Bulles spéculatives et transmission d’information sur le marché d’un bien stockable

Nous étudions l’évolution du prix d’équilibre pour un bien stockable à titre spéculatif. L’impact des différents paramètres structurels sur l’amplitude des bulles spéculatives est mis en évidence. De plus le paramètre auxiliaire lié à la présence d’anticipations rationnelles est interprété comme une mesure de la confiance accordée par les agents à leurs propres anticipations. Lorsque les agents sont différenciés, notamment par le niveau de l’information dont ils disposent, nous montrons que tous les spéculateurs atteignant un seuil d’information forment les mêmes anticipations. De la sorte, on peut caractériser les cas où le marché est efficient.We are interested in the evolution of the equilibrium price of a stockable commodity which can be demanded for speculative purposes. Using a model "à la Grossman", we determine all the possible price evolutions and we analyse the effect of the structural parameters on the growth of speculative bubbles. The model can be extended to the case of agents having diverse informations. It is shown that, if they have a minimal level of information, they form necessarily the same equilibrium price expectations. Then it is possible to characterize the cases where the market is efficient

Bulles spéculatives et transmission d’information sur le marché d’un bien stockable

We are interested in the evolution of the equilibrium price of a stockable commodity which can be demanded for speculative purposes. Using a model "à la Grossman", we determine all the possible price evolutions and we analyse the effect of the structural parameters on the growth of speculative bubbles. The model can be extended to the case of agents having diverse informations. It is shown that, if they have a minimal level of information, they form necessarily the same equilibrium price expectations. Then it is possible to characterize the cases where the market is efficient. Nous étudions l’évolution du prix d’équilibre pour un bien stockable à titre spéculatif. L’impact des différents paramètres structurels sur l’amplitude des bulles spéculatives est mis en évidence. De plus le paramètre auxiliaire lié à la présence d’anticipations rationnelles est interprété comme une mesure de la confiance accordée par les agents à leurs propres anticipations. Lorsque les agents sont différenciés, notamment par le niveau de l’information dont ils disposent, nous montrons que tous les spéculateurs atteignant un seuil d’information forment les mêmes anticipations. De la sorte, on peut caractériser les cas où le marché est efficient.

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Contribution of Host-Derived Tissue Factor to Tumor Neovascularization

The role of host-derived tissue factor (TF) in tumor growth, angiogenesis and metastasis has hitherto been unclear, and was investigated in this study

Perception of isolated chords: Examining frequency of occurrence, instrumental timbre, acoustic descriptors and musical training

This study investigated the perception of isolated chords using a combination of experimental manipulation and exploratory analysis. Twelve types of chord (five triads and seven tetrads) were presented in two instrumental timbres (piano and organ) to listeners who rated the chords for consonance, pleasantness, stability and relaxation. Listener ratings varied by chord, by timbre, and according to musical expertise, and revealed that musicians distinguished consonance from the other variables in a way that other listeners did not. To further explain the data, a principal component analysis and linear regression examined three potential predictors of the listener ratings. First, each chord’s frequency of occurrence was obtained by counting its appearances in selected works of music. Second, listeners rated their familiarity with the instrumental timbre in which the chord was played. Third, chords were described using a set of acoustic features derived using the Timbre Toolbox and MIR Toolbox. Results of the study indicated that listeners’ ratings of both consonance and stability were influenced by the degree of musical training and knowledge of tonal hierarchy. Listeners’ ratings of pleasantness and relaxation, on the other hand, depended more on the instrumental timbre and other acoustic descriptions of the chord

Genetic background determines response to hemostasis and thrombosis

BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5(A/J), B6-Chr11(A/J), and B6-Chr17(A/J), were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5(A/J )and B6-Chr17(A/J), were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. CONCLUSION: These results indicate that susceptibility to arterial thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk

Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system

DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice

A Family of Diverse Kunitz Inhibitors from Echinococcus granulosus Potentially Involved in Host-Parasite Cross-Talk

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (KI*) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection