Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Metric Training for the Transportation Industry Module II - Construction and Maintenance Operations and Reporting, HR-376

"Metric Training For The Highway Industry", HR-376 was designed to produce training materials for the various divisions of the Iowa DOT, local government and the highway construction industry. The project materials were to be used to introduce the highway industry in Iowa to metric measurements in their daily activities. Five modules were developed and used in training over 1,000 DOT, county, city, consultant and contractor staff in the use of metric measurements. The training modules developed deal with the planning through operation areas of highway transportation. The materials and selection of modules were developed with the aid of an advisory personnel from the highway industry. Each module is design as a four hour block of instruction and a stand along module for specific types of personnel. Each module is subdivided into four chapters with chapter one and four covering general topics common to all subjects. Chapters two and three are aimed at hands on experience for a specific group and subject. This module includes: Module 2 - Construction and Maintenance Operations and Reporting. This module provides hands on examples of applications of metric measurements in the construction and maintenance field operations.

Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Improved Asphalt Surfaces and Asphalt Resurfacing Performance through Crack Maintenance, HR-213, 1987

In 1980, a Vanguard High Pressure Water Blaster capable of providing 10 gallons of water per minute at 2000 psi was purchased to evaluate water blasting as a crack cleaning method prior to crack filling on asphalt concrete pavements. Afer some iniital trials demonstrated its effectiveness of removing dirt, debris and vegetation, it was included in joint and crack maintenance research on Iowa 7 in Webster County. The objective of the research was to evaluate six crack preparation methods and seven "sealant" materials. The cleaning and sealing was performed in the spring of 1983. Visual evaluations of the performance were made in the fall of 1983 and spring of 1985. Compressed air and/or high pressure water did not adequately prepare cracks less than 3/8 inch wide. Routing or sawing was necessary to provide a sealant reservoir. The water blaster was more effective than compressed air in removing dirt, debris and vegetation but this did not yield significant improvement in sealant adhesion or longevity. Periodic crack filling is necessary on ACC surfaces throughout the remaining life of the pavement.

Engineering Study for the Evaluation of Public Road Administration and Maintenance Alternatives, Executive Summary for HR-265, 1985

Iowa's public road system of 112,000 miles is one of the largest and the best in the nation. It represents a considerable financial investment of taxpayer revenues over the years. And, it requires a sustained investment to preserve an economical level of transport service into the future. In 1982, a Governor's Blue Ribbon Transportation Task Force evaluated the effectiveness of Iowa's entire transportation system. Four important Task Force recommendations dealt with public road administrative issues in Iowa. These issues were related to: 1. design criteria and levels of maintenance 2. consistency in the use of standards among jurisdictions 3. consolidation of maintenance operations at one jurisdictional level and 4. jurisdictional authority for roads. The issues formed the background for Research Project HR-265.

Evaluation of Appropriate Maintenance, Repair and Rehabilitation Methods for Iowa Bridges, TR-429, 2003

Most states, including Iowa, have a significant number of substandard bridges. This number will increase significantly unless some type of preventative maintenance is employed. Both the Iowa Department of Transportation and Iowa counties have successfully employed numerous maintenance, repair and rehabilitation (MR&R) strategies for correcting various types of deficiencies. However, successfully employed MR&R procedures are often not systematically documented or defined for those involved in bridge maintenance. This study addressed the need for a standard bridge MR&R manual for Iowa with emphasis for secondary road applications. As part of the study, bridge MR&R activities that are relevant to the state of Iowa have been systematically categorized into a manual, in a standardized format. Where pertinent, design guidelines have been presented. Material presented in this manual is divided into two major categories: 1) Repair and Rehabilitation of Bridge Superstructure Components, and 2) Repair and Rehabilitation of Bridge Substructure Components. There are multiple subcategories within both major categories that provide detailed information. Some of the detailed information includes step-by-step procedures for accomplishing MR&R activities, material specifications and detailed drawings where available. The source of information contained in the manual is public domain technical literature and information provided by Iowa County Engineers. A questionnaire was sent to all 99 counties in Iowa to solicit information and the research team personally solicited input from many Iowa counties as a follow-up to the questionnaire.

A Study of Portland Cement Maintenance Mix and Set Accelerators, R-249, 1970

The large volume of traffic on the interstate system makes it difficult to make pavement repairs. The maintenance crew needs 4-5 hours to break out the concrete to be replaced and prepare the hole for placing new concrete. Because of this it is usually noon before the patch can be placed. Since it is desirable to remove the barricades before dark there are only 7-8 hours for the concrete to reach the required strength. There exists a need for a concrete that can reach the necessary strength (modulus of rupture = 500 psi) in 7-8 hours. The purpose of this study is to determine if type III cement and/or an accelerator can be used in an M-4 mix to yield a fast setting patch with very little shrinkage. It is recognized that calcium chloride is a corrosive material and may therefore have detrimental effects upon the reinforcing steel. The study of these effects, however, is beyond the scope of this investigation.

Maintenance of Pavement Skid Resistance (Open Graded Asphalt Friction Courses), Progress Report, HR-170, 1976

This project involved the evaluation of several aggregates previously rated poor to excellent with respect to skid resistance and certain mix design parameters. An open graded asphalt friction course was evaluated using 4 comparably graded aggregates: quartzite, fine grained limestone, coarse limestone and lightweight expanded shale. The performance investigations involved the verification of observations of the quartzite test sections, evaluation of the effect of blending the superior quartzite with a typical coarse grained-textured limestone, and the evaluation of the limestone. The effects of traffic on the aggregates used in the test sections were studied, as well as the relationship between asphalt content levels and traffic with respect to performance. The bond of the open graded friction course mixture was also evaluated. The SN performance of all test sections after sixteen months of exposure was found to be satisfactory in that none of the material combinations had polished to the point where unacceptable SN levels developed. When material combinations were compared, significant differences were noted.

Examination of Closing the Existing Highway Maintenance Garage at Hamlin, Iowa, 1983

An optimum allocation model has been utilized to examine the existing allocation of highway segments to maintenance garages in the Hamlin study area. The model has also been used to evaluate the financial effect of closing the garage at Hamlin. The examination of the study area shows that only three of 48 highway segments should be reallocated at an annual operational savings of approximately $1,400. The study concludes there would be an annual operational savings of approximately 128,700 if the garage at Hamlin were closed.

Examination of Existing Highway Maintenance Garage Locations in Two Study Areas in Iowa, 1982

During the 1980-81 fiscal year, the Office of Transportation Research conducted a study to examine the existing locations of highway maintenance garages in a study area provided by the Office of Maintenance. The study successfully identified a model referred to as an "Optimum Allocation Model" for examining highway maintenance garage locations in a given area. This model can optimally assign highway segments to maintenance garages and can also be used to evaluate the financial impact of closing or relocating a highway maintenance garage utilizing the highway maintenance-related data currently available at the Iowa DOT. The present study employs the optimum allocation model to examine the existing highway maintenance garage locations in two selected areas in the southeastern and southwestern parts of the state. These areas were selected by the Office of Maintenance and are referred to as "Study Area No. 1" and "Study Area No. 2" in this study. These study areas are shown in Appendices 1 and 2, respectively.

Examination of Existing Highway Maintenance Garage Locations in Tama and Blairstown Study Area, 1983

An optimum allocation model has been utilized to examine the existing allocation of highway segments to maintenance garages in the Tama and Blairstown study area. The model has also been used to evaluate the financial impact of closing the highway maintenance garages at Tama and Blairstown and building a new garage at the junction of U.S. 30 and Iowa 21. The examination of the study area shows that only 13 of 91 highway segments were reallocated under optimum procedures at an annual operational savings of approximately $13,200. The study concludes there would be an annual operational savings of approximately $48,200 if the garages at Tama and Blairstown were closed and a new garage was built at the junction of U.S. 30 and Iowa 21.

Examination of Highway Maintenance Garages in the U.S. 30 Corridor between Ames and Cedar Rapids, 1988

A linear programming model is used to optimally assign highway segments to highway maintenance garages using existing facilities. The model is also used to determine possible operational savings or losses associated with four alternatives for expanding, closing and/or relocating some of the garages in a study area. The study area contains 16 highway maintenance garages and 139 highway segments. The study recommends alternative No. 3 (close Tama and Blairstown garages and relocate new garage at Jct. U.S. 30 and Iowa 21) at an annual operational savings of approximately $16,250. These operational savings, however, are only the guidelines for decisionmakers and are subject to the required assumptions of the model used and limitations of the study.

History and Design of Iowa's Highway Maintenance and Weighing Facilities, 2003

In June 2001, the Iowa Department of Transportation announced the imminent closure and disposal of selected highway maintenance facilities as part of cost-cutting measures mandated by the Iowa legislature, an action that was to be completed by July 31, 2001. The DOT recognized that some of these facilities might be "historical sites," which in the Iowa Code are defined as any district, site, building or structure listed on the National Register of Historic Places or identified as eligible for listing in the National Register by the State Historic Preservation Office. Section 303 of the Code requires state agencies to "enter into an agreement with the Department of Cultural Affairs [in which the SHPO is located] to ensure the proper management, maintenance and development of historical sites." The DOT saw this disposal action as an opportunity to compile information about its highway maintenance facilities that could be employed in development of a management program for historic highway maintenance facilities in the future. Subsequently, the DOT authorized a similar study of highway weigh stations.

Needs Assessment Study of the Iowa DOT Maintenance Facility Construction Needs, 1989

The purpose of this study is to provide recommendations relative to the location and construction needs for highway maintenance facilities within the state of Iowa. These recommendations were to be developed with consideration being given to the public's expectations and priorities for highway maintenance services. As a part of the study effort, a review was made of the methods used by other states to deliver highway maintenance services. To accomplish the study, Wilbur Smith Associates undertook a series of tasks. These efforts included gathering of data and information to characterize the various maintenance programs and the delivery of maintenance and operations services by the Department. We researched the delivery of highway maintenance services in other states. Interviews with Iowa DOT maintenance personnel were accomplished. A schedule of public hearings was developed and ten hearings were held. All the information was integrated and various analyses were made. From these analyses we drew conclusions and developed recommendations.

An Optimum Allocation Approach to Closing or Relocating Highway Maintenance Garages in Iowa, 1981

Highway maintenance engineers and administrators are often confronted with a number of problems related to highway maintenance work programs. One of these problems is concerned with determining the optimum number and locations of highway maintenance garages in a given area. Serious decline in highway revenues and a high inflation rate have made it necessary to examine existing maintenance practices and to allocate reduced financial resources more effectively and efficiently. Searching for and providing of reasonable solutions to these problems is the focus of this research project. The methodology used is to identify and modify for use (if necessary) those models which have already been developed. Models which could give optimum number and locations of highway maintenance garages were found to be too theoretical and/or practically infeasible. Consequently, research focus was shifted from these models to other models that could compare alternatives and select the best among these alternatives. Three such models -- the Alabama model, California model, and Louisiana model, were identified and studied.