Preference versus performance: Investigating the dissociation between objective measures and subjective ratings of usability for schematic metro maps and intuitive theories of design

Three experiments are reported in which objective measures and subjective ratings of schematic metro map usability were investigated. Experiment 1 used a within-subjects design to compare octolinear and curvilinear Paris Metro maps. This replicated and extended Roberts et al. (2013); the curvilinear map was associated with faster journey planning times, and yet preference between the two was unrelated to this measure. In Experiment 2, nine matched versions of the London Underground map were rated for usability and attractiveness, and a clear octolinear bias was displayed. It was also possible to identify individuals who held a simplicity theory of effective design, versus an octolinearity theory. Experiment 3 investigated the relationship between usability ratings and journey planning times for three Berlin network maps, all optimized for simplicity of line trajectories. No differences in times were found, and yet usability ratings after experience at using the maps differed significantly, in line with the findings for the London designs in Experiment 2. Overall, the dissociation between objective measures of performance and subjective ratings of usability is robust, and appears to reflect expectations and prejudices concerning effective design. The octolinearity as a gold standard conjecture for achieving optimum usability continues to be refuted

CX 3 CR1 Deficiency Does Not Influence Trafficking of Adipose Tissue Macrophages in Mice With Diet‐Induced Obesity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93703/1/oby.2012.7.pd

Differential Ligand Binding to a Human Cytomegalovirus Chemokine Receptor Determines Cell Type–Specific Motility

While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX3C-chemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding of both RANTES and Fractalkine activate FAK and ERK-1/2, RANTES signals through Gα12 and Fractalkine through Gαq. These findings represent the first example of differential chemotactic signaling via a multiple chemokine family binding receptor that results in migration of two different cell types. Additionally, the demonstration that US28-mediated chemotaxis is both ligand-specific and cell type–specific has important implications in the role of US28 in HCMV pathogenesis

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

A Randomized, Controlled Pilot Study to Evaluate the Immediate Effect of Targeted Exercise Therapy on Cancer-Related Fatigue in Cancer Survivors: The FatiGO Study

Objectives: Cancer-related fatigue (CRF) is a clinically relevant side effect that impairs cancer survivors after treatment cessation. Exercise interventions have proven effective; however, specific exercise modalities remain untested. The purpose of this study was to evaluate the feasibility of daily fatigue screenings and to show the impact of various exercise interventions on CRF. Methods: The randomized controlled pilot study ran for 4 weeks with 3 training sessions per week, in 5 groups: endurance versus strength (moderate- and vigorous-intensity levels for each) compared to a non-active control group. The primary outcome was feasibility; more specifically, it was evaluated whether the documentation with the Numerical Rating Scale (NRS) on a daily basis and the Multidimensional Fatigue Inventory (MFI) on a weekly basis are usable assessments to generate information about CRF. Results: Over the course of the 4-week intervention, 8.3% of the participants (n = 3) dropped out. Thirty-three of the initial 36 participants completed the exercise sessions with an adherence of 95%. Measurements of daily fatigue were collected three times per day, 85% of which were completely filled out. In regard to weekly fatigue, all but one of the questionnaires were submitted (99.5%). Neither during the intervention nor during the tests did any serious adverse events occur within the FatiGO study; hence, the exercise intervention is considered to be feasible for participants. Conclusions: This pilot study showed the feasibility of close-meshed daily fatigue screening. Preliminary data indicate that cancer survivors are able to train in high-intensity ranges with tendencies toward decreased fatigue. Therefore, practicability of the study design is shown. Further results are expected within the prospective multicenter trial

Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity

International audienceObesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders

CX3CL1 Up-Regulation Is Associated with Recruitment of CX3CR1+ Mononuclear Phagocytes and T Lymphocytes in the Lungs during Cigarette Smoke-Induced Emphysema

CX3CR1 is expressed on monocytes, dendritic cells, macrophages, subsets of T lymphocytes, and natural killer cells and functions in diverse capacities such as leukocyte adhesion, migration, and cell survival on ligand binding. Expression of the CX3CL1 gene, whose expression product is the sole ligand for CX3CR1, is up-regulated in human lungs with chronic cigarette smoke-induced obstructive lung disease. At present, it is unknown whether CX3CL1 up-regulation is associated with the recruitment and accumulation of immune cells that express CX3CR1. We show that mice chronically exposed to cigarette smoke up-regulate CX3CL1 gene expression, which is associated with an influx of CX3CR1+ cells in the lungs. The increase in CX3CR1+ cells is primarily comprised of macrophages and T lymphocytes and is associated with the development of emphysema. In alveolar macrophages, cigarette smoke exposure increased the expression of both CX3CR1 and CX3CL1 genes. The inducibility of CX3CR1 expression was not solely dependent on a chronic stimulus because lipopolysaccharide up-regulated CX3CR1 in RAW264.7 cells in vitro and in mononuclear phagocytes in vivo. Our findings suggest a mechanism by which macrophages amplify and promote CX3CR1+ cell accumulation within the lungs during both acute and chronic inflammatory stress. We suggest that one function of the CX3CR1-CX3CL1 pathway is to recruit and sustain divergent immune cell populations implicated in the pathogenesis of cigarette smoke-induced emphysema

Reproducibility Project: Cancer Biology

The Reproducibility Project: Cancer Biology was an initiative to independently replicate selected experiments from a number of high-profile papers in the field of cancer biology. In the end 50 experiments from 23 papers were repeated. The final two outputs from the project recount in detail the challenges the project team encountered while repeating these experiments ('Challenges for assessing replicability in preclinical cancer biology': https://elifesciences.org/articles/67995), and report the results of a meta-analysis that combined the results from all the experiments ('Investigating the replicability of preclinical cancer biology': https://elifesciences.org/articles/71601). The project was a collaboration between the Center for Open Science and Science Exchange with all papers published by eLife