A Study of Integrated Document and Connection Caching in the WWW

Document caching and connection caching are extensively studied problems. In document caching, one has to maintain caches containing documents accessible in a network. In connection caching, one has to maintain a set of open network connections that handle data transfer. Previous work investigated these two problems separately while in practice the problems occur together: In order to load a document, one has to establish a connection between network nodes if the required connection is not already open. In this paper we present the first study that integrates document and connection caching. We first consider a very basic model in which all documents have the same size and the cost of loading a document or establishing a connection is equal to 1. We present deterministic and randomized online algorithms that achieve nearly optimal competitive ratios unless the size of the connection cache is extremely small. We then consider general settings where documents have varying sizes. We investigate a FAULT model in which the loading cost of a document is 1 as well as a BIT model in which the loading cost is equal to the size of the document.     

Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF)

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.     

Enthalpies of formation of transition-metal lanthanide laves phases with the MgCu2 structure

Experimental information and theoretical estimates for the enthalpy of formation at 298 K for the RM₂ (whereM = Fe, Co,orNi andR = La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb, or Lu) lanthanide Laves phases with the MgCu₂ (C15) structure are reviewed and discussed in the light of information on lattice parameters and atomic volume. The purpose of the present study is to analyze all the available experimental information on enthalpies of formation for transition-metal lanthanide Laves phases and then plot the data in order to reveal tendencies and allow reliable estimates of data that have not yet been measured. It is concluded that as the lanthanide atomic number increases the enthalpy of formation is almost constant or becomes slightly more negative. The accompanying volume contraction is slightly larger than expected from the lanthanide contraction, 7.6 %. From the so-called Gschneidner correlation one would have expected the contrary behavior, that is, that the bonding strength would become slightly lower when going from LaM₂ to LuM₂. An increase in the transition-metal atomic number has a stronger effect on the enthalpy of formation and atomic volume than an increase in the lanthanide atomic number.     

The effects of Cl-induced alloying in Pt–Sn/Al2O3 catalysts on butane/H2 reactions

The effects of oxidation/reduction regeneration treatments, with and without 1,2-dichloropropane present as a chlorinating agent, on the structure of Pt(3%)–Sn(4.5%)/Al₂O₃ catalysts have been correlated with selectivities for butane/H₂ reactions. Particles of Pt⁰ fin Cl-free catalysts were partly covered by Sn⁰, but retained exposed ensembles of Pt atoms which were active for isomerisation, hydrogenolysis and dehydrogenation reactions, the latter becoming dominant at high reaction temperatures. Coking reduced Pt ensemble size and, hence, also favoured high selectivities for dehydrogenation as hydrogenolysis and isomerisation sites became poisoned. In contrast, the addition of 1,2-dichloropropane in an oxychlorination step before reduction promoted 1:1 Pt⁰–Sn⁰ alloy formation after reduction, the proportion of the total Pt in alloy being enhanced by increasing 1,2-dichloropropane concentration and oxychlorination temperature. The alloy surfaces were inactive for isomerisation and hydrogenolysis reactions, giving dehydrogenation as the sole catalytic reaction.     

Combination of computational prescreening and experimental library construction can accelerate enzyme optimization by directed evolution

Chiral compounds can be produced efficiently by using biocatalysts. However, wild-type enzymes often do not meet the requirements of a production process, making optimization by rational design or directed evolution necessary. Here, we studied the lipase-catalyzed hydrolysis of the model substrate 1-(2-naphthyl)ethyl acetate both theoretically and experimentally. We found that a computational equivalent of alanine scanning mutagenesis based on QM/MM methodology can be applied to identify amino acid positions important for the activity of the enzyme. The theoretical results are consistent with concomitant experimental work using complete saturation mutagenesis and high-throughput screening of the target biocatalyst, a lipase from Bacillus subtilis. Both QM/MM-based calculations and molecular biology experiments identify histidine 76 as a residue that strongly affects the catalytic activity. The experiments demonstrate its important influence on enantioselectivity.     

Chemical inhibitors when timing is critical: a pharmacological concept for the maturation of T cell contacts

Cellular signal transduction proceeds through a complex network of molecular interactions and enzymatic activities. The timing of these molecular events is critical for the propagation of a signal and the generation of a specific cellular response. To define the timing of signalling events, we introduce the combination of high-resolution confocal microscopy with the application of small-molecule inhibitors at various stages of signal transduction in T cells. Inhibitors of Src-family tyrosine kinases and actin dynamics were employed to dissect the role of the lymphocyte-specific tyrosine kinase Lck in the formation and maintenance of T cell receptor/CD3-dependent contacts. Anti-CD3epsilon-coated coverslips served as a highly defined stimulus. The kinetics of the recruitment of the yellow fluorescent protein-tagged signalling protein ZAP-70 were detected by high-resolution confocal microscopy. The analysis revealed that at 5 min after receptor engagement, Lck activity was required for maintenance of contacts. In contrast, after 20 min of receptor engagement, the contacts were Lck-independent. The relevance of the timing of inhibitor application provides a pharmacological concept for the maturation of T cell-substrate contacts.