Socially Conscious Decision Making

For individually motivated agents to work collaboratively to satisfy shared goals, they must make decisions about actions and intentions that take into account their commitments to group activities. This paper examines the role of social consciousness in the process of reconciling intentions to do group-related actions with other, conflicting intentions. We operationalize the notion of social consciousness and provide a first attempt to formally add social consciousness to a cooperative decision-making model. We define a measure of social consciousness; describe its incorporation into the SPIRE experimental system, a simulation environment that allows the process of intention reconciliation in team contexts to be studied; and present results of several experiments that investigate the interaction in decision-making of measures of group and individual good. In particular, we investigate the effect of varying levels of social consciousness on the utility of the group and the individuals it comprises. A key finding is that an intermediate level of social consciousness yields better results in certain circumstances than an extreme commitment. We suggest preliminary principles for designers of collaborative agents based on the results.Engineering and Applied Science

Federal Funding Programs: Benefit-Cost Analyses and Low to Moderate Income Communities

“Global average sea level has risen by about 7-8 inches (about 16-21cm) since 1990, with about 3 of those inches (about 7 cm) occurring since 1993.” Since both the ocean and the atmosphere are getting warmer, global sea levels are projected to rise at an increased rate over the coming centuries. Unsurprisingly, rise in sea level disproportionately negatively impacts coastal communities. For instance, a combination of high magnitude storms and sea level rise causes dangerous flooding to occur farther inland than in the past. Higher sea levels will also cause communities to flood more frequently around high tide even in the absence of precipitation, a phenomenon known as “sunny day flooding.” “In the United States, almost 40 percent of the population lives in relatively high-population-density coastal areas, where sea level plays a role in flooding, shoreline erosion, and hazards from storms.” The aforementioned situation has forced the federal government to take a larger role in ensuring that coastal communities become more “resilient.” Government agencies facilitate this objective by providing federal grants to states and localities or partnering in infrastructure projects to achieve resilience in local communities. To qualify for federal funding, federal agencies require that applicants include a benefit-cost analysis (BCA) in their grant applications, or as part of the project feasibility study. Numerous factors, including the method used to conduct the BCA can influence low to moderate income (LMI) communities’ ability to receive funding. In an effort to shed more light on this issue, this white paper analyzes select federal funding programs of three government agencies: the Federal Emergency Management Agency (FEMA), United States Department of Housing and Urban Development (HUD), and the United States Army Corps of Engineers (USACE). The paper also aims to summarize how these agencies conduct their BCAs, illustrating their similarities and differences; demonstrate how BCAs are used in real-life application through the case studies of City Line Apartments, Chesterfield Heights, and Norfolk and the Lafayette River; provide recommendations to localities on how to more effectively apply for grants or project funding; and lastly, make recommendations on how to better structure federal agencies’ BCAs to ensure that projects involving LMI communities are fairly evaluated. This abstract has been taken from Section I of the paper

Intention Reconciliation in the Context of Teamwork: An Initial Empirical Investigation

With growing opportunities for individually motivated agents to work collaboratively to satisfy shared goals, it becomes increasingly important to design agents that can make intelligent decisions in the context of commitments to group activities. In particular, agents need to be able to reconcile their intentions to do team-related actions with other, conflicting intentions. We present the SPIRE experimental system that allows the process of intention reconciliation in team contexts to be simulated and studied. SPIRE enables us to examine the influence of team norms and environmental factors on team members faced with conflicting intentions, as well as the effectiveness of different intention-reconciliation strategies. We discuss results from pilot experiments that confirm the reasonableness of our model of the problem and illustrate some of the issues involved, and we lay the groundwork for future experiments that will allow us to derive principles for designers of collaboration-capable agents.Engineering and Applied Science

Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer

BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer. METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models. RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model. CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Creating Socially Conscious Agents: Decision-Making in the Context of Group Commitments

With growing opportunities for individually motivated agents to work collaboratively to satisfy shared goals, it becomes increasingly important to design agents that can make intelligent decisions in the context of commitments to group activities. In particular, agents need to be able to reconcile their intentions to do group-related actions with other, conflicting actions. In this thesis, I present the framework for the SPIRE experimental system that al lows the process of intention reconciliation in team contexts to be simulated and studied. I define a measure of social consciousness and show how it can be incorporated into the SPIRE system. Using SPIRE, I then investigate the effect of infinite and limited time horizons on agents with varying levels of social consciousness, as well as the resulting effect on the utility of the group as a whole. Using these experiments as a basis for theoretic conclusions, I suggest preliminary principles for designers of collaborative agents.Engineering and Applied Science