977 resultados para HEISENBERG, WERNER


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Price bubbles in an Arrow-Debreu valuation equilibrium in infinite-timeeconomy are a manifestation of lack of countable additivity of valuationof assets. In contrast, known examples of price bubbles in sequentialequilibrium in infinite time cannot be attributed to the lack of countableadditivity of valuation. In this paper we develop a theory of valuation ofassets in sequential markets (with no uncertainty) and study the nature ofprice bubbles in light of this theory. We consider an operator, calledpayoff pricing functional, that maps a sequence of payoffs to the minimumcost of an asset holding strategy that generates it. We show that thepayoff pricing functional is linear and countably additive on the set ofpositive payoffs if and only if there is no Ponzi scheme, and providedthat there is no restriction on long positions in the assets. In the knownexamples of equilibrium price bubbles in sequential markets valuation islinear and countably additive. The presence of a price bubble indicatesthat the asset's dividends can be purchased in sequential markers at acost lower than the asset's price. We also present examples of equilibriumprice bubbles in which valuation is nonlinear but not countably additive.

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Epigenetic silencing of essential components of DNA repair pathways is a common event in many tumor types, and comprise O6-methylguanine-DNA methyltransferase (MGMT), human mut L homolog 1 (hMLH1), Werner syndrome gene (WRN), breast cancer susceptibility gene 1 (BRCA1), and genes of the Fanconi anemia pathway. Most interestingly, some of these alterations become the Achilles heel of the affected tumors upon treatment with certain classes of anticancer agents. That is, patients whose tumors carry such defects can be stratified for respective therapy rendering some classic DNA damaging agents, such as alkylators or DNA crosslinking agents, into "targeted therapies." Here we review some of the affected repair pathways that, when inactivated, sensitize the tumors to specific drugs and are thus exploitable for individualized therapy.

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This study investigates the intra-individual stability of the speed of several motor tasks and the intensity of associated movements in 256 children (131 girls, 125 boys) from the Zurich generational study using the Zurich neuromotor assessment battery (ZNA) over a 12-year period from the age of 6 to 18 years. The stability was assessed by correlograms of standard deviation scores calculated from age- and gender-adjusted normative values and compared with standing height and full scale intelligence quotient (IQ). While motor tasks of hand, finger and foot (HFT) and contralateral associated movements (CAM) exhibited a moderate stability (summary measure as correlation coefficients between two measurements made 4 years apart: .61 and .60), other tasks (dynamic balance, static balance and pegboard) were only weakly stable (.46, .47 and .49). IQ and height were more stable than neuromotor components (.72 and .86). We conclude that the moderately stable HFT and CAM may reflect "motor traits", while the stability of the pegboard and balance tasks is weaker because these skills are more experience related and state-dependent.

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Evaluating leaf litter beetle data sampled by Winkler extraction from Atlantic forest sites in southern Brazil. To evaluate the reliability of data obtained by Winkler extraction in Atlantic forest sites in southern Brazil, we studied litter beetle assemblages in secondary forests (5 to 55 years after abandonment) and old-growth forests at two seasonally different points in time. For all regeneration stages, species density and abundance were lower in April compared to August; but, assemblage composition of the corresponding forest stages was similar in both months. We suggest that sampling of small litter inhabiting beetles at different points in time using the Winkler technique reveals identical ecological patterns, which are more likely to be influenced by sample incompleteness than by differences in their assemblage composition. A strong relationship between litter quantity and beetle occurrences indicates the importance of this variable for the temporal species density pattern. Additionally, the sampled beetle material was compared with beetle data obtained with pitfall traps in one old-growth forest. Over 60% of the focal species captured with pitfall traps were also sampled by Winkler extraction in different forest stages. Few beetles with a body size too large to be sampled by Winkler extraction were only sampled with pitfall traps. This indicates that the local litter beetle fauna is dominated by small species. Hence, being aware of the exclusion of large beetles and beetle species occurring during the wet season, the Winkler method reveals a reliable picture of the local leaf litter beetle community.

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The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators.

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Abstract

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Recently, using HIV-1-derived lentivectors, we obtained efficient transduction of primary human B lymphocytes cocultured with murine EL-4 B5 thymoma cells, but not of isolated B cells activated by CD40 ligation. Coculture with a cell line is problematic for gene therapy applications or study of gene functions. We have now found that transduction of B cells in a system using CpG DNA was comparable to that in the EL-4 B5 system. A monocistronic vector with a CMV promoter gave 32 +/- 4.7% green fluorescent protein (GFP)+ cells. A bicistronic vector, encoding IL-4 and GFP in the first and second cistrons, respectively, gave 14.2 +/- 2.1% GFP+ cells and IL-4 secretion of 1.3 +/- 0.2 ng/10(5) B cells/24 h. This was similar to results obtained in CD34+ cells using the elongation factor-1alpha promoter. Activated memory and naive B cells were transducible. After transduction with a bicistronic vector encoding a viral FLIP molecule, vFLIP was detectable by FACS or Western blot in GFP+, but not in GFP-, B cells, and 57% of sorted GFP+ B cells were protected against Fas ligand-induced cell death. This system should be useful for gene function research in primary B cells and development of gene therapies.

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