The apparent exponential radiation of Phanerozoic land vertebrates reflects spatial sampling biases

There is no consensus about how terrestrial biodiversity was assembled through deep time, and in particular whether it has risen exponentially over the Phanerozoic. Using a database of 60,859 fossil occurrences, we show that the spatial extent of the worldwide terrestrial tetrapod fossil record itself expands exponentially through the Phanerozoic. Changes in spatial sampling explain up to 67% of the change in known fossil species counts and, because these changes are decoupled from variation in habitable land area that existed through time, this therefore represents a real and profound sampling bias that cannot be explained as redundancy. To address this bias, we estimate terrestrial tetrapod diversity for palaeogeographic regions of approximately equal size. We find that regional-scale diversity was constrained over timespans of tens to hundreds of millions of years, and similar patterns are recovered for major subgroups, such as dinosaurs, mammals, and squamates. Although Cretaceous/Paleogene mass extinction catalysed an abrupt two- to three-fold increase in regional diversity 66 million years ago, no further increases occurred, and recent levels of regional diversity do not exceed those of the Paleogene. These results parallel those recovered in analyses of local community-level richness. Taken together, our findings strongly contradict past studies that suggested unbounded diversity increases at local and regional scales over the last 100 million years

Hydrodynamics and Nonlocal Conductivities in Vortex States of Type II Superconductors

A hydrodynamical description for vortex states in type II superconductors is presented based on the time-dependent Ginzburg-Landau equation (TDGL). In contrast to the familiar extension of a single vortex dynamics based on the force balance, our description is consistent with the known hydrodynamics of a rotating neutral superfluid and correctly includes informations on the Goldstone mode. Further it enables one to examine nonlocal conductivities perpendicular to the magnetic field in terms of Kubo formula. The nonlocal conductivities deviate from the usual vortex flow expressions typically when the nonlocality parallel to the field becomes weaker than the perpendicular one measuring a degree of positional correlations, and, for instance, the superconducting contribution of dc Hall conductivity nonlocal only in directions perpendicular to the field becomes vanishingly small in the situations with large shear viscosity, leading to an experimentally measurable relation $\rho_{xy} \sim {\rho_{xx}^2}$ among the total resistivity components. Other situations are also discussed on the basis of the resulting expressions.Comment: 12 pages, no figures, to appear in J. Phys. Soc. Jpn. in October, 199

Biomechanical evolution of solid bones in large animals: a microanatomical investigation

International audienc

Siderophilin Metal Coordination. 1. Complexation of Thorium by Transferrin: Structure-Function Implications

As part of a program to develop actinide-specific sequestering agents, the coordination of actinide ions by human transferrin is being investigated. Therapeutically useful synthetic ligands must be able to compete with this iron-transport protein for the bound actinide ion. As in the Fe(III) complex of the native protein, two Th(IV) ions bind at pH 7. This coordination has been monitored at several pH values by using difference ultraviolet spectroscopy. The corresponding coordination of a phenolic ligand, ethylene-bis-(o-hydroxyphenylglycine) [EHPG], has been used to determine {Delta}{epsilon} for a tyrosyl group coordinated to Th(IV), in contrast to the common practice of assuming the {Delta}{epsilon} for protons and all metal ions is the same. This in turn is used to determine, from the observed {Delta}{epsilon} upon protein coordination, the number of transferrin tyrosine residues that coordinate. Maxima in the Th(IV) + EHPG difference UV spectra occur at 292 and 238 nm, with corresponding {Delta}{epsilon} values per phenolic group of 2330 and 8680 cm{sup -1} M{sup -1}, respectively. At pH 7.2, the Th(IV) transferrin spectrum is closely similar to the TH(IV) EHPG spectrum, with maxima at 292 and 240 nm. The {Delta}{epsilon} at 240 nm reaches a maximum of 24700 cm{sup -1} M{sup -1}, which corresponds to coordination of three tyrosine residues in the dithorium-transferrin complex; the stronger binding site (“A” or C-terminal) coordinates via two tyrosines and the weaker (“B” or N-terminal) via one. There is evidence suggesting that the N-terminal site is slightly smaller than the C-terminal site; while Th(IV) easily fits into the C-terminal site, the large ionic radius of Th(IV) makes this ion of borderline size to fit into the N-terminal site. This may be an important biological difference between Th(IV) and the slightly smaller Pu(IV), which should easily fit into both sites. At pH values below 7, the complexation of Th(IV) by transferrin decreases rapidly. At pH 6 and a Th(IV)/transferrin ratio of 2, only ~0.3 Th(IV) are bound per protein ([Th] = 10{sup -5}M). The N-terminal site is more rapidly affected by lowering the pH, so that coordination is entirely at the C-terminal site at low pH. Above pH 9, the conformation at the C-terminal site (two tyrosines) changes such that only one tyrosine is bound, the same that pertains at the N-terminal site at neutral pH. In addition to the three protons released by the coordinating tyrosine residues, the complexation of two Th(IV) ions releases two more protons at pH 8.6, which are ascribed to hydrolysis, so that the metal is bound as a monohydroxo species. It is suggested that diferric transferrin undergoes a similar reaction, and the other implications of these results for the structure and function of the native ferric transferrin are discussed

Advanced microinstrumentation for rapid DNA sequencing and large DNA fragment separation

Our efforts to develop novel technology for a rapid DNA sequencer and large fragment analysis system based upon gel electrophoresis are described. We are using microfabrication technology to build dense arrays of high speed micro electrophoresis lanes that will ultimately increase the sequencing rate of DNA by at least 100 times the rate of current sequencers. We have demonstrated high resolution DNA fragment separation needed for sequencing in polyacrylamide microgels formed in glass microchannels. We have built prototype arrays of microchannels having up to 48 channels. Significant progress has also been made in developing a sensitive fluorescence detection system based upon a confocal microscope design that will enable the diagnostics and detection of DNA fragments in ultrathin microchannel gels. Development of a rapid DNA sequencer and fragment analysis system will have a major impact on future DNA instrumentation used in clinical, molecular and forensic analysis of DNA fragments

Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo

Malignant mesothelioma (MM) is a rare orphan aggressive neoplasia with low survival rates. Among the other signaling pathways, ErbB receptors and Hh signaling are deregulated in MM. Thus, molecules involved in these signaling pathways could be used for targeted therapy approaches. The aim of this study was to evaluate the effects of inhibitors of Hh- (GANT-61) and ErbB receptors (Afatinib)-mediated signaling pathways, when used alone or in combination, on growth, cell cycle, cell death and autophagy, modulation of molecules involved in transduction pathways, in three human MM cell lines of different histotypes. The efficacy of the combined treatment was also evaluated in a murine epithelioid MM cell line both in vitro and in vivo. This study demonstrated that combined treatment with two inhibitors counteracting the activation of two different signaling pathways involved in neoplastic transformation and progression, such as those activated by ErbB and Hh signaling, is more effective than the single treatments in reducing MM growth in vitro and in vivo. This study may have clinical implications for the development of targeted therapy approaches for MM

Phase retrieval for adaptive optics system calibration

Our objective in this report is to develop methods to determine the output pupil wavefront using intensity measurements directly from the science detector. This wavefront can then be used to determine a reference wavefront which will precorrect for the non-common-path aberrations and produce the desired wavefront at the science detector. We describe two phase retrieval algorithms that can be used and a set of simulation studies of AO system calibration. We present the initial experimental results of applying this technique in calibration of the Lick Observatory laser guidestar AO system in a later paper