Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor

The X-ray crystallographic structure of Torpedo californica acetylcholinesterase (TcAChE) in complex with the bifunctional inhibitor NF595, a potentially new anti-Alzheimer drug, has been solved. For the first time in TcAChE, a major conformational change in the peripheral-site tryptophan residue is observed upon complexation. The observed conformational flexibility highlights the dynamic nature of protein structures and is of importance for structure-based drug design.     

Optimal predictive densities and fractional moments

The maximum entropy approach used together with fractional moments has proven to be a flexible and powerful tool for density approximation of a positive random variable. In this paper we consider an optimality criterion based on the Kullback–Leibler distance in order to select appropriate fractional moments. We discuss the properties of the proposed procedure when all the available information comes from a sample of observations. The method is applied to the size distribution of the U.S. family income. Copyright © 2008 John Wiley & Sons, Ltd.     

<Emphasis Type="Italic">L</Emphasis>(<Emphasis Type="Italic">h</Emphasis>, 1, 1)-labeling of outerplanar graphs

An L(h, 1, 1)-labeling of a graph is an assignment of labels from the set of integers {0, . . . , λ} to the nodes of the graph such that adjacent nodes are assigned integers of at least distance h ≥ 1 apart and all nodes of distance three or less must be assigned different labels. The aim of the L(h, 1, 1)-labeling problem is to minimize λ, denoted by λ _{h, 1, 1} and called span of the L(h, 1, 1)-labeling. As outerplanar graphs have bounded treewidth, the L(1, 1, 1)-labeling problem on outerplanar graphs can be exactly solved in O(n ³), but the multiplicative factor depends on the maximum degree Δ and is too big to be of practical use. In this paper we give a linear time approximation algorithm for computing the more general L(h, 1, 1)-labeling for outerplanar graphs that is within additive constants of the optimum values. This research is partially supported by the European Research Project Algorithmic Principles for Building Efficient Overlay Computers (AEOLUS) and was done during the visit of Richard B. Tan at the Department of Computer Science, University of Rome “Sapienza”, supported by a visiting fellowship from the University of Rome “Sapienza”.     

One-way multiparty communication lower bound for pointer jumping with applications

In this paper we study the one-way multiparty communication model, in which every party speaks exactly once in its turn. For every k, we prove a tight lower bound of Ω(n ^1/(k?1)}) on the probabilistic communication complexity of pointer jumping in a k-layered tree, where the pointers of the i-th layer reside on the forehead of the i-th party to speak. The lower bound remains nontrivial even for k = (logn)^1/2?? parties, for any constant ? > 0. Previous to our work a lower bound was known only for k =3 (Wigderson, see [7]), and in restricted models for k>3 [2},24,18,4,13]. Our results have the following consequences to other models and problems, extending previous work in several directions. The one-way model is strong enough to capture general (not one-way) multiparty protocols with a bounded number of rounds. Thus we generalize two problem areas previously studied in the 2-party model (cf. [30,21,29]). The first is a rounds hierarchy: we give an exponential separation between the power of r and 2r rounds in general probabilistic k-party protocols, for any k and r. The second is the relative power of determinism and nondeterminism: we prove an exponential separation between nondeterministic and deterministic communication complexity for general k-party protocols with r rounds, for any k,r. The pointer jumping function is weak enough to be a special case of the well-studied disjointness function. Thus we obtain a lower bound of Ω(n ^1/(k?1)) on the probabilistic complexity of k-set disjointness in the one-way model, which was known only for k = 3 parties. Our result also extends a similar lower bound for the weaker simultaneous model, in which parties simultaneously send one message to a referee [12]. Finally, we infer an exponential separation between the power of any two different orders in which parties send messages in the one-way model, for every k. Previous results [29, 7] separated orders based on who speaks first. Our lower bound technique, which handles functions of high discrepancy over cylinder intersections, provides a “party-elimination” induction, based on a restricted form of a direct-product result, specific to the pointer jumping function.     

Linear extensions of partial orders and reverse mathematics

We introduce the notion of τ‐like partial order, where τ is one of the linear order types ω, ω*, ω + ω*, and ζ. For example, being ω‐like means that every element has finitely many predecessors, while being ζ‐like means that every interval is finite. We consider statements of the form “any τ‐like partial order has a τ‐like linear extension” and “any τ‐like partial order is embeddable into τ” (when τ is ζ this result appears to be new). Working in the framework of reverse mathematics, we show that these statements are equivalent either to $\mathsf {B}{\Sigma }^{0}_{2}$ or to $\mathsf {ACA}_0$ over the usual base system $\mathsf {RCA}_0$.     

Characterization of cocoa liquors by GC-MS and LC-MS/MS: focus on alkylpyrazines and flavanols

Flavor is one of the most important characteristics of chocolate products and is due to a complex volatile fraction, depending both on the cocoa bean genotype and the several processes occurring during chocolate production (fermentation, drying, roasting and conching). Alkylpyrazines are among the most studied volatiles, being one of the main classes of odorant compounds in cocoa products. In this work, a mass spectrometric approach was used for the comparison of cocoa liquors from different countries. A headspace solid-phase microextraction gas chromatography-mass spectrometry method was developed for the qualitative study of the volatile fraction; the standard addition method was then used for the quantitative determination of five pyrazines (2-methylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2,3,5-trimethylpyrazine and tetramethylpyrazine). Satisfactory figures of merit were obtained: Limits of quantitation were in the range 0.1-2.7?ng/g; repeatability and reproducibility varied between 3% and 7% and between 8% and 14%, respectively. The total content of the pyrazines was remarkably different in the considered samples, ranging from 99 to 708?ng/g. Tetramethylpyrazine showed the highest concentration in all samples, with a maximum value of 585?ng/g. A preliminary study was also performed on the nonvolatile fraction using LC-MS/MS, identifying some flavanols such as catechin, epicatechin and procyanidins. Copyright ? 2012 John Wiley & Sons, Ltd.     

Expanding the Chemical Space of Non-Proteinogenic N4-Substituted Asparagine: Racemic,Enantioenriched, and Deuterated Derivatives

A site-selective carbamoylation strategy to access non-proteinogenic N⁴-modified asparagines has been described. The protocol is characterized by mild reaction conditions, high functional group compatibility, and a wide diversity of functionalized carbamoyl radicals making possible the access to peptides, pharmaceuticals, and natural N⁴-asparagine conjugates, as well as enantioenriched unnatural N⁴-asparagines. Besides that, deuterated analogues were achieved with the insertion of D₂O and enantioenriched derivatives could be obtained in 15 min in continuous-flow conditions.     

The configurational free energy of a polymer chain

The configurational, or elastic, free energy A_el of a polymer chain is discussed in terms of the Fourier configurational approach. The importance of accounting for all degrees of freedom of the chain is shown in comparison with affine mean-field theories and with scaling theories of chain expansion and contraction. In case of strong contraction the chain does show neither affinity nor self-similarity, and we get A_el ∼ N^1/3, N being the number of chain bonds. Conversely, in case of good-solvent expansion we find A_el ∼ N. The same result holds in the vicinity of the Θ-temperature, where A_el is also proportional to [(T − Θ)/T]².