Publisher Summary This chapter addresses the universals in the content and structure of values, concentrating on the theoretical advances and empirical tests in 20 countries, and its four basic issues: substantive contents of human values; identification of comprehensive set of values; extent to which the meaning of particular values was equivalent for different groups of people; and how the relations among different values was structured. Substantial progress has been made toward resolving each of these issues. Ten motivationally distinct value types that were likely to be recognized within and across cultures and used to form value priorities were identified. Set of value types that was relatively comprehensive, encompassing virtually all the types of values to which individuals attribute at least moderate importance as criteria of evaluation was demonstrated. The evidence from 20 countries was assembled, showing that the meaning of the value types and most of the single values that constitute them was reasonably equivalent across most groups. Two basic dimensions that organize value systems into an integrated motivational structure with consistent value conflicts and compatibilities were discovered. By identifying universal aspects of value content and structure, the chapter has laid the foundations for investigating culture-specific aspects in the future.

Universals in the Content and Structure of Values: Theoretical Advances and Empirical Tests in 20 Countries

Well-being : the foundations of hedonic psychology

There is wide agreement about the major goals of economic policy: high employment, stable prices, and rapid growth. There is less agreement that these goals are mutually compatible or, among those who regard them as incompatible, about the terms at which they can and should be substituted for one another. There is least agreement about the role that various instruments of policy can and should play in achieving the several goals.

/pdf/the-role-of-monetary-policy-42dlhe1ho6.pdf

The role of monetary policy

Prior to the twentieth century, theories of knowledge were inherently perceptual. Since then, developments in logic, statis- tics, and programming languages have inspired amodal theories that rest on principles fundamentally different from those underlying perception. In addition, perceptual approaches have become widely viewed as untenable because they are assumed to implement record- ing systems, not conceptual systems. A perceptual theory of knowledge is developed here in the context of current cognitive science and neuroscience. During perceptual experience, association areas in the brain capture bottom-up patterns of activation in sensory-motor areas. Later, in a top-down manner, association areas partially reactivate sensory-motor areas to implement perceptual symbols. The stor- age and reactivation of perceptual symbols operates at the level of perceptual components - not at the level of holistic perceptual expe- riences. Through the use of selective attention, schematic representations of perceptual components are extracted from experience and stored in memory (e.g., individual memories of green, purr, hot). As memories of the same component become organized around a com- mon frame, they implement a simulator that produces limitless simulations of the component (e.g., simulations of purr). Not only do such simulators develop for aspects of sensory experience, they also develop for aspects of proprioception (e.g., lift, run) and introspec- tion (e.g., compare, memory, happy, hungry). Once established, these simulators implement a basic conceptual system that represents types, supports categorization, and produces categorical inferences. These simulators further support productivity, propositions, and ab- stract concepts, thereby implementing a fully functional conceptual system. Productivity results from integrating simulators combinato- rially and recursively to produce complex simulations. Propositions result from binding simulators to perceived individuals to represent type-token relations. Abstract concepts are grounded in complex simulations of combined physical and introspective events. Thus, a per- ceptual theory of knowledge can implement a fully functional conceptual system while avoiding problems associated with amodal sym- bol systems. Implications for cognition, neuroscience, evolution, development, and artificial intelligence are explored.

/pdf/perceptual-symbol-systems-4spsk97r61.pdf

Perceptual symbol systems.

Consumer researchers' growing interest in consumer experiences has revealed that many consumption activities produce both hedonic and utilitarian outcomes. Thus, there is an increasing need for scales to assess consumer perceptions of both hedonic and utilitarian values. This article describes the development of a scale measuring both values obtained from the pervasive consumption experience of shopping. The authors develop and validate the scale using a multistep process. The results demonstrate that distinct hedonic and utilitarian shopping value dimensions exist and are related to a number of important consumption variables. Implications for further applications of the scale are discussed.

https://www.jstor.org/stable/pdfplus/2489765.pdf

Work and/or Fun: Measuring Hedonic and Utilitarian Shopping Value

Portions of mankind who are not fitted or not disposed to live under the same internal government may often, with advantage, be federally united as to their relations with foreigners both to prevent wars among themselves, and for the sake of more effectual protection against the aggression of powerful States.

Of Federal Representative Governments

That there is, or may be, a Science of Human Nature


 Background: The dual-specificity tyrosine-regulated kinase 1A (DYRK1A) can phosphorylate multiple targets involved in key cellular processes that have been associated with the hallmarks of cancer, including proliferation, survival, cell cycle regulation and the DNA damage response1. In addition, compounds that inhibit DYRK1A have demonstrated anti-tumor activity both in vitro and in vivo. However, until recently, there was a paucity of potent, specific, and bioavailable DYRK1A inhibitors that did not target the related cdc2-like kinases (CLKs) and glycogen synthase kinase 3β. In this study, we describe a set of next-generation DYRK1A inhibitors and used them to evaluate the specific contribution of DYRK1A activity to tumor biology and evaluate the therapeutic potential of DYRK1A inhibition in cancer.
 Methods: DYRK1A expression was analyzed in The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases. Cancer cell growth dependencies were evaluated by DepMap analysis. Cell-based target engagement (TE) was assessed by NanoBRETTM. Cell viability was assayed with CellTiter-Glo® following 4-day treatment with DYRK1A inhibitors. Synergy was calculated using Chalice software. Pharmacokinetics (PK) were evaluated in rodents and Tumor Growth Inhibition (TGI) in nude mice. Preliminary toxicology was assessed in a 14 day rat study.
 Results: DYRK1A expression and a systematic DYRK dependencies analysis in human cancers revealed that hematological malignancies, Small Cell Lung and Ovarian cancers rely on DYRK1A expression for their proliferation. A series of potent (biochemical IC50s 3nM to 10nM, TE 19 nM to 134 nM) and highly selective ATP-competitive DYRK1A inhibitors were designed with minimal inhibition of the rest of the kinome (1%-2.3% of kinases inhibited > 90%) Cancer cell lines (n=160) were treated with DYRK1A inhibitors and those belonging to hematological lineages were among the most sensitive (P<0.01). In vitro combination of DYRK1A inhibitors with the anti-leukemia agent venetoclax revealed high synergy in 3 out of the 5 AML cell lines tested (synergy score >20). Compounds that showed good oral bioavailability and plasma exposures in rodents were selected for further characterization in vivo. In the MV-4-11 xenograft model, mice treated daily with 25mg/kg, or 50mg/kg of 2 different DYRK1A showed 72-99% TGI compared to vehicle. Preclinical toxicity profile in rats showed next generation DYRK1A inhibitors were well tolerated.
 Concluding Remarks: these studies support further evaluation of DYRK1A inhibitors as a therapeutic strategy for some cancers, especially hematological malignancies including AML.
 1 Boni, J.; Rubio-Perez, C.; López-Bigas, N.; Fillat, C.; de la Luna, S. The DYRK Family of Kinases in Cancer: Molecular Functions and Therapeutic Opportunities. Cancers 2020, 12, 2106. https://doi.org/10.3390/cancers12082106
 Citation Format: Matthew C. Jarvis, Gopi Mittapalli, Emily Creger, Chelsea Nora, Maureen Ibanez, Deepti Bhat, Brian Hofilena, Josh Stewart, Elizabeth A. McMillan, Hadi Falahatpisheh, Chi-Ching Mak, Michael White, John S. Hill, Carine Bossard. Next-generation DYRK1A inhibitors as a new therapeutic approach for the treatment of hematological malignancies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5019.

John Stuart Mill

Papers

Of Federal Representative Governments

That there is, or may be, a Science of Human Nature

Abstract 5019: Next-generation DYRK1A inhibitors as a new therapeutic approach for the treatment of hematological malignancies

Of what sort of proof the principle of utility is susceptible

Additional elucidations of the science of history.