Stochastic Feedback and the Regulation of Biological Rhythms

We propose a general approach to the question of how biological rhythms spontaneously self-regulate, based on the concept of ``stochastic feedback''. We illustrate this approach by considering the neuroautonomic regulation of the heart rate. The model generates complex dynamics and successfully accounts for key characteristics of cardiac variability, including the $1/f$ power spectrum, the functional form and scaling of the distribution of variations, and correlations in the Fourier phases. Our results suggest that in healthy systems the control mechanisms operate to drive the system away from extreme values while not allowing it to settle down to a constant output.Comment: 15 pages, latex2e using rotate and epsf, with 4 ps figures. Submitted to PR

Cross-continental emergence of Nannizziopsis barbatae disease may threaten wild Australian lizards

Members of the genus Nannizziopsis are emerging fungal pathogens of reptiles that have been documented as the cause of fatal mycoses in a wide range of reptiles in captivity. Cases of severe, proliferative dermatitis, debility and death have been detected in multiple free-living lizard species from locations across Australia, including a substantial outbreak among Eastern water dragons (Intellagama lesueurii) in Brisbane, Queensland. We investigated this disease in a subset of severely affected lizards and identified a clinically consistent syndrome characterized by hyperkeratosis, epidermal hyperplasia, dermal inflammation, necrosis, ulceration, and emaciation. Using a novel fungal isolation method, histopathology, and molecular techniques, we identified the etiologic agent as Nannizziopsis barbatae, a species reported only once previously from captive lizards in Australia. Here we report severe dermatomycosis caused by N. barbatae in five species of Australian lizard, representing the first cases of Nannizziopsis infection among free-living reptiles, globally. Further, we evaluate key pathogen and host characteristics that indicate N. barbatae-associated dermatomycosis may pose a concerning threat to Australian lizards

Gene expression profiling of Naïve sheep genetically resistant and susceptible to gastrointestinal nematodes

BACKGROUND: Gastrointestinal nematodes constitute a major cause of morbidity and mortality in grazing ruminants. Individual animals or breeds, however, are known to differ in their resistance to infection. Gene expression profiling allows us to examine large numbers of transcripts simultaneously in order to identify those transcripts that contribute to an animal's susceptibility or resistance. RESULTS: With the goal of identifying genes with a differential pattern of expression between sheep genetically resistant and susceptible to gastrointestinal nematodes, a 20,000 spot ovine cDNA microarray was constructed. This array was used to interrogate the expression of 9,238 known genes in duodenum tissue of four resistant and four susceptible female lambs. Naïve animals were used in order to look at genes that were differentially expressed in the absence of infection with gastrointestinal nematodes. Forty one unique known genes were identified that were differentially expressed between the resistant and susceptible animals. Northern blotting of a selection of the genes confirmed differential expression. The differentially expressed genes had a variety of functions, although many genes relating to the stress response and response to stimulus were more highly expressed in the susceptible animals. CONCLUSION: We have constructed the first reported ovine microarray and used this array to examine gene expression in lambs genetically resistant and susceptible to gastrointestinal nematode infection. This study indicates that susceptible animals appear to be generating a hyper-sensitive immune response to non-nematode challenges. The gastrointestinal tract of susceptible animals is therefore under stress and compromised even in the absence of gastrointestinal nematodes. These factors may contribute to the genetic susceptibility of these animals

Forecasting Player Behavioral Data and Simulating in-Game Events

Understanding player behavior is fundamental in game data science. Video games evolve as players interact with the game, so being able to foresee player experience would help to ensure a successful game development. In particular, game developers need to evaluate beforehand the impact of in-game events. Simulation optimization of these events is crucial to increase player engagement and maximize monetization. We present an experimental analysis of several methods to forecast game-related variables, with two main aims: to obtain accurate predictions of in-app purchases and playtime in an operational production environment, and to perform simulations of in-game events in order to maximize sales and playtime. Our ultimate purpose is to take a step towards the data-driven development of games. The results suggest that, even though the performance of traditional approaches such as ARIMA is still better, the outcomes of state-of-the-art techniques like deep learning are promising. Deep learning comes up as a well-suited general model that could be used to forecast a variety of time series with different dynamic behaviors

Rethinking media responsibility in the refugee ‘crisis’: a visual typology of European news

In this paper, we analyse how news images of the 2015 Syrian refugee ‘crisis’ visualise refugees and how, in so doing, they mobilise various forms of moral responsibility in ‘our’ mediated public life – various practical dispositions of action towards the misfortunes of migrants and refugees at Europe’s border. On the basis of empirical material from European news (June-December 2015), we construct a typology of visibilities of the ‘crisis’, each of which situates refugees within a different regime of visibility and claim to action: i) visibility as biological life, associated with monitorial action; ii) visibility as empathy associated with charitable action; iii) visibility as threat, associated with state security; iv) visibility as hospitality, associated with political activism; and v) visibility as selfreflexivity, associated with a post-humanitarian engagement with people like ‘us’. In conclusion, we argue that, important as these five categories of visibility are in introducing public dispositions to action towards the vulnerable, they nonetheless ultimately fail to humanise migrants and refugees. This failure to portray them as human beings with lives that are worth sharing should compel us, we urge, to radically re-think how we understand the media’s responsibility towards vulnerable others

Multiple shades of grey: Opening the black box of public sector executives' hybrid role identities

Public sector reforms of recent decades in Europe have promoted managerialism and aimed at introducing private sector thinking and practices. However, with regard to public sector executives' self-understanding, managerial role identities have not replaced bureaucratic ones; rather, components from both paradigms have combined. In this article, we introduce a bi-dimensional approach (attitudes and practices) that allows for different combinations and forms of hybridity. Empirically, we explore the role identities of public sector executives across Europe, building on survey data from over 7,000 top public officials in 19 countries (COCOPS survey). We identify country-level profiles, as well as patterns across countries, and find that administrative traditions can account for these profiles and patterns only to a limited extent. Rather, they have to be complemented by factors such as stability of the institutional environment (indicating lower shares of hybrid combinations) or extent of reform pressures (indicating higher shares of hybrid combinations)

Loss of Tumor Suppressor TMEM127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin-coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation