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Classical statistical analysis of data can be complemented or replaced with data analysis based on machine learning. However, in certain disciplines, such as education research, studies are frequently limited to small datasets, which raises several questions regarding biases and coincidentally positive results. In this study, we present a refined approach for evaluating the performance of a binary classification based on machine learning for small datasets. The approach includes a non-parametric permutation test as a method to quantify the probability of the results generalising to new data. Furthermore, we found that a repeated nested cross-validation is almost free of biases and yields reliable results that are only slightly dependent on chance. Considering the advantages of several evaluation metrics, we suggest a combination of more than one metric to train and evaluate machine learning classifiers. In the specific case that both classes are equally important, the Matthews correlation coefficient exhibits the lowest bias and chance for coincidentally good results. The results indicate that it is essential to avoid several biases when analysing small datasets using machine learning. [ABSTRACT FROM AUTHOR]

Connecting human minds to various technological devices and applications through brain-computer interfaces (BCIs) affords intriguingly novel ways for humans to engage and interact with the world. Not only do BCIs play an important role in restorative medicine, they are also increasingly used outside of medical or therapeutic contexts (e.g., gaming or mental state monitoring). A striking peculiarity of BCI technology is that the kind of actions it enables seems to differ from paradigmatic human actions, because, effects in the world are brought about by devices such as robotic arms, prosthesis, or other machines, and their execution runs through a computer directed by brain signals. In contrast to usual forms of action, the sequence does not need to involve bodily or muscle movements at all. A motionless body, the epitome of inaction, might be acting. How do theories of action relate to such BCI-mediated forms of changing the world? We wish to explore this question through the lenses of three perspectives on agency: subjective experience of agency, philosophical action theory, and legal concepts of action. Our analysis pursues three aims: First, we shall discuss whether and which BCI-mediated events qualify as actions, according to the main concepts of action in philosophy and law. Secondly, en passant, we wish to highlight the ten most interesting novelties or peculiarities of BCI-mediated movements. Thirdly, we seek to explore whether these novel forms of movement may have consequences for concepts of agency. More concretely, we think that convincing assessments of BCI-movements require more fine-grained accounts of agency and a distinction between various forms of control during movements. In addition, we show that the disembodied nature of BCI-mediated events causes troubles for the standard legal account of actions as bodily movements. In an exchange with views from philosophy, we wish to propose that the law ought to reform its concept of action to include some, but not all, BCI-mediated events and sketch some of the wider implications this may have, especially for the venerable legal idea of the right to freedom of thought. In this regard, BCIs are an example of the way in which technological access to yet largely sealed-off domains of the person may necessitate adjusting normative boundaries between the personal and the social sphere., Author(s): Steffen Steinert [sup.1] [sup.2] , Christoph Bublitz [sup.3] , Ralf Jox [sup.2] , Orsolya Friedrich [sup.2] Author Affiliations: (Aff1) 0000 0001 2097 4740, grid.5292.c, Philosophy Department, Faculty of Technology, [...]

This article discusses the integration of large language models (LLMs), such as ChatGPT, into physics education. LLMs are artificial intelligence methods that can generate human-like text and have the potential to enhance personalized learning and provide immediate formative feedback to students. However, there are concerns about the accuracy and reliability of the feedback provided by LLMs. The article presents an application called LEAP (Learning with AI about Physics) that allows students to interact with ChatGPT for physics problem solving, with predetermined prompts to ensure focused and relevant feedback. The article emphasizes the need for careful integration of LLMs into teaching practices and highlights the potential benefits and challenges of using LLMs in physics education. [Extracted from the article]

Technology helps to solve problems, but it may also lead to unintended consequences. For example, biofuels may help to overcome the disadvantages of fossil fuels, but their production might compete with food production leading to higher food prices and hunger. Therefore, in recent decades, the societal impact of technology has come to the center of attention. To deal with potential ethical issues related to technology, many scholars have emphasized the importance of addressing values already during the design phase of new technology. Values are understood as beliefs about what is good or desirable, like human autonomy, safety, sustainability, or privacy. Researchers in ethics and philosophy of technology have developed a variety of approaches, like value-sensitive design (VSD) and responsible research and innovation, to help engineers embed values in technological design (e.g.,). [ABSTRACT FROM AUTHOR]

In this paper, I argue that machines can create works of art. My argument is based on an analysis of the so-called creative machines and focuses on technical functions and intentions. If my proposal is correct, then creative machines are technical artifacts with the proper function to bring about works of art. My account is based on sensible conceptual connections between makers, technical artifacts, intentions, and the creation of art. One upshot of the account presented here is that we do not need a new conceptual framework or dubious assumptions about artistic agency on part of machines in order to arrive at the conclusion that creative machines make art. I will conclude the paper with some remarks regarding the artistic value of items produced by creative machines., Author(s): Steffen Steinert [sup.1] Author Affiliations: (1) Research Center for Neurophilosophy and Ethics of Neuroscience, Ludwig-Maximilians-Universität München, 0000 0004 1936 973X, grid.5252.0, , Schellingstraße 10, room J 309, 80799, Munich, [...]

In this paper, I will focus on the extension theories of technology. I will identify four influential positions that have been put forward: (1) technology as an extension of the human organism, (2) technology as an extension of the lived body and the senses, (3) technology as an extension of our intentions and desires, and (4) technology as an extension of our faculties and capabilities. I will describe and critically assess these positions one by one and highlight their advantages and their shortcomings and limitations. Along the way, I will explicate some of the differences and similarities between the various approaches. I conclude the paper with some suggestions for future research directions that will be beneficial for advancing theory building and that will drive forward the philosophical refinement of extension theory., Author(s): Steffen Steinert[sup.1] Author Affiliations: (1) Research Center for Neurophilosophy and Ethics of Neuroscience, Ludwig-Maximilians-Universität München, Schellingstraße 10, room J 309, 80799, Munich, Germany Introduction The focus of this paper [...]

Research has documented robust associations between greater disgust sensitivity and (1) concerns about disease, and (2) political conservatism. However, the COVID-19 disease pandemic raised challenging questions about these associations. In particular, why have conservatives—despite their greater disgust sensitivity—exhibited less concern about the pandemic? Here, we investigate this "conservatism-disgust paradox" and address several outstanding theoretical questions regarding the interrelations among disgust sensitivity, ideology, and pandemic response. In four studies (N = 1,764), we identify several methodological and conceptual factors—in particular, an overreliance on self-report measures—that may have inflated the apparent associations among these constructs. Using non-self-report measures, we find evidence that disgust sensitivity may be a less potent predictor of disease avoidance than is typically assumed, and that ideological differences in disgust sensitivity may be amplified by self-report measures. These findings suggest that the true pattern of interrelations among these factors may be less "paradoxical" than is typically believed. [ABSTRACT FROM AUTHOR]

It is often suggested that social media is a hostile environment for critical thinking and that a major source for epistemic problems concerning social media is that it facilitates emotions. We argue that emotions per se are not the source of the epistemic problems concerning social media. We propose that instead of focusing on emotions, we should focus on the affective scaffolding of social media. We will show that some affective scaffolds enable desirable epistemic practices, while others obstruct beneficial epistemic practices, or enable hostile epistemic practices. Particularly, we will show that emotions play a crucial role in the epistemic practice of critical thinking and that the affective scaffolding of social media can support, or hinder, online critical thinking. The upshot of our argument is that affective scaffoldings of social media can harness emotions to support beneficial epistemic practices, like online critical thinking. [ABSTRACT FROM AUTHOR]

In this article, we discuss the importance of emotions for ethical reflection on technological developments, as well as the role that art can play in this. We review literature that argues that emotions can and should play an important role in the assessment and acceptance of technological risk and in designing morally responsible technologies. We then investigate how technologically engaged art can contribute to critical, emotional-moral reflection on technological risks. The role of art that engages with technology is unexplored territory and gives rise to many fascinating philosophical questions that have not yet been sufficiently addressed in the literature. [ABSTRACT FROM AUTHOR]

We value a sense of humor in people, and amusement is something that we enjoy. So why not enhance and train your ability to be amused? In this paper, I investigate whether our ability to be amused can be trained. I adopt the idea that training a capacity requires improving control. If we cannot improve the control of a capacity, then we cannot train that capacity. I show that we cannot improve the control of our capacity of amusement because of the cognitive process underlying amusement. Hence, you cannot train your funny bone! [ABSTRACT FROM AUTHOR]

In number 35 of Think, James Spiegel presents reasons for why flatulence is funny. In this article I will address five issues that I find problematic in his account: (1)His claim that laughter always results from a pleasant psychological shift is false.(2)His argumentative move from what makes paradigm cases funny to what makes flatulence funny is unwarranted.(3)His notion of a psychological shift is not specific enough and lacks explanatory power.(4)The claim that funniness of flatulence involves superiority is doubtful.(5)His talk about ‘nervous energy’ is questionable and has implausible implications. [ABSTRACT FROM PUBLISHER]

Doping of carbon nanoparticles with impurity atoms is central to their application. However, doping has proven elusive for very small carbon nanoparticles because of their limited availability and a lack of fundamental understanding of impurity stability in such nanostructures. Here, we show that isolated diamond nanoparticles as small as 1.6 nm, comprising only ∼400 carbon atoms, are capable of housing stable photoluminescent colour centres, namely the silicon vacancy (SiV). Surprisingly, fluorescence from SiVs is stable over time, and few or only single colour centres are found per nanocrystal. We also observe size-dependent SiV emission supported by quantum-chemical simulation of SiV energy levels in small nanodiamonds. Our work opens the way to investigating the physics and chemistry of molecular-sized cubic carbon clusters and promises the application of ultrasmall non-perturbative fluorescent nanoparticles as markers in microscopy and sensing. [ABSTRACT FROM AUTHOR]

Magnetic field fluctuations arising from fundamental spins are ubiquitous in nanoscale biology, and are a rich source of information about the processes that generate them. However, the ability to detect the few spins involved without averaging over large ensembles has remained elusive. Here, we demonstrate the detection of gadolinium spin labels in an artificial cell membrane under ambient conditions using a single-spin nanodiamond sensor. Changes in the spin relaxation time of the sensor located in the lipid bilayer were optically detected and found to be sensitive to nearindividual (4 ± 2) proximal gadolinium atomic labels. The detection of such small numbers of spins in a model biological setting, with projected detection times of 1 s [corresponding to a sensitivity of ∼5 Gd spins per Hz1/2], opens a pathway for in situ nanoscale detection of dynamical processes in biology. [ABSTRACT FROM AUTHOR]

Background: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Aβ, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al [1] in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. Methodology/Principal Findings: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB). Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol. Conclusions/Significance: The current work presents the characterization and trafficking behavior of a novel sphingolipid-binding fluorescent probe, the SBD peptide. We show that SBD binding to membranes is dependent on the presence of cholesterol, sphingomyelin, and complex glycolipids. In addition, SBD targeting through the endolysosomal pathway in neurons is highly sensitive to cholesterol perturbations, making it a potentially useful tool for the analysis of sphingolipid trafficking in disease models that involve changes in cholesterol metabolism and storage. [ABSTRACT FROM AUTHOR]

Abstract: The proinflammatory cytokine tumor necrosis factor (TNF) binds two distinct plasma membrane receptors, TNFR1 and TNFR2. We have produced different receptor mutants fused with enhanced green fluorescent protein to study their membrane dynamics by fluorescence correlation spectroscopy (FCS). TNFR1 mutants show diffusion constants of approximately 1.2×10−9 cm2/s and a broad distribution of diffusion times, which is hardly affected by ligand binding. However, cholesterol depletion enhances their diffusion, suggesting a constitutive affinity to cholesterol rich membrane microdomains. In contrast, TNFR2 and mutants thereof diffuse rather fast (D̄ =3.1×10−9 cm2/s) with a marked reduction after 30min of TNF treatment (D̄ =0.9×10−9 cm2/s). This reduction cannot be explained by the formation of higher ordered receptor clusters, since the fluorescence intensity of TNF treated receptors indicate the presence of a few receptor molecules per complex only. Together, these data point to a topological segregation of the two TNF receptors in different microcompartments of the plasma membrane independent of the cytoplasmic signaling domains of the receptors. [Copyright &y& Elsevier]

Abstract: Ciliary neurotrophic factor (CNTF) signals via a receptor complex consisting of the specific CNTF receptor (CNTFR) and two promiscuous signal transducers, gp130 and leukemia inhibitory factor receptor (LIFR). Whereas earlier studies suggested that the signaling complex is a hexamer, more recent analyses strongly support a tetrameric structure. However, all studies so far analyzed the stoichiometry of the CNTF receptor complex in vitro and not in the context of living cells. We generated and expressed in mammalian cells acyl carrier protein-tagged versions of both CNTF and CNTFR. After labeling CNTF and CNTFR with different dyes we analyzed their diffusion behavior at the cell surface. Fluorescence (cross) correlation spectroscopy (FCS/FCCS) measurements reveal that CNTFR diffuses with a diffusion constant of about 2×10−9 cm2 s−1 independent of whether CNTF is bound or not. FCS and FCCS measurements detect the formation of receptor complexes containing at least two CNTFs and CNTFRs. In addition, we measured Förster-type fluorescence resonance energy transfer between two differently labeled CNTFs within a receptor complex indicating a distance of 5–7 nm between the two. These findings are not consistent with a tetrameric structure of the CNTFR complex suggesting that either hexamers and or even higher-order structures (e.g. an octamer containing two tetramers) are formed. [Copyright &y& Elsevier]

Modern-day CMOS-based computation technology is reaching its fundamental limitations. The emerging field of magnonics, which utilizes spin waves for data transport and processing, proposes a promising path to overcome these limitations. Different devices have been demonstrated recently on the macro- and microscale, but the feasibility of the magnonics approach essentially relies on the scalability of the structure feature size down to the extent of a few 10 nm, which are typical sizes for the established CMOS technology. Here, we present a study of propagating spin-wave packets in individual yttrium iron garnet (YIG) conduits with lateral dimensions down to 50 nm. Space and time-resolved microfocused Brillouin-light-scattering (BLS) spectroscopy is used to characterize the YIG nanostructures and measure the spin-wave decay length and group velocity directly. The revealed magnon transport at the scale comparable to the scale of CMOS proves the general feasibility of magnon-based data processing.

Sensing and imaging paramagnetic species under physiological conditions is a key technology in chemical and biochemical analytics, cell biology, and medical sciences. At submicrometer length scales, nitrogen-vacancy (NV) centers in diamond offer atom-sized probes for magnetic fields. We show that spin relaxation of an ensemble NV sensor allows sensing of adsorbed and freely diffusing manganese(II) ions and adsorbed ferritin. Sensitivities approach 175 Mn ions and 10 ferritin proteins per diffraction limited spot under ambient conditions.

In lipid storage diseases, the intracellular trafficking of sphingolipids is altered by conditions of aberrant cholesterol accumulation. Drosophila has been used recently to model lipid storage diseases, but the effects of sterol accumulation on sphingolipid trafficking are not known in the fly, and the trafficking of sphingolipids in general has not been studied in this model organism. Here, we examined the uptake and intracellular distribution of a fluorescent glycolipid analog, BODIPY-lactosyl-ceramide, in Drosophila neurons. The uptake mechanism and intracellular trafficking route of this simple glycolipid are largely conserved. Our principle finding is that cholesterol steers trafficking of the glycolipid between Golgi, lysosome, and recycling compartments. Our analyses support the idea that cholesterol storage in Drosophila triggers a switch in glycolipid trafficking from the biosynthetic to the degradative endolysosomal pathway, whereas cholesterol depletion eliminates recycling of the glycolipid. Unexpectedly, we observe a novel phenomenon we term "hijacking," whereby lactosyl-ceramide diverts the trafficking pathway of an endocytic cargo, dextran, completely away from its lysosomal target. This work establishes that glycolipid trafficking in Drosophila undergoes changes similar to those seen in mammalian cells under conditions of cholesterol storage and therefore validates Drosophila as a suitable model organism in which to study lipid storage diseases.

We have designed a tagged probe [sphingolipid binding domain (SBD)] to facilitate the tracking of intracellular movements of sphingolipids in living neuronal cells. SBD is a small peptide consisting of the SBD of the amyloid precursor protein. It can be conjugated to a fluorophore of choice and exogenously applied to cells, thus allowing for in vivo imaging. Here, we present evidence to describe the characteristics of the SBD association with the plasma membrane. Our experiments demonstrate that SBD binds to isolated raft fractions from human neuroblastomas and insect neuronal cells. In protein-lipid overlay experiments, SBD interacts with a subset of glycosphingolipids and sphingomyelin, consistent with its raft association in neurons. We also provide evidence that SBD is taken up by neuronal cells in a cholesterol- and sphingolipid-dependent manner via detergent-resistant microdomains. Furthermore, using fluorescence correlation spectroscopy to assay the mobility of SBD in live cells, we show that SBD's behavior at the plasma membrane is similar to that of the previously described raft marker cholera toxin B, displaying both a fast and a slow component. Our data suggest that fluorescently tagged SBD can be used to investigate the dynamic nature of glycosphingolipid-rich detergent-resistant microdomains that are cholesterol-dependent.

Background: Continuous flow immunomagnetic separation is an attractive alternative to current batch mode immunomagnetic separation methods because it is capable of high sorting speeds at mild cell conditions, and grants the operator better control of separation process. The control of the separation is dependent on knowledge of the amount of magnetic label attached to the cell (magnetic labeling intensity), however. Determination of the magnetic labeling is accomplished by measuring cell magnetophoretic mobility using a newly developed technique of Cell Tracking Velocimetry (CTV)., Methods: Flow cytometry was used to define the antibody binding characteristics of a fluorescently tagged primary antibody. Subsequently, CTV was used to measure antibody-binding characteristics of a magnetically tagged secondary antibody., Results: The results of this study show that CTV is capable of providing valuable information concerning the cell labeling by magnetically tagged antibodies. It was demonstrated that the magnetically conjugated antibody binding curve exhibits the same exponential increase to saturation characteristics as that seen with the fluorescently tagged antibody. Further, it was shown that the intensity of the secondary magnetic labeling is directly proportional to the intensity of the primary fluorescent label., Conclusions: CTV is an accurate tool for evaluation of magnetically conjugated antibodies. The ability to determine the intensity of magnetic labeling is necessary for the development of continuous flow immunomagnetic separations based on cell magnetophoresis., ((c) 2005 Wiley-Liss, Inc.)