ASU Scholarship Showcase

As part of a larger trend across industrialized nations, European research policy discourse has placed increasing emphasis on socio-technical integration: the explicit incorporation of activities devoted to broader social aspects into scientific activities. In order to compare these high-level integration discourses against patterns at the level of resource allocation, we analyze nearly 2500 research solicitations from the three European Framework Programmes for R&D during the period 1998-2010. We identify four distinct types of integration (socio-ethical, stakeholder, socio-economic and industrial) that occur either as core or parallel components of R&D solicitations. Quantitative analysis reveals an overall trend towards increasing integration, with requests integrating industrial and socio-economic aspects substantially outnumbering those integrating socio-ethical and stakeholder aspects-by a 2 to 1 margin. Meanwhile, calls for socio-technical integration have become slightly more extensive (ranging across a broader range of research areas addressed), significantly more pervasive (shifting from the periphery to the core of R&D practices), and arguably less diverse (involving a wider variety of integration types) over time. The relative lack of attention to socio-ethical aspects and stakeholder participation in European research is particularly notable given that we focus on potentially controversial areas (life sciences, energy, and nanotechnology), which likely overemphasizes the prevalence of integration throughout the Framework Programmes.

The similarity attraction hypothesis posits that humans are drawn toward others who behave and appear similar to themselves. Two experiments examined this hypothesis with middle-school students learning electrical circuit analysis in a computer-based environment with an Animated Pedagogical Agent (APA). Experiment 1 was designed to determine whether matching the gender of the APA to the student has a positive impact on learning outcomes or student perceptions. One hundred ninety-seven middle-school students learned with the computer-based environment using an APA that matched their gender or one which was opposite in gender. Female students reported higher program ratings when the APA matched their gender. Male students, on the other hand, reported higher program ratings than females when the APA did not match their gender. Experiment 2 systematically tested the impact of providing learners the choice among four APAs on learning outcomes and student perceptions. Three hundred thirty-four middle-school students received either a pre-assigned random APA or were free to choose from four APA options: young male agent, older male agent, young female agent, or older female agent. Learners had higher far transfer scores when provided a choice of animated agent, but student perceptions were not impacted by having the ability to make this choice. We suggest that offering students learner control positively impacts student motivation and learning by increasing student perceptions of autonomy, responsibility for the success of the instructional materials, and global satisfaction with the design of materials.

Recent advances in nonequilibrium statistical physics have provided unprecedented insight into the thermodynamics of dynamic processes. The author recently used these advances to extend Landauer’s semi-formal reasoning concerning the thermodynamics of bit erasure, to derive the minimal free energy required to implement an arbitrary computation. Here, I extend this analysis, deriving the minimal free energy required by an organism to run a given (stochastic) map π from its sensor inputs to its actuator outputs. I use this result to calculate the input-output map π of an organism that optimally trades off the free energy needed to run π with the phenotypic fitness that results from implementing π. I end with a general discussion of the limits imposed on the rate of the terrestrial biosphere’s information processing by the flux of sunlight on the Earth.

Quiescin sulfhydryl oxidase 1 (QSOX1) is a highly conserved disulfide bond-generating enzyme that is overexpressed in diverse tumor types. Its enzymatic activity promotes the growth and invasion of tumor cells and alters extracellular matrix composition. In a nude mouse-human tumor xenograft model, tumors containing shRNA for QSOX1 grew significantly more slowly than controls, suggesting that QSOX1 supports a proliferative phenotype in vivo. High throughput screening experiments identified ebselen as an in vitro inhibitor of QSOX1 enzymatic activity. Ebselen treatment of pancreatic and renal cancer cell lines stalled tumor growth and inhibited invasion through Matrigel in vitro. Daily oral treatment with ebselen resulted in a 58% reduction in tumor growth in mice bearing human pancreatic tumor xenografts compared to controls. Mass spectrometric analysis of ebselen-treated QSOX1 mechanistically revealed that C165 and C237 of QSOX1 covalently bound to ebselen. This report details the anti-neoplastic properties of ebselen in pancreatic and renal cancer cell lines. The results here offer a “proof-of-principle” that enzymatic inhibition of QSOX1 may have clinical relevancy.

Autoantibodies refer to antibodies that target self-antigens, which can play pivotal roles in maintaining homeostasis, distinguishing normal from tumor tissue and trigger autoimmune diseases. In the last three decades, tremendous efforts have been devoted to elucidate the generation, evolution and functions of autoantibodies, as well as their target autoantigens. However, reports of these countless previously identified autoantigens are randomly dispersed in the literature. Here, we constructed an AAgAtlas database 1.0 using text-mining and manual curation. We extracted 45 830 autoantigen-related abstracts and 94 313 sentences from PubMed using the keywords of either ‘autoantigen’ or ‘autoantibody’ or their lexical variants, which were further refined to 25 520 abstracts, 43 253 sentences and 3984 candidates by our bio-entity recognizer based on the Protein Ontology. Finally, we identified 1126 genes as human autoantigens and 1071 related human diseases, with which we constructed a human autoantigen database (AAgAtlas database 1.0). The database provides a user-friendly interface to conveniently browse, retrieve and download human autoantigens as well as their associated diseases. The database is freely accessible at http://biokb.ncpsb.org/aagatlas/. We believe this database will be a valuable resource to track and understand human autoantigens as well as to investigate their functions in basic and translational research.

We find that the flow of attention on the Web forms a directed, tree-like structure implying the time-sensitive browsing behavior of users. Using the data of a news sharing website, we construct clickstream networks in which nodes are news stories and edges represent the consecutive clicks between two stories. To identify the flow direction of clickstreams, we define the “flow distance” of nodes (L_i), which measures the average number of steps a random walker takes to reach the ith node. It is observed that L_i is related with the clicks (C_i) to news stories and the age (T_i) of stories. Putting these three variables together help us understand the rise and decay of news stories from a network perspective. We also find that the studied clickstream networks preserve a stable structure over time, leading to the scaling between users and clicks. The universal scaling behavior is confirmed by the 1,000 Web forums. We suggest that the tree-like, stable structure of clickstream networks reveals the time-sensitive preference of users in online browsing. To test our assumption, we discuss three models on individual browsing behavior, and compare the simulation results with empirical data.

Many adaptive systems sit near a tipping or critical point. For systems near a critical point small changes to component behaviour can induce large-scale changes in aggregate structure and function. Criticality can be adaptive when the environment is changing, but entails reduced robustness through sensitivity. This tradeoff can be resolved when criticality can be tuned. We address the control of finite measures of criticality using data on fight sizes from an animal society model system (Macaca nemestrina, n=48). We find that a heterogeneous, socially organized system, like homogeneous, spatial systems (flocks and schools), sits near a critical point; the contributions individuals make to collective phenomena can be quantified; there is heterogeneity in these contributions; and distance from the critical point (DFC) can be controlled through biologically plausible mechanisms exploiting heterogeneity. We propose two alternative hypotheses for why a system decreases the distance from the critical point.

S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC–electrospray ionization–MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at −80 °C, −20 °C, and room temperature and exposed to multiple freeze-thaw cycles and other adverse conditions in order to assess the possibility that protein oxidation may occur as a result of poor sample storage or handling. Samples from a healthy donor and a participant with poorly controlled type 2 diabetes started at the same low level of protein oxidation and behaved similarly; significant increases in albumin oxidation via S-cysteinylation were found to occur within hours at room temperature and days at −20 °C. Methionine oxidation of apoA-I took place on a longer time scale, setting in after albumin oxidation reached a plateau. Freeze–thaw cycles had a minimal effect on protein oxidation. In matched collections, protein oxidation in serum was the same as that in plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the degree to which vials were sealed. ApoA-I, however, was unexpectedly found to oxidize faster in samples with lower surface-area-to-volume ratios. An initial survey of samples from patients with inflammatory conditions normally associated with elevated oxidative stress-including acute myocardial infarction and prostate cancer—demonstrated a lack of detectable apoA-I oxidation. Albumin S-cysteinylation in these samples was consistent with known but relatively brief exposures to temperatures above −30 °C (the freezing point of blood plasma). Given their properties and ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma specimen integrity based on direct measurement of oxidative molecular damage that can occur under suboptimal storage conditions.

There are many proteomic applications that require large collections of purified protein, but parallel production of large numbers of different proteins remains a very challenging task. To help meet the needs of the scientific community, we have developed a human protein production pipeline. Using high-throughput (HT) methods, we transferred the genes of 31 full-length proteins into three expression vectors, and expressed the collection as N-terminal HaloTag fusion proteins in Escherichia coli and two commercial cell-free (CF) systems, wheat germ extract (WGE) and HeLa cell extract (HCE). Expression was assessed by labeling the fusion proteins specifically and covalently with a fluorescent HaloTag ligand and detecting its fluorescence on a LabChip[superscript ®] GX microfluidic capillary gel electrophoresis instrument. This automated, HT assay provided both qualitative and quantitative assessment of recombinant protein. E. coli was only capable of expressing 20% of the test collection in the supernatant fraction with ≥20 μg yields, whereas CF systems had ≥83% success rates. We purified expressed proteins using an automated HaloTag purification method. We purified 20, 33, and 42% of the test collection from E. coli, WGE, and HCE, respectively, with yields ≥1 μg and ≥90% purity. Based on these observations, we have developed a triage strategy for producing full-length human proteins in these three expression systems.

Sequential affect dynamics generated during the interaction of intimate dyads, such as married couples, are associated with a cascade of effects - some good and some bad - on each partner, close family members, and other social contacts. Although the effects are well documented, the probabilistic structures associated with micro-social processes connected to the varied outcomes remain enigmatic. Using extant data we developed a method of classifying and subsequently generating couple dynamics using a Hierarchical Dirichlet Process Hidden semi-Markov Model (HDP-HSMM). Our findings indicate that several key aspects of existing models of marital interaction are inadequate: affect state emissions and their durations, along with the expected variability differences between distressed and nondistressed couples are present but highly nuanced; and most surprisingly, heterogeneity among highly satisfied couples necessitate that they be divided into subgroups. We review how this unsupervised learning technique generates plausible dyadic sequences that are sensitive to relationship quality and provide a natural mechanism for computational models of behavioral and affective micro-social processes.