Showing papers by "Aix-Marseille University published in 2008"

Sorafenib in Advanced Hepatocellular Carcinoma

Abstract: Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.

Plant host habitat and root exudates shape soil bacterial community structure

Abstract: The rhizosphere is active and dynamic in which newly generated carbon, derived from root exudates, and ancient carbon, in soil organic matter (SOM), are available for microbial growth. Stable isotope probing (SIP) was used to determine bacterial communities assimilating each carbon source in the rhizosphere of four plant species. Wheat, maize, rape and barrel clover (Medicago truncatula) were grown separately in the same soil under 13CO2 (99% of atom 13C) and DNA extracted from rhizosphere soil was fractionated by isopycnic centrifugation. Bacteria-assimilating root exudates were characterized by denaturing gradient gel electrophoresis (DGGE) analysis of 13C-DNA and root DNA, whereas those assimilating SOM were identified from 12C-DNA. Plant species root exudates significantly shaped rhizosphere bacterial community structure. Bacteria related to Sphingobacteriales and Myxococcus assimilated root exudates in colonizing roots of all four plants, whwereas bacteria related to Sphingomonadales utilized both carbon sources, and were identified in light, heavy and root compartment DNA. Sphingomonadales were specific to monocotyledons, whereas bacteria related to Enterobacter and Rhizobiales colonized all compartments of all four plants, used both fresh and ancient carbon and were considered as generalists. There was also evidence for an indirect important impact of root exudates, through stimulation of SOM assimilation by a diverse bacterial community.

ATLAS pixel detector electronics and sensors

Abstract: The silicon pixel tracking system for the ATLAS experiment at the Large Hadron Collider is described and the performance requirements are summarized. Detailed descriptions of the pixel detector electronics and the silicon sensors are given. The design, fabrication, assembly and performance of the pixel detector modules are presented. Data obtained from test beams as well as studies using cosmic rays are also discussed.

Phanerozoic trends in the global diversity of marine invertebrates.

Abstract: It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing 3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.

Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence

Abstract: Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis–infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria.

Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.

Abstract: The morphogenesis of developing embryos and organs relies on the ability of cells to remodel their contacts with neighbouring cells. Using quantitative modelling and laser nano-dissection, we probed the mechanics of a morphogenetic process, the elongation of Drosophila melanogaster embryos, which results from polarized cell neighbour exchanges. We show that anisotropy of cortical tension at apical cell junctions is sufficient to drive tissue elongation. We estimated its value through comparisons between in silico and in vivo data using various tissue descriptors. Nano-dissection of the actomyosin network indicates that tension is anisotropically distributed and depends on myosin II accumulation. Junction relaxation after nano-dissection also suggests that cortical elastic forces are dominant in this process. Interestingly, fluctuations in vertex position (points where three or more cells meet) facilitate neighbour exchanges. We delineate the contribution of subcellular tensile activity polarizing junction remodelling, and the permissive role of vertex fluctuations during tissue elongation.

Ab initio determination of light hadron masses.

Abstract: More than 99% of the mass of the visible universe is made up of protons and neutrons. Both particles are much heavier than their quark and gluon constituents, and the Standard Model of particle physics should explain this difference. We present a full ab initio calculation of the masses of protons, neutrons, and other light hadrons, using lattice quantum chromodynamics. Pion masses down to 190 mega-electron volts are used to extrapolate to the physical point, with lattice sizes of approximately four times the inverse pion mass. Three lattice spacings are used for a continuum extrapolation. Our results completely agree with experimental observations and represent a quantitative confirmation of this aspect of the Standard Model with fully controlled uncertainties.

Organized Formation of 2D Extended Covalent Organic Frameworks at Surfaces

Abstract: The development of nanoscale masking for particle deposition is exceedingly important to push the future of nanoelectronics beyond the current limits of lithography We present the first example of ordered hexagonal covalent nanoporous structures deposited in extended arrays of near monolayer coverage across a Ag(111) surface The networks were formed from the deposition of the reagents from a heated molybdenum crucible between 370 and 460 K under ultrahigh vacuum (UHV) onto a cleaned Ag(111) substrate and imaged using a scanning tunneling microscope (STM) Two surface covalent organic frameworks (SCOFs) are presented; the first is formed from the deposition of 1,4-benzenediboronic acid (BDBA) and its dehydration to form the boroxine-linked SCOF-1, the second is formed from the co-deposition of BDBA and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) to form a dioxaborole-linked SCOF-2 network The networks were found to produce nanoporous structures of 15 A for SCOF-1 and 29 A for SCOF-2, which agreed with

Relation between the redox state of iron-based nanoparticles and their cytotoxicity toward Escherichia coli.

Abstract: Iron-based nanoparticles have been proposed for an increasing number of biomedical or environmental applications although in vitro toxicity has been observed. The aim of this study was to understand the relationship between the redox state of iron-based nanoparticles and their cytotoxicity toward a Gram-negative bacterium, Escherichia coli. While chemically stable nanoparticles (γFe2O3) have no apparent cytotoxicity, nanoparticles containing ferrous and, particularly, zerovalent iron are cytotoxic. The cytotoxic effects appear to be associated principally with an oxidative stress as demonstrated using a mutant strain of E. coli completely devoid of superoxide dismutase activity. This stress can result from the generation of reactive oxygen species with the interplay of oxygen with reduced iron species (FeII and/or Fe0) or from the disturbance of the electronic and/or ionic transport chains due to the strong affinity of the nanoparticles for the cell membrane.

MYBL2 is a new regulator of flavonoid biosynthesis in Arabidopsis thaliana.

Abstract: In Arabidopsis thaliana, several MYB and basic helix-loop-helix (BHLH) proteins form ternary complexes with TTG1 (WD-Repeats) and regulate the transcription of genes involved in anthocyanin and proanthocyanidin (PA) biosynthesis. Similar MYB-BHLH-WDR (MBW) complexes control epidermal patterning and cell fates. A family of small MYB proteins (R3-MYB) has been shown to play an important role in the regulation of epidermal cell fates, acting as inhibitors of the MBW complexes. However, so far none of these small MYB proteins have been demonstrated to regulate flavonoid biosynthesis. The genetic and molecular analyses presented here demonstrated that Arabidopsis MYBL2, which encodes a R3-MYB-related protein, is involved in the regulation of flavonoid biosynthesis. The loss of MYBL2 activity in the seedlings of two independent T-DNA insertion mutants led to a dramatic increase in the accumulation of anthocyanin. In addition, overexpression of MYBL2 in seeds inhibited the biosynthesis of PAs. These changes in flavonoid content correlate well with the increased level of mRNA of several structural and regulatory anthocyanin biosynthesis genes. Interestingly,transient expression analyses in A. thaliana cells suggested that MYBL2 interacts with MBW complexes in planta and directly modulates the expression of flavonoid target genes. These results are fully consistent with the molecular interaction of MYBL2 with BHLH proteins observed in yeast. Finally, MYBL2 expression studies, including its inhibition by light-induced stress, allowed us to hypothesise a physiological role for MYBL2. Taken together, these results bring new insights into the transcriptional regulation of flavonoid biosynthesis and provide new clues and tools for further investigation of its developmental and environmental regulation.

Broadband cylindrical acoustic cloak for linear surface waves in a fluid.

Abstract: We describe the first practical realization of a cylindrical cloak for linear surface liquid waves. This structured metamaterial bends surface waves radiated by a closely located acoustic source over a finite interval of Hertz frequencies. We demonstrate theoretically its unique mechanism using homogenization theory: the cloak behaves as an effective anisotropic fluid characterized by a diagonal stress tensor in a cylindrical basis. A low azimuthal viscosity is achieved, where the fluid flows most rapidly. Numerical simulations demonstrate that the homogenized cloak behaves like the actual structured cloak. We experimentally analyze the decreased backscattering of a fluid with low viscosity and finite density (methoxynonafluorobutane) from a cylindrical rigid obstacle surrounded by the cloak when it is located a couple of wavelengths away from the acoustic source.

Break-induced replication : What is it and what is it for?

Abstract: Homologous recombination (HR) is considered to be an error-free mechanism for the repair of DNA double-strand breaks (DSBs). Indeed, most DSB repair events occur by a non-crossover mechanism limiting loss of heterozygosity (LOH) for markers downstream of the site of repair and preventing chromosome rearrangements. However, DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). As BIR from one of the two ends of a DSB would result in a long tract of LOH it suggests BIR is suppressed when DSBs have two ends in order for repair to occur by a more conservative HR mechanism. Recent studies showed that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation resulting in chromosome rearrangements when dissociation and reinvasion occur within dispersed repeated sequences. Thus template s...

Cutting Edge: Priming of NK Cells by IL-18

Abstract: Recent evidence suggests that NK cells require priming to display full effector activity. In this study, we demonstrate that IL-18 contributed to this phenomenon. IL-18 signaling-deficient NK cells were found to be unable to secrete IFN-gamma in response to ex vivo stimulation with IL-12. This was not due to a costimulatory role of IL-18, because blocking IL-18 signaling during the ex vivo stimulation with IL-12 did not alter IFN-gamma production by wild-type NK cells. Rather, we demonstrate that IL-18 primes NK cells in vivo to produce IFN-gamma upon subsequent stimulation with IL-12. Importantly, IL-12-induced IFN-gamma transcription by NK cells was comparable in IL-18 signaling-deficient and -sufficient NK cells. This suggests that priming by IL-18 leads to an improved translation of IFN-gamma mRNA. These results reveal a novel type of cooperation between IL-12 and IL-18 that requires the sequential action of these cytokines.

Direct imaging of photonic nanojets

Abstract: We report the direct experimental observation of photonic nanojets created by single latex microspheres illuminated by a plane wave at a wavelength of 520 nm. Measurements are performed with a fast scanning confocal microscope in detection mode, where the detection pinhole defines a diffraction-limited observation volume that is scanned in three dimensions over the microsphere vicinity. From the collected stack of images, we reconstruct the full 3 dimensional photonic nanojet beam. Observations are conducted for polystyrene spheres of 1, 3 and 5 µm diameter deposited on a glass substrate, the upper medium being air or water. Experimental results are compared to calculations performed using the Mie theory. We measure nanojet sizes as small as 270 nm FWHM for a 3 µm sphere at a wavelength λ of 520 nm. The beam keeps a subwavelength FWHM over a propagation distance of more than 3 λ, displaying all the specificities of a photonic nanojet.

Cracking the orthographic code: An introduction

Abstract: In this introduction to the special issue, I will first briefly summarise past research on orthographic processing, describing some of the central areas of empirical investigation and the major theories guiding that work. Next, I will describe the more recent lines of empirical and theoretical research that have emerged over the last decade or so, and that serve as the focus of the current special issue. I will attempt to summarise the key evidence that has emerged from this research, and examine how this evidence can guide model selection. Finally, I will discuss some possible avenues for future research on orthographic processing in the hope of finally ‘cracking the orthographic code’.

Brucella Control of Dendritic Cell Maturation Is Dependent on the TIR-Containing Protein Btp1

Abstract: Brucella is an intracellular pathogen able to persist for long periods of time within the host and establish a chronic disease. We show that soon after Brucella inoculation in intestinal loops, dendritic cells from ileal Peyer's patches become infected and constitute a cell target for this pathogen. In vitro, we found that Brucella replicates within dendritic cells and hinders their functional activation. In addition, we identified a new Brucella protein Btp1, which down-modulates maturation of infected dendritic cells by interfering with the TLR2 signaling pathway. These results show that intracellular Brucella is able to control dendritic cell function, which may have important consequences in the development of chronic brucellosis.

Modulation of phasic and tonic muscle synergies with reaching direction and speed.

Abstract: How the CNS masters the many degrees of freedom of the musculoskeletal system to control goal-directed movements is a long-standing question. We have recently provided support to the hypothesis that the CNS relies on a modular control architecture by showing that the phasic muscle patterns for fast reaching movements in different directions are generated by combinations of a few time-varying muscle synergies: coordinated recruitment of groups of muscles with specific activation profiles. However, natural reaching movements occur at different speeds and require the control of both movement and posture. Thus we have investigated whether muscle synergies also underlie reaching at different speeds as well as the maintenance of stable arm postures. Hand kinematics and shoulder and elbow muscle surface EMGs were recorded in five subjects during reaches to eight targets in the frontal plane at different speeds. We found that the amplitude modulation of three time-invariant synergies captured the variations in the postural muscle patterns at the end of the movement. During movement, three phasic and three tonic time-varying synergies could reconstruct the time-normalized muscle pattern in all conditions. Phasic synergies were modulated in both amplitude and timing by direction and speed. Tonic synergies were modulated only in amplitude by direction. The directional tuning of both types of synergies was well described by a single or a double cosine function. These results suggest that muscle synergies are basic control modules that allow generating the appropriate muscle patterns through simple modulation and combination rules.

Measurement of the inclusive jet cross section in pp̄ collisions at s=1.96TeV

Abstract: We report on a measurement of the inclusive jet cross section in p (p) over bar collisions at a center-of-mass energy root s = 1.96 TeV using data collected by the D0 experiment at the Fermilab Tevatron Collider corresponding to an integrated luminosity of 0: 70 fb(-1). The data cover jet transverse momenta from 50 to 600 GeV and jet rapidities in the range -2.4 to 2.4. Detailed studies of correlations between systematic uncertainties in transverse momentum and rapidity are presented, and the cross section measurements are found to be in good agreement with next-to-leading order QCD calculations.

Coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'O)-methyltransferase activity

Abstract: The coronavirus family of positive-strand RNA viruses includes important pathogens of livestock, companion animals, and humans, including the severe acute respiratory syndrome coronavirus that was responsible for a worldwide outbreak in 2003. The unusually complex coronavirus replicase/transcriptase is comprised of 15 or 16 virus-specific subunits that are autoproteolytically derived from two large polyproteins. In line with bioinformatics predictions, we now show that feline coronavirus (FCoV) nonstructural protein 16 (nsp16) possesses an S-adenosyl-L-methionine (AdoMet)-dependent RNA (nucleoside-2'O)-methyltransferase (2'O-MTase) activity that is capable of cap-1 formation. Purified recombinant FCoV nsp16 selectively binds to short capped RNAs. Remarkably, an N7-methyl guanosine cap ((7Me)GpppAC(3-6)) is a prerequisite for binding. High-performance liquid chromatography analysis demonstrated that nsp16 mediates methyl transfer from AdoMet to the 2'O position of the first transcribed nucleotide, thus converting (7Me)GpppAC(3-6) into (7Me)GpppA(2')(O)(Me)C(3-6). The characterization of 11 nsp16 mutants supported the previous identification of residues K45, D129, K169, and E202 as the putative K-D-K-E catalytic tetrad of the enzyme. Furthermore, residues Y29 and F173 of FCoV nsp16, which may be the functional counterparts of aromatic residues involved in substrate recognition by the vaccinia virus MTase VP39, were found to be essential for both substrate binding and 2'O-MTase activity. Finally, the weak inhibition profile of different AdoMet analogues indicates that nsp16 has evolved an atypical AdoMet binding site. Our results suggest that coronavirus mRNA carries a cap-1, onto which 2'O methylation follows an order of events in which 2'O-methyl transfer must be preceded by guanine N7 methylation, with the latter step being performed by a yet-unknown N7-specific MTase.

Aeroelastic instability of cantilevered flexible plates in uniform flow

Abstract: We address the flutter instability of a flexible plate immersed in an axial flow This instability is similar to flag flutter and results from the competition between destabilising pressure forces and stabilising bending stiffness In previous experimental studies, the plates have always appeared much more stable than the predictions of two-dimensional models This discrepancy is discussed and clarified in this paper by examining experimentally and theoretically the effect of the plate aspect ratio on the instability threshold We show that the two-dimensional limit cannot be achieved experimentally because hysteretical behaviour and three-dimensional effects appear for plates of large aspect ratio The nature of the instability bifurcation (sub- or supercritical) is also discussed in the light of recent numerical results

Fractional Laplacian phase transitions and boundary reactions: a geometric inequality and a symmetry result

Abstract: We deal with symmetry properties for solutions of nonlocal equations of the type $(-\Delta)^s v= f(v)\qquad {in $\R^n$,}$ where $s \in (0,1)$ and the operator $(-\Delta)^s$ is the so-called fractional Laplacian. The study of this nonlocal equation is made via a careful analysis of the following degenerate elliptic equation ${-div (x^\a abla u)=0 \qquad {on $\R^n\times(0,+\infty)$} -x^\a u_x = f(u) \qquad {on $\R^n\times\{0\}$} $ where $\a \in (-1,1)$. This equation is related to the fractional Laplacian since the Dirichlet-to-Neumann operator $\Gamma_\a: u|_{\partial \R^{n+1}_+} \mapsto -x^\a u_x |_{\partial \R^{n+1}_+} $ is $(-\Delta)^{\frac{1-\a}{2}}$. This equation is related to the fractional Laplacian since the Dirichlet-to-Neumann operator $\Gamma_\a: u|_{\partial \R^{n+1}_+} \mapsto -x^\a u_x |_{\partial \R^{n+1}_+} $ is $(-\Delta)^{\frac{1-\a}{2}}$. More generally, we study the so-called boundary reaction equations given by ${-div (\mu(x) abla u)+g(x,u)=0 {on $\R^n\times(0,+\infty)$} - \mu(x) u_x = f(u) {on $\R^n\times{0}$}$ under some natural assumptions on the diffusion coefficient $\mu$ and on the nonlinearities $f$ and $g$. We prove a geometric formula of Poincar\'e-type for stable solutions, from which we derive a symmetry result in the spirit of a conjecture of De Giorgi.

Natural variation and functional analyses provide evidence for co‐evolution between plant eIF4E and potyviral VPg

Abstract: Amino acid substitutions in the eukaryotic translation initiation factor 4E (eIF4E) result in recessive resistance to potyviruses in a range of plant species, including Capsicum spp. Correspondingly, amino acid changes in the central part of the viral genome-linked protein (VPg) are responsible for the potyvirus's ability to overcome eIF4E-mediated resistance. A key observation was that physical interaction between eIF4E and the VPg is required for viral infection, and eIF4E mutations that cause resistance prevent VPg binding and inhibit the viral cycle. In this study, polymorphism analysis of the pvr2-eIF4E coding sequence in a worldwide sample of 25 C. annuum accessions identified 10 allelic variants with exclusively non-synonymous variations clustered in two surface loops of eIF4E. Resistance and genetic complementation assays demonstrated that pvr2 variants, each with signature amino acid changes, corresponded to potyvirus resistance alleles. Systematic analysis of the interactions between eIF4E proteins encoded by the 10 pvr2 alleles and VPgs of virulent and avirulent potato virus Y (PVY) and tobacco etch virus (TEV) strains demonstrated that resistance phenotypes arose from disruption of the interaction between eIF4E and VPg, and that viral adaptation to eIF4E-mediated resistance resulted from restored interaction with the resistance protein. Complementation of an eIF4E knockout yeast strain by C. annuum eIF4E proteins further shows that amino acid changes did not impede essential eIF4E functions. Altogether, these results argue in favour of a co-evolutionary 'arms race' between Capsicum eIF4E and potyviral VPg.

Latest view on the mechanism of action of deep brain stimulation

Abstract: How does deep brain stimulation (DBS) applied at high frequency (100 Hz and above, HFS) in diverse points of cortico-basal ganglia thalamo-cortical loops alleviate symptoms of neurological disorders such as Parkinson's disease, dystonia, and obsessive compulsive disorders? Do the effects of HFS stem solely or even largely from local effects on the stimulated brain structure or are they also mediated by actions of HFS on distal structures? Indeed, HFS as an extracellular stimulation is expected to activate subsets of both afferent and efferent axons, leading to antidromic spikes that collide with ongoing spontaneous ones and orthodromic spikes that evoke synaptic responses in target neurons. The present review suggests that HFS interfere with spontaneous pathological patterns by introducing a regular activity in several nodal points of the network. Therefore, the best site of implantation of the HFS electrode may be in a region where the HFS-driven activity spreads to most of the identified, dysrhythmic, neuronal populations without causing additional side effects. This should help tackling the most difficult issue namely, how does the regular HFS-driven activity that dampens the spontaneous pathological one, restore neuronal processing along cortico-basal ganglia-thalamo-cortical loops?

Native language influences on word recognition in a second language: a megastudy.

Abstract: Many studies have reported that word recognition in a second language (L2) is affected by the native language (L1). However, little is known about the role of the specific language combination of the bilinguals. To investigate this issue, the authors administered a word identification task (progressive demasking) on 1,025 monosyllabic English (L2) words to native speakers of French, German, and Dutch. A regression approach was adopted, including a large number of within- and between-language variables as predictors. A substantial overlap of reaction time patterns was found across the groups of bilinguals, showing that word recognition results obtained for one group of bilinguals generalize to bilinguals with different mother tongues. Moreover, among the set of significant predictors, only one between-language variable was present (cognate status); all others reflected characteristics of the target language. Thus, although influences across languages exist, word recognition in L2 by proficient bilinguals is primarily determined by within-language factors, whereas cross-language effects appear to be limited. An additional comparison of the bilingual data with a native control group showed that there are subtle but significant differences between L1 and L2 processing.