Ocean-atmospheric state dependence of the atmospheric response to Arctic sea ice loss

This is the final version of the article. Available from American Meteorological Society via the DOI in this record.The Arctic is warming faster than the global average. This disproportionate warming – known as Arctic amplification – has caused significant local changes to the Arctic system and more uncertain remote changes across the Northern Hemisphere midlatitudes. Here, we use an atmospheric general circulation model (AGCM) to test the sensitivity of the atmospheric and surface response to Arctic sea ice loss to the phase of the Atlantic Multidecadal Oscillation (AMO), which varies on (multi-)decadal timescales. Four experiments are performed, combining low and high sea ice states with global sea surface temperature (SST) anomalies associated with opposite phases of the AMO. A trough-ridge-trough response to wintertime sea ice loss is seen in the PacificNorth America sector in the negative phase of the AMO. We propose that this is a consequence of an increased meridional temperature gradient in response to sea ice loss, just south of the climatological maximum, in the central midlatitude North Pacific. This causes a southward shift in the North Pacific storm track, which strengthens the Aleutian Low with circulation anomalies propagating into North America. While the climate response to sea ice loss is sensitive to AMO-related SST anomalies in the North Pacific, there is little sensitivity to larger magnitude SST anomalies in the North Atlantic. With background ocean-atmospheric states persisting for a number of years, there is the potential to improve predictions of the impacts of Arctic sea ice loss on decadal timescalesThis work was supported by the Natural Environment Research Council grants NE/M006123/1 and NE/J019585/1. The HadGAM2 simulations were performed on the ARCHER UK National Supercomputing Service. For the provision of observed and reanalysis data the Met Office Hadley Centre and NOAA ESRL are thanked. Model data are available from the authors upon request

Role of Reversal Learning Impairment in Social Disinhibition following Severe Traumatic Brain Injury

OBJECTIVES: The current study aimed to determine whether reversal learning impairments and feedback-related negativity (FRN), reflecting reward prediction error signals generated by negative feedback during the reversal learning tasks, were associated with social disinhibition in a group of participants with traumatic brain injury (TBI). METHODS: Number of reversal errors on a social and a non-social reversal learning task and FRN were examined for 21 participants with TBI and 21 control participants matched for age. Participants with TBI were also divided into low and high disinhibition groups based on rated videotaped interviews. RESULTS: Participants with TBI made more reversal errors and produced smaller amplitude FRNs than controls. Furthermore, participants with TBI high on social disinhibition made more reversal errors on the social reversal learning task than did those low on social disinhibition. FRN amplitude was not related to disinhibition. CONCLUSIONS: These results suggest that impairment in the ability to update behavior when social reinforcement contingencies change plays a role in social disinhibition after TBI. Furthermore, the social reversal learning task used in this study may be a useful neuropsychological tool for detecting susceptibility to acquired social disinhibition following TBI. Finally, that the FRN amplitude was not associated with social disinhibition suggests that reward prediction error signals are not critical for behavioral adaptation in the social domain

Software development practices in academia: a case study comparison

Academic software development practices often differ from those of commercial development settings, yet only limited research has been conducted on assessing software development practises in academia. Here we present a case study of software development practices in four open-source scientific codes over a period of nine years, characterizing the evolution of their respective development teams, their scientific productivity, and the adoption (or discontinuation) of specific software engineering practises as the team size changes. We show that the transient nature of the development team results in the adoption of different development strategies. We relate measures of publication output to accumulated numbers of developers and find that for the projects considered the time-scale for returns on expended development effort is approximately three years. We discuss the implications of our findings for evaluating the performance of research software development, and in general any computationally oriented scientific project.Computational Horizons in Cancer (CHIC) project under EU FP7 grant agreement number 600841 (JG); CRESTA project under EU FP7 grant agreement number 287703 (DG,US); UK Engineering and Physical Sciences Research Council under grant numbers EP/I017909/1 (www.2020science.net, DG,JG,JMO) and EP/I034602/1 (US)

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

INTRODUCTION: Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. METHODS: To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. RESULTS: Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). CONCLUSIONS: Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an attractive candidate molecular predictor of antiestrogen responsiveness

Strategically Equivalent Contests

Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research

Infectious Disease Ontology

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Complex Pediatric Elbow Injury: An Uncommon Case

BACKGROUND: There is paucity of literature describing complex elbow trauma in the pediatric population. We described a case of an uncommon pediatric elbow injury comprised of lateral condyle fracture associated with posterolateral dislocation of elbow. CASE PRESENTATION: A 12-year-old boy sustained a direct elbow trauma and presented with Milch type II lateral condyle fracture associated with posterolateral dislocation of elbow. Elbow dislocation was managed by closed reduction. The elbow stability was assessed under general anaesthesia, followed by open K-wiring for the lateral condylar fracture fixation. The patient had an uneventful recovery with an excellent outcome at 39 months follow-up. CONCLUSION: Complex pediatric elbow injuries are quite unusual to encounter, the management of such fractures can be technically demanding. Concomitant elbow dislocation should be managed by closed reduction followed by open reduction and internal fixation (K-wires or cannulated screws) of the lateral condyle fracture

The narrative self, distributed memory, and evocative objects

In this article, I outline various ways in which artifacts are interwoven with autobiographical memory systems and conceptualize what this implies for the self. I first sketch the narrative approach to the self, arguing that who we are as persons is essentially our (unfolding) life story, which, in turn, determines our present beliefs and desires, but also directs our future goals and actions. I then argue that our autobiographical memory is partly anchored in our embodied interactions with an ecology of artifacts in our environment. Lifelogs, photos, videos, journals, diaries, souvenirs, jewelry, books, works of art, and many other meaningful objects trigger and sometimes constitute emotionally-laden autobiographical memories. Autobiographical memory is thus distributed across embodied agents and various environmental structures. To defend this claim, I draw on and integrate distributed cognition theory and empirical research in human-technology interaction. Based on this, I conclude that the self is neither defined by psychological states realized by the brain nor by biological states realized by the organism, but should be seen as a distributed and relational construct