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•This study suggests new feeding patterns for children offered during the Capacocha.•It is possible that the child’s diet included seaweed.•The Quehuar volcano child lived at high altitude before being offered in sacrifice.

Gordon Moore designed Moore’s Law as a multifunctional tool to drive process and product innovation, sell Fairchild’s and Intel’s microchips, and outcompete other semiconductor firms. Because Intel’s ability to stay on Moore’s Law depended upon other corporations developing materials and manufacturing equipment for exponential scaling, Moore and his closest associates heavily promoted Moore’s Law in the microelectronics community. They also established the national and international technology roadmaps for semiconductors in order to set the direction and cadence of innovation in microelectronics at the national and, later, global scales. Moore’s and his successors’ relentless pursuit of Moore’s Law and their deft management of the roadmaps significantly reinforced Intel’s competitiveness and helped it to dominate semiconductor technology and industry until the mid-2010s.

Pneumocystis jiroveciipneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.

During the last 20 years, a new field of research delineating the importance of the microbiota in health and diseases has emerged. Inappropriate host-microbiota interactions have been shown to trigger a wide range of chronic inflammatory diseases, and defining the exact mechanisms behind perturbations of such relationship, as well as ways by which these disturbances can lead to disease states, both remain to be fully elucidated. The mucosa-associated microbiota constitutes a recently studied microbial population closely linked with the promotion of chronic intestinal inflammation and associated disease states. This review will highlight seminal works that have brought into light the importance of the mucosa-associated microbiota in health and diseases, emphasizing the challenges and promises of expending the mucosal microbiology field of research.

BackgroundClinical assessment of patients with mild traumatic brain injury (mTBI) is challenging and overuse of head CT in the ED is a major problem. Several studies have attempted to reduce unnecessary head CTs following a mTBI by identifying new tools aiming to predict intracranial bleeding. Higher levels of S100B protein have been associated with intracranial haemorrhage following a mTBI in previous literature. The main objective of this study is to assess whether plasma S100B protein level is associated with clinically significant brain injury and could be used to reduce the number of head CT post-mTBI.MethodsStudy design:secondary analysis of a prospective multicentre cohort study conducted between 2013 and 2016 in five Canadian EDs. Inclusion criteria:non-hospitalised patients with mTBI with a GCS score of 13–15 in the ED and a blood sample drawn within 24 hours after the injury. Data collected:sociodemographic and clinical data were collected in the ED. S100B protein was analysed using ELISA. All CT scans were reviewed by a radiologist blinded to the biomarker results. Main outcome:the presence of clinically important brain injury.Results476 patients were included. Mean age was 41±18 years old and 150 (31.5%) were women. Twenty-four (5.0%) patients had a clinically significant intracranial haemorrhage. Thirteen patients (2.7%) presented a non-clinically significant brain injury. A total of 37 (7.8%) brain injured patients were included in our study. S100B median value (Q1–Q3) was: 0.043 µg/L (0.008–0.080) for patients with clinically important brain injury versus 0.039 µg/L (0.023–0.059) for patients without clinically important brain injury. Sensitivity and specificity of the S100B protein level, if used alone to detect clinically important brain injury, were 16.7% (95% CI 4.7% to 37.4%) and 88.5% (95% CI 85.2% to 91.3%), respectively.ConclusionPlasma S100B protein level was not associated with clinically significant intracranial lesion in patients with mTBI.

For the first time, we present a decadal-scale stable isotope record (δ18O, δ13C) of 67 speleothem calcite samples coming from an artificial tunnel network located in Graz, Austria. Stable isotope data are interpreted with the help of time series (TS) analysis of mean air temperatures (MAT) and mean annual precipitations (MAP) that have been monitored and recorded in a neighbouring meteorological station. Speleothem records have proved to be very useful in reconstructing changes of environmental conditions. For studied stalagmites, which grew between 1945 and 2018, the δ18O values average −18.64‰ and range from −23‰ to −17‰ (VPDB, Vienna Pee Dee Belemnite), suggesting variable climatic conditions. The δ18O values of calcite increase along the growth axis and are correlated with high temporal resolution MAT, MAP and weighted mean annual δ18O of precipitations. For the same time interval, while the temperature TS show an increasing trend, with a steeper gradient since the 1980s, the precipitation TS presents a weak decreasing tendency. Increase in the δ13C values of speleothems from −33‰ to −24‰ (VPDB) is correlated with increasing temperature and drought, associated CO2degassing and soil erosion over the tunnel system.

δ2H and δ18O values of precipitations follow an empirical linear relationship at the global scale that is called the Global Meteoric Water Line (GMWL) and characterized by a slope of 8. However, Local Meteoric Water Lines (LMWLs) may have different slopes Sdepending on their geographic situation. Monthly δ2H and δ18O of precipitation have been compiled from European International Atomic Energy Agency (IAEA) stations. Those data allowed the calculation of the slopes Sof the δ2H–δ18O LMWL determined for each station. Sincreases with longitude ϕfrom c.5 (Portugal) to c.9 (Russia) – they are positively correlated with relative humidity (RH), negatively with temperature and positively with the mean intra-annual amplitude of temperatures, which is a proxy of continentality. Slopes of 5–6, recorded in SW Europe, reflect mean RH (70–75%) and sea surface temperatures (c.25°C) of the Central Atlantic Ocean where the main flux of moisture is formed before being transported by the westerlies. In addition, falling water droplets within an air column with a high RH (>80%) and low temperature are expected to escape sub-cloud evaporation. Therefore, slopes with values close to 9 are considered to reflect isotopic equilibrium conditions during the condensation of water vapour in clouds.

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1and Roadmap Epigenomics2data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

AbstractEscape room experiences have been used as an educational tool in several health professions, and to the authors’ knowledge, it is not yet documented in veterinary medicine. They are an example of gamification in a simulated environment where course objectives guide puzzle development. Veterinary emergency medicine can be very stressful as veterinarians often have to make quick decisions. The element of a time limit adds stress to the experience as learners must complete the puzzles within a specified time to successfully escapethe room. This article describes the development and delivery of an escape room experience in emergency veterinary medicine to third year students at the Western College of Veterinary Medicine at the University of Saskatchewan. In a survey following the experience, learners indicated they enjoyed participating in the learning activity. They felt it encouraged the use of communication, collaboration, and leadership skills which have been identified as core competencies in veterinary education. While on average learners would disagree with the experience being stressful, several commented that it was a “good stress”. This indicates that the experience may have been considered challenging to learners, which in simulation, supports a positive way to achieving learning objectives that may not overstress participants.

The fish-to-tetrapod transition—followed later by terrestrialization—represented a major step in vertebrate evolution that gave rise to a successful clade that today contains more than 30,000 tetrapod species. The early tetrapod Ichthyostegawas discovered in 1929 in the Devonian Old Red Sandstone sediments of East Greenland (dated to approximately 365 million years ago). Since then, our understanding of the fish-to-tetrapod transition has increased considerably, owing to the discovery of additional Devonian taxa that represent early tetrapods or groups evolutionarily close to them. However, the aquatic environment of early tetrapods and the vertebrate fauna associated with them has remained elusive and highly debated. Here we use a multi-stable isotope approach (δ13C, δ18O and δ34S) to show that some Devonian vertebrates, including early tetrapods, were euryhaline and inhabited transitional aquatic environments subject to high-magnitude, rapid changes in salinity, such as estuaries or deltas. Euryhalinity may have predisposed the early tetrapod clade to be able to survive Late Devonian biotic crises and then successfully colonize terrestrial environments. An approach using multiple stable isotopes reveals that early tetrapods of the Devonian period were euryhaline animals that inhabited aquatic environments of highly variable salinity.

The secondary adaptation of Cetacea to a fully marine lifestyle raises the question of their ability to maintain their water balance in a hyperosmotic environment. Cetacea have access to four potential sources of water: surrounding salt oceanic water, dietary free water, metabolic water and inhaled water vapour to a lesser degree. Here, we measured the 18O/16O oxygen isotope ratio of blood plasma from 13 specimens belonging to two species of Cetacea raised under human care (four killer whales Orcinus orca, nine common bottlenose dolphins Tursiops truncatus) to investigate and quantify the contribution of preformed water (dietary free water, surrounding salt oceanic water) and metabolic water to Cetacea body water using a box-modelling approach. The oxygen isotope composition of Cetacea blood plasma indicates that dietary free water and metabolic water contribute to more than 90% of the total water input in weight for cetaceans, with the remaining 10% consisting of inhaled water vapour and surrounding water accidentally ingested or absorbed through the skin. Moreover, the contribution of metabolic water appears to be more important in organisms with a more lipid-rich diet. Beyond these physiological and conservation biology implications, this study opens up questions that need to be addressed, such as the applicability of the oxygen isotope composition of cetacean body fluids and skeletal elements as an environmental proxy of the oxygen isotope composition of present and past marine waters.

ABSTRACTNeisseria meningitidisis the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known as purpura fulminans. Meningococcemia is characterized by bacterial adhesion to human endothelial cells of the microvessels. Host specificity has hampered studies on the role of blood vessels colonization in N. meningitidisassociated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in an in vivocontext we demonstrate that meningococcal colonization of human blood vessels is a prerequisite to the establishment of sepsis and lethality. To identify the molecular pathways involved in bacterial virulence, we performed transposon insertion site sequencing (Tn-seq) in vivo. Our results demonstrate that 36% of the genes that are important for growth in the blood of mice are dispensable when bacteria colonize human blood vessels, suggesting that human endothelial cells lining the blood vessels are feeding niches for N. meningitidis in vivo. Altogether, our work proposes a new paradigm for meningococcal virulence in which colonization of blood vessels is associated with metabolic adaptation and sustained bacteremia responsible for sepsis and subsequent lethality.

Abstract:This article argues that labor activists initiated Silicon Valley's antitoxics movement and were the driving force behind environmental remediation in the region in the first half of the 1980s. In order to unionize semiconductor plants, activists associated with SCCOSH and United Electrical, Radio, and Machine Workers, a left-wing union, attacked corporate negligence regarding worker safety and health. SCCOSH later allied itself with the Central Labor Council of Santa Clara County to push for the cleanup of aquifers contaminated by the semiconductor industry. The activists ultimately failed to organize Silicon Valley, but their campaigns led to a revolution in safety among microelectronics firms and to large-scale remediation efforts conducted under the EPA's Superfund program.

Microchip entrepreneur and architect of Moore’s Law.

•Located in the Southern Alps, the Cerveyrette area is a watershed of 100 km2.•It includes a torrent and a high-altitude plain dominated by a nival regime.•The river waters have a rather constant mean annual δ18O of −14.4 ± 0.6 ‰.•This composition is buffered by snowpack melting and preserved downstream.•MAAT are underestimated when inferred from bioapatite δ18O of local humans.

The blood–brain barrier, which is one of the tightest barriers in the body, protects the brain from insults, such as infections. Indeed, only a few of the numerous blood-borne bacteria can cross the blood–brain barrier to cause meningitis. In this Review, we focus on invasive extracellular pathogens, such as Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus and Escherichia coli, to review the obstacles that bacteria have to overcome in order to invade the meninges from the bloodstream, and the specific skills they have developed to bypass the blood–brain barrier. The medical importance of understanding how these barriers can be circumvented is underlined by the fact that we need to improve drug delivery into the brain.

When walking within a CAVE-like system, accommodation distance, parallax, and angular resolution vary according to the distance between the user and the projection walls, which can alter spatial perception. As these systems get bigger, there is a need to assess the main factors influencing spatial perception in order to better design immersive projection systems and virtual reality applications. In this paper, we present two experiments that analyze distance perception when considering the distance toward the projection screens and parallax as main factors. Both experiments were conducted in a large immersive projection system with up to 10-meter interaction space. The first experiment showed that both the screen distance and parallax have a strong asymmetric effect on distance judgments. We observed increased underestimation for positive parallax conditions and slight distance overestimation for negative and zero parallax conditions. The second experiment further analyzed the factors contributing to these effects and confirmed the observed effects of the first experiment with a high-resolution projection setup providing twice the angular resolution and improved accommodative stimuli. In conclusion, our results suggest that space is the most important characteristic for distance perception, optimally requiring about 6- to 7-meter distance around the user, and virtual objects with high demands on accurate spatial perception should be displayed at zero or negative parallax.

Haptic feedback is known to improve 3D interaction in virtual environments but current haptic interfaces remain complex and tailored to desktop interaction. In this paper, we describe an alternative approach called “Elastic-Arm” for incorporating haptic feedback in immersive virtual environments in a simple and cost-effective way. The Elastic-Arm is based on a body-mounted elastic armature that links the user's hand to the body and generates a progressive egocentric force when extending the arm. A variety of designs can be proposed with multiple links attached to various locations on the body in order to simulate different haptic properties and sensations such as different levels of stiffness, weight lifting, and bimanual interaction. Our passive haptic approach can be combined with various 3D interaction techniques and we illustrate the possibilities offered by the Elastic-Arm through several use cases based on well-known techniques such as the Bubble technique, redirected touching, and pseudo-haptics. A user study was conducted which showed the effectiveness of our pseudo-haptic technique as well as the general appreciation of the Elastic-Arm. We believe that the Elastic-Arm could be used in various VR applications which call for mobile haptic feedback or human-scale haptic sensations.

Growing evidence supports a role for IL-1 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), but how it impacts neuroinflammation is poorly understood. We show that susceptibility to EAE requires activation of IL-1R1 on radiation-resistant cells via IL-1β secreted by bone marrow–derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1β and produce this cytokine as a result of their transmigration across the inflamed blood–spinal cord barrier. IL-1R1 expression in the spinal cord is found in endothelial cells (ECs) of the pial venous plexus. Accordingly, leukocyte infiltration at EAE onset is restricted to IL-1R1+ subpial and subarachnoid vessels. In response to IL-1β, primary cultures of central nervous system ECs produce GM-CSF, G-CSF, IL-6, Cxcl1, and Cxcl2. Initiation of EAE or subdural injection of IL-1β induces a similar cytokine/chemokine signature in spinal cord vessels. Furthermore, the transfer of Gr1+ cells on the spinal cord is sufficient to induce illness in EAE-resistant IL-1β knockout (KO) mice. Notably, transfer of Gr1+ cells isolated from C57BL/6 mice induce massive recruitment of recipient myeloid cells compared with cells from IL-1β KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1β–dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation.

Does the stimulation used during the training on an SSVEP-based BCI have to be similar to that of the end use? We recorded six-channel EEG data from 12 subjects in various conditions of distance between targets, and of difference in color between targets. Our analysis revealed that the stimulation configuration used for training which leads to the best classification accuracy is not always the one which is closest to the end use configuration. We found that the distance between targets during training is of little influence if the end use targets are close to each other, but that training at far distance can lead to a better accuracy for far distance end use (p< .01). Additionally, an interaction effect is observed between training and testing color (p< .001): while training with monochrome targets leads to good performance only when the test context involves monochrome targets as well, a classifier trained on colored targets can be efficient for both colored and monochrome targets. In a nutshell, in the context of SSVEP-based BCI, training using distant targets of different colors seems to lead to the best and more robust performance in all end use contexts.

L’objectif est de décrire les soins palliatifs hospitaliers en médecine–chirurgie–obstétrique, soins de suite et de réadaptation et hospitalisation à domicile chez l’adulte en région Centre, de 2009 à 2011, dans un contexte de restructuration de l’offre.

The mode of life of the early Tertiary giant bird Gastornishas long been a matter of controversy. Although it has often been reconstructed as an apex predator feeding on small mammals, according to other interpretations, it was in fact a large herbivore. To determine the diet of this bird, we analyze here the carbon isotope composition of the bone apatite from Gastornisand contemporaneous herbivorous mammals. Based on 13C-enrichment measured between carbonate and diet of carnivorous and herbivorous modern birds, the carbonate δ13C values of Gastornisbone remains, recovered from four Paleocene and Eocene French localities, indicate that this bird fed on plants. This is confirmed by a morphofunctional study showing that the reconstructed jaw musculature of Gastorniswas similar to that of living herbivorous birds and unlike that of carnivorous forms. The herbivorous Gastorniswas the largest terrestrial tetrapod in the Paleocene biota of Europe, unlike the situation in North America and Asia, where Gastornisis first recorded in the early Eocene, and the largest Paleocene animals were herbivorous mammals. The structure of the Paleocene terrestrial ecosystems of Europe may have been similar to that of some large islands, notably Madagascar, prior to the arrival of humans.

The regulated intracellular trafficking and localized translation of mRNA molecules represents an important and prevalent mechanism of gene regulation. This process plays a key role in modulating asymmetric protein distribution linked to a wide variety of biological processes in different organisms and cell types. In this review, we begin by discussing the diverse biological functions, advantages, and mechanisms of mRNA localization that have been characterized to date. We then review recent technological innovations in RNA imaging and functional genomics methods that will undoubtedly provide powerful new strategies for the elucidation of mRNA trafficking pathways. Finally, we discuss several examples linking human disease pathogenesis to defects in transcript localization, which further underlines the critical importance of this gene regulatory mechanism. WIREs Dev Biol2013, 2:781–796. doi: 10.1002/wdev.113 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory MechanismsGene Expression and Transcriptional Hierarchies > Regulatory RNATechnologies > Analysis of Cell, Tissue, and Animal PhenotypesTechnologies > Analysis of the Transcriptome

We introduce the Elastic Images, a novel pseudo-haptic feedback technique which enables the perception of the local elasticity of images without the need of any haptic device. The proposed approach focus on whether visual feedback is able to induce a sensation of stiffness when the user interacts with an image using a standard mouse. The user, when clicking on a Elastic Image, is able to deform it locally according to its elastic properties. To reinforce the effect, we also propose the generation of procedural shadows and creases to simulate the compressibility of the image and several mouse cursors replacements to enhance pressure and stiffness perception. A psychophysical experiment was conducted to quantify this novel pseudo-haptic perception and determine its perceptual threshold (or its Just Noticeable Difference). The results showed that users were able to recognize up to eight different stiffness values with our proposed method and confirmed that it provides a perceivable and exploitable sensation of elasticity. The potential applications of the proposed approach range from pressure sensing in product catalogs and games, or its usage in graphical user interfaces for increasing the expressiveness of widgets.

ABSTRACTMatrix-associated laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a rapid and simple microbial identification method. Previous reports using the Biotyper system suggested that this technique requires a preliminary extraction step to identify Gram-positive rods (GPRs), a technical issue that may limit the routine use of this technique to identify pathogenic GPRs in the clinical setting. We tested the accuracy of the MALDI-TOF MS Andromas strategy to identify a set of 659 GPR isolates representing 16 bacterial genera and 72 species by the direct colony method. This bacterial collection included 40 C. diphtheriae, 13 C. pseudotuberculosis, 19 C. ulcerans, and 270 other Corynebacteriumisolates, 32 L. monocytogenesand 24 other Listeriaisolates, 46 Nocardia, 75 Actinomyces, 18 Actinobaculum, 11 Propionibacterium acnes, 18 Propionibacterium avidum, 30 Lactobacillus, 21 Bacillus, 2 Rhodococcus equi, 2 Erysipelothrix rhusiopathiae, and 38 other GPR isolates, all identified by reference techniques. Totals of 98.5% and 1.2% of non-ListeriaGPR isolates were identified to the species or genus level, respectively. Except for L. grayiisolates that were identified to the species level, all other Listeriaisolates were identified to the genus level because of highly similar spectra. These data demonstrate that rapid identification of pathogenic GPRs can be obtained without an extraction step by MALDI-TOF mass spectrometry.

The blood-cerebrospinal fluid barrier physiologically protects the meningeal spaces from blood-borne bacterial pathogens, due to the existence of specialized junctional interendothelial complexes. Few bacterial pathogens are able to reach the subarachnoidal space and among those, Neisseria meningitidisis the one that achieves this task the most constantly when present in the bloodstream. Meningeal invasion is a consequence of a tight interaction of meningococci with brain endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of endothelial docking structures resembling those elicited by the interaction of leukocytes with endothelial cells during extravasation. The consequence of these bacterial-induced signaling events is the recruitment of intercellular junction components in the docking structure and the subsequent opening of the intercellular junctions.

An open question in research nowadays is the usability of brain–computer interfaces (BCI) conceived to extend human capabilities of interaction within a virtual environment. Several paradigms are used for BCI, but the steady-state visual-evoked potential (SSVEP) stands out as it provides a higher information transfer rate while requiring less training. It is an electroencephalographic response detectable when the user looks at a flickering visual stimulus. This research proposes a novel approach for SSVEP-based BCI controller used here for navigation within a 3D virtual environment. For the first time, the flickering stimuli were integrated into virtual objects as a part of the virtual scene in a more transparent and ecological way. As an example, when navigating inside a virtual natural outdoor scene, we could embed the SSVEP flashes in the wings of virtual butterflies surrounding the user. We could also introduce the use of animated and moving stimulations when using SSVEP-based BCI, as the virtual butterflies were left with the possibility of moving and flying in front of the user. Moreover, users received real-time feedback of their mental activity and were thus aware of their detected SSVEP directly and continuously. An experiment has been conducted to assess the influence of both the feedback and the integrated controller on navigation performance and subjective preference. We found that the usage of a controller integrated within the virtual scene along with the feedback seems to improve subjective preference and feeling of presence, despite reduced performance in terms of speed. This suggests that SSVEP-based BCI interfaces for virtual environments could move on from static targets and use integrated and animated stimuli presented in an ecological way for controls in systems where performance demands could be relaxed to benefit an improvement in interaction naturalness.

ABSTRACTFollowing adhesion on brain microvasculature, Neisseria meningitidisis able to cross the blood-brain barrier (BBB) by recruiting the polarity complex and the cell junction proteins, thus allowing the opening of the paracellular route. This feature is the consequence of the activation by the type IV pili of the β2-adrenergic receptor/β-arrestin signaling pathway. Here, we have extended this observation to primary peripheral endothelial cells, and we report that the interaction of N. meningitidiswith the epithelium is strikingly different. The recruitment of the junctional components by N. meningitidisis indeed restricted to endothelial cell lines, and no alteration of the cell-cell junctions can be seen in epithelial monolayers following meningococcal type IV pilus-mediated colonization. Consistently, the β2-adrenergic receptor/β-arrestin pathway was not hijacked by bacteria adhering on epithelial cells. In addition, we showed that the consequences of the bacterial signaling on epithelial cells is different from that of endothelial cells, since N. meningitidis-induced signaling which protects the microcolonies from shear stress on endothelial cells is unable to do so on epithelial cells. Finally, we report that the minor pilin PilV, which has been shown to be essential for endothelial cell response, is not a required bacterial determinant to induce an epithelial cell response. These data demonstrate that even though pilus-mediated signaling induces an apparently similar cortical plaque, in epithelial and endothelial cell lineages, the signaling pathways are strikingly different in both models.

Taking advantage of their rapid growth and capacity for continuous genetic adaptation, prokaryotes have colonized all possible ecological environments on earth, including the body surfaces of eukaryotes and their gastrointestinal tract. The mammalian gut contains a complex community of 1014bacteria with a meta-genome containing 1500-fold more genes than the human genome. The forces that control the relationships between eukaryotic hosts and their intestinal bacterial symbionts have, thus, become a major focus of interest.

Varicella, a widespread disease of childhood, is usually benign but may in some instances lead to complications and eventually death. The aim of this study was to assess whether varicella severity in infants below one year of age was associated with the level of anti-varicella zoster virus (VZV) maternal antibodies. Two different data sets were used. Data on varicella-associated complications were collected through a national surveillance network involving 175 hospital-based pediatric wards. Data on levels of maternal acquired antibodies according to infants’ age were extracted from a cohort of 345 full term infants enrolled in a prospective multicenter study in seven pediatric wards and/or pediatric emergency units. Among infants hospitalized for varicella complications, the overall prevalence of complications increased regularly from 10.4% in infants below 1 month of age to over 72.4% at 5 months of age. Conversely, the mean antibody titre decreased from 536 mIU/mL in the [0–1 [month group to below the 150 mIU/mL threshold at 3–4 months [Pearson coefficient = -0.956 (p < 0.001)]. Based on large numbers of infants, our results show for the first time, a strong inverse correlation between the levels of circulating anti-VZV maternal antibodies in full term infants and occurrence of varicella complications below one year of age. Infant protection could be optimized by increasing herd immunity, reducing the susceptibility of women in childbearing age and lowering the age of routine vaccination to 9 months. Additional vaccination for unprotected persons in close contact with infants below 12 months of age could be promoted.

An interview with composer and music conductor Richard Bonynge is presented. When asked why he was attracted to operas of composer Jules Massenet, Bonynge says that the variety of vocal scores in Massenet's operas fascinated him. He comments that in Massenet's operas, singers are of equal importance as is the orchestration. According to him, Massenet's opera "Le Roi de Lahore," is the most lyrical opera by Massenet.

This paper describes the OpenViBE software platform which enables researchers to design, test, and use brain–computer interfaces (BCIs). BCIs are communication systems that enable users to send commands to computers solely by means of brain activity. BCIs are gaining interest among the virtual reality (VR) community since they have appeared as promising interaction devices for virtual environments (VEs). The key features of the platform are (1) high modularity, (2) embedded tools for visualization and feedback based on VR and 3D displays, (3) BCI design made available to non-programmers thanks to visual programming, and (4) various tools offered to the different types of users. The platform features are illustrated in this paper with two entertaining VR applications based on a BCI. In the first one, users can move a virtual ball by imagining hand movements, while in the second one, they can control a virtual spaceship using real or imagined foot movements. Online experiments with these applications together with the evaluation of the platform computational performances showed its suitability for the design of VR applications controlled with a BCI. OpenViBE is a free software distributed under an open-source license.

Brain–computer interfaces (BCI) are interaction devices that enable users to send commands to a computer by using brain activity only. In this paper, we propose a new interaction technique to enable users to perform complex interaction tasks and to navigate within large virtual environments (VE) by using only a BCI based on imagined movements (motor imagery). This technique enables the user to send high-level mental commands, leaving the application in charge of most of the complex and tedious details of the interaction task. More precisely, it is based on points of interest and enables subjects to send only a few commands to the application in order to navigate from one point of interest to the other. Interestingly enough, the points of interest for a given VE can be generated automatically thanks to the processing of this VE geometry. As the navigation between two points of interest is also automatic, the proposed technique can be used to navigate efficiently by thoughts within any VE. The input of this interaction technique is a newly-designed self-paced BCI which enables the user to send three different commands based on motor imagery. This BCI is based on a fuzzy inference system with reject options. In order to evaluate the efficiency of the proposed interaction technique, we compared it with the state of the art method during a task of virtual museum exploration. The state of the art method uses low-level commands, which means that each mental state of the user is associated with a simple command such as turning left or moving forward in the VE. In contrast, our method based on high-level commands enables the user to simply select its destination, leaving the application performing the necessary movements to reach this destination. Our results showed that with our interaction technique, users can navigate within a virtual museum almost twice as fast as with low-level commands, and with nearly half the commands, meaning with less stress and more comfort for the user. This suggests that our technique enables efficient use of the limited capacity of current motor imagery-based BCI in order to perform complex interaction tasks in VE, opening the way to promising new applications.

This paper presents a survey of the main results obtained in the field of “pseudo-haptic feedback”: a technique meant to simulate haptic sensations in virtual environments using visual feedback and properties of human visuo-haptic perception. Pseudo-haptic feedback uses vision to distort haptic perception and verges on haptic illusions. Pseudo-haptic feedback has been used to simulate various haptic properties such as the stiffness of a virtual spring, the texture of an image, or the mass of a virtual object. This paper describes the several experiments in which these haptic properties were simulated. It assesses the definition and the properties of pseudo-haptic feedback. It also describes several virtual reality applications in which pseudo-haptic feedback has been successfully implemented, such as a virtual environment for vocational training of milling machine operations, or a medical simulator for training in regional anesthesia procedures.

In previous work on so-called pseudo-haptic textures, we investigated the possibility of simulating sensations of texture without haptic devices by using the sole manipulation of the speed of a mouse cursor (a technique called speed technique). In this paper, we describe another technique (called Size technique) to enhance the speed technique and simulate texture sensations by varying the size of the cursor according to the local height of the texture displayed on the computer screen. With the size technique, the user would see an increase (decrease) in cursor size corresponding to a positive (negative) slope of the texture. We have conducted a series of experiments to study and compare the use of both the size and speed technique for simulating simple shapes like bumps and holes. In Experiment 1, our results showed that participants could successfully identify bumps and holes using the size technique alone. Performances obtained with the size technique reached a similar level of accuracy as found previously with the speed technique alone. In Experiment 2, we determined a point of subjective equality between bumps simulated by each technique separately, which suggests that the two techniques provide information that can be perceptually equivalent. In Experiment 3, using paradoxical situations of conflict between the two techniques, we have found that participants' answers were more influenced by the size technique, suggesting a dominance of the size over the speed technique. Furthermore, we have found a mutual reinforcement of the techniques, i.e., when the two techniques were consistently combined, the participants were more efficient in identifying the simulated shapes. In Experiment 4, we further observed the complex interactions between the information associated with the two techniques in the perception and in the decision process related to the accurate identification of bumps and holes. Taken together, our results promote the use of both techniques for the low-cost simulation of texture sensations in applications, such as videogames, internet, and graphical user interfaces.

A high‐precision, and rapid on‐line method for oxygen isotope analysis of silver phosphate is presented. The technique uses high‐temperature elemental analyzer (EA)‐pyrolysis interfaced in continuous flow (CF) mode to an isotopic ratio mass spectrometer (IRMS). Calibration curves were generated by synthesizing silver phosphate with a 13‰ spread in δ18O values. Calibration materials were obtained by reacting dissolved potassium dihydrogen phosphate (KH2PO4) with water samples of various oxygen isotope compositions at 373 K. Validity of the method was tested by comparing the on‐line results with those obtained by classical off‐line sample preparation and dual inlet isotope measurement. In addition, silver phosphate precipitates were prepared from a collection of biogenic apatites with known δ18O values ranging from 12.8 to 29.9‰ (V–SMOW). Reproducibility of ± 0.2‰ was obtained by the EA‐Py‐CF‐IRMS method for sample sizes in the range 400–500 µg. Both natural and synthetic samples are remarkably well correlated with conventional 18O/16O determinations. Silver phosphate is a very stable material and easy to degas and, thus, could be considered as a good candidate to become a reference material for the determination of 18O/16O ratios of phosphate by high‐temperature pyrolysis. Copyright © 2006 John Wiley & Sons, Ltd.

How do we perceive objects when what we see and what we touch is not at the same place? In a virtual environment, we observed that spatial delocation promotes visual dominance when judging the rotation angle of a hand-operated handle. Thus, the delocation of perceptual information appears to increase considerably the weight of the dominant sense at the expense of the other. We relate this result to the design of teleoperation and virtual reality systems, in which, typically, the visual and haptic sensory information originates in spatially distinct devices.

Since teaching and learning has become a major economic activity of modern society, different learning models can be considered in order to increase its effectiveness and efficiency. For a long time infant cognitive psychology was influenced by nativist theories and, thus, early learning has been underestimated and insufficiently studied. However, in recent years, infant psychology has described developmental sequences, learning situations, and social mechanisms that influence development. Thus, infant psychology appears again to be developmental. Since infant learning is fast and efficient, this paper proposes that it can be considered as a model for teaching and learning in older children and adults. Some examples of early acquired knowledge and some acquisition situations are presented. Conversely, some examples of later failures are exposed. The relevant theoretical contexts are discussed. The consequences of learning mechanisms observed in infants for pedagogy are considered.

The combinatorial interaction among transcription factors is believed to determine hematopoietic cell fate. Stem cell leukemia (SCL, also known as TAL1 [T-cell acute lymphoblastic leukemia 1]) is a tissue-specific basic helix-loop-helix (bHLH) factor that plays a central function in hematopoietic development; however, its target genes and molecular mode of action remain to be elucidated. Here we show that SCL and the c-Kit receptor are coexpressed in hematopoietic progenitors at the single-cell level and that SCL induces c-kit in chromatin, as ectopic SCL expression in transgenic mice sustains c-kittranscription in developing B lymphocytes, in which both genes are normally down-regulated. Through transient transfection assays and coimmunoprecipitation of endogenous proteins, we define the role of SCL as a nucleation factor for a multifactorial complex (SCL complex) that specifically enhances c-kit promoter activity without affecting the activity of myelomonocytic promoters. This complex, containing hematopoietic-specific (SCL, Lim-only 2 (LMO2), GATA-1/GATA-2) and ubiquitous (E2A, LIM- domain binding protein 1 [Ldb-1]) factors, is tethered to DNA via a specificity protein 1 (Sp1) motif, through direct interactions between elements of the SCL complex and the Sp1 zinc finger protein. Furthermore, we demonstrate by chromatin immunoprecipitation that SCL, E2A, and Sp1 specifically co-occupy thec-kit promoter in vivo. We therefore conclude thatc-kit is a direct target of the SCL complex. Proper activation of the c-kit promoter depends on the combinatorial interaction of all members of the complex. Since SCL is down-regulated in maturing cells while its partners remain expressed, our observations suggest that loss of SCL inactivates the SCL complex, which may be an important event in the differentiation of pluripotent hematopoietic cells.

The combinatorial interaction among transcription factors is believed to determine hematopoietic cell fate. Stem cell leukemia (SCL, also known as TAL1 [T-cell acute lymphoblastic leukemia 1]) is a tissue-specific basic helix-loop-helix (bHLH) factor that plays a central function in hematopoietic development; however, its target genes and molecular mode of action remain to be elucidated. Here we show that SCL and the c-Kit receptor are coexpressed in hematopoietic progenitors at the single-cell level and that SCL induces c-kitin chromatin, as ectopic SCL expression in transgenic mice sustains c-kittranscription in developing B lymphocytes, in which both genes are normally down-regulated. Through transient transfection assays and coimmunoprecipitation of endogenous proteins, we define the role of SCL as a nucleation factor for a multifactorial complex (SCL complex) that specifically enhances c-kitpromoter activity without affecting the activity of myelomonocytic promoters. This complex, containing hematopoietic-specific (SCL, Lim-only 2 (LMO2), GATA-1/GATA-2) and ubiquitous (E2A, LIM- domain binding protein 1 [Ldb-1]) factors, is tethered to DNA via a specificity protein 1 (Sp1) motif, through direct interactions between elements of the SCL complex and the Sp1 zinc finger protein. Furthermore, we demonstrate by chromatin immunoprecipitation that SCL, E2A, and Sp1 specifically co-occupy thec-kitpromoter in vivo. We therefore conclude thatc-kitis a direct target of the SCL complex. Proper activation of the c-kitpromoter depends on the combinatorial interaction of all members of the complex. Since SCL is down-regulated in maturing cells while its partners remain expressed, our observations suggest that loss of SCL inactivates the SCL complex, which may be an important event in the differentiation of pluripotent hematopoietic cells.

The nucleus of mammalian spermatozoa is surrounded by a rigid layer, the perinuclear theca, which is divided into a subacrosomal layer and a postacrosomal calyx. Among the proteins characterized in the perinuclear theca, calicin is one of the main components of the calyx. Its sequence contains three kelch repeats and a BTB/POZ domain. We have studied the association of boar calicin with F-actin and the distribution of boar and human calicin during spermiogenesis compared with the distribution of actin. Calicin was purified from boar sperm heads under nondenaturating conditions. The molecule bound actin with high affinity (Kd= ∼5 nM), and a stoichiometry of approximately one calicin per 12 actin monomers was observed. Gel filtration studies showed that calicin forms homomultimers (tetramers and higher polymers). According to immunocytochemical results, calicin is present (together with actin) in the acrosomal region of round spermatids and is mainly localized in the postacrosomal region of late spermatids and spermatozoa. Taken together, the results suggest that the affinity of calicin to F-actin allows targeting of calicin at the subacrosomal space of round spermatids, and that its ability to form homomultimers contributes to the formation of a rigid calyx.

The present study is focused on the so-called High Temprature Reaction Zone of the Oman ophiolite, a thin zone located between the roots of the sheeted dyke complex and the high-level gabbros marking the roof of the fossil magma chambers. The distribution of diabases, chloritised dykes, spilitized dykes and epidosites (in the order of increasing hydrothermal alteration) was studied along continuous outcrops of the lower sheeted dyke complex in three selected areas. The Muwaylah section, in the Haylayn massif, representing a fossil axial discontinuity, is the most massively epidotised area, with epidosite zones of 3–15 m wide and an average spacing of 12 m. In this area, there are two directions of dyking, and a massive sulfide deposit (Daris prospect). The wadi Andam area (Samail massif), representing a much less tectonised site, close to a mantle diapir and located probably midway between the tip and the center of an accretion segment, is also well epidotised, with epidosites spacing of 10–25 m. The wadi Salahi area probably represents the central part of a fossil accretion segment and is by far the least altered site, in spite of being located quite beneath the Zuha sulfide prospect. This confirms that the hot ascending fluids in major discharge zones are strongly focused. Fluid inclusions from about 50 samples collected in the plagiogranites, gabbros and sheeted dykes of the Muwaylah and wadi Falah areas (SE Haylayn massif), consist of: (1) monophase (liquid) inclusions, generally stretched and deformed; (2) vapour-dominated, low-salinity, 2-phase inclusions, with average salinity of 3.8 wt% eq. NaCl and an average Th of 370 °C; (3) liquid-dominated, low-salinity, 2-phase inclusions, with an average salinity of 4.2 wt% eq. NaCl and an average Th of 325 °C, and (4) liquid-dominated, high-salinity inclusions, containing a solid halite daughter phase, dissolving at higher temperature (292–441 °C ) than homogenisation of the fluid phases (230–403 °C ). One plagiogranite sample collected in the Muwaylah area (Haylayn massif) is particularly rich in quartz-epidote hydrothermal veins. Xenomorphic globular quartz is rich in high-salinity, brine-rich inclusions, with halite cubes dissolving at very high temperatures (358–496 °C ) yielding very high salinities (43 to 59.2% NaCl eq.), and with liquid-vapour homogenisation of 275 °C on average. Molecular Raman Spectroscopy analyses have confirmed the aqueous nature of these inclusions and the absence of detectable CO2, NH4, N2and SO2. Daughter solid phases other than NaCl were determined as hematite and anhydrite, and a third phase is hydroxyl-bearing (amphibole?). PIXE analyses on six brine-rich inclusions allowed to detect significant but variable contents in Cl, Fe, Mn, K, Ca, Zn and Br. Copper, remarkably, was never detected, and two measured Cl/Br ratios are close to that of seawater. The measurement of oxygen isotopic ratios of the fluids extracted from some fluid inclusions and of associated host-minerals (quartz, epidote) suggest that both seawater-derived and magma-derived fluids have mixed in the High Temperature Reaction Zone. PIXE data yield a similar conclusion, based on the contrasted Fe and Mn-contents and Cl/Br ratios of the analysed inclusions. However, the oxidised and Cu-depleted nature of the brine-rich inclusions suggests that the magma-derived or seawater-derived brines are residual liquids that have degassed. Present V-X properties of most NaCl-saturated inclusions do not keep the record of the boiling process, as they homogenise by halite disappearance and not by vapour disappearance. Probably they have been modified by several post-trapping changes, for instance by necking.

Oxygen isotope compositions of Silurian calcitic brachiopod shells from Gotland are compared with those of phosphatic inarticulate brachiopod shells and conodonts from identical stratigraphic horizons. The δ18Ophosphatevalues of inarticulate brachiopod shells vary widely (13.0 to 17.5‰ V-SMOW) and are significantly lower than those of coeval conodont samples (17.5 to 19.5‰ V-SMOW). Conodont samples from individual beds have homogenous δ18Ophosphatevalues with variations close to the analytical precision (±0.2‰). Together with a significant correlation of conodont δ18Ophosphateand articulate brachiopod shell δ18Ocarbonatevalues (r = 0.85), this observation suggests that primary marine oxygen isotope compositions are better preserved in conodont apatite than in inarticulate brachiopod shell apatite. However, with decreasing δ18Ocarbonatevalues, the δ18Ophosphatevalues of conodonts are higher than expected for theoretical isotopic equilibrium with brachiopod calcite. Different habitats of conodonts and brachiopods cannot account for the observed offset in δ18O because both organisms were thriving on a broad shallow marine carbonate platform. Whereas δ18Ophosphatevalues of Silurian conodonts are close to δ18Ophosphatevalues of modern and Mesozoic tropical biogenic apatites, most Silurian calcitic brachiopod shells from Gotland are depleted in 18O when compared to modern or Mesozoic brachiopods. We therefore suggest that Silurian conodonts from Gotland record paleotemperature and δ18O of Silurian sea water more faithfully than coeval calcitic brachiopod shells.

The adsorption of NO at room temperature on a H-ZSM-5 catalyst exchanged with Pd(NH3)42+ complex and activated in oxygen at 773 K has been examined by FTIR spectroscopy. After the oxidizing treatment, the Pd tetrammine complex decomposed into Pd(II) ions and/or Pd(II) hydroxyl complexes dispersed in the zeolite channels. The subsequent adsorption of NO at room temperature led to the reduction of Pd(II) to Pd(I) entities, resulting in the formation and adsorption of NO2 on H-ZSM-5. The Pd(I) entities were shown to adsorb NO and form mononitrosyl complexes dispersed in the zeolite porosity and characterized by a single infrared absorption band at 1881 cm-1. The Pd(I) mononitrosyl complex was shown to reversibly coordinate water and NO2 molecules. The resulting nitrosyl complex was characterized by a single NO vibration band at 1836 cm-1.

Study aimFrom 1971 to 1995, 39 patients underwent curative resection of a malignant tumor of the ampulla of Vater. The aim of this retrospective study was to report long-term results and to determine factors influencing survival in these patients.Patients and methodsData was collected from patient record analysis, correspondence with patients, their family or general physician. Kaplan-Meier method was used to compare survival data by the log-rank test. Multivariate analysis evaluated the impact of each variable on survival. Values with a P value of 0.05 or less were considered statistically significant.ResultsResection consisted of pylorus preserving pancreaticoduodenectomy (n = 21) or pancreatico-duodenectomy associated with an antrectomy (n = 18). Overall mortality rate after resection was 10% (n = 4). General and specific morbidity rates were 71% and 2.5%. During the course of the follow-up (completeness: 100%) mean survival was 80 months (median: 37 months, range: 6–227 months). Five-year survival rate was 35%. Factors favorably influencing long-term outcome were exposed protruding and well differentiated tumors (P = 0.03, P = 0.01, respectively) and negative lymph node status (P = 0.0001). Prognosis was poorer if tumor was extended into the pancreas (P= 0.04). Among proposed histoprognostic classifications (classifications of Martin, Talbot, Shiraï, Yamaguchi), an excellent correlation was obtained only with TNM classification (P = 0.0001).ConclusionResults of the present study suggest that prolonged survival can be obtained following radical resection of a malignant tumor of the ampulla of Vater, especially for exposed protruding and well differentiated tumors, without extension into the pancreas or lymph node metastasis. TNM classification provides an excellent predictive value and should be used more systematically.