Between Philosophy and Art

Similarity and difference, patterns of variation, consistency and coherence: these are the reference points of the philosopher. Understanding experience, exploring ideas through particular instantiations, novel and innovative thinking: these are the reference points of the artist. However, at certain points in the proceedings of our Symposium titled, Next to Nothing: Art as Performance, this characterisation of philosopher and artist respectively might have been construed the other way around. The commentator/philosophers referenced their philosophical interests through the particular examples/instantiations created by the artist and in virtue of which they were then able to engage with novel and innovative thinking. From the artists’ presentations, on the other hand, emerged a series of contrasts within which philosophical and artistic ideas resonated. This interface of philosopher-artist bore witness to the fact that just as art approaches philosophy in providing its own analysis, philosophy approaches art in being a co-creator of art’s meaning. In what follows, we discuss the conception of philosophy-art that emerged from the Symposium, and the methodological minimalism which we employed in order to achieve it. We conclude by drawing out an implication of the Symposium’s achievement which is that a counterpoint to Institutional theories of art may well be the point from which future directions will take hold, if philosophy-art gains traction

Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library

<p>Abstract</p> <p>Background</p> <p>Amino acid sequence diversity is introduced into a phage-displayed peptide library by randomizing library oligonucleotide DNA. We recently evaluated the diversity of peptide libraries displayed on T7 lytic phage and M13 filamentous phage and showed that T7 phage can display a more diverse amino acid sequence repertoire due to differing processes of viral morphogenesis.</p> <p>Methods</p> <p>In this study, we evaluated and compared the diversity of a 12-mer T7 phage-displayed peptide library randomized using codon-corrected trinucleotide cassettes with a T7 and an M13 12-mer phage-displayed peptide library constructed using the degenerate codon randomization method.</p> <p>Results</p> <p>We herein demonstrate that the combination of trinucleotide cassette amino acid codon randomization and T7 phage display construction methods resulted in a significant enhancement to the functional diversity of a 12-mer peptide library. This novel library exhibited superior amino acid uniformity and order-of-magnitude increases in amino acid sequence diversity as compared to degenerate codon randomized peptide libraries. Comparative analyses of the biophysical characteristics of the 12-mer peptide libraries revealed the trinucleotide cassette-randomized library to be a unique resource.</p> <p>Conclusion</p> <p>The combination of T7 phage display and trinucleotide cassette randomization resulted in a novel resource for the potential isolation of binding peptides for new and previously studied molecular targets.</p

Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1

Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70S6K1-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin), it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target) and HIF-1α (a pVHL-target), implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition

A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells

BACKGROUND: Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-γ2 (PLCγ2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCγ2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCγ2-deficient DT40 B cell line. RESULTS: Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCγ2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCγ2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCγ2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis. CONCLUSIONS: These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCγ2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types

Oligosaccharide and Glycoprotein Microarrays as Tools in HIV Glycobiology Glycan-Dependent gp120/Protein Interactions

AbstractDefining HIV envelope glycoprotein interactions with host factors or binding partners advances our understanding of the infectious process and provides a basis for the design of vaccines and agents that interfere with HIV entry. Here we employ carbohydrate and glycoprotein microarrays to analyze glycan-dependent gp120-protein interactions. In concert with new linking chemistries and synthetic methods, the carbohydrate arrays combine the advantages of microarray technology with the flexibility and precision afforded by organic synthesis. With these microarrays, we individually and competitively determined the binding profiles of five gp120 binding proteins, established the carbohydrate structural requirements for these interactions, and identified a potential strategy for HIV vaccine development

Horizontal Lloyd mirror patterns from straight and curved nonlinear internal waves

Author Posting. © Acoustical Society of America, 2012. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 131 (2012): 1689-1700, doi:10.1121/1.3666004.Experimental observations and theoretical studies show that nonlinear internal waves occur widely in shallow water and cause acoustic propagation effects including ducting and mode coupling. Horizontal ducting results when acoustic modes travel between internal wave fronts that form waveguide boundaries. For small grazing angles between a mode trajectory and a front, an interference pattern may arise that is a horizontal Lloyd mirror pattern. An analytic description for this feature is provided along with comparisons between results from the formulated model predicting a horizontal Lloyd mirror pattern and an adiabatic mode parabolic equation. Different waveguide models are considered, including boxcar and jump sound speed profiles where change in sound speed is assumed 12 m/s. Modifications to the model are made to include multiple and moving fronts. The focus of this analysis is on different front locations relative to the source as well as on the number of fronts and their curvatures and speeds. Curvature influences mode incidence angles and thereby changes the interference patterns. For sources oriented so that the front appears concave, the areas with interference patterns shrink as curvature increases, while convexly oriented fronts cause patterns to expand.The authors thank the Office of Naval Research for funding this work. Additionally, the first author is supported through an ONR Ocean Acoustics Traineeship

Pennsylvania Folklife Vol. 38, No. 2

• Asseba un Sabina: The Flower of Pennsylvania German Folk Theater • An Elizabeth Furnace Tenant House: A Pennsylvania German Structure in Transition • A Tribute to Tradition and Necessity: The Schwenkfelder Schools in America • Enchanting Prospects : John Penn in Central Pennsylvania • Aldes un Neies (Old and New)https://digitalcommons.ursinus.edu/pafolklifemag/1122/thumbnail.jp

Barriers to integrating direct oral anticoagulants into anticoagulation clinic care: A mixedâ methods study

BackgroundOutpatient anticoagulation clinics were initially developed to care for patients taking vitamin K antagonists such as warfarin. There has not been a systematic evaluation of the barriers and facilitators to integrating direct oral anticoagulant (DOAC) care into outpatient anticoagulation clinics.MethodsWe performed a mixed methods study consisting of an online survey of anticoagulation clinic providers and semiâ structured interviews with anticoagulation clinic leaders and managers between March and May of 2017. Interviews were transcribed and coded, exploring for themes around barriers and facilitators to DOAC care within anticoagulation clinics. Survey questions pertaining to the specific themes identified in the interviews were analyzed using summary statistics.ResultsSurvey responses were collected from 159 unique anticoagulation clinics and 20 semiâ structured interviews were conducted. Three primary barriers to DOAC care in the anticoagulation clinic were described by the interviewees: (a) a lack of provider awareness for ongoing monitoring and services provided by the anticoagulation clinic; (b) financial challenges to providing care to DOAC patients in an anticoagulation clinic model; and (c) clinical knowledge versus scope of care by the anticoagulation staff. These themes linked to three key areas of variation, including: (a) the size and hospital affiliation of the anticoagulation clinic; (b) the use of faceâ toâ face versus telephoneâ based care; and (c) the use of nurses or pharmacists in the anticoagulation clinic.ConclusionsAnticoagulation clinics in the United States experience important barriers to integrating DOAC care. These barriers vary based on the clinic size, model for warfarin care, and staff credentials (nursing or pharmacy).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/1/rth212157.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/2/rth212157_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147845/3/rth212157-sup-0001-Supinfo.pd

Understanding the Engineering Design Process Through the Evolution of Engineering Digital Objects

The generation of digital objects are present throughout the work that is undertaken during the engineering design process. Although it is self-evident that these objects have been created by engineers to support their work, little research has been performed to understand whether there are underlying signatures in their generation that could provide useful insights to the management of the project. In order to address this, this paper presents some initial insights from the analysis of the generation of digital objects from an engineering project, and discusses potential signatures

Economics of residential gas furnaces and water heaters in United States new construction market

New single-family home construction represents a significant and important market for the introduction of energy-efficient gas-fired space heating and water-heating equipment. In the new construction market, the choice of furnace and water-heater type is primarily driven by first cost considerations and the availability of power vent and condensing water heaters. Few analysis have been performed to assess the economic impacts of the different combinations of space and water-heating equipment. Thus, equipment is often installed without taking into consideration the potential economic and energy savings of installing space and water-heating equipment combinations. In this study, we use a life-cycle cost analysis that accounts for uncertainty and variability of the analysis inputs to assess the economic benefits of gas furnace and water-heater design combinations. This study accounts not only for the equipment cost but also for the cost of installing, maintaining, repairing, and operating the equipment over its lifetime. Overall, this study, which is focused on US single-family new construction households that install gas furnaces and storage water heaters, finds that installing a condensing or power-vent water heater together with condensing furnace is the most cost-effective option for the majority of these houses. Furthermore, the findings suggest that the new construction residential market could be a target market for the large-scale introduction of a combination of condensing or power-vent water heaters with condensing furnaces