Structural assessment of single amino acid mutations: application to TP53 function.

Single amino acid substitution is the type of protein alteration most related to human diseases. Current studies seek primarily to distinguish neutral mutations from harmful ones. Very few methods offer an explanation of the final prediction result in terms of the probable structural or functional effect on the protein. In this study, we describe the use of three novel parameters to identify experimentally-verified critical residues of the TP53 protein (p53). The first two parameters make use of a surface clustering method to calculate the protein surface area of highly conserved regions or regions with high nonlocal atomic interaction energy (ANOLEA) score. These parameters help identify important functional regions on the surface of a protein. The last parameter involves the use of a new method for pseudobinding free-energy estimation to specifically probe the importance of residue side-chains to the stability of protein fold. A decision tree was designed to optimally combine these three parameters. The result was compared to the functional data stored in the International Agency for Research on Cancer (IARC) TP53 mutation database. The final prediction achieved a prediction accuracy of 70% and a Matthews correlation coefficient of 0.45. It also showed a high specificity of 91.8%. Mutations in the 85 correctly identified important residues represented 81.7% of the total mutations recorded in the database. In addition, the method was able to correctly assign a probable functional or structural role to the residues. Such information could be critical for the interpretation and prediction of the effect of missense mutations, as it not only provided the fundamental explanation of the observed effect, but also helped design the most appropriate laboratory experiment to verify the prediction results.

Structural motifs of biomolecules.

Biomolecular structures are assemblies of emergent anisotropic building modules such as uniaxial helices or biaxial strands. We provide an approach to understanding a marginally compact phase of matter that is occupied by proteins and DNA. This phase, which is in some respects analogous to the liquid crystal phase for chain molecules, stabilizes a range of shapes that can be obtained by sequence-independent interactions occurring intra- and intermolecularly between polymeric molecules. We present a singularity-free self-interaction for a tube in the continuum limit and show that this results in the tube being positioned in the marginally compact phase. Our work provides a unified framework for understanding the building blocks of biomolecules.

Structural Analysis of Aggregate Blends Using the SHRP Gyratory Compactor, MLR-95-8, 1996

The Iowa Department of Transportation (IDOT) received a Strategic Highway Research Program (SHRP) gyratory compactor in December 1994. Since then IDOT has been studying the ability of the compactor to analyze fundamental properties of aggregates such as shape, texture, and gradation by studying the volumetrics of the aggregate blends under a standard load using the SHRP gyratory compactor. This method of analyzing the volumetrics of aggregate blends is similar to SHRP's fine aggregate angularity procedure, which analyzes void levels in noncompacted aggregate blends, which in turn can be used to evaluate the texture or shape of aggregates, what SHRP refers to as angularity. Research is showing that by splitting the aggregate blend on the 2.36-mm (#8) sieve and analyzing the volumetrics or angularity of the separated blend, important fundamental properties can be determined. Most important is structure (the degree and location of aggregate interlock). In addition, analysis of the volumes of the coarse and fine portions can predict the voids in the mineral aggregate and the desired asphalt content. By predicting these properties, it can be determined whether the combined aggregate blend, when mixed with asphalt cement, will produce a mix with structural adequacy to carry the designed traffic load.

Asphalt Resurfacing Structural Research, HR-556, Construction Report, 1995

Discarded tires present major disposal and environmental problems. One method of recycling tires is to use finely ground rubber from tires in asphalt cement concrete (ACC). This process has been researched in Iowa since 1991. There are currently eight projects being researched. This project involved using crumb rubber modifier (CRM) in ACC using a dry process. This project is located on US 63 in Howard County. It involved 17 test sections. There were five test sections using 20 lb of CRM per ton, four test sections using 10 lb of CRM per ton and eight test sections using a conventional mix. Not only were different mixes used, but the overlay was also placed in various thicknesses ranging from 2 in. to 8 in. (5 cm to 20 cm). The project was completed in August 1994. The project construction went well with only minor problems. This report contains information about procedures and tests that were completed and those that will be completed. Evaluation on the project will continue for five years.

Protection of Structural Concrete Substructures, HR-220, Progress Report, 1984

The corrosion of reinforcing steel within concrete has always been a problem in construction of bridge decks. With low slump concrete and epoxy rebar, progress has been made in controlling the corrosion. There is concern, however, that the chloride also attacks the substructures, specifically the pier columns. They are subject to chloride attack by chemical deicers in the drainage from the bridge deck. Piers supporting grade separation bridges are also subject to chlorides contained in the direct splash from the lower level traffic. In this project, a field evaluation was conducted to evaluate the effectiveness of commercially available products in preventing chloride intrusion.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

Dynamic Deflections for Determining Structural Rating of Flexible Pavements, HR-178, 1979

The Road Rater is a dynamic deflection measuring apparatus for flexible base pavements. The Road Rater replaces the Benkelman Beam which was last used by the Iowa DOT in 1977. Road Rater test results correlate reasonably well (correlation coefficient = 0.83) with Benkelman Beam test data. The basic differences between the Road Rater and Benkelman Beam are as follows: 1. The Benkelman Beam uses a static 18,000 lb. load while the Road Rater uses a dynamic 800 to 2,000 lb. loading. 2. The Road Rater tests much faster and more economically than the Benkelman Beam. 3. The Road Rater better simulates a moving truck than the Benkelman Beam. The basic operating principle of the Road Rater is to impart a dynamic loading and measure the resultant movement of the pavement with velocity sensors. This data, when properly adjusted for temperature by use of a nomograph included in this report, can be used to determine pavement life expectancy and estimate overlay thickness required. Road Rater testing will be conducted in the spring, when pavements are in their weakest condition, until seasonal correction factors can be developed. The Road Rater does not have sufficient ram weight to effectively evaluate load carrying capacity of rigid pavements. All rigid pavements react similarly to Road Rater testing and generally deflect from 0.65 to 1.30 mils. Research will be contined to evaluate rigid pavements with the Road Rater, however. The Road Rater has proven to be a reliable, troublefree pavement evaluation machine. The deflection apparatus was originally front-mounted,but was rear-mounted during the winter of 1977-78. Since that time, van handling has greatly improved, and front suspension parts are no longer overstressed due to improper weight distribution.

Structural Analysis and Overlay Design of Pavements Using the Road Rater, MLR-84-3, 1986

In recent years the Iowa DOT has shifted emphasis from the construction of new roads to the maintenance and preservation of existing highways. A need has developed for analyzing pavements structurally to select the correct rehabilitation strategy and to properly design a pavement overlay if necessary. This need has been fulfilled by Road Rater testing which has been used successfully on all types of pavements to evaluate pavement and subgrade conditions and to design asphaltic concrete overlays. The Iowa Road Rater Design Method has been simplified so that it may be easily understood and used by the widely diverse groups of individuals which may be involved in pavement restoration and management. Road Rater analysis techniques have worked well to date and have been verified by pavement coring, soils sampling and testing, and pavement removal by block sampling. Void detection testing has also been performed experimentally in Iowa, and results indicate that the Road Rater can be used to locate pavement voids and that Road Rater analysis techniques are reasonably accurate. The success of Road Rater research and development has made deflection test data one of the most important pavement management inputs.

Martensitic phase transformation in rapidly solidified Mn50Ni40In10 alloy ribbons

Heusler alloy Mn50Ni40In10 was produced as preferentially textured ribbon flakes by melt spinning, finding the existence of martensitic-austenic transformation with both phases exhibiting ferromagnetic ordering. A microcrystalline three-layered microstructure of ordered columnar grains grown perpendicularly to ribbon plane was formed between two thin layers of smaller grains. The characteristic temperatures of the martensitic transformation were MS=213 K, Mf=173 K, AS=222 K, and Af=243 K. Austenite phase shows a cubic L21 structure (a=0.6013(3) nm at 298 K and a Curie point of 311 K), transforming into a modulated fourteen-layer modulation monoclinic martensite

Agrobacterium-mediated genetic transformation of 'Hamlin' sweet orange

The development and optimization of efficient transformation protocols is essential in new citrus breeding programs, not only for rootstock, but also for scion improvement. Transgenic 'Hamlin' sweet orange (Citrus sinensis (L.) Osbeck) plants were obtained by Agrobacterium tumefaciens-mediated transformation of epicotyl segments collected from seedlings germinated in vitro. Factors influencing genetic transformation efficiency were evaluated including seedling incubation conditions, time of inoculation with Agrobacterium and co-culture conditions. Epicotyl segments were adequate explants for transformation, regenerating plants by direct organogenesis. Higher percentage of transformation was obtained with explants collected from seedlings germinated in darkness, transferred to 16 hours photoperiod for 2-3 weeks, and inoculated with Agrobacterium for 15-45 min. The best co-culture condition was the incubation of the explants in darkness, for three days in culture medium supplemented with 100 muM of acetosyringone. Genetic transformation was confirmed by performing beta-glucoronidase (GUS) assays and, subsequently, by PCR amplification for the nptII and GUS genes.

Structural development accounting

We construct and estimate a unified model combining three of the main sources ofcross-country income disparities: differences in factor endowments, barriers to technologyadoption and the inappropriateness of frontier technologies to local conditions. The keycomponents are different types of workers, distortions to capital accumulation, directedtechnical change, costly adoption and spillovers from the world technology frontier. Despiteits parsimonious parametrization, our empirical model provides a good fit of GDP data forup to 86 countries in 1970 and 122 countries in 2000. Removing barriers to technologyadoption would increase the output per worker of the average non-OECD country relativeto the US from 0.19 to 0.61, while increasing skill premia in all countries. Removing barriersto trade in goods amplifies income disparities, induces skill-biased technology adoptionand increases skill premia in the majority of countries. These results are reverted if tradeliberalization is coupled with international IPR protection.

Structural Characterization of UHPC Waffle Bridge Deck and Connections, TR-614, 2014

The AASHTO strategic plan in 2005 for bridge engineering identified extending the service life of bridges and accelerating bridge construction as two of the grand challenges in bridge engineering. These challenges have the objective of producing safer and more economical bridges at a faster rate with a minimum service life of 75 years and reduced maintenance cost to serve the country’s infrastructure needs. Previous studies have shown that a prefabricated full-depth precast concrete deck system is an innovative technique that accelerates the rehabilitation process of a bridge deck, extending its service life with reduced user delays and community disruptions and lowering its life-cycle costs. Previous use of ultra-high performance concrete (UHPC) for bridge applications in the United States has been considered to be efficient and economical because of its superior structural characteristics and durability properties. Full-depth UHPC waffle deck panel systems have been developed over the past three years in Europe and the United States. Subsequently, a single span, 60-ft long and 33-ft wide prototype bridge with full-depth prefabricated UHPC waffle deck panels has been designed and built for a replacement bridge in Wapello County, Iowa. The structural performance characteristics and the constructability of the UHPC waffle deck system and its critical connections were studied through an experimental program at the structural laboratory of Iowa State University (ISU). Two prefabricated full-depth UHPC waffle deck (8 feet by 9 feet 9 inches by 8 inches) panels were connected to 24-ft long precast girders, and the system was tested under service, fatigue, overload, and ultimate loads. Three months after the completion of the bridge with waffle deck system, it was load tested under live loads in February 2012. The measured strain and deflection values were within the acceptable limits, validating the structural performance of the bridge deck. Based on the laboratory test results, observations, field testing of the prototype bridge, and experience gained from the sequence of construction events such as panel fabrication and casting of transverse and longitudinal joints, a prefabricated UHPC waffle deck system is found to be a viable option to achieve the goals of the AASHTO strategic plan.