The hidden impact of inter-individual genomic variations on cellular function

An analysis of the degree of genomic variation between two individual genomes suggests that there may be considerable biochemical differences among individuals. Examination of DNA sequence variations in 14 canonical signaling pathways and Monte-Carlo simulation modeling suggest that the kinetic and quantitative behavior of signaling pathways in many individuals may be significantly perturbed from the 'healthy' norm. Signal transduction pathways in some individuals may suffer context-specific failures, or they may function normally but fail easily in the face of additional environmental perturbations or somatic mutations. These findings argue for new systems biology approaches that can predict pathway status in individuals using personal genome sequences and biomarker data

Molecular self-organisation in a developmental model for the evolution of large-scale artificial neural networks

We argue that molecular self-organisation during embryonic development allows evolution to perform highly nonlinear combinatorial optimisation. A structured approach to architectural optimisation of large-scale Artificial Neural Networks using this principle is presented. We also present simulation results demonstrating the evolution of an edge detecting retina using the proposed methodology

Computational Challenges of Personal Genomics

It is widely predicted that cost and efficiency gains in sequencing will usher in an era of personal genomics and personalized, predictive, preventive, and participatory medicine within a decade. I review the computational challenges ahead and propose general and specific directions for research and development. There is an urgent need to develop semantic ontologies that span genomics, molecular systems biology, and medical data. Although the development of such ontologies would be costly and difficult, the benefits will far outweigh the costs. I argue that availability of such ontologies would allow a revolution in web-services for personal genomics and medicine

Cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control

The endo16 gene of Strongylocentrotus purpuratus encodes a secreted protein of the embryonic and larval midgut. The overall functional organization of the spatial and temporal control system of this gene are relatively well known from a series of earlier cis-regulatory studies. Our recent computational model for the logic operations of the proximal region of the endo16 control system (Module A) specifies the function of interactions at each transcription factor target site of Module A. Here, we extend sequence level functional analysis to the adjacent cis-regulatory region, Module B. The computational logic model is broadened to include B/A interactions as well as other Module B functions. Module B drives expression later in development and its major activator is responsible for a sharp, gut-specific increase in transcription after gastrulation. As shown earlier, Module B output undergoes a synergistic amplification that requires interactions within Module A. The interactions within Module B that are required to generate and transmit its output to Module A are identified. Logic considerations predicted an internal cis-regulatory switch by which spatial control of endo16 expression is shifted from Module A (early) to Module B (later). This prediction was confirmed experimentally and a distinct set of interactions in Module B that mediate the switch function was demonstrated. The endo16 computational model now provides a detailed explanation of the information processing functions executed by the cis-regulatory system of this gene throughout embryogenesis. Early in development the gene participates in the specification events that define the endomesoderm; later it functions as a gut-specific differentiation gene. The cis-regulatory switch mediates this functional change

An animal model of sport related concussive brain injury

A new animal model for concussion of the type seen in professional football was developed, since current animal models did not simulate these conditions. The model is characterized by a high velocity-low mass impact to the head of a freely moving object. Structural damages and functional effects of the model have been investigated. Paper I describes the rat model. A pneumatically driven projectile impacted the temporal region of the head. A 50 g projectile matches the concussions in football players scaled to the rat. Exposures were also performed with a 100 g impactor. The pressure accelerated the projectile to velocities of 7.4 m/s, 9.3 m/s and 11.2 m/s. The head was protected with a padded aluminum helmet. A small accelerometer was attached on the opposite side of the head, inline with the impact, for recording the acceleration of the head. Rats were exposed to a single or repeated (3, with 6 hour intervals) impacts and were sacrificed 1, 4 or 10 days later. Peak head acceleration, ΔV, duration and energy transfer were determined. Brains were perfused and surface injuries identified. Skull fractures were never found. Impact velocity and head ΔV and acceleration were within 1% and 3% of the target. In paper II, neuronal injury was assessed with immunohistochemistry for NF-200, the heaviest neurofilament subunit, and GFAP, an intermediate filament protein in astrocytes. Hemorrhages were visualized with unspecific peroxidase. NF-200 immunoreactivity was accumulated in neuronal perikarya and was reduced in the axons 10 days after impact. Reactive astrocytes were found in the midline regions of the cerebral cortex and periventricularly. Erythrocyte-loaded blood capillaries indicated brain edema in regions of the cerebral cortex, brain stem and cerebellum. A single impact at 7.4 and 9.3 m/s with the 50 g projectile resulted in minimal neuronal injury and astrocytosis. Repeated impacts with the 100 g projectile at 11.2 m/s and 9.3 m/s led to injury bilaterally in the cerebral cortex, subcortical white matter, hippocampus CA1, corpus callosum and the striatum. The pattern of injury is suggestive of Diffuse Neuronal Injury (DAI). In paper III, cognitive function and exploratory behavior were investigated following repeated head impacts. Rats were trained daily for 6 days in the Morris Water Maze. The time of latency to find a hidden platform was reduced from 50 secs on day 1 to 15 secs on day 6. They were then exposed with the 50 g or the 100 g projectile at 9.3 or 11.2 m/s. Spontaneous exploratory activity was assessed with the open field test 2-4 days and 1 and 2 weeks after impacts with the 50 g projectile at 9.3 and 11.2 m/s. The results showed that rats exposed at 11.2 m/s (x3) with the 50 g projectile or 9.3 m/s (x3) and 11.2 m/s (x2) with the 100 g projectile had a significantly increased time of latency to the platform, while those exposed with the 50 g at 9.3 m/s did not differ from the controls. Rats impacted with 50 g (x3) at 9.3 or 11.2 m/s showed a significant decrease in spontaneous exploratory activity. In conclusion, the model fulfilled the conditions of concussion in the freely moving animal, without preparatory surgery, still with good reproducibility. Some aspects of the neuropathology and functional effects were investigated and both showed dose-response effects. The functional changes were cognitive deficits and reduced exploratory activity. Key words: Animal model, football, concussion, brain injury, neuropathology, cognitive function. ISBN Gothenburg 200

The Experience of Immersive Virtual Reality: A Phenomenology Inspired Inquiry

Immersive Virtual Reality (IVR) technology is becoming central for Information Systems (IS) research. However, existing studies in IS fall short in providing insights about how the IVR experience becomes meaningful for end-users. To increase granularity and specificity in this regard, researchers have suggested that the IVR experience can become meaningful due to its fleeting feeling of escapism. In this paper, I explore and characterize how individuals use the IVR experience to create meaning in the context of meaningful escapism, by undertaking a phenomenology inspired inquiry, based on Heideggerian views on meaning, meaningfulness, and world. Interviews and analysis were conducted within an empirical case of IVR fire safety training. As a result, four characteristics of the IVR experience as a meaningful form of escapism were unveiled: a sense of content, a sense of familiarity, a sense of mood, and a sense of care. Throughout this study, I offer a nuanced perspective on how the characteristics contribute to clarify the distinctions and relationship between meaning and meaningfulness, as well as how the IVR experience becomes a meaningful escapism that provides an alternative of individual’s being-in-the-world, into a being-in-the-virtual-world, also known as Virtual Dasein. Further, this study contributes to the IS field by advancing the current discourse on IVR research and escapism, from a phenomenological perspective

Investigating The Sustainable Development of Tabriz University Based on Green Management Parameters and Preferences of University Managers

In recent years, the destruction of the environment on the one hand and the increase in awareness of the consequences of this great danger on the other hand, has led to global actions and consequently, local actions to protect the environment and sustainable development. One of these actions is the sustainable development of universities. The reason for the importance of this case is, firstly, the goal of the universities themselves, which as the center of knowledge and training of the country's elites, is also at the top of environmental affairs, and secondly, as a center with a large number of students and staff which can have a great impact with action for environment. In this research, by using library studies, field observations and interviews, we try to identify sustainability measures of Iranian universities in order to achieve sustainable development and finally present the results of these measures to improve the methods of establishing sustainable development in universities and provide a comprehensive and complete model taking into account all aspects of sustainable development in universities with special emphasis on the campus and its green management. A questionnaire-based on international and domestic standards on the effectiveness of green management parameters in the sustainable development of Tabriz University was prepared and sent to university administrators and faculty members, and then the top ten rankings of this questionnaire were used using interviews with Tabriz university administrators to be determined their preferences in this regard

The gene regulatory network basis of the “community effect,” and analysis of a sea urchin embryo example

The “Community Effect” denotes intra-territorial signaling amongst cells which constitute a particular tissue or embryonic progenitor field. The cells of the territory express the same transcriptional regulatory state, and the intra-territorial signaling is essential to maintenance of this specific regulatory state. The structure of the underlying gene regulatory network (GRN) subcircuitry explains the genomically wired mechanism by which community effect signaling is linked to the continuing transcriptional generation of the territorial regulatory state. A clear example is afforded by the oral ectoderm GRN of the sea urchin embryo where cis-regulatory evidence, experimental embryology, and network analysis combine to provide a complete picture. We review this example and consider less well known but similar cases in other developing systems where the same subcircuit GRN topology is present. To resolve mechanistic issues that arise in considering how community effect signaling could operate to produce its observed effects, we construct and analyze the behavior of a quantitative model of community effect signaling in the sea urchin embryo oral ectoderm. Community effect network topology could constitute part of the genomic regulatory code that defines transcriptional function in multicellular tissues composed of cells in contact, and hence may have arisen as a metazoan developmental strategy

Proposing Design Principles for Sustainable Fire Safety Training in Immersive Virtual Reality

Immersive Virtual Reality (IVR) technologies are frequently adopted by organizations for safety training. Safety training in IVR engages and motivates employees to develop skills in how to manage hazardous situations. By employing IVR for safety training, organizations and employees can develop safety knowledge and increase their sustainability awareness. In this paper we develop design principles for sustainable fire safety training in IVR. The principles were developed through an Action Design Research (ADR) case. The paper demonstrates how ADR can be used to design individual training environments and how the method supports the development of more generic design principles for such environments. The design principles are subsequently proposed as: Design for Multimodal Risk Perception, Design for Empathetic Safety Cognition, Design for Formative Hazard Inspection, and Design for Comfort in Uncomfortable Decision Making

Transient Rheological Behavior of Semisolid SEED-Processed 7075 Aluminum Alloys in Rapid Compression

© 2018, The Author(s). The transient rheological behavior and microstructure evolution of semisolid SEED-processed 7075 aluminum alloys were studied using the rapid compression tests. The effects of the TiB2 grain refinement on the grain morphology and size of semisolid slurries were investigated. Results indicated that the grain refiner could reduce the grain size and improve the globularity of α-Al grains. The grain-refined alloy can be easily deformed at a wide range of solid contents (0.42 to 0.53 Fs), in which the deformation level appears to be independent from the solid content. Under the transient state, the apparent viscosity decreased with increasing shear rate to a minimum value and followed by an increase as the shear rate decreased. The apparent viscosity of the base alloy exhibited a dependency on the solid content, while the apparent viscosity of the grain-refined alloy in the decreasing or increasing shear rate periods was not substantially influenced by the solid content. The viscosity as a function of applied shear rate can be described using the power law viscosity model. The differences in the flow behavior index (n) and the consistency index (k) for two alloys were discussed