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.

Implicaciones de la accesibilidad configuracional en la movilidad peatonal. El caso de Madrid = The implications of configurational accessibility in pedestrian mobility. The case of Madrid

- Resumen La hipótesis que anima esta tesis doctoral es que algunas de las características del entorno urbano, en particular las que describen la accesibilidad de su red de espacio público, podrían estar relacionadas con la proporción de viajes a pie o reparto modal, que tiene cada zona o barrio de Madrid. Uno de los puntos de partida de dicha hipótesis que el entorno urbano tiene una mayor influencia sobre los viaje a pie que en sobre otros modos de transporte, por ejemplo que en los viajes de bicicleta o en transporte público; y es que parece razonable suponer que estos últimos van a estar más condicionadas por ejemplo por la disponibilidad de vías ciclistas, en el primer caso, o por la existencia de un servicio fiable y de calidad, en el segundo. Otra de las motivaciones del trabajo es que la investigación en este campo de la accesibilidad del espacio público, en concreto la denominada “Space Syntax”, ha probado en repetidas ocasiones la influencia de la red de espacio público en cómo se distribuye la intensidad del tráfico peatonal por la trama urbana, pero no se han encontrado referencias de la influencia de dicho elemento sobre el reparto modal. De acuerdo con la hipótesis y con otros trabajos anteriores se propone una metodología basada en el análisis empírico y cuantitativo. Su objetivo es comprobar si la red de espacio público, independientemente de otras variables como los usos del suelo, incluso de las variables de ajenas entorno no construido, como las socioeconómicas, está o no relacionada estadísticamente con la proporción de peatones viajes en las zonas urbanas. Las técnicas estadísticas se utilizan para comprobar sistemáticamente la asociación de las variables del entorno urbano, denominadas variables independientes, con el porcentaje de viajes a pie, la variable dependiente. En términos generales, la metodología es similar a la usada en otros trabajos en este campo como los de CERVERÓ y KOCKLEMAN (1997), CERVERÓ y DUNCAN (2003), o para los que se utilizan principalmente en la revisión general de TRB (2005) o, más recientemente, en ZEGRAS (2006) o CHATMAN (2009). Otras opciones metodológicas, como los métodos de preferencias declaradas (ver LOUVIERE, HENSHER y SWAIT, 2000) o el análisis basado en agentes (PENN & TURNER, 2004) fueron descartados, debido a una serie de razones, demasiado extensas para ser descritas aquí. El caso de estudio utilizado es la zona metropolitana de Madrid, abarcándola hasta la M-50, es decir en su mayor parte, con un tamaño aproximado de 31x34 Km y una población de 4.132.820 habitantes (aproximadamente el 80% de la población de la región). Las principales fuentes de datos son la Encuesta Domiciliaria de Movilidad de 2004 (EDM04), del Consorcio Regional de Transportes de Madrid que es la última disponible (muestra: > 35.000 familias,> 95.000 personas), y un modelo espacial del área metropolitana, integrando el modelo para calcular los índices de Space Syntax y un Sistema de Información Geográfica (SIG). La unidad de análisis, en este caso las unidades espaciales, son las zonas de transporte (con una población media de 7.063 personas) y los barrios (con una población media de 26.466 personas). Las variables del entorno urbano son claramente el centro del estudio. Un total de 20 índices (de 21) se seleccionan de entre los más relevantes encontrados en la revisión de la producción científica en este campo siendo que, al mismo tiempo, fueran accesibles. Nueve de ellos se utilizan para describir las características de los usos del suelo, mientras que otros once se usan para describir la red de espacios públicos. Estos últimos incluyen las variables de accesibilidad configuracional, que son, como se desprende de su título, el centro del estudio propuesto. La accesibilidad configuracional es un tipo especial de accesibilidad que se basa en la configuración de la trama urbana, según esta fue definida por HILLIER (1996), el autor de referencia dentro de esta línea de investigación de Space Syntax. Además se incluyen otras variables de la red de espacio público más habituales en los estudios de movilidad, y que aquí se denominan características geométricas de los elementos de la red, tales como su longitud, tipo de intersección, conectividad, etc. Por último se incluye además una variable socioeconómica, es decir ajena al entorno urbano, para evaluar la influencia de los factores externos, pues son varios los que pueden tener un impacto en la decisión de caminar (edad, género, nivel de estudios, ingresos, tasa de motorización, etc.). La asociación entre las variables se han establecido usando análisis de correlación (bivariante) y modelos de análisis multivariante. Las primeras se calculan entre por pares entre cada una de las 21 variables independientes y la dependiente, el porcentaje de viajes a pie. En cuanto a los segundos, se han realizado tres tipos de estudios: modelo multivariante general lineal, modelo multivariante general curvilíneo y análisis discriminante. Todos ellos son capaces de generar modelos de asociación entre diversas variables, pudiéndose de esta manera evaluar con bastante precisión en qué medida cada modelo reproduce el comportamiento de la variable dependiente, y además, el peso o influencia de cada variable en el modelo respecto a las otras. Los resultados fundamentales del estudio se expresan en dos modelos finales alternativos, que demuestran tener una significativa asociación con el porcentaje de viajes a pie (R2 = 0,6789, p <0,0001), al explicar las dos terceras partes de su variabilidad. En ellos, y en general en todo el estudio realizado, se da una influencia constante de tres índices en particular, que quedan como los principales. Dos de ellos, de acuerdo con muchos de los estudios previos, corresponden a la densidad y la mezcla de usos del suelo. Pero lo más novedoso de los resultados obtenidos es que el tercero es una medida de la accesibilidad de la red de espacio público, algo de lo que no había referencias hasta ahora. Pero, ¿cuál es la definición precisa y el peso relativo de cada uno en el modelo, es decir, en la variable independiente? El de mayor peso en la mayor parte de los análisis realizados es el índice de densidad total (n º residentes + n º puestos de trabajo + n º alumnos / Ha). Es decir, una densidad no sólo de población, sino que incluye algunas de las actividades más importantes que pueden darse una zona para generar movilidad a pie. El segundo que mayor peso adquiere, llegando a ser el primero en alguno de los análisis estadísticos efecturados, es el índice de accesibuilidad configuracional denominado integración de radio 5. Se trata de una medida de la accesibilidad de la zona, de su centralidad, a la escala de, más un menor, un distrito o comarca. En cuanto al tercero, obtiene una importancia bastante menor que los anteriores, y es que representa la mezcla de usos. En concreto es una medida del equilibrio entre los comercios especializados de venta al por menor y el número de residentes (n º de tiendas especializadas en alimentación, bebidas y tabaco / n º de habitantes). Por lo tanto, estos resultados confirman buena parte de los de estudios anteriores, especialmente los relativas a los usos del suelo, pero al mismo tiempo, apuntan a que la red de espacio público podría tener una influir mayor de la comprobada hasta ahora en la proporción de peatones sobre el resto de modos de transportes. Las razones de por qué esto puede ser así, se discuten ampliamente en las conclusiones. Finalmente se puede precisar que dicha conclusión principal se refiere a viajes de una sola etapa (no multimodales) que se dan en los barrios y zonas del área metropolitana de Madrid. Por supuesto, esta conclusión tiene en la actualidad, una validez limitada, ya que es el resultado de un solo caso — Abstract The research hypothesis for this Ph.D. Thesis is that some characteristics of the built environment, particularly those describing the accessibility of the public space network, could be associated with the proportion of pedestrians in all trips (modal split), found in the different parts of a city. The underlying idea is that walking trips are more sensitive to built environment than those by other transport modes, such as for example those by bicycle or by public transport, which could be more conditioned by, e.g. infrastructure availability or service frequency and quality. On the other hand, it has to be noted that the previously research on this field, in particular within Space Syntax’s where this study can be referred, have tested similar hypothesis using pedestrian volumes as the dependent variable, but never against modal split. According to such hypothesis, research methodology is based primarily on empirical quantitative analysis, and it is meant to be able to assess whether public space network, no matter other built environment and non-built environment variables, could have a relationship with the proportion of pedestrian trips in urban areas. Statistical techniques are used to check the association of independent variables with the percentage of walking in all trips, the dependent one. Broadly speaking this methodology is similar to that of previous studies in the field such as CERVERO&KOCKLEMAN (1997), CERVERO & DUNCAN (2003), or to those used mainly in the general review of T.R.B. (2005) or, more recently in ZEGRAS (2006) or CHATMAN (2009). Other methodological options such as stated choice methods (see LOUVIERE, HENSHER & SWAIT, 2000) or agent based analysis (PENN & TURNER, 2004), were discarded, due to a number of reasons, too long to be described here. The case study is not the entire Madrid’s metropolitan area, but almost (4.132.820 inhabitants, about 80% of region´s population). Main data sources are the Regional Mobility Home Based Survey 2004 (EDM04), which is the last available (sample: >35.000 families, > 95.000 individuals), and a spatial model of the metropolitan area, developed using Space Syntax and G.I.S. techniques. The analysis unit, in this case spatial units, are both transport zones (mean population = 7.063) and neighborhoods (mean population = 26.466). The variables of the built environment are clearly the core of the study. A total of 20 (out of 21) are selected from among those found in the literature while, at the same time, being accessible. Nine out of them are used to describe land use characteristics while another eleven describe the network of public spaces. Latter ones include configurational accessibility or Space Syntax variables. This is a particular sort of accessibility related with the concept of configuration, by HILLIER (1996), one of the main authors of Space Syntax, But it also include more customary variables used in mobility research to describe the urban design or spatial structure (here public space network), which here are called geometric characteristics of the such as its length, type of intersection, conectivity, density, etc. Finally a single socioeconomic variable was included in order to assess the influence non built environment factors that also may have an impact on walking (age, income, motorization rate, etc.). The association among variables is worked out using bi-variate correlation analysis and multivariate-analysis. Correlations are calculated among the 21 independent variables and the dependent one, the percentage of walking trips. Then, three types of multi-variate studies are run: general linear, curvilinear and discriminant multi-variate analysis. The latter are fully capable of generating complex association models among several variables, assessing quite precisely to what extent each model reproduces the behavior of the dependent variable, and also the weight or influence of each variable in the model. This study’s results show a consistent influence of three particular indexes in the two final alternative models of the multi-variate study (best, R2=0,6789, p<0,0000). Not surprisingly, two of them correspond to density and mix of land uses. But perhaps more interesting is that the third one is a measure of the accessibility of the public space network, a variable less important in the literature up to now. Additional precisions about them and their relative weight could also be of some interest. The density index is not only about population but includes most important activities in an area (nº residents + nº jobs+ nº students/Ha). The configurational index (radius 5 integration) is a measure of the accessibility of the area, i.e. centrality, at the scale of, more a less, a district. Regarding the mix of land uses index, this one is a measure of the balance between retail, in fact local basic retail, and the number of residents (nº of convenience shops / nº of residents). Referring to their weights, configurational index (radius 5 integration) gets the higher standardized coefficient of the final equation. However, in the final equations, there are a higher number of indexes coming from the density or land use mix categories than from public space network enter. Therefore, these findings seem to support part of the field’s knowledge, especially those concerning land uses, but at the same time they seem to bring in the idea that the configuration of the urban grid could have an influence in the proportion of walkers (as a part of total trips on any transport mode) that do single journey trips in the neighborhoods of Madrid, Spain. Of course this conclusion has, at present, a limited validity since it’s the result of a single case. The reasons of why this can be so, are discussed in the last part of the thesis.

Consolidation of a wsn and minimax method to rapidly neutralise intruders in strategic installations

Due to the sensitive international situation caused by still-recent terrorist attacks, there is a common need to protect the safety of large spaces such as government buildings, airports and power stations. To address this problem, developments in several research fields, such as video and cognitive audio, decision support systems, human interface, computer architecture, communications networks and communications security, should be integrated with the goal of achieving advanced security systems capable of checking all of the specified requirements and spanning the gap that presently exists in the current market. This paper describes the implementation of a decision system for crisis management in infrastructural building security. Specifically, it describes the implementation of a decision system in the management of building intrusions. The positions of the unidentified persons are reported with the help of a Wireless Sensor Network (WSN). The goal is to achieve an intelligent system capable of making the best decision in real time in order to quickly neutralise one or more intruders who threaten strategic installations. It is assumed that the intruders’ behaviour is inferred through sequences of sensors’ activations and their fusion. This article presents a general approach to selecting the optimum operation from the available neutralisation strategies based on a Minimax algorithm. The distances among different scenario elements will be used to measure the risk of the scene, so a path planning technique will be integrated in order to attain a good performance. Different actions to be executed over the elements of the scene such as moving a guard, blocking a door or turning on an alarm will be used to neutralise the crisis. This set of actions executed to stop the crisis is known as the neutralisation strategy. Finally, the system has been tested in simulations of real situations, and the results have been evaluated according to the final state of the intruders. In 86.5% of the cases, the system achieved the capture of the intruders, and in 59.25% of the cases, they were intercepted before they reached their objective.

Intentions: a confident-based interaction design for smart spaces

The paradigm of ubiquitous computing has become a reference for the design of Smart Spaces. Current trends in Ambient Intelligence are increasingly related to the scope of Internet of Things. This paradigm has the potential to support cost-effective solutions in the fields of telecare, e-health and Ambient Assisted Living. Nevertheless, ubiquitous computing does not provide end users with a role for proactive interactions with the environment. Thus, the deployment of smart health care services at a private space like the home is still unsolved. This PhD dissertation aims to define a person-environment interaction model to foster acceptability and users confidence in private spaces by applying the concept of user-centred security and the human performance model of seven stages of action.

Hybridization Processes: The case of the urban game: Hybrid Hunt: Petrified

The proposal highlights certain design strategies and a case study that can link the material urban space to digital emerging realms. The composite nature of urban spaces ?material/ digital- is understood as an opportunity to reconfigure public urban spaces without high-cost, difficult to apply interventions and, furthermore, to reactivate them by inserting dynamic, interactive and playful conditions that engage people and re-establish their relations to the cities. The structuring of coexisting and interconnected material and digital aspects in public urban spaces is proposed through the implementation of hybridization processes. Hybrid spaces can fascinate and provoke the public and especially younger people to get involved and interact with physical aspects of urban public spaces as well as digital representations or interpretations of those. Digital game?s design in urban public spaces can be comprehended as a tool that allows architects to understand and to configure hybrids of material and digital conceptions and project all in one, as an inseparable totality. Digital technologies have for a long time now intervened in our perception of traditional dipoles such as subject - environment. Architects, especially in the past, have been responsible for material mediations and tangible interfaces that permit subjects to relate to their physical environments in a controlled and regulated manner; but, nowadays, architects are compelled to embody in design, the transition that is happening in all aspects of everyday life, that is, from material to digital realities. In addition, the disjunctive relation of material and digital realms is ceding and architects are now faced with the challenge that supposes the merging of both in a single, all-inclusive reality. The case study is a design project for a game implemented simultaneously in a specific urban space and on the internet. This project developed as the spring semester course New Media in Architecture at the Department of Architecture, Democritus University of Thrace, Greece is situated at the city of Xanthi. Composite cities can use design strategies and technological tools to configure augmented and appealing urban spaces that articulate and connect different realms in a single engaging reality.

The structure of the acto-myosin subfragment 1 complex: Results of searches using data from electron microscopy and x-ray crystallography

Surmises of how myosin subfragment 1 (S1) interacts with actin filaments in muscle contraction rest upon knowing the relative arrangement of the two proteins. Although there exist crystallographic structures for both S1 and actin, as well as electron microscopy data for the acto–S1 complex (AS1), modeling of this arrangement has so far only been done “by eye.” Here we report fitted AS1 structures obtained using a quantitative method that is both more objective and makes more complete use of the data. Using undistorted crystallographic results, the best-fit AS1 structure shows significant differences from that obtained by visual fitting. The best fit is produced using the F-actin model of Holmes et al. [Holmes, K. C., Popp, D., Gebhard, W. & Kabsch, W. (1990) Nature (London) 347, 44–49]. S1 residues at the AS1 interface are now found at a higher radius as well as being translated axially and rotated azimuthally. Fits using S1 plus loops missing from the crystal structure were achieved using a homology search method to predict loop structures. These improved fits favor an arrangement in which the loop at the 50- to 20-kDa domain junction of S1 is located near the N terminus of actin. Rigid-body movements of the lower 50-kDa domain, which further improve the fit, produce closure of the large 50-kDa domain cleft and bring conserved residues in the lower 50-kDa domain into an apparently appropriate orientation for close interaction with actin. This finding supports the idea that binding of ATP to AS1 at the end of the ATPase cycle disrupts the actin binding site by changing the conformation of the 50-kDa cleft of S1.

Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: Implications for allosteric regulation

A central problem in understanding enzyme regulation is to define the conformational states that account for allosteric changes in catalytic activity. For Escherichia coli aspartate transcarbamoylase (ATCase; EC 2.1.3.2) the active, relaxed (R state) holoenzyme is generally assumed to be represented by the crystal structure of the complex of the holoenzyme with the bisubstrate analog N-phosphonacetyl-l-aspartate (PALA). It is unclear, however, which conformational differences between the unliganded, inactive, taut (T state) holoenzyme and the PALA complex are attributable to localized effects of inhibitor binding as contrasted to the allosteric transition. To define the conformational changes in the isolated, nonallosteric C trimer resulting from the binding of PALA, we determined the 1.95-Å resolution crystal structure of the C trimer–PALA complex. In contrast to the free C trimer, the PALA-bound trimer exhibits approximate threefold symmetry. Conformational changes in the C trimer upon PALA binding include ordering of two active site loops and closure of the hinge relating the N- and C-terminal domains. The C trimer–PALA structure closely resembles the liganded C subunits in the PALA-bound holoenzyme. This similarity suggests that the pronounced hinge closure and other changes promoted by PALA binding to the holoenzyme are stabilized by ligand binding. Consequently, the conformational changes attributable to the allosteric transition of the holoenzyme remain to be defined.

Nonatomic games on Loeb spaces

In the setting of noncooperative game theory, strategic negligibility of individual agents, or diffuseness of information, has been modeled as a nonatomic measure space, typically the unit interval endowed with Lebesgue measure. However, recent work has shown that with uncountable action sets, for example the unit interval, there do not exist pure-strategy Nash equilibria in such nonatomic games. In this brief announcement, we show that there is a perfectly satisfactory existence theory for nonatomic games provided this nonatomicity is formulated on the basis of a particular class of measure spaces, hyperfinite Loeb spaces. We also emphasize other desirable properties of games on hyperfinite Loeb spaces, and present a synthetic treatment, embracing both large games as well as those with incomplete information.

Transcytosis of α1-acidic glycoprotein in the continuous microvascular endothelium

By using perfusions and bolus administration, coupled with postembedding immunocytochemical procedures, we have identified the structures involved in the transport of derivatized orosomucoid (α1-acidic glycoprotein) across the continuous microvascular endothelium of the murine myocardium. Our findings indicate that: (i) monomeric orosomucoid binds to the luminal surface of the endothelium; (ii) it is restricted to caveolae during its transport across the endothelium; (iii) it is detected in the perivascular spaces at early time points (by 1 min) and in larger quantities at later time points (>5 min) from the beginning of its perfusion or its intravascular administration; (iv) no orosomucoid molecules are found in the intercellular junctions or at the abluminal exits of interendothelial spaces; and (v) the vesicular transport of orosomucoid is strongly inhibited by N-ethylmaleimide (>80%). Because, by size and shape, the orosomucoid qualifies as a preferential probe for the postulated small pore system, our results are discussed in relation to the pore theory of capillary permeability.

Growth factors regulate phototransduction in retinal rods by modulating cyclic nucleotide-gated channels through dephosphorylation of a specific tyrosine residue

Illumination of vertebrate rod photoreceptors leads to a decrease in the cytoplasmic cGMP concentration and closure of cyclic nucleotide-gated (CNG) channels. Except for Ca2+, which plays a negative feedback role in adaptation, and 11-cis-retinal, supplied by the retinal pigment epithelium, all of the biochemical machinery of phototransduction is thought to be contained within rod outer segments without involvement of extrinsic regulatory molecules. Here we show that insulin-like growth factor-I (IGF-I), a paracrine factor released from the retinal pigment epithelium, alters phototransduction by rapidly increasing the cGMP sensitivity of CNG channels. The IGF-I-signaling pathway ultimately involves a protein tyrosine phosphatase that catalyzes dephosphorylation of a specific residue in the α-subunit of the rod CNG channel protein. IGF-I conjointly accelerates the kinetics and increases the amplitude of the light response, distinct from events that accompany adaptation. These effects of IGF-I could result from the enhancement of the cGMP sensitivity of CNG channels. Hence, in addition to long-term control of development and survival of rods, growth factors regulate phototransduction in the short term by modulating CNG channels.

Substrate-specific regulation of the ribosome– translocon junction by N-terminal signal sequences

Amino-terminal signal sequences target nascent secretory and membrane proteins to the endoplasmic reticulum for translocation. Subsequent interactions between the signal sequence and components of the translocation machinery at the endoplasmic reticulum are thought to be important for the productive engagement of the translocon by the ribosome-nascent chain complex. However, it is not clear whether all signal sequences carry out these posttargeting steps identically, or if there are differences in the interactions directed by one signal sequence versus another. In this study, we find substantial differences in the ability of signal sequences from different substrates to mediate closure of the ribosome–translocon junction early in translocation. We also show that these differences in some cases necessitate functional coordination between the signal sequence and mature domain for faithful translocation. Accordingly, the translocation of some proteins is sensitive to replacement of their signal sequences. In a particularly dramatic example, the topology of the prion protein was found to depend highly on the choice of signal sequence used to direct its translocation. Taken together, our results reveal an unanticipated degree of substrate-specific functionality encoded in N-terminal signal sequences.

The structure of bovine F1-ATPase complexed with the antibiotic inhibitor aurovertin B.

In the structure of bovine mitochondrial F1-ATPase that was previously determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies. Adenylyl-imidodiphosphate is bound to one beta-subunit (betaTP), ADP is bound to the second (betaDP), and no nucleotide is bound to the third (betaE). Here we show that the uncompetitive inhibitor aurovertin B binds to bovine F1 at two equivalent sites in betaTP and betaE, in a cleft between the nucleotide binding and C-terminal domains. In betaDP, the aurovertin B pocket is incomplete and is inaccessible to the inhibitor. The aurovertin B bound to betaTP interacts with alpha-Glu399 in the adjacent alphaTP subunit, whereas the aurovertin B bound to betaE is too distant from alphaE to make an equivalent interaction. Both sites encompass betaArg-412, which was shown by mutational studies to be involved in binding aurovertin. Except for minor changes around the aurovertin pockets, the structure of bovine F1-ATPase is the same as determined previously. Aurovertin B appears to act by preventing closure of the catalytic interfaces, which is essential for a catalytic mechanism involving cyclic interconversion of catalytic sites.

High-resolution physical mapping by combined Alu-hybridization/PCR screening: construction of a yeast artificial chromosome map covering 31 centimorgans in 3p21-p14.

We describe an integrated approach to large-scale physical mapping using an Alu-PCR hybridization screening strategy in conjunction with direct PCR-based screening to construct a continuous yeast artificial chromosome map covering >20 mb in human chromosome 3, bands p14-p21, composed of 205 loci, connected by 480 yeast artificial chromosomes, with average interlocus distance of approximately equal to 100 kb. We observe an inverse distribution of Alu-PCR and (CA)n markers. These results suggest that the two screening methods may be complementary and demonstrate the utility of Alu-PCR hybridization screening in the closure of high-resolution human physical maps.

On the mechanism of skin wound "contraction": a granulation tissue "knockout" with a normal phenotype.

This report explores the mechanism of spontaneous closure of full-thickness skin wounds. The domestic pig, often used as a human analogue for skin wound repair studies, closes these wounds with kinetics similar to those in the guinea pig (mobile skin), even though the porcine dermis on the back is thick and nearly immobile. In the domestic pig, as in the guinea pig, daily full-thickness excisions of the central granulation tissue up to but not including the wound edges in both back and flank wounds do not alter the rate or completeness of wound closure or the final pattern of the scar. A purse-string mechanism of closure was precluded by showing that surgical interruption of wound edge continuity does not alter closure kinetics or wound shape. We conclude that "tightness" of skin is not a key factor nor is the central granulation tissue required for normal wound closure. These data imply that in vitro models such as contraction of isolated granulation tissue or of the cell-populated collagen lattice may not be relevant for understanding the cell biology of in vivo wound closure. Implications for the mechanism for wound closure are discussed.

On paracompactness, completeness and boundedness in uniform spaces

Recently two new types of completeness in metric spaces, called Bourbaki-completeness and cofinal Bourbaki-completeness, have been introduced in [7]. The purpose of this note is to analyze these completeness properties in the general context of uniform spaces. More precisely, we are interested in how they are related with uniform paracompactness properties, as well as with some kind of uniform boundedness.