mu^-

A sensitive search for the lepton-number-violating decay $\Xi^-\to p \mu^-\mu^-$ has been performed using a sample of $\sim10^9$ $\Xi^-$ hyperons produced in 800 GeV/$c$ $p$-Cu collisions. We obtain $\mathcal{B}(\Xi^-\to p \mu^-\mu^-)< 4.0\times 10^{-8}$ at 90% confidence, improving on the best previous limit by four orders of magnitude.Comment: 9 pages, 5 figures, to be published in Phys. Rev. Let

A side-by-side comparison of Daya Bay antineutrino detectors

The Daya Bay Reactor Neutrino Experiment is designed to determine precisely the neutrino mixing angle $\theta_{13}$ with a sensitivity better than 0.01 in the parameter sin$^22\theta_{13}$ at the 90% confidence level. To achieve this goal, the collaboration will build eight functionally identical antineutrino detectors. The first two detectors have been constructed, installed and commissioned in Experimental Hall 1, with steady data-taking beginning September 23, 2011. A comparison of the data collected over the subsequent three months indicates that the detectors are functionally identical, and that detector-related systematic uncertainties exceed requirements.Comment: 24 pages, 36 figure

A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay

We report a new measurement of electron antineutrino disappearance using the fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9$\times$10$^5$ GW$_{\rm th}$-ton-days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six $^{241}$Am-$^{13}$C radioactive calibration sources reduced the background by a factor of two for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of $\sin^{2}2\theta_{13}$ and $|\Delta m^2_{ee}|$ were halved as a result of these improvements. Analysis of the relative antineutrino rates and energy spectra between detectors gave $\sin^{2}2\theta_{13} = 0.084\pm0.005$ and $|\Delta m^{2}_{ee}|= (2.42\pm0.11) \times 10^{-3}$ eV$^2$ in the three-neutrino framework.Comment: Updated to match final published versio