Learning About Metadata and Machines: Teaching Students Using a Novel Structured Database Activity

Machines produce and operate using complex systems of metadata that need to be catalogued, sorted, and processed. Many students lack the experience with metadata and sufficient knowledge about it to understand it as part of their data literacy skills. This paper describes an educational and interactive database activity designed for teaching undergraduate communication students about the creation, value, and logic of structured data. Through a set of virtual instructional videos and interactive visualizations, the paper describes how students can gain experience with structured data and apply that knowledge to successfully find, curate, and classify a digital archive of media artifacts. The pedagogical activity, teaching materials, and archives are facilitated through and housed in an online resource called Fabric of Digital Life (fabricofdigitallife.com). We end by discussing the activity’s relevance for the emerging field of human-machine communication

Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator

In Escherichia coli, protein degradation in synthetic circuits is commonly achieved by the ssrA-tagged degradation system. In this work, we show that the degradation kinetics for the green fluorescent protein fused with the native ssrA tag in each cell exhibits the zeroth-order limit of the Michaelis–Menten kinetics, rather than the commonly assumed first-order. When measured in a population, the wide distribution of protein levels in the cells distorts the true kinetics and results in a first-order protein degradation kinetics as a population average. Using the synthetic gene-metabolic oscillator constructed previously, we demonstrated theoretically that the zeroth-order kinetics significantly enlarges the parameter space for oscillation and thus enhances the robustness of the design under parametric uncertainty

Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone

The transition zone (TZ) of primary cilia serves as a diffusion barrier to regulate ciliogenesis and receptor localization for key signaling events such as sonic hedgehog signaling. Its gating mechanism is poorly understood due to the tiny volume accommodating a large number of ciliopathy-associated molecules. Here we performed stimulated emission depletion (STED) imaging of collective samples and recreated superresolved relative localizations of eight representative species of ciliary proteins using position averages and overlapped with representative electron microscopy (EM) images, defining an architectural foundation at the ciliary base. Upon this framework, transmembrane proteins TMEM67 and TCTN2 were accumulated at the same axial level as MKS1 and RPGRIP1L, suggesting that their regulation roles for tissue-specific ciliogenesis occur at a specific level of the TZ. CEP290 is surprisingly localized at a different axial level bridging the basal body (BB) and other TZ proteins. Upon this molecular architecture, two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growth, are present: one colocalized with the transition fibers (TFs) while the other situated beyond the distal edge of the TZ. Together, our results reveal an unprecedented structural framework of the TZ, facilitating our understanding in molecular screening and assembly at the ciliary base

Murine versus human apolipoprotein E4: Differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models

INTRODUCTION: Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer’s disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans. Studies in mouse models that develop Aβ deposition have shown that murine apoE and human apoE4 have different abilities to facilitate plaque or CAA formation when studied independently. To better understand and compare the effects of murine apoE and human apoE4, we bred 5XFAD (line 7031) transgenic mice so that they expressed one copy of murine apoE and one copy of human apoE4 under the control of the normal murine apoE regulatory elements (5XFAD/apoE(m/4)). RESULTS: The 5XFAD/apoE(m/4) mice contained levels of parenchymal CAA that were intermediate between 5XFAD/apoE(m/m) and 5XFAD/apoE(4/4) mice. In 5XFAD/apoE(m/4) mice, we found that Aβ parenchymal plaques co-localized with much more apoE than did parenchymal CAA, suggesting differential co-aggregation of apoE with Aβ in plaques versus CAA. More importantly, within the brain parenchyma of the 5XFAD/apoE(m/4) mice, plaques contained more murine apoE, which on its own results in more pronounced and earlier plaque formation, while CAA contained more human apoE4 which on its own results in more pronounced CAA formation. We further confirmed the co-aggregation of mouse apoE with Aβ in plaques by showing a strong correlation between insoluble mouse apoE and insoluble Aβ in PS1APP-21/apoE(m/4) mice which develop plaques without CAA. CONCLUSIONS: These studies suggest that both murine apoE and human apoE4 facilitate differential opposing effects in influencing Aβ plaques versus CAA via different co-aggregation with these two amyloid lesions and set the stage for understanding these effects at a molecular level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0250-y) contains supplementary material, which is available to authorized users

Development, test and comparison of two Multiple Criteria Decision Analysis(MCDA) models: A case of healthcare infrastructure location

When planning a new development, location decisions have always been a major issue. This paper examines and compares two modelling methods used to inform a healthcare infrastructure location decision. Two Multiple Criteria Decision Analysis (MCDA) models were developed to support the optimisation of this decision-making process, within a National Health Service (NHS) organisation, in the UK. The proposed model structure is based on seven criteria (environment and safety, size, total cost, accessibility, design, risks and population profile) and 28 sub-criteria. First, Evidential Reasoning (ER) was used to solve the model, then, the processes and results were compared with the Analytical Hierarchy Process (AHP). It was established that using ER or AHP led to the same solutions. However, the scores between the alternatives were significantly different; which impacted the stakeholders‟ decision-making. As the processes differ according to the model selected, ER or AHP, it is relevant to establish the practical and managerial implications for selecting one model or the other and providing evidence of which models best fit this specific environment. To achieve an optimum operational decision it is argued, in this study, that the most transparent and robust framework is achieved by merging ER process with the pair-wise comparison, an element of AHP. This paper makes a defined contribution by developing and examining the use of MCDA models, to rationalise new healthcare infrastructure location, with the proposed model to be used for future decision. Moreover, very few studies comparing different MCDA techniques were found, this study results enable practitioners to consider even further the modelling characteristics to ensure the development of a reliable framework, even if this means applying a hybrid approach

TTBK2: A Tau Protein Kinase beyond Tau Phosphorylation

Tau tubulin kinase 2 (TTBK2) is a kinase known to phosphorylate tau and tubulin. It has recently drawn much attention due to its involvement in multiple important cellular processes. Here, we review the current understanding of TTBK2, including its sequence, structure, binding sites, phosphorylation substrates, and cellular processes involved. TTBK2 possesses a casein kinase 1 (CK1) kinase domain followed by a ∼900 amino acid segment, potentially responsible for its localization and substrate recruitment. It is known to bind to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. In addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. Mutations of TTBK2 are associated with spinocerebellar ataxia type 11. In addition, TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. Reported sites of TTBK2 localization include the centriole/basal body, the midbody, and possibly the mitotic spindles. Together, TTBK2 is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its functions

A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and Rationale

Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages