A structural and metamorphic study of the southern Menderes Massif (Western Turkey)

P-T conditions, paragenetic studies and the relation between mineral growth, deformation and - when possible- isograd minerals have been used to describe the type of metamorphism involved within lower units of the southern Menderes Massif of the Anatolide Belt in western Turkey. The study areas mainly consist of Proterozoic orthogneiss and surrounding schists of presumed Paleozoic age. Both units are seen as nappes in the southern study area, the Çine and the Selimiye nappe, on the whole corresponding to Proterozoic orthogneiss and surrounding schists, respectively. The Çine and Selimiye nappes are part of a complex geological structure within the core series of the Menderes Massif. Their emplacement under lower greenschist facies conditions, would result from closure of the northern Neo-Thethys branch during the Eocene. These two nappes are separated by a major tectonic structure, the Selimiye shear zone, which records top-to-the-S shearing under greenschist facies conditions. Amphibolite to upper amphibolite facies metamorphism is widely developed within the metasedimentary rocks of the Çine nappe whereas no metamorphism exceeding lower amphibolite facies has been observed in the Selimiye nappe. In the southern margin of the Çine Massif, around Selimiye and Millas villages, detailed sampling has been undertaken in order to map mineral isograds within the Selimiye nappe and to specify P-T conditions in this area. The data collected in this area reveals a global prograde normal erosion field gradient from south to north and toward the orthogneiss. The mineralogical parageneses and P-T estimates are correlated with Barrovian-type metamorphism. A jump of P-T conditions across the Selimiye shear zone has been identified and estimated c. 2 kbar and 100 °C which evidences the presence of amphibolite facies metasedimentary rocks near the orthogneiss. Metasedimentary rocks from the overlying Selimiye nappe have maximum P-T conditions of c. 4-5 kbar and c. 525 °C near the base of the nappe. Metasedimentary rocks from the Çine nappe underneath the Selimiye shear zone record maximum P-T conditions of about 7 kbar and >550 °C. Kinematic indicators in both nappes consistently show a top-S shear sense. Metamorphic grade in the Selimiye nappe decreases structurally upwards as indicated by mineral isograds defining the garnet-chlorite zone at the base, the chloritoid-biotite zone and the biotite-chlorite zone at the top of the nappe. The mineral isograds in the Selimiye nappe run parallel to the regional SR foliation. 40Ar/39Ar mica ages indicate an Eocene age of metamorphism in the Selimiye nappe and underneath the Çine nappe in this area. Metasedimentary rocks of the Çine nappe 20-30 km north of the Selimiye shear zone record maximum P-T conditions of 8-11 kbar and 600-650 °C. Kinematic indicators show mainly top-N shear sense associated with prograde amphibolite facies metamorphism. An age of about 550 Ma could be indicated for amphibolite facies metamorphism and associated top-N shear in the orthogneiss and metasedimentary rocks of the Çine nappe. However, there is no evidence for polymetamorphism in the 6 metasedimentary rocks of the Çine nappe, making tectonic interpretations about late Neoproterozoic to Cambrian and Tertiary metamorphic events speculative. In the western margin of the Çine Massif metamorphic mineral parageneses and pressure– temperature conditions lead to similar conclusion regarding the erosion field gradient, prograde normal toward the orthogneiss. The contact between orthogneiss and surrounding metasedimentary rocks is mylonitic and syn-metamorphism. P-T estimates are those already observed within the Selimiye nappe and correlated with lower amphibolite facies parageneses. Finally additional data in the eastern part and a general paragenetic study within the Menderes Massif lower units, the Çine and the Selimiye nappes, strongly suggest a single Barrovian-type metamorphism predating Eocene emplacement of the high pressure–low temperature Lycean and Cycladic blueschist nappes. Metamorphic mineral parageneses and pressure–temperature conditions do not support the recently proposed model of high pressure–low temperature metamorphic overprinting, which implies burial of the lower units of the Menderes Massif up to depth of 30 km, as a result of closure of the Neo-Tethys. According to the geochronological problem outlined during this thesis, there are two possible schemes: either Barrovian-type metamorphism is Proterozoic in age and part of the sediments from Selimiye nappe (lower amphibolite facies) has to be proterozoic of age too, or Barrovian-type metamorphism in Eocene of age. In the first case the structure observed now in the core series would correspond to simple exhumation of Proterozoic basement. In the latter case a possible correlation with closure of Neo-Tethys (sensu stricto, southern branch) is envisaged.

Multimethodological study of molecular recognition phenomena

The study of the bio-recognition phenomena behind a biological process is nowadays considered a useful tool to deeply understand physiological mechanisms allowing the discovery of novel biological target and the development of new lead candidates. Moreover, understanding this kind of phenomena can be helpful in characterizing absorption, distribution, metabolism, elimination and toxicity properties of a new drug (ADMET parameters). Recent estimations show that about half of all drugs in development fail to make it to the market because of ADMET deficiencies; thus a rapid determination of ADMET parameters in early stages of drug discovery would save money and time, allowing to choose the better compound and to eliminate any losers. The monitoring of drug binding to plasma proteins is becoming essential in the field of drug discovery to characterize the drug distribution in human body. Human serum albumin (HSA) is the most abundant protein in plasma playing a fundamental role in the transport of drugs, metabolites and endogenous factors; so the study of the binding mechanism to HSA has become crucial to the early characterization of the pharmacokinetic profile of new potential leads. Furthermore, most of the distribution experiments carried out in vivo are performed on animals. Hence it is interesting to determine the binding of new compounds to albumins from different species to evaluate the reliability of extrapolating the distribution data obtained in animals to humans. It is clear how the characterization of interactions between proteins and drugs determines a growing need of methodologies to study any specific molecular event. A wide variety of biochemical techniques have been applied to this purpose. High-performance liquid affinity chromatography, circular dichroism and optical biosensor represent three techniques that can be able to elucidate the interaction of a new drug with its target and with others proteins that could interfere with ADMET parameters.

Expériences du sacré et (dé)figurations du Christ. Artaud, Beckett, Pasolini

« Dieu est mort » proclame à l’envi le fou nietzschéen. C’est sous l’égide inquiète de cette assertion paroxystique, traduisant ce «malaise de la culture» qu’évoquait Freud, que la pensée, la littérature et l’art du XXe siècle européen évoluent. Cependant, le christianisme dont ce cri signe l’extrême décadence, n’est pas seul à imprégner les productions artistiques de ce siècle, même les plus prétendument athées, mais avant tout la figure du Christ - autour de laquelle sont structurés tant cette religion que son système de croyance – semble, littéralement et paradoxalement, infester l’imaginaire du XXe siècle, sous des formes plus ou moins fantasmatiques. Ce travail se propose ainsi précisément d’étudier, dans une optique interdisciplinaire entre littérature, art et cinéma, cette dynamique controversée, ses causes, les processus qui la sous-tendent ainsi que ses effets, à partir des œuvres de trois auteurs : Artaud, Beckett et Pasolini. L’objectif est de fournir une clé de lecture de cette problématique qui mette en exergue comment « la conversion de la croyance », comme la définit Deleuze, à laquelle ces auteurs participent, n’engendre pas un rejet purement profanatoire du christianisme mais, à l’inverse, la mise en œuvre d’un mouvement aussi violent que libératoire qualifié par Nancy de « déconstruction du christianisme ». Ce travail entend donc étudier tout d’abord à la lumière de l’expérience intérieure de Bataille, l’imaginaire christique qui sous-tend leurs productions ; puis, d’en analyser les mouvements et les effets en les questionnant sur la base de cette dynamique ambivalente que Grossman nomme la « défiguration de la forme christique ». Les excès délirants d’Artaud, l’ironie tranchante de Beckett et la passion ambiguë de Pasolini s’avèrent ainsi participer à un mouvement commun qui, oscillant entre reprise et rejet, débouche sur une attitude tout aussi destructive que revitalisante des fondements du christianisme.

Repetitive behaviours in patients with Gilles de la Tourette syndrome: tics, compulsions, or both?

Background Repetitive behaviours (RB) in patients with Gilles de la Tourette syndrome (GTS) are frequent. However, a controversy persists whether they are manifestations of obssessive-compulsive disorder (OCD) or correspond to complex tics. Methods 166 consecutive patients with GTS aged 15–68 years were recruited and submitted to extensive neurological, psychiatric and psychological evaluations. RB were evaluated by the YBOCS symptom checklist and Mini International Neuropsychiatric Interview (M.I.N.I), and classified on the basis of a semi-directive psychiatric interview as compulsions or tics. Results RB were present in 64.4% of patients with GTS (107/166) and categorised into 3 major groups: a ‘tic-like’ group (24.3%–40/166) characterised by RB such as touching, counting, ‘just right’ and symmetry searching; an ‘OCD-like’ group (20.5%–34/166) with washing and checking rituals; and a ‘mixed’ group (13.2%–22/166) with both ‘tics-like’ and ‘OCD-like’ types of RB present in the same patient. In 6.3% of patients, RB could not be classified into any of these groups and were thus considered ‘undetermined’. Conclusions The results confirm the phenomenological heterogeneity of RB in GTS patients and allows to distinguish two types: tic-like behaviours which are very likely an integral part of GTS; and OCD-like behaviours, which can be considered as a comorbid condition of GTS and were correlated with higher score of complex tics, neuroleptic and SSRIs treatment frequency and less successful socio-professional adaptation. We suggest that a meticulous semiological analysis of RB in GTS patients will help to tailor treatment and allow to better classify patients for future pathophysiologic studies. Trial Registration ClinicalTrials.gov NCT00169351

A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms

Background Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. Methodology/Principal Findings We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. Conclusions/Significance IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.

Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions

The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4.

A 5-year comparison of performance of sentinel and mandatory notification surveillance systems for measles in Switzerland

A sensitive, specific and timely surveillance is necessary to monitor progress towards measles elimination. We evaluated the performance of sentinel and mandatory-based surveillance systems for measles in Switzerland during a 5-year period by comparing 145 sentinel and 740 mandatory notified cases. The higher proportion of physicians who reported at least one case per year in the sentinel system suggests underreporting in the recently introduced mandatory surveillance for measles. Accordingly, the latter reported 2-36-fold lower estimates for incidence rates than the sentinel surveillance. However, these estimates were only 0.6-12-fold lower when we considered confirmed cases alone, which indicates a higher specificity of the mandatory surveillance system. In contrast, the sentinel network, which covers 3.5% of all outpatient consultations, detected only weakly and late a major national measles epidemic in 2003 and completely missed 2 of 10 cantonal outbreaks. Despite its better timeliness and greater sensitivity in case detection, the sentinel system, in the current situation of low incidence, is insufficient to perform measles control and to monitor progress towards elimination.