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Showing papers by "University of Geneva published in 2005"


Journal ArticleDOI
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.

6,018 citations


Journal ArticleDOI
TL;DR: This critical review has been tailored for a broad audience of chemists, biochemists and materials scientists; the basics of lanthanide photophysics are highlighted together with the synthetic strategies used to insert these ions into mono- and polymetallic molecular edifices.
Abstract: Lanthanide ions possess fascinating optical properties and their discovery, first industrial uses and present high technological applications are largely governed by their interaction with light. Lighting devices (economical luminescent lamps, light emitting diodes), television and computer displays, optical fibres, optical amplifiers, lasers, as well as responsive luminescent stains for biomedical analysis, medical diagnosis, and cell imaging rely heavily on lanthanide ions. This critical review has been tailored for a broad audience of chemists, biochemists and materials scientists; the basics of lanthanide photophysics are highlighted together with the synthetic strategies used to insert these ions into mono- and polymetallic molecular edifices. Recent advances in NIR-emitting materials, including liquid crystals, and in the control of luminescent properties in polymetallic assemblies are also presented. (210 references.)

3,242 citations


Journal ArticleDOI
20 Oct 2005-Nature
TL;DR: Cardif is described, a new CARD-containing adaptor protein that interacts with RIG-I and recruits IKKα, IKKβ and IKKɛ kinases by means of its C-terminal region, leading to the activation of NF-κB and IRF3.
Abstract: Antiviral immunity against a pathogen is mounted upon recognition by the host of virally associated structures. One of these viral 'signatures', double-stranded (ds) RNA, is a replication product of most viruses within infected cells and is sensed by Toll-like receptor 3 (TLR3) and the recently identified cytosolic RNA helicases RIG-I (retinoic acid inducible gene I, also known as Ddx58) and Mda5 (melanoma differentiation-associated gene 5, also known as Ifih1 or Helicard). Both helicases detect dsRNA, and through their protein-interacting CARD domains, relay an undefined signal resulting in the activation of the transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB. Here we describe Cardif, a new CARD-containing adaptor protein that interacts with RIG-I and recruits IKKalpha, IKKbeta and IKKvarepsilon kinases by means of its C-terminal region, leading to the activation of NF-kappaB and IRF3. Overexpression of Cardif results in interferon-beta and NF-kappaB promoter activation, and knockdown of Cardif by short interfering RNA inhibits RIG-I-dependent antiviral responses. Cardif is targeted and inactivated by NS3-4A, a serine protease from hepatitis C virus known to block interferon-beta production. Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes.

2,328 citations


Journal ArticleDOI
TL;DR: In this article, the authors introduce the current state of development in the application of ferroelectric thin films for electronic devices and discuss the physics relevant for the performance and failure of these devices.
Abstract: This review covers important advances in recent years in the physics of thin-film ferroelectric oxides, the strongest emphasis being on those aspects particular to ferroelectrics in thin-film form. The authors introduce the current state of development in the application of ferroelectric thin films for electronic devices and discuss the physics relevant for the performance and failure of these devices. Following this the review covers the enormous progress that has been made in the first-principles computational approach to understanding ferroelectrics. The authors then discuss in detail the important role that strain plays in determining the properties of epitaxial thin ferroelectric films. Finally, this review ends with a look at the emerging possibilities for nanoscale ferroelectrics, with particular emphasis on ferroelectrics in nonconventional nanoscale geometries.

1,908 citations


Journal ArticleDOI
TL;DR: A positive margin after resection of hepatic colorectal metastases is associated with adverse biologic factors and increased risk of surgical-margin recurrence, and a predicted margin of <1 cm should not be used as an exclusion criterion for resection.
Abstract: Liver resection currently represents the only potentially curative therapeutic option for hepatic colorectal metastasis (CRM), and 5-year survival rates of 25% to 58% have been reported.1–6 Traditionally, primary tumor stage, preoperative carcinoembryonic antigen (CEA) level, hepatic tumor size, number of hepatic metastases, time from primary tumor treatment to diagnosis of hepatic metastases, and presence of extrahepatic disease have been reported to be independent predictors of survival after resection.7,8 Surgical margin status is an additional factor that has been evaluated for its influence on long-term survival after resection of CRM, but its significance remains controversial. Several series concerning liver resection for colorectal liver metastasis have reported that surgical margins of less than 1 cm are an absolute9,10 or relative contraindication to surgery.11 Cady et al10 have reported that a surgical margin less than 1 cm was associated on univariate analysis with a significantly shorter disease-free survival. As a result, major centers have adopted a 1-cm margin as a target during resection to minimize hepatic recurrence and improve survival after resection of CRM.12,13 In fact, a 1-cm margin has been proposed as the minimally acceptable margin even for ablative techniques.14,15 Despite the emphasis on a 1-cm margin, some investigators16 have reported that the actual width of the surgical margin has no effect on survival as long as the margin is negative. Altendorf-Hofmann and Scheele16 noted that patients with a microscopically positive margin (R1) had a worse prognosis compared with patients who had a microscopically negative margin (R0), but survival was not associated with the width of the negative surgical margin. More recently, Adam et al17 reported a 5-year survival rate of 33% in 138 patients, among whom 67% had less than 1-mm surgical margins. All of these studies, however, examined only the effect of surgical margin status on survival but not local recurrence. If margin status or width of margin is important, it has practical implications. Specifically, margin considerations may dictate which patients are resectable, the extent of resection, and the treatment of residual positive margins at the time of surgery.10,18 The objective of the current study was to evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for CRM at 3 hepatobiliary centers.

1,004 citations


Journal ArticleDOI
TL;DR: Evaluating the impact of methicillin resistance in S. aureus bacteremia in patients admitted to the hospital between July 1, 1997, and June 1, 2000 found it was associated with significant increases in length of hospitalization and hospital charges.
Abstract: OBJECTIVE To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges. DESIGN A cohort study of patients admitted to the hospital between July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections. SETTING A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts. PATIENTS Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score. RESULTS Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars. CONCLUSION Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.

948 citations


Journal ArticleDOI
TL;DR: This review will discuss the factors that can influence this delicate balance in plant peroxidases, which can prevent biological and chemical attacks by raising physical barriers or by counterattacking with a large production of ROS.
Abstract: Plant peroxidases (class III peroxidases) are present in all land plants. They are members of a large multigenic family. Probably due to this high number of isoforms, and to a very heterogeneous regulation of their expression, plant peroxidases are involved in a broad range of physiological processes all along the plant life cycle. Due to two possible catalytic cycles, peroxidative and hydroxylic, peroxidases can generate reactive oxygen species (ROS) (•OH, HOO•), polymerise cell wall compounds, and regulate H2O2 levels. By modulating their activity and expression following internal and external stimuli, peroxidases are prevalent at every stage of plant growth, including the demands that the plant meets in stressful conditions. These multifunctional enzymes can build a rigid wall or produce ROS to make it more flexible; they can prevent biological and chemical attacks by raising physical barriers or by counterattacking with a large production of ROS; they can be involved in a more peaceful symbiosis. They are finally present from the first hours of a plant’s life until its last moments. Although some functions look paradoxical, the whole process is probably regulated by a fine-tuning that has yet to be elucidated. This review will discuss the factors that can influence this delicate balance.

928 citations


Journal ArticleDOI
01 Dec 2005-Nature
TL;DR: In this article, the in vitro substrates recognized by most yeast protein kinases were identified, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits.
Abstract: Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

921 citations


Journal ArticleDOI
TL;DR: This MRI study of prematurely born infants further defines the nature of quantitative cerebral structural abnormalities present as early as term equivalent and is related most significantly to the degree of immaturity at birth and to concomitant WM injury.
Abstract: Background. Long-term studies of the outcome of very prematurely born infants have clearly documented that the majority of such infants have significant motor, cognitive, and behavioral deficits. However, there is a limited understanding of the nature of the cerebral abnormality underlying these adverse neurologic outcomes. Aim. The overall aim of this study was to define quantitatively the alterations in cerebral tissue volumes at term equivalent in a large longitudinal cohort study of very low birth weight premature infants in comparison to term-born infants by using advanced volumetric 3-dimensional magnetic resonance imaging (MRI) techniques. We also aimed to define any relationship of such perinatal lesions as white matter (WM) injury or other potentially adverse factors to the quantitative structural alterations. Additionally, we wished to identify the relationship of the structural alterations to short-term neurodevelopmental outcome. Methods. From November 1998 to December 2000, 119 consecutive premature infants admitted to the neonatal intensive care units at Christchurch Women’s Hospital (Christchurch, New Zealand) and the Royal Women’s Hospital (Melbourne, Australia) were recruited (88% of eligible) after informed parental consent to undergo an MRI scan at term equivalent. Twenty-one term-born infants across both sites were recruited also. Postacquisition advanced 3-dimensional tissue segmentation with 3-dimensional reconstruction was undertaken to estimate volumes of cerebral tissues: gray matter (GM; cortical and deep nuclear structures), WM (myelinated and unmyelinated), and cerebrospinal fluid (CSF). Results. In comparison to the term-born infants, the premature infants at term demonstrated prominent reductions in cerebral cortical GM volume (premature infants [mean ± SD]: 178 ± 41 mL; term infants: 227 ± 26 mL) and in deep nuclear GM volume (premature infants: 10.8 ± 4.1 mL; term infants: 13.8 ± 5.2 mL) and an increase in CSF volume (premature infants: 45.6 ± 22.1 mL; term infants: 28.9 ± 16 mL). The major predictors of altered cerebral volumes were gestational age at birth and the presence of cerebral WM injury. Infants with significantly reduced cortical GM and deep nuclear GM volumes and increased CSF volume volumes exhibited moderate to severe neurodevelopmental disability at 1 year of age. Conclusions. This MRI study of prematurely born infants further defines the nature of quantitative cerebral structural abnormalities present as early as term equivalent. The abnormalities particularly involve cerebral neuronal regions including both cortex and deep nuclear structures. The pattern of cerebral alterations is related most significantly to the degree of immaturity at birth and to concomitant WM injury. The alterations are followed by abnormal short-term neurodevelopmental outcome.

855 citations


Journal ArticleDOI
TL;DR: The morphology of superficial and nonprotruding neoplastic lesions is relevant to the prognosis and is an important criterion for the necessity of additional surgical resection after endoscopic resection.
Abstract: Background and Study Aims: Neoplastic lesions in the digestive-tract mucosa are termed superficial when the depth of invasion is limited to the mucosa and submucosa. The endoscopic appearance has a predictive value for invasion into the submucosa, which is critical for the risk of nodal metastases. Materials and Methods: The endoscopic morphology of superficial lesions can be assessed with a standard video endoscope after spraying of a dye - an iodine-potassium iodide solution for the stratified squamous epithelium, or an indigo carmine solution for the columnar epithelium. In 2002, a workshop was held in Paris to explore the relevance of the Japanese classification. The conclusions were revised in 2003 in Osaka in relation to the definition of the subtypes used in endoscopy and the evaluation of the depth of invasion into the submucosa. In Japan, the description of advanced cancer in the digestive-tract mucosa using types 1 -4 is supplemented by a type 0 when the endoscopic appearance is that of a superficial lesion. Type 0 is divided into three categories: protruding (0-1), nonprotruding and nonexcavated (0-11), and excavated (0-III). Type 0-II lesions are then subdivided into slightly elevated (IIa), flat (IIb), or depressed (IIc). Nonprotruding depressed lesions are associated with a higher risk of submucosal invasion. After endoscopic resection, invasion into the submucosa is an important criterion for the necessity of additional surgical resection. Micrometer analysis of the depth of invasion in the specimen is more precise, and distinct cut-off limits have been established in the esophagus, stomach, and large bowel. Conclusions: The morphology of superficial and nonprotruding neoplastic lesions is relevant to the prognosis. Following endoscopic detection, the lesions are analyzed using chromoendoscopy and assigned a subtype of the type 0 classification. The choice between endoscopicorsurgical treatment is based on this description.

730 citations


Journal ArticleDOI
24 Feb 2005-Nature
TL;DR: In stn7 mutant plants the plastoquinone pool is more reduced and growth is impaired under changing light conditions, indicating that STN7, and probably state transitions, have an important role in response to environmental changes.
Abstract: Photosynthetic organisms are able to adjust to changing light conditions through state transitions, a process that involves the redistribution of light excitation energy between photosystem II (PSII) and photosystem I (PSI). Balancing of the light absorption capacity of these two photosystems is achieved through the reversible association of the major antenna complex (LHCII) between PSII and PSI (ref. 3). Excess stimulation of PSII relative to PSI leads to the reduction of the plastoquinone pool and the activation of a kinase; the phosphorylation of LHCII; and the displacement of LHCII from PSII to PSI (state 2). Oxidation of the plastoquinone pool by excess stimulation of PSI reverses this process (state 1). The Chlamydomonas thylakoid-associated Ser-Thr kinase Stt7, which is required for state transitions, has an orthologue named STN7 in Arabidopsis. Here we show that loss of STN7 blocks state transitions and LHCII phosphorylation. In stn7 mutant plants the plastoquinone pool is more reduced and growth is impaired under changing light conditions, indicating that STN7, and probably state transitions, have an important role in response to environmental changes.

Journal ArticleDOI
03 Jun 2005-Science
TL;DR: The MWC theory and its applications for the understanding of signal transduction in biology are reviewed, and remaining issues that deserve theoretical and experimental substantiation are identified.
Abstract: Forty years ago, a simple model of allosteric mechanisms (indirect interactions between distinct sites), used initially to explain feedback-inhibited enzymes, was presented by Monod, Wyman, and Changeux. We review the MWC theory and its applications for the understanding of signal transduction in biology, and also identify remaining issues that deserve theoretical and experimental substantiation.

Journal ArticleDOI
TL;DR: The presented results demonstrate that the nanoprecipitation technique is more versatile and flexible than previously thought and that a wide range of parameters can be modified.

Journal ArticleDOI
TL;DR: It is demonstrated that Shh is required for cell proliferation in the mouse forebrain's subventricular zone (SVZ) stem cell niche and for the production of new olfactory interneurons in vivo, and the role of Shh signaling in the regulation of stem cell lineages in the adult mammalian brain is demonstrated.
Abstract: Sonic hedgehog (Shh) signaling controls many aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in the control of cell proliferation in the adult ventral forebrain and in the hippocampus. However, it remains unclear whether it regulates adult stem cell lineages in an equivalent manner. Similarly, it is not known which cells respond to Shh signaling in stem cell niches. Here we demonstrate that Shh is required for cell proliferation in the mouse forebrain's subventricular zone (SVZ) stem cell niche and for the production of new olfactory interneurons in vivo. We identify two populations of Gli1+ Shh signaling responding cells: GFAP+ SVZ stem cells and GFAP- precursors. Consistently, we show that Shh regulates the self-renewal of neurosphere-forming stem cells and that it modulates proliferation of SVZ lineages by acting as a mitogen in cooperation with epidermal growth factor (EGF). Together, our data demonstrate a critical and conserved role of Shh signaling in the regulation of stem cell lineages in the adult mammalian brain, highlight the subventricular stem cell astrocytes and their more abundant derived precursors as in vivo targets of Shh signaling, and demonstrate the requirement for Shh signaling in postnatal and adult neurogenesis.

Journal ArticleDOI
TL;DR: An appraisal-based emotion theory, the Component Process Model (CPM), is described that seems particularly suited to modeling with the help of artificial neural network approaches, due to its high degree of specificity in postulating underlying mechanisms including efferent physiological and behavioral manifestations.

Journal ArticleDOI
TL;DR: In this paper, various approaches based on bounding volume hierarchies, distance fields and spatial partitioning are discussed for collision detection of deformable objects in interactive environments for surgery simulation and entertainment technology.
Abstract: Interactive environments for dynamically deforming objects play an important role in surgery simulation and entertainment technology. These environments require fast deformable models and very efficient collision handling techniques. While collision detection for rigid bodies is well investigated, collision detection for deformable objects introduces additional challenging problems. This paper focuses on these aspects and summarizes recent research in the area of deformable collision detection. Various approaches based on bounding volume hierarchies, distance fields and spatial partitioning are discussed. In addition, image-space techniques and stochastic methods are considered. Applications in cloth modeling and surgical simulation are presented.

Journal ArticleDOI
TL;DR: A role of BDNF and NT-3 neurotrophin, in the pathophysiology of suicidal behavior is supported, which may implicate the hippocampus and the PFC but not the entorhinal cortex, and both neurotrophins are mediators of psychotropic drugs.

Journal ArticleDOI
TL;DR: The results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I) HapMap has sufficient density to enable linkage disequilibrium mapping in humans.
Abstract: The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12–13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs) with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis-) to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I) HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

Book
16 Sep 2005
TL;DR: The Public Policy Process as discussed by the authors is essential reading for anyone trying to understand the process by which public policy is made and explains clearly the importance of the relationship between theoretical and practical aspects of policy making, giving a thorough overview of the people and organisations involved in the process.
Abstract: The Public Policy Process is essential reading for anyone trying to understand the process by which public policy is made. Explaining clearly the importance of the relationship between theoretical and practical aspects of policy making, the book gives a thorough overview of the people and organisations involved in the process. Fully revised and updated for a seventh edition, The Public Policy Process provides: • Clear exploration, using many illustrations, of how policy is made and implemented. • A new chapter on comparative theory and methods. • New material on studying advocacy coalitions, policy changes, governance and evaluation. • More European and international examples

Journal ArticleDOI
26 Aug 2005-Cell
TL;DR: It is shown that the small GTPase Sar1p directly initiates membrane curvature during vesicle biogenesis and couples the generation of membranes curvature with coat-protein assembly and cargo capture.

Journal ArticleDOI
TL;DR: This software, implemented as a Java plug-in for the public-domain ImageJ software, is used to track the movement of chromosomal loci within nuclei of budding yeast cells to reveal different classes of constraints on mobility of telomeres, reflecting differences in nuclear envelope association.
Abstract: We present a new, robust, computational procedure for tracking fluorescent markers in time-lapse microscopy. The algorithm is optimized for finding the time-trajectory of single particles in very noisy dynamic (two- or three-dimensional) image sequences. It proceeds in three steps. First, the images are aligned to compensate for the movement of the biological structure under investigation. Second, the particle's signature is enhanced by applying a Mexican hat filter, which we show to be the optimal detector of a Gaussian-like spot in 1//spl omega//sup 2/ noise. Finally, the optimal trajectory of the particle is extracted by applying a dynamic programming optimization procedure. We have used this software, which is implemented as a Java plug-in for the public-domain ImageJ software, to track the movement of chromosomal loci within nuclei of budding yeast cells. Besides reducing trajectory analysis time by several 100-fold, we achieve high reproducibility and accuracy of tracking. The application of the method to yeast chromatin dynamics reveals different classes of constraints on mobility of telomeres, reflecting differences in nuclear envelope association. The generic nature of the software allows application to a variety of similar biological imaging tasks that require the extraction and quantitation of a moving particle's trajectory.

Journal ArticleDOI
TL;DR: It is suggested that the VMPFC is crucial for representing knowledge pertaining to the self and that this is an important function of the resting state.

Journal ArticleDOI
TL;DR: Overall, the findings implicate leukocytes, most likely neutrophils, as a key cellular source of MMP-9, which, in turn, promotes leukocyte recruitment, causes BBB breakdown secondary to microvascular basal lamina proteolysis, and ultimately contributes to neuronal injury after transient focal stroke.
Abstract: Results of recent studies reveal vascular and neuroprotective effects of matrix metalloproteinase-9 (MMP-9) inhibition and MMP-9 gene deletion in experimental stroke. However, the cellular source o...

Journal ArticleDOI
TL;DR: In this paper, a technique for proving the security of quantum-key-distribution (QKD) protocols is presented based on direct information-theoretic arguments and thus also applies if no equivalent entanglement purification scheme can be found.
Abstract: We present a technique for proving the security of quantum-key-distribution (QKD) protocols. It is based on direct information-theoretic arguments and thus also applies if no equivalent entanglement purification scheme can be found. Using this technique, we investigate a general class of QKD protocols with one-way classical post-processing. We show that, in order to analyze the full security of these protocols, it suffices to consider collective attacks. Indeed, we give new lower and upper bounds on the secret-key rate which only involve entropies of two-qubit density operators and which are thus easy to compute. As an illustration of our results, we analyze the Bennett-Brassard 1984, the six-state, and the Bennett 1992 protocols with one-way error correction and privacy amplification. Surprisingly, the performance of these protocols is increased if one of the parties adds noise to the measurement data before the error correction. In particular, this additional noise makes the protocols more robust against noise in the quantum channel.

Journal ArticleDOI
TL;DR: Two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody are reported, reflecting a fundamental principle of human brain organization shared by voice and face perception.
Abstract: We report two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody. This emotional enhancement was voice specific, unrelated to isolated acoustic amplitude or frequency cues in angry prosody, and distinct from any concomitant task-related attentional modulation. Attention and emotion seem to have separate effects on stimulus processing, reflecting a fundamental principle of human brain organization shared by voice and face perception.

Posted Content
TL;DR: The authors analyzes theoretically and empirically the relationship between trade and war and finds that countries more open to global trade have a higher probability of war because multilateral trade openness decreases bilateral dependence to any given country.
Abstract: This paper analyzes theoretically and empirically the relationship between trade and war. We show that the intuition that trade promotes peace is only partially true even in a model where trade is beneficial to all, war reduces trade and leaders take into account the costs of war. When war can occur because of the presence of asymmetric information, the probability of escalation is indeed lower for countries that trade more bilaterally because of the opportunity cost associated with the loss of trade gains. However, countries more open to global trade have a higher probability of war because multilateral trade openness decreases bilateral dependence to any given country. Using a theoretically-based econometric model, we test our predictions on a large dataset of military conflicts in the period 1948-2001. We find strong evidence for the contrasting effects of bilateral and multilateral trade. Our empirical results also confirm our theoretical prediction that multilateral trade openness increases more the probability of war between proximate countries. This may explain why military conflicts have become more localized and less global over time.

Journal ArticleDOI
TL;DR: In this article, the authors discuss the physics potential and the experimental challenges of an upgraded LHC running at an instantaneous luminosity of 1035 cm-2s-1, and the detector R&D needed to operate ATLAS and CMS in a very high radiation environment and the expected detector performance.
Abstract: We discuss the physics potential and the experimental challenges of an upgraded LHC running at an instantaneous luminosity of 1035 cm-2s-1. The detector R&D needed to operate ATLAS and CMS in a very high radiation environment and the expected detector performance are discussed. A few examples of the increased physics potential are given, ranging from precise measurements within the Standard Model (in particular in the Higgs sector) to the discovery reach for several New Physics processes.

Journal ArticleDOI
TL;DR: In this paper, differential activation of the three independent promoters that drive expression of the gene encoding the class II transactivator ultimately determines the exquisitely regulated pattern of MHC class II gene expression.
Abstract: MHC class II molecules are pivotal for the adaptive immune system, because they guide the development and activation of CD4+ T helper cells. Fulfilling these functions requires that the genes encoding MHC class II molecules are transcribed according to a strict cell-type-specific and quantitatively modulated pattern. This complex gene-expression profile is controlled almost exclusively by a single master regulatory factor, which is known as the class II transactivator. As we discuss here, differential activation of the three independent promoters that drive expression of the gene encoding the class II transactivator ultimately determines the exquisitely regulated pattern of MHC class II gene expression.

Journal ArticleDOI
TL;DR: The basic principles behind various physical methods for gene transfer are described and the advantages and performance of such approaches, compared to other transfection systems, are assessed.

Journal ArticleDOI
01 Sep 2005-Nature
TL;DR: A demonstration of qubit transfer between photons of wavelength 1,310 nm and 710‬nm is reported, a nonlinear up-conversion process, with a success probability of greater than 5 per cent.
Abstract: Quantum communication is the art of transferring quantum states, or quantum bits of information (qubits), from one place to another. On the fundamental side, this allows one to distribute entanglement and demonstrate quantum nonlocality over significant distances. On the more applied side, quantum cryptography offers, for the first time in human history, a provably secure way to establish a confidential key between distant partners. Photons represent the natural flying qubit carriers for quantum communication, and the presence of telecom optical fibres makes the wavelengths of 1310 and 1550 nm particulary suitable for distribution over long distances. However, to store and process quantum information, qubits could be encoded into alkaline atoms that absorb and emit at around 800 nm wavelength. Hence, future quantum information networks made of telecom channels and alkaline memories will demand interfaces able to achieve qubit transfers between these useful wavelengths while preserving quantum coherence and entanglement. Here we report on a qubit transfer between photons at 1310 and 710 nm via a nonlinear up-conversion process with a success probability greater than 5%. In the event of a successful qubit transfer, we observe strong two-photon interference between the 710 nm photon and a third photon at 1550 nm, initially entangled with the 1310 nm photon, although they never directly interacted. The corresponding fidelity is higher than 98%.