Trigger factor slows co-translational folding through kinetic trapping while sterically protecting the nascent chain from aberrant cytosolic interactions

The E. coli chaperone trigger factor (TF) interacts directly with nascent polypeptide chains as they emerge from the ribosome exit tunnel. Small protein domains can fold under the cradle created by TF, but the co-translational folding of larger proteins is slowed down by its presence. Because of the great experimental challenges in achieving high spatial and time resolution, it is not yet known whether or not TF alters the folding properties of small proteins and if the reduced rate of folding of larger proteins is the result of kinetic or thermodynamic effects. We show, by molecular simulations employing a coarse-grained model of a series of ribosome nascent-chain complexes, that TF does not alter significantly the co-translational folding process of a small protein G domain but delays that of a large β-galactosidase domain as a result of kinetic trapping of its unfolded ensemble. We demonstrate that this trapping occurs through a combination of three distinct mechanisms: a decrease in the rate of structural rearrangements within the nascent chain, an increase in the effective exit tunnel length due to folding outside the cradle, and entanglement of the nascent chain with TF. We present evidence that this TF-induced trapping represents a trade-off between promoting co-translational folding and sterically shielding the nascent chain from aberrant cytosolic interactions that could lead to its aggregation or degradation.     

Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam

The T2K experiment observes indications of ν(μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3) eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.     

Trends of the bonding effect on the performance of DFT methods in electric properties calculations: A pattern recognition and metric space approach on some XY2 (X = O,S and Y = H,O, F,S, Cl) molecules

A test set of 10 molecules (open and ring forms of ozone and sulfur dioxide as well as water and hydrogen sulfide and their respective fluoro‐ and chloro‐substituted analogs) of specific atmospheric interest has been formed as to assess the performance of various density functional theory methods in (hyper)polarizability calculations against well‐established ab initio methods. The choice of these molecules was further based on (i) the profound change in the physics between isomeric systems, e.g., open (C_2v) and ring (D_3h) forms of ozone, (ii) the relation between isomeric forms, e.g., open and ring form of sulfur dioxide (both of C_2v symmetry), and (iii) the effect of the substitution, e.g., in fluoro‐ and chloro‐substituted water analogs. The analysis is aided by arguments chosen from the information theory, graph theory, and pattern recognition fields of Mathematics: In brief, a multidimensional space is formed by the methods which are playing the role of vectors with the independent components of the electric properties to act as the coordinates of these vectors, hence the relation between different vectors (e.g., methods) can be quantified by a proximity measure. Results are in agreement with previous studies revealing the acceptable and consistent behavior of the mPW1PW91, B3P86, and PBE0 methods. It is worth noting the remarkable good performance of the double hybrid functionals (namely: B2PLYP and mPW2PLYP) which are for the first time used in calculations of electric response properties. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

Tandem Favorskii Intermediate/Cyclization Leading to Tricyclo[4.4.0.0]decanediones

The mechanism of dehydrobromination of the bromodiketone 8 leading to the unusual ring system of tricyclo[4.4.0.0]decanediones (9 and 10) is described. An entry into the ring system of the sesquiterpenoid hydrocarbons copaene and ylangene, 8 to 9, is achieved in three steps starting with enone 6. Compound 9 was either derived from a direct internal S_N2 cyclization of 8 or the Favorskii intermediate 8a. Formation of compound 10, on the other hand, can only occur via the Favorskii intermediate 8a. Structure assignments of 9 and 10 were determined using both one‐ and two‐dimensional NMR experiments.     

Facile preparation of polysaccharide‐coated capillaries using a room temperature ionic liquid for chiral separations

In this study, the dissolution of polysaccharides into an ionic liquid was investigated and applied as a coating onto the capillary walls of a fused‐silica capillary in open‐tubular CEC. The coating was evaluated by examining the chiral separation of two analytes (thiopental, sotalol) with three cellulose derivatives (cellulose acetate, cellulose acetate phthalate, and cellulose acetate butyrate). Baseline separation of thiopental enantiomers was achieved by use of each polysaccharide coating (Rs: 7.0, 8.1, 7.1), while sotalol provided partial resolution (Rs: 0.7, 1.0, 0.9). In addition, reproducibility of the cellulose‐coated capillaries was evaluated by estimating the run‐to‐run and capillary‐to‐capillary RSD values of the EOF. Both stability and reproducibility were very good with RSD values of less than 7%.     

Proposal for generating a two-photon added coherent state via down-conversion with a single crystal

Zavatta et al. [A. Zavatta, S. Viciani, M. Bellini, Science 306 (2004) 660; A. Zavatta, S. Viciani, M. Bellini, Phys. Rev. A 72 (2006) 023820], using parametric down-conversion, have carried out experiments to conditionally generate a single-photon added coherent state. In this Letter, we propose an extension of their method in order to generate the two-photon added coherent state, and point the way toward generating m-photon added coherent states for m>2, all using only one down-conversion crystal.     

On Waiting Time Problems Associated with Runs in Markov Dependent Trials

A general technique is developed to study the waiting time distribution for the r-th occurrence of a success run of length k in a sequence of Markov dependent trials. Sooner and later waiting time problems are also discussed.     

Improving the Performance of the Chi-square Control Chart via Runs Rules

The most popular multivariate process monitoring and control procedure used in the industry is the chi-square control chart. As with most Shewhart-type control charts, the major disadvantage of the chi-square control chart, is that it only uses the information contained in the most recently inspected sample; as a consequence, it is not very efficient in detecting gradual or small shifts in the process mean vector. During the last decades, the performance improvement of the chi-square control chart has attracted continuous research interest. In this paper we introduce a simple modification of the chi-square control chart which makes use of the notion of runs to improve the sensitivity of the chart in the case of small and moderate process mean vector shifts.