Devolatilization-induced pressure build-up: Implications for reaction front movement and breccia pipe formation

Generation of fluids during metamorphism can significantly influence the fluid overpressure, and thus the fluid flow in metamorphic terrains. There is currently a large focus on developing numerical reactive transport models, and with it follows the need for analytical solutions to ensure correct numerical implementation. In this study, we derive both analytical and numerical solutions to reaction-induced fluid overpressure, coupled to temperature and fluid flow out of the reacting front. All equations are derived from basic principles of conservation of mass, energy and momentum. We focus on contact metamorphism, where devolatilization reactions are particularly important owing to high thermal fluxes allowing large volumes of fluids to be rapidly generated. The analytical solutions reveal three key factors involved in the pressure build-up: (i) The efficiency of the devolatilizing reaction front (pressure build-up) relative to fluid flow (pressure relaxation), (ii) the reaction temperature relative to the available heat in the system and (iii) the feedback of overpressure on the reaction temperature as a function of the Clapeyron slope. Finally, we apply the model to two geological case scenarios. In the first case, we investigate the influence of fluid overpressure on the movement of the reaction front and show that it can slow down significantly and may even be terminated owing to increased effective reaction temperature. In the second case, the model is applied to constrain the conditions for fracturing and inferred breccia pipe formation in organic-rich shales owing to methane generation in the contact aureole.

Prevention of atelectasis formation during the induction of general anesthesia in morbidly obese patients

Résumé: La formation des atélectasies durant l'induction de l'anesthésie générale est plus importante chez le patient obèse morbide. Nous avons démontré dans des travaux de recherche antérieurs que l'utilisation de la PEEP (Pression Positive en Fin d'Expiration) durant l'induction de l'anesthésie prévient la formation d'atélectasies chez des patients non obèses. Par conséquent, nous voulions étudier l'efficacité de la pression positive en fin d'expiration chez le patient obèse morbide dans la prévention de la formation d'atélectasies. Nous avons fait une étude de 23 patients obèses morbides (BMI > 35 kg / m2) dans 2 groupes. Dans le groupe utilisant la pression positive en fin d'expiration, les patients respiraient 100% d'oxygène pendant 5 minutes par l'intermédiaire d'un masque facial type CPAP avec une pression de 10 cm H20. Après l'induction de l'anesthésie, nous avons ventilé les patients au masque facial avec une PEEP de 10 cm H20. Dans le groupe de contrôle, nous avons procédé au même type d'induction sans utiliser la pression positive en fin d'expiration. La surface de poumon atélectatique a été évaluée par tomographie (CT scann). L'étude des échanges gazeux se faisait à 2 reprises, à partir de gazométries réalisées juste avant l'induction de l'anesthésie puis juste après l'intubation. Après l'induction de l'anesthésie et l'intubation, les patients du groupe de contrôle présentaient une quantité d'atélectasies plus importante que les patients du groupe où la PEEP avait été utilisée (10.4% + 4.8% dans le groupe de contrôle versus 1.3% dans le groupe utilisant la pression positive en fin d'expiration p < 0.001). Après l'intubation, en présence d'une fraction inspirée en oxygène à 100%, la Pa02 était significativement supérieure dans le groupe ayant utilisé la pression positive en fin d'expiration en comparaison avec le groupe de contrôle (respectivement 457 ± 130 mmHg versus 315 ± 100 mmHg). Nous avons conclu que chez le patient obèse morbide, le recours à la pression positive en fin d'expiration lors de l'induction de l'anesthésie permet de prévenir largement la formation d'atélectasies et s'accompagne d'une meilleure oxygénation. Abstract: Atelectasis caused by general anesthesia is increased in morbidly obese patients. We have shown that application of positive end-expiratory pressure (PEEP) during the induction of anesthesia prevents atelectasis formation in nonobese patients. We therefore studied the efficacy of PEEP in morbidly obese patients to prevent atelectasis. Twenty-three adult morbidly obese patients (b ody mass index >35 kg/m2) were randomly assigned to one of two groups. In the PEEP group, patients breathed 100% oxygen (5 min) with a continuous positive airway pressure of 10 cm H20 and, after the induction, mechanical ventilation via a face mask with a PEEP of 10 cm H2O. In the control group, the same induction was applied but without continuous positive airway pressure or PEEP. Atelectasis, determined by computed tomography, and blood gas analysis were measured twice: before the induction and directly after intubation. After endotracheal intubation, patients of the control group showed an increase in the amount of atelectasis, which was much larger than in the PEEP group (10.4% -± 4.8% in control group versus 1.7% ± 1.3% in PEEP group; P <0.001). After in.tubation with a fraction of inspired oxygen of 1.0, Pao, was significantly higher in the PEEP group compared with the control group (457 ±- 130 mm Hg versus 315 ± 100 mm Hg, respectively; P = 0.035) We conclude that in morbidly obese patients, atelectasis formation is largely prevented by PEEP applied during the anesthetic induction and is associated with a better oxygenation.

Blockade of both alpha1A- and alpha1B-adrenergic receptor subtype signaling is required to inhibit neointimal formation in the mouse femoral artery.

Attenuation of early restenosis after percutaneous coronary intervention (PCI) is important for the successful treatment of coronary artery disease. Some clinical studies have shown that hypertension is a risk factor for early restenosis after PCI. These findings suggest that alpha(1)-adrenergic receptors (alpha(1)-ARs) may facilitate restenosis after PCI because of alpha(1)-AR's remarkable contribution to the onset of hypertension. In this study, we examined the neointimal formation after vascular injury in the femoral artery of alpha(1A)-knockout (alpha(1A)-KO), alpha(1B)-KO, alpha(1D)-KO, alpha(1A)-/alpha(1B)-AR double-KO (alpha(1AB)-KO), and wild-type mice to investigate the functional role of each alpha(1)-AR subtype in neointimal formation, which is known to promote restenosis. Neointimal formation 4 wk after wire injury was significantly (P < 0.05) smaller in alpha(1AB)-KO mice than in any other group of mice, while blood pressures were not altered in any of the groups of mice after wire injury compared with those before it. These results suggest that lack of both alpha(1A)- and alpha(1B)-ARs could be necessary to inhibit neointimal formation in the mouse femoral artery.

Optimisation of the formation and distribution of protoporphyrin IX in the urothelium: an in vitro approach.

PURPOSE: To optimize conditions for photodynamic detection (PDD) and photodynamic therapy (PDT) of bladder carcinoma, urothelial accumulation of protoporphyrin IX (PpIX) and conditions leading to cell photodestruction were studied. MATERIALS AND METHODS: Porcine and human bladder mucosae were superfused with derivatives of 5-aminolevulinic acid (ALA). PpIX accumulation and distribution across the mucosa was studied by microspectrofluorometry. Cell viability and structural integrity were assessed by using vital dyes and microscopy. RESULTS: ALA esters, especially hexyl-ALA, accelerated and regularized urothelial PpIX accumulation and allowed for necrosis upon illumination. CONCLUSIONS: hexyl-ALA used at micromolar concentrations is the most efficient PpIX precursor for PDD and PDT.

A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans.

Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus,we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.

Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.

Sequential analysis of trans-SNARE formation in intracellular membrane fusion.

SNARE complexes are required for membrane fusion in the endomembrane system. They contain coiled-coil bundles of four helices, three (Q(a), Q(b), and Q(c)) from target (t)-SNAREs and one (R) from the vesicular (v)-SNARE. NSF/Sec18 disrupts these cis-SNARE complexes, allowing reassembly of their subunits into trans-SNARE complexes and subsequent fusion. Studying these reactions in native yeast vacuoles, we found that NSF/Sec18 activates the vacuolar cis-SNARE complex by selectively displacing the vacuolar Q(a) SNARE, leaving behind a Q(bc)R subcomplex. This subcomplex serves as an acceptor for a Q(a) SNARE from the opposite membrane, leading to Q(a)-Q(bc)R trans-complexes. Activity tests of vacuoles with diagnostic distributions of inactivating mutations over the two fusion partners confirm that this distribution accounts for a major share of the fusion activity. The persistence of the Q(bc)R cis-complex and the formation of the Q(a)-Q(bc)R trans-complex are both sensitive to the Rab-GTPase inhibitor, GDI, and to mutations in the vacuolar tether complex, HOPS (HOmotypic fusion and vacuolar Protein Sorting complex). This suggests that the vacuolar Rab-GTPase, Ypt7, and HOPS restrict cis-SNARE disassembly and thereby bias trans-SNARE assembly into a preferred topology.

Bilan de santé à 50 ans: formation des médecins praticiens en prévention clinique

En 1994, l'entreprise Ciba SC située à Monthey (canton du Valais, Suisse) a décidé d'élargir ses actions de promotion de la santé en offrant à ses collaborateurs de 50 ans une consultation médicale intitulée "Bilan de santé". 1.1. Historique. 1.2. Prolongation du projet auprès des praticiens. 2. Population et méthodes. 2.1. Médecins et module de formation : Réalisation du "Module de consultation des 50 ans en pratique ambulatoire, remboursement, évaluation du module de formation. 2.2. Collaborateurs des usines de Monthey. 2.3. Réalisation pratique et déroulement de la consultation. 2.4. Evaluation de l'impact du projet. 3. Résultats. 3.1. Participation, habitudes de vie et santé des participants : tabagisme, alimentation, activité physique, alcool, drogues, médicaments, situation de vie et état psychique, prévention routière, vaccinations, hypercholestérolémie, données cliniques, facteurs de risques identifiés et reportés par le médecin. 3.2. Evaluation, l'opinion des patients : satisfaction, conséquences sur les habitudes de vie. 3.3. Evaluation, l'opinion des praticiens : satisfaction, impact et souhaits perçus chez les médecins, déroulement de la consultation, examens de laboratoire, rémunération. 4. Discussion. 5. Conclusion.