59 research outputs found

    Pozorišta u Vojvodini i u Srbiji od 1733. do 1874.

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    "Gajeći u prvom redu naš nacionalan repertoar, pozorišta su bila večita straža ideje našeg oslobođenja. I pored dužnosti da naš narod upoznaju s našom istorijom, naša su pozorišta, dajući predstave i iz hrvatskih narodnih komada, budila svest zbliženja i bratstva s Hrvatima. Takvim radom, pozorišta u Vojvodini i Srbiji, učinila su dakle mnogo, i ona su potpuno opravdala svoj zadatak u starije doba.

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Predicting Salesforce Reactions to New Territory Design According to Equity Theory Propositions

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    This paper analyzes the various parameters that affect the design of fair sales territories. Among these parameters are the effects of age, seniority, compensation schemes, and market structure. Since human motivation plays a part, there is considerable complexity in modeling the parameters

    Sales management : concepts and cases, 10th ed./ Cron

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    xix, 345 hal,; 25 cm

    Solving the Supply Shortage at ICC India

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    Sales management : concepts and cases, 10th ed./ Cron

    No full text
    xix, 345 hal,; 25 cm

    A maximum likelihood methodology for clusterwise linear regression

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    This paper presents a conditional mixture, maximum likelihood methodology for performing clusterwise linear regression. This new methodology simultaneously estimates separate regression functions and membership in K clusters or groups. A review of related procedures is discussed with an associated critique. The conditional mixture, maximum likelihood methodology is introduced together with the E-M algorithm utilized for parameter estimation. A Monte Carlo analysis is performed via a fractional factorial design to examine the performance of the procedure. Next, a marketing application is presented concerning the evaluations of trade show performance by senior marketing executives. Finally, other potential applications and directions for future research are identified.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45937/1/357_2005_Article_BF01897167.pd

    Sales management: Concepts and cases

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    xix+345hlm.;25c
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