Identification of ligands that target the HCV-E2 binding site on CD81

Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.     

Synthetic studies on C14 cembranoids: synthesis of C4-12 fragment of sarcophytonolides E-G and L and C5-11 fragment of sarcophytonolide L

An efficient stereoselective synthesis of C4-12 fragment of the cembranoids, sarcophytonolides E-G and L and C5-11 fragment of sarcophytonolide L is described. The C4-12 building block is efficiently assembled starting from chiral pool material (R)-carvone employing the Baeyer-Villiger oxidation, modified Knoevenagel condensation and asymmetric dihydroxylation as the key steps. The synthesis of C5-11 fragment is based on orthoester Johnson-Claisen rearrangement as the key step.     

Associated primes of graded components of local cohomology modules

The -th local cohomology module of a finitely generated graded module over a standard positively graded commutative Noetherian ring , with respect to the irrelevant ideal , is itself graded; all its graded components are finitely generated modules over , the component of of degree . It is known that the -th component of this local cohomology module is zero for all > 0$">. This paper is concerned with the asymptotic behaviour of as .

The smallest for which such study is interesting is the finiteness dimension of relative to , defined as the least integer for which is not finitely generated. Brodmann and Hellus have shown that is constant for all (that is, in their terminology, is asymptotically stable for ). The first main aim of this paper is to identify the ultimate constant value (under the mild assumption that is a homomorphic image of a regular ring): our answer is precisely the set of contractions to of certain relevant primes of whose existence is confirmed by Grothendieck's Finiteness Theorem for local cohomology.

Brodmann and Hellus raised various questions about such asymptotic behaviour when f$">. They noted that Singh's study of a particular example (in which ) shows that need not be asymptotically stable for . The second main aim of this paper is to determine, for Singh's example, quite precisely for every integer , and, thereby, answer one of the questions raised by Brodmann and Hellus.

     

A multiple regression model for urban traffic noise in Hong Kong

This article describes the roadside traffic noise surveys conducted in heavily built-up urban areas in Hong Kong. Noise measurements were carried out along 18 major roads in 1999. The measurement data included L10, L50, L90, Leq, Lmax, the number of light vehicles, the number of heavy vehicles, the total traffic flow, and the average speed of vehicles. Statistical analysis using the analysis of variance (ANOVA) and Tukey test (p<0.05) reveals that the total traffic flow and the number of heavy vehicles are the most significant factors of urban traffic noise. Multiple regression was used to derive a set of empirical formulas for predicting L10 noise level due to road traffic. The accuracy of these empirical formulas is quantified and compared to that of another widely used prediction model in Hong Kong--the Calculation of Road Traffic Noise. The applicability of the selected multiple regression model is validated by the noise measurements performed in the winter of 2000.     

The Dirichlet problem for the minimal surface equation in non-regular domains

Summary In this paper we study the Dirichlet problem for the minimal surface equation in a open set Ω without any assumption about the regularity of ϖΩ. We prove an existence theorem using only the pseudoconvexity of Ω.

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Riassunto In questo lavoro studiamo il problema di Dirichlet per l'equazione delle superfici minime in un aperto Ω diR ⁿ sulla cui frontiera non si fa nessuna ipotesi di regolarità. Si ottiene un teorema di esistenza usando la sola pseudoconvessità di Ω.

     

Invariants of the group of a third order differential element

Summary In this note we discuss the invariant properties of the group of homographies which leave a third order differential element E₃ invariant.     

Real-time evolution of the distribution of nanoparticles in an ultrathin-polymer-film-based waveguide

We report a novel application of an ultrathin-polymer-film-based, resonance-enhanced x-ray waveguide as a real-time nanoprobe for elucidating dilute, yet disordered, gold nanoparticles embedded in the polymer matrix. This nanoprobe promises a sensitivity enhancement of several orders of magnitude, hence revealing in real time the lateral nanoparticle distribution with subnanometer spatial resolution. We observed that the motion of the nanoparticles is strongly anisotropic, with in-plane coalescence taking place more rapidly than out-of-plane diffusion, which can ultimately facilitate the formation of two-dimensional structures.     

Ideals in a perfect closure, linear growth of primary decompositions, and tight closure

This paper is concerned with tight closure in a commutative Noetherian ring of prime characteristic , and is motivated by an argument of K. E. Smith and I. Swanson that shows that, if the sequence of Frobenius powers of a proper ideal of has linear growth of primary decompositions, then tight closure (of ) `commutes with localization at the powers of a single element'. It is shown in this paper that, provided has a weak test element, linear growth of primary decompositions for other sequences of ideals of that approximate, in a certain sense, the sequence of Frobenius powers of would not only be just as good in this context, but, in the presence of a certain additional finiteness property, would actually imply that tight closure (of ) commutes with localization at an arbitrary multiplicatively closed subset of .

Work of M. Katzman on the localization problem for tight closure raised the question as to whether the union of the associated primes of the tight closures of the Frobenius powers of has only finitely many maximal members. This paper develops, through a careful analysis of the ideal theory of the perfect closure of , strategies for showing that tight closure (of a specified ideal of ) commutes with localization at an arbitrary multiplicatively closed subset of and for showing that the union of the associated primes of the tight closures of the Frobenius powers of is actually a finite set. Several applications of the strategies are presented; in most of them it was already known that tight closure commutes with localization, but the resulting affirmative answers to Katzman's question in the various situations considered are believed to be new.