Scrutinizing thing knowledge

In his book Thing Knowledge Davis Baird argues that our accustomed understanding of knowledge as justified true beliefs is not enough to understand progress in science and technology. To be more accurate he argues that scientific instruments are to be seen as a form of “objective knowledge” in the sense of Karl Popper.I want to examine if this idea is plausible. In a first step I want to show that this proposal implies that nearly all man-made artifacts are materialized objective knowledge. I argue that this radical change in our concept of knowledge demands strong reasons and that Baird does not give them. I take a look at the strongest strand of arguments of Baird's book—the arguments from cognitive autonomy—and conclude that they do not suffice to make Baird's view of scientific instruments tenable.     

Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper

Staphylococcus aureus and Streptococcus pyogenes, two important human pathogens, target host fibronectin (Fn) in their adhesion to and invasion of host cells. Fibronectin-binding proteins (FnBPs), anchored in the bacterial cell wall, have multiple Fn-binding repeats in an unfolded region of the protein. The bacterium-binding site in the amino-terminal domain (1-5F1) of Fn contains five sequential Fn type 1 (F1) modules. Here we show the structure of a streptococcal (S. dysgalactiae) FnBP peptide (B3) in complex with the module pair 1F12F1. This identifies 1F1- and 2F1-binding motifs in B3 that form additional antiparallel beta-strands on sequential F1 modules-the first example of a tandem beta-zipper. Sequence analyses of larger regions of FnBPs from S. pyogenes and S. aureus reveal a repeating pattern of F1-binding motifs that match the pattern of F1 modules in 1-5F1 of Fn. In the process of Fn-mediated invasion of host cells, therefore, the bacterial proteins seem to exploit the modular structure of Fn by forming extended tandem beta-zippers. This work is a vital step forward in explaining the full mechanism of the integrin-dependent FnBP-mediated invasion of host cells.     

A multi-component Fermi surface in the vortex state of an underdoped high-Tc superconductor

To understand the origin of superconductivity, it is crucial to ascertain the nature and origin of the primary carriers available to participate in pairing. Recent quantum oscillation experiments on high-transition-temperature (high-T(c)) copper oxide superconductors have revealed the existence of a Fermi surface akin to that in normal metals, comprising fermionic carriers that undergo orbital quantization. The unexpectedly small size of the observed carrier pocket, however, leaves open a variety of possibilities for the existence or form of any underlying magnetic order, and its relation to d-wave superconductivity. Here we report experiments on quantum oscillations in the magnetization (the de Haas-van Alphen effect) in superconducting YBa(2)Cu(3)O(6.51) that reveal more than one carrier pocket. In particular, we find evidence for the existence of a much larger pocket of heavier mass carriers playing a thermodynamically dominant role in this hole-doped superconductor. Importantly, characteristics of the multiple pockets within this more complete Fermi surface impose constraints on the wavevector of any underlying order and the location of the carriers in momentum space. These constraints enable us to construct a possible density-wave model with spiral or related modulated magnetic order, consistent with experimental observations.     

An African origin for the intimate association between humans and Helicobacter pylori

Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation, the age of an association between these bacteria with humans remains highly controversial. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.     

Premature ageing in mice expressing defective mitochondrial DNA polymerase

Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing process, their possible causative effects have been intensely debated because of their low abundance and purely correlative connection with ageing. We have now addressed this question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase. Here we show that the knock-in mice develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals.     

Seismological constraints on a possible plume root at the core-mantle boundary

Recent seismological discoveries have indicated that the Earth's core-mantle boundary is far more complex than a simple boundary between the molten outer core and the silicate mantle. Instead, its structural complexities probably rival those of the Earth's crust. Some regions of the lowermost mantle have been observed to have seismic wave speed reductions of at least 10 per cent, which appear not to be global in extent. Here we present robust evidence for an 8.5-km-thick and approximately 50-km-wide pocket of dense, partially molten material at the core-mantle boundary east of Australia. Array analyses of an anomalous precursor to the reflected seismic wave ScP reveal compressional and shear-wave velocity reductions of 8 and 25 per cent, respectively, and a 10 per cent increase in density of the partially molten aggregate. Seismological data are incompatible with a basal layer composed of pure melt, and thus require a mechanism to prevent downward percolation of dense melt within the layer. This may be possible by trapping of melt by cumulus crystal growth following melt drainage from an anomalously hot overlying region of the lowermost mantle. This magmatic evolution and the resulting cumulate structure seem to be associated with overlying thermal instabilities, and thus may mark a root zone of an upwelling plume.     

Dimensional reduction at a quantum critical point

Competition between electronic ground states near a quantum critical point (QCP)--the location of a zero-temperature phase transition driven solely by quantum-mechanical fluctuations--is expected to lead to unconventional behaviour in low-dimensional systems. New electronic phases of matter have been predicted to occur in the vicinity of a QCP by two-dimensional theories, and explanations based on these ideas have been proposed for significant unsolved problems in condensed-matter physics, such as non-Fermi-liquid behaviour and high-temperature superconductivity. But the real materials to which these ideas have been applied are usually rendered three-dimensional by a finite electronic coupling between their component layers; a two-dimensional QCP has not been experimentally observed in any bulk three-dimensional system, and mechanisms for dimensional reduction have remained the subject of theoretical conjecture. Here we show evidence that the Bose-Einstein condensate of spin triplets in the three-dimensional Mott insulator BaCuSi2O6 (refs 12-16) provides an experimentally verifiable example of dimensional reduction at a QCP. The interplay of correlations on a geometrically frustrated lattice causes the individual two-dimensional layers of spin-(1/2) Cu2+ pairs (spin dimers) to become decoupled at the QCP, giving rise to a two-dimensional QCP characterized by linear power law scaling distinctly different from that of its three-dimensional counterpart. Thus the very notion of dimensionality can be said to acquire an 'emergent' nature: although the individual particles move on a three-dimensional lattice, their collective behaviour occurs in lower-dimensional space.     

ClustNails:Visual Analysis of Subspace Clusters

Subspace clustering addresses an important problem in clustering multi-dimensional data.In sparse multi-dimensional data,many dimensions are irrelevant and obscure the cluster boundaries.Subspace clustering helps by mining the clusters present in only locally relevant subsets of dimensions.However,understanding the result of subspace clustering by analysts is not trivial.In addition to the grouping information,relevant sets of dimensions and overlaps between groups,both in terms of dimensions and records,need to be analyzed.We introduce a visual subspace cluster analysis system called ClustNails.It integrates several novel visualization techniques with various user interaction facilities to support navigating and interpreting the result of subspace clustering.We demonstrate the effectiveness of the proposed system by applying it to the analysis of real world data and comparing it with existing visual subspace cluster analysis systems.     

Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate

Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyses their polymerization and mediates pilus translocation across the outer membrane. Here we report the crystal structure of the full-length FimD usher bound to the FimC-FimH chaperone-adhesin complex and that of the unbound form of the FimD translocation domain. The FimD-FimC-FimH structure shows FimH inserted inside the FimD 24-stranded β-barrel translocation channel. FimC-FimH is held in place through interactions with the two carboxy-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a marked conformational change in the β-barrel. The amino-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone-subunit complex. The FimD-FimC-FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.