An Application of the Utah State University Watershed Simulation Model to the Entiat Experimental Watershed, Washington State

To study the effects of a forest fire on runoff characteristics, the Utah State University Watershed Simulation Model (USUWSM) has been applied to three small drainage areas in the Entiat Experimental Watershed which is located within the Wenatchee National Forest of central Washington. Each component of the USUWSM has been described in the report, including structural changes to the model that were necessary to achieve reasonable agreement between observed and simulated runoff hydrographs. Lack of information on the spatial distribution and precipitation due to the absence of an adequate precipitation gaging network on or close to the study area was a severe handicap to the simulation study. Only a very short period of post-fire streamflow record was available and thus it was possible to make only qualative conclusions regarding the effects of the forest fire on runoff characteristics

Hydrologic Model Studies of the Mt. Olympus Cove Area of Salt Lake County

Urban development on any natural drainage basin causes marked changes in the runoff characteristics of the basin. Urbanization alters natural drainage channels and reduces average infiltration rates. Thus, flood conditions are enhanced both within the urbanizing area itself and at downstream locations, where existing channels might not be able to cope with the increased rates of water flow. The Olympus Cove area in Salt Lake County is undergoing rapid urban development, and potential flood hazards within the area and at downstream locations are thereby increasing. Recognizing this situation, officials of the Sale Lake County took the initiative in organizing an ‘ad hoc’ interagency technical team to study and evaluate the problem. The particular responsibilities which were undertaken by the representatives of the Utah Water Research Laboratory on this study team were to synthesize all existing information, and what which might be developed during the study period, and on this basis to formulate computer models to represent the hydrology of the area. The report describes the model development process and discusses the application of the models to the three source areas being considered, namely: (1) the Neff’s Canyon drainage; (2) the northern slopes of Mt. Olympus; and (3) the urbanizing area of Olympus Cove. Runoff from the short-term, high-intensity, convective storms is emphasized. Hydrologic response was found to be particularl

Modeling the Total Hydrologic-Sociologic Flow System of Urban Areas - Phase II

Introduction and Overview: This is an interim report on Phase II of the three phase study. The objectives covered in this phase were: 1. To gather social and hydrologic data needed to calibrate and test the model. 2. The expand the physical model to include the rural part of the watersheds. 3. To test and improve techniques of the logical linking of the hydrologic and sociologic systems. 4. To begin adapting the model to the computer. During the second phase for the hydrologic component of the model major emphasis was placed on the expansion of the hydrologic area and the collection and analysis of additional physical data. The major emphasis for the sociologic part of the model was on the gathering of social data by the re-designing and testing of an improved research instrument (schedule or questionaire_ and administration of this schedule to a random sample of the general population in the urbanized area. The urbanized area is related to the physical hydrologic area of the study. The data were collected to improve the basic methodology and conceptualizations for linking the hydrologic and sociologic systems together in one model. Division of this report: Section II of this interim report deals with development of the physical component of they hydrologic-sociologic model. It describes the expansion of the hydrologic to include the rural parts of the watershed and tests for validation of they physical submodel. Section III review the ype of work done in Phase II of the sociological work. This consisted of: (1) reviewing the accomplishments and limitations of the first phase; (2) redesigning the questionaire to correct deficiencies in the one used in the first study, to measure additional variables throught to perhaps be relevant to the problem, and where desireable, to adapt them to the general population of the area rather than to specialized populations; (3) pretesting of component parts of the revised schedule; (4) drawing of a random sample from the population; (5) interviewing of the sample; (6) coding and processing of data for analysis; and (7) preliminary analysis of the results of the data. Progress made in the mathematical formulations of social elements is vital. The refinement of meaurement of the population data for use in the model is of central importance since the effectiveness of the testing, verification, and consequent improvement of the model depends on the accuracy of the measurement of the variables involved. Section IV shows some details on the work performed in interrelating the sociologic and hydrologic components of the model, and on one possible mathematical formulation which shows some of the interrelationships between these components. It is hoped that the formulation achieved will be useful to planners, not only in increased understanding of the total system, but also in the analysis of the merits of flood-control proposals relative to the social characteristics of particular areas. Section V discusses the purposes of the work in Phase II and the objectives expected to be met during the coming phase

A Preliminary Model of the Hydrologic-Sociologic Flow System of an Urban Area

This report describes the first phase of a larger study which is directed toward the development of a general technique for analyzing and solving urban metropolitan hydrologic problems through a joint consideration of both the physical and social dimensions. This report is limited to the preliminary work of identification of social variables, the first steps in assigning mathematical values to them, and developing a mathematical format for these variables. In addition, the physical-hydrologic system is identified for purposes of clarifying the elements in that system. The ultimate objective of the entire study is directed toward discovering a theoretical and generally applicable mathematical model of both the physical and social dimensions involved in metropolitan flooding problems

Application of a Hydrologic Model to the Planning and Design of Storm Drainage Systems for Urban Areas

A generally applicable hybrid computer program is developed to simulate runoff from urban watersheds, and is applied to represent the outflow hydrographs of three urban watersheds located within Salt Lake County, Utah. The gaged outflow of the watersheds provided a means for comparing the observed and the simulated final outflow hydrographs. Each of the three watersheds was subdivided into spatial units or subzones, and the outflow hydrographs for each subzone were obtained by abstracting interceptions, infiltration, and depression storage from the rainfall hyetograph of each subzone. The resulting hydrograph outflow of each subzone was routed to the Jordan River, the final outflow point of the three watersheds. The final hydrographs of the three watersheds were combined and compared with the gaged flow. The unique features of this model are its ability to (1) accept a wide range of input hyetographs, (2) accommodate variable loss rates, (3) combine subzone hydrographs, and (4) combine watershed hydrographs into a single runoff function. In addition to numerical output, graphs can be plotted for visual inspection. This characteristic enables designers and planners to use the model to examine quickly both the physical and economic impacts of various possible input conditions and management alternatives. An economic analysis follows the hydrologic study. Areas subject to flooding within the study watersheds were mapped and measured in accordance with peak discharge rates. Flood damages per unit area were estimated as a function of degree or urbanization. Projected population growth within the area is used as a basis for estimating the rate of urbanization of the next 100 years. The utility of the procedure (which depends heavily upon the hydrologic model) for design and planning purposes is demonstrated through an example of a benefit-cost analysis which is applied to a proposed flood control structure within a portion of the study area. The study emphasized that reliable planning and management solutions from the modeling approach depend heavily upon the availability of adequate and accurate field data. For this reason, “barometer” urban hydrology watersheds situated at strategic locations throughout the nation would provide invaluable information for the broad application of this procedure. In addition, it is considered that future work also should emphasize the expansion of the model to include the economic dimension, and ultimately various aspects of the social dimension

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Pharmacodynamic Modeling of Anti-Cancer Activity of Tetraiodothyroacetic Acid in a Perfused Cell Culture System

Unmodified or as a poly[lactide-co-glycolide] nanoparticle, tetraiodothyroacetic acid (tetrac) acts at the integrin αvβ3 receptor on human cancer cells to inhibit tumor cell proliferation and xenograft growth. To study in vitro the pharmacodynamics of tetrac formulations in the absence of and in conjunction with other chemotherapeutic agents, we developed a perfusion bellows cell culture system. Cells were grown on polymer flakes and exposed to various concentrations of tetrac, nano-tetrac, resveratrol, cetuximab, or a combination for up to 18 days. Cells were harvested and counted every one or two days. Both NONMEM VI and the exact Monte Carlo parametric expectation maximization algorithm in S-ADAPT were utilized for mathematical modeling. Unmodified tetrac inhibited the proliferation of cancer cells and did so with differing potency in different cell lines. The developed mechanism-based model included two effects of tetrac on different parts of the cell cycle which could be distinguished. For human breast cancer cells, modeling suggested a higher sensitivity (lower IC50) to the effect on success rate of replication than the effect on rate of growth, whereas the capacity (Imax) was larger for the effect on growth rate. Nanoparticulate tetrac (nano-tetrac), which does not enter into cells, had a higher potency and a larger anti-proliferative effect than unmodified tetrac. Fluorescence-activated cell sorting analysis of harvested cells revealed tetrac and nano-tetrac induced concentration-dependent apoptosis that was correlated with expression of pro-apoptotic proteins, such as p53, p21, PIG3 and BAD for nano-tetrac, while unmodified tetrac showed a different profile. Approximately additive anti-proliferative effects were found for the combinations of tetrac and resveratrol, tetrac and cetuximab (Erbitux), and nano-tetrac and cetuximab. Our in vitro perfusion cancer cell system together with mathematical modeling successfully described the anti-proliferative effects over time of tetrac and nano-tetrac and may be useful for dose-finding and studying the pharmacodynamics of other chemotherapeutic agents or their combinations

Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.

Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN