Virtual Las Vegas: Regulate or Prohibit?

With online gambling becoming increasingly accessible and popular, state and federal politicians are asking themselves how to make the prohibition on online gambling effective. Nevertheless, questions still linger as to whether outright prohibition is truly the right answer

Internet Securities Fraud: Old Trick, New Medium

Billions of securities are traded every day in public and private markets around the world. This practice is hundreds of years old and as long as securities have been traded, someone has tried to defraud the system to make a quick buck. With the advent of the Internet, new securities fraud schemes have appeared

Roots to Reasons: A Podcast Series - Emotional, Intellectual, & Substantive Environmental Conversations

As six students of the Resources and Sustainability Global Theme of the Franke GLI program our capstone project addresses the need for emotional, intellectual and substantive environmental conversations, a lack thereof we all have observed in our studies and daily lives. We conducted research of scholarly sources that found experience, upbringing, biases, and emotions are influencers of a person’s attitude and behavior toward the environment and climate change. Attitude is expressed through a person’s morals that inform behavior. The topics of environment and climate change are largely interpreted and expressed through pathos, which is easily manipulated by social media, marketing, and news sources. The second half of our research focused on conversation and interview techniques that would help us discuss these influences with others and learn how they manifest themselves in individuals\u27 lives. Finding agreement, listening intently, providing a safe atmosphere, creating rapport, being cognisant of pacing, tone, and emotions are crucial to conducting an emotionally, politically, or personally challenging conversation. We compiled our sources into a literature review that identifies what shapes a person’s relationship with the environment and climate change and how to hold conversations about these topics. The culmination of work is a podcast series, “Roots to Reason,” that models these environmental conversations. We conducted nine conversations with individuals such as ranchers, professors, small business owners and tribal members about their upbringing and relationship with the environment and climate change. These conversations were analyzed and synthesized into a podcast format to deliver conversation models to scholars and laymen. Not considering the background that shapes an individual’s morals, attitudes, and behaviors impedes productivity and collaboration that is critical to solving environmental challenges. This project models how differing backgrounds can cooperate from a place of mutual understanding and acceptance

The European Forest and Agriculture Optimisation Model -- EUFASOM

Land use is a key factor to social wellbeing and has become a major component in political negotiations. This paper describes the mathematical structure of the European Forest and Agricultural Sector Optimization Model. The model represents simultaneously observed resource and technological heterogeneity, global commodity markets, and multiple environmental qualities. Land scarcity and land competition between traditional agriculture, forests, nature reserves, pastures, and bioenergy plantations is explicitly captured. Environmental change, technological progress, and policies can be investigated in parallel. The model is well-suited to estimate competitive economic potentials of land based mitigation, leakage, and synergies and trade-offs between multiple environmental objectives.Land Use Change Optimization, Resource Scarcity, Market Competition, Welfare Maximization, Bottom-up Partial Equilibrium Analysis, Agricultural Externality Mitigation, Forest Dynamics, Global Change Adaptation, Environmental Policy Simulation, Integrated Assessment, Mathematical Programming, GAMS

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins

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

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