L'application de la spectroscopie Raman en criminalistique pour l'analyse du colorant des fibres textiles en acrylique, coton et laine

RESUME La méthode de la spectroscopie Raman est une technique d'analyse chimique basée sur l'exploitation du phénomène de diffusion de la lumière (light scattering). Ce phénomène fut observé pour la première fois en 1928 par Raman et Krishnan. Ces observations permirent à Raman d'obtenir le Prix Nobel en physique en 1930. L'application de la spectroscopie Raman a été entreprise pour l'analyse du colorant de fibres textiles en acrylique, en coton et en laine de couleurs bleue, rouge et noire. Nous avons ainsi pu confirmer que la technique est adaptée pour l'analyse in situ de traces de taille microscopique. De plus, elle peut être qualifiée de rapide, non destructive et ne nécessite aucune préparation particulière des échantillons. Cependant, le phénomène de la fluorescence s'est révélé être l'inconvénient le plus important. Lors de l'analyse des fibres, différentes conditions analytiques ont été testées et il est apparu qu'elles dépendaient surtout du laser choisi. Son potentiel pour la détection et l'identification des colorants imprégnés dans les fibres a été confirmé dans cette étude. Une banque de données spectrale comprenant soixante colorants de référence a été réalisée dans le but d'identifier le colorant principal imprégné dans les fibres collectées. De plus, l'analyse de différents blocs de couleur, caractérisés par des échantillons d'origine inconnue demandés à diverses personnes, a permis de diviser ces derniers en plusieurs groupes et d'évaluer la rareté des configurations des spectres Raman obtenus. La capacité de la technique Raman à différencier ces échantillons a été évaluée et comparée à celle des méthodes conventionnelles pour l'analyse des fibres textiles, à savoir la micro spectrophotométrie UV-Vis (MSP) et la chromatographie sur couche mince (CCM). La technique Raman s'est révélée être moins discriminatoire que la MSP pour tous les blocs de couleurs considérés. C'est pourquoi dans le cadre d'une séquence analytique nous recommandons l'utilisation du Raman après celle de la méthode d'analyse de la couleur, à partir d'un nombre de sources lasers le plus élevé possible. Finalement, la possibilité de disposer d'instruments équipés avec plusieurs longueurs d'onde d'excitation, outre leur pouvoir de réduire la fluorescence, permet l'exploitation d'un plus grand nombre d'échantillons. ABSTRACT Raman spectroscopy allows for the measurement of the inelastic scattering of light due to the vibrational modes of a molecule when irradiated by an intense monochromatic source such as a laser. Such a phenomenon was observed for the first time by Raman and Krishnan in 1928. For this observation, Raman was awarded with the Nobel Prize in Physics in 1930. The application of Raman spectroscopy has been undertaken for the dye analysis of textile fibers. Blue, black and red acrylics, cottons and wools were examined. The Raman technique presents advantages such as non-destructive nature, fast analysis time, and the possibility of performing microscopic in situ analyses. However, the problem of fluorescence was often encountered. Several aspects were investigated according to the best analytical conditions for every type/color fiber combination. The potential of the technique for the detection and identification of dyes was confirmed. A spectral database of 60 reference dyes was built to detect the main dyes used for the coloration of fiber samples. Particular attention was placed on the discriminating power of the technique. Based on the results from the Raman analysis for the different blocs of color submitted to analyses, it was possible to obtain different classes of fibers according to the general shape of spectra. The ability of Raman spectroscopy to differentiate samples was compared to the one of the conventional techniques used for the analysis of textile fibers, like UV-Vis Microspectrophotometry (UV-Vis MSP) and thin layer chromatography (TLC). The Raman technique resulted to be less discriminative than MSP for every bloc of color considered in this study. Thus, it is recommended to use Raman spectroscopy after MSP and light microscopy to be considered for an analytical sequence. It was shown that using several laser wavelengths allowed for the reduction of fluorescence and for the exploitation of a higher number of samples.

Nutrition transition in a middle-income country: 22-year trends in the Seychelles.

BACKGROUND/OBJECTIVES: There is little objective information regarding nutrition transition in African countries. We assessed trends in nutrition patterns in the Seychelles between 1989 and 2011. SUBJECTS/METHODS: Population-based samples were obtained in 1989, 1994 and 2011 and participants aged 25-44 are considered in this study (n=493, 599 and 471, respectively). Similar, although not identical, food frequency questionnaires (FFQs) were used in each survey and the variables were collapsed into homogenous categories for the purpose of this study. RESULTS: Between 1989 and 2011, consumption frequency of fish (5+/week) decreased from 93 to 74%, whereas the following increased: meat (5+/week) 25 to 51%, fruits (1+/week) 48 to 94%, salty snacks (1+/week) 22 to 64% and sweet snacks (1+/week) 38 to 67% (P<0.001 for all). Consumption frequency decreased for home-brewed alcoholic drinks (1+/week) 16 to 1%, but increased for wine (1+/week) 5 to 33% (both P<0.001). Between 2004 and 2011, consumption frequency decreased for rice (2/day) 62 to 57% and tea (1+/day) 72 to 68%, increased for poultry (1+/week) 86 to 96% (all P<0.01), and did not change for vegetables (70.3 to 69.8%, P=0.65). CONCLUSIONS: Seychelles is experiencing nutrition transition characterized by a decreased consumption frequency of traditional staple foods (fish, polished rice), beverages (tea) and of inexpensive home brews, and increased consumption frequency of meat, poultry and snacks. Food patterns also became more varied along with a broader availability of products in the 22-year interval. The health impact of these changes should be further studied.

Jésus historique: une quête de l'inaccessible étoile? Bilan de la "troisième quête"

La «troisième Quête» du Jésus historique relance le débat sur des acquis de la recherche. Bien qu'il s'agisse d'une nébuleuse de positions dissemblables plutôt que d'un courant homogène, cette constellation de chercheurs remet en cause le consensus antérieur. Son nouveau paradigme peut être saisi sur cinq points : 1) Les sources documentaires sur Jésus sont étendues et leur exploitation modifiée. 2) On relève un puissant retour à la judaïté du Nazaréen. 3) Le coeur de l'agir de Jésus n'est plus nécessairement une position millénariste, mais une conviction sapientiale. 4) L'histoire sociale met en valeur la réaction du messianisme populaire contre une politique d'acculturation gréco-romaine en Palestine. 5) Une christologie implicite redevient pensable au niveau de Jésus lui-même. The third Quest for the historical Jesus has re-opened the debate concerning research findings. Although this consists of a nebulous set of dissimilar positions rather than a homogenous trend, five previous points of consensus are being challenged by the constellation of researchers. The new paradigm may be summarised in five points: 1) The documentary sources on Jesus are spread out and their use is thereby modified. 2) A notable return to the Jewishness of Jesus of Nazareth. 3) The heart of Jesus' action is no longer seen as a millenarist position, but more as a conviction informed by Wisdom. 4) Social history emphasises the reaction of popular messianism confronting Greek-Roman political acculturation. 5) An implicit Christology becomes possible once more at the level of Jesus Himself.

Cell Adhesion Peptide RGDSP and Laminin Support Proliferation and Migration of Postnatal Retinal Stem Cells in a 3D Hydrogel Culture System

Purpose: Retinal stem cells (RSCs) can be isolated from radial glia population of the newborn mouse retina (Angénieux et al., 2006). These RSCs have great capacity to renew and generate neurons including cells differentiated towards the photoreceptor lineage (Mehri-Soussi et al., 2006). However, our published results showed poor integration and survival rate after cell grafting into the retina. The uncontrollable environment of retina seems to be the problem. To bypass this, we are trying to generate hemi-retinal tissue in vitro that can be used for transplantation. Methods: Expanded RSCs were seeded in a mixture of poly-ethylene-glycol (PEG)-polymer-based hydrogels crosslinked by peptides that also serve as substrates for matrix metalloproteinases. Different doses of crosslinker peptides were tested. Several growth factors were studied to stimulate cell proliferation and differentiation. Results: Cells were trapped in hydrogels and cultured in the presence of FGF2 and EGF. Spherical cell clusters indicating proliferation appeared within several days, but there was no cell migration within the gel. We then added cell adhesion molecules integrin ligand RGDSP, or laminin, or a combination of both, into the gel. Cells grown with laminin showed the best proliferation. Cells grown with RGDSP proliferated a few times and then started to spread out. Cells grown with the combination of RGDSP and laminin showed better proliferation than with RGDSP alone and larger spread-outs than with laminin alone. After stimulations with first FGF2 and EGF, and then only FGF2, some cells showed neuronal morphology after 2 weeks. The neuronal population was assessed by the presence of neuronal marker b-tubulin-III. Glial cells were also present. Further characterizations are undergoing. Conclusions: RSC can grow and migrate in 3D hydrogel with the addition of FGF2, EGF, RGDSP and laminin. Further developments are necessary to form a homogenous tissue containing retinal cells.

Structural characterization of Turtle Mountain anticline (Alberta, Canada) and impact on rock slope failure

his paper proposes a structural investigation of the Turtle Mountain anticline (Alberta, Canada) to better understand the role of the different tectonic features on the development of both local and large scale rock slope instabilities occurring in Turtle Mountain. The study area is investigated by combining remote methods with detailed field surveys. In particular, the benefit of Terrestrial Laser Scanning for ductile and brittle tectonic structure interpretations is illustrated. The proposed tectonic interpretation allows the characterization of the fracturing pattern, the fold geometry and the role of these tectonic features in rock slope instability development. Ten discontinuity sets are identified in the study area, their local variations permitting the differentiation of the study zone into 20 homogenous structural domains. The anticline is described as an eastern verging fold that displays considerable geometry differences along its axis and developed by both flexural slip and tangential longitudinal strain folding mechanisms. Moreover, the origins of the discontinuity sets are determined according to the tectonic phases affecting the region (pre-folding, folding, post-folding). The localization and interpretation of kinematics of the different instabilities revealed the importance of considering the discrete brittle planes of weakness, which largely control the kinematic release of the local instabilities, and also the rock mass damage induced by large tectonic structures (fold hinge, thrust).

Comparison of Methods for Evaluation of the Bactericidal Activity of Copper-Sputtered Surfaces against Methicillin-Resistant Staphylococcus aureus.

Bacteria can survive on hospital textiles and surfaces, from which they can be disseminated, representing a source of health care-associated infections (HCAIs). Surfaces containing copper (Cu), which is known for its bactericidal properties, could be an efficient way to lower the burden of potential pathogens. The antimicrobial activity of Cu-sputtered polyester surfaces, obtained by direct-current magnetron sputtering (DCMS), against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The Cu-polyester microstructure was characterized by high-resolution transmission electron microscopy to determine the microstructure of the Cu nanoparticles and by profilometry to assess the thickness of the layers. Sputtering at 300 mA for 160 s led to a Cu film thickness of 20 nm (100 Cu layers) containing 0.209% (wt/wt) polyester. The viability of MRSA strain ATCC 43300 on Cu-sputtered polyester was evaluated by four methods: (i) mechanical detachment, (ii) microcalorimetry, (iii) direct transfer onto plates, and (iv) stereomicroscopy. The low efficacy of mechanical detachment impeded bacterial viability estimations. Microcalorimetry provided only semiquantitative results. Direct transfer onto plates and stereomicroscopy seemed to be the most suitable methods to evaluate the bacterial inactivation potential of Cu-sputtered polyester surfaces, since they presented the least experimental bias. Cu-polyester samples sputtered for 160 s by DCMS were further tested against 10 clinical MRSA isolates and showed a high level of bactericidal activity, with a 4-log(10) reduction in the initial MRSA load (10(6) CFU) within 1 h. Cu-sputtered polyester surfaces might be of use to prevent the transmission of HCAI pathogens.

Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet.

C57BL/6J mice were fed a high-fat, carbohydrate-free diet (HFD) for 9 mo. Approximately 50% of the mice became obese and diabetic (ObD), approximately 10% lean and diabetic (LD), approximately 10% lean and nondiabetic (LnD), and approximately 30% displayed intermediate phenotype. All of the HFD mice were insulin resistant. In the fasted state, whole body glucose clearance was reduced in ObD mice, unchanged in the LD mice, and increased in the LnD mice compared with the normal-chow mice. Because fasted ObD mice were hyperinsulinemic and the lean mice slightly insulinopenic, there was no correlation between insulin levels and increased glucose utilization. In vivo, tissue glucose uptake assessed by 2-[(14)C]deoxyglucose accumulation was reduced in most muscles in the ObD mice but increased in the LnD mice compared with the values of the control mice. In the LD mice, the glucose uptake rates were reduced in extensor digitorum longus (EDL) and total hindlimb but increased in soleus, diaphragm, and heart. When assessed in vitro, glucose utilization rates in the absence and presence of insulin were similar in diaphragm, soleus, and EDL muscles isolated from all groups of mice. Thus, in genetically homogenous mice, HFD feeding lead to different metabolic adaptations. Whereas all of the mice became insulin resistant, this was associated, in obese mice, with decreased glucose clearance and hyperinsulinemia and, in lean mice, with increased glucose clearance in the presence of mild insulinopenia. Therefore, increased glucose clearance in lean mice could not be explained by increased insulin level, indicating that other in vivo mechanisms are triggered to control muscle glucose utilization. These adaptive mechanisms could participate in the protection against development of obesity.

Status epilepticus: an independent outcome predictor after cerebral anoxia.

BACKGROUND: Prognosis of status epilepticus (SE) depends on its cause, but there is uncertainty as to whether SE represents an independent outcome predictor for a given etiology. Cerebral anoxia is a relatively homogenous severe encephalopathy. Postanoxic SE is associated to a nearly 100% mortality in this setting; however, it is still unclear whether this is a severity marker of the underlying encephalopathy, or an independent factor influencing outcome. The goal of this study was to assess if postanoxic SE is independently associated with mortality after cerebral anoxia. METHODS: This was a retrospective observation of consecutive comatose survivors of cardiac arrest, including subjects treated with hypothermia. On the subgroup with EEG recordings in the first hospitalization days, univariate and multivariate analyses were applied to potential determinants of in-hospital mortality, and included the following variables: age, gender, type and length of cardiac arrest, occurrence of circulatory shock, presence of therapeutic hypothermia, and electrographic SE. RESULTS: Out of 166 postanoxic patients, 107 (64%) had an EEG (median latency from admission, 2 days); in this group, therapeutic hypothermia was administered in 59%. Death occurred in 71 (67%) patients. Postanoxic SE was associated with mortality regardless of type of acute cardiac rhythm and administration of hypothermic treatment. CONCLUSION: In this hospital-based cohort, postanoxic status epilepticus (SE) seems to be independently related to death in cardiac arrest survivors, suggesting that SE might determine a bad prognosis for a given etiology. Confirmation of these results in a prospective assessment is needed.

Insulated retroviral vectors towards safe and efficient genetic modification of stem cells

In otherwise successful gene therapy trials for the treatment of SCID patients and others, insertional mutagenesis has resulted in leukemia development. Besides the integration of vectors that including strong enhancers, more recently, SIN-vectors have been shown to partially retain oncogenic potential. The identification of genetic elements which would both prevent such activation effects and shield the transgene from silencing, is a main challenge. Previous attempts met with difficulties in producing the vectors and poor efficacy of the insulators (GIE). The improvement of integrating vectors safety has been investigated using new candidate synthetic GIEs. The latter have been introduced in retroviral and lentiviral vectors. Native LTRs, SIN-LTRs, and SIN-insulated constructs have been designed and compared, using two sets of internal promoter, i.e. strong and housekeeping. We could establish that a specific insulator translates at best into functional activity and boundary effect in both vector types. We could also determine that other genetic elements are key determinants in order to achieve accurate expression and viral titre, from these insulated vectors. A dramatic shift in the expression profile is observed in target cells, with a homogenous pattern including data on both cell-lines and primary HSCs from cord blood. The assessment of potential genotoxicity will be presented, based on the comparison of the integration patterns ingenuity in human target cells sampled over a three months period with both reference LTRs and SIN versus test insulated vectors, using high-throughput pyro-sequencing.

Fine-scale genetic structure and marginal processes in an expanding population of Biscutella laevigata L. (Brassicaceae).

Evolutionary processes acting at the expanding margins of a species' range are still poorly understood. Genetic drift is considered prevalent in marginal populations, and the maintenance of genetic diversity during recolonization might seem puzzling. To investigate such processes, a fine-scale investigation of 219 individuals was performed within a population of Biscutella laevigata (Brassicaceae), located at the leading edge of its range. The survey used amplified fragment length polymorphisms (AFLPs). As commonly reported across the whole species distribution range, individual density and genetic diversity decreased along the local axis of recolonization of this expanding population, highlighting the enduring effect of the historical colonization on present-day diversity. The self-incompatibility system of the plant may have prevented local inbreeding in newly found patches and sustained genetic diversity by ensuring gene flow from established populations. Within the more continuously populated region, spatial analysis of genetic structure revealed restricted gene flow among individuals. The distribution of genotypes formed a mosaic of relatively homogenous patches within the continuous population. This pattern could be explained by a history of expansion by long-distance dispersal followed by fine-scale diffusion (that is, a stratified dispersal combination). The secondary contact among expanding patches apparently led to admixture among differentiated genotypes where they met (that is, a reshuffling effect). This type of dynamics could explain the maintenance of genetic diversity during recolonization.

Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps

Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Résumé grand public Comme toute matière, la roche est sensible à son environnement et cherche à s'adapter pour acquérir un état stable (état d'équilibre). Les changements des conditions physiques (température et pression) vont ainsi impliquer des modifications dans la roche. Le métamorphisme est l'étude de ces changements. Les minéraux qui constituent la roche peuvent modifier, leur structure, leur chimie ou être remplacer par d'autres minéraux plus stables. Il est ainsi crucial de déterminer les processus responsables et limitant de la croissance minérale. Trois processus permettent la croissance ; (1) la dissolution des éléments du réactant, (2) le transport de ces éléments vers le site de croissance, (3) l'incorporation de ces éléments dans la nouvelle structure. Cette thèse se focalise sur les structures des minéraux de haute pression (forme, zonation chimique, structure interne) pour essayer de déterminer les facteurs importants à l'origine de leur état final. Les zones d'étude se situent dans la zone de Sésia. La première partie traite de la problématique liée à l'incorporation d'un élément dans une structure minérale. A l'image de la croissance humaine, les irrégularités minéralogiques permettent de mettre en lumière un dysfonctionnement de la croissance due à un excès ou à une carence d'un élément. Bien dosé, cet élément est cependant essentiel à la croissance. Les zoisites (épidotes) des métabasites de la région de Cima di Bonze montrent une zonation chimique en sablier. Dans cette zonation la teneur en fer excède la capacité maximum que peut contenir la structure orthorhombique de la zoisite. Des défauts de structure permettent l'accommodation de cet excès. La zoisite peut ainsi adapter sa structure pour permettre l'incorporation d'une relativement grande quantité de fer. Les études précédentes montraient, pour des conditions similaires, la formation de deux épidotes distinctes. La deuxième partie se penche sur la compétition entre le minéral qui fait sa croissance et les minéraux (réactants) qui l'entourent. Les métapélites de la région du Monte Mucrone contiennent des grenats atollaires. Des études détaillées de la texture et de la zonation chimique du grenat ainsi qu'une modélisation thermodynamique ont permis de mieux cerner les facteurs importants responsables de la forme atollaire. Cette structure est obtenue par un changement du comportement de la croissance du grenat le long d'un chemin P-T hercynien. Dans un premier stade, le grenat croît rapidement et consume peu le quartz de la matrice. La croissance se fait ainsi le long des jointures des grains de quartz. Dans un second temps, les changements de conditions PT donnent une croissance lente du grenat et une forte consommation du quartz. Le grenat peut ainsi développer sa forme dodécaédrale classique. La troisième partie s'intéresse aux distances de transport par diffusion d'un élément (ici l'argon) durant la haute pression. Pour ce faire, un profile d'âges 40Ar/39Ar sur biotite a été mesuré depuis un veine de haute pression riche en argon jusque dans son encaissant (granitoïd du Monte Mucrone). Le profile montre une répartition des âges suivant une courbe de diffusion. Le transport se fait sur une longueur de deux centimètre avec l'aide d'un fluide. Il est réduit à une échelle millimétrique quand la phase fluide disparaît. Cette étude montre ainsi les difficultés de transport des éléments durant la haute pression ne permettant pas un rééquilibrage de la roche à grande échelle. Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Résumé de thèse Les processus de croissance (diffusion des éléments et les réactions d'interface) et les conditions dans lesquelles les minéraux grandissent (température, pression, fluide, composition chimique de la roche), déterminent la texture ainsi que la zonation des minéraux. Cette thèse se focalise, par le biais de textures peu communes, sur trois différents processus impliqués dans la croissance minérale à haute pression (Zone de Sésia, Alpes de l'Ouest, Italie). L'incorporation d'un élément dans une structure minérale ne peut se faire que dans des sites en accord avec la taille et la charge ionique de l'élément. De plus, la balance de charge doit être maintenue dans le minéral. La régularité de la structure cristalline fixe ainsi une limite maximum de concentration d'un élément donné. Les zoisites provenant des métabasites de la région de Cima di Bonze montrent des zonations en sablier caractérisées par une concentration anormale en fer. La zonation se marque par une différente teinte de biréfringence et par un plus grand angle d'extinction que le reste de la zoisite. Une inter-croissance de clinozoisite à l'intérieur de la structure orthorhombique de la zoisite peut ainsi être suspectée. Les analyses XRD (diffraction des rayons x) ainsi que les analyses Raman ne confirment pas cette suspicion. Seules les analyses TEM (microscope à électrons transmis) montrent des défauts de structure pouvant être interprétés comme des modules de clinozoisite. Ils ne peuvent cependant pas être considérés comme une phase thermodynamique. Un nouveau trou d'immiscibilité entre deux zoisite (X ep= 0.1 and Xep = 0.15) a ainsi pu être établi. Dans les métapélites la région du Monte Mucrone, des grenats fortement zonés montrent une évolution texturale singulière. Ils présentent une forme initiale de `champignon' qui se développe pour former une structure atollaire finale. L'étude conjuguée de la structure 3D et des zonations, ainsi que l'établissement d'un model thermodynamique, indiquent que ces structures proviennent de deux épisodes de croissances : (1) La croissance du grenat durant un chemin prograde hercynien (de 525 °C et 6.2 kbar à 640 °C et 9 kbar) permet la formation des textures atollaires. Elles sont le résultat d'une croissance poecilitique initiale suivie d'une croissance idiomorphique du grenat. (2) La structure est rendue plus complexe par la cristallisation d'un grenat homogène tout autour ainsi qu'à l'intérieur du grenat hercynien durant la haute pression alpine (550 °C and 20 kbar). L'arrivée de l'eau durant la haute pression facilite le transport d'éléments et permet une cristallisation rapide du grenat. La diffusion peut être un facteur limitant de la croissance minéralogique. Elle a aussi une grande importance pour la géochronologie. Une veine de haute pression à l'intérieur du granitoïde du Monte Mucrone a été étudiée dans le but de déterminer la distance de diffusion de l'argon. Le profile d'âges 40Ar/39Ar sur biotites, établi de la veine vers le métagranitoïde, suit une courbe de diffusion. Les âges sont élevés proche de la veine (800 Ma) puis décroissent jusqu'à des âges homogènes (170-150 Ma) à deux centimètres de la veine. La présence de fluide, marqué par de hautes concentrations en chlore, permet une diffusion centimétrique. Cependant, la distance est réduite à une échelle millimétrique quand le fluide est absent. Les très faibles distances de diffusion préservent les âges pré-alpins et impliquent un événement géologique pour les âges de 170-150 Ma. Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Thesis abstract Rock textures and zonings are the consequence of growth processes (element diffusion and interface reaction) steered by the environment in which they grew (pressure, differential stress, temperature, fluid and rock composition). The thesis presented here focuses on three different topics, each of it dealing with aspects of mineral growth processes during subduction, in a high-pressure environment. All studies were conducted in the Sesia Zone of the Western European Alps, Italy. The first study addresses the crystallography and geochemistry of element incorporation in zoisite, one of the major hydrous minerals found in subduction zone rocks. Elements can be incorporated into a mineral structure only on crystallographic sites that offer enough space for the ion and the overall charge balance has to be maintained. Element concentrations are hence limited. Incorporation of some elements produces complex zoning, including hourglass like patterns, which are the focus of the first contribution. Zoisites from Cima di Bonze (Sesia Zone) show spectacular hourglass zoning defined by Fe-content variations. The hourglass zones have a distinct birefringence and a different extinction angle than the regular part of the zoisite. We show by detailed XRD (X-ray diffraction) and confocal Raman analyses that the high Fe-zones are nevertheless zoisite, and not clinozoisite as one might expect. High resolution TEM (transmission electron microscopy) analyses show planar defects on (100) that can be interpreted as small-scale clinozoisite modules. However, these clinozoisites cannot be interpreted as a distinctive thermodynamic phase and the entire mineral has to be considered as zoisite. The miscibility gap between two zoisites (Xep = 0.1 and Xep = 0.15) can be then definite at 550 ± 50°C and 14 to 20 Kbar. Strongly zoned garnets in quartz rich metapelite from the Monte Mucrone area (Sesia Zone) show evolution form 3D mushroom to atoll structure. The second contribution presents textural investigations, garnet zoning and thermodynamic modeling that demonstrate that atoll garnets are the result of two distinctive growth events. (1) Garnet atoll structure is already formed during a prograde Hercynian path from 525 °C and 6.2 kbar to 640 °C and 9 kbar. It results in an initial poikilitic growth followed by a final idiomorphic growth event. (2) Alpine HP garnet are homogenous (550 °C and 20 kbar) and grew around and also inside the Hercynian garnet. Lack of prograde Alpine garnet and fast growth of the HP garnet is explained by the absence of water during much of the prograde path. Water saturation was only observed towards the end, close towards the peak metamorphic conditions. Diffusion could be a limiting factor for crystal growth. It has also a great importance in geochronology. HP vein inside the metagranitoide of the Monte Mucrone (~300 Ma) was investigated to determine argon diffusion scales during high-pressure metamorphism. 40Ar/39Ar biotite ages profile from the vein toward the metagranodiorite show a diffusion curve: old ages (800 Ma) located close to the vein decrease until homogenous 170-150 Ma ages are obtained, two centimeter away from the vein. Centimeter-scale diffusion occurs with help of a fluid phase marked by high chlorine concentrations. Argon diffusion is reduced to a millimeter scale when free fluid is absent. Very short diffusion distance permits to preserve pre-Alpine ages. The 170-150 Ma ages are considered to be geologic meaningful, probably resulting from the extensional tectonics linked to opening of the Tethian ocean.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

PURPOSE: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity. The authors present here an adaptation of the simple sphere-based model from which cellular level dosimetry for macroscopic tumors and their end point quantities, such as TCP, may be extrapolated more reliably. METHODS: Ten homogenous spheres representing tumors of different sizes were constructed in GEANT4. The radionuclide 131I was randomly allowed to decay for each model size and for seven different ratios of number of decays to number of cells, N(r): 1000, 500, 200, 100, 50, 20, and 10 decays per cell. The deposited energy was collected in radial bins and divided by the bin mass to obtain the average bin absorbed dose. To simulate a cellular model, the number of cells present in each bin was calculated and an absorbed dose attributed to each cell equal to the bin average absorbed dose with a randomly determined adjustment based on a Gaussian probability distribution with a width equal to the statistical uncertainty consistent with the ratio of decays to cells, i.e., equal to Nr-1/2. From dose volume histograms the surviving fraction of cells, equivalent uniform dose (EUD), and TCP for the different scenarios were calculated. Comparably sized spherical models containing individual spherical cells (15 microm diameter) in hexagonal lattices were constructed, and Monte Carlo simulations were executed for all the same previous scenarios. The dosimetric quantities were calculated and compared to the adjusted simple sphere model results. The model was then applied to the Bortezomib-induced enzyme-targeted radiotherapy (BETR) strategy of targeting Epstein-Barr virus (EBV)-expressing cancers. RESULTS: The TCP values were comparable to within 2% between the adjusted simple sphere and full cellular models. Additionally, models were generated for a nonuniform distribution of activity, and results were compared between the adjusted spherical and cellular models with similar comparability. The TCP values from the experimental macroscopic tumor results were consistent with the experimental observations for BETR-treated 1 g EBV-expressing lymphoma tumors in mice. CONCLUSIONS: The adjusted spherical model presented here provides more accurate TCP values than simple spheres, on par with full cellular Monte Carlo simulations while maintaining the simplicity of the simple sphere model. This model provides a basis for complementing and understanding laboratory and clinical results pertaining to radiopharmaceutical therapy.

Total knee arthroplasty - a clinical and numerical study of the micromovements of the tibial implant

Introduction The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant.Material and Methods Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms.The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the microvements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion.Results 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present.Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns).Discussion Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established.Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

Intracisternal delivery of NFκB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFκB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFκB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance viral particles penetration into the brain.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.