Continuous Equilibrium in Affine and Information-Based Capital Asset Pricing Models

We consider a class of generalized capital asset pricing models in continuous time with a finite number of agents and tradable securities. The securities may not be sufficient to span all sources of uncertainty. If the agents have exponential utility functions and the individual endowments are spanned by the securities, an equilibrium exists and the agents' optimal trading strategies are constant. Affine processes, and the theory of information-based asset pricing are used to model the endogenous asset price dynamics and the terminal payoff. The derived semi-explicit pricing formulae are applied to numerically analyze the impact of the agents' risk aversion on the implied volatility of simultaneously-traded European-style options.Comment: 24 pages, 4 figure

Proučavanje 194Ir uhvatom termičkih neutrona I (d, p) reakcijom

Levels of 194Ir were studied using thermal neutron capture reaction. A pair spectrometer was used to measure the high-energy γ-ray spectrum from thermal-neutron capture in enriched 193Ir target over the energy range 4640 - 6100 keV. The low-energy γ-radiation from the reaction was studied with crystal diffraction spectrometers, and conversion electrons were observed with magnetic spectrometers. The high-sensitivity measurements at the Grenoble reactor, evaluated for transition energies up to 500 keV, are compared with lower-sensitivity measurements at the Wuerenlingen and Salaspils reactors. The comparison helped to obtain reliable isotopic identification for a number of 194Ir lines. The multipolarity admixtures for 29 γ-transitions were determined on the basis of conversion lines from different electron subshells. Prompt and delayed γ-γ coincidences were measured using semiconductor and scintillation detectors. The 193Ir(d,p) high-resolution spectra, observed with a magnetic spectrometer, are given. All these data contributed to establishing a detailed level scheme of 194Ir. Additional data and the interpretation of the results in terms of current models will be presented in a forthcoming paper.Proučavala su se stanja u 194Ir reakcijama 193Ir(n, γ) i 193Ir(d, p). Mjerenja uhvata termičkih neutrona načinjena su uz reaktore u Grenoblu, Wuerenlingenu i Salapsisu. Za mjerenja γ-zračenja visoke energije upotrebljavao se spektrometar parova, a za niske energije difraktometar. Konverzijske elektrone se mjerilo magnetskim spektrometrom. Mjerenja reakcije (d, p) visokog razlučivanja izvedena su magnetskim spektrometrom. Usporedbe tih mjerenja omogućile su pouzdano izotopno prepoznavanje prijelaza u 194 Ir, a spektri konverzijskih elektrona i određivanje multipolnosti prijelaza. Dobiveni su podaci osnova sheme raspada 194Ir

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands

Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule - CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage

Proteomic Identification of IPSE/alpha-1 as a Major Hepatotoxin Secreted by Schistosoma mansoni Eggs

The flatworm disease, schistosomiasis, is a major public health problem in sub-Saharan Africa, South America and East Asia. A hallmark of infection with Schistosoma mansoni is the immune response to parasite eggs trapped in the liver and other organs. This response involves an infiltration of cells that surround the parasite egg forming a “granuloma.” In mice deprived of T-cells, this granulomatous response is lacking, and toxic products released by eggs quickly cause liver damage and death. Thus the granulomata protect the host from toxic egg products. Only one hepatotoxic molecule, omega-1, has been described to date. We set out to identify other S. mansoni egg hepatotoxins using liver cells grown in culture. We first showed that live eggs, their secretions, and pure omega-1 are toxic. Using a physical separation technique to prepare fractions from whole egg secretions, we identified the presence of IPSE/alpha-1, a protein that is known to strongly influence the immune system. We showed that IPSE/alpha-1 is also hepatotoxic, and that toxicity of both omega-1 and IPSE/alpha-1 can be prevented by first mixing the proteins with specific neutralizing antibodies. Both proteins constitute the majority of hepatotoxicity released by eggs

A Novel Metagenomic Short-Chain Dehydrogenase/Reductase Attenuates Pseudomonas aeruginosa Biofilm Formation and Virulence on Caenorhabditis elegans

In Pseudomonas aeruginosa, the expression of a number of virulence factors, as well as biofilm formation, are controlled by quorum sensing (QS). N-Acylhomoserine lactones (AHLs) are an important class of signaling molecules involved in bacterial QS and in many pathogenic bacteria infection and host colonization are AHL-dependent. The AHL signaling molecules are subject to inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N-acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report on the identification and structural characterization of the first NADP-dependent short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and derived from a metagenome library. The corresponding gene was isolated from a soil metagenome and designated bpiB09. Heterologous expression and crystallographic studies established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not the native substrate of this metagenome-derived enzyme, its expression in P. aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans. Furthermore, a genome-wide transcriptome study suggested that the level of lasI and rhlI transcription together with 36 well known QS regulated genes was significantly (≥10-fold) affected in P. aeruginosa strains expressing the bpiB09 gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools for the development of quorum quenching strategies

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system