A Small World Perspective on Urban Systems

The theory of small-world networks as initiated by Watts and Strogatz (1998) has drawn new insights in spatial analysis as well as systems theory. The theoryâeuro?s concepts and methods are particularly relevant to geography, where spatial interaction is mainstream and where interactions can be described and studied using large numbers of exchanges or similarity matrices. Networks are organized through direct links or by indirect paths, inducing topological proximities that simultaneously involve spatial, social, cultural or organizational dimensions. Network synergies build over similarities and are fed by complementarities between or inside cities, with the two effects potentially amplifying each other according to the âeurooepreferential attachmentâeuro hypothesis that has been explored in a number of different scientific fields (Barabási, Albert 1999; Barabási A-L 2002; Newman M, Watts D, Barabàsi A-L). In fact, according to Barabási and Albert (1999), the high level of hierarchy observed in âeurooescale-free networksâeuro results from âeurooepreferential attachmentâeuro, which characterizes the development of networks: new connections appear preferentially close to nodes that already have the largest number of connections because in this way, the improvement in the network accessibility of the new connection will likely be greater. However, at the same time, network regions gathering dense and numerous weak links (Granovetter, 1985) or network entities acting as bridges between several components (Burt 2005) offer a higher capacity for urban communities to benefit from opportunities and create future synergies. Several methodologies have been suggested to identify such denser and more coherent regions (also called communities or clusters) in terms of links (Watts, Strogatz 1998; Watts 1999; Barabási, Albert 1999; Barabási 2002; Auber 2003; Newman 2006). These communities not only possess a high level of dependency among their member entities but also show a low level of âeurooevulnerabilityâeuro, allowing for numerous redundancies (Burt 2000; Burt 2005). The SPANGEO project 2005âeuro"2008 (SPAtial Networks in GEOgraphy), gathering a team of geographers and computer scientists, has included empirical studies to survey concepts and measures developed in other related fields, such as physics, sociology and communication science. The relevancy and potential interpretation of weighted or non-weighted measures on edges and nodes were examined and analyzed at different scales (intra-urban, inter-urban or both). New classification and clustering schemes based on the relative local density of subgraphs were developed. The present article describes how these notions and methods contribute on a conceptual level, in terms of measures, delineations, explanatory analyses and visualization of geographical phenomena.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

BACKGROUND: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species.METHODS: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species.RESULTS: Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001).CONCLUSIONS: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Interactive readings of children's literature in day care: Microgenetic analysis of the semiopictorial construction.

In line with educational issues involved in emergent literacy practices in preschool, in particular those concerning comprehension processes, this paper focuses on picture-based narrative comprehension during an interactive reading session of a wordless picture book, involving a group of children aged three and their teacher. Children are asked to make inferences about the meaning and outcome of the story, a procedure which gradually elicits their responses on how events link together, thus enhancing their capacity to use prior and implicit knowledge to build the story meaning. Moreover, this study highlights the importance of interaction for developing comprehension. Data collected was analysed following didactic microgenesis, an analytical approach showing that knowledge built during interaction depends on the joint construction of a zone of common meaning by which teacher and children try to adjust to each other. In order to help the process of merging different meanings of the story built online, a text written by researchers, following the narrative structure of the story, was read by the teacher after the picture-based reading. This led us to examine through interactional analysis which semiotic cues were used during recall on the following day, as an additional measure of knowledge construction.

Different antigen-presenting cells differ in their capacity to induce lymphokine production and proliferation of an apo-cytochrome c-specific T cell clone.

The activation of an apo-cytochrome c-specific T cell clone was found to differ, depending on the antigen-presenting cell population. Whereas total syngeneic spleen cells and bone marrow macrophages could be shown to trigger proliferation, IL 2, and MAF production by the T cell clone, a B cell lymphoma only induced MAF secretion. Further studies demonstrated that this effect was not due to a different antigen processing by the B lymphoma or to limiting amounts of Ia and antigen molecules on the B lymphoma cell surface. The dissociation of induction of MAF production from IL-2 production/proliferation found with the different antigen-presenting cells indicates strongly that molecules other than Ia and antigen may be required for the complete functional activation of antigen-specific T cell clones.

Neuropeptide Y: a missing link?

Yet another 'orphan' molecule that had to find its place in life after isolation and sequencing, neuropeptide Y appears to be an important cardiovascular neuroregulator and also links the sympathetic and renin-angiotensin systems. The peptide's physiologic and pathophysiologic roles, as well as its potential therapeutic value, are examined.

Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man.

The metabolic balance method was performed on three men to investigate the fate of large excesses of carbohydrate. Glycogen stores, which were first depleted by diet (3 d, 8.35 +/- 0.27 MJ [1994 +/- 65 kcal] decreasing to 5.70 +/- 1.03 MJ [1361 +/- 247 kcal], 15% protein, 75% fat, 10% carbohydrate) and exercise, were repleted during 7 d carbohydrate overfeeding (11% protein, 3% fat, and 86% carbohydrate) providing 15.25 +/- 1.10 MJ (3642 +/- 263 kcal) on the first day, increasing progressively to 20.64 +/- 1.30 MJ (4930 +/- 311 kcal) on the last day of overfeeding. Glycogen depletion was again accomplished with 2 d of carbohydrate restriction (2.52 MJ/d [602 kcal/d], 85% protein, and 15% fat). Glycogen storage capacity in man is approximately 15 g/kg body weight and can accommodate a gain of approximately 500 g before net lipid synthesis contributes to increasing body fat mass. When the glycogen stores are saturated, massive intakes of carbohydrate are disposed of by high carbohydrate-oxidation rates and substantial de novo lipid synthesis (150 g lipid/d using approximately 475 g CHO/d) without postabsorptive hyperglycemia.

Assessment of the capacity to consent to treatment in patients admitted to acute medical wards.

BACKGROUND: Assessment of capacity to consent to treatment is an important legal and ethical issue in daily medical practice. In this study we carefully evaluated the capacity to consent to treatment in patients admitted to an acute medical ward using an assessment by members of the medical team, the specific Silberfeld's score, the MMSE and an assessment by a senior psychiatrist. METHODS: Over a 3 month period, 195 consecutive patients of an internal medicine ward in a university hospital were included and their capacity to consent was evaluated within 72 hours of admission. RESULTS: Among the 195 patients, 38 were incapable of consenting to treatment (unconscious patients or severe cognitive impairment) and 14 were considered as incapable of consenting by the psychiatrist (prevalence of incapacity to consent of 26.7%). Agreement between the psychiatrist's evaluation and the Silberfeld questionnaire was poor (sensitivity 35.7%, specificity 91.6%). Experienced clinicians showed a higher agreement (sensitivity 57.1%, specificity 96.5%). A decision shared by residents, chief residents and nurses was the best predictor for agreement with the psychiatric assessment (sensitivity 78.6%, specificity 94.3%). CONCLUSION: Prevalence of incapacity to consent to treatment in patients admitted to an acute internal medicine ward is high. While the standardized Silberfeld questionnaire and the MMSE are not appropriate for the evaluation of the capacity to consent in this setting, an assessment by the multidisciplinary medical team concurs with the evaluation by a senior psychiatrist.

IgG subclass switch capacity is low in switched and in IgM-only, but high in IgD+IgM+, post-germinal center (CD27+) human B cells.

Recent studies have shown that in humans the germinal center reactions produce three types of V(D)J mutated B cells in similar proportions, i.e. Ig-switched, IgD-IgM+ (IgM-only) and IgD+IgM+ cells, and that together they form the CD27+ compartment of recirculating B cells. We investigated the Ig isotype switch capacity of these cells. Peripheral blood B subsets were sorted and IgG subclass secretion in presence or absence of IL-4 was compared in B cell assays which lead to Ig secretion in all (coculture with EL-4 thymoma cells) or only in CD27+ (CD40L stimulation) B cells. Already switched IgG+ B cells showed no significant sequential switch and IgM-only cells also had a low switch capacity, but IgD+CD27+ switched as much as IgD+CD27- B cells to all IgG subclasses. Thus, in switched B cells some alterations compromising further switch options occur frequently; IgM-only cells may result from aborted switch. However, IgD+CD27+ human B cells, extensively V(D)J mutated and "naive" regarding switch, build up a repertoire of B cells combining (1) novel cross-reactive specificities, (2) increased differentiation capacity (including after T-independent stimulation by Staphylococcus aureus Cowan I) and (3) the capacity to produce appropriate isotypes when they respond to novel pathogens.

Experience-dependent plasticity in the mouse barrel cortex

Abstract : Host-Cell Factor 1 (HCF-1) was first discovered in the study of the herpes simplex virus (HSV) infection. HCF-1 is one of the two cellular proteins that compose the VP16-induced complex, a key activator of HSV lytic infection. lncleed, when HSV infects human cells, it is able to enter two modes of infection: lytic or latent. The V`P16-induced complex promotes the lytic mode and in so doing the virus targets important cellular regulatory proteins, such as HCF-1, to manipulate the status of the infected cell. Indeed, HCF-1 regulates human cell proliferation and the cell cycle at different steps. In human, HCF-1 is unusual in that it undergoes a process of proteolytic maturation that results from cleavages at six centrally located 26 amino acid repeats called HCF-1pro repeats. This generates a heterodimeric complex of stably associated amino- (HCF-1n) and carboxy- (HCF-1c) terminal subunits. The absence of the HCF-1 N or HCF-1; subunit leads predominantly to either G1 or M phase defects, respectively. We have hypothesized that HCF-1 forms a heterodimeric complex to permit communication between the two subunits of HCF-1 involved in regulating different phases of the cell cycle. Indeed, there is evidence for such inter-subunit communication because a point mutation called P134S in the HCF-1N subunit in the temperature-sensitive hamster cell line tsBN67 causes, addition to G1- phase defects associated with the HCF-1n subunit, M-phase defects similar to the defects seen upon loss of HCF-1 function. Furthermore, inhibition of the proteolytic maturation of HCF-1 by deletion of the six HCF-1pro repeats (HCF-1Aimo) also leads to M-phase defects, specifically cytokinesis defects leading to binucleation, indicating that there is loss of HCF-15 function in the absence of HCF-1 maturation. I demonstrate that individual point mutations in each of the six HCF-1pro repeats that prevent HCF-1 proteolytic maturation also lead to binucleation; however, this defect can be latgely rescued by the presence of just one HCF-1pRO sequence in I-ICF»1. These results argue that processing itself is important for the HCF-1g function. In fact, until now, the hypothesis was that the proteolytic processing per se is more important for HCF-1C function than the proteolytic processing region. But I show that processing per se is not sufticient to rescue multinucleation, but that the HCF-lpm sequence itself is crucial. This discovery leads to the conclusion that the I-ICF-1pRO repeats have an additional function important for HCF-le function. From the studies of others, one potential function of the HCF-lrxo tepeats is as a binding site for O-link NAcetyl glycosamine tansferase (OGT) to glycosylate an HCF-1n-sunbunit region called the Basic region. This new function suggests the Basic region of HCF-1n is also implicated in the communication between the two subunits. This inter-subunit communication was analyzed in more detail with the studies of the Pl34S mutation and the residues 382-450 region of HCF-l that when removed prevents HCF-l subunit association. I demonstrate that the point mutation also leads to a binucleation defect in Hela cells as well as in the tsBN67 cells. In addition, the effect of this mutation on the regulation of HCF-1c activity seems to interfere with that of the HCF-lpgg repeats because the sum of the deletion of the proteolytic processing region and the point mutation surprisingly leads to re-establishment of correct cytokinesis. The study of the 382-450 HCF-lN region also yielded surprising results. This region important for the association of the two subunits is also important for both HCF-1c function in M phase and G1 phase progression. Thus, I have discovered two main functions of this region: its role in the regulation of HCF-lc function in M phase and its involvement in the regulation of G1/S phase ?- an HCF-1n function. These results support the importance of inter-subunit communication in HCF-1 functions. My research illuminates the understanding of the interaction of the two subunits by showing that the whole HCF-1n subunit is involved in the inter-subunit communication in order to regulate HCF-1c function. For this work, I was concentrated on the study of cytokinesis; the first phenotype showing the role of HCF-1c in the M phase. Then, I extended the study of the M phase with analysis of steps earlier to cytokinesis. Because some defects in the chromosome segregation was already described in the absence of HCF-1, I decided to continue the study of M phase by checking effects on the chromosome segregation. I showed that the HCF-1n subunit and HCF-1pro repeats are both important for this key step of M phase. I show that the binucleation phenotype resulting from deletion or mutation in HCF-1pro repeats, Pl34S point mutation or the lack of the region 382-450 are correlated with micronuclei, and chromosome segregation and alignment defects. This suggests that HCF«lç already regulates M phase during an early step and could be involved in the complex regulation of chromosome segregation. Because one of the major roles of HCF-1 is to be a transcription regulator, I also checked the capacity of HCF-1 to bind to the chromatin in my different cell lines. All my recombinant proteins can bind the chromatin, except for, as previously described, the HCF-1 with the P134S point mutation, This suggests that the binding of HCF-1 to the chromatin is not dependant to the Basic and proteolytic regions but more to the Kelch domain. Thus, if the function of HCF-ig in M phase is dependant to its chromatin association, the intercommunication and the proteolytic region are not involved in the ability to bind to the chromatin but more to bind to the right place of the chromatin or to be associated with the co-factors. Résumé : L'étude de l'infection par le virus Herpes Simplex (HSV) a permis la découverte de la protéine HCF-1 (Host-Cell Factor). HCF-1 est une des protéines cellulaires qui font partie du complexe induit par VP16 ; ce complexe est la clef pour l'activation de la phase lytique de HSV. Afin de manipuler les cellules infectées, le complexe induit pas le VPIG devrait donc cibler les protéines importantes pour la régulation cellulaire, telles que la protéine HCF-1. Cette dernière s'avère donc être un senseur pour la cellule et devrait également jouer un rôle de régulation lors des différentes phases du cycle cellulaire. Chez l'humain, HCF-1 a la particularité de devoir passer par une phase de maturation pour devenir active. Lors de cette maturation, la protéine subit une coupure protéolytique au niveau de six répétitions composées de 26 acides aminés, appelé HCF-1pro repeats. Cette coupure engendre la formation d'un complexe formé de deux sous-unités, HCF-1n et HCF-1c, associées l'une à l'autre de façon stable. Enlever la sous-unité HCF-IN ou C entraîne respectivement des défauts dans la phase G1 et M. Nous pensons donc que HCF-1 forme un complexe hétérodimérique afin de permettre la communication entre les molécules impliquées dans la régulation des différentes phases du cycle cellulaire. Cette hypothèse est déduite suite à deux études: l'une réalisée sur la lignée cellulaire tsBN67 et l'autre portant sur l'inhibition de la maturation protéolytique. La lignée cellulaire tsBN67, sensible à la température, porte la mutation Pl 345 dans la sous-unité HCF-1n. Cette mutation, en plus d'occasionner des défauts dans la phase G1 (défauts liés à la sous-unité HCF-1N), a aussi pour conséquence d'entrainer des défauts dans la phase M, défauts similaires à ceux dus a la perte de la sous-unité HCF-1c. Quant à la maturation protéolytique, l'absence de la région de la protéolyse provoque la binucléation, défaut lié à la cytokinèse, indiquant la perte de la fonction de la sous-unité HCF-1c. Au cours de ma thèse, j'ai démontré que des mutations dans les HCF-1=no repeats, qui bloquent la protéolyse, engendrent la binucléation ; cependant ce défaut peut être corrigé pas l'ajout d'un HCF-1pro repeat dans un HCF-1 ne contenant pas la région protéolytique. Ces résultats soutiennent l'idée que la région protéolytique est importante pour le bon fonctionnement de HCF-1c. En réalité jusqu'a maintenant on supposait que le mécanisme de coupure était plus important que la région impliquée pour la régulation de la fonction de HCF-1;. Mais mon étude montre que la protéolyse n'est pas suffisante pour éviter la binucléation ; en effet, les HCF-1pro repeats semblent jouer le rôle essentiel dans le cycle cellulaire. Cette découverte conduit à la conclusion que les HCF-1pro repeats ont sûrement une fonction autre qui serait cruciale pour la foncton de HCF-1c. Une des fonctions possibles est d'être le site de liaison de l'O-linked N-acetylglucosamine transférase (OGT) qui glycosylerait la région Basique de HCF-1n. Cette nouvelle fonction suggère que la région Basique est aussi impliquée dans la communication entre les deux sous- unités. L'intercommunication entre les deux sous-unités ai été d'ailleurs analysée plus en détail dans mon travail à travers l'étude de la mutation Pl34S et de la région 382-450, essentielle pour l'association des deux sous»unités. J'ai ainsi démontré que la mutation P134S entraînait aussi des défauts dans la cytokinése dans la lignée cellulaire Hela, de plus, son influence sur HCF-1c semble interférer avec celle de la région protéolytique. En effet, la superposition de ces deux modifications dans HCF-1 conduit au rétablissement d'une cytokinése correcte. Concernant la région 382 à 450, les résultats ont été assez surprenants, la perte de cette région provoque l'arrêt du cycle en G1 et la binucléation, ce qui tend à prouver son importance pour le bon fonctionnement de HCF-1n et de HCF-1c. Cette découverte appuie par conséquent l'hypotl1èse d'une intercommunicatzion entre les deux sous-unités mettant en jeu les différentes régions de HCF-1n. Grâce à mes recherches, j'ai pu améliorer la compréhension de l'interaction des deux sous-unités de HCF-1 en montrant que toutes les régions de HCF-1n sont engagées dans un processus d'intercommunication, dont le but est de réguler l'action de HCF-1c. J'ai également mis en évidence une nouvelle étape de la maturation de HCF-1 qui représente une phase importante pour l'activation de la fonction de HCF-1c. Afin de mettre à jour cette découverte, je me suis concentrée sur l'étude de l'impact de ces régions au niveau de la cytokinése qui fut le premier phénotype démontrant le rôle de HCF-1c dans la phase M. A ce jour, nous savons que HCF-1c joue un rôle dans la cytokinèse, nous ne connaissons pas encore sa fonction précise. Dans le but de cerner plus précisément cette fonction, j'ai investigué des étapes ultérieures ai la cytokinèse. Des défauts dans la ségrégation des chromosomes avaient déjà été observés, ai donc continué l'étude en prouvant que HCF-1n et les HCF-1pro repeats sont aussi importants pour le bon fonctionnement de cette étape clef également régulée par HCF-1c. J' ai aussi montré que la région 382-450 et la mutation P134S sont associées à un taux élevé de micronoyaux, de défauts dans la ségrégation des chromosomes. L'une des fonctions principales de HCF-1 étant la régulation de la transcription, j'ai aussi contrôlé la capacité de HCF-1 à se lier à la chromatine après insertion de mutations ou délétions dans HCF-1n et dans la région protéolytique. Or, à l'exception des HCF-1 contenant la mutation P134S, la sous-unité HCF-1c des HCF-1 tronquées se lie correctement à la chromatine. Cette constatation suggère que la liaison entre HCF-1c et chromatine n'est pas dépendante de la région Basique ou Protéolytique mais peut-être vraisemblablement de la région Kelch. Donc si le rôle de HCF-1c est dépendant de sa capacité â activer la transcription, l'intercommunication entre les deux sous-unités et la région protéolytique joueraient un rôle important non pas dans son habileté à se lier à la chromatine, mais dans la capacité de HCF-1 à s'associer aux co-facteurs ou à se placer sur les bonnes régions du génome.

Colonisation capacity of the Greater white-toothed shrew Crocidura russula : an experimental study

greater white toothed shrew; Crocidura russula; colonisation capacity