Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. We assemble a model of a capped tropomyosin-actin minifilament (...) to demonstrate the utility of combining structures determined by different techniques. Finally, we survey the methods that attempt to transform high resolution structural biology into more physiological environments, such as the cell. Together these techniques promise a compelling decade for structural biology and, more importantly, they will provide exciting discoveries in understanding the designs and purposes of biological machines. Structural biology is undergoing technological advancements that now reveal the structures of previously inaccessible biological machines. Microfocus synchrotron beamlines, X-ray free electron lasers, and MicroED cope with vanishingly small crystals, while cryo-electron microscopy targets single molecules at near atomic resolution. These advances promise an exciting decade for structural biology. (shrink)

Assistive systems based on Artificial Intelligence (AI) are bound to reshape decision-making in all areas of society. One of the most intricate challenges arising from their implementation in high-stakes environments such as medicine concerns their frequently unsatisfying levels of explainability, especially in the guise of the so-called black-box problem: highly successful models based on deep learning seem to be inherently opaque, resisting comprehensive explanations. This may explain why some scholars claim that research should focus on rendering AI systems understandable, rather (...) than explainable. Yet, there is a grave lack of agreement concerning these terms in much of the literature on AI. We argue that the seminal distinction made by the philosopher and physician Karl Jaspers between different types of explaining and understanding in psychopathology can be used to promote greater conceptual clarity in the context of Machine Learning (ML). Following Jaspers, we claim that explaining and understanding constitute multi-faceted epistemic approaches that should not be seen as mutually exclusive, but rather as complementary ones as in and of themselves they are necessarily limited. Drawing on the famous example of Watson for Oncology we highlight how Jaspers’ methodology translates to the case of medical AI. Classical considerations from the philosophy of psychiatry can therefore inform a debate at the centre of current AI ethics, which in turn may be crucial for a successful implementation of ethically and legally sound AI in medicine. (shrink)

This book explores the nature and implications of positive, creative, and loving mimesis and brings together the interdisciplinary fields of Girardian studies and creativity studies in new and original ways. Scientists, philosophers, psychologists, theologians and ancient thinkers are brought into thought provoking and insightful dialogue with Girardian conceptions of mimetic desire, scapegoating, and hominization.

Zusammenfassung Die Zahl jener Akteure, die sich in ihrer Freizeit exzessiv und unter Absehen der dadurch ausgelösten psychischen, physischen und sozialen Konsequenzen dem Sport hingeben, ist in den letzten Jahren stark angestiegen. Sportmedizin und Sportpsychologie haben hierfür den Begriff „exercise addiction“ geprägt und eine Vielzahl wichtiger Erkenntnisse hervorgebracht. Im Unterschied zu der in diesen Disziplinen üblichen Vorgehensweise, die psychischen und physischen Aspekte des Themas personalisierend in den Vordergrund zu rücken, um das stoffungebundene Suchtverhalten im Sport zu erklären, wählt der vorliegende (...) Beitrag einen soziologischen Zugang. Die Sportsucht wird folglich als soziales Phänomen behandelt und analytisch auf einer makro-, meso- und mikrogesellschaftlichen Ebene verortet. Die soziokulturellen Bedingungen sportsüchtigen Handelns lassen sich so präzise herausarbeiten. Vor allem wird auch deutlich gemacht, warum immer mehr Menschen gerade den Sport als Suchtfeld nutzen. Damit präsentiert der Text erstmalig den Entwurf einer Soziologie der Sportsucht. (shrink)

Der Kinder- und Jugendgesundheitssurvey soll repräsentative, gültige Daten und Erkenntnisse zur gesundheitlichen Situation von Kindern und Jugendlichen in Deutschland als entscheidende Voraussetzung für die Bewertung und die Verbesserung von deren gesundheitlicher Lage schaffen. Forschung und insbesondere Blutentnahmen an nichteinwilligungsfähigen Personen erfordern eine profunde ethische und rechtliche Überprüfung. Der Beitrag befasst sich damit, welche medizinethischen Empfehlungen und welche rechtlichen Grundsätze in Deutschland für die Bewertung relevant sind. Nach geltendem deutschen Recht können Eltern zu Blutentnahmen bei ihren Kindern nur zustimmen, wenn diese (...) in deren individuellem gesundheitlichen Interesse liegen. Ein „gruppenspezifischer Nutzen“, wie er von Medizinethikern national und international als Voraussetzung für ethische Akzeptabilität (bei minimalem Risiko der Untersuchungen) ebenfalls für sinnvoll und wichtig angesehen wird, und der in dem geplanten Survey in jedem Falle gegeben wäre, genügt deutschen Rechtsansprüchen nicht. Im Pretest hat sich der potenzielle individuelle Nutzen der Blutentnahmen bestätigt: Viele Kinder hatten biochemisch nachweisbare Gesundheitsrisiken (z. B. verborgener Nährstoffmangel, allergische Sensibilisierung, Hinweise auf Impflücken oder langfristige Gesundheitsrisiken), die ohne Blutuntersuchung nicht feststellbar gewesen wären. Bei über 90% der Kinder waren nach schriftlicher Einwilligung der Eltern und Jugendlichen sowie informeller Zustimmung der Kinder, die in jedem einzelnen Falle berücksichtigt wurde, Blutentnahmen möglich. Nach der Befragung einer Unterstichprobe ist die Akzeptanz insgesamt gut. (shrink)

Der Kinder- und Jugendgesundheitssurvey soll repräsentative, gültige Daten und Erkenntnisse zur gesundheitlichen Situation von Kindern und Jugendlichen in Deutschland als entscheidende Voraussetzung für die Bewertung und die Verbesserung von deren gesundheitlicher Lage schaffen. Forschung und insbesondere Blutentnahmen an nichteinwilligungsfähigen Personen erfordern eine profunde ethische und rechtliche Überprüfung. Der Beitrag befasst sich damit, welche medizinethischen Empfehlungen und welche rechtlichen Grundsätze in Deutschland für die Bewertung relevant sind. Nach geltendem deutschen Recht können Eltern zu Blutentnahmen bei ihren Kindern nur zustimmen, wenn diese (...) in deren individuellem gesundheitlichen Interesse liegen. Ein „gruppenspezifischer Nutzen“, wie er von Medizinethikern national und international als Voraussetzung für ethische Akzeptabilität (bei minimalem Risiko der Untersuchungen) ebenfalls für sinnvoll und wichtig angesehen wird, und der in dem geplanten Survey in jedem Falle gegeben wäre, genügt deutschen Rechtsansprüchen nicht. Im Pretest hat sich der potenzielle individuelle Nutzen der Blutentnahmen bestätigt: Viele Kinder hatten biochemisch nachweisbare Gesundheitsrisiken (z. B. verborgener Nährstoffmangel, allergische Sensibilisierung, Hinweise auf Impflücken oder langfristige Gesundheitsrisiken), die ohne Blutuntersuchung nicht feststellbar gewesen wären. Bei über 90% der Kinder waren nach schriftlicher Einwilligung der Eltern und Jugendlichen sowie informeller Zustimmung der Kinder, die in jedem einzelnen Falle berücksichtigt wurde, Blutentnahmen möglich. Nach der Befragung einer Unterstichprobe ist die Akzeptanz insgesamt gut. (shrink)

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. (...) The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank. (shrink)

Neurotrophins (NTs) are {?AUTHOR} a family of structurally related, secreted proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons.1,2 Among these, BDNF (brain‐derived neurotrophic factor) has drawn considerable interest because both its synthesis and secretion are increased by physiological levels of activity, indicating a unique role of this neurotrophin in coupling neuronal activity to structural and functional properties of neuronal circuits. In addition to its classical neurotrophic effects, which are evident within (...) hours or days and which usually result from changes in cellular gene expression, BDNF exerts acute effects on synaptic transmission and is involved in the induction of long‐term potentiation. Many of these rapid effects of BDNF are mediated by its modulation of ion channel properties following TrkB‐mediated activation of intracellular second messenger cascades and protein phosphorylation. However, recent reports have shown that BDNF not only acts as a modulator of ion channels, but can also directly and rapidly gate a Na+ channel, thereby assigning BDNF the properties of a classical excitatory transmitter. Thus, BDNF, in addition its role as a potent neuromodulator, emerges as an excitatory transmitter‐like substance which acutely controls resting membrane potential, neuronal excitability, synaptic transmission and participates in the induction of synaptic plasticity. BioEssays 26:1185–1194, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Epikurs Lehre erfreut sich wachsender Aufmerksamkeit. Doch verdient auch die Geschichte des Epikureismus, insbesondere der Kaiserzeit, Interesse. Keineswegs verschwindet die diesseits orientierte Lehre Epikurs trotz wachsendem Streben der Philosophie nach Transzendenz in der Spatantike. Eine Analyse paganer wie auch christlicher Autoren zeigt, dass insbesondere Epikurs Ethik und ihr Angebot praktischer Lebenshilfe als Teil einer "praeparatio philosophica" uberlebt, ins Mittelalter vermittelt wurde und in der Renaissance Auferstehung feierte. Die Vortrage dieses Bandes begeben sich deshalb auf Spurensuche. Unter verschiedenen Gesichtspunkten gehen sie (...) der Tradition des Epikureismus in der spaten Republik und der Kaiserzeit nach und folgen ihnen bis zur Renaissance. Inhalt: Einleitung Graziano Arrighetti: Filodemo fra poesia, mito e storia Marcello Gigante: Seneca, ein Nachfolger Philodems? Dieter Timpe: Der Epikureismus in der romischen Gesellschaft der Kaiserzeit Martin F. Smith: Digging up Diogenes: New Epicurean texts from Oinoanda in Lycia Diskin Clay: Diogenes and his gods Matthias Baltes: Epikureische Theologie Mauro Tulli: L'epitome die Epicuro e la trasmissione del sapere nel Medioplatonismo Carlos Levy: Philon d'Alexandrie et l'epicurisme Tiziano Dorandi: Plotina, Adriano e gli Epicurei di Atene Franco Ferrari: La falsita delle asserzioni relative al futuro: un argomento epicureo contro la mantica in Plut. Pyth. orac. 10 Keimpe A. Algra: The Treatise of Cleomedes and its Critique of Epicurean Cosmology Christoph Markschies: Epikureismus bei Origenes und in der origenistischen Tradition Jose Kany-Turpin: Lactance, un critique mesestime de l'epicurisme Therese Fuhrer: Zwischen Skeptizismus und Platonismus: Augustins Auseinandersetzung mit der epikureischen Lehre in conf. 6 Dominic O'Meara: Epikur bei Simplikios Clemens Zintzen: Epikur in der Renaissance Michael Erler: Epikur in Raffaels "Schule von Athen"? Register. (shrink)

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks (...) of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent. (shrink)

Biological evolution provides a creative fount of complex and subtle adaptations, often surprising the scientists who discover them. However, because evolution is an algorithmic process that transcends the substrate in which it occurs, evolution’s creativity is not limited to nature. Indeed, many researchers in the field of digital evolution have observed their evolving algorithms and organisms subverting their intentions, exposing unrecognized bugs in their code, producing unexpected adaptations, or exhibiting outcomes uncannily convergent with ones in nature. Such stories routinely reveal (...) creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This paper is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems. (shrink)

This is explained in a new introduction that goes beyond the interpretative enterprise of the rest of the book to assess Marx in relation to contemporary ...

Studie over de filosofie van de in Oostenrijk geboren Engelse wijsgeer.