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In this paper we discuss to what extent one can infer details of the interior structure of a black hole based on its horizon. Recalling that black hole thermal properties are connected to the non-classical nature of gravity, we circumvent the restrictions of the no-hair theorem by postulating that the black hole interior is singularity free due to violations of the usual energy conditions. Further these conditions allow one to establish a one-to-one, holographic projection between Planckian areal “bits” on the horizon and “voxels”, representing the gravitational degrees of freedom in the black hole interior. We illustrate the repercussions of this idea by discussing an example of the black hole interior consisting of a de Sitter core postulated to arise from the local graviton quantum vacuum energy. It is shown that the black hole entropy can emerge as the statistical entropy of a gas of voxels.
Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas with a very poor prognosis. Current therapies, based on historical regimens for aggressive B-cell lymphomas, have resulted in insufficient patient outcomes. The majority of patients relapse rapidly, and current 5-year overall survival rates are only 10–30%. It is evident that new approaches to treat patients with PTCL are required. In recent years, prospective studies in PTCL have been initiated, mainly in patients with relapsed/refractory disease. In some of these, selected histologic subtypes have been evaluated in detail. As a consequence, numerous new therapies have been developed and shown activity in PTCL, including: agents targeting the immune system (e.g. brentuximab vedotin, alemtuzumab, lenalidomide); histone deacetylase inhibitors (romidepsin, belinostat); antifolates (pralatrexate); fusion proteins (denileukin diftitox); nucleoside analogs (pentostatin, gemcitabine); and other agents (e.g. alisertib, plitidepsin, bendamustine, bortezomib). A variety of interesting novel combinations is also emerging. It is hoped that these innovative approaches, coupled with a greater understanding of the clinicopathologic features, pathogenesis, molecular biology, and natural history of PTCL will advance the field and improve outcomes in this challenging group of diseases. This review summarizes the currently available clinical evidence on the various approaches to treating relapsed/refractory PTCL, including the role of stem cell transplantation, with an emphasis on potential new drug therapies.
Based on a meta-analysis, Redick and Lindsey (2013) found that complex span and n-back tasks show an average correlation of r = 0.20, and concluded that "complex span and n-back tasks cannot be used interchangeably as working memory measures in research applications" (p. 1102). Here, we comment on this conclusion from a psychometric perspective. In addition to construct variance, performance on a test contains measurement error, task-specific variance, and paradigm-specific variance. Hence, low correlations among dissimilar indicators do not provide strong evidence for the existence, or absence, of a construct common to both indicators. One way to arrive at such evidence is to fit hierarchical latent factors that model task-specific, paradigm-specific, and construct variance. We report analyses for 101 younger and 103 older adults who worked on nine different working memory tasks. The data are consistent with a hierarchical model of working memory, according to which both complex span and n-back tasks are valid indicators of working memory. The working memory factor predicts 71% of the variance in a factor of reasoning among younger adults (83% for among older adults). When the working memory factor was restricted to any possible triplet of working memory tasks, the correlation between working memory and reasoning was inversely related to the average magnitude of the correlations among the indicators, indicating that more highly intercorrelated indicators may provide poorer coverage of the construct space. We stress the need to go beyond specific tasks and paradigms when studying higher-order cognitive constructs, such as working memory.
Smac (second mitochondria-derived activator of caspase) mimetics are considered as promising anticancer therapeutics and used to induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are often abundantly expressed in cancer cells. Here, we identify interferon regulatory factor 1 (IRF1) as a novel critical regulator of Smac mimetic BV6-induced apoptosis and proinflammatory cytokine secretion with impact on the immune response. IRF1 knockdown rescues cells from BV6-induced apoptosis and attenuates BV6-stimulated upregulation of tumor necrosis factor-α (TNFα), indicating that IRF1 mediates BV6-triggered cell death, at least in part, by inducing TNFα. This notion is supported by data showing that exogenous supply of TNFα restores BV6-induced cell death in IRF-knockdown cells. Interestingly, IRF1 selectively controls the induction of nuclear factor-κB (NF-κB) target genes, as IRF1 depletion attenuates BV6-stimulated upregulation of TNFα and interleukin-8 (IL-8) but not p100 and RelB. Concomitant knockdown of IRF1 and p65 cooperate to inhibit BV6-induced cell death, implying a cooperative interaction of IRF1 and NF-κB. In addition, IRF1 silencing hampers TNFα induction by TNFα itself as an another prototypical NF-κB stimulus. Importantly, IRF1 depletion impedes BV6-stimulated secretion of additional proinflammatory cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IL-6 and monocyte chemoattractant protein-1, and migration of primary monocytes to BV6-treated tumor cells. In conclusion, this identification of IRF1 as a dual regulator of BV6-induced apoptosis and inflammatory cytokine secretion provides novel insights into determinants of sensitivity towards Smac mimetic and possible implications of Smac mimetic treatment on tumor microenvironment and immune response.
How to write (international) legal histories that would be true to their protagonists while simultaneously relevant to present audiences? Most of us would also want to write "critically" – that is to say, at least by aiming to avoid Eurocentrism, hagiography and commitment to an altogether old-fashioned view of international law as an instrument of progress. Hence we write today our histories "in context". But this cannot be all. Framing the relevant "context" is only possible by drawing upon more or less conscious jurisprudential and political preferences. Should attention be focused on academic debates, military power, class structures or assumptions about the longue durée? Such choices determine for us what we think of as relevant "contexts", and engage us as participants in large conversations about law and power that are not only about what once "was" but also what there will be in the future.
Political theology’s recent rise to academic prominence has, no doubt, been inspired by the sense of a certain staleness of standard (read: Anglo-American) analytical political and legal theory. Especially postcolonial and postmodern philosophy has resuscitated debates about the reality of secularization in Europe, pointing out that much of our shared political metaphysic is indeed that – a metaphysic – with close historical links to debates in theology. That should be no surprise. For almost half a millennium theology stood as the primus inter pares among the three "higher faculties" at European universities. The best minds at work in Europe explained the social and political changes to European audiences within a fully God-centric intellectual universe. Awareness of that fact, as Wim Decock points out in this massive and brilliant work, not only assists us in understanding the development of our political and legal vocabularies. It also enables us to grasp the contingency of our present debates, the way opposite standpoints on political and legal obligation refer back to assumptions about human nature, the roles of individual and society and the nature of "law" that are hard to detach from religious speculation. ...
The children's book "Duck! Rabbit!" dramatizes the lesson that just because one is right, others don’t have to be wrong. An endless dispute is quickly settled once the quarrellers experience an aspect change or gestalt switch and thereby realize that the same picture can be seen in different ways. This simple scenario offers an intriguing model for arbitrating between conflicting positions by going back and forth between different aspects and thereby realizing that conflicting accounts can be equally valid.
The notion of ambivalence currently seems to be an invigorating figure with heuristic potential in political, social, and art theory. It refers to a plurality of possibilities, a paradoxical multiplicity, and a complex relationality. It foregrounds thinking in terms of indeterminacy and incommensurability, as well as in terms of the possible. Ambivalence has been deployed in positive ways, as offering political promise, while, at the same time, being regarded with suspicion.
In 1989 the triumphant discourse on the 'end of history' brought the death of socialism and the expansion of liberal democracy. The proclamation of the end of history could also be read literally, as the death of 'history' as a discipline with a homogenized narrative. It is in the same year that Pierra Nora wrote a groundbreaking article, which disentangled the fundamental opposition between history and memory, and at the end assumed the standpoint of memory. The article departs from the diagnosis of post-Yugoslav contemporary accounts of Yugoslav and partisan events. The critique of nationalist and Yugonostalgic discourses discloses shared assumptions that are based on the 'romantic' temporality of Nation and on history as a closed process. In the main part of the article the author works on the special, multiple temporality of partisan poetry that emerged during the WWII partisan struggle. The special temporality hinges on the productive and tensed relationship between the 'not yet existing' - the position of the new society free of foreign occupation, but also in a radically transformed society - and the contemporary struggle within war, which is also marked by the fear that the rupture of the struggle might not be remembered rightly, if at all. The memory of the present struggle remains to be the task to be realized not only for poets, but for everyone participating in the struggle. This is where the revolutionary temporality of the unfinished process comes to its fore, relating poetry to struggle, but again producing a form of poetry in the struggle.
Identity politics redux
(2014)
Pornography reappropriated by feminist and queer pornographers is being reimagined as a site of activist productions, be it through the reshaping of desire or engaging with wider discussions of representational politics. Here, K. Heintzman takes up Shine Louise Houston's feature length film, "The Wild Search", as a unique case study for addressing the relationship between debates of identity politics and queer activist practice.
In his major theoretical work on experimentation, "Towards a History of Epistemic Things" (1997), Hans-Jörg Rheinberger writes: 'If experimental systems have a life of their own, precisely what kind of life they have remains to be determined.' Rheinberger is alluding to the slogan Ian Hacking gave to the post-Kuhnian 'practical turn' in the history and epistemology of science.
This paper deals with the general topic of subjectivity and subjectivation, considered through a philosophical tradition opposed to the 'philosophies of consciousness': that is, a philosophical tradition, from Spinoza to Althusser, that rejects as a myth the supposed primacy and presocial character of subjective identity.
The Rubin vase and duck-rabbit have two things in common: not only are they famous multistable figures, or 'Kippbilder', but before being discovered by scientists and philosophers, they both started their career as simple jokes. In contrast to usual understandings of 'Kippbilder', this paper will try to demonstrate that 'Kippbilder' can be a helpful model for understanding better dramatic, existential, and even religious events and their consequences. Multistable figures or 'Kippbilder' combine reversibility and irreversibility in an interesting way. While the so called first aspect change introduces an irreversible split, all subsequent aspect changes can be understood as an endless chain of reversible changes. After discussing the specificity of the Rubin vase and its aspect changes and focussing then on the distinction between first and further aspect changes, Di Blasi suggests the productive potential of the multistable figure as model for eventful events in discussing the conversion of Paul and his 'hōs mē' ('as if not').
Aspects and abstracta
(2014)
Philosophers of perception and psychologists first studied 'multistable' or 'reversible' figures, 'Kippbilder', in the nineteenth century. The earliest description of the phenomenon of a 'sudden and involuntary change in the apparent position' of a represented object occurred in a letter written by Louis Albert Necker in Geneva to Sir David Brewster on 24 May 1832 and published six months later in the "Philosophical Magazine". The picture in question would become known as the Necker cube.
KippCity
(2014)
On 28 April 2011, on the Rathausplatz of Neukölln, Christine Hentschel's puzzlement vis-à-vis Neukölln's liberation met the neighbourhood's flickering urbanity, which she seeks to capture in a project called KippCity. KippCity is an experiment in tracing urban change while it happens. If space is the 'event of place', as Doreen Massey holds, the space of KippCity is the transformation of Neukölln. This chapter explores the potentials of multistable figures (Kippbilder) for conceptualizing urban change. This potential, Hentschel argues, lies in the flip-moment itself, in the space-time of urban transformation. In Berlin-Neukölln, a neighbourhood long branded as poor and failing, multiple and partly conflicting flip-scenarios have begun to inspire and haunt the neighbourhood and its self-reflective talk. KippCity Neukölln is thus a flickering figure. But unlike an artefact Kippbild, which flickers between duck and rabbit, for example, KippCity Neukölln does not simply tip into a new pre-fabricated form, but rather wavers between different future scenarios. Neukölln's flickering urbanity is thus nervous, full of uncertainty, frustration and enthusiasm. The article shows how the neighbourhood seeks escape from the dystopia of two dominant flip scenarios of ghettoization and gentrification by digging its claws into its 'Now'.
Introduction
(2014)
The experience of multistable figures or so-called Kippbilder - the sudden and repeated 'kippen' of perception as the same object is seen under different aspects - is fascinating in its own right. However, what animated the year-long discussion leading to this volume was a critical exploration of the proposition that such figures may offer a helpful model for thinking through the intercultural and interdisciplinary effort of productively negotiating between conflicting positions.
Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride. To address the role of GlnA2 in the biosynthesis of the osmolytes glutamate and glutamine, a deletion mutant (ΔglnA2) was generated and characterized in detail. We compared the pool of compatible solutes and performed transcriptional analyses of the principal genes controlling the solute production in the wild type strain and the deletion mutant. These measurements did not confirm the hypothesized role of GlnA2 in the osmolyte production. Most likely the presence of another, yet to be identified enzyme has the main contribution in the measured activity in crude extracts and probably determines the total chloride-modulated profile. The role of GlnA2 remains to be elucidated.
The article aims to investigate, under the aspect of translation, the process of legal appropriation and reproduction of international law during the course of the 19th century. An occidental understanding of translation played an important role in the so-called process of universalization in the 19th century, as it made the complexity of global circulation of ideas invisible. Approaches proposed by scholars of Postcolonial, Cultural and Translation Studies are useful for re-reading histories of the circulation of European ideas, particularly the international law doctrines, from a different perspective. The great strides made in Translation and Cultural Studies in the last decades, as well as the discernment practiced in the scholarship of Postcolonial Studies, are important for a broader and more differentiated understanding of the processes of appropriation and reproduction of the doctrines of international law during the 19th century. The present article begins by tracing the connection between translation and universalization of concepts in 19th century international law; after a short excursus on the Western idea of translation, the attention is focused on the translation of international law textbooks. The conclusive section is dedicated to a comparison between Emer de Vattel’s Droit des gens and Andrés Bello’s Principios de Derecho de Jentes.
During embryonic development a large number of widely differing and specialized cell types with identical genomes are generated from a single totipotent zygote. Tissue specific transcription factors cooperate with epigenetic modifiers to establish cellular identity in differentiated cells and epigenetic regulatory mechanisms contribute to the maintenance of distinct chromatin states and cell-type specific gene expression patterns, a phenomenon referred to as epigenetic memory. This is accomplished via the stable maintenance of various epigenetic marks through successive rounds of cell division. Preservation of DNA methylation patterns is a well-established mechanism of epigenetic memory, but more recently it has become clear that many other epigenetic modifications can also be maintained following DNA replication and cell division. In this review, we present an overview of the current knowledge regarding the role of histone lysine methylation in the establishment and maintenance of stable epigenetic states.
The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters. However, it is unknown why these distinct nerve terminal configurations are used on the same postsynaptic muscle fiber. To systematically dissect the biophysical properties of these boutons we developed a full three-dimensional model of such boutons, their release sites and transmitter-harboring vesicles and analyzed the local vesicle dynamics of various configurations during stimulation. Here we show that the rate of transmission of a bouton is primarily limited by diffusion-based vesicle movements and that the probability of vesicle release and the size of a bouton affect bouton-performance in distinct temporal domains allowing for an optimal transmission of the neural signals at different time scales. A comparison of our in silico simulations with in vivo recordings of the natural motor pattern of both neurons revealed that the bouton properties resemble a well-tuned cooperation of the parameters release probability and bouton size, enabling a reliable transmission of the prevailing firing-pattern at diffusion-limited boutons. Our findings indicate that the prevailing firing-pattern of a neuron may determine the physiological and morphological parameters required for its synaptic terminals.