96,174 research outputs found
In Search of a Fair Bet in the Lottery
No full textAlthough state-operated lotto games have the worst average expected payoffs among common games of chance, because the jackpot can accumulate, the maximum expected payoff is potentially unlimited. It is possible, therefore, that lotto can exhibit a positive expected return. This paper examines 18,000 drawings in 34 American lotteries and finds approximately 1% of these drawings provided players with a fair bet. If it were possible for a bettor to purchase every possible combination, however, most lotteries commonly experience circumstances where such a purchase would provide a positive return with 11% of the drawings providing a fair bet to the player.lotto, lottery, public finance, gambling
In Search of a Fair Bet in the Lottery
No full textAlthough state-operated lotto games have the worst average expected payoffs among common games of chance, because the jackpot can accumulate, the maximum expected payoff is potentially unlimited. It is possible, therefore, that lotto can exhibit a positive expected return. This paper examines 18,000 drawings in 34 American lotteries and finds approximately 1 percent of these drawings provided players with a fair bet. If it were possible for a bettor to purchase every possible combination, however, most lotteries commonly experience circumstances where such a purchase would provide a positive return with 11 percent of the drawings providing a fair bet to the player.
IMMUNOTHERAPEUTIC ACTION OF T-BET GENE MODIFIED DENDRITIC CELLS
No full textT-bet is a Type-1 transcription factor that regulates the development of Type-1 T cell and Type-1 anti-tumor immunity. T-bet expression in Dendritic Cells (DC) is required for the ability of these antigen-presenting cells (APC) to prime Type-1-polarized T cell responses. Since T-bet is typically expressed by very low frequencies of activated DC (< 1%), we hypothesized that ectopic expression of T-bet as a consequence of recombinant adenovirus (rAd).T-bet transfection would yield a robust population of DC that were capable of (re)polarizing Type-1 anti-tumor T cell responses in vitro and in vivo. Indeed, human DC engineered to express high levels of T-bet strongly potentiated the development of Type-1 T cells from naïve T cells and concomitantly suppressed Th2 and Regulatory T cell (Treg) development in vitro. Interestingly, the superior Type-1 functionality of DC.Tbet seems to be largely independent of intrinsic Interleukin-12 (IL-12) production, as IL-12 neutralizing antibody failed to affect the Type-1 T cell development driven by DC.Tbet. Furthermore, murine DC.Tbet displayed strong anti-tumor function when delivered into tumor sites as a cancer therapeutic modality. The therapeutic efficacy of mDC.Tbet requires the participation of host NK cells and CD8+ T cells, whose induction was independent of the ability of injected mDC.Tbet to produce IL-12 family member cytokines or IFN-γ, or to migrate to tumor-draining lymph nodes (TDLN) based on CCR7 ligand chemokine recruitment. However, optimal therapeutic protection afforded by i.t. delivered mDC.Tbet did require that the injected DC express MHC class I molecules. Analysis of effectively treated tumors revealed early recruitment/activation of NK cells and naïve T cells in the tumor microenvironment within 2 days of intratumoral delivery of DC.Tbet. Hence, my data support a model in which the injected mDC.Tbet serve as dominant drivers for the extranodal (cross)priming of therapeutic immunity within the tumor microenvironment (TME).
Gene array analyses performed on human DC.Tbet and control DCs (DC.ψ5) derived from 5 healthy donors revealed numerous differentially expressed genes between DC.Tbet and DC.ψ5 that might associate with the Type-1 polarizing function of DC.Tbet.
When taken together, my data suggest that DC.Tbet promote Type-1 anti-tumor immunity through multifaceted cellular and molecular mechanisms
Stability of the Bet v 1 cross-reactive allergens Api g 1 and Dau c 1 : a biophysical approach
No full textThe allergen Bet v 1 is known as the primary sensitizer for birch pollen-related food allergy and is responsible for IgE cross-reactivity to pathogenesis-related 10 (PR-10) proteins from, in particular, fruits from the Rosaceae and vegetables from the Apiaceae families. The allergenic potential of PR-10 proteins is mainly characterized for specific recombinantly produced isoforms, which are used for research and diagnostic purposes. However, in natural food sources these allergens are often present as isoform mixtures. The first aim of this research was to purify and characterize PR-10 allergens as natural isoform mixtures to determine whether differences could be observed between natural and recombinant allergens and between plant families. The second aim was to find a relationship between the physico-chemical stability of PR-10 proteins and structural characteristics to explain differences in IgE binding potential and cross-reactivity. The PR-10 allergens Bet v 1 from birch, Api g 1 from celery, and Dau c 1 from carrot were purified under mild conditions following a standardized protocol. Different allergen isoforms were determined and circular dichorism (CD) analyses of the allergen mixtures showed a similar secondary structure composition as observed for other PR-10 proteins. The allergen mixtures and recombinant allergens were characterized by stability studies to pH, temperature and denaturant where CD was used to detect structural changes. Minor differences were observed in stability between natural isoform mixtures and between the recombinant isoforms, although recombinant Dau c 1 was likely destabilized by its attached His-tag. A general trend was observed for allergen stability, structural differences and their relationship to the IgE binding capacity in aqueous solutions. The allergenic potential decreases in the following order: Bet v 1, the primary allergen of birch pollen-related allergies, Mal d 1, Api g 1 and Dau c 1, in accordance with their amino acid sequence identity. Bet v 1 cross-reactive IgE antibodies preferably bind to the charged and polar residues of Mal d 1 for which the positive charge can be increased by the physiological pH of fruit. Api g 1 appears to be more stable than Dau c 1 as the result of a tighter hydrophobic packing. However, the thermodynamic stability of Api g 1 is similar to that of Bet v 1, but the higher proportion of hydrophobic residues and the reduced proportion of charged residues are responsible for the lower IgE binding capacity. Furthermore, the IgE binding capacity is not severely affected, as long as the protein is able to refold. The implications of these findings are discussed in the context of the development of allergic symptoms upon exposure to these PR-10 proteins. <br/
I-BET-762 treatment suppresses AHR and inflammatory cell infiltration in RSV-induced exacerbation.
No full textBALB/c mice were sensitised i.p with OVA or PBS plus alum on day 0 and exposed to OVA aerosol on days 13–16. Some mice were inoculated with RSV on day 19 and treated with I-BET-762 or vehicle (hydroxyl-β cyclodextrin) i.v twice on day 23. Lung function and airway inflammation were assessed on day 24. (A) AHR lung assessments, (B) viral copies in total lung tissue and (C) total BALF cell counts. Differential microscopy counts for macrophages (D), neutrophils (E) eosinophils (F), and lymphocyte (G) performed by light microscopy. n = 6–8 mice per group, presented as mean ± SEM. *Designates significant differences to PBS-treated controls (*P#Designates significant differences from OVA/RSV/I-BET-762-treated mice (#P##P<0.01).</p
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