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<jats:p> At birth, several motoneurons supply neural signals to each muscle fiber, but 2 weeks later all but the input of a single neuron is gone. This process of synapse elimination has now been carefully described in electrophysiological terms in this week's issue in a report by Colman <jats:italic>et al</jats:italic> . ( <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="356" related-article-type="in-this-issue" vol="275" xlink:href="10.1126/science.275.5298.356" xlink:type="simple">p. 356</jats:related-article> ). In his Perspective, Frank explains how the new data fit with what we already know about the changes occurring during synapse elimination and predicts that molecular understanding of this key process will come soon. </jats:p>

<jats:p>A digital library enables users to interact effectively with information distributed across a network. These network information systems support search and display of items from organized collections. In the historical evolution of digital libraries, the mechanisms for retrieval of scientific literature have been particularly important. Grand visions in 1960 led first to the development of text search, from bibliographic databases to full-text retrieval. Next, research prototypes catalyzed the rise of document search, from multimedia browsing across local-area networks to distributed search on the Internet. By 2010, the visions will be realized, with concept search enabling semantic retrieval across large collections.</jats:p>

<jats:p>Mathematical and computational approaches provide powerful tools in the study of problems in population biology and ecosystems science. The subject has a rich history intertwined with the development of statistics and dynamical systems theory, but recent analytical advances, coupled with the enhanced potential of high-speed computation, have opened up new vistas and presented new challenges. Key challenges involve ways to deal with the collective dynamics of heterogeneous ensembles of individuals, and to scale from small spatial regions to large ones. The central issues—understanding how detail at one scale makes its signature felt at other scales, and how to relate phenomena across scales—cut across scientific disciplines and go to the heart of algorithmic development of approaches to high-speed computation. Examples are given from ecology, genetics, epidemiology, and immunology.</jats:p>

<jats:p> Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI <jats:sub>50</jats:sub> ) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI <jats:sub>50</jats:sub> values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents. </jats:p>

<jats:p>Quantum computation remains an enormously appealing but elusive goal. It is appealing because of its potential to perform superfast algorithms, such as finding prime factors in polynomial time, but also elusive because of the difficulty of simultaneously manipulating quantum degrees of freedom while preventing environmentally induced decoherence. A new approach to quantum computing is introduced based on the use of multiple-pulse resonance techniques to manipulate the small deviation from equilibrium of the density matrix of a macroscopic ensemble so that it appears to be the density matrix of a much lower dimensional pure state. A complete prescription for quantum computing is given for such a system.</jats:p>

<jats:p>Permanent removal of axonal input to postsynaptic cells helps shape the pattern of neuronal connections in response to experience, but the process is poorly understood. Intracellular recording from newborn and adult mouse muscle fibers temporarily innervated by two axons showed an increasing disparity in the synaptic strengths of the two inputs before one was eliminated. The connection that survived gained strength by increasing the amount of neurotransmitter released (quantal content), whereas the input that was subsequently removed became progressively weaker, because of a reduction in quantal content and a reduction in quantal efficacy associated with reduced postsynaptic receptor density. Once the synaptic strengths of two inputs began to diverge, complete axonal withdrawal of the weaker input occurred within 1 to 2 days. These experiments provide a link between experience-driven changes in synaptic strength and long-term changes in connectivity in the mammalian nervous system.</jats:p>

<jats:p> The regio- and stereospecificity of bimolecular phenoxy radical coupling reactions, of especial importance in lignin and lignan biosynthesis, are clearly controlled in some manner in vivo; yet in vitro coupling by oxidases, such as laccases, only produce racemic products. In other words, laccases, peroxidases, and comparable oxidases are unable to control regio- or stereospecificity by themselves and thus some other agent must exist. A 78-kilodalton protein has been isolated that, in the presence of an oxidase or one electron oxidant, effects stereoselective bimolecular phenoxy radical coupling in vitro. Itself lacking a catalytically active (oxidative) center, its mechanism of action is presumed to involve capture of <jats:italic>E</jats:italic> -coniferyl alcohol-derived free-radical intermediates, with consequent stereoselective coupling to give (+)-pinoresinol. </jats:p>

<jats:p> Magneto-optical imaging was used to visualize the inhomogeneous penetration of magnetic flux into polycrystalline TlBa <jats:sub>2</jats:sub> Ca <jats:sub>2</jats:sub> Cu <jats:sub>3</jats:sub> O <jats:sub> <jats:italic>x</jats:italic> </jats:sub> films with high critical current densities, to reconstruct the local two-dimensional supercurrent flow patterns and to correlate inhomogeneities in this flow with the local crystallographic misorientation. The films have almost perfect <jats:italic>c</jats:italic> -axis alignment and considerable local <jats:italic>a</jats:italic> - and <jats:italic>b</jats:italic> -axis texture because the grains tend to form colonies with only slightly misaligned <jats:italic>a</jats:italic> and <jats:italic>b</jats:italic> axes. Current flows freely over these low-angle grain boundaries but is strongly reduced at intermittent colony boundaries of high misorientation. The local (&lt;10-micrometer scale) critical current density <jats:italic>J</jats:italic> <jats:sub>c</jats:sub> varies widely, being up to 10 times as great as the transport <jats:italic>J</jats:italic> <jats:sub>c</jats:sub> (scale of ∼1 millimeter), which itself varies by a factor of about 5 in different sections of the film. The combined experiments show that the magnitude of the transport <jats:italic>J</jats:italic> <jats:sub>c</jats:sub> is largely determined by a few high-angle boundaries. </jats:p>

<jats:p>Bedrock landsliding is a dominant geomorphic process in a number of high-relief landscapes, yet is neglected in landscape evolution models. A physical model of sliding in beans is presented, in which incremental lowering of one wall simulates baselevel fall and generates slides. Frequent small slides produce irregular hillslopes, on which steep toes and head scarps persist until being cleared by infrequent large slides. These steep segments are observed on hillslopes in high-relief landscapes and have been interpreted as evidence for increases in tectonic or climatic process rates. In certain cases, they may instead reflect normal hillslope evolution by landsliding.</jats:p>

<jats:p>Paleomagnetic data show less than ∼1000 kilometers of motion between the paleomagnetic and hotspot reference frames—that is, true polar wander—during the past 100 million years, which implies that Earth's rotation axis has been very stable. This long-term rotational stability can be explained by the slow rate of change in the large-scale pattern of plate tectonic motions during Cenozoic and late Mesozoic time, provided that subducted lithosphere is a major component of the mantle density heterogeneity generated by convection. Therefore, it is unnecessary to invoke other mechanisms, such as sluggish readjustment of the rotational bulge, to explain the observed low rate of true polar wander.</jats:p>