scispace - formally typeset
Search or ask a question

Showing papers by "Pierre-and-Marie-Curie University published in 2007"


Journal ArticleDOI
TL;DR: The NINCDS-ADRDA and DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge as discussed by the authors.
Abstract: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

3,951 citations


Journal ArticleDOI
TL;DR: Although there was evidence of an off-target effect of torcetrapib, it cannot rule out adverse effects related to CETP inhibition, and the trial was terminated prematurely because of an increased risk of death and cardiac events.
Abstract: Background Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. Methods We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. Results At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both compari...

2,832 citations


Journal ArticleDOI
TL;DR: In this article, the Lagrangian conservation principle for potential vorticity and potential temperature is extended to take the lower boundary condition into account, where the total mass under each isentropic surface is specified.
Abstract: The two main principles underlying the use of isentropic maps of potential vorticity to represent dynamical processes in the atmosphere are reviewed, including the extension of those principles to take the lower boundary condition into account. the first is the familiar Lagrangian conservation principle, for potential vorticity (PV) and potential temperature, which holds approximately when advective processes dominate frictional and diabatic ones. the second is the principle of ‘invertibility’ of the PV distribution, which holds whether or not diabatic and frictional processes are important. the invertibility principle states that if the total mass under each isentropic surface is specified, then a knowledge of the global distribution of PV on each isentropic surface and of potential temperature at the lower boundary (which within certain limitations can be considered to be part of the PV distribution) is sufficient to deduce, diagnostically, all the other dynamical fields, such as winds, temperatures, geopotential heights, static stabilities, and vertical velocities, under a suitable balance condition. the statement that vertical velocities can be deduced is related to the well-known omega equation principle, and depends on having sufficient information about diabatic and frictional processes. Quasi-geostrophic, semigeostrophic, and ‘nonlinear normal mode initialization’ realizations of the balance condition are discussed. an important constraint on the mass-weighted integral of PV over a material volume and on its possible diabatic and frictional change is noted. Some basic examples are given, both from operational weather analyses and from idealized theoretical models, to illustrate the insights that can be gained from this approach and to indicate its relation to classical synoptic and air-mass concepts. Included are discussions of (a) the structure, origin and persistence of cutoff cyclones and blocking anticyclones, (b) the physical mechanisms of Rossby wave propagation, baroclinic instability, and barotropic instability, and (c) the spatially and temporally nonuniform way in which such waves and instabilities may become strongly nonlinear, as in an occluding cyclone or in the formation of an upper air shear line. Connections with principles derived from synoptic experience are indicated, such as the ‘PVA rule’ concerning positive vorticity advection on upper air charts, and the role of disturbances of upper air origin, in combination with low-level warm advection, in triggering latent heat release to produce explosive cyclonic development. In all cases it is found that time sequences of isentropic potential vorticity and surface potential temperature charts—which succinctly summarize the combined effects of vorticity advection, thermal advection, and vertical motion without requiring explicit knowledge of the vertical motion field—lead to a very clear and complete picture of the dynamics. This picture is remarkably simple in many cases of real meteorological interest. It involves, in principle, no sacrifices in quantitative accuracy beyond what is inherent in the concept of balance, as used for instance in the initialization of numerical weather forecasts.

2,763 citations


Journal ArticleDOI
TL;DR: Clinical diagnostic criteria for probable and possible PD‐D are proposed, characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent.
Abstract: Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.

2,454 citations



Journal ArticleDOI
01 Sep 2007-Allergy
TL;DR: Even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas.
Abstract: The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas. Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers. Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.

1,129 citations


Journal ArticleDOI
Oluseun Adewumi1, Behrouz Aflatoonian2, Lars Ährlund-Richter3, Michal Amit4, Peter W. Andrews2, Gemma Beighton5, Paul Bello6, Nissim Benvenisty7, Lorraine S. Berry1, Simon Bevan, Barak Blum7, Justin Brooking8, Kevin G. Chen9, Andre Bh Choo, Gary A. Churchill, Marie Corbel10, Ivan Damjanov11, John S Draper12, Petr Dvorak13, Petr Dvorak14, Katarina Emanuelsson, Roland A. Fleck1, Angela Ford2, Karin Astrid Maria Gertow6, Karin Astrid Maria Gertow3, Marina Gertsenstein12, Paul J. Gokhale2, Rebecca S. Hamilton9, Alex Hampl14, Alex Hampl13, Lyn Healy1, Outi Hovatta3, Johan Hyllner, Marta P. Imreh15, Marta P. Imreh3, Joseph Itskovitz-Eldor4, Jamie P. Jackson2, Jackie Johnson6, Mark Jones2, Kehkooi Kee16, Benjamin L. King, Barbara B. Knowles, Majlinda Lako17, Franck Lebrin18, Barbara S. Mallon9, Daisy Manning19, Yoav Mayshar7, Ronald D.G. McKay9, Anna E. Michalska6, Milla Mikkola20, Masha Mileikovsky12, Stephen L. Minger21, Harry Moore2, Christine L. Mummery, Andras Nagy, Norio Nakatsuji22, Carmel M. O’Brien6, Steve Oh, Cia Olsson20, Timo Otonkoski20, Kye-Yoon Park9, Robert Passier, Hema Patel1, Minal Patel21, Roger A. Pedersen10, Martin F. Pera23, Marian S Piekarczyk19, Renee A. Reijo Pera16, Benjamin Reubinoff, Allan J. Robins, Janet Rossant12, Peter J. Rugg-Gunn10, Peter J. Rugg-Gunn12, Thomas C Schulz, Henrik Semb, Eric S Sherrer, Henrike Siemen16, Glyn Stacey1, Miodrag Stojkovic17, Hirofumi Suemori22, Jin P. Szatkiewicz, Tikva Turetsky, Timo Tuuri20, Steineke van den Brink, Kristina Vintersten12, Sanna Vuoristo20, Dorien Ward, Thomas A Weaver, Lesley Young1, Weidong Zhang 
TL;DR: The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide and found that despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers ofhuman embryonic stem cells.
Abstract: The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.

1,064 citations


Journal ArticleDOI
TL;DR: The main focus of this article is to operationalize the diagnosis of PD‐D and to propose pratical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment.
Abstract: A preceding article described the clinical features of Parkinson's disease dementia (PD-D) and proposed clinical diagnostic criteria for "probable" and "possible" PD-D. The main focus of this article is to operationalize the diagnosis of PD-D and to propose practical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time-consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD-D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD-D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence-based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.

907 citations


Journal ArticleDOI
TL;DR: In this article, the authors provide a basic understanding of the information micro-Raman Spectroscopy (mRS) may yield when applied to nanomaterials, a generic term for describing nano-sized crystals and bulk homogeneous materials with a structural disorder at the nanoscale.

905 citations


Journal ArticleDOI
TL;DR: In this paper, a spatially explicit, global typology of the so-called "water towers" at the 0.5° × 0. 5° resolution is proposed to identify critical regions where disproportionality of mountain runoff as compared to lowlands is maximum, and an Earth systems perspective is considered with incorporation of lowland climates, distinguishing four different types of water towers.
Abstract: [1] Mountains are important sources of freshwater for the adjacent lowlands. In view of increasingly scarce freshwater resources, this contribution should be clarified. While earlier studies focused on selected river systems in different climate zones, we attempt here a first spatially explicit, global typology of the so-called “water towers” at the 0.5° × 0.5° resolution in order to identify critical regions where disproportionality of mountain runoff as compared to lowlands is maximum. Then, an Earth systems perspective is considered with incorporation of lowland climates, distinguishing four different types of water towers. We show that more than 50% of mountain areas have an essential or supportive role for downstream regions. Finally, the potential significance of water resources in mountains is illustrated by including the actual population in the adjacent lowlands and its water needs: 7% of global mountain area provides essential water resources, while another 37% delivers important supportive supply, especially in arid and semiarid regions where vulnerability for seasonal and regional water shortage is high.

871 citations


Journal ArticleDOI
TL;DR: In this paper, a short review of matrix ansatz, the additivity principle or macroscopic fluctuation theory, developed recently in the theory of non-equilibrium phenomena is given.
Abstract: These lecture notes give a short review of methods such as the matrix ansatz, the additivity principle or the macroscopic fluctuation theory, developed recently in the theory of non-equilibrium phenomena. They show how these methods allow us to calculate the fluctuations and large deviations of the density and the current in non-equilibrium steady states of systems like exclusion processes. The properties of these fluctuations and large deviation functions in non-equilibrium steady states (for example, non-Gaussian fluctuations of density or non-convexity of the large deviation function which generalizes the notion of free energy) are compared with those of systems at equilibrium.

Journal ArticleDOI
TL;DR: Dealing with Madin–Darby canine kidney cells on various surfaces, it is found that a sudden release of the available surface is sufficient to trigger collective motility, which is characterized by a duality between collective and individual behaviors.
Abstract: Using an original microfabrication-based technique, we experimentally study situations in which a virgin surface is presented to a confluent epithelium with no damage made to the cells. Although inspired by wound-healing experiments, the situation is markedly different from classical scratch wounding because it focuses on the influence of the free surface and uncouples it from the other possible contributions such as cell damage and/or permeabilization. Dealing with Madin-Darby canine kidney cells on various surfaces, we found that a sudden release of the available surface is sufficient to trigger collective motility. This migration is independent of the proliferation of the cells that mainly takes place on the fraction of the surface initially covered. We find that this motility is characterized by a duality between collective and individual behaviors. On the one hand, the velocity fields within the monolayer are very long range and involve many cells in a coordinated way. On the other hand, we have identified very active "leader cells" that precede a small cohort and destabilize the border by a fingering instability. The sides of the fingers reveal a pluricellular actin "belt" that may be at the origin of a mechanical signaling between the leader and the followers. Experiments performed with autocrine cells constitutively expressing hepatocyte growth factor (HGF) or in the presence of exogenous HGF show a higher average velocity of the border and no leader.

Journal ArticleDOI
TL;DR: In this article, the authors present a scheme for the calculation of magnetic response parameters in insulators using ultrasoft pseudopotentials, which uses the gauge-including projector augmented wave method to obtain allelectron accuracy for both finite and infinitely periodic systems.
Abstract: We present a scheme for the calculation of magnetic response parameters in insulators using ultrasoft pseudopotentials. It uses the gauge-including projector augmented wave method [C. J. Pickard and F. Mauri, Phys. Rev. B 63, 245101 (2001)] to obtain all-electron accuracy for both finite and infinitely periodic systems. We consider in detail the calculation of NMR chemical shieldings. The approach is successfully validated first for molecular systems by comparing calculated chemical shieldings for a range of molecules with quantum chemistry results and then in the solid state by comparing $^{17}\mathrm{O}$ NMR parameters calculated for silicates with experiment.

Journal ArticleDOI
01 Sep 2007-Glia
TL;DR: Very recent experimental evidence as well as theoretical arguments strongly supporting the original astrocyte‐neuron lactate shuttle concept are reviewed, with new perspectives offered by the application of this concept.
Abstract: Astrocytes play a critical role in the regulation of brain metabolic responses to activity. One detailed mechanism proposed to describe the role of astrocytes in some of these responses has come to be known as the astrocyte-neuron lactate shuttle hypothesis (ANLSH). Although controversial, the original concept of a coupling mechanism between neuronal activity and glucose utilization that involves an activation of aerobic glycolysis in astrocytes and lactate consumption by neurons provides a heuristically valid framework for experimental studies. In this context, it is necessary to provide a survey of recent developments and data pertaining to this model. Thus, here, we review very recent experimental evidence as well as theoretical arguments strongly supporting the original model and in some cases extending it. Aspects revisited include the existence of glutamate-induced glycolysis in astrocytes in vitro, ex vivo, and in vivo, lactate as a preferential oxidative substrate for neurons, and the notion of net lactate transfer between astrocytes and neurons in vivo. Inclusion of a role for glycogen in the ANLSH is discussed in the light of a possible extension of the astrocyte-neuron lactate shuttle (ANLS) concept rather than as a competing hypothesis. New perspectives offered by the application of this concept include a better understanding of the basis of signals used in functional brain imaging, a role for neuron-glia metabolic interactions in glucose sensing and diabetes, as well as novel strategies to develop therapies against neurodegenerative diseases based upon improving astrocyte-neuron coupled energetics.

Journal ArticleDOI
TL;DR: In this article, the authors demonstrate that the calcification rates of the edible mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas) decline linearly with increasing CO2.
Abstract: [1] Ocean acidification resulting from human emissions of carbon dioxide has already lowered and will further lower surface ocean pH. The consequent decrease in calcium carbonate saturation potentially threatens calcareous marine organisms. Here, we demonstrate that the calcification rates of the edible mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas) decline linearly with increasing pCO2. Mussel and oyster calcification may decrease by 25 and 10%, respectively, by the end of the century, following the IPCC IS92a scenario (∼740 ppmv in 2100). Moreover, mussels dissolve at pCO2 values exceeding a threshold value of ∼1800 ppmv. As these two species are important ecosystem engineers in coastal ecosystems and represent a large part of worldwide aquaculture production, the predicted decrease of calcification in response to ocean acidification will probably have an impact on coastal biodiversity and ecosystem functioning as well as potentially lead to significant economic loss.

Journal ArticleDOI
26 Apr 2007-Nature
TL;DR: It is found that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean was sustained by the supply of iron and major nutrients to surface waters from iron-rich deep water below, suggesting that changes in iron supply from below may have a more significant effect on atmospheric carbon dioxide concentrations than previously thought.
Abstract: The availability of iron limits primary productivity and the associated uptake of carbon over large areas of the ocean. Iron thus plays an important role in the carbon cycle, and changes in its supply to the surface ocean may have had a significant effect on atmospheric carbon dioxide concentrations over glacial-interglacial cycles. To date, the role of iron in carbon cycling has largely been assessed using short-term iron-addition experiments. It is difficult, however, to reliably assess the magnitude of carbon export to the ocean interior using such methods, and the short observational periods preclude extrapolation of the results to longer timescales. Here we report observations of a phytoplankton bloom induced by natural iron fertilization--an approach that offers the opportunity to overcome some of the limitations of short-term experiments. We found that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean was sustained by the supply of iron and major nutrients to surface waters from iron-rich deep water below. The efficiency of fertilization, defined as the ratio of the carbon export to the amount of iron supplied, was at least ten times higher than previous estimates from short-term blooms induced by iron-addition experiments. This result sheds new light on the effect of long-term fertilization by iron and macronutrients on carbon sequestration, suggesting that changes in iron supply from below--as invoked in some palaeoclimatic and future climate change scenarios--may have a more significant effect on atmospheric carbon dioxide concentrations than previously thought.

Journal ArticleDOI
TL;DR: It is shown that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity, which constitute the basis for effective control of HIV-1 replication.
Abstract: The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.


Journal ArticleDOI
28 Sep 2007-Vaccine
TL;DR: To meet the challenge of antigenic drift, vaccines that confer broad protection against heterovariant strains are needed against seasonal, epidemic and pandemic influenza.

Journal ArticleDOI
08 Nov 2007-Nature
TL;DR: An experiment combining a fibre-based cavity with atom-chip technology enables single-atom cavity quantum electrodynamics experiments with a simplified set-up and realizes the situation of many atoms in a cavity, each of which is identically and strongly coupled to the cavity mode.
Abstract: An optical cavity enhances the interaction between atoms and light, and the rate of coherent atom-photon coupling can be made larger than all decoherence rates of the system. For single atoms, this 'strong coupling regime' of cavity quantum electrodynamics has been the subject of many experimental advances. Efforts have been made to control the coupling rate by trapping the atom and cooling it towards the motional ground state; the latter has been achieved in one dimension so far. For systems of many atoms, the three-dimensional ground state of motion is routinely achieved in atomic Bose-Einstein condensates (BECs). Although experiments combining BECs and optical cavities have been reported recently, coupling BECs to cavities that are in the strong-coupling regime for single atoms has remained an elusive goal. Here we report such an experiment, made possible by combining a fibre-based cavity with atom-chip technology. This enables single-atom cavity quantum electrodynamics experiments with a simplified set-up and realizes the situation of many atoms in a cavity, each of which is identically and strongly coupled to the cavity mode. Moreover, the BEC can be positioned deterministically anywhere within the cavity and localized entirely within a single antinode of the standing-wave cavity field; we demonstrate that this gives rise to a controlled, tunable coupling rate. We study the heating rate caused by a cavity transmission measurement as a function of the coupling rate and find no measurable heating for strongly coupled BECs. The spectrum of the coupled atoms-cavity system, which we map out over a wide range of atom numbers and cavity-atom detunings, shows vacuum Rabi splittings exceeding 20 gigahertz, as well as an unpredicted additional splitting, which we attribute to the atomic hyperfine structure. We anticipate that the system will be suitable as a light-matter quantum interface for quantum information.

Journal ArticleDOI
TL;DR: In this article, mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called "laminopathies." Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders.

Journal ArticleDOI
TL;DR: It is observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative.
Abstract: Changes in chloride (Cl-) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl- homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneous interictal-like activity that was initiated in the subiculum. Records from a minority of subicular pyramidal cells revealed depolarizing GABA(A) receptor-mediated postsynaptic events, indicating a perturbed Cl- homeostasis. We assessed possible contributions of changes in expression of the potassium-chloride cotransporter KCC2. Double in situ hybridization showed that mRNA for KCC2 was absent from approximately 30% of CaMKIIalpha (calcium/calmodulin-dependent protein kinase IIalpha)-positive subicular pyramidal cells. Combining intracellular recordings with biocytin-filled electrodes and KCC2 immunochemistry, we observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative. Bumetanide, at doses that selectively block the chloride-importing potassium-sodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABA(A) reversal potentials and suppressed interictal activity. Changes in Cl- transporter expression thus contribute to human epileptiform activity, and molecules acting on these transporters may be useful antiepileptic drugs.

Journal ArticleDOI
TL;DR: This article reports significant gains in recognition performance and model compactness as a result of discriminative training based on MCE training applied to HMMs, in the context of three challenging large-vocabulary speech recognition tasks.
Abstract: The minimum classification error (MCE) framework for discriminative training is a simple and general formalism for directly optimizing recognition accuracy in pattern recognition problems. The framework applies directly to the optimization of hidden Markov models (HMMs) used for speech recognition problems. However, few if any studies have reported results for the application of MCE training to large-vocabulary, continuous-speech recognition tasks. This article reports significant gains in recognition performance and model compactness as a result of discriminative training based on MCE training applied to HMMs, in the context of three challenging large-vocabulary (up to 100 k word) speech recognition tasks: the Corpus of Spontaneous Japanese lecture speech transcription task, a telephone-based name recognition task, and the MIT Jupiter telephone-based conversational weather information task. On these tasks, starting from maximum likelihood (ML) baselines, MCE training yielded relative reductions in word error ranging from 7% to 20%. Furthermore, this paper evaluates the use of different methods for optimizing the MCE criterion function, as well as the use of precomputed recognition lattices to speed up training. An overview of the MCE framework is given, with an emphasis on practical implementation issues

Journal ArticleDOI
01 Nov 2007-Nature
TL;DR: The analytical approach provides a universal scaling dependence of the mean FPT on both the volume of the confining domain and the source–target distance, which is applicable to a broad range of stochastic processes characterized by length-scale-invariant properties.
Abstract: How long does it take a random walker to reach a given target point? This quantity, known as a first-passage time (FPT), has led to a growing number of theoretical investigations over the past decade. The importance of FPTs originates from the crucial role played by first encounter properties in various real situations, including transport in disordered media, neuron firing dynamics, spreading of diseases or target search processes. Most methods of determining FPT properties in confining domains have been limited to effectively one-dimensional geometries, or to higher spatial dimensions only in homogeneous media. Here we develop a general theory that allows accurate evaluation of the mean FPT in complex media. Our analytical approach provides a universal scaling dependence of the mean FPT on both the volume of the confining domain and the source-target distance. The analysis is applicable to a broad range of stochastic processes characterized by length-scale-invariant properties. Our theoretical predictions are confirmed by numerical simulations for several representative models of disordered media, fractals, anomalous diffusion and scale-free networks.

Journal ArticleDOI
TL;DR: In this paper, the authors extended the reduced-basis approximations developed earlier for linear elliptic and parabolic partial differential equations with affine parameter dependence to problems in volving.
Abstract: In this paper, we extend the reduced-basis approximations developed earlier for linear elliptic and parabolic partial differential equations with affine parameter dependence to problems in- volving (a) nonaffine dependence on the parameter, and (b) nonlinear dependence on the field variable. The method replaces the nonaffine and nonlinear terms with a coefficient function approximation which then permits an efficient offline-online computational decomposition. We first review the coefficient function approximation procedure: the essential ingredients are (i) a good collateral reduced-basis approximation space, and (ii) a stable and inexpensive interpolation procedure. We then apply this approach to linear nonaffine and nonlinear elliptic and parabolic equations; in each instance, we discuss the reduced-basis approximation and the associated offline-online computational procedures. Numeri- cal results are presented to assess our approach.

Journal ArticleDOI
TL;DR: In this article, the diffuse attenuation coefficients for downward irradiance, Kd(l), and the irradiance reflectances, R(l) were derived from hyperspectral (downward and upward) irradiance measurements, and they exhibited very uncommon values that reflect the exceptional clarity of this huge water body.
Abstract: Optical measurements within both the visible and near ultraviolet (UV) parts of the spectrum (305–750 nm) were recently made in hyperoligotrophic waters in the South Pacific gyre (near Easter Island). The diffuse attenuation coefficients for downward irradiance, Kd(l), and the irradiance reflectances, R(l), as derived from hyperspectral (downward and upward) irradiance measurements, exhibit very uncommon values that reflect the exceptional clarity of this huge water body. The Kd(l) values observed in the UV domain are even below the absorption coefficients found in current literature for pure water. The R(l) values (beneath the surface) exhibit a maximum as high as 13% around 390 nm. From these apparent optical properties, the absorption and backscattering coefficients can be inferred by inversion and compared to those of (optically) pure seawater. The total absorption coefficient (atot) exhibits a flat minimum (, 0.007 m21) around 410–420 nm, about twice that of pure water. At 310 nm, atot may be as low as 0.045 m21, i.e., half the value generally accepted for pure water. The particulate absorption is low compared to those of yellow substance and water and represents only ,15% of atot in the 305–420-nm domain. The backscattering coefficient is totally dominated by that of water molecules in the UV domain. Because direct laboratory determinations of pure water absorption in the UV domain are still scarce and contradictory, we determine a tentative upper bound limit for this elusive coefficient as it results from in situ measurements.

Journal ArticleDOI
TL;DR: In this paper, the authors studied the sparsity oracle properties of l1-penalized least squares in nonparametric regression with random design and showed that the penalized least square estimator satisfies sparsity inequalities, i.e., bounds in terms of the number of nonzero components of the oracle vector.
Abstract: This paper studies oracle properties of l1-penalized least squares in nonparametric regression setting with random design. We show that the penalized least squares estimator satisfies sparsity oracle inequalities, i.e., bounds in terms of the number of non-zero components of the oracle vector. The results are valid even when the dimension of the model is (much) larger than the sample size and the regression matrix is not positive definite. They can be applied to high-dimensional linear regression, to nonparametric adaptive regression estimation and to the problem of aggregation of arbitrary estimators.

Journal ArticleDOI
23 Aug 2007-Nature
TL;DR: The observation of such a step-by-step collapse by non-destructively measuring the photon number of a field stored in a cavity is reported, which illustrates all the postulates of quantum measurement (state collapse, statistical results and repeatability) and should facilitate studies of non-classical fields trapped in cavities.
Abstract: The irreversible evolution of a microscopic system under measurement is a central feature of quantum theory. From an initial state generally exhibiting quantum uncertainty in the measured observable, the system is projected into a state in which this observable becomes precisely known. Its value is random, with a probability determined by the initial system's state. The evolution induced by measurement (known as 'state collapse') can be progressive, accumulating the effects of elementary state changes. Here we report the observation of such a step-by-step collapse by non-destructively measuring the photon number of a field stored in a cavity. Atoms behaving as microscopic clocks cross the cavity successively. By measuring the light-induced alterations of the clock rate, information is progressively extracted, until the initially uncertain photon number converges to an integer. The suppression of the photon number spread is demonstrated by correlations between repeated measurements. The procedure illustrates all the postulates of quantum measurement (state collapse, statistical results and repeatability) and should facilitate studies of non-classical fields trapped in cavities.

Journal ArticleDOI
16 Mar 2007-Science
TL;DR: Aerosols and ozone could be perturbing the radiative budget of the Arctic through processes specific to the region: Absorption of solar radiation by aerosols is enhanced by highly reflective snow and ice surfaces; deposition of light- absorption aerosols on snow or ice can decrease surface albedo; and tropospheric ozone forcing may also be contributing to warming in this region.
Abstract: Notable warming trends have been observed in the Arctic. Although increased human-induced emissions of long-lived greenhouse gases are certainly the main driving factor, air pollutants, such as aerosols and ozone, are also important. Air pollutants are transported to the Arctic, primarily from Eurasia, leading to high concentrations in winter and spring (Arctic haze). Local ship emissions and summertime boreal forest fires may also be important pollution sources. Aerosols and ozone could be perturbing the radiative budget of the Arctic through processes specific to the region: Absorption of solar radiation by aerosols is enhanced by highly reflective snow and ice surfaces; deposition of light-absorbing aerosols on snow or ice can decrease surface albedo; and tropospheric ozone forcing may also be contributing to warming in this region. Future increases in pollutant emissions locally or in mid-latitudes could further accelerate global warming in the Arctic.

Journal ArticleDOI
TL;DR: In this paper, the role of reactive oxygen species (ROS) in after-ripening of sunflower seeds was investigated at the cellular level by electron microscopy, concomitantly with lipid peroxidation and oxidation of specific embryo proteins.
Abstract: *Summary At harvest, sunflower (Helianthus annuus L.) seeds are dormant and unable to germinate at temperatures below 15 � C. Seed storage in the dry state, known as after-ripening, is associated with an alleviation of embryonic dormancy allowing subsequent germination at suboptimal temperatures. To identify the process by which dormancy is broken during after-ripening, we focused on the role of reactive oxygen species (ROS) in this phenomenon. After-ripening entailed a progressive accumulation of ROS, namely superoxide anions and hydrogen peroxide, in cells of embryonic axes. This accumulation, which was investigated at the cellular level by electron microscopy, occurred concomitantly with lipid peroxidation and oxidation (carbonylation) of specific embryo proteins. Incubation of dormant seeds for 3 h in the presence of hydrogen cyanide (a compound that breaks dormancy) or methylviologen (a ROS-generating compound) also released dormancy and caused the oxidation of a specific set of embryo proteins. From these observations, we propose a novel mechanism for seed dormancy alleviation. This mechanism involves ROS production and targeted changes in protein carbonylation patterns.