Inleiding in het denken van drie vroeg-christelijke auteurs, zoals dat zich ontwikkelde tijdens de confrontatie van het christendom met het jodendom en de hellenistische filosofie.

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

© 2015 Elsevier Inc.Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides within an intracellular parasitophorous vacuole that is selectively permeable to small molecules through unidentified mechanisms. We have identified GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous vacuole membrane and mediates passive transport of small molecules across the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites have aberrant morphology, reduced permeability to (...) small molecules, and structural instability. GRA17-deficient parasites proliferate slowly and are avirulent in mice. These GRA17-deficient phenotypes are rescued by complementation with Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23. Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus, GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient access. (shrink)

The current research investigates a combination of two instructional approaches, tutored problem solving and worked examples. Tutored problem solving with automated tutors has proven to be an effective instructional method. Worked‐out examples have been shown to be an effective complement to untutored problem solving, but it is largely unknown whether they are an effective complement to tutored problem solving. Further, while computer‐based learning environments offer the possibility of adaptively transitioning from examples to problems while tailoring to an individual learner, the (...) effectiveness of such machine‐adapted example fading is largely unstudied. To address these research questions, one lab and one classroom experiment were conducted. Both studies compared a standard Cognitive Tutor with two example‐enhanced Cognitive Tutors, in which the fading of worked‐out examples occurred either in a fixed way or adaptively. Results indicate that the adaptive fading of worked‐out examples leads to higher transfer performance on delayed posttests than the other two methods. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the (...) 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

We present here a direct elementary construction of continuous utility functions on perfectly separable totally preordered sets that does not make use of the well-known Debreu’s open gap lemma. This new construction leans on the concept of a separating countable decreasing scale. Starting from a perfectly separable totally ordered structure, we give an explicit construction of a separating countable decreasing scale, from which we show how to get a continuous utility map.

In the midst of recent ethical decision-making failures in business in the past ten or more years, businesses are beginning to prioritize the moral fiber of their new-hire business graduates. In addition to academic performance, intellectual drive, and personality match, perhaps there are other key characteristics that employers seek which speak to the importance of ethical decision makers in practice. The question remains, how can academic institutions help instill such values into their students so that ethical decision making transcends their (...) lives? This article suggests that experiential learning through an institutional-sponsored business forum can help enhance an individual’s self-efficacy and awareness of the school’s value-based education, which ultimately will lead students towards ethical decision making in practice. Five years of survey data collected at business forum events suggests that business forums are making a difference in the students’ self-assessed abilities to show greater self-efficacy, better ethical decision making, and an increased awareness of their institution’s value-based education. Specifically, data collected illustrate a mediating effect of self-efficacy and awareness of a value-based education en route to ethical decision making. Further, support is found for the primary hypothesis that attendance at business forums does result in a higher propensity to make ethical decisions. Because of these positive findings, higher education institutions looking to place a greater emphasis on the ethical leadership of their business students may want to explore adding such experiential learning programs. (shrink)

The inverse of the distance between two structures $\mathscr{A} \not\equiv \mathscr{B}$ of finite type $\tau$ is naturally measured by the smallest integer $q$ such that a sentence of quantifier rank $q - 1$ is satisfied by $\mathscr{A}$ but not by $\mathscr{B}$. In this way the space $\operatorname{Str}^\tau$ of structures of type $\tau$ is equipped with a pseudometric. The induced topology coincides with the elementary topology of $\operatorname{Str}^\tau$. Using the rudiments of the theory of uniform spaces, in this elementary note we (...) prove the convergence of every Cauchy net of structures, for any type $\tau$. (shrink)

Mark Coeckelbergh (Int J Soc Robot 1:217–221, 2009) argues that robot ethics should investigate what interaction with robots can do to humans rather than focusing on the robot’s moral status. We should ask what robots do to our sociality and whether human–robot interaction can contribute to the human good and human flourishing. This paper extends Coeckelbergh’s call and investigate what it means to live with disembodied AI-powered agents. We address the following question: Can the human–AI interaction contribute to our moral (...) development? We present an empirically informed philosophical analysis of how the AI personal assistant Siri changes its users’ way of life, based on the responses obtained from 20 semi-directive individual interviews with Siri users. We identify changes in the users’ social interaction associated with the adoption of Siri. These changes include: (1) the indirect effect of reducing opportunities of human interaction, (2) the second-order effect of diminished expectations toward each other in a community, and (3) the acquired preference to obtain hassle-free interaction with Siri over human interaction. We examine them in relation to concerns that are voiced in the current debates over the rise of AI, namely the suspicion that humans could become overly reliant on AI (Danaher 2019) and the worry that social AI could impede on moral development (Fröding and Peterson, Ethics Inf Technol 23:207–214, 2012; Li, Ethics Inf Technol 23:543–550, 2021). We analyze the ethical costs that come from these changes in light of virtue ethics and address potential objections along the way. We end by offering directions for thinking about how to live with AI personal assistant while preserving favorable conditions for moral development. (shrink)

The inverse of the distance between two structures $\mathscr{A} \not\equiv \mathscr{B}$ of finite type τ is naturally measured by the smallest integer q such that a sentence of quantifier rank q - 1 is satisfied by A but not by B. In this way the space $\operatorname{Str}^\tau$ of structures of type τ is equipped with a pseudometric. The induced topology coincides with the elementary topology of $\operatorname{Str}^\tau$ . Using the rudiments of the theory of uniform spaces, in this elementary note (...) we prove the convergence of every Cauchy net of structures, for any type τ. (shrink)

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined “perioperative tumour growth” and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget1Sir James Paget (1814–1899) was a surgeon and physiologist who is widely held (along with Rudolph Virchow) to be the father of the science of pathology. Paget (...) described Paget's disease of the nipple as well as Paget's disease of bone. himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host–tumour interactions that may occur during the perioperative period. BioEssays 28: 433–437, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The Declaration of Helsinki and the Council of the International Organization of Medical Sciences provide guidance on standards of care and prevention in clinical trials. In the current and increasingly challenging research environment, the ethical status of a trial design depends not only on protection of participants, but also on social value, feasibility, and scientific validity. Using the example of a study assessing efficacy of a vaccine to prevent human papilloma virus in HIV-1 infected adolescent girls in low resource countries (...) without access to the vaccine, we compare several trial designs which rank lower on some criteria and higher on others, giving rise to difficult trade-offs. This case demonstrates the need for developing more nuanced guidance documents to help researchers balance these often conflicting criteria. (shrink)