Reinventing Maine Government: How Mainers Can Shape a Sustainable Government and a New Prosperity

In this commentary the authors highlight the challenges Maine faces. They suggest areas where the state could spend less, based on national comparative figures. They discuss what they call the “three ticking time bombs” in the state: the aging workforce, unfunded pension liabilities, and escalating costs of healthcare, and review what they consider to be inefficient structures in government at all levels. They argue that new thinking and new approaches are needed, and make a number of recommendations for “reinventing government” in Maine

Neuronal Heterotopias in the Developing Cerebral Cortex Produced by Neurotrophin-4

AbstractThe marginal zone (MZ) of embryonic neocortex is crucial to its normal development. We report that neurotrophin-4 (but not NT3 or NGF), applied to embryonic rodent cortex in vitro or in vivo, produces heterotopic accumulations of neurons in the MZ. Although heterotopia production is TrkB mediated, BDNF is >10-fold less effective than NT4. Heterotopic neurons have the same birth date and phenotype as normal MZ neurons; they are not the result of NT4-induced proliferation or rescue from apoptosis. We suggest that NT4 causes excess neurons to migrate into the MZ and thus may play a role in normal MZ formation as well as in the pathogenesis of certain human cortical dysplasias

The trap of tracking: Digital methods, surveillance, and the far right

Computational methods and network analysis are vital means for understanding how digital platforms are employed by political extremists. Western democracies focused on the security threat of jihadi extremism have been comparatively slow to recognise the threat of the far-right extremism (see Crosby 2021 and Rostami and Askanius 2021). Understandably, scholars have reacted to the knowledge gap about far-right extremists by practicing what we call “surveillance-as-method,” or the use of computational methods to gather data on far-right activities on digital media platforms, typically in order to track keywords or phrases or to map network connections. As we suggest here, the limits of surveillance-as-method include reproducing problems associated with state surveillance (van Dijck 2014) and underestimating the messiness (Pink, Lanzeni, and Horst 2018) of digital culture. Those limits need to be appreciated and approaches combined if we are to understand online politics. In this dialogue, we urge greater caution and reflexivity in reproducing surveillant methods, and greater attention to the historical, ideological context of far-right politic

Playing with the News on Reddit: The Politics Game on r/The_Donald

Research into online forms of far-right, alt-right, populist and supremacist politics has raised questions about the extent to which social media enables or constitutes extremist affects and ideologies. Building on this research, and through a case study of how a pro-Trump community on Reddit made sense of news events and sought to contest their representation, this paper explores the relationship between games and politics, arguing that digital platforms encourage people to apprehend, interpret and contest political ideas and information as if engaged in a kind of video game. We show how the group sought to manipulate platform affordances, waging a kind of Info War rooted in an understanding of politics as a pure space of conflict. We show how social media orients people to politics, phenomenologically, through the logics, structures and narratives of online games and argue that this affects not only online behaviours but more general apprehensions of politics

BACK TO THE FUTURE: FACILITATING ASSESSMENT DESIGN, COLLABORATION, AND OUTCOMES ALIGNMENT WITH AN ASSESSMENT FRAMEWORK

Aligning assessment questions to content and process variables is a collaborative activity. Robust practice requires participants to first make an individual judgement about the alignment, and then share their judgements and adjust them to work towards building consensus. In this workshop, attendees will participate in an interactive activity using the Australian Council for Educational Research's Swift platform to judge exam questions against the content and process variables of an assessment framework and then build consensus as a group. This will inform academics how they can use the framework in their own practice and within their own institution. People from any disciplinary background are welcome to join us. We will be using life science example questions, but it will only be necessary to understand the intent of the question, not be able to answer it

Interaction between tetraethylammonium and amino acid residues in the pore of cloned voltage-dependent potassium channels

Extracellular tetraethylammonium (TEA) inhibits currents in Xenopus oocytes that have been injected with mRNAs encoding voltage-dependent potassium channels. Concentration-response curves were used to measure the affinity of TEA; this differed up to 700-fold among channels RBK1 (KD 0.3 mM), RGK5 (KD 11 mM), and RBK2 (KD greater than 200 mM). Studies in which chimeric channels were expressed localized TEA binding to the putative extracellular loop between trans-membrane domains S5 and S6. Site-directed mutagenesis of residues in this region identified the residue Tyr379 of RBK1 as a crucial determinant of TEA sensitivity; substitution of Tyr in the equivalent positions of RBK2 (Val381) and RGK5 (His401) made these channels as sensitive to TEA as RBK1. Nonionic forces are involved in TEA binding because (i) substitution of the Phe for Tyr379 in RBK1 increased its affinity, (ii) protonation of His401 in RGK5 selectively reduced its affinity, and (iii) the affinity of TEA was unaffected by changes in ionic strength. The results suggest an explanation for the marked differences in TEA sensitivity that have been observed among naturally occurring and cloned potassium channels and indicate that the amino acid corresponding to residue 379 in RBK1 lies within the external mouth of the ion channel

Computational Knowledge Integration in Biopharmaceutical Research

An initiative to increase biopharmaceutical research productivity by capturing, sharing and computationally integrating proprietary scientific discoveries with public knowledge is described. This initiative involves both organisational process change and multiple interoperating software systems. The software components rely on mutually supporting integration techniques. These include a richly structured ontology, statistical analysis of experimental data against stored conclusions, natural language processing of public literature, secure document repositories with lightweight metadata, web services integration, enterprise web portals and relational databases. This approach has already begun to increase scientific productivity in our enterprise by creating an organisational memory (OM) of internal research findings, accessible on the web. Through bringing together these components it has also been possible to construct a very large and expanding repository of biological pathway information linked to this repository of findings which is extremely useful in analysis of DNA microarray data. This repository, in turn, enables our research paradigm to be shifted towards more comprehensive systems-based understandings of drug action

Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice

Background Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO) mice. Methods 3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM), β-hydroxy-β-methyl butyrate (HMB) (5 μM) or Resveratrol (200 nM) alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet) or high (10 g/kg diet) dose HMB, Leucine (24 g/kg diet; 200% of normal level) or low (12.5 mg/kg diet) or high (225 mg/kg diet) dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol. Results Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT), insulin sensitivity (HOMAIR), improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin) and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Conclusion These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more practical dosing of resveratrol in the management of obesity, insulin-resistance and diabetes