Developing Guidelines for Two-Dimensional Model Review and Acceptance

Two independent modelers ran two hydraulic models, SRH-2D and HEC-RAS 2D. The models were applied to the Lakina River (MP 44 McCarthy Road) and to Quartz Creek (MP 0.7 Quartz Creek Road), which approximately represent straight and bend flow conditions, respectively. We compared the results, including water depth, depth averaged velocity, and bed shear stress, from the two models for both modelers. We found that the extent and density of survey data were insufficient for Quartz Creek. Neither model was calibrated due to the lack of basic field data (i.e., discharge, water surface elevation, and sediment characteristics). Consequently, we were unable to draw any conclusion about the accuracy of the models. Concerning the time step and the equations used (simplified or full) to solve the momentum equation in the HEC-RAS 2D model, we found that the minimum time step allowed by the model must be used if the diffusion wave equation is used in the simulations. A greater time step can be used if the full momentum equation is used in the simulations. We developed a set of guidelines for reviewing model results, and developed and provided a two-day training workshop on the two models for ADOT&PF hydraulic engineers

Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops

Establishment of cell polarity-or symmetry breaking-relies on local accumulation of polarity regulators. Although simple positive feedback is sufficient to drive symmetry breaking, it is highly sensitive to stochastic fluctuations typical for living cells. Here, by integrating mathematical modelling with quantitative experimental validations, we show that in the yeast Saccharomyces cerevisiae a combination of actin- and guanine nucleotide dissociation inhibitor-dependent recycling of the central polarity regulator Cdc42 is needed to establish robust cell polarity at a single site during yeast budding. The guanine nucleotide dissociation inhibitor pathway consistently generates a single-polarization site, but requires Cdc42 to cycle rapidly between its active and inactive form, and is therefore sensitive to perturbations of the GTPase cycle. Conversely, actin-mediated recycling of Cdc42 induces robust symmetry breaking but cannot restrict polarization to a single site. Our results demonstrate how cells optimize symmetry breaking through coupling between multiple feedback loops

Algorithms for Graph Connectivity and Cut Problems - Connectivity Augmentation, All-Pairs Minimum Cut, and Cut-Based Clustering

We address a collection of related connectivity and cut problems in simple graphs that reach from the augmentation of planar graphs to be k-regular and c-connected to new data structures representing minimum separating cuts and algorithms that smoothly maintain Gomory-Hu trees in evolving graphs, and finally to an analysis of the cut-based clustering approach of Flake et al. and its adaption to dynamic scenarios

Epigenetic Etiology of Intellectual Disability.

Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked to IDDs often target common downstream genes and cellular processes, the impact of research in individual syndromes goes well beyond each syndrome and can also contribute to the understanding and therapy of other IDDs. Furthermore, the investigation of these disorders helps us to understand the role of chromatin regulators in brain development, plasticity, and gene expression, thereby answering fundamental questions in neurobiology

Antagonistic Gcn5-Hda1 interactions revealed by mutations to the Anaphase Promoting Complex in yeast

<p>Abstract</p> <p>Background</p> <p>Histone post-translational modifications are critical for gene expression and cell viability. A broad spectrum of histone lysine residues have been identified in yeast that are targeted by a variety of modifying enzymes. However, the regulation and interaction of these enzymes remains relatively uncharacterized. Previously we demonstrated that deletion of either the histone acetyltransferase (HAT) <it>GCN5 </it>or the histone deacetylase (HDAC) <it>HDA1 </it>exacerbated the temperature sensitive (<it>ts</it>) mutant phenotype of the Anaphase Promoting Complex (APC) <it>apc5^CA</it>allele. Here, the <it>apc5^CA</it>mutant background is used to study a previously uncharacterized functional antagonistic genetic interaction between Gcn5 and Hda1 that is not detected in <it>APC5 </it>cells.</p> <p>Results</p> <p>Using Northerns, Westerns, reverse transcriptase PCR (rtPCR), chromatin immunoprecipitation (ChIP), and mutant phenotype suppression analysis, we observed that Hda1 and Gcn5 appear to compete for recruitment to promoters. We observed that the presence of Hda1 can partially occlude the binding of Gcn5 to the same promoter. Occlusion of Gcn5 recruitment to these promoters involved Hda1 and Tup1. Using sequential ChIP we show that Hda1 and Tup1 likely form complexes at these promoters, and that complex formation can be increased by deleting <it>GCN5</it>.</p> <p>Conclusions</p> <p>Our data suggests large Gcn5 and Hda1 containing complexes may compete for space on promoters that utilize the Ssn6/Tup1 repressor complex. We predict that in <it>apc5^CA</it>cells the accumulation of an APC target may compensate for the loss of both <it>GCN5 </it>and <it>HDA1</it>.</p

The Human Activity-Travel Rescheduling Decision Process

Over the past few decades the activity scheduling decision process has become an important topic for transportation researchers, including how people reschedule their daily activities and travel in reaction to change. Rescheduling decisions include modifications/updates to timing, location/route, involved persons, event/mode type, and other attributes of activities/trips, as well as addition and deletion of completely new events. Such decisions occur as part of an ongoing process over time, space and across individuals. This thesis developed and applied a new data collection methodology for exploring the rescheduling decision process. The methodology had four main stages: capturing preplanned schedules; Global Positioning System (GPS) tracking; an internetbased prompted recall diary; and a final open-ended in-depth interview to explore how and why rescheduling decisions were made. A total of 40 subjects participated in the study from the Kitchener/Waterloo area of Ontario, Canada. Results strongly suggest the development of a preplan is an on-going process, wherein tentative decisions on many attributes are often made (leaving them partially elaborated on the preplan), and that certain attributes (end times, involved persons) are more likely to evolve over a longer time period, whereas others (start time, activity/mode type, and location) are planned in advance and not likely to be elaborated upon. With regard to subsequent rescheduling decisions, the methodology was able to elicit a much greater number and variety of activity conflicts and modifications from subjects compared to previous studies. The causes of these rescheduling changes also varied substantially beyond the typical activity “p;conflicts” considered in existing models, particularly interpersonal and personal impetuses of change. Past time-geography concepts are supported by these results, although there are some aspects that are unique to these rescheduling decisions. Previous conceptualizations of the activity scheduling process can also be elaborated upon given these findings. Methodologically, the strengths of this study include the successful capturing of preplans (especially partial elaboration), utilization of GPS technologies to reduce the burden of capturing observed activity-travel patterns, and the ability to fully detail each rescheduling decisions through the open ended final interview