While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

It is important to understand the processes behind how and why individuals emerge as leaders, so that the best and most capable individuals may occupy leadership positions. So far, most literature in this area has focused on individual characteristics, such as personality or cognitive ability. While interactions between individuals and context do get research attention, we still lack a comprehensive understanding of how the social context at work may help individuals to emerge as leaders. Such knowledge could make an important (...) contribution toward getting the most capable, rather than the most dominant or narcissistic individuals, into leadership positions. In the present work, we contribute toward closing this gap by testing a mediation chain linking a leader's leader self-awareness to a follower's leadership emergence with two time-lagged studies (nstudy1 = 449, nstudy2 = 355). We found that the leader's leader self-awareness was positively related to (a) the follower's leadership emergence and (b) the follower's nomination for promotion and that both relationships were serially mediated by the follower's self-leadership and the follower's leader self-efficacy. We critically discuss our findings and provide ideas for future research. (shrink)

Artificial social intelligence (ASI) agents have great potential to aid the success of individuals, human–human teams, and human–artificial intelligence teams. To develop helpful ASI agents, we created an urban search and rescue task environment in Minecraft to evaluate ASI agents’ ability to infer participants’ knowledge training conditions and predict participants’ next victim type to be rescued. We evaluated ASI agents’ capabilities in three ways: (a) comparison to ground truth—the actual knowledge training condition and participant actions; (b) comparison among different ASI (...) agents; and (c) comparison to a human observer criterion, whose accuracy served as a reference point. The human observers and the ASI agents used video data and timestamped event messages from the testbed, respectively, to make inferences about the same participants and topic (knowledge training condition) and the same instances of participant actions (rescue of victims). Overall, ASI agents performed better than human observers in inferring knowledge training conditions and predicting actions. Refining the human criterion can guide the design and evaluation of ASI agents for complex task environments and team composition. (shrink)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from (...) social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic. (shrink)

Excerpt from Studies in Human Nature The aim of these studies is to examine with all possible freedom from theoretical bias some phases of human nature which are of great interest in themselves, and in the light of the analysis to draw certain conclusions. It would have been natural to have included in such a series the consideration of certain other aspects of human nature, more especially those which concern morality and civic institutions. Morality and the conditions of citizenship arc (...) in many ways the most important forms of human life which can engage our attention at the present time; and the influence of the recent upheaval in our experience has brought before us many moral problems with a peculiar, and perhaps even a new', prominence. It has seemed better, however, to reserve the consideration of these and kindred subjects for another occasion. It is not the purpose of these papers to defend or support any of the familiarly accepted theories, whether of idealism or realism. Human nature is far more interesting and much more important than any theory, and on that account perhaps is tolerant of many theories. It may be remarked, however, that the momentum which carried forward one peculiar form of idealism - the confident and confiding idealism of a generation ago - seems now to have spent its force; and that a realism which takes the form of a new materialism can hardly claim to be in a position to show a better way. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

In general, epistemic internalists hold that an individual’s justification for a belief is exhausted by her reflectively accessible reasons for thinking that the contents of her beliefs are true. Applying this to the epistemology of testimony, a hearer’s justification for beliefs acquired through testimony is exhausted by her reflectively accessible reasons to think that the contents of the speaker’s testimony is true. A consequence of internalism is that subjects that are alike with respect to their reflectively accessible reasons are alike (...) with respect to what they have justification to believe. Testimony should be thought no different: hearers that are alike with respect to reflectively accessible reasons to think that a speaker’s testimony is true are alike with respect to their justification for beliefs based upon that testimony. But it has been recently argued that this view faces powerful counterexamples. So the central question is this: assuming that a hearer can acquire justification to believe a proposition through the testimony of a speaker, can epistemic internalism provide the resources to explain how such justification is possible? My aim in this paper is to address these counterexamples, and in so doing, defend epistemic internalist accounts of testimony. (shrink)

The role of microaggressions has gained increasing philosophical attention in recent years. However, microaggressions only tell part of the story. An often-overlooked component of inequality is the uneven and unjust distribution of microaffirmations. In this paper, I give a new definition of microaffirmations as signals that a recipient belongs to some valued or high-status class. Microaffirmations can—but need not—lead individuals to gain a sense of confidence, belonging, and merit. I then explain the harms of microaffirmations, arguing that when microaffirmations are (...) distributed inequitably, they can have larger ramifications for injustice, harming some vulnerable groups more than others. In addition, microaffirmations can lead individual actors to make choices based on who gives them microaffirmations and where they receive them, and thus can have outsized influence over the direction of an individual’s life because individuals tend to migrate to where they feel valued, appreciated, and included. I then turn to solutions to the problems I raise. I argue we should attend to and attempt to rectify inequalities in microaffirmations because doing so can help ensure not just the absence of negative attention, but also that the presence of positive attention is flowing in a just and equitable way. (shrink)

The New Evil Demon problem has been hotly debated since the case was introduced in the early 1980’s (e.g. Lehrer and Cohen 1983; Cohen 1984), and there seems to be recent increased interest in the topic. In a forthcoming collection of papers on the New Evil Demon problem (Dutant and Dorsch, forthcoming), at least two of the papers, both by prominent epistemologists, attempt to resist the problem by appealing to the distinction between justification and excuses. My primary aim here is (...) to critically evaluate this new excuse maneuver as a response to the New Evil Demon problem. -/- Their response attempts to give us reason to reject the idea that victims of the New Evil Demon have justification for believing as they do. I shall argue that this approach is ultimately unsuccessful, however much of value can be learned from these attempts. In particular, progress in the debate can be made by following those who advance the excuse maneuver and make explicit the connection between epistemic justification and epistemic norms. By doing so, the questions being debated are clarified, as is the methodology being used to attempt to answer them. (shrink)

The ELSI Program: Closing the Loop was an interpretive policy study undertaken to identify how the research and the researchers funded through the program to study the ethical, legal, and social implications of mapping the human genome contributed to the construction of a public policy agenda. The stated goals of this federal grant program, known as ELSI and administered through the National Center for Human Genome Research within the National Institutes of Health, was to maximize the benefits and minimize the (...) harms of the genetic information developed as a result of the government supported genomic research. The purpose of the research project was to generate meaning and understanding regarding the social constructions of this community of researchers. Specifically, identifying themes in the process and outcomes of the research activity was intended to inform future public policy actions, thereby, closing the loop on the reflexive activity generated by the ELSI Program. The activities of the sixty-four researchers granted awards between 1990 and 1993 comprised the core sample for the study. The research process was embedded in a constructivist philosophy and the design included participant observation and an analysis of textual materials generated by the grantees. Data included periodical articles, authored and edited books, videos, popular print and visual media materials, conference papers and presentations, forum reports, interviews, and materials generated by the researcher in the process of the research--notes and analytic memos. Data analysis was an interpretive synthesis of a content analysis, contextual analysis, grounded theory coding categories, and the reflexive process of the researcher. ;The phenomena under investigation were the interactional activities of the ELSI group of researchers through which meaning was shaped on the ethical, legal, and social implications of genomic mapping. A theoretical model of the constructions of the researchers as developed included two core categories: "Framing Academic Constructions" and "Institutionalizing the Myth". The ELSI researchers used a variety of strategies, including rhetorical questioning, professional blocking and impersonalizing, plying a trade, and academic time in generating constructions. The research and researchers contributed to institutionalizing a myth of a genome through strategies that included being the expert, narrowing the focus, and marveling. The consequence of these social interactions was a process of "Making Points Not Meaning", participation in symbolic activities that generated few issues for the public policy agenda. The constructions of the policy study were then situated in the context of the discipline of public administration and policy studies. Significant to the impact of the research findings was understanding how the cooptation of these researchers might effect an health care delivery system dominated by commercial interests such as biotechnology and managed care organizations. The study concluded with a discussion of how situated knowledge constructions, social epistemology, interdisciplinarity, and interpretive research methods might contribute to enhanced credibility in public policy actions. (shrink)

When fcc single crystals with high-symmetry crystal orientations are deformed to moderate strains by rolling, tension or channel die compression, long dislocation boundaries inclined to the extension axis form. Similarly, long dislocation boundaries are often found in grains embedded in polycrystals deformed in the same manner. These extended planar boundaries are characteristically - 30-40° from the extension direction and contain the transverse specimen axis. The objective of the present article is to demonstrate that EPBs formed during plane strain deformation are (...) parallel to equivalent slip planes, a pair of hypothetical slip systems used for analyses of the strain and crystal rotation components in place of the larger number of physical slip systems. The coincidence of EPBs and equivalent slip plane inclinations is shown to account for persistent observations of EPBs in the angle range - 30-40° from the rolling direction, in rolled single crystals of various initial orientations. The tendency of EPBs towards tilt or twist boundary character can also be rationalized on the basis of the equivalent slip system concept and consideration of the dislocation types available to be incorporated into EPBs. (shrink)

A new ecumenical confession of faithRecently theologians, church leaders and even churches from all over the world expressed the desirability of a new confession of faith, preferably an ecumenical confession. The Reformed Church in America proposed a new confession with their Song of Hope. They still maintain large parts of their 16th century reformed confessions but the following motives played a role in their desire for a new confession:• The necessity to correct the existing, 'old' confessions in the light of (...) modem scientific Bible-research, e g on the doctrine of predestination.• The need for additional confession-pronouncements on modern-day issues and experiences, unknown to the church in the 16th century.• The desirability of a new form to communicate with modem man.• The sensitivity of the churches of today towards church-unity and the trends living in the oikouménè, e g their social awareness.We then proceed to treat the motives why a reformed Church überhaupt needs and forms a confession. In the light of these motives the question arises whether our Church really needs a new confession today; is the exposition of the existing confessions in theology, catechesis, preaching and modem church-hymns not enough to translate and communicate the existing confessions to modem man and to address modern-day issues? (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

n this note I wish to reopen discussion of the role of Cornelius Nepos in Catullus' dedicatory poem. The Callimachean features of Catullus' assessment of his own work have been well documented. However I believe that, since this is a poem where Catullus evaluates not only his own work, but also that of Nepos, a closer examination of the latter is called for.

What obligations do global actors have to prevent terrorism? Is consent required to create an international obligation, or does the correctness of its goals ground its legitimacy? In this paper, I consider these questions with respect to a subset of international law often overlooked: anti-money laundering and combating the financing of terrorism . AML/CFT comprises peaceful response to violence and terrorism, making it a significant component of international justice and diplomacy. First, I present the current legal framework for AML/CFT institutions (...) and identify two conflicting sources of justification: objective value and consent. The fix for this problem, I argue, does not come from either component alone. Objective value cannot provide the sole source of justification because it cannot settle the choice between multiple competing norms that would achieve the same objective goods were we to follow them . Consent cannot provide the sole source of justification (‘the const.. (shrink)