Initiation of Protein Synthesis with Non-Canonical Amino Acids In Vivo

By transplanting identity elements into E. coli tRNA^fMet, we have engineered an orthogonal initiator tRNA (itRNA^Ty2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNA^Ty2 can initiate translation in vivo with aromatic non-canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNA^fMet from the genome afforded an E. coli strain in which the efficiency of non-canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biology and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo.     

One Guest or Two? A Crystallographic and Solution Study of Guest Binding in a Cubic Coordination Cage

A crystallographic investigation of a series of host–guest complexes in which small-molecule organic guests occupy the central cavity of an approximately cubic M₈L₁₂ coordination cage has revealed some unexpected behaviour. Whilst some guests form 1:1 H⋅G complexes as we have seen before, an extensive family of bicyclic guests—including some substituted coumarins and various saturated analogues—form 1:2 H⋅G₂ complexes in the solid state, despite the fact that solution titrations are consistent with 1:1 complex formation, and the combined volume of the pair of guests significantly exceeds the Rebek 55±9 % packing for optimal guest binding, with packing coefficients of up to 87 %. Re-examination of solution titration data for guest binding in two cases showed that, although conventional fluorescence titrations are consistent with 1:1 binding model, alternative forms of analysis—Job plot and an NMR titration—at higher concentrations do provide evidence for 1:2 H⋅G₂ complex formation. The observation of guests binding in pairs in some cases opens new possibilities for altered reactivity of bound guests, and also highlights the recently articulated difficulties associated with determining stoichiometry of supramolecular complexes in solution.     

Microporosity of a Guanidinium Organodisulfonate Hydrogen‐Bonded Framework

Guanidinium organosulfonates (GSs) are a large and well‐explored archetypal family of hydrogen‐bonded organic host frameworks that have, over the past 25 years, been regarded as nonporous. Reported here is the only example to date of a conventionally microporous GS host phase, namely guanidinium 1,4‐benzenedisulfonate ( p ‐G₂BDS ). p ‐G₂BDS is obtained from its acetone solvate, AcMe@ G₂BDS , by single‐crystal‐to‐single‐crystal (SC‐SC) desolvation, and exhibits a Type I low‐temperature/pressure N₂ sorption isotherm (SA_BET=408.7(2) m² g^?1, 77 K). SC‐SC sorption of N₂, CO₂, Xe, and AcMe by p ‐G₂BDS is explored under various conditions and X‐ray diffraction provides a measurement of the high‐pressure, room temperature Xe and CO₂ sorption isotherms. Though p ‐G₂BDS is formally metastable relative to the “collapsed”, nonporous polymorph, np ‐G₂BDS , a sample of p ‐G₂BDS survived for almost two decades under ambient conditions. np ‐G₂BDS reverts to zCO₂@ p ‐G₂BDS or yXe@ p ‐G₂BDS (y,z=variable) when pressure of CO₂ or Xe, respectively, is applied.     

Initiation of Protein Synthesis with Non‐Canonical Amino Acids In Vivo

By transplanting identity elements into E. coli tRNA^fMet, we have engineered an orthogonal initiator tRNA (itRNA^Ty2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNA^Ty2 can initiate translation in vivo with aromatic non‐canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNA^fMet from the genome afforded an E. coli strain in which the efficiency of non‐canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biology and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo.     

BIMP‐Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones

A bifunctional iminophosphorane (BIMP)‐catalysed enantioselective synthesis of α,β‐unsaturated cyclohexenones through a facially selective 1,3‐prototropic shift of β,γ‐unsaturated prochiral isomers, under mild reaction conditions and in short reaction times, on a range of structurally diverse substrates, is reported. α,β‐Unsaturated cyclohexenone products primed for downstream derivatisation were obtained in high yields (up to 99 %) and consistently high enantioselectivity (up to 99 % ee). Computational studies into the reaction mechanism and origins of enantioselectivity, including multivariate linear regression of TS energy, were carried out and the obtained data were found to be in good agreement with experimental findings.     

Iterative Suzuki‐Miyaura Cross‐coupling/Bromo‐desilylation Reaction Sequences for the Assembly of Chemically Well‐defined,Acyclic Oligopyrrole/Benzenoid Hybrids Embodying Mixed Modes of Connectivity

Syntheses of a range of chemically well‐defined oligopyrrole/benzenoid hybrids are described using tandem Suzuki‐Miyaura cross‐coupling/bromo‐desilyation reaction sequences for linking borylated pyrroles, halogenated pyrroles and/or dibromobenzenes to one another. By such means, including iterative variants, a range of all α‐linked, all β‐linked oligopyrroles as well as certain combinations thereof have been assembled, some of them for the first time. The conductivities of iodine‐treated thin films formed from certain such systems have been determined.     

Comment on the paper: H.-E. Hwang, P. Han, Theoretical analysis for surface tilt and translation detection based on speckle photography in the Fresnel domain, Opt. Commun. 282 (2009) 351-354

In a recent paper [H.-E. Hwang, P. Han, Opt. Commun. 282 (2009) 351] a speckle based metrology system is proposed which it is claimed provides significant advantages over existing systems. In this paper, we show that the discussion presented in [H.-E. Hwang, P. Han, Opt. Commun. 282 (2009) 351] is deficient, and that several of the statements made are incorrect and/or misleading.     

Different Epidemic Models on Complex Networks

Models for diseases spreading are not just limited to SIS or SIR. For instance, for the spreading of AIDS/HIV, the susceptible individuals can be classified into different cases according to their immunity, and similarly, the infected individuals can be sorted into different classes according to their infectivity. Moreover, some diseases may develop through several stages. Many authors have shown that the individuals＇ relation can be viewed as a complex network. So in this paper, in order to better explain the dynamical behavior of epidemics, we consider different epidemic models on complex networks, and obtain the epidemic threshold for each ease. Finally, we present numerical simulations for each case to verify our results.     

What you as a manager can do to overcome verbal abuse of staff

Employees and their work performance determine the success of any business. Permitting verbal abuse and other disruptive behaviors is bad management. Well-written policies, physician champions, strong executives, and the willingness of OR managers to try new approaches to assist the staff to develop new skill sets will help to create healthier workplaces where everyone knows words don't hurt.