Ways of Relating: Hospitality and the acknowledgement of otherness

This paper considers the relevance of the work of Emmanuel Levinas and Jacques Derrida to geography’s engagements with both mainstream moral philosophy and poststructuralist theory. This relevance lies in the way in which their work unsettles the ascription of normative value to relations of proximity and distance. Distance is usually understood to be a medium of moral harm or indifference. In contrast, Levinas presents distance as the very condition of responsibility. Grasping the significance of this argument requires an appreciation of the temporality of responsibility and responsiveness that both Levinas and Derrida emphasise. They present an alternative way of understanding the relationality of subjectivity and social processes. Through a schematic exposition of key themes in Levinas’ work, prevalent understandings of the spatiality of relations are shown to harbour their own forms of indifference and moral harm. The full effect of Levinas’ reconsideration of the value of relations between proximity and distance is bought out in Derrida’s recent writings on hospitality. For both thinkers, there is no natural geographical scene for the cultivation of responsibility. Rather, their shared focus upon temporality emphasizes the degree to which responsibility is motivated in response to the activities of others. The implication of this argument is that critical analysis should be reoriented towards practices that shape individual and collective dispositions to acknowledge the claims of others

PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells.

Increased mRNA translation drives carcinogenesis and is an attractive target for the development of new anti-cancer drugs. In this work, we investigated effects of phenethylisothiocyanate (PEITC), a phytochemical with chemopreventive and anti-cancer activity, on mRNA translation. PEITC rapidly inhibited global mRNA translation in human breast cancer-derived MCF7 cells and mouse embryonic fibroblasts (MEFs). In addition to the known inhibitory effects of PEITC on mTORC1 activity, we demonstrate that PEITC increased eIF2α phosphorylation. PEITC also increased formation of stress granules which are typically associated with eIF2α phosphorylation and accumulation of translationally stalled mRNAs. Analysis of genetically modified MEFs demonstrated that optimal inhibition of global mRNA translation by PEITC was dependent on eIF2α phosphorylation, but not mTORC1 inhibition. We extended this study into primary leukemic B cells derived from patients with chronic lymphocytic leukaemia (CLL). CLL cells were stimulated in vitro with anti-IgM to mimic binding of antigen, a major driver of this leukemia. In CLL cells, PEITC increased eIF2α phosphorylation, inhibited anti-IgM-induced mTORC1 activation and decreased both basal and anti-IgM-induced global mRNA translation. PEITC also inhibited transcription and translation of MYC mRNA and accumulation of the MYC oncoprotein, in anti-IgM-stimulated cells. Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone. Therefore, PEITC can inhibit both global and mRNA specific translation (including MYC) via effects on multiple regulatory pathways. Inhibition of mRNA translation may contribute to the chemopreventive and anti-cancer effects of PEITC

Optical monitoring of polymerizations in droplets with high temporal dynamic range

The ability to optically monitor a chemical reaction and generate an in situ readout is an important enabling technology, with applications ranging from the monitoring of reactions in flow, to the critical assessment step for combinatorial screening, to mechanistic studies on single reactant and catalyst molecules. Ideally, such a method would be applicable to many polymers and not require only a specific monomer for readout. It should also be applicable if the reactions are carried out in microdroplet chemical reactors, which offer a route to massive scalability in combinatorial searches. We describe a convenient optical method for monitoring polymerization reactions, fluorescence polarization anisotropy monitoring, and show that it can be applied in a robotically generated microdroplet. Further, we compare our method to an established optical reaction monitoring scheme, the use of Aggregation-Induced Emission (AIE) dyes, and find the two monitoring schemes offer sensitivity to different temporal regimes of the polymerization, meaning that the combination of the two provides an increased temporal dynamic range. Anisotropy is sensitive at early times, suggesting it will be useful for detecting new polymerization “hits” in searches for new reactivity, while the AIE dye responds at longer times, suggesting it will be useful for detecting reactions capable of reaching higher molecular weights

Mapping Forbidden Emission to Structure in Self-Assembled Organic Nanoparticles

© 2018 American Chemical Society. The interplay between micromorphology and electronic properties is an important theme in organic electronic materials. Here, we show that a spirofluorene-functionalized boron-dipyrromethene (BODIPY) with an alkyl norbornyl tail self-assembles into nanoparticles with qualitatively different properties as compared to the polymerized species. Further, the nanoparticles exhibit a host of unique emissive properties, including photobrightening, a blue satellite peak, and spectral diffusion. Extensive photophysical characterization, including single-particle imaging and spectroscopy, and time-resolved fluorescence, coupled with electronic structure calculations based on an experimentally determined crystal structure, allow a mechanism to be developed. Specifically, BODIPY chromophores are observed to form quasi-two-dimensional layers, where stacking of unit cells adds either J-aggregate character or H-aggregate character depending on the direction of the stacking. Particularly strongly H-coupled domains show the rare process of emission from an upper exciton state, in violation of Kasha's rule, and result in the blue satellite peak. The spatial heterogeneity of structure thus maps onto a gradient of photophysical behavior as seen in single-particle imaging, and the temporal evolution of structure maps onto fluctuating emissive behavior, as seen in single-particle spectroscopy. Taken together, this system provides a striking example of how physical structure and electronic properties are intertwined, and a rare opportunity to use one to chart the other

Ethics and ‘fracking’: A review of (the limited) moral thought on shale gas development

Whilst claims about the ethicality of shale gas development via hydraulic fracturing (‘fracking’) are commonplace in everyday discourse, little scholarly attention has been afforded explicitly to this aspect of unconventional fossil fuel extraction. The limited research that speaks to ethical considerations largely describes ethical concerns associated with development – extremely few claims in research literature make an ethical case for development. The most common ethical concerns cited in research stem from issues of distributive justice, with procedural justice, the precautionary principle, exposure to involuntary risks, rights-based arguments, and changes in community character and way of life as next most common. Additional research hints implicitly at ethical dilemmas associated with shale gas development, but does not openly identify these issues as having moral implications. Many ethical considerations relate closely to concerns about water quality and the volume/supply of water available for other purposes. The limited scholarship in this area reveals the import of understanding the ways in which ethics permeate thoughts about shale gas development for designing policy that responds to constituent needs and concerns. Even more limited than research on ethical claims in association with shale gas development is well-reasoned scholarship that analyses the extent to which ethical claims about development are well justified and philosophically justifiable. A comprehensive and systematic analysis of the range of ethical claims potentially relevant to shale gas development and their usefulness for informing policy on this topic would contribute greatly to informed decision-making on this controversial issue – something that science alone cannot achieve

Analysis of Gene Expression in Resynthesized Brassica napus Allopolyploids Using Arabidopsis 70mer Oligo Microarrays

Background Studies in resynthesized Brassica napus allopolyploids indicate that homoeologous chromosome exchanges in advanced generations (S5:6) alter gene expression through the loss and doubling of homoeologous genes within the rearrangements. Rearrangements may also indirectly affect global gene expression if homoeologous copies of gene regulators within rearrangements have differential affects on the transcription of genes in networks. Methodology/Principal Findings We utilized Arabidopsis 70mer oligonucleotide microarrays for exploring gene expression in three resynthesized B. napus lineages at the S0:1 and S5:6 generations as well as their diploid progenitors B. rapa and B. oleracea. Differential gene expression between the progenitors and additive (midparent) expression in the allopolyploids were tested. The S5:6 lines differed in the number of genetic rearrangements, allowing us to test if the number of genes displaying nonadditive expression was related to the number of rearrangements. Estimates using per-gene and common variance ANOVA models indicated that 6–15% of 26,107 genes were differentially expressed between the progenitors. Individual allopolyploids showed nonadditive expression for 1.6–32% of all genes. Less than 0.3% of genes displayed nonadditive expression in all S0:1lines and 0.1–0.2% were nonadditive among all S5:6 lines. Differentially expressed genes in the polyploids were over-represented by genes differential between the progenitors. The total number of differentially expressed genes was correlated with the number of genetic changes in S5:6 lines under the common variance model; however, there was no relationship using a per-gene variance model, and many genes showed nonadditive expression in S0:1 lines. Conclusions/Significance Few genes reproducibly demonstrated nonadditive expression among lineages, suggesting few changes resulted from a general response to polyploidization. Furthermore, our microarray analysis did not provide strong evidence that homoeologous rearrangements were a determinant of genome-wide nonadditive gene expression. In light of the inherent limitations of the Arabidopsis microarray to measure gene expression in polyploid Brassicas, further studies are warranted

The role of experimental noise in a hybrid classical-molecular computer to solve combinatorial optimization problems

Chemical and molecular-based computers may be promising alternatives to modern silicon-based computers. In particular, hybrid systems, where tasks are split between a chemical medium and traditional silicon components, may provide access and demonstration of chemical advantages such as scalability, low power dissipation, and genuine randomness. This work describes the development of a hybrid classical-molecular computer (HCMC) featuring an electrochemical reaction on top of an array of discrete electrodes with a fluorescent readout. The chemical medium, optical readout, and electrode interface combined with a classical computer generate a feedback loop to solve several canonical optimization problems in computer science such as number partitioning and prime factorization. Importantly, the HCMC makes constructive use of experimental noise in the optical readout, a milestone for molecular systems, to solve these optimization problems, as opposed to in silico random number generation. Specifically, we show calculations stranded in local minima can consistently converge on a global minimum in the presence of experimental noise. Scalability of the hybrid computer is demonstrated by expanding the number of variables from 4 to 7, increasing the number of possible solutions by 1 order of magnitude. This work provides a stepping stone to fully molecular approaches to solving complex computational problems using chemistry

Fact and fiction in housing research: utilizing the creative imagination

As much of our conceptual framework is informed by the experience of the imagination, there is much to be learnt from a study of various creative forms. Narrative fiction can be one such form, allowing us to gain a useful insight into complex features of social life. The purpose of this article is to investigate the treatment of housing issues in contemporary literature in order to gain insights into attitudes, experiences and interpretations from the perspective of a broad cultural milieu. Discussions of professionalism, housing tenure and homelessness have tended to be conducted within a narrow framework and adopted orthodox modes of evaluation. Consequently, the neglect of housing within a wider cultural context has reinforced the isolation of housing issues. The article argues that although discussions of housing and housing policy have been seriously limited within the contemporary novel, there are a number of key insights that can be gained from a discussion of issues within a fictional setting

A randomised controlled trial of the efficacy of the ABCD Parenting Young Adolescents Program: rationale and methodology

Background: The transition to adolescence is a time of increased vulnerability for risk taking and poor health, social and academic outcomes. Parents have an important role in protecting their children from these potential harms. While the effectiveness of parenting programs in reducing problem behavior has been demonstrated, it is not known if parenting programs that target families prior to the onset of significant behavioral difficulties in early adolescence (9-14 years) improve the wellbeing of adolescents and their parents. This paper describes the rationale and methodology of a randomised controlled trial testing the efficacy of a parenting program for the promotion of factors known to be associated with positive adolescent outcomes, such as positive parenting practices, parent-adolescent relationships and adolescent behavior.Methods/Design: One hundred and eighty parents were randomly allocated to an intervention or wait list control group. Parents in the intervention group participated in the ABCD Parenting Young Adolescents Program, a 6-session behavioral family intervention program which also incorporates acceptance-based strategies. Participants in the Wait List control group did not receive the intervention during a six month waiting period. The study was designed to comply with recommendations of the CONSORT statement. The primary outcome measures were reduction in parent-adolescent conflict and improvements in parent-adolescent relationships. Secondary outcomes included improvements in parent psychosocial wellbeing, parenting self-efficacy and perceived effectiveness, parent-adolescent communication and adolescent behavior.Conclusions: Despite the effectiveness of parenting programs in reducing child behavioral difficulties, very few parenting programs for preventing problems in adolescents have been described in the peer reviewed literature. This study will provide data which can be used to examine the efficacy of a universal parenting interventions for the promotion of protective factors associated with adolescent wellbeing and will add to the literature regarding the relationships between parent, parenting and adolescent factors