A Rubbish Idea: The material dump, and casting trash talk in a new light

Inspired by the trash-art creations of artists such as Tim Noble and Sue Webster, this creative article-assemblage was gathered together over several months by the UNNC Litter Lovers collective. The aleatoric article attempts to provocatively explore alternative ways of thinking about (or with) trash, modern life and recycling. The article is formed by found, chanced upon, and recycled fragments of used cultural material, at times united by original-organic discussions and catalytic ideas, but ultimately demands the intellectual light of the reader to cast the concepts into relief. The collective utilises form and content to generate new ways of seeing and thinking about waste and rubbish, and like the actual trash heaps and trash-art that inspired this work, they attempt to show how matter itself and (used) material is not inert and passive but rather vibrant, expressive and alive: boasting productive powers and forces capable of bringing about unforeseen reactions and new forms of synthesis. The article is designed to ignite new processes within, between, across and ‘below’ the chaotically assembled fragments. The piece is in part motivated by a drive to ethically recycle in an inspiring and creative way, and be part of new things emerging out of the old. This alternative intellectual happening is also in part designed to help people ‘clean’ their collective conscience and learn to 'love rubbish.' We hope that this is in part achieved by de-centering the human, and foregrounding a polysemous concept of the material dump that forces readers to reinterrogate everyday (non-thought) notions of waste, nature, (human) resources, thought and art.Additional co-author: the UNNC Litter Lovers (a creative academic collective

A Rubbish Idea: The material dump, and casting trash talk in a new light

Inspired by the trash-art creations of artists such as Tim Noble and Sue Webster, this creative article-assemblage was gathered together over several months by the UNNC Litter Lovers collective. The aleatoric article attempts to provocatively explore alternative ways of thinking about (or with) trash, modern life and recycling. The article is formed by found, chanced upon, and recycled fragments of used cultural material, at times united by original-organic discussions and catalytic ideas, but ultimately demands the intellectual light of the reader to cast the concepts into relief. The collective utilises form and content to generate new ways of seeing and thinking about waste and rubbish, and like the actual trash heaps and trash-art that inspired this work, they attempt to show how matter itself and (used) material is not inert and passive but rather vibrant, expressive and alive: boasting productive powers and forces capable of bringing about unforeseen reactions and new forms of synthesis. The article is designed to ignite new processes within, between, across and ‘below’ the chaotically assembled fragments. The piece is in part motivated by a drive to ethically recycle in an inspiring and creative way, and be part of new things emerging out of the old. This alternative intellectual happening is also in part designed to help people ‘clean’ their collective conscience and learn to 'love rubbish.' We hope that this is in part achieved by de-centering the human, and foregrounding a polysemous concept of the material dump that forces readers to reinterrogate everyday (non-thought) notions of waste, nature, (human) resources, thought and art

PI3K-δ and PI3K-γ Inhibition by IPI-145 Abrogates Immune Responses and Suppresses Activity in Autoimmune and Inflammatory Disease Models

SummaryPhosphoinositide-3 kinase (PI3K)-δ and PI3K-γ are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-δ and PI3K-γ inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. We explored the therapeutic value of combined PI3K-δ and PI3K-γ blockade, and IPI-145 showed potent activity in collagen-induced arthritis, ovalbumin-induced asthma, and systemic lupus erythematosus rodent models. These findings support the hypothesis that inhibition of immune function can be achieved through PI3K-δ and PI3K-γ blockade, potentially leading to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases

Smallpox, Interiority and the Emergence of the Modern European Autobiography

My dissertation examines episodes of childhood smallpox illness in the autobiographies of Franz Xaver Bronner, Giacomo Casanova, Katharina II, Wilhelmine von Bayreuth, Goethe and Johanna Schopenhauer. Drawing from Habermas’ theory of the public sphere and Friedrich Kittler’s theory of Bildung as Sozialisationsspiel, my project examines the degree to which autobiographical accounts of childhood smallpox episodes initiate a “constructed” Bildungsgeschichte, one that disguises the process of socialization through a narrative of self-fulfillment (Kittler); conversely, my project also explores the degree to which such smallpox episodes present the author’s initiation into adulthood as a moment of growth that is independent of Bildung. As an inner bodily experience, smallpox equates a subjective inner transformation of the autobiographical subject; smallpox invokes interiority as a modern construction of the body (Butler) and expresses subjective experiences of the modern self, both within the autobiographical Bildungsgeschichte as a constructed narrative of socialization (traditionally associated with the Bildungsroman) and within the autobiographies that do not express a linear Bildungsgeschichte (such as the more episodic memoirs of Casanova and Wilhelmine von Bayreuth)

Abstract B133: Identification of elatol as a novel eIF4A inhibitor and stress response activator

Abstract It is well established that protein translation can contribute the most adaptable regulation of protein-coding gene expression, is frequently hijacked during oncogenesis, and can be targeted therapeutically. Most regulation of protein translation occurs at the initiation step with formation and function of the eIF4F complex. Many different avenues, both direct and indirect, have been explored to inhibit eIF4F and thus protein translation initiation, in particular drugs targeting eIF4F’s core-enzymatic subunit, the DEAD-box RNA helicase eIF4A. Despite extensive preclinical evaluation and high antitumor activity of these compounds, none has progressed to evaluation in cancer patients, due to a variety of pharmacokinetic and pharmacodynamic issues. We designed a novel screen to identify eIF4A inhibitors by measuring ATP hydrolysis and screened a collection of ~1,200 natural compounds and purified extracts. The marine natural product elatol was the top hit in our screen, that not only showed selectivity for eIF4A over other dead box family helicases and a panel of 97 common kinases, but also induced apoptosis in a broad range of cancer cell lines from the NCI-60 cancer cell line and CCLE panels. Elatol is well tolerated in mice at a single dose of up to 65mg/kg and showed antitumor activity. Elatol treatment reduced global protein translation measured through polysome profiling and O-propargyl puromycin incorporation as well as cap-dependent translation measured by luciferase reporter and Western blotting. The effects of elatol are similar to the rocaglate silvestrol, which inhibits eIF4A although through a very different mechanism, but elatol requires higher concentrations to achieve these effects. Interestingly, elatol treatment causes strong immediate induction of the stress response transcription factor ATF4, though assessment in ATF4-deficient cells showed the toxicity of elatol is not dependent on ATF4. Unlike with silvestrol treatment, loss of translationally regulated proteins MYC and CYCLIN D3 following elatol treatment can be partially rescued by blocking the eIF2α-mediated stress response with ISRIB. Which eIF2α kinase may be mediating these effects is still under investigation. The novel mechanism of inhibition of ATP hydrolysis may be driving these unique observations compared to other eIF4A inhibitors. We believe this study provides a novel approach for identification of small molecules that have greater clinical promise for eIF4A inhibition. Citation Format: Tara L. Peters, Joseph Tillotson, Lingxiao Li, Eli Chapman, Jonathan H. Schatz. Identification of elatol as a novel eIF4A inhibitor and stress response activator [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B133

THE EFFECTS OF FATIGUE ON KNEE VALGUS ANGLES DURING FUNCTIONAL TASKS

BACKGROUND: As supporting musculature fatigues, generalized knee laxity increases, specifically dynamic knee valgus (DKV), which results in risk of musculoskeletal injury. While there is moderate research on how fatigue affects DKV in athletic populations, there is a gap in the literature relating to the general, untrained population. The purpose of this study was to determine the effect fatigue has on the DKV angle in untrained populations. METHODS: A sample of 31 subjects (age 22.29+2.47 years; 58% female) performed a drop vertical jump (DJV) test from a 30 cm plyometric box in front of the VST ProTM system by VirtuSense Technologies, measuring the DKV angles (in degrees). The DVJ test was performed before and after completion of a fatigue protocol which included wall sits, squats, and vertical jumps. Participants were considered fatigued once reached a 15% decrease of their pre-fatigue max vertical jump height, as measured with the Vertec Vertical Jump device standard protocol. Pre- and post-fatigue measurements were analyzed with paired t-tests.​ RESULTS: Results indicated a statistically significant difference in DKV angles for both the right lower extremity (RLE) (-1.18+2.26, p=0.007) and left lower extremity (LLE) (-1.19+2.2; p=0.005). In males, there was a statistically significant difference in comparing the LLE (-1.40+1.08; p\u3c0.001) pre- and post-fatigue knee valgus angles, however there was no statistically significant difference in the RLE (-.7879+1.59; p=0.103). In females, results indicated no statistically significant difference in pre- and post-fatigue DKV angle for the LLE (-1.03+2.76; p=1.32) but did find statistical significance in the RLE (-1.46+2.65; p=0.031). CONCLUSIONS: The results of our study suggest quadriceps fatigue may not play as large of a role in the increase of DKV angles as the fatigue protocol within the procedures primarily biased quadriceps muscles. Although there was a statistically significant change in DKV angles in the RLE and LLE of all participants, it did not surpass the minimal detectable change for DKV measured by the VST ProTM, but it was above the level of the standard error measurement of 1 degree. Additional research should investigate the comparison of a quadriceps versus hip musculature fatigue protocol. GRANT OR FUNDING INFORMATION: Funding received from Western Kentucky University, College of Health and Human Services Quick Turn-Around Grant (QTAG

Mechanisms of Liquid-Phase Exfoliation for the Production of Graphene

Liquid- phase exfoliation (LPE) is the principal method of producing two-dimensional (2D) materials such as graphene in large quantities with a good balance between quality and cost and is now widely adopted by both the academic and industrial sectors. The fragmentation and exfoliation mechanisms involved have usually been simply attributed to the force induced by ultrasound and the interaction with the solvent molecules. Nonetheless, little is known about how they actually occur, i.e., how thick and large graphite crystals can be exfoliated into thin and small graphene flakes. Here, we demonstrate that during ultrasonic LPE the transition from graphite flakes to graphene takes place in three distinct stages. First, sonication leads to the rupture of large flakes and the formation of kink band striations on the flake surfaces, primarily along zigzag directions. Second, cracks form along these striations, and together with intercalation of solvent, lead to the unzipping and peeling off of thin graphite strips that in the final stage are exfoliated into graphene. The findings will be of great value in the quest to optimize the lateral dimensions, thickness, and yield of graphene and other 2D materials in large-scale LPE for various applications

ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A

Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies. To this end, we have used a simple ATPase biochemical screen to survey several hundred marine and terrestrial derived natural products. Herein, we report the discovery of two natural products from marine sources, elisabatin A (1) and allolaurinterol (2), which show low mu M inhibition of eIF4A ATPase activity. Enzymological analyses revealed 1 and 2 to be ATP-competitive, and cellular evaluations showed reasonable cytotoxicity against A549 (lung cancer) and MDA-MA-468 (breast cancer) cell lines. However, only compound 2 showed potent inhibition of helicase activity congruent with its ATPase inhibitory activity. (C) 2017 Elsevier Ltd. All rights reserved.University of Arizona; National Institutes of Health (NIH) Training Grant [T32 GM008804, T32 HL007249]; National Institute of Environmental Health Sciences Training Grant [T32 ES007091]24 month embargo; available online 19 July 2017.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]