Inverse computation and the Universal Resolving Algorithm

We survey fundamental concepts for inverse programming and then present the Universal Resolving Algorithm, an algorithm for inverse computation in a first-order, functional programming language. We discuss the key concepts of the algorithm, including a three-step approach based on the notion of a perfect process tree, and demonstrate our implementation with several examples of inverse computation.     

A precision measurement of the mass of the top quark

The standard model of particle physics contains parameters--such as particle masses--whose origins are still unknown and which cannot be predicted, but whose values are constrained through their interactions. In particular, the masses of the top quark (M(t)) and W boson (M(W)) constrain the mass of the long-hypothesized, but thus far not observed, Higgs boson. A precise measurement of M(t) can therefore indicate where to look for the Higgs, and indeed whether the hypothesis of a standard model Higgs is consistent with experimental data. As top quarks are produced in pairs and decay in only about 10(-24) s into various final states, reconstructing their masses from their decay products is very challenging. Here we report a technique that extracts more information from each top-quark event and yields a greatly improved precision (of +/- 5.3 GeV/c2) when compared to previous measurements. When our new result is combined with our published measurement in a complementary decay mode and with the only other measurements available, the new world average for M(t) becomes 178.0 +/- 4.3 GeV/c2. As a result, the most likely Higgs mass increases from the experimentally excluded value of 96 to 117 GeV/c2, which is beyond current experimental sensitivity. The upper limit on the Higgs mass at the 95% confidence level is raised from 219 to 251 GeV/c2.     

Phylogeography of the Eurasian red squirrel (Sciurus vulgaris orientis) on the boreal island of Hokkaido,Japan

To test postglacial population expansion in small arboreal mammals dependent on boreal and subboreal forests, we used complete mitochondrial cytochrome b gene sequences (1140 bases) to investigate the phylogeography of the Eurasian red squirrel (Sciurus vulgaris orientis) on the Hokkaido Island of Japan. This subspecies is common in the boreal and subboreal forests of Hokkaido. We examined 61 specimens from 27 localities in Hokkaido. Phylogenetic relationships among 29 haplotypes found in the Hokkaido populations were not associated with geographic distribution of sampling localities. There were four mitochondrial DNA phylogroups. Phylogeographic analyses support sudden expansion of S. vulgaris orientis from restricted refugium in the southern part of Hokkaido during the last glacial period. The phylogeographic structure of this subspecies directly reflects the boreal and subboreal forest dynamics occurring in Hokkaido.     

The large-conductance Ca2+-activated K+ channel is essential for innate immunity

Neutrophil leukocytes have a pivotal function in innate immunity. Dogma dictates that the lethal blow is delivered to microbes by reactive oxygen species (ROS) and halogens, products of the NADPH oxidase, whose impairment causes immunodeficiency. However, recent evidence indicates that the microbes might be killed by proteases, activated by the oxidase through the generation of a hypertonic, K+-rich and alkaline environment in the phagocytic vacuole. Here we show that K+ crosses the membrane through large-conductance Ca2+-activated K+ (BK(Ca)) channels. Specific inhibitors of these channels, iberiotoxin and paxilline, blocked oxidase-induced 86Rb+ fluxes and alkalinization of the phagocytic vacuole, whereas NS1619, a BK(Ca) channel opener, enhanced both. Characteristic outwardly rectifying K+ currents, reversibly inhibited by iberiotoxin, were demonstrated in neutrophils and eosinophils and the expression of the alpha-subunit of the BK channel was confirmed by western blotting. The channels were opened by the combination of membrane depolarization and elevated Ca2+ concentration, both consequences of oxidase activity. Remarkably, microbial killing and digestion were abolished when the BK(Ca) channel was blocked, revealing an essential and unexpected function for this K+ channel in the microbicidal process.