The digital public humanities: giving new arguments and new ways to argue

ABSTRACT

In response to the latest “crisis” in the humanities, advocates have marched, rallied, fundraised, and—especially—argued. This essay contends that communication scholars can support the growing “case for the humanities” by analyzing argumentative strategies, and more specifically, by offering ethical argumentative strategies that avoid replicating structures of domination. In particular, we look to Mari Lee Mifsud's theorization of rhetoric as gift, which follows Henry W. Johnstone in conceptualizing argument as something other than winning over an adversary. We place Mifsud's theorization of the gift in conversation with the methods of the digital public humanities (DPH), which acknowledge and offer abundant resources for meaning-making. Through the methods of DPH, we offer a response to the humanities “crisis” that activates the humanities’ already broad constituencies by giving resources for humanistic inquiry rather than seeking to capture adversaries. Our case study is Photogrammar, a DPH project for organizing, searching, and visualizing the New Deal and World War II era photographs funded by the U.S. federal government. The project forefronts visual, nonlinear, and interactive argumentation in order to engage publics in generative humanistic inquiry. By enlisting participants and sharing expertise, Photogrammar shows how humanities advocates can deepen attachments to the humanities and build broad constituencies of collaborators and allies.     

Integrated Saltwater Desalination and Energy Storage through a pH Neutral Aqueous Organic Redox Flow Battery

Here, a pH neutral aqueous organic redox flow battery (AORFB) consisting of three electrolytes channels (i.e., an anolyte channel, a catholyte channel, and a central salt water channel) to achieve integrated energy storage and desalination is reported. Employing a low cost, chemically stable methyl viologen (MV) anolyte, and sodium ferrocyanide catholyte, this desalination AORFB is capable of desalinating simulated seawater (0.56 m NaCl) down to 0.023 m salt concentration at an energy cost of 2.4 W h L^?1 of fresh water—competitive with current reverse osmosis technologies. Simultaneously, the cell delivers stored energy at 79.7% efficiency with a cell voltage of 0.85 V. Furthermore, the cell is also capable of higher current operation up to 15 mA cm^?2, providing 4.55 mL of fresh water per hour. Combining energy storage and water desalination into such a bifunctional device offers the opportunity to address two growing global issues from one hardware installation.     

Anti‐HIV Small‐Molecule Binding in the Peptide Subpocket of the CXCR4:CVX15 Crystal Structure

The CXC chemokine receptor 4 (CXCR4) is involved in chemotaxis and serves as a coreceptor for T‐tropic HIV‐1 viral entry, thus making this receptor an attractive drug target. Recently, crystal structures of CXCR4 were reported as complexes with the small molecule IT1t and the CVX15 peptide. Follow‐up efforts to model different antagonists into the small molecule CXCR4:IT1t crystal structure did not generate poses consistent with either the X‐ray crystal structure or site‐directed mutagenesis (SDM). Here, we compare the binding pockets of the two CXCR4 crystal structures, revealing differences in helices IV, V, VI, and VII, with major differences for the His203 residue buried in the binding pocket. The small molecule antagonist AMD11070 was docked into both CXCR4 crystal structures. An AMD11070 pose identified from the CXCR4:CVX15 model presented interactions with Asp171, Glu288, Trp94, and Asp97, consistent with published SDM data, thus suggesting it is the bioactive pose. A CXCR4 receptor model was optimized around this pose of AMD11070, and the resulting model correlated HIV‐1 inhibition with MM‐GBSA docking scores for a congeneric AMD11070‐like series. Subsequent NAMFIS NMR results successfully linked the proposed binding pose to an independent experimental structure. These results strongly suggest that not all small molecules will bind to CXCR4 in a similar manner as IT1t. Instead, the CXCR4:CVX15 crystal structure may provide a binding locus for small organic molecules that is more suitable than the secondary IT1t site. This work is expected to provide modeling insights useful for future CXCR4 antagonist and X4‐tropic HIV‐1 based drug design efforts.     

Discovery of 5′′‐Chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064): A Selective Orexin 2 Receptor Antagonist (2‐SORA) for the Treatment of Insomnia

The field of small‐molecule orexin antagonist research has evolved rapidly in the last 15 years from the discovery of the orexin peptides to clinical proof‐of‐concept for the treatment of insomnia. Clinical programs have focused on the development of antagonists that reversibly block the action of endogenous peptides at both the orexin 1 and orexin 2 receptors (OX₁R and OX₂R), termed dual orexin receptor antagonists (DORAs), affording late‐stage development candidates including Merck’s suvorexant (new drug application filed 2012). Full characterization of the pharmacology associated with antagonism of either OX₁R or OX₂R alone has been hampered by the dearth of suitable subtype‐selective, orally bioavailable ligands. Herein, we report the development of a selective orexin 2 antagonist (2‐SORA) series to afford a potent, orally bioavailable 2‐SORA ligand. Several challenging medicinal chemistry issues were identified and overcome during the development of these 2,5‐disubstituted nicotinamides, including reversible CYP inhibition, physiochemical properties, P‐glycoprotein efflux and bioactivation. This article highlights structural modifications the team utilized to drive compound design, as well as in vivo characterization of our 2‐SORA clinical candidate, 5′′‐chloro‐N‐[(5,6‐dimethoxypyridin‐2‐yl)methyl]‐2,2′:5′,3′′‐terpyridine‐3′‐carboxamide (MK‐1064), in mouse, rat, dog, and rhesus sleep models.     

Comparison of anaerobic dechlorinating enrichment cultures maintained on tetrachloroethene,trichloroethene, cis-dichloroethene and vinyl chloride

An anaerobic mixed microbial culture was enriched from soil and groundwater taken from a site contaminated with trichloroethene (TCE). This enrichment culture was divided into four subcultures amended separately with either perchloroethene (PCE), TCE, cis-dichloroethene (cDCE) or vinyl chloride (VC). In each of the four subcultures, the chlorinated ethenes were rapidly, consistently, and completely converted to ethene at rates of 30-50 micromol/l of culture per day, or an average 160 micro-electron equivalents/l of culture per day. These cultures were capable of sustained and rapid dechlorination of VC, and could not dechlorinate 1,2-dichloroethane, differentiating them from Dehalococcoides ethenogenes, the only known isolate capable of complete dechlorination of PCE to ethene. Chloroform (CF) and 1,1,1-trichloroethane, frequent groundwater co-contaminants with TCE and PCE, inhibited chlorinated ethene dechlorination. Most strongly inhibited was the final conversion of VC to ethene, with complete inhibition occurring at an aqueous CF concentration of 2.5 microM. Differences in rates and community composition developed between the different subcultures, including the loss of the VC enrichment culture's ability to dechlorinate PCE. Denaturing gradient gel electrophoresis of amplified bacterial 16S rRNA gene fragments identified three different DNA sequences in the enrichment cultures, all phylogenetically related to D. ethenogenes. Based on the PCR-DGGE results and substrate utilization patterns, it is apparent that significant mechanistic differences exist between each step of dechlorination from TCE to ethene, especially for the last important dechlorination step from VC to ethene.     

Characterizing In‐Plane Geometrical Variability in Textile Ceramic Composites

We present a methodology for characterizing and reconstructing in‐plane weave variability in textile composites. Surface topography of a partially processed C‐fiber/SiC matrix composite panel was measured using digital image correlation. The centroids of tow segments that appear periodically on the fabric surface were located by image analysis and used as fiducial markers. Stochastic deviations of the fiducial markers from the ideal periodic weave structure indicate geometrical variance. Fourier analysis shows that spatial wavelengths of the deviations range from the size of one unit cell to the dimensions of the entire panel. Long‐range deviations are attributed principally to fabric deformation after manufacture, during handling. Short‐range fluctuations, extracted by computing spatial derivatives of the positions of the fiducial markers, are attributed to variations in tow packing density that arises during weaving. A simple set of statistics for these deviations is presented and its use in generating stochastic virtual specimens is demonstrated.     

Accelerating protein release from microparticles for regenerative medicine applications

There is a need to control the spatio-temporal release kinetics of growth factors in order to mitigate current usage of high doses. A novel delivery system, capable of providing both structural support and controlled release kinetics, has been developed from PLGA microparticles. The inclusion of a hydrophilic PLGA–PEG–PLGA triblock copolymer altered release kinetics such that they were decoupled from polymer degradation. A quasi zero order release profile over four weeks was produced using 10% w/w PLGA–PEG–PLGA with 50:50 PLGA whereas complete and sustained release was achieved over ten days using 30% w/w PLGA–PEG–PLGA with 85:15 PLGA and over four days using 30% w/w PLGA–PEG–PLGA with 50:50 PLGA. These three formulations are promising candidates for delivery of growth factors such as BMP-2, PDGF and VEGF. Release profiles were also modified by mixing microparticles of two different formulations providing another route, not previously reported, for controlling release kinetics. This system provides customisable, localised and controlled delivery with adjustable release profiles, which will improve the efficacy and safety of recombinant growth factor delivery.     

Some Systematic Supersaturated Designs

Supersaturated designs are factorial designs in which the number of factors exceeds the number of observations. Satterthwaite has suggested constructing such designs by a randomization procedure (random balance designs). In the present paper systematic designs are constructed which are, in a certain sense, m nearly orthogonal M possible. Examples of such designs are given constructed on an electronic computer and some properties of the designs are discussed.     

Effects of short-term repeated exposure to different flooring surfaces on the behavior and physiology of dairy cattle

Dairy cattle managed in some pasture-based systems such as in New Zealand are predominantly kept outdoors all year around, but are often taken off pasture for periods of time in wet weather to avoid soil damage. It is common to keep cattle on concrete surfaces during such “stand-off” practices and we investigated whether the addition of rubber matting onto concrete areas improves the welfare of dairy cattle. Sixteen groups of 5 cows (4 groups/treatment, 5 cows/group) were allocated to 1 of 4 treatments (concrete, 12-mm-thick rubber mat, 24-mm-thick rubber mat, or deep-bedded wood chips) and kept on these surfaces for 18 h/24 h for 4 consecutive days (6 h on pasture/24 h). Each 4-d stand-off period was repeated 4 times (with 7 d of recovery between periods) to study the accumulated effects of repeated stand-off. Lying behavior was recorded continuously during the experiment. Gait score, stride length, hygiene score, live weight, and blood samples for cortisol analysis were recorded immediately before and after each stand-off period. Cows on wood chips spent the most time lying, and cows on concrete spent the least time lying compared with those on other surfaces [wood chips: 10.8 h, 24-mm rubber mat: 7.3 h, 12-mm rubber mat: 6.0 h, and concrete: 2.8 h/18 h, standard error of the difference (SED): 0.71 h]. Cows on concrete spent more time lying during the 6 h on pasture, likely compensating for the reduced lying during the stand-off period. Similarly, cows on concrete spent more time lying on pasture between stand-off periods (concrete: 12.1 h, 12-mm rubber mat: 11.1 h, 24-mm rubber mat: 11.2 h, and wood chips: 10.7 h/24 h, SED: 0.28 h). Cows on concrete had higher gait score and shorter stride length after the 4-d stand-off period compared with cows on the other surface types, suggesting a change in gait pattern caused by discomfort. Cows on rubber mats were almost 3 times dirtier than cows on concrete or wood chips. Cortisol and live weight decreased for all treatment groups during the stand-off period. We observed no major effect of the repeated stand-off exposure. In summary, adding rubber matting onto concrete surfaces for stand-off purposes is beneficial for animal welfare. A well-managed wood chip surface offered the best welfare for dairy cows removed from pasture, and the findings of this study confirm that a concrete surface decreases the welfare of cows removed from pasture.     

Design modelling and measured performance of the vacuum system of the Diamond Light Source storage ring

A one-dimensional diffusion model of the Diamond Light Source storage ring vacuum system is described and its predictions are compared with actual measured static (without beam) and dynamic (with beam) pressures over more than 2000 A h of beam conditioning at 3 GeV. An average specific thermal outgassing yield of 1·10⁻¹¹ mbar l/(s cm²) during initial beam circulation is obtained, which reduces to 2·10⁻¹² mbar l/(s cm²) after an accumulated beam dose of 1000 A h and an elapsed time of 769 days. In the presence of stored electron beam, the pressure rises as expected due to photon stimulated desorption (PSD). The PSD yield reduces with beam dose according to a (−2/3) power law as was applied in the model. Predicted and measured dynamic pressures generally agree within a factor of 2 over the whole range of beam conditioning dose studied.