Asymptotics of Largest Components in Combinatorial Structures

Given integers m and n, we study the probability that structures of size n have all components of size at most m. The results are given in term of a generalized Dickman function of n/m.     

LONG TERM STORAGE STABILITY OF MIDDLE DISTILLATE FUELS FROM A CHEMICAL MECHANISTIC POINT OF VIEW. PART 2.

The objective of this review is to (i) articulate the current level of understanding of the types of “reactive molecules” intimately involved in the long term oxidative storage instability of middle distillates, (11) review the types of chemical reaction mechanisms most likely involved in the “oxidative phase” of insoluble formation, (iii) review the postulated chemical mechanisms of stabilizer (additive) operation, and (iv) discuss future research areas that must be explored if a greater understanding and control of middle distillate instability is to be realized.     

When is less treatment better? The role of social anxiety in matching methadone patients to psychosocial treatments.

In response to a need to match drug users to the most appropriate and cost-effective level of care, it was hypothesized that socially anxious methadone-maintained patients would attain greater benefit from coping skills training provided in the context of a low-intensity enhanced standard methadone maintenance intervention (E-STD) than in the context of a high-intensity, socially demanding day treatment program (DTP). Social anxiety was assessed in 307 methadone-maintained patients using the Social Anxiety and Distress Scale prior to randomization to either E-STD or DTP. The hypothesis was supported: Socially anxious patients were drug free longer during treatment, were more likely to be abstinent at treatment completion, and had greater reductions in HIV risk behaviors if assigned to the lower intensity intervention, which was provided at ? the cost of the DTP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation

Actin filament assembly at the cell surface of the pathogenic bacterium Listeria monocytogenes requires the bacterial ActA surface protein and the host cell Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin polymerization in vitro, but pure ActA had no effect. However, when combined, the Arp2/3 complex and ActA synergistically stimulated the nucleation of actin filaments. This mechanism of activating the host Arp2/3 complex at the L. monocytogenes surface may be similar to the strategy used by cells to control Arp2/3 complex activity and hence the spatial and temporal distribution of actin polymerization.     

The additivity of substrate fragments in enzyme-ligand binding

BACKGROUND: Enzymes have evolved to recognise their target substrates with exquisite selectivity and specificity. Whether fragments of the substrate--perhaps never available to the evolving enzyme--are bound in the same manner as the parent substrate addresses the fundamental basis of specificity. An understanding of the relative contributions of individual portions of ligand molecules to the enzyme-binding interaction may offer considerable insight into the principles of substrate recognition. RESULTS: We report 12 crystal structures of Escherichia coli thymidylate synthase in complexes with available fragments of the substrate (dUMP), both with and without the presence of a cofactor analogue. The structures display considerable fidelity of binding mode and interactions. These complexes reveal several interesting features: the cofactor analogue enhances the localisation of substrate and substrate fragments near the reactive thiol; the ribose moiety reduces local disorder through additional specific enzyme-ligand interactions; the pyrimidine has multiple roles, ranging from stereospecificity to mechanistic competence; and the glycosidic linkage has an important role in the formation of a covalent attachment between substrate and enzyme. CONCLUSIONS: The requirements of ligand-protein binding can be understood in terms of the binding of separate fragments of the ligand. Fragments which are subsystems of the natural substrate for the enzyme confer specific contributions to the binding affinity, orientation or electrostatics of the enzymatic mechanism. This ligand-binding analysis provides a complementary method to the more prevalent approaches utilising site-directed mutagenesis. In addition, these observations suggest a modular approach for rational drug design utilising chemical fragments.     

Selectors Make Set-Based Analysis Too Hard

A set-based program analysis establishes constraints between sets of abstract values for all expressions in a program. Solving the system of constraints produces a conservative approximation to the program's runtime flow of values. Some practical set-based analyses use explicit selectors to extract the relevant values from an approximation set. For example, if the analysis needs to determine the possible return values of a procedure, it uses the appropriate selector to extract the relevant component from the abstract representation of the procedure. In this paper, we show that this selector-based approach complicates the constraint solving phase of the analysis too much and thus fails to scale up to realistic programming languages. We demonstrate this claim with a full-fledged value flow analysis for case-lambda, a multi-branched version of lambda. We show how both the theoretical underpinnings and the practical implementation become too complex. In response, we present a variant of set-based closure analysis that computes equivalent results in a much more efficient manner.