Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system.

Rifaximin, a rifamycin derivative, has been reported to induce clinical remission of active Crohn's disease (CD), a chronic inflammatory bowel disorder. In order to understand how rifaximin affects the colonic microbiota and its metabolism, an in vitro human colonic model system was used in this study. We investigated the impact of the administration of 1800 mg/day of rifaximin on the faecal microbiota of four patients affected by colonic active CD [Crohn's disease activity index (CDAI > 200)] using a continuous culture colonic model system. We studied the effect of rifaximin on the human gut microbiota using fluorescence in situ hybridization, quantitative PCR and PCR–denaturing gradient gel electrophoresis. Furthermore, we investigated the effect of the antibiotic on microbial metabolic profiles, using 1H-NMR and solid phase microextraction coupled with gas chromatography/mass spectrometry, and its potential genotoxicity and cytotoxicity, using Comet and growth curve assays. Rifaximin did not affect the overall composition of the gut microbiota, whereas it caused an increase in concentration of Bifidobacterium, Atopobium and Faecalibacterium prausnitzii. A shift in microbial metabolism was observed, as shown by increases in short-chain fatty acids, propanol, decanol, nonanone and aromatic organic compounds, and decreases in ethanol, methanol and glutamate. No genotoxicity or cytotoxicity was attributed to rifaximin, and conversely rifaximin was shown to have a chemopreventive role by protecting against hydrogen peroxide-induced DNA damage. We demonstrated that rifaximin, while not altering the overall structure of the human colonic microbiota, increased bifidobacteria and led to variation of metabolic profiles associated with potential beneficial effects on the host.

Relaxing the Tropics to an ‘observed’ state: analysis using a simple baroclinic model

The technique of relaxation of the tropical atmosphere towards an analysis in a month-season forecast model has previously been successfully exploited in a number of contexts. Here it is shown that when tropical relaxation is used to investigate the possible origin of the observed anomalies in June–July 2007, a simple dynamical model is able to reproduce the observed component of the pattern of anomalies given by an ensemble of ECMWF forecast runs. Following this result, the simple model is used for a range of experiments on time-scales of relaxation, variables and regions relaxed based on a control model run with equatorial heating in a zonal flow. A theory based on scale analysis for the large-scale tropics is used to interpret the results. Typical relationships between scales are determined from the basic equations, and for a specified diabatic heating a chain of deductions for determining the dependent variables is derived. Different critical time-scales are found for tropical relaxation of different dependent variables to be effective. Vorticity has the longest critical time-scale, typically 1.2 days. For temperature and divergence, the time-scales are 10 hours and 3 hours, respectively. However not all the tropical fields, in particular the vertical motion, are reproduced correctly by the model unless divergence is heavily damped. To obtain the correct extra-tropical fields, it is crucial to have the correct rotational flow in the subtropics to initiate the Rossby wave propagation from there. It is sufficient to relax vorticity or temperature on a time-scale comparable or less than their critical time-scales to obtain this. However if the divergent advection of vorticity is important in the Rossby Wave Source then strong relaxation of divergence is required to accurately represent the tropical forcing of Rossby waves.

Improving a convection-permitting model simulation of a cold air outbreak

A convection-permitting local-area model was used to simulate a cold air outbreak crossing from the Norwegian Sea into the Atlantic Ocean near Scotland. A control model run based on an operational configuration of the Met Office UKV high-resolution (1.5 km grid spacing) NWP model was compared to satellite, aircraft and radar data. While the control model captured the large-scale features of the synoptic situation, it was not able to reproduce the shallow (<1.5 km) stratiform layer to the north of the open cellular convection. Liquid water paths were found to be too low in both the stratiform and convective cloud regions. Sensitivity analyses including a modified boundary-layer diagnosis to generate a more well-mixed boundary layer and inhibition of ice formation to lower temperatures improved cloud morphology and comparisons with observational data. Copyright © 2013 Royal Meteorological Society and British Crown Copyright, the Met Office

O poder judiciário e o movimento da qualidade total : aspectos determinantes na implantação do pgqj em um estudo exploratório

Este trabalho analisa fatores que viabilizaram a implantação do Plano de Gestão pela Qualidade do Judiciário em algumas Unidades do Poder Judiciário do RS. Com base na teoria geral da administração, especialmente na teoria clássica, na burocracia e na teoria comportamental, em autores de obras sobre organizações que aprendem e em obras de W. Edwards Deming sobre a nova economia no governo, desenvolve-se essa pesquisa. O estudo analisa a implantação do Plano de Gestão, os resultados dos projetos-piloto e programa de adesão, como os atores do processo perceberam as mudanças ocorridas e como é definida a situação por aqueles que estão à margem dos acontecimentos por diferentes motivos, por meio da análise de documentos do acervo da organização, de dados coletados nas entrevistas com integrantes de Unidades com e sem implantação do gerenciamento da rotina, preconizado pelo modelo da Qualidade Total. Estabelece-se, assim, o quadro de aspectos determinantes na implantação do PGQJ, quais sejam: a estrutura da tarefa, as relações interpessoais e a liderança, o processo decisório e o comprometimento com a organização. Os resultados obtidos delineiam a percepção dos atores quanto ao processo de mudança e suas expectativas quanto à capacidade da organização de absorver novos modelos de gestão, acarretando, em determinados momentos, uma completa quebra de paradigmas. Demonstram, ainda, a distância existente entre a proposição do Plano de Gestão, quanto ao comportamento administrativo, ao desenvolvimento dos recursos humanos, ao envolvimento com o trabalho, e o que efetivamente se verifica nas Unidades da organização. Por fim, discute-se alternativa para a implantação de modelo de gestão baseado na Qualidade Total e na aprendizagem organizacional, sugerindo-se estudos mais aprofundados desses aspectos determinantes, com o objetivo de melhorar o desempenho do projeto em andamento.

Integrating on-line process control and imperfect corrective maintenance: An economical design

Existing studies of on-line process control are concerned with economic aspects, and the parameters of the processes are optimized with respect to the average cost per item produced. However, an equally important dimension is the adoption of an efficient maintenance policy. In most cases, only the frequency of the corrective adjustment is evaluated because it is assumed that the equipment becomes "as good as new" after corrective maintenance. For this condition to be met, a sophisticated and detailed corrective adjustment system needs to be employed. The aim of this paper is to propose an integrated economic model incorporating the following two dimensions: on-line process control and a corrective maintenance program. Both performances are objects of an average cost per item minimization. Adjustments are based on the location of the measurement of a quality characteristic of interest in a three decision zone. Numerical examples are illustrated in the proposal. (c) 2012 Elsevier B.V. All rights reserved.

Functional evaluation of hTM, CD46 and HLA-E transgenes in vitro and in pig leg xenoperfusion experiments

Background Besides α1,3 galactosyltransferase (Gal) gene knockout several transgene combinations to prevent pig-to-human xenograft rejection are being investigated. hCD46/HLA-E double transgenic pigs were tested for prevention of xenograft rejection in an ex vivo pig-to-human xenoperfusion model. In addition, expression of human thrombomodulin (hTM-) on wild-type and/or multi-transgenic (GalTKO/hCD46) background was evaluated to overcome pig-to-human coagulation incompatibility. Methods hCD46/HLA-E double transgenic as well as wild-type pig forelimbs were ex vivo perfused with whole, heparinized human blood and autologous blood, respectively. Blood samples were analyzed for production of porcine and/or human inflammatory cytokines. Biopsy samples were examined for deposition of complement proteins as well as E-selectin and VCAM-1 expression. Serial blood cell counts were performed to analyze changes in human blood cell populations. In vitro, PAEC were analyzed for ASGR1 mediated human platelet phagocytosis. In addition, a biochemical assay was performed using hTM-only and multi-transgenic (GalTKO/hCD46/hTM) pig aortic endothelial cells (PAEC) to evaluate the ability of hTM to generate activated protein C (APC). Subsequently, the anti-coagulant properties of hTM were tested in a microcarrier based coagulation assay with PAEC and human whole blood. Results No hyperacute rejection was seen in the ex vivo perfusion model. Extremity perfusions lasted for up to 12 h without increase of vascular resistance and had to be terminated due to continuous small blood losses. Plasma levels of porcine IL1β (P < 0.0001), and IL-8 (P = 0.019) as well as human C3a, C5a and soluble C5b-9 were significantly (P < 0.05–<0.0001) lower in blood perfused through hCD46/HLA-E transgenic as compared to wild-type limbs. C3b/c, C4b/c, and C6 deposition as well as E-selectin and VCAM-1 expression were significantly (P < 0.0001) higher in tissue of wild-type as compared to transgenic limbs. Preliminary immunofluorescence staining results showed that the expression of hCD46/HLA-E is associated with a reduction of NK cell tissue infiltration (P < 0.05). A rapid decrease of platelets was observed in all xenoperfusions. In vitro findings showed that PAEC express ASGR1 and suggest that this molecule is involved in human platelet phagocytosis. In vitro, we found that the amount of APC in the supernatant of hTM transgenic cells increased significantly (P < 0.0001) with protein C concentration in a dose-dependent manner as compared to control PAEC lacking hTM, where the turnover of the protein C remained at the basal level for all of the examined concentration. In further experiments, hTM also showed the ability to prevent blood coagulation by three- to four-fold increased (P < 0.001) clotting time as compared to wild-type PAEC. The formation of TAT complexes was significantly lower when hTM-transgenic cells (P < 0.0001) were used as compared to wild-type cells. Conclusions Transgenic hCD46/HLA-E expression clearly reduced humoral xenoresponses since the terminal pathway of complement, endothelial cell activation, inflammatory cytokine production and NK-cell tissue infiltration were all down-regulated. We also found ASGR1 expression on the vascular endothelium of pigs, and this molecule may thus be involved in binding and phagocytosis of human platelets during pig-to-human xenotransplantation. In addition, use of the hTM transgene has the potential to overcome coagulation incompatibilities in pig-to-human xenotransplantation.

Complement dependent early immunological responses during ex vivo xenoperfusion of hCD46/HLA-E double transgenic pig forelimbs with human blood.

BACKGROUND Besides α1,3-galactosyltransferase gene (GGTA1) knockout, several transgene combinations to prevent pig-to-human xenograft rejection are currently being investigated. In this study, the potential of combined overexpression of human CD46 and HLA-E to prevent complement- and NK-cell-mediated xenograft rejection was tested in an ex vivo pig-to-human xenoperfusion model. METHODS α1,3-Galactosyltransferase knockout heterozygous, hCD46/HLA-E double transgenic (transgenic) as well as wild-type pig forelimbs were ex vivo perfused with whole, heparinized human and autologous pig blood, respectively. Blood samples were analyzed for the production of porcine and/or human inflammatory cytokines as well as complement activation products. Biopsy samples were examined for deposition of human and porcine C3b/c, C4b/c, and C6 as well as CD62E (E-selectin) and CD106 (VCAM-1) expression. Apoptosis was measured in the porcine muscle tissue using TUNEL assays. Finally, the formation of thrombin-antithrombin (TAT) complexes was measured in EDTA plasma samples. RESULTS No hyperacute rejection was seen in this model. Extremity perfusions lasted for up to 12 h without increase in vascular resistance and were terminated due to continuous small blood losses. Plasma levels of porcine cytokines IL1β, IL-6, IL-8, IL-10, TNF-α, and MCP-1 as well as human complement activation markers C3a (P = 0.0002), C5a (P = 0.004), and soluble C5b-9 (P = 0.03) were lower in blood perfused through transgenic as compared to wild-type limbs. Human C3b/c, C4b/c, and C6 as well as CD62E and CD106 were deposited in tissue of wild-type limbs, but significantly lower levels (P < 0.0001) of C3b/c, C4b/c, and C6 deposition as well as CD62E and CD106 expression were detected in transgenic limbs perfused with human blood. Transgenic porcine tissue was protected from xenoperfusion-induced apoptosis (P < 0.0001). Finally, TAT levels were significantly lower (P < 0.0001) in transgenic limb as compared to wild-type limb xenoperfusions. CONCLUSION Transgenic hCD46/HLA-E expression clearly reduced humoral xenoresponses since all, the terminal pathway of complement activation, endothelial cell activation, muscle cell apoptosis, inflammatory cytokine production, as well as coagulation activation, were all downregulated. Overall, this model represents a useful tool to study early immunological responses during pig-to-human vascularized xenotransplantation in the absence of hyperacute rejection.

Face Lift Surgery for Reconstructed Virtual Humans

We introduce an innovative, semi-automatic method to transform low resolution facial meshes into high definition ones, based on the tailoring of a generic, neutral human head model, designed by an artist, to fit the facial features of a specific person. To determine these facial features we need to select a set of "control points" (corners of eyes, lips, etc.) in at least two photographs of the subject's face. The neutral head mesh is then automatically reshaped according to the relation between the control points in the original subject's mesh through a set of transformation pyramids. The last step consists in merging both meshes and filling the gaps that appear in the previous process. This algorithm avoids the use of expensive and complicated technologies to obtain depth maps, which also need to be meshed later.

A Model of Emotion as Patterned Metacontrol

Adaptive systems use feedback as a key strategy to cope with uncertainty and change in their environments. The information fed back from the sensorimotor loop into the control architecture can be used to change different elements of the controller at four different levels: parameters of the control model, the control model itself, the functional organization of the agent and the functional components of the agent. The complexity of such a space of potential configurations is daunting. The only viable alternative for the agent ?in practical, economical, evolutionary terms? is the reduction of the dimensionality of the configuration space. This reduction is achieved both by functionalisation —or, to be more precise, by interface minimization— and by patterning, i.e. the selection among a predefined set of organisational configurations. This last analysis let us state the central problem of how autonomy emerges from the integration of the cognitive, emotional and autonomic systems in strict functional terms: autonomy is achieved by the closure of functional dependency. In this paper we will show a general model of how the emotional biological systems operate following this theoretical analysis and how this model is also of applicability to a wide spectrum of artificial systems.

A Model of Emotion as Patterned Metacontrol

Adaptive agents use feedback as a key strategy to cope with un- certainty and change in their environments. The information fed back from the sensorimotor loop into the control subsystem can be used to change four different elements of the controller: parameters associated to the control model, the control model itself, the functional organization of the agent and the functional realization of the agent. There are many change alternatives and hence the complexity of the agent’s space of potential configurations is daunting. The only viable alternative for space- and time-constrained agents —in practical, economical, evolutionary terms— is to achieve a reduction of the dimensionality of this configuration space. Emotions play a critical role in this reduction. The reduction is achieved by func- tionalization, interface minimization and by patterning, i.e. by selection among a predefined set of organizational configurations. This analysis lets us state how autonomy emerges from the integration of cognitive, emotional and autonomic systems in strict functional terms: autonomy is achieved by the closure of functional dependency. Emotion-based morphofunctional systems are able to exhibit complex adaptation patterns at a reduced cognitive cost. In this article we show a general model of how emotion supports functional adaptation and how the emotional biological systems operate following this theoretical model. We will also show how this model is also of applicability to the construction of a wide spectrum of artificial systems1.

A framework for building distributed social network websites

Las redes son la esencia de comunidades y sociedades humanas; constituyen el entramado en el que nos relacionamos y determinan cómo lo hacemos, cómo se disemina la información o incluso cómo las cosas se llevan a cabo. Pero el protagonismo de las redes va más allá del que adquiere en las redes sociales. Se encuentran en el seno de múltiples estructuras que conocemos, desde las interaciones entre las proteínas dentro de una célula hasta la interconexión de los routers de internet. Las redes sociales están presentes en internet desde sus principios, en el correo electrónico por tomar un ejemplo. Dentro de cada cliente de correo se manejan listas contactos que agregadas constituyen una red social. Sin embargo, ha sido con la aparición de los sitios web de redes sociales cuando este tipo de aplicaciones web han llegado a la conciencia general. Las redes sociales se han situado entre los sitios más populares y con más tráfico de la web. Páginas como Facebook o Twitter manejan cifras asombrosas en cuanto a número de usuarios activos, de tráfico o de tiempo invertido en el sitio. Pero las funcionalidades de red social no están restringidas a las redes sociales orientadas a contactos, aquellas enfocadas a construir tu lista de contactos e interactuar con ellos. Existen otros ejemplos de sitios que aprovechan las redes sociales para aumentar la actividad de los usuarios y su involucración alrededor de algún tipo de contenido. Estos ejemplos van desde una de las redes sociales más antiguas, Flickr, orientada al intercambio de fotografías, hasta Github, la red social de código libre más popular hoy en día. No es una casualidad que la popularidad de estos sitios web venga de la mano de sus funcionalidades de red social. El escenario es más rico aún, ya que los sitios de redes sociales interaccionan entre ellos, compartiendo y exportando listas de contactos, servicios de autenticación y proporcionando un valioso canal para publicitar la actividad de los usuarios en otros sitios web. Esta funcionalidad es reciente y aún les queda un paso hasta que las redes sociales superen su condición de bunkers y lleguen a un estado de verdadera interoperabilidad entre ellas, tal como funcionan hoy en día el correo electrónico o la mensajería instantánea. Este trabajo muestra una tecnología que permite construir sitios web con características de red social distribuída. En primer lugar, se presenta una tecnología para la construcción de un componente intermedio que permite proporcionar cualquier característica de gestión de contenidos al popular marco de desarrollo web modelo-vista-controlador (MVC) Ruby on Rails. Esta técnica constituye una herramienta para desarrolladores que les permita abstraerse de las complejidades de la gestión de contenidos y enfocarse en las particularidades de los propios contenidos. Esta técnica se usará también para proporcionar las características de red social. Se describe una nueva métrica de reusabilidad de código para demostrar la validez del componente intermedio en marcos MVC. En segundo lugar, se analizan las características de los sitios web de redes sociales más populares, con el objetivo de encontrar los patrones comunes que aparecen en ellos. Este análisis servirá como base para definir los requisitos que debe cumplir un marco para construir redes sociales. A continuación se propone una arquitectura de referencia que proporcione este tipo de características. Dicha arquitectura ha sido implementada en un componente, Social Stream, y probada en varias redes sociales, tanto orientadas a contactos como a contenido, en el contexto de una asociación vecinal tanto como en proyectos de investigación financiados por la UE. Ha sido la base de varios proyectos fin de carrera. Además, ha sido publicado como código libre, obteniendo una comunidad creciente y está siendo usado más allá del ámbito de este trabajo. Dicha arquitectura ha permitido la definición de un nuevo modelo de control de acceso social que supera varias limitaciones presentes en los modelos de control de acceso para redes sociales. Más aún, se han analizado casos de estudio de sitios de red social distribuídos, reuniendo un conjunto de caraterísticas que debe cumplir un marco para construir redes sociales distribuídas. Por último, se ha extendido la arquitectura del marco para dar cabida a las características de redes sociales distribuídas. Su implementación ha sido validada en proyectos de investigación financiados por la UE. Abstract Networks are the substance of human communities and societies; they constitute the structural framework on which we relate to each other and determine the way we do it, the way information is diseminated or even the way people get things done. But network prominence goes beyond the importance it acquires in social networks. Networks are found within numerous known structures, from protein interactions inside a cell to router connections on the internet. Social networks are present on the internet since its beginnings, in emails for example. Inside every email client, there are contact lists that added together constitute a social network. However, it has been with the emergence of social network sites (SNS) when these kinds of web applications have reached general awareness. SNS are now among the most popular sites in the web and with the higher traffic. Sites such as Facebook and Twitter hold astonishing figures of active users, traffic and time invested into the sites. Nevertheless, SNS functionalities are not restricted to contact-oriented social networks, those that are focused on building your own list of contacts and interacting with them. There are other examples of sites that leverage social networking to foster user activity and engagement around other types of content. Examples go from early SNS such as Flickr, the photography related networking site, to Github, the most popular social network repository nowadays. It is not an accident that the popularity of these websites comes hand-in-hand with their social network capabilities The scenario is even richer, due to the fact that SNS interact with each other, sharing and exporting contact lists and authentication as well as providing a valuable channel to publize user activity in other sites. These interactions are very recent and they are still finding their way to the point where SNS overcome their condition of data silos to a stage of full interoperability between sites, in the same way email and instant messaging networks work today. This work introduces a technology that allows to rapidly build any kind of distributed social network website. It first introduces a new technique to create middleware that can provide any kind of content management feature to a popular model-view-controller (MVC) web development framework, Ruby on Rails. It provides developers with tools that allow them to abstract from the complexities related with content management and focus on the development of specific content. This same technique is also used to provide the framework with social network features. Additionally, it describes a new metric of code reuse to assert the validity of the kind of middleware that is emerging in MVC frameworks. Secondly, the characteristics of top popular SNS are analysed in order to find the common patterns shown in them. This analysis is the ground for defining the requirements of a framework for building social network websites. Next, a reference architecture for supporting the features found in the analysis is proposed. This architecture has been implemented in a software component, called Social Stream, and tested in several social networks, both contact- and content-oriented, in local neighbourhood associations and EU-founded research projects. It has also been the ground for several Master’s theses. It has been released as a free and open source software that has obtained a growing community and that is now being used beyond the scope of this work. The social architecture has enabled the definition of a new social-based access control model that overcomes some of the limitations currenly present in access control models for social networks. Furthermore, paradigms and case studies in distributed SNS have been analysed, gathering a set of features for distributed social networking. Finally the architecture of the framework has been extended to support distributed SNS capabilities. Its implementation has also been validated in EU-founded research projects.

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.

Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or O-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.

Identificação de sistemas para o estudo de controle motor.

Qualquer tarefa motora ativa se dá pela ativação de uma população de unidades motoras. Porém, devido a diversas dificuldades, tanto técnicas quanto éticas, não é possível medir a entrada sináptica dos motoneurônios em humanos. Por essas razões, o uso de modelos computacionais realistas de um núcleo de motoneurônios e as suas respectivas fibras musculares tem um importante papel no estudo do controle humano dos músculos. Entretanto, tais modelos são complexos e uma análise matemática é difícil. Neste texto é apresentada uma abordagem baseada em identificação de sistemas de um modelo realista de um núcleo de unidades motoras, com o objetivo de obter um modelo mais simples capaz de representar a transdução das entradas do núcleo de unidades motoras na força do músculo associado ao núcleo. A identificação de sistemas foi baseada em um algoritmo de mínimos quadrados ortogonal para achar um modelo NARMAX, sendo que a entrada considerada foi a condutância sináptica excitatória dendrítica total dos motoneurônios e a saída foi a força dos músculos produzida pelo núcleo de unidades motoras. O modelo identificado reproduziu o comportamento médio da saída do modelo computacional realista, mesmo para pares de sinal de entrada-saída não usados durante o processo de identificação do modelo, como sinais de força muscular modulados senoidalmente. Funções de resposta em frequência generalizada do núcleo de motoneurônios foram obtidas do modelo NARMAX, e levaram a que se inferisse que oscilações corticais na banda-beta (20 Hz) podem influenciar no controle da geração de força pela medula espinhal, comportamento do núcleo de motoneurônios até então desconhecido.

A new approach to control of MIMO processes with static nonlinearities using an extended IMC framework

In this paper, a new control design method is proposed for stable processes which can be described using Hammerstein-Wiener models. The internal model control (IMC) framework is extended to accommodate multiple IMC controllers, one for each subsystem. The concept of passive systems is used to construct the IMC controllers which approximate the inverses of the subsystems to achieve dynamic control performance. The Passivity Theorem is used to ensure the closed-loop stability. (c) 2005 Elsevier Ltd. All rights reserved.

Fixed or variable noise in contrast discrimination? The jury's still out

The ability to distinguish one visual stimulus from another slightly different one depends on the variability of their internal representations. In a recent paper on human visual-contrast discrimination, Kontsevich et al (2002 Vision Research 42 1771 - 1784) re-considered the long-standing question whether the internal noise that limits discrimination is fixed (contrast-invariant) or variable (contrast-dependent). They tested discrimination performance for 3 cycles deg-1 gratings over a wide range of incremental contrast levels at three masking contrasts, and showed that a simple model with an expansive response function and response-dependent noise could fit the data very well. Their conclusion - that noise in visual-discrimination tasks increases markedly with contrast - has profound implications for our understanding and modelling of vision. Here, however, we re-analyse their data, and report that a standard gain-control model with a compressive response function and fixed additive noise can also fit the data remarkably well. Thus these experimental data do not allow us to decide between the two models. The question remains open. [Supported by EPSRC grant GR/S74515/01]