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1.
Sci Eng Ethics ; 25(2): 399-418, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29357047

RESUMO

Ethical thought experiments such as the trolley dilemma have been investigated extensively in the past, showing that humans act in utilitarian ways, trying to cause as little overall damage as possible. These trolley dilemmas have gained renewed attention over the past few years, especially due to the necessity of implementing moral decisions in autonomous driving vehicles (ADVs). We conducted a set of experiments in which participants experienced modified trolley dilemmas as drivers in virtual reality environments. Participants had to make decisions between driving in one of two lanes where different obstacles came into view. Eventually, the participants had to decide which of the objects they would crash into. Obstacles included a variety of human-like avatars of different ages and group sizes. Furthermore, the influence of sidewalks as potential safe harbors and a condition implicating self-sacrifice were tested. Results showed that participants, in general, decided in a utilitarian manner, sparing the highest number of avatars possible with a limited influence by the other variables. Derived from these findings, which are in line with the utilitarian approach in moral decision making, it will be argued for an obligatory ethics setting implemented in ADVs.


Assuntos
Inteligência Artificial/ética , Automação/ética , Condução de Veículo/psicologia , Automóveis/ética , Tomada de Decisões/ética , Teoria Ética , Altruísmo , Guias como Assunto , Humanos , Princípios Morais , Realidade Virtual
2.
BMC Cancer ; 12: 213, 2012 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22672427

RESUMO

BACKGROUND: The Wnt/ß-catenin signalling is aberrantly activated in primary B cell chronic lymphocytic leukaemia (CLL). Epigenetic silencing of pathway inhibitor genes may be a mechanism for its activation. In this study, we investigated systematically and quantitatively the methylation status of 12 Wnt/ß-catenin pathway inhibitor genes - CDH1, DACT1, DKK1, DKK2, DKK3, DKK4, SFRP1, SFRP2, SFRP3, SFRP4, SFRP5 and WIF1 - in the cell lines EHEB and MEC-1 as well as patient samples. METHODS: Quantification of DNA methylation was performed by means of bisulphite pyrosequencing and confirmed by bisulphite Sanger sequencing. Gene expression was analysed by qPCR using GAPDH as internal control. E-cadherin and ß-catenin protein quantification was carried out by microsphere-based immunoassays. Methylation differences observed between the patient and control groups were tested using generalised least squares models. RESULTS: For 10 genes, a higher methylation level was observed in tumour material. Only DKK4 exhibited similarly high methylation levels in both tumour and normal specimens, while DACT1 was always essentially unmethylated. However, also for these inhibitors, treatment of cells with the demethylating agent 5-aza-2´-deoxycytidine resulted in an induction of their expression, as shown by quantitative PCR, suggesting an indirect epigenetic control of activity. While the degree of demethylation and its transcriptional consequences differed between the genes, there was an overall high correlation of demethylation and increased activity. Protein expression studies revealed that no constitutive Wnt/ß-catenin signalling occurred in the cell lines, which is in discrepancy with results from primary CLL. However, treatment with 5-aza-2´-deoxycytidine caused accumulation of ß-catenin. Simultaneously, E-cadherin expression was strongly induced, leading to the formation of a complex with ß-catenin and thus demonstrating its epigenetically regulated inhibition effect. CONCLUSIONS: The results suggest an epigenetic silencing mechanism of the Wnt/ß-catenin pathway inhibitor genes in CLL. Hypermethylation and silencing of functionally related genes may not be completely stochastic but result from the tumour epigenome reprogramming orchestrated by Polycomb-group repressive complexes. The data are of interest in the context of epigenetic-based therapy.


Assuntos
Epigênese Genética , Inativação Gênica , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Mapeamento Cromossômico , Ilhas de CpG , Metilação de DNA , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ligação Proteica
3.
Front Psychol ; 13: 875680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837636

RESUMO

The origin of moral agency is a much-debated issue. While rationalists or Kantians have argued that moral agency is rooted in reason, sentimentalists or Humeans have ascribed its origin to empathic feelings. This debate between rationalists and sentimentalists still stands with respect to persons with mental disorders, such as individuals diagnosed with mild forms of Autism Spectrum Disorder (ASD), without intellectual impairment. Individuals with ASD are typically regarded as moral agents, however their ability for empathy remains debated. The goal of this paper is to investigate the mechanisms of moral actions in people with ASD, by finding arguments for the origin of their moral actions, supporting either the sentimentalist or the rationalist view of the dispute. We propose to revisit the debate using Interpretative Phenomenological Analysis to study the autobiographies of individuals with High-Functioning Autism (HFA) and Asperger Syndrome (AS). While conducting the systematic analysis of 10 autobiographies, we re-examined both the rationalist and the sentimentalist positions, considering the links between empathic feelings and moral agency. The investigation of the temporal dimensions of emotional experiences, an aspect overlooked by previous research, indicated that individuals with ASD empathize with others, but in different ways as compared to neurotypicals. A relationship between emotional experience and the type of moral agency exhibited by individuals with forms of ASD was established. As a consequence, our analyses support the sentimentalist stance on moral action.

4.
Cells ; 11(6)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35326381

RESUMO

The cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP. Subsequent alterations in viability, proliferation, and phenotype were analyzed via flow cytometry and metabolic alterations by Seahorse Cell Mito Stress Tests. It was found that cells generally exhibited reduced viability and proliferation, stemming from CAP induced G2/M cell cycle arrest and subsequent apoptosis, as well as increased mitochondrial stress following CAP treatment. Overall, sensitivity to CAP treatment was found to be cell type dependent with T cells being the most affected. Interestingly, CAP influenced the polarization of M0 macrophages to a "M0/M2-like" phenotype, and M1 macrophages were found to display a heightened sensitivity to CAP induced mitochondrial stress. CAP also inhibited the growth and killed melanoma cells in 2D and 3D in vitro cell culture models in a dose-dependent manner. Improving our understanding of oxidative stress, mechanisms to manipulate it, and its implications for the tumor microenvironment may help in the discovery of new therapeutic targets.


Assuntos
Melanoma , Gases em Plasma , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Humanos , Melanoma/patologia , Estresse Oxidativo , Microambiente Tumoral
5.
Cogn Process ; 12(4): 375-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21476065

RESUMO

Emotions have long been seen as counteracting rational thought, but over the last decades, they have been viewed as adaptive processes to optimize human (but also animal) behaviour. In particular, positive affect appears to be a functional aspect of emotions closely related to that. We argue that positive affect as understood in Kuhl's PSI model of the human cognitive architecture appears to have an interpretation in state-of-the-art hybrid robot control architectures, which might help tackle some open questions in the field.


Assuntos
Comportamento/fisiologia , Cognição/fisiologia , Emoções/fisiologia , Robótica/métodos , Humanos , Modelos Psicológicos
6.
Front Psychol ; 11: 205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32132953

RESUMO

Affective bonding to radical organizations is one of the most prominent features of a recruit's personality. To better understand how affective bonding is established during the recruitment of youth for radicalization and how it is maintained afterward, it seems promising to adopt new insights and developments from the field of situated cognition and affectivity, particularly the concepts of Affective Scaffolding, Mind Invasion, and Self-Stimulatory Loops of Affectivity (SSLA). The three notions highlight both the intended structuring of the affective bonding by the recruiting organizations and the immersive influence these settings have on the individuals. We will study the affective bonding between an individual and a radical group from two perspectives: first, from an organizational perspective, and second from a personal perspective. The first aims at understanding how extremist organizations "invade the mind" of young people, by providing carefully designed affective scaffolding: (a) during the recruitment process and (b) while being a full member of the organization. The second aims at identifying some of the affective loops which individuals who have joined the radical organization enter.

7.
Front Psychol ; 11: 524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32269543

RESUMO

This article argues that one should consider online and offline radicalization in an integrated way. Occasionally, the design of some counter-measure initiatives treats the internet and the "real" world as two separate and independent realms. New information communication technologies (ICTs) allow extremists to fuse digital and physical settings. As a result, our research contends that radicalization takes place in onlife spaces: hybrid environments that incorporate elements from individuals' online and offline experiences. This study substantiates this claim, and it examines how algorithms structure information on social media by tracking users' online and offline activities. Then, it analyzes how the Islamic State promoted onlife radicalization. We focus on how the Islamic State used Telegram, specific media techniques, and videos to connect the Web to the territories it controlled in Syria. Ultimately, the article contributes to the recalibration of the current debate on the relationship between online and offline radicalization on a theoretical level and suggests, on a practical level, potential counter measures.

8.
Front Psychol ; 10: 2415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749736

RESUMO

Self-driving cars have the potential to greatly improve public safety. However, their introduction onto public roads must overcome both ethical and technical challenges. To further understand the ethical issues of introducing self-driving cars, we conducted two moral judgement studies investigating potential differences in the moral norms applied to human drivers and self-driving cars. In the experiments, participants made judgements on a series of dilemma situations involving human drivers or self-driving cars. We manipulated which perspective situations were presented from in order to ascertain the effect of perspective on moral judgements. Two main findings were apparent from the results of the experiments. First, human drivers and self-driving cars were largely judged similarly. However, there was a stronger tendency to prefer self-driving cars to act in ways to minimize harm, compared to human drivers. Second, there was an indication that perspective influences judgements in some situations. Specifically, when considering situations from the perspective of a pedestrian, people preferred actions that would endanger car occupants instead of themselves. However, they did not show such a self-preservation tendency when the alternative was to endanger other pedestrians to save themselves. This effect was more prevalent for judgements on human drivers than self-driving cars. Overall, the results extend and agree with previous research, again contradicting existing ethical guidelines for self-driving car decision making and highlighting the difficulties with adapting public opinion to decision making algorithms.

9.
Conscious Cogn ; 17(2): 506-13, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18417362

RESUMO

We elaborate and defend the claim that human affective states ("feelings") are, among other things, self-disclosing. We will show why affective intentionality has to be considered in order to understand human self-consciousness. One specific class of affective states, so-called existential feelings, although often neglected in philosophical treatments of emotions, will prove central. These feelings importantly pre-structure affective and other intentional relations to the world. Our main thesis is that existential feelings are an important manifestation of self-consciousness and figure prominently in human self-understanding. We offer an ordering of four levels of existential feelings and also give considerations in favour of the essential bodily nature of these feelings.


Assuntos
Afeto , Estado de Consciência , Existencialismo , Autoimagem , Humanos
10.
Front Behav Neurosci ; 12: 31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29541023

RESUMO

Autonomous vehicles, though having enormous potential, face a number of challenges. As a computer system interacting with society on a large scale and human beings in particular, they will encounter situations, which require moral assessment. What will count as right behavior in such situations depends on which factors are considered to be both morally justified and socially acceptable. In an empirical study we investigated what factors people recognize as relevant in driving situations. The study put subjects in several "dilemma" situations, which were designed to isolate different and potentially relevant factors. Subjects showed a surprisingly high willingness to sacrifice themselves to save others, took the age of potential victims in a crash into consideration and were willing to swerve onto a sidewalk if this saved more lives. The empirical insights are intended to provide a starting point for a discussion, ultimately yielding societal agreement whereby the empirical insights should be balanced with philosophical considerations.

11.
Nucleic Acids Res ; 31(19): e119, 2003 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-14500847

RESUMO

Several strategies have been developed for the production of peptide nucleic acid (PNA) microarrays by parallel probe synthesis and selective coupling of full-length molecules. Such microarrays were used for direct detection of the hybridisation of unlabelled DNA by time-of-flight secondary ion mass spectrometry. PNAs were synthesised by an automated process on filter-bottom microtitre plates. The resulting molecules were released from the solid support and attached without any purification to microarray surfaces via the terminal amino group itself or via modifications, which had been chemically introduced during synthesis. Thus, only full-length PNA oligomers were attached whereas truncated molecules, produced during synthesis because of incomplete condensation reactions, did not bind. Different surface chemistries and fitting modifications of the PNA terminus were tested. For an examination of coupling selectivity, bound PNAs were cleaved off microarray surfaces and analysed by MALDI-TOF mass spectrometry. Additionally, hybridisation experiments were performed to compare the attachment chemistries, with fully acetylated PNAs spotted as controls. Upon hybridisation of unlabelled DNA to such microarrays, binding events could be detected by visualisation of phosphates, which are an integral part of nucleic acids but missing entirely in PNA probes. Overall best results in terms of selectivity and sensitivity were obtained with thiol-modified PNAs on maleimide surfaces.


Assuntos
DNA/análise , Sondas de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Ácidos Nucleicos Peptídicos , Sequência de Bases , Sondas de Ácido Nucleico/síntese química , Sondas de Ácido Nucleico/química , Sondas de Ácido Nucleico/isolamento & purificação , Ácidos Nucleicos Peptídicos/síntese química , Ácidos Nucleicos Peptídicos/química , Ácidos Nucleicos Peptídicos/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Methods Mol Biol ; 283: 283-93, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15197319

RESUMO

A fast and economical procedure for the production of peptide nucleic acid (PNA) microarrays is presented. PNA oligomers are synthesized in a fully automatic manner in 96-well plates using standard Fmoc chemistry. Subsequently, the oligomers are released from the support and spotted onto glass or silicone slides, which were activated by succinimidyl ester. This process allows for a concomitant purification of the oligomers directly on the chip surface. Although the terminal primary amino groups of the full-length products bind selectively to this surface, none of the byproducts of synthesis, such as truncated sequences or cleaved side chain protection groups, will bind and are therefore washed away. In this chapter, protocols are presented for the whole production process as well as sample hybridization.


Assuntos
Análise de Sequência com Séries de Oligonucleotídeos/métodos , Ácidos Nucleicos Peptídicos/síntese química , Hibridização de Ácido Nucleico/métodos
13.
PLoS One ; 4(8): e6726, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21949675

RESUMO

BACKGROUND: Neuroimaging has demonstrated that voluntary emotion regulation is effective in reducing amygdala activation to aversive stimuli during regulation. However, to date little is known about the sustainability of these neural effects once active emotion regulation has been terminated. METHODOLOGY/PRINCIPAL FINDINGS: We addressed this issue by means of functional magnetic resonance imaging (fMRI) in healthy female subjects. We performed an active emotion regulation task using aversive visual scenes (task 1) and a subsequent passive viewing task using the same stimuli (task 2). Here we demonstrate not only a significantly reduced amygdala activation during active regulation but also a sustained regulation effect on the amygdala in the subsequent passive viewing task. This effect was related to an immediate increase of amygdala signal in task 1 once active emotion regulation has been terminated: The larger this peak postregulation signal in the amygdala in task 1, the smaller the sustained regulation effect in task 2. CONCLUSIONS/SIGNIFICANCE: In summary, we found clear evidence that effects of voluntary emotion regulation extend beyond the period of active regulation. These findings are of importance for the understanding of emotion regulation in general, for disorders of emotion regulation and for psychotherapeutic interventions.


Assuntos
Tonsila do Cerebelo/fisiologia , Emoções/fisiologia , Lateralidade Funcional/fisiologia , Imageamento por Ressonância Magnética , Neuroimagem , Adulto , Mapeamento Encefálico , Feminino , Humanos , Estimulação Luminosa
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