bluuebunny/crossref_metadata_2025 huggingface dataset:
Microfabrication of fractal polymeric structures for capillary morphogenesis: Applications in therapeutic angiogenesis and in the engineering of vascularized tissue
Authors: Bianchi F. , Rosi M. , Vozzi G. , Emanueli C. , Madeddu P. , Ahluwalia A.
Published: October 2006

Microfabrication techniques were combined with fractal algorithms to realize polymeric scaffolds resembling capillary networks. The scaffolds were seeded with human endothelial cells in monoculture as well as in coculture with human fibroblasts. To enhance the process of angiogenesis, endothelial cells were transfected with an adenoviral vector carrying the gene for human tissue kallikrien. The results demonstrate that both the presence of a structured scaffold as well as fibroblasts in coculture contribute synergically to the promotion of a metabolically active network. The fractal scaffolds have several possible applications for example in vascularized tissue engineering and therapeutic angiogenesis. A broader implication of these results is that cell‐extra cellular matrix and cell‐cell interactions cooperate dynamically both at a biochemical as well as microstructural level. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Growing tissue‐like constructs with Hep3B/HepG2 liver cells on PHBV microspheres of different sizes
Authors: Zhu Xin Hao , Wang Chi‐Hwa , Tong Yen Wah
Published: October 2006

In this study, an oil‐in‐water emulsion solvent evaporation technique was used to fabricate poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV, 8% PHV), microspheres as scaffold, to guide liver cell growth. Human hepatoma cell lines, HepG2 and Hep3B, were cultured in vitro on both the microspheres and polymer films. SEM and optical microscope images showed that multilayer cells were formed among the microspheres to bridge them together and developed into cell‐construct aggregates after 1 week of culture. MTT results showed that the cell proliferation on the microspheres was more than two times higher than that on the films after 12 days of culture. The cells seeded on microspheres secreted albumin 2–4 times more than that on the positive control after 1 week of culture, which indicated that this hepatic function was greatly improved by the aggregation of cells on microspheres. Although HepG2 failed to express P‐450 activity, this hepatic function was preserved when Hep3B cultured on microspheres. All the results indicated that PHBV microspheres are appropriate scaffolds for liver tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Safety evaluation of large external fixation clamps and frames in a magnetic resonance environment
Authors: Luechinger Roger , Boesiger Peter , Disegi John A.
Published: October 2006

Large orthopedic external fixation clamps and related components were evaluated for force, torque, and heating response when subjected to the strong electromagnetic fields of magnetic‐resonance (MR) imaging devices. Forces induced by a 3‐Tesla (T) MR scanner were compiled for newly designed nonmagnetic clamps and older clamps that contained ferromagnetic components. Heating trials were performed in a 1.5 and in a 3 T MR scanner with two assembled external fixation frames. Forces of the newly designed clamps were more than a factor 2 lower as the gravitational force on the device whereas, magnetic forces on the older devices showed over 10 times the force induced by earth acceleration of gravity. No torque effects could be found for the newly designed clamps. Temperature measurements at the tips of Schanz screws in the 1.5 T MR scanner showed a rise of 0.7°C for a pelvic frame and of 2.1°C for a diamond knee bridge frame when normalized to a specific absorption rate (SAR) of 2 W/kg. The normalized temperature increases in the 3 T MR scanner were 0.9°C for the pelvic frame and 1.1°C for the knee bridge frame. Large external fixation frames assembled with the newly designed clamps (390 Series Clamps), carbon fiber reinforced rods, and implant quality 316L stainless steel Schanz screws met prevailing force and torque limits when tested in a 3‐T field, and demonstrated temperature increase that met IEC‐60601 guidelines for extremities. The influence of frame‐induced eddy currents on the risk of peripheral nerve stimulation was not investigated. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Scattering from infinite rough tubular surfaces
Authors: Claeys Xavier , Haddar Houssem
Published: October 2006

We study the Helmholtz equation in the exterior of an infinite perturbed cylinder with a Dirichlet boundary condition. Existence and uniqueness of solutions are established using the variational technique introduced (SIAM J. Math. Anal. 2005; 37(2):598–618). We also provide stability estimates with explicit dependence of the constants in terms of the frequency and the perturbed cylinder thickness. Copyright © 2006 John Wiley & Sons, Ltd.
On existence and regularity of solutions for 2‐D micropolar fluid equations with periodic boundary conditions
Authors: Szopa Piotr
Published: October 2006

In this paper, we prove the existence and uniqueness of a global solution for 2‐D micropolar fluid equation with periodic boundary conditions. Then we restrict ourselves to the autonomous case and show the existence of a global attractor. Copyright © 2006 John Wiley & Sons, Ltd.
Coupled solution of heat and moisture flow in unsaturated clay barriers in a repository geometry
Authors: Chen G. J. , Ledesma A.
Published: October 2006

An analytical solution in the Laplace transform domain is obtained for the transient heat and moisture transport in an unsaturated clay buffer with a geometry simulating repository conditions. A numerical inversion scheme based on Crump's method is used to obtain the time‐domain solution. The coupled effect of thermally driven moisture transport is especially investigated because of its importance to alter the flow field in low‐permeability buffers. The practical background is based on the case of an engineering bentonite barrier placed in a drift excavated in rock in the context of underground disposal of high‐level radioactive waste. Parametric study has been performed to assess the effects of dimensionless geometry and material parameters on flow field. Despite the simplified assumptions required in order to obtain analytical expressions, the results incorporate the main mechanisms involved in the coupled thermo‐hydraulic (T–H) problem, and they may be eventually used for validation purposes. Copyright © 2006 John Wiley & Sons, Ltd.
Insect gonadotropic peptide hormones: some recent developments
Authors: Kuczer Mariola , Rosiński Grzegorz , Konopińska Danuta
Published: October 2006

Gonadotropic peptides are a new generation of peptide hormone regulators of insect reproduction. They have been isolated from ovaries, oviducts, or brains of insects. The subject of this paper is insect peptides that exert stimulatory or inhibitory effects on ovarian development and oocyte maturation. On the basis of the literature data and the results of our investigations, the structure and biological properties of different groups of peptides are presented. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.
Quantitative Structure Vasodilatory Activity Relationship – Synthesis and “In Silico” and “In Vitro” Evaluation of Resveratrol‐Coumarin Hybrids
Authors: Vilar Santiago , Quezada Elías , Alcaide Carlos , Orallo Francisco , Santana Lourdes , Uriarte Eugenio
Published: October 2006

Three theoretical models have been developed for the prediction of vasodilatory activity through a series of 2‐D molecular descriptors. A database of 501 compounds was selected from the literature and, of these compounds, 86 have vasodilatory activity. The QSAR models are capable of differentiating between active and inactive compounds with a level of classification greater than 80%. The models were used to predict the activity of a series of coumarins derived from resveratrol (a natural compound that is present in wine and has good vasodilatory activity) and led to the synthesis of three selected molecules. The sysnthesis of the resveratrol‐coumarin hybrids was efficiently achieved through a straightforward and direct route, and their vasodilatory activities were determined experimentally in rat aorta rings that were precontreated with noradrenaline. The theoretical results (“in silico” evaluation) show very good agreement with the experimental data (“in vitro” evaluation), which provide evidence of the reliability of the theoretical calculations and show their applicability in the rational design of new compounds. The compound predicted by the three models to be active (compound6) was confirmed to be the more active thantrans‐resveratrol.
Partnering with the state for sustainable development: Shell's experience in the Niger Delta, Nigeria
Authors: Ite Uwem E.
Published: October 2006

There is now growing consensus that moves towards sustainable development should involve constructive inputs from business, government and civil society. This paper critically examines the emerging partnership for human, institutional development and provision of physical infrastructure between the Shell Petroleum Development Company (SPDC) and the Niger Delta Development Commission (NDDC) in Nigeria. It argues that although SPDC is undertaking partnership with NDDC as part of its overall CSR strategy for the region its success will be influenced by four key challenges. These are political support for NDDC, funding constraints, public perceptions and expectations of NDDC, as well as institutional priorities. The implications of the findings for current debates on partnership and the role of business in society are highlighted. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Coarse woody debris mass and nutrients in forest ecosystems of Korea
Authors: Kim Rae‐Hyun , Son Yowhan , Lim Jong Hwan , Lee Im Kyun , Seo Kyung Won , Koo Jin Woo , Noh Nam Jin , Ryu Soung‐Ryoul , Hong Sun Kee , Ihm Byung Sun
Published: October 2006

Coarse woody debris (CWD) is an essential component of forests. However, quantification of both the mass and nutrient content of CWD within a given environment tends to be a fairly labor‐intensive proposition that requires long‐term studies to be conducted for viable data to be obtained. As a result, various aspects of CWD in forest ecosystems remain somewhat poorly understood. In this review, we have compiled all available estimates of CWD mass and nutrients from both coniferous and deciduous forests in Korea. The CWD mass data varied substantially by forest type, age, location, and sampling time, ranging from 1.5 to 24.5 Mg ha−1, and for the amount (kg ha−1) of nutrients in the CWD, ranging from 3.5 to 23.6 for nitrogen (N), 0.8 to 4.7 for phosphorus (P), 3.9 to 13.3 for potassium (K), 25.9 to 30.9 for calcium (Ca), 1.4 to 4.2 for magnesium (Mg), and 0.1 to 0.6 for sodium (Na). The mass of CWD transferred from live trees to the forest floor ranged between 0.1 and 4.9 Mg ha−1year−1, and these values were roughly equivalent to 26–42% of the annual litterfall inputs (2.5–10.8 Mg ha−1year−1) for mixedQuercusspp. forests within the relevant region. Annual nutrients inputs (kg ha−1year−1) through CWD decomposition were 0.7–1.6 for N, 0.04–0.3 for P, 0.3–1.0 for K, 1.7–3.1 for Ca, and 0.1–0.3 for Mg. Consequently, these results revealed that the ecological value of CWD for C and nutrient cycling was relatively insignificant. However, only a limited number of studies have been conducted on CWD in different coniferous or mixed deciduous forests in the region. As a direct result of this paucity of data, further long‐term studies on CWD mass and nutrients in a variety of forest types are required in order to be able to evaluate accurately the ecological value of CWD on biodiversity and physical properties in Korean forest ecosystems.
Posterior Approach for Double Nerve Transfer for Restoration of Shoulder Function in Upper Brachial Plexus Palsy
Authors: Colbert Stephen H. , Mackinnon Susan
Published: October 2006

Restoration of shoulder function is one of the most critical goals of treatment of brachial plexus injuries. Primary repair or nerve grafting of avulsion injuries of the upper brachial plexus in adults often leads to poor recovery. Nerve transfers have provided an alternative treatment with great potential for improved return of function. Many different nerves have been utilized as donor nerves for transfer to the suprascapular nerve and axillary nerve for return of shoulder function with variable results. As our knowledge of shoulder neuromuscular anatomy and physiology improves and our experience with nerve transfers increases, so evolve the specific transfer procedures. This article presents a technique and rationale for reconstructing shoulder function by transferring the distal spinal accessory nerve to the suprascapular nerve and the nerve branch to the medial head of the triceps to the axillary nerve, both through a posterior approach.
The Upper Miocene of the southern North Sea Basin (northern Belgium): a palaeoenvironmental and stratigraphical reconstruction using dinoflagellate cysts
Authors: LOUWYE STEPHEN , DE SCHEPPER STIJN , LAGA PIETER , VANDENBERGHE NOËL
Published: October 2006

Organic-walled palynomorph assemblages from the Kasterlee Formation in northern Belgium provide new insights into the Late Miocene depositional history and palaeoenvironments of the southernmost North Sea Basin. Ranges of key dinoflagellate cysts constrain the unit between 7.5 and 5.32 Ma, that is, a latest Tortonian to Messinian age. The palynomorph assemblage is characterized, amongst others, by Geonettia clineae, an opportunistic species that thrives in mesotrophic, coastal embayments with a low sediment influx. This environmental setting is corroborated by the notable presence of Gramocysta verricula, a species with preference for shallow marine environments. The occurrence of species of the fresh water green alga Pediastrum indicates manifest river discharge in a near-shore environment or embayment. The coastal depositional environment mirrored by the palynomorphs of the Kasterlee Formation succeeds the distinct transgressive and fully marine environments of the underlying Diest Formation in the Campine area. The results from the palynological study, combined with lithological and geophysical data, show that both Upper Miocene formations are two distinct depositional cycles separated by an erosional or regressive phase. The upper boundary of the Kasterlee Formation is correlated with the Me2 sequence boundary at 5.73 Ma. The Kasterlee Formation is herein formally moved from the Lower Pliocene series to the Upper Miocene series. The coastal environment, probably characterized by a shoaling phase, recorded at the border of the southern North Sea Basin, matches the global record of regressive phases in Messinian sedimentary sequences, which are linked to cooling and increasing global ice volume.
The relevance of repair for classroom correction
Authors: MACBETH DOUGLAS
Published: October 2006

This article attempts to align a familiar task of classroom teaching, eliciting from students correct answers about their lessons, with a major organizational domain in studies of natural conversation, that of conversational repair. Numerous studies have analyzed correction sequences in classroom discourse, and our discussion pays special attention to McHoul's (1990) treatment of “repair in classroom talk.” McHoul directly measures the findings on repair in studies of natural conversation to the regularities of correction sequences in classroom lessons. It is argued, contra McHoul, that repair is a different, and prior, order of discursive work, and one that premises the very possibility of classroom correction. Further, the difference may have wider relevance for understanding repair and correction as “co-operating” organizations of talk-in-interaction more generally.
Robert Bayley and Sandra R. Schecter (eds.), Language
socialization in bilingual and multilingual societies. Clevedon,
UK: Multilingual Matters Ltd., 2003. Pp. xii, 311. Hb $79.95, pb
$29.95.
Authors: Garrett Paul B.
Published: October 2006

The title of this edited volume leads one to expect a timely
contribution to the literature on language socialization, which has
become increasingly concerned with bilingual and multilingual settings
over the past decade or so. Some readers with general interests in
bilingual and multilingual situations, or with special interests in
education in such settings, may find this collection worthwhile. Those
with a particular interest in language socialization, however, will be
disappointed – and perhaps irritated to have been misled by the
title. The volume's 16 chapters present a broad variety of
interesting case studies, but very few among them can accurately be
characterized as language socialization studies.
Machiko Achiba, Learning to request in a second
language: A study of child interlanguage pragmatics. Clevedon, UK:
Multilingual Matters, 2003. Pp. xii, 223. HB £42.95/US
$69.95/Can $99.95.
Authors: Kato-Yoshioka Akiko
Published: October 2006

The question of “how second languages are learned” (Gass & Selinker 1994:1) is central to second
language acquisition (SLA) research; however, although a number of
longitudinal studies have been carried out examining second language
(L2) grammatical development, very little attention has been devoted to
L2 learners' development of pragmatic competence over time. As
Achiba points out, the majority of previous studies on L2 (or
interlanguage) pragmatics have observed the single-moment pragmatic
realization of a group of L2 learners with similar proficiency levels
and compared it with that of native speakers or L2 learners with
different proficiency levels or first language (L1) backgrounds. The
current paucity of knowledge regarding the developmental aspect of L2
pragmatic competence has led to calls for detailed longitudinal
interlanguage pragmatic studies (cf. Kasper &
Schmidt 1996, Kasper & Rose 1999).
Achiba's study, which carefully observes the pragmatic development
in English requestive realization of a seven-year-old Japanese girl
over a period of 17 months, certainly meets these essential needs.
Andrew Dalby, Language in danger: The loss of
linguistic diversity and the threat to our future. New York:
Columbia University Press. 329 pages. Hb $27.95.
Authors: Rottet Kevin J.
Published: October 2006

Recent years have seen several general introductions to the study of
endangered languages, aimed primarily at readers with no special
training in linguistics. This is true of Dalby's book as well, and
he succeeds in providing the general public with a highly readable
account of a current and important linguistic topic.
Who killed the International Studies Conference?
Authors: LONG DAVID
Published: October 2006

This article considers the rise and fall of the first institution of international academic cooperation on international relations, the International Studies Conference (ISC), which was established in 1928 and continued activities into the 1950s. Its formation preceded by decades the present ISA as well as the international organisation of political scientists. The demise of the ISC was a result of the failings of the ISC itself, the influence of UNESCO especially its Department of Social Sciences, and the challenge posed to the ISC by the formation of the International Political Science Association.
Negotiating ethics: Campbell, ontopology and hospitality
Authors: BULLEY DAN
Published: October 2006

David Campbell has been at the forefront of showing how deconstruction, and the philosophy of Jacques Derrida, can help us to think international relations differently. Like Derrida himself, Campbell has eschewed the goal of an ethical theory in favour of an ‘ethos of political criticism’ concerned to question and go beyond our assumptions and limits. In order to continue such an ethos of criticism, to push our understanding of ethics in international relations further still, it is surely important to question the assumptions and limits Campbell himself imposes. It is with this in mind that I wish to take a particular political intervention by Derrida in 1993 and read it against Campbell’s Derridean analysis of the Bosnian conflict which began in 1992.
Electrostatic force microscopy as a tool to estimate the number of active potential barriers in dense non-Ohmic polycrystalline SnO2 devices
Authors: Vasconcelos J. S. , Vasconcelos N. S. L. S. , Orlandi M. O. , Bueno P. R. , Varela J. A. , Longo E. , Barrado C. M. , Leite E. R.
Published: October 2006

In the present work, electroactive grain boundaries of highly dense metal oxide SnO2-based polycrystalline varistors were determined by electrostatic force microscopy (EFM). The EFM technique was applied to identify electroactive grain boundaries and thus estimate the amount of active grain boundary, which, in the metal oxide SnO2-based varistor, was calculated at around 85%, i.e., much higher than that found in traditional metal oxide ZnO-based varistors. The mean potential barrier height value obtained from the EFM analysis was in complete agreement with the values calculated from the C-V measurements, together with a complex capacitance plane analysis that validates the methodology proposed here.
Development of a novel bioreactor to apply shear stress and tensile strain simultaneously to cell monolayers
Authors: Breen Liam T. , McHugh Peter E. , McCormack Brendan A. , Muir Gordon , Quinlan Nathan J. , Heraty Kevin B. , Murphy Bruce P.
Published: October 2006

To date many bioreactor experiments have investigated the cellular response to isolated in vitro forces. However, in vivo, wall shear stress (WSS) and tensile hoop strain (THS) coexist. This article describes the techniques used to build and validate a novel vascular tissue bioreactor, which is capable of applying simultaneous wall shear stress and tensile stretch to multiple cellular substrates. The bioreactor design presented here combines a cone and plate rheometer with flexible substrates. Using such a combination, the bioreactor is capable of applying a large range of pulsatile wall shear stress (−30to+30dyn∕cm2) and tensile hoop strain (0%–12%). The WSS and THS applied to the cellular substrates were validated and calibrated. In particular, curves were produced that related the desired WSS to the bioreactor control parameters. The bioreactor was shown to be biocompatible and noncytotoxic and suitable for cellular mechanical loading studies in physiological condition, i.e., under simultaneous WSS and THS conditions.
Nonlinear dust drift Alfvén waves in rotating planetary magnetospheres
Authors: Haque Q. , Saleem H.
Published: October 2006

Linear and nonlinear electromagnetic waves are investigated in the dusty magnetospheres of rotating planets. In the presence of heavy dust, the plasma may support very low frequency waves that can be affected by the plasma rotation. It is also shown that Alfvén waves can couple with the electrostatic dust drift waves induced by the planetary rotation. A comparison of the results with a previous work has also been made in the electrostatic limit. The electromagnetic vortex structures can be formed in rotating planetary dusty plasmas in the nonlinear regime. An application of this theory to dusty plasmas of the magnetospheres of Saturn and Jupiter is pointed out.
Intersubband resonant enhancement of second-harmonic generation in GaN∕AlN quantum wells
Authors: Nevou L. , Tchernycheva M. , Julien F. , Raybaut M. , Godard A. , Rosencher E. , Guillot F. , Monroy E.
Published: October 2006

This letter reports on the observation of resonant enhancement by intersubband transitions of the second-harmonic generation of ∼1μm radiation in GaN∕AlN quantum wells grown on AlN∕c-sapphire templates. Quantum wells with a nominal well thickness of 10 ML have been investigated in terms of intersubband linear and nonlinear optical properties. A strong increase of the second-harmonic conversion is observed at a pump wavelength of ∼2μm, which is attributed to double-resonance enhancement of the nonlinear susceptibility by intersubband transitions. The second-order susceptibility at resonance is of the order of 114pm∕V, in good agreement with calculations.
Quantum-confined Stark effect in interdiffused quantum dots
Authors: Wang Y. , Djie H. S. , Ooi B. S.
Published: October 2006

The authors theoretically investigate the effects of isotropic composition interdiffusion on the optical transition energy of quantum-dot (QD) structures under an electric field. Their three-dimensional QD calculation is based on coupled InAs∕GaAs QDs arranged periodically in a tetragonal superlattice, taking into account the effects of finite band offset, valence-band mixing, strain, effective mass anisotropicity, and different QD shapes. The electron and hole Hamiltonians with the interdiffusion effect are solved in the momentum space domain. The enhanced Stark shifts and the reduced built-in dipole moment have been found for the interdiffused QD structures.
Temperature compensation of Wheatstone bridge magnetoresistive sensors based on generalized impedance converter with input reference current
Authors: Ramírez Muñoz Diego , Sánchez Moreno J. , Casans Berga Silvia , Castro Montero Enrique , Reig Escrivà Càndid , Navarro Antón A. Edith
Published: October 2006

A compensation method of the sensitivity drift of the Wheatstone bridge sensor is proposed. The technique was carried out by placing a temperature sensor and the bridge to be compensated inside a generalized impedance converter with input reference current. No internal modification of the bridge arms is required so that the circuit is capable to compensate practical industrial sensors. The method is based on the temperature modulation of the current supplied to the bridge, which improves previous solutions based on constant current compensation. Experimental results are shown using a commercial magnetoresistive bridge sensor.
Investigation of effective mass of carriers in Bi2Te3̸Sb2Te3 superlattices via electronic structure studies on its component crystals
Authors: Wang Guofeng , Cagin Tahir
Published: October 2006

The electronic structures of Bi2Te3 and Sb2Te3 were computed and related to the thermoelectric properties of Bi2Te3̸Sb2Te3 superlattices. The authors found that the similarity of the electronic structure of the two materials permits the Bi2Te3̸Sb2Te3 superlattices inherit high band edge degeneracy, and thus have high electrical conductivity. From the calculated effective mass along the superlattice growth direction, we infer that presence of more Sb2Te3 than Bi2Te3 in the superlattice leads to a smaller effective mass and enhanced carrier mobility. Furthermore, our results suggest that external tensile strain parallel to the interface may further improve the thermoelectric performance of the Bi2Te3̸Sb2Te3 superlattices.
Transition-metal-doping-enhanced hydrogen storage in boron nitride systems
Authors: Shevlin S. A. , Guo Z. X.
Published: October 2006

The authors perform spin-polarized density functional theory simulations on the 3d transition metal (TM) series (Sc to Fe) doped system borazine (B3N3H6). The Sc and Ti bind most strongly to borazine but Cr and Mn do not bind at all. With increasing hydrogen content the bound hydrogen species becomes molecular. The maximum amount of hydrogen that can be stored is 4H2 per TM atom for Sc, Ti, and V dopants (∼6wt% bound hydrogen). The binding energy of hydrogen in these systems is of the order of −0.3to−0.7eV∕H2, desirable for practical hydrogen storage applications. The optimum dopant is titanium.
Band structure mapping of photonic crystal intersubband detectors
Authors: Schartner S. , Golka S. , Pflügl C. , Schrenk W. , Andrews A. M. , Roch T. , Strasser G.
Published: October 2006

The authors report on a quantum well infrared detector embedded in a surface-plasmon waveguide and processed into a deeply etched photonic crystal structure. The device was characterized by collecting the polarization dependent response spectra at different angles of incidence. With this method it is possible to map the photonic band structure by directly detecting the modes of the photonic crystal. It therefore represents a new and direct characterization procedure for photonic crystals. The device shows a strong mixing between TE and TM polarized modes, which is caused by the asymmetric vertical waveguide design.
Uncertainty in predictions of disease spread and public health responses to bioterrorism and emerging diseases
Authors: Elderd Bret D. , Dukic Vanja M. , Dwyer Greg
Published: October 2006

Concerns over bioterrorism and emerging diseases have led to the widespread use of epidemic models for evaluating public health strategies. Partly because epidemic models often capture the dynamics of prior epidemics remarkably well, little attention has been paid to how uncertainty in parameter estimates might affect model predictions. To understand such effects, we used Bayesian statistics to rigorously estimate the uncertainty in the parameters of an epidemic model, focusing on smallpox bioterrorism. We then used a vaccination model to translate the uncertainty in the model parameters into uncertainty in which of two vaccination strategies would provide a better response to bioterrorism, mass vaccination, or vaccination of social contacts, so-called “trace vaccination.” Our results show that the uncertainty in the model parameters is remarkably high and that this uncertainty has important implications for vaccination strategies. For example, under one plausible scenario, the most likely outcome is that mass vaccination would save ≈100,000 more lives than trace vaccination. Because of the high uncertainty in the parameters, however, there is also a substantial probability that mass vaccination would save 200,000 or more lives than trace vaccination. In addition to providing the best response to the most likely outcome, mass vaccination thus has the advantage of preventing outcomes that are only slightly less likely but that are substantially more horrific. Rigorous estimates of uncertainty thus can reveal hidden advantages of public health strategies, suggesting that formal uncertainty estimation should play a key role in planning for epidemics.
Divergent mtDNA lineages of goats in an Early Neolithic site, far from the initial domestication areas
Authors: Fernández Helena , Hughes Sandrine , Vigne Jean-Denis , Helmer Daniel , Hodgins Greg , Miquel Christian , Hänni Catherine , Luikart Gordon , Taberlet Pierre
Published: October 2006

Goats were among the first farm animals domesticated, ≈10,500 years ago, contributing to the rise of the “Neolithic revolution.” Previous genetic studies have revealed that contemporary domestic goats (
Capra hircus
) show far weaker intercontinental population structuring than other livestock species, suggesting that goats have been transported more extensively. However, the timing of these extensive movements in goats remains unknown. To address this question, we analyzed mtDNA sequences from 19 ancient goat bones (7,300–6,900 years old) from one of the earliest Neolithic sites in southwestern Europe. Phylogenetic analysis revealed that two highly divergent goat lineages coexisted in each of the two Early Neolithic layers of this site. This finding indicates that high mtDNA diversity was already present >7,000 years ago in European goats, far from their areas of initial domestication in the Near East. These results argue for substantial gene flow among goat populations dating back to the early neolithisation of Europe and for a dual domestication scenario in the Near East, with two independent but essentially contemporary origins (of both A and C domestic lineages) and several more remote and/or later origins.
The deepest divergences in land plants inferred from phylogenomic evidence
Authors: Qiu Yin-Long , Li Libo , Wang Bin , Chen Zhiduan , Knoop Volker , Groth-Malonek Milena , Dombrovska Olena , Lee Jungho , Kent Livija , Rest Joshua , Estabrook George F. , Hendry Tory A. , Taylor David W. , Testa Christopher M. , Ambros Mathew , Crandall-Stotler Barbara , Duff R. Joel , Stech Michael , Frey Wolfgang , Quandt Dietmar , Davis Charles C.
Published: October 2006

Phylogenetic relationships among the four major lineages of land plants (liverworts, mosses, hornworts, and vascular plants) remain vigorously contested; their resolution is essential to our understanding of the origin and early evolution of land plants. We analyzed three different complementary data sets: a multigene supermatrix, a genomic structural character matrix, and a chloroplast genome sequence matrix, using maximum likelihood, maximum parsimony, and compatibility methods. Analyses of all three data sets strongly supported liverworts as the sister to all other land plants, and analyses of the multigene and chloroplast genome matrices provided moderate to strong support for hornworts as the sister to vascular plants. These results highlight the important roles of liverworts and hornworts in two major events of plant evolution: the water-to-land transition and the change from a haploid gametophyte generation-dominant life cycle in bryophytes to a diploid sporophyte generation-dominant life cycle in vascular plants. This study also demonstrates the importance of using a multifaceted approach to resolve difficult nodes in the tree of life. In particular, it is shown here that densely sampled taxon trees built with multiple genes provide an indispensable test of taxon-sparse trees inferred from genome sequences.
Global roles of Ste11p, cell type, and pheromone in the control of gene expression during early sexual differentiation in fission yeast
Authors: Mata Juan , Bähler Jürg
Published: October 2006

Fission yeast cells belong to one of two specialized cell types, M or P. Specific environmental conditions trigger sexual differentiation, which leads to an internal program starting with pheromone signaling between M and P cells, followed by mating, meiosis, and sporulation. The initial steps of this process are controlled by Ste11p, a master transcriptional regulator that activates the expression of cell type-specific genes (only expressed in either M or P cells) as well as genes expressed in both M and P cells. Pheromone signaling is activated by Ste11p-dependent transcription and, in turn, enhances some of this transcription in a positive feedback. To obtain a genomewide view of Ste11p target genes, their cell-type specificity, and their dependence on pheromone, we used DNA microarrays along with different genetic and environmental manipulations of fission yeast cells. We identified 78 Ste11p-dependent genes, 12 and 4 of which are only expressed in M and P cells, respectively. These genes show differing grades of pheromone dependencies for Ste11p-activated transcription, ranging from complete independence to complete dependence on pheromone. We systematically deleted all novel cell type-specific genes and characterized their phenotype during sexual differentiation. A comparison with a similar data set from the distantly related budding yeast reveals striking conservation in both number and types of the proteins that define cell types. Given the divergent mechanisms regulating cell type-specific gene expression, our results highlight the plasticity of regulatory circuits, which evolve to allow adaptation to changing environments and lifestyles.
High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition
Authors: Chiu Ya-Lin , Witkowska H. Ewa , Hall Steven C. , Santiago Mario , Soros Vanessa B. , Esnault Cécile , Heidmann Thierry , Greene Warner C.
Published: October 2006

APOBEC3G (A3G) and related deoxycytidine deaminases are potent intrinsic antiretroviral factors. A3G is expressed either as an enzymatically active low-molecular-mass (LMM) form or as an enzymatically inactive high-molecular-mass (HMM) ribonucleoprotein complex. Resting CD4 T cells exclusively express LMM A3G, where it functions as a powerful postentry restriction factor for HIV-1. Activation of CD4 T cells promotes the recruitment of LMM A3G into 5- to 15-MDa HMM complexes whose function is unknown. Using tandem affinity purification techniques coupled with MS, we identified Staufen-containing RNA-transporting granules and Ro ribonucleoprotein complexes as specific components of HMM A3G complexes. Analysis of RNAs in these complexes revealed Alu and small Y RNAs, two of the most prominent nonautonomous mobile genetic elements in human cells. These retroelement RNAs are recruited into Staufen-containing RNA-transporting granules in the presence of A3G. Retrotransposition of Alu and hY RNAs depends on the reverse transcriptase machinery provided by long interspersed nucleotide elements 1 (L1). We now show that A3G greatly inhibits L1-dependent retrotransposition of marked Alu retroelements not by inhibiting L1 function but by sequestering Alu RNAs in cytoplasmic HMM A3G complexes away from the nuclear L1 enzymatic machinery. These findings identify nonautonomous Alu and hY retroelements as natural cellular targets of A3G and highlight how different forms of A3G uniquely protect cells from the threats posed by exogenous retroviruses (LMM A3G) and endogenous retroelements (HMM A3G).
Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1
Authors: Shiba Tomoo , Koga Hiroshi , Shin Hye-Won , Kawasaki Masato , Kato Ryuichi , Nakayama Kazuhisa , Wakatsuki Soichi
Published: October 2006

Family of Rab11-interacting protein (FIP)3/Arfophlin-1 and FIP4/Arfophilin-2 are dual effectors for Rab11 and ADP ribosylation factor (ARF)5/ARF6, which are involved in membrane delivery from recycling endosomes to the plasma membrane during cytokinesis. Here, we define the distinct C-terminal binding regions of FIP3 and FIP4 for Rab11 and ARF5/ARF6. Furthermore, we determined the crystal structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. The long amphiphilic α-helix of FIP3-RBD forms a parallel coiled-coil homodimer, with two symmetric interfaces with two Rab11 molecules. The hydrophobic side of the RBD helix is involved in homodimerization and mediates the interaction with the Rab11 switch 1 region, whereas the opposite hydrophilic side interacts with the Rab11 switch 2 and is the major factor contributing to the binding specificity. The bivalent interaction of FIP3 with Rab11 at the C terminus allows FIP3 to coordinately function with other binding partners, including ARFs.
Cell-free formation of misfolded prion protein with authentic prion infectivity
Authors: Weber Petra , Giese Armin , Piening Niklas , Mitteregger Gerda , Thomzig Achim , Beekes Michael , Kretzschmar Hans A.
Published: October 2006

Prion propagation has been modeled
in vitro
; however, the low infectious titer of PrP
Sc
thus generated has cast doubt on the “protein-only” hypothesis. Here we show that prion delivery on suitable nitrocellulose carrier particles abrogates the apparent dissociation of PrP
Sc
and infectivity. Misfolded prion protein generated by protein misfolding cyclic amplification is as infectious as authentic brain-derived PrP
Sc
provided that confounding effects related to differences in the size distribution of prion protein aggregates generated
in vitro
and consecutive differences in regard to biological clearance are abolished.
Pinoresinol: A lignol of plant origin serving for defense in a caterpillar
Authors: Schroeder Frank C. , del Campo Marta L. , Grant Jacqualine B. , Weibel Douglas B. , Smedley Scott R. , Bolton Kelly L. , Meinwald Jerrold , Eisner Thomas
Published: October 2006

Pinoresinol, a lignan of wide distribution in plants, is found to occur as a minor component in the defensive secretion produced by glandular hairs of caterpillars of the cabbage butterfly,
Pieris rapae
. The compound or a derivative is appropriated by the larva from its normal food plant (the cabbage,
Brassica oleracea
). Pinoresinol was shown to be absent from the secretion if the larva was given a cabbage-free diet but present in the effluent if that diet was supplemented with pinoresinol. Pinoresinol is shown to be a feeding deterrent to ants (
Formica exsectoides
), indicating that it can complement the defensive action of the primary components of the secretion, a set of previously reported lipids called mayolenes. In the test with
F. exsectoides
, pinoresinol proved to be more potent than concomitantly tested mayolene-16.
Pseudomonas aeruginosa
type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple steps
Authors: Shafikhani Sasha H. , Engel Joanne
Published: October 2006

Pseudomonas aeruginosa
is an opportunistic pathogen that requires preexisiting epithelial injury to cause acute infections. We report that
P. aeruginosa
inhibits mammalian cytokinesis in a type III secretion system and exotoxin T (ExoT)-dependent manner. ExoT is a bifunctional type III secretion system effector protein that contains an N-terminal GTPase-activating protein domain and a C-terminal ADP-ribosyl transferase domain. Each of its domains inhibits cytokinesis in a kinetically, morphologically, and mechanistically distinct manner. The GTPase-activating protein-mediated inhibition of cytokinesis occurs early, likely as a consequence of its inhibitory effect on RhoA. The ADP-ribosyl transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2 localization to the midbody, an event essential for completion of cytokinesis. These findings provide an example of a bacterial pathogen targeting cytokinesis.
Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate controls endosome morphology and selective cargo sorting
Authors: Fili N. , Calleja V. , Woscholski R. , Parker P. J. , Larijani B.
Published: October 2006

It is increasingly recognized that the compartmental organization of signaling processes has a profound influence on cellular behavior. However, our inability to influence these compartmental events in a spatially restricted and acute manner limits our understanding of causation. To determine whether local compartmental loss of a phosphoinositide disrupts the normal traffic of specific cargoes through endosomes, we developed the use of a regulated dimerization device, here designed to compartmentally modify the phosphoinositide content of Rab5-positive endosomes. This modification is effected through the specific regulated recruitment of the 3-phosphatase myotubularin to endosomal membranes in intact cells. The selective manipulation of endosomal phosphatidylinositols (PIs) demonstrates that it is the phosphatidylinositol 3-phosphate (PtdIns3P) or its metabolite PtdIns(
3
,
5
)P
2
within this compartment that determines the normal maturation of the endosomal compartment and the flux of receptors through it. On local loss of PtdIns3P/PtdIns(
3
,
5
)P
2
, the endosomal compartment itself fails to continue its normal maturation process, leading to the microtubule-dependent tubularization of the endosomal network. Furthermore, it is shown that endosomal PtdIns3P/PtdIns(
3
,
5
)P
2
is necessary for transferrin receptor traffic through this compartment while having an effect on EGF receptor (EGFR) entry into and sorting from this endosome compartment. The ability to acutely and selectively influence compartmental behavior as exemplified here for endomsomes clearly illustrates the power of the approach used to dissect the role of localized signals and events.
Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses
Authors: Navarini Alexander A. , Recher Mike , Lang Karl S. , Georgiev Panco , Meury Susanne , Bergthaler Andreas , Flatz Lukas , Bille Jacques , Landmann Regine , Odermatt Bernhard , Hengartner Hans , Zinkernagel Rolf M.
Published: October 2006

The reason why severe localized or systemic virus infections enhance and aggravate bacterial superinfection is poorly understood. Here we show that virus-induced IFN type I caused apoptosis in bone marrow granulocytes, drastically reduced granulocyte infiltrates at the site of bacterial superinfection, caused up to 1,000-fold higher bacterial titers in solid organs, and increased disease susceptibility. The finding that the innate antiviral immune response reduces the antibacterial granulocyte defense offers an explanation for enhanced susceptibility to bacterial superinfection during viral disease.
Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospinal tract
Authors: Canty Alison J. , Greferath Ursula , Turnley Ann M. , Murphy Mark
Published: October 2006

Fine movement in the body is controlled by the motor cortex, which signals in a topographically specific manner to neurons in the spinal cord by means of the corticospinal tract (CST). How the correct topography of the CST is established is unknown. To investigate the possibility that the Eph tyrosine kinase receptor EphA4 is involved in this process, we have traced CST axons in mice in which the EphA4 gene has been deleted. The forelimb subpopulation of CST axons is unaffected in the
EphA4
−/−
mice, but the hindlimb subpopulation branches too early within the cord, both temporally and spatially. EphA4 shows a dynamic expression pattern in the environment of the developing CST in the spinal cord: high at the time of forelimb branching and down-regulated before hindlimb branching. To examine whether the fore- and hindlimb subpopulations of CST axons respond differently to EphA4 in their environment, neurons from fore- and hindlimb motor cortex were cultured on a substrate containing EphA4. Neurons from the hindlimb cortex showed reduced branching on the EphA4 substrate compared with their forelimb counterparts. Neurons from the hindlimb cortex express ephrinA5, a high-affinity ligand for EphA4, at higher levels compared with forelimb cortex neurons, and this expression is down-regulated before hindlimb branching. Together, these findings suggest that EphA4 regulates topographic mapping of the CST by controlling the branching of CST axons in the spinal cord.
Programming social, cognitive, and neuroendocrine development by early exposure to novelty
Authors: Tang Akaysha C. , Akers Katherine G. , Reeb Bethany C. , Romeo Russell D. , McEwen Bruce S.
Published: October 2006

Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (
i
) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (
ii
) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.