Ethiques de la description: naissance de l'imagination typologique en France, dans le roman et la sociologie (1820-1860)

Résumé: Ce travail d'histoire comparée de la littérature et de la sociologie s'interroge sur l'émergence de la notion de type dans les pratiques de description du monde social au cours des années 1820-1860. A partir de l'analyse des opérations de schématisation engagées par Honoré Balzac dans La Comédie humaine et par Frédéric Le Play dans Les Ouvriers européens, soit deux oeuvres que tout semble éloigner du point de vue de leurs ambitions, de leur forme, et de la trajectoire de leur auteur, mais qui toutes deux placent cependant la typification au centre de leur dispositif, il s'est agi de produire une histoire de l'imagination typologique, et des ontologies, sociales ou non, qui lui furent associées. Aussi le corpus intègre-t-il des textes d'histoire naturelle, de sciences médicales, d'histoire, de chimie, de géologie, de métallurgie, et, bien évidemment, les genres du roman sentimental, du roman historique et de la littérature panoramique, ainsi que les enquêtes ouvrières et la statistique. Abstract: This work offers a compared history of literature and sociology in France between 1820 and 1860. During that period, the notion of type appears in the literary and sociological descriptions of social reality, and becomes more and more central in the apprehension of the differenciations among classes, communities or groups. Based on the analysis of Honoré Balzac's La Comédie humaine and Frédéric Le Play's Les Ouvriers européens, this study shows that these two series of novels and of workers' monographies put typification at the center of their descriptive ambition. More broadly, it proposes a history of the uses of a typological imagination and of the ontologies, above all social, that were underlying them. That is why the texts also taken into account in this study ranges from natural history, medical sciences, history, chemistry geology and metallurgy, to the sentimental novel, the historical novel and the panoramic literature, as well as social inquiries and statistics.

Food traditions and landscape histories of the Indian Ocean World : theoretical and methodological reflections

Environmental histories of plant exchanges have largely centred on their eco- nomic importance in international trade and on their ecological and social impacts in the places where they were introduced. Yet few studies have at- tempted to examine how plants brought from elsewhere become incorporated over time into the regional cultures of material life and agricultural landscapes. This essay considers the theoretical and methodological problems in inves- tigating the environmental history, diversity and distribution of food plants transferred across the Indian Ocean over several millennia. It brings together concepts of creolisation, syncretism, and hybridity to outline a framework for understanding how biotic exchanges and diffusions have been translated into regional landscape histories through food traditions, ritual practices and articu- lation of cultural identity. We use the banana plant - which underwent early domestication across New Guinea, South-east Asia and peninsular India and reached East Africa roughly two thousand years ago - as an example for il- lustrating the diverse patterns of incorporation into the cultural symbolism, material life and regional landscapes of the Indian Ocean World. We show that this cultural evolutionary approach allows new historical insights to emerge and enriches ongoing debates regarding the antiquity of the plant's diffusion from South-east Asia to Africa.

The HVEM network: new directions in targeting novel costimulatory/co-inhibitory molecules for cancer therapy.

The regulation of the immune system is controlled by many cell surface receptors. A prominent representative is the 'molecular switch' HVEM (herpes virus entry mediator) that can activate either proinflammatory or inhibitory signaling pathways. HVEM ligands belong to two distinct families: the TNF-related cytokines LIGHT and lymphotoxin-α, and the Ig-related membrane proteins BTLA and CD160. HVEM and its ligands have been involved in the pathogenesis of various autoimmune and inflammatory diseases, but recent reports indicate that this network may also be involved in tumor progression and resistance to immune response. Here we summarize the recent advances made regarding the knowledge on HVEM and its ligands in cancer cells, and their potential roles in tumor progression and escape to immune responses. Blockade or enhancement of these pathways may help improving cancer therapy.

Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event.

The HVEM network: new directions in targeting novel costimulatory/co-inhibitory molecules for cancer therapy.

The regulation of the immune system is controlled by many cell surface receptors. A prominent representative is the 'molecular switch' HVEM (herpes virus entry mediator) that can activate either proinflammatory or inhibitory signaling pathways. HVEM ligands belong to two distinct families: the TNF-related cytokines LIGHT and lymphotoxin-α, and the Ig-related membrane proteins BTLA and CD160. HVEM and its ligands have been involved in the pathogenesis of various autoimmune and inflammatory diseases, but recent reports indicate that this network may also be involved in tumor progression and resistance to immune response. Here we summarize the recent advances made regarding the knowledge on HVEM and its ligands in cancer cells, and their potential roles in tumor progression and escape to immune responses. Blockade or enhancement of these pathways may help improving cancer therapy.

A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.

Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated.

Saccamoeba lacustris, sp. nov. (Amoebozoa: Lobosea: Hartmannellidae), a new lobose amoeba, parasitized by the novel chlamydia 'Candidatus Metachlamydia lacustris' (Chlamydiae: Parachlamydiaceae).

An amoeba isolated from an aquatic biotope, identified morphologically as Saccamoeba limax, was found harbouring mutualistic rod-shaped gram-negative bacteria. During their cultivation on agar plates, a coinfection also by lysis-inducing chlamydia-like organisms was found in some subpopulations of that amoeba. .Here we provide a molecular-based identification of both the amoeba host and the two bacterial endosymbionts. Analysis of the 18S rRNA gene revealed that this strain is the sister-group to Glaeseria, for which we proposed the name Saccamoeba lacustris. The rod-shaped endosymbiont was identified as a member of Variovorax paradoxus group (Comamonadaceae, Beta-Proteobacteria). No growth on bacteriological agars was recorded, hence this symbiont might be strictly intracellular. The chlamydia-like parasite was unable to infect Acanthamoeba and other amoebae in coculture, showing high host specificity. Phylogenetic analysis based on the 16S rDNA indicated that it is a new member of the family Parachlamydiaceae (order Chlamydiales), for which we proposed the name 'Candidatus Metachlamydia lacustris'.

New York City: "gilt cage" or "promised land" ? : representations of urban space in Edith Wharton and Anzia Yezierska

This thesis explores the importance of literary New York City in the urban narratives of Edith Wharton and Anzia Yezierska. It specifically looks at the Empire City of the Progressive Period when the concept of the city was not only a new theme but also very much a typical American one which was as central to the American experience as had been the Western frontier. It could be argued, in fact, that the American city had become the new frontier where modern experiences like urbanization, industrialization, immigration, and also women's emancipation and suffrage, caused all kinds of sensations on the human scale from smoothly lived assimilation and acculturation to deeply felt alienation because of the constantly shifting urban landscape. The developing urban space made possible the emergence of new female literary protagonists like the working girl, the reformer, the prostitute, and the upper class lady dedicating her life to 'conspicuous consumption'. Industrialization opened up city space to female exploration: on the one hand, upper and middle class ladies ventured out of the home because of the many novel urban possibilities, and on the other, lower class and immigrant girls also left their domestic sphere to look for paid jobs outside the home. New York City at the time was not only considered the epicenter of the world at large, it was also a city of great extremes. Everything was constantly in flux: small brownstones made way for ever taller skyscrapers and huge waves of immigrants from Europe pushed native New Yorkers further uptown on the island, adding to the crowdedness and intensity of the urban experience. The city became a polarized urban space with Fifth Avenue representing one end of the spectrum and the Lower East Side the other. Questions of space and the urban home greatly mattered. It has been pointed out that the city setting functions as an ideal means for the display of human nature as well as social processes. Narrative representations of urban space, therefore, provide a similar canvas for a protagonist's journey and development. From widely diverging vantage points both Edith Wharton and Anzia Yezierska thus create a polarized city where domesticity is a primal concern. Looking at all of their New York narratives by close readings of exterior and interior city representations, this thesis shows how urban space greatly affects questions of identity, assimilation, and alienation in literary protagonists who cannot escape the influence of their respective urban settings. Edith Wharton's upper class "millionaire" heroines are framed and contained by the city interiors of "old" New York, making it impossible for them to truly participate in the urban landscape in order to develop outside of their 'Gilt Cages'. On the other side are Anzia Yezierska's struggling "immigrant" protagonists who, against all odds, never give up in their urban context of streets, rooftops, and stoops. Their New York City, while always challenging and perpetually changing, at least allows them perspectives of hope for a 'Promised Land' in the making. Central for both urban narrative approaches is the quest for a home as an architectural structure, a spiritual resting place, and a locus for identity forming. But just as the actual city embraces change, urban protagonists must embrace change also if they desire to find fulfillment and success. That this turns out to be much easier for Anzia Yezierska's driven immigrants rather than for Edith Wharton's well established native New Yorkers is a surprising conclusion to this urban theme.

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

On the applicability of mathematics : philosophical and historical perspectives

The present thesis is a contribution to the debate on the applicability of mathematics; it examines the interplay between mathematics and the world, using historical case studies. The first part of the thesis consists of four small case studies. In chapter 1, I criticize "ante rem structuralism", proposed by Stewart Shapiro, by showing that his so-called "finite cardinal structures" are in conflict with mathematical practice. In chapter 2, I discuss Leonhard Euler's solution to the Königsberg bridges problem. I propose interpreting Euler's solution both as an explanation within mathematics and as a scientific explanation. I put the insights from the historical case to work against recent philosophical accounts of the Königsberg case. In chapter 3, I analyze the predator-prey model, proposed by Lotka and Volterra. I extract some interesting philosophical lessons from Volterra's original account of the model, such as: Volterra's remarks on mathematical methodology; the relation between mathematics and idealization in the construction of the model; some relevant details in the derivation of the Third Law, and; notions of intervention that are motivated by one of Volterra's main mathematical tools, phase spaces. In chapter 4, I discuss scientific and mathematical attempts to explain the structure of the bee's honeycomb. In the first part, I discuss a candidate explanation, based on the mathematical Honeycomb Conjecture, presented in Lyon and Colyvan (2008). I argue that this explanation is not scientifically adequate. In the second part, I discuss other mathematical, physical and biological studies that could contribute to an explanation of the bee's honeycomb. The upshot is that most of the relevant mathematics is not yet sufficiently understood, and there is also an ongoing debate as to the biological details of the construction of the bee's honeycomb. The second part of the thesis is a bigger case study from physics: the genesis of GR. Chapter 5 is a short introduction to the history, physics and mathematics that is relevant to the genesis of general relativity (GR). Chapter 6 discusses the historical question as to what Marcel Grossmann contributed to the genesis of GR. I will examine the so-called "Entwurf" paper, an important joint publication by Einstein and Grossmann, containing the first tensorial formulation of GR. By comparing Grossmann's part with the mathematical theories he used, we can gain a better understanding of what is involved in the first steps of assimilating a mathematical theory to a physical question. In chapter 7, I introduce, and discuss, a recent account of the applicability of mathematics to the world, the Inferential Conception (IC), proposed by Bueno and Colyvan (2011). I give a short exposition of the IC, offer some critical remarks on the account, discuss potential philosophical objections, and I propose some extensions of the IC. In chapter 8, I put the Inferential Conception (IC) to work in the historical case study: the genesis of GR. I analyze three historical episodes, using the conceptual apparatus provided by the IC. In episode one, I investigate how the starting point of the application process, the "assumed structure", is chosen. Then I analyze two small application cycles that led to revisions of the initial assumed structure. In episode two, I examine how the application of "new" mathematics - the application of the Absolute Differential Calculus (ADC) to gravitational theory - meshes with the IC. In episode three, I take a closer look at two of Einstein's failed attempts to find a suitable differential operator for the field equations, and apply the conceptual tools provided by the IC so as to better understand why he erroneously rejected both the Ricci tensor and the November tensor in the Zurich Notebook.

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

Uptake of new treatment strategies for deep vein thrombosis: an international audit.

OBJECTIVE: Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals. DESIGN: Historical review of medical records. SETTING AND PARTICIPANTS: We reviewed the medical records of 3043 patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French, and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored independent clinical variables associated with LMW heparin use and outpatient treatment, and determined crude and adjusted rates of LMW heparin use and outpatient treatment across hospitals. RESULTS: For the years studied, the overall rates of LMW heparin use and outpatient treatment in the study sample were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many comorbidities were negatively associated with outpatient treatment, and risk-adjusted rates of use of these new approaches varied significantly across hospitals. CONCLUSION: There has been a relatively rapid uptake of LMW heparins and outpatient treatment for DVT in their early years of availability, but the pace of uptake has varied considerably across hospitals and countries.

Stem cell transplantation in brain tumors: a new field for molecular imaging?

Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.