RNA interference mitigates motor and neuropathological deficits in a cerebellar mouse model of machado-joseph disease.

Machado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the disease when initiated before onset of the disease had not been explored. Here, using a lentiviral-mediated allele-specific silencing of mutant ataxin-3 in an early pre-symptomatic cerebellar mouse model of Machado-Joseph disease we show that this strategy hampers the development of the motor and neuropathological phenotypic characteristics of the disease. At the histological level, the RNA-specific silencing of mutant ataxin-3 decreased formation of mutant ataxin-3 aggregates, preserved Purkinje cell morphology and expression of neuronal markers while reducing cell death. Importantly, gene silencing prevented the development of impairments in balance, motor coordination, gait and hyperactivity observed in control mice. These data support the therapeutic potential of RNA interference for Machado-Joseph disease and constitute a proof of principle of the beneficial effects of early allele-specific silencing for therapy of this disease.

Effects of Special Aggregate on Bridge Deck Overlay Frictional Properties, HR-205, 1986

The Iowa DOT has been using the "Iowa Method" thin bonded low-slump dense Portland Cement Concrete (PCC) bridge deck overlay for rehabilitation of delaminated decks since 1963. In time, continued use of studded tires will wear away the transverse grooved texture. The objective of this research was to evaluate the benefit of incorporating a hard durable aggregate into a dense PCC overlay to provide frictional property longevity. The project included three overlays on I-35 near Ankeny. The texture and friction properties of two overlays, one constructed with crushed granite and the other with crushed quartzite coarse aggregate, were compared to an overlay constructed with locally available crushed limestone. There were no construction problems resulting from the use of crushed granite or quartzite. There was no significant frictional property benefit from the crushed granite or crushed quartzite through six years.

The Relationship of Ferroan Dolomite Aggregate to Rapid Concrete Deterioration, HR-266, 1987

Some of Iowa's 13,200 miles of portland cement concrete (pcc) pavement have remained structurally sound for over 50 years while others have suffered premature deterioration. Research has shown that the type of coarse aggregate used in the pcc is the major cause of this premature deterioration. Some coarse aggregates for concrete exhibit a nonuniform performance history. They contribute to premature deterioration on heavily salted primary roadways while providing long maintenance-free life on unsalted secondary pavements. This inconsistency supports the premise that there are at least two mechanisms that contribute to the deterioration. Previous research has shown that one of these mechanisms is a bad pore system. The other is apparently a chemical reaction. The objective of this research is to develop simple rapid test methods to predict the durability of carbonate aggregate in pcc pavement. X-ray diffraction analyses of aggregate samples have been conducted on various beds from numerous quarries producing diffraction plots for more than 200 samples of dolomitic or dolomite aggregates. The crystalline structures of these dolomitic aggregates show maximum-intensity dolomite/ankerite peaks ranging from a d-spacing of 2.884 angstroms for good aggregates to a d-spacing of 2.914 angstroms for nondurable aggregates. If coarse aggregates with known bad pore systems are removed from this summary, the d-spacing values of the remaining aggregates correlate very well with expected service life. This may indicate that the iron substitution for magnesium in the dolomite crystal is associated with the instability of the ferroan dolomite aggregates in pcc pavement.

Development of a Conductometric Test for Frost Resistance of Concrete, HR-272, Phase II, 1986

The purpose of this report is to describe the major research activities during the period of February 1, 1985 - October 30, 1986 for the Iowa Highway Research Board under the research contract entitled "Development of a Conductometric Test for Frost Resistance of Concrete." The objective of this research, as stated in the project proposal, is to develop a test method which can be reasonably rapidly performed in the laboratory and in the field to predict the behavior of concrete subjected to the action of alternate freezing and thawing with a high degree of certainty. In the work plan of the proposal it was stated that the early part of the first year would be devoted to construction of testing equipment and preparation of specimens and the remainder of the year would be devoted to the testing of specimens. It was also stated that the second and third years would be devoted to performance and refinements of tests, data analysis, preparation of suggested specifications, and performance of tests covering variables which need to be studied such as types of aggregates, fly ash replacements and other admixtures. The objective of this report is to describe the progress made during the first 20 months of this project and assess the significance of the results obtained thus far and the expected significance of the results obtainable during the third year of the project.

The Effects of Crushed Particles in Asphalt Mixtures, HR-311 and MLR-88-16, Part 1, 1990

One of the most serious impediments to the continued successful use of hot mix asphalt (HMA) pavements is rutting. The Iowa Department of Transportation has required 85% crushed particles and 75 blow Marshall mix design in an effort to prevent rutting on interstate roadways. The objective of this research and report is to develop relation~hips between the percent of crushed particles and resistance to rutting in pavement through the use of various laboratory test procedures. HMA mixtures were made with 0, 30, 60, 85 and 100% crushed gravel, crushed limestone and crushed quartzite combined with uncrushed sand and gravel. These aggregate combinations were used with 4, 5 and 6% asphalt cement (ac). Laboratory testing included Marshall stability, resilient modulus, indirect tensile and creep. A creep resistance factor (CRF) was developed to provide a single numeric value for creep test results. The CRF values relate well to the amount of crushed particles and the perceived resistance to rutting. The indirect tensile test is highly dependent on the ac with a small effect from the percent of crushed particles. The Marshall stability from 75 blow compaction relates well to the percent of crushed particles. The resilient modulus in some cases is highly affected by grade of ac.

Investigation of Rapid Thermal Analysis Procedures for Prediction of the Service Life of PCCP Carbonate Coarse Aggregate, HR-337, 1993

The major objective of this research project was to use thermal analysis techniques in conjunction with x-ray analysis methods to identify and explain chemical reactions that promote aggregate related deterioration in portland cement concrete. Twenty-two different carbonate aggregate samples were subjected to a chemical testing scheme that included: • bulk chemistry (major, minor and selected trace elements) • bulk mineralogy (minor phases concentrated by acid extraction) • solid-solution in the major carbonate phases • crystallite size determinations for the major carbonate phases • a salt treatment study to evaluate the impact of deicer salts Test results from these different studies were then compared to information that had been obtained using thermogravimetric analysis techniques. Since many of the limestones and dolomites that were used in the study had extensive field service records it was possible to correlate many of the variables with service life. The results of this study have indicated that thermogravimetric analysis can play an important role in categorizing carbonate aggregates. In fact, with modern automated thermal analysis systems it should be possible to utilize such methods on a quality control basis. Strong correlations were found between several of the variables that were monitored in this study. In fact, several of the variables exhibited significant correlations to concrete service life. When the full data set was utilized (n = 18), the significant correlations to service life can be summarized as follows ( a = 5% level): • Correlation coefficient, r, = -0.73 for premature TG loss versus service life. • Correlation coefficient, r, = 0.74 for relative crystallite size versus service life. • Correlation coefficient, r, = 0.53 for ASTM C666 durability factor versus service life. • Correlation coefficient, r, = -0.52 for acid-insoluble residue versus service life. Separation of the carbonate aggregates into their mineralogical categories (i.e., calcites and dolomites) tended to increase the correlation coefficients for some specific variables (r sometimes approached 0.90); however, the reliability of such correlations was questionable because of the small number of samples that were present in this study.

Sprinkle Treatment (Bristowes Spreader), HR-512

Safety is an important aspect of highway design. Texture and frictional properties are important characteristics in providing safe roadways. Longevity of desirable frictional properties is highly dependent on the aggregate within asphalt pavement. Iowa unfortunately has areas of the State where the locally available aggregate will not give long lasting desirable frictional properties. Iowa has utilized sprinkle treatments to improve the safety of many new asphalt concrete pavements.

Foamed Asphalt Shoulders City of Muscatine, HR-529, 1993

Foamed asphalt shoulders were placed on an Industrial Connector road at the south edge of Muscatine. The foamed asphalt was produced by injecting 1 to 2 percent water into hot asphalt cement in a patented foaming chamber. A foam develops which is 10 to 15 times the original volume. of the asphalt cement. A 3/8" limestone aggregate was used in the foamed asphalt mixture. This foamed asphalt was placed on the shoulders and in the radii on the Industrial Connector road in May 1987. The radii were later replaced due to reconstruction, but the shoulders remain and performed fairly well with some recent stripping and potholing. The performance appeared to be lower than expected from conventional hot mix on projects with similar traffic.

Recycling of Asphalt Concrete From I-80 in Cass County, HR-1011, 1978

Approximately 40,000 tons of deteriorated asphalt concrete has been removed from Interstate 80 in Cass County and stockpiled. Laboratory tests indicate that this material has considerable value when upgraded with new aggregate and asphalt cement. This report documents the procedures used and results obtained on an experimental recycling project. It was demonstrated that present drum mixing-recycling equipment and procedures can be used to utilize this material with satisfactory results. Laboratory analyses of material components and mixtures were performed; these analyses indicate mixture can be produced that is uniform, stable, and very closely resembles mixture produced with all virgin material. A 1700 foot long test section was constructed on US 169 in Kossuth County wherein salvaged asphalt concrete from I-80 in Cass County was utilized. The salvaged mix was blended with virgin aggregate and recycled through a modified drum mixing plant, the reprocessed mixture was satisfactorily placed 1 1/2 inches thick as a resurfacing course on an old PCC pavement. An inspection of the test section was made in December of 1978 to evaluate the performance after one full year of service. There was no evidence of rutting or shoving from traffic. The surface does, however, have a very dry and somewhat ravelled appearance. This can be related to a low asphalt content in the mix and some temperature control problems which were difficult to get fully corrected on such a short project and with a short supply of readily available materials.

Factors Relating to Aggregate Durability in Portland Cement Concrete, HR-2022, Interim Report, 1983

Over the past several years we conducted a comprehensive study on the pore systems of limestones used as coarse aggregate in portland cement concrete (pee) and their relationship to freeze-thaw aggregate failure. A simple test called the Iowa Pore Index Test was developed and used to identify those coarse aggregates that had freeze-thaw susceptible pore systems. Basically, it identified those aggregates that could take on a considerable amount of water but only at a slow rate. The assumption was that if an aggregate would take on a considerable amount of water at a slow rate, its pore system would impede the outward movement of water through a critically saturated particle during freezing, causing particle fracture. The test was quite successful when used to identify aggregates containing susceptible pore systems if the aggregates were clean carbonates containing less than 2% or 3% insolubles. The correlation between service record, ASTM C666B and the pore index test was good, but not good enough. It became apparent over the past year that there were factors other than the pore system that could cause an aggregate to fail when used in pee. The role that silica and clay play in aggregate durability was studied.

Air Content and Permeability of PCC Pavements: 1909 to 2006, MLR-05-02, 2007

Portland cement concrete pavements have given excellent service history for Iowa. Many of these pavements placed during the 1920’s and 1930’s are still in service today. Many factors go in to achieve a long term durable concrete pavement. Probably the most important is the durability of the aggregate. Until the 1930’s, pit run gravel was the most predominant aggregate used. Many of these gravels provided long term performance and their durability is dependent upon the carbonate fraction of the gravel. Later, limestone (calcium carbonate) and dolomite (calcium, magnesium carbonate) sources were mined across Iowa. The durability of these carbonate aggregates is largely dependent upon the pore system which can cause freeze thaw problems known as D-cracking, which was a problem with some sources during the 1960’s. Also, some of these carbonate aggregates are also susceptible to deterioration from deicing salts. Geologists have identified the major components that affect the durability of these carbonate aggregates and sources are tested to ensure long term performance in Portland cement concrete. Air entrainment was originally put in concrete to improve scaling resistance. It is well known that air entrainment is required to provide freeze thaw protection in concrete pavements today. In Iowa, air entrainment was not introduced in concrete pavements until 1952. This research investigates properties that made older concrete pavements durable without air entrainment.

An Investigation of the Chemical Method of Determining the Cement Content of Hardened Concrete, MLR-71-01 and R-248, 1971

The Iowa State Highway Commission Laboratory is called upon to determine the cement content of hardened concrete when field problems relating to batch weights are encountered. The standard test for determining the cement content is ASTM C-85. An investigation of this method by the New Jersey State Highway Department involving duplicate samples and four cooperating laboratories produced very erratic results, however, the results obtained by this method have not been directly compared to known cement contents of concrete made with various cements and various aggregates used in Iowa.

A Study of the Frictional Properties of New Asphaltic Concrete Pavements in Iowa, MLR-78-03, 1978

Seven asphaltic concrete resurfacing projects were tested for their frictional properties to determine the age-friction relationship of new paving. Projects studied included Type A asphaltic concrete which is generally used for higher traffic volume roads and Type B asphaltic concrete, a lower type material. Also included in the study were asphaltic concretes containing Type 3 and Type 4 coarse aggregate texture classifications. The classifications are based upon material type and grain size composition. Surfaces both with and without sprinkle treatment aggregates were also included. The data gathered suggests that properly designed and placed dense graded asphaltic concrete mixes are adequate to serve the traveling public at all ages tested.

Penetration Characteristics of Asphalt in a Recycled Mixture, MLR-79-03, 1979

Samples of both recycled and nonrecycled asphaltic concrete were extracted in increments by the Abson Recovery Method and the penetration of the asphalt from each increment determined. The recycled projects were plantsite operations containing various amounts of virgin gravel. Cored samples were taken from the pavements on Kossuth County roads that were constructed as recycled projects in 1975, 1976, and 1977. Cored samples were also taken from a Kossuth County paving project done in 1975, that was not recycled. Comparison mix samples from 1978 construction projects in Marshall and Woodbury Counties of non - recycled projects are included. The test data from the penetrations of the recovered asphalt indicates that mixing of the old and new asphalt occurs very extensively in the hot recycling process. In laboratory controlled conditions it is difficult to coat aggregates with different penetration asphalts and prevent them from mixing.

Special Report on Alkali-Aggregate Reactivity in Iowa, MLR-80-03, 1980

The purpose of this investigation was to obtain information relative to the alkali-silica reaction in Iowa aggregates. Of particular concern were those aggregates in southwestern Iowa thought to be potentially alkali reactive. Further, should those aggregates have proven to be alkali-reactive, at what cement alkali content could these aggregates be considered to be deleteriously reactive? If the aggregates were proven to be reactive, what types of effects might show up in a structure in which an alkali-silica reaction has occurred? Also, what environmental conditions would cause the reaction? Finally, based on the information obtained from the investigation, would it be possible to raise the cement alkali content specifications? Would the Iowa DOT eliminate the alkali content limits altogether except for cement used with reactive aggregate in the same manner as AASHTO or ASTM? Also, would there be any other side effects that might occur as the result of using high alkali-cement?