True happiness: The role of morality in the folk concept of happiness

Recent scientific research has settled on a purely descriptive definition of happiness that is focused solely on agents’ psychological states (high positive affect, low negative affect, high life satisfaction). In contrast to this understanding, recent research has suggested that the ordinary concept of happiness is also sensitive to the moral value of agents’ lives. Five studies systematically investigate and explain the impact of morality on ordinary assessments of happiness. Study 1 demonstrates that moral judgments influence assessments of happiness not only for untrained participants, but also for academic researchers and even in those who study happiness specifically. Studies 2 and 3 then respectively ask whether this effect may be explained by general motivational biases or beliefs in a just world. In both cases, we find evidence against these explanations. Study 4 shows that the impact of moral judgments cannot be explained by changes in the perception of descriptive psychological states. Finally, Study 5 compares the impact of moral and non-moral value, and provides evidence that unlike non-moral value, moral value is part of the criteria that govern the ordinary concept of happiness. Taken together, these studies provide a specific explanation of how and why the ordinary concept of happiness deviates from the definition used by researchers studying happiness

Statutes of Limitations and Personal Identity

Legal theorists have proposed several theories to justify statutes of limitations in the criminal law, but none of these normative theories is generally accepted. This chapter investigates the related descriptive question as to whether ordinary people have the intuition that legal punishment becomes less appropriate as time passes from the date of the offense and, if they do, what factors play a role in these intuitions. Five studies demonstrate that there is an intuitive statute of limitations on both legal punishment and moral criticism, and that these intuitions arise, in part, from judgments about changes in psychological connectedness over time

Socially-distributed cognition and cognitive architectures: towards an ACT-R-based cognitive social simulation capability

ACT-R is one of the most widely used cognitive architectures, and it has been used to model hundreds of phenomena described in the cognitive psychology literature. In spite of this, there are relatively few studies that have attempted to apply ACT-R to situations involving social interaction. This is an important omission since the social aspects of cognition have been a growing area of interest in the cognitive science community, and an understanding of the dynamics of collective cognition is of particular importance in many organizational settings. In order to support the computational modeling and simulation of socially-distributed cognitive processes, a simulation capability based on the ACT-R architecture is described. This capability features a number of extensions to the core ACT-R architecture that are intended to support social interaction and collaborative problem solving. The core features of a number of supporting applications and services are also described. These applications/services support the execution, monitoring and analysis of simulation experiments. Finally, a system designed to record human behavioral data in a collective problem-solving task is described. This system is being used to undertake a range of experiments with teams of human subjects, and it will ultimately support the development of high fidelity ACT-R cognitive models. Such models can be used in conjunction with the ACT-R simulation capability to test hypotheses concerning the interaction between cognitive, social and technological factors in tasks involving socially-distributed information processing

Blanket Guarantees Survey

This paper surveys 10 blanket guarantee (BG) programs across 13 Key Design Decisions. The defining characteristics of these programs in terms of their inclusion in our BG series are (a) that they guaranteed a broader range of liabilities beyond deposit accounts and (b) that the guarantees covered existing liabilities in addition to newly issued ones. Each case represents an effort to eliminate creditors’ incentive to withdraw funding from institutions by guaranteeing that the funding will be paid back even if the institutions are unable to do so themselves. The main themes that emerge are: (a) the inability of blanket guarantees to address underlying problems without complementary liquidity support and restructuring measures; (b) the importance of credibility, particularly as related to the amount of liabilities guaranteed relative to fiscal resources; (c) the need to address the moral hazards that a blanket guarantee creates, by restricting banks’ behavior during the acute phase of a crisis—for example, through interest-rate caps or bans on aggressive marketing—and by promising to increase official supervisory oversight as the crisis extends into its chronic phase; (d) the importance of effective communication; and (e) the importance of clear political support for a program that represents potentially substantial fiscal costs, which authorities may be unable to quantify at the time of the announcement

Survey of Resolution and Restructuring in Europe: Pre- and Post-BRRD

This paper surveys 19 case studies of bank resolutions and restructurings across 15 Key Design Decisions. It focuses on interventions that occurred in Europe both in the years leading up to the adoption of the Bank Recovery and Resolution Directive (BRRD) in 2014 (when many jurisdictions were constrained by a lack of legal authority) and in the years after the BRRD was in place. The main themes that emerge are: (a) the need for resolution and restructuring to eliminate uncertainty about an institution’s solvency by closing it, recapitalizing it, or merging it with a healthier institution; (b) the importance of effective valuation in achieving this result; (c) the necessity of clarity in the treatment of creditors; and (d) the value of a credible bail-in tool to incentivize creditors to agree to solutions outside of resolution

Dynamical fluctuations for semi-Markov processes

We develop an Onsager-Machlup-type theory for nonequilibrium semi-Markov processes. Our main result is an exact large time asymptotics for the joint probability of the occupation times and the currents in the system, establishing some generic large deviation structures. We discuss in detail how the nonequilibrium driving and the non-exponential waiting time distribution influence the occupation-current statistics. The violation of the Markov condition is reflected in the emergence of a new type of nonlocality in the fluctuations. Explicit solutions are obtained for some examples of driven random walks on the ring.Comment: Minor changes, accepted for publication in Journal of Physics

Cellular inhibitor of apoptosis 1 (cIAP-1) degradation by caspase 8 during TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.

TNF-related apoptosis-inducing ligand (TRAIL) is a potential chemotherapeutic agent with high selectivity for malignant cells. Many tumors, however, are resistant to TRAIL cytotoxicity. Although cellular inhibitors of apoptosis 1 and 2 (cIAP-1 and -2) are often over-expressed in cancers, their role in mediating TRAIL resistance remains unclear. Here, we demonstrate that TRAIL-induced apoptosis of liver cancer cells is associated with degradation of cIAP-1 and X-linked IAP (XIAP), whereas cIAP-2 remains unchanged. Lower concentrations of TRAIL causing minimal or no apoptosis do not alter cIAP-1 or XIAP protein levels. Silencing of cIAP-1 expression, but not XIAP or cIAP-2, as well as co-treatment with a second mitochondrial activator of caspases (SMAC) mimetic (which results in rapid depletion of cIAP-1), sensitizes the cells to TRAIL. TRAIL-induced loss of cIAP-1 and XIAP requires caspase activity. In particular, caspase 8 knockdown stabilizes both cIAP-1 and XIAP, while caspase 9 knockdown prevents XIAP, but not cIAP-1 degradation. Cell-free experiments confirmed cIAP-1 is a substrate for caspase 8, with likely multiple cleavage sites. These results suggest that TRAIL-mediated apoptosis proceeds through caspase 8-dependent degradation of cIAP-1. Targeted depletion of cIAP-1 by SMAC mimetics in conjunction with TRAIL may be beneficial for the treatment of human hepatobiliary malignancies

miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma.

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of miR-25 in culture sensitized cells to apoptotic death. Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential novel miR-25 target, and this prediction was confirmed by immunoblot, cell staining, and reporter assays. CONCLUSION: These data implicate elevated miR-25 levels in the control of tumor cell apoptosis in cholangiocarcinoma. The identification of the novel miR-25 target DR4 provides a mechanism by which miR-25 contributes to evasion of TRAIL-induced cholangiocarcinoma apoptosis

A smac mimetic reduces TNF related apoptosis inducing ligand (TRAIL)-induced invasion and metastasis of cholangiocarcinoma cells.

UNLABELLED: Cholangiocarcinoma (CCA) cells paradoxically express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand that, failing to kill CCA cells, instead promotes their tumorigenicity and especially the metastatic behaviors of cell migration and invasion. Second mitochondria-derived activator of caspase (smac) mimetics are promising cancer therapeutic agents that enhance proapoptotic death receptor signaling by causing cellular degradation of inhibitor of apoptosis (IAP) proteins. Our aim was to examine the in vitro and in vivo effects of the smac mimetic JP1584 in CCA. Despite JP1584-mediated loss of cellular inhibitor of apoptosis-1 (cIAP-1) and cIAP-2, TRAIL failed to induce apoptosis in KMCH-1, TFK-1, and BDEneu CCA cells; a finding consistent with a downstream block in death signaling. Because cIAP-1 and cIAP-2 also promote nuclear factor kappa B (NF-kappaB) activation by the canonical pathway, the effect of JP1584 on this signaling pathway was examined. Treatment with JP1584 inhibited TRAIL-induced NF-kappaB activation as well as TRAIL-mediated up-regulation of the NF-kappaB target gene, matrix metalloproteinase 7 (MMP7). JP1584 also reduced TRAIL-mediated CCA cell migration and invasion in vitro. Finally, in a syngeneic rat orthotopic CCA model, JP1584 administration reduced MMP7 messenger RNA levels and extrahepatic metastases. CONCLUSION: : Although the smac mimetic JP1584 does not sensitize cells to apoptosis, it reduces TRAIL-induced CCA cell metastatic behavior. These data support the emerging concept that IAPs are prometastatic and represent targets for antimetastatic therapies