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Trends in Immunology Mar 2021'Reverse vaccinology 2.0' aims to rationally reproduce template antibody responses, such as broadly neutralizing antibodies against human immunodeficiency virus-1. While... (Review)
Review
'Reverse vaccinology 2.0' aims to rationally reproduce template antibody responses, such as broadly neutralizing antibodies against human immunodeficiency virus-1. While observations of antibody convergence across individuals support the assumption that responses may be replicated, the diversity of humoral immunity and the process of antibody selection are rooted in stochasticity. Drawing from experience with in vitro antibody engineering by directed evolution, we consider how antibody selection may be driven, as in germline-targeting vaccine approaches to elicit broadly neutralizing antibodies and illustrate the potential consequences of over-defining a template antibody response. We posit that the prospective definition of template antibody responses and the odds of replicating them must be considered within the randomness of humoral immunity.
Topics: Antibodies, Neutralizing; Antibody Formation; HIV Antibodies; HIV-1; Humans; Prospective Studies
PubMed: 33514459
DOI: 10.1016/j.it.2021.01.001 -
Medical Anthropology 2022The development of the health care system in Switzerland has recently been driven by different processes such as economic rationalization, bureaucratization, or...
The development of the health care system in Switzerland has recently been driven by different processes such as economic rationalization, bureaucratization, or digitalization, while maintaining professional notions of 'good cure and care.' Drawing on qualitative data from a Swiss acute hospital, we analyze how potentially market driven modes of governance manifest themselves in the everyday activities of nurses and physicians. We show how professional understandings of 'good cure and care' remain persistent and intermingle with logics that we call economic rationalities, manifesting in the four interrelated issues of financial pressure, bureaucratization, time pressure, and staff shortage.
Topics: Anthropology, Medical; Delivery of Health Care; Humans; Physicians; Switzerland
PubMed: 35266841
DOI: 10.1080/01459740.2022.2037082 -
The Journal of Physical Chemistry. B Feb 2022Glycoside hydrolases and glycosyltransferases are the main classes of enzymes that synthesize and degrade carbohydrates, molecules essential to life that are a challenge... (Review)
Review
Glycoside hydrolases and glycosyltransferases are the main classes of enzymes that synthesize and degrade carbohydrates, molecules essential to life that are a challenge for classical chemistry. As such, considerable efforts have been made to engineer these enzymes and make them pliable to human needs, ranging from directed evolution to rational design, including mechanism engineering. Such endeavors fall short and are unreported in numerous cases, while even success is a necessary but not sufficient proof that the chemical rationale behind the design is correct. Here we review some of the recent work in CAZyme mechanism engineering, showing that computational simulations are instrumental to rationalize experimental data, providing mechanistic insight into how native and engineered CAZymes catalyze chemical reactions. We illustrate this with two recent studies in which (i) a glycoside hydrolase is converted into a glycoside phosphorylase and (ii) substrate specificity of a glycosyltransferase is engineered toward forming -, -, or -glycosidic bonds.
Topics: Carbohydrates; Computer Simulation; Glycoside Hydrolases; Glycosyltransferases; Humans; Substrate Specificity
PubMed: 35073079
DOI: 10.1021/acs.jpcb.1c09536 -
Philosophical Transactions of the Royal... Aug 2012Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one's own desires and beliefs, but also those of others.... (Review)
Review
Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one's own desires and beliefs, but also those of others. Whether it is uniquely human or not is controversial, but it is clear that humans are, at least, significantly better at ToM than any other animal. Economists and game theorists have developed sophisticated and powerful models of ToM and we provide a detailed summary of this here. This economic ToM entails a hierarchy of beliefs. I know my preferences, and I have beliefs (a probabilistic distribution) about your preferences, beliefs about your beliefs about my preferences, and so on. We then contrast this economic ToM with the theoretical approaches of neuroscience and with empirical data in general. Although this economic view provides a benchmark and makes useful suggestions about empirical tendencies, it does not always generate a close fit with the data. This provides an opportunity for a synergistic interdisciplinary production of a falsifiable theory of bounded rationality. In particular, a ToM that is founded on evolutionary biology might well be sufficiently structured to have predictive power, while remaining quite general. We sketch two papers that represent preliminary steps in this direction.
Topics: Bayes Theorem; Biological Evolution; Cognition; Decision Making; Economics; Economics, Behavioral; Game Theory; Humans; Neurosciences; Rationalization; Theory of Mind
PubMed: 22734065
DOI: 10.1098/rstb.2012.0124 -
Philosophical Studies 2023The discussion about deep disagreement has gained significant momentum in the last several years. This discussion often relies on the intuition that deep disagreement...
The discussion about deep disagreement has gained significant momentum in the last several years. This discussion often relies on the intuition that deep disagreement is, in some sense, rationally irresolvable. In this paper, I will provide a theory of rationally irresolvable disagreement. Such a theory is interesting in its own right, since it conflicts with the view that rational attitudes and procedures are paradigmatic tools for resolving disagreement. Moreover, I will suggest replacing discussions about deep disagreement with an analysis of rationally irresolvable disagreement, since this notion can be more clearly defined than deep disagreement and captures the basic intuitions underlying deep disagreement. I will first motivate this project by critically assessing the current debate about deep disagreement. I then detail the notions of rationality and resolvable disagreement which are crucial for a suitable theory of rationally irresolvable disagreement before sketching various instances of rationally irresolvable disagreement. Finally, I argue for replacing theories of deep disagreement with theories of rationally irresolvable disagreement, an approach that has significant advantages over existing theories of deep disagreement which focus on hinge propositions or fundamental epistemic principles.
PubMed: 37124938
DOI: 10.1007/s11098-023-01933-7 -
Frontiers in Chemistry 2020Hydrogels are polymeric three-dimensional network structures with high water content. Due to their superior biocompatibility and low toxicity, hydrogels play a... (Review)
Review
Hydrogels are polymeric three-dimensional network structures with high water content. Due to their superior biocompatibility and low toxicity, hydrogels play a significant role in the biomedical fields. Hydrogels are categorized by the composition from natural polymers to synthetic polymers. To meet the complicated situation in the biomedical applications, suitable host-guest supramolecular interactions are rationally selected. This review will have an introduction of hydrogel classification based on the formulation molecules, and then a discussion over the rational design of the intelligent hydrogel to the environmental stimuli such as temperature, irradiation, pH, and targeted biomolecules. Further, the applications of rationally designed smart hydrogels in the biomedical field will be presented, such as tissue repair, drug delivery, and cancer therapy. Finally, the perspectives and the challenges of smart hydrogels will be outlined.
PubMed: 33614595
DOI: 10.3389/fchem.2020.615665 -
Topics in Cognitive Science Jul 2022Goal-directed behavior is a deeply important part of human psychology. People constantly set goals for themselves and pursue them in many domains of life. In this paper,...
Goal-directed behavior is a deeply important part of human psychology. People constantly set goals for themselves and pursue them in many domains of life. In this paper, we develop computational models that characterize how humans pursue goals in a complex dynamic environment and test how well they describe human behavior in an experiment. Our models are motivated by the principle of resource rationality and draw upon psychological insights about people's limited attention and planning capacities. We find that human goal pursuit is qualitatively different and substantially less efficient than optimal goal pursuit in our simulated environment. Models of goal pursuit based on the principle of resource rationality capture human behavior better than both a model of optimal goal pursuit and heuristics that are not resource-rational. We conclude that the way humans pursue goals is shaped by the need to achieve goals effectively as well as cognitive costs and constraints on planning and attention. Our findings are an important step toward understanding humans' goal pursuit as cognitive limitations play a crucial role in shaping people's goal-directed behavior.
Topics: Attention; Goals; Heuristics; Humans; Motivation
PubMed: 34435728
DOI: 10.1111/tops.12562 -
Frontiers in Psychology 2019How should we define inferential reasoning in high-level cognition? Can non-conscious representations guide or even determine high-level cognition? If so, what are the...
How should we define inferential reasoning in high-level cognition? Can non-conscious representations guide or even determine high-level cognition? If so, what are the properties of such non-conscious representations? Two contemporary debates on high-level cognition center on these issues. The first concerns the possibility of cognitive penetration, or the degree and extent to which high-level cognition influences or determines low-level cognition. The second focuses on the epistemic status of conscious cognition, and on whether or not non-conscious cognition could play a similar, albeit not as fundamental, justificatory role as conscious cognition. This latter issue is at the heart of the question concerning the epistemic status of conscious awareness. This paper focuses on the epistemic standard required for inference, or inferential reasoning, to count as justificatory. The debates on the epistemic status of consciousness and cognitive penetration typically assume such a standard because high-level cognition is associated with rationality, inferentially structured thought, and the epistemic responsibility one has for the conclusions drawn through one's inferences. The paper proposes an account of that explains how cognitive penetration of non-phenomenally conscious cognition and perception is possible, and why there are unconscious processes that should be considered as essential components of high-level cognition. Sections "Defining Inference" and "Accuracy Constraints: The Agency-First Account of Inference" provide a theoretical framework for understanding the multiple criteria that an adequate account of inference and rational thought must satisfy. Sections "Attention: High- and Low-Level Inferential Cognition in Various Domains" and "Advantages Concerning Rule-Following and Rationality: Not Necessarily-Phenomenal Inferential Reasoning" articulate the inferential-attention account and explain how it meets the descriptive and normative criteria for epistemic responsibility and rationality. In particular, section "Attention: High- and Low-Level Inferential Cognition in Various Domains" defends an interpretation of inferential-attention, which offers a resolution of the tension between conservative or consciousness-based approaches to inference and liberal approaches that allow for types of unconscious or subdoxastic processes. An agency condition on inference explains how inference is a psychological process under the of the agent, and at the same time, it satisfies the normative condition that an inference should be responsive to reasons or evidence by being cognitively available for personal level assessment and evaluation. The key is to identify this kind of epistemic agency with attention. Section "Advantages Concerning Rule-Following and Rationality: Not Necessarily-Phenomenal Inferential Reasoning" compares this inferential-attention account with an influential agential account of inference based on conscious intuition, and it argues that the former account is preferable. This section also demonstrates the significance of inferential-attention in higher cognition, even when it is non-phenomenally conscious.
PubMed: 31849739
DOI: 10.3389/fpsyg.2019.02580 -
International Journal of Environmental... Feb 2022Whistleblowers who expose wrongdoing often face several concerns, pressures, and threats of retaliation before reaching a final decision. Specifically, this study...
Whistleblowers who expose wrongdoing often face several concerns, pressures, and threats of retaliation before reaching a final decision. Specifically, this study examines the effects of perceived seriousness of wrongdoing (PSW) and perceived threat of retaliation (PTR), as well as the impact of rationalization (RNL), comparing perceived seriousness of wrongdoing, perceived threat of retaliation and whistleblowing intention. Furthermore, this study aims to determine the mediating effect of anticipated regret (AR) on the relationship between perceived seriousness of wrongdoing and whistleblowing intention. We validated our model by analyzing data gathered across three stages from employees in the telecom sector in Pakistan. The key findings of our research may be summarized as follows: (i) individuals' willingness to 'blow the whistle' increases as a result of perceived seriousness of wrongdoing; (ii) whistleblowers are more likely to opt to remain silent if they anticipate a greater threat of retaliation, and (iii) our study establishes a positive connection between perceived seriousness of wrongdoing and whistleblowing intention, indicating that perceived seriousness of wrongdoing enhances people's willingness to blow the whistle, and whistleblowers are more likely to choose to emerge if the behaviour is more serious in nature; (iv) the data we have uncovered indicates a moderating role of rationalization in regulating the connections between perceived seriousness of wrongdoing, perceived threat of retaliation, and whistleblowing intention; and (v) the findings demonstrate that anticipated regret mediates the connection between perceived seriousness of wrongdoing and the intention to report wrongdoing. Additionally, the results are discussed in terms of their significance for corporate ethics researchers and managers, as well as for end-users who are interested in whistleblowing.
Topics: Emotions; Humans; Intention; Pakistan; Rationalization; Whistleblowing
PubMed: 35162775
DOI: 10.3390/ijerph19031752 -
Sociology of Health & Illness Sep 2022Since the 1990s, the sociology of rationing has developed in explicit opposition to health economic and bioethical approaches to healthcare rationing. This implies a... (Review)
Review
Since the 1990s, the sociology of rationing has developed in explicit opposition to health economic and bioethical approaches to healthcare rationing. This implies a limited engagement with other disciplines and a limited impact on political debates. To bring the sociology of rationing into an interdisciplinary dialogue, it is important to understand the disciplines' analytical differences and similarities. Based on a critical interpretive literature synthesis, this article examines four disciplinary perspectives on healthcare rationing and priority setting: (1) Health economics, which seeks to develop decision models to provide for more rational resource allocation; (2) Bioethics, which seeks to develop normative principles and procedures to facilitate a just allocation of resources; (3) Health policy studies, which focus on issues of legitimacy and implementation of decision models; and lastly (4) Sociology, which analyses the uncertainty of rationing and the resulting value conflicts and negotiations. The article provides an analytical overview and suggestions on how to advance the impact of sociological arguments in future rationing debates: Firstly, we discuss how to develop the concepts and assumptions of the sociology of rationing. Secondly, we identify specific themes relevant for sociological inquiry, including the recurring problem of how to translate administrative priority setting decisions into clinical practice.
Topics: Health Care Rationing; Health Policy; Humans; Sociology; Uncertainty
PubMed: 35692110
DOI: 10.1111/1467-9566.13507