Report of Highway Research Board Research and Development Activities FY2007

The Highway Division of the Iowa Department of Transportation (Iowa DOT) engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; second, to identify and implement improved engineering and management practices. This report, entitled “Iowa Highway Research Board Research and Development Activities FY2007” is submitted in compliance with Sections 310.36 and 312.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund respectively. It is a report of the status of research and development projects, which were in progress on June 30, 2007; it is also a report on projects completed during the fiscal year beginning July 1, 2006, and ending June 30, 2007. Detailed information on each of the research and development projects mentioned in this report is available in the Research and Technology Bureau in the Highway Division of the Iowa Department of Transportation.

Report and Recommendations of the Iowa Vertical Infrastructure Advisory Committee, December 17, 2007

This report summaries the work of the committee over the last year and its vision for the future. The committee is followed with interest the work of the Department of Corrections and the Department of Veterans Affairs in evaluating the needs of their facilities and recommends similar evaluations of facilities around the state by other agencies. The committee members are ready to offer advice on the needs of the state's again infrastructure and steps that could be taken to evaluate vacant and underutilized buildings and reduce operational and maintenance costs.

The p63 target HBP1 is required for skin differentiation and stratification.

Genetic experiments established that p63 is crucial for the development and maintenance of pluristratified epithelia. In the RNA interference (RNAi) screening for targets of p63 in keratinocytes, we identified the transcription factor, High Mobility Group (HMG) box protein 1 (HBP1). HBP1 is an HMG-containing repressor transiently induced during differentiation of several cell lineages. We investigated the relationship between the two factors: using RNAi, overexpression, chromatin immunoprecipitations and transient transfections with reporter constructs, we established that HBP1 is directly repressed by p63. This was further confirmed in vivo by evaluating expression in p63 knockout mice and in transgenics expressing p63 in basal keratinocytes. Consistent with these findings, expression of HBP1 increases upon differentiation of primary keratinocytes and HaCaT cells in culture, and it is higher in the upper layers of human skin. Inactivation of HBP1 by RNAi prevents differentiation of keratinocytes and stratification of organotypic skin cultures. Finally, we analyzed the keratinocyte transcriptomes after HBP1 RNAi; in addition to repression of growth-promoting genes, unexpected activation of differentiation genes was uncovered, coexisting with repression of other genes involved in epithelial cornification. Our data indicate that suppression of HBP1 is part of the growth-promoting strategy of p63 in the lower layers of epidermis and that HBP1 temporally coordinates expression of genes involved in stratification, leading to the formation of the skin barrier.

Annual Report of Iowa Highway Research Board Research and Development Activities FY 08

RESEARCH AND DEVELOPMENT The Highway Division of the Iowa Department of Transportation (Iowa DOT) engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; second, to identify and implement improved engineering and management practices. This report, entitled "Iowa Highway Research Board Research and Development Activities FY2008" is submitted in compliance with Sections 310.36 and 3 I2.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund respectively. It is a report of the status of research and development projects in progress on June 30, 2008; it is also a report on projects completed during the fiscal year beginning July 1, 2007, and ending June 30, 2008. Detailed information on each of the research and development projects mentioned in this report is available in the Research and Technology Bureau in the Highway Division of the Iowa Department of Transportation. IOWA HIGHWAY RESEARCH BOARD In developing a progressive, continuing and coordinated program of research and development, the Highway Division is assisted by the Iowa Highway Research Board. This advisory group was established in 1949 by the Iowa State Highway Commission to respond to the research denoted in Section 310.36 of the Code of Iowa and now is denoted by 312.3A. The Research Board consists of 15 regular members: seven Iowa county engineers, four Iowa DOT engineers, one representative from Iowa State University, one from The University of Iowa, and two engineers employed by Iowa municipalities. Each regular member may have an alternate who will serve at the request of the regular member. The regular members and their alternates are appointed for a three-year term. The membership of the Research Board as of June 30, 2008, is listed in Table I. The Research Board held nine regular meetings during the period ofJuly 1, 2007, to June 30, 2008. Suggestions for research and development were reviewed at these meetings and recommendations were made by the Board.

Influence of learning on range expansion and adaptation to novel habitats.

Learning has been postulated to 'drive' evolution, but its influence on adaptive evolution in heterogeneous environments has not been formally examined. We used a spatially explicit individual-based model to study the effect of learning on the expansion and adaptation of a species to a novel habitat. Fitness was mediated by a behavioural trait (resource preference), which in turn was determined by both the genotype and learning. Our findings indicate that learning substantially increases the range of parameters under which the species expands and adapts to the novel habitat, particularly if the two habitats are separated by a sharp ecotone (rather than a gradient). However, for a broad range of parameters, learning reduces the degree of genetically-based local adaptation following the expansion and facilitates maintenance of genetic variation within local populations. Thus, in heterogeneous environments learning may facilitate evolutionary range expansions and maintenance of the potential of local populations to respond to subsequent environmental changes.

Molecularly defined vaccines for cancer immunotherapy, and protective T cell immunity.

Malignant cells are frequently recognized and destroyed by T cells, hence the development of T cell vaccines against established tumors. The challenge is to induce protective type 1 immune responses, with efficient Th1 and CTL activation, and long-term immunological memory. These goals are similar as in many infectious diseases, where successful immune protection is ideally induced with live vaccines. However, large-scale development of live vaccines is prevented by their very limited availability and vector immunogenicity. Synthetic vaccines have multiple advantages. Each of their components (antigens, adjuvants, delivery systems) contributes specifically to induction and maintenance of T cell responses. Here we summarize current experience with vaccines based on proteins and peptide antigens, and discuss approaches for the molecular characterization of clonotypic T cell responses. With carefully designed step-by-step modifications of innovative vaccine formulations, T cell vaccination can be optimized towards the goal of inducing therapeutic immune responses in humans.

Endogeneous matching in university-industry collaboration: Theory and empirical evidence from the UK

We develop a two-sided matching model to analyze collaboration between heterogeneousacademics and firms. We predict a positive assortative matching in terms of both scientificability and affinity for type of research, but negative assortative in terms of ability on one sideand affinity in the other. In addition, the most able and most applied academics and the mostable and most basic firms shall collaborate rather than stay independent. Our predictionsreceive strong support from the analysis of the teams of academics and firms that proposeresearch projects to the UK's Engineering and Physical Sciences Research Council.

Report and Recommendations of the Iowa Vertical Infrastructure Advisory Committee, December 15, 2008

This report summaries the work of the committee over the last year and its vision for the future. The committee is followed with interest the work of the Department of Corrections and the Department of Veterans Affairs in evaluating the needs of their facilities and recommends similar evaluations of facilities around the state by other agencies. The committee members are ready to offer advice on the needs of the state's again infrastructure and steps that could be taken to evaluate vacant and underutilized buildings and reduce operational and maintenance costs.

A randomized crossover study to compare efavirenz and etravirine treatment.

BACKGROUND: Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavourable blood lipid profile. We investigated the effect of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels. METHOD: Study participants did not complain of side-effects, had tolerated EFV for at least 3 months, with less than 50 copies/ml HIV-RNA. After randomization, the ETR-first group started with ETR (400 mg daily) [DOSAGE ERROR CORRECTED] with EFV-placebo and the EFV-first group with EFV with ETR-placebo. After 6 weeks, both groups switched to the alternate regimen. Nucleoside reverse transcriptase inhibitors were continued without any change. The primary end point was patient preference for the first or the second regimen, assessed after 12 weeks. RESULTS: Fifty-eight patients were enrolled with a median CD4 cell count of 589 cells/μl and the duration of previous EFV therapy was 3.9 years. Fifty-five patients completed the study. When asked about treatment preference after 12 weeks, 16 preferred EFV and 22 preferred ETR, whereas 17 did not express a preference (P = NS). Patients who continued EFV during the first phase of the trial preferred EFV (15/21, 71%), whereas patients who started with ETR were more likely to prefer ETR (n = 16/17, 94%). This order effect was strongly significant (P < 0.0001). Quality of sleep, depression, anxiety and stress scores did not differ significantly between groups. Median plasma cholesterol levels decreased by 0.7 mmol (29 mg/100 ml) after replacing EFV with ETR (P < 0.002). CONCLUSION: After substitution of EFV by ETR, patients did not express a significant preference for ETR. There was no measurable effect on neuropsychiatric symptoms and sleep. Cholesterol decreased.

Annual Report of Iowa Highway Research Board Research and Development Activities 2007

RESEARCH AND DEVELOPMENT The Highway Division of the Iowa Department of Transportation (Iowa DOT) engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; second, to identify and implement improved engineering and management practices. This report, entitled "Iowa Highway Research Board Research and Development Activities FY2008" is submitted in compliance with Sections 310.36 and 3 I2.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund respectively. It is a report of the status of research and development projects in progress on June 30, 2008; it is also a report on projects completed during the fiscal year beginning July 1, 2007, and ending June 30, 2008. Detailed information on each of the research and development projects mentioned in this report is available in the Research and Technology Bureau in the Highway Division of the Iowa Department of Transportation. IOWA HIGHWAY RESEARCH BOARD In developing a progressive, continuing and coordinated program of research and development, the Highway Division is assisted by the Iowa Highway Research Board. This advisory group was established in 1949 by the Iowa State Highway Commission to respond to the research denoted in Section 310.36 of the Code of Iowa and now is denoted by 312.3A. The Research Board consists of 15 regular members: seven Iowa county engineers, four Iowa DOT engineers, one representative from Iowa State University, one from The University of Iowa, and two engineers employed by Iowa municipalities. Each regular member may have an alternate who will serve at the request of the regular member. The regular members and their alternates are appointed for a three-year term. The membership of the Research Board as of June 30, 2008, is listed in Table I. The Research Board held nine regular meetings during the period ofJuly 1, 2007, to June 30, 2008. Suggestions for research and development were reviewed at these meetings and recommendations were made by the Board.

Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells.

Growth of numerous cancer types is believed to be driven by a subpopulation of poorly differentiated cells, often referred to as cancer stem cells (CSCs), that have the capacity for self-renewal, tumor initiation, and generation of nontumorigenic progeny. Despite their potentially key role in tumor establishment and maintenance, the energy requirements of these cells and the mechanisms that regulate their energy production are unknown. Here, we show that the oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, IGF2BP2) regulates oxidative phosphorylation (OXPHOS) in primary glioblastoma (GBM) sphere cultures (gliomaspheres), an established in vitro model for CSC expansion. We demonstrate that IMP2 binds several mRNAs that encode mitochondrial respiratory chain complex subunits and that it interacts with complex I (NADH:ubiquinone oxidoreductase) proteins. Depletion of IMP2 in gliomaspheres decreases their oxygen consumption rate and both complex I and complex IV activity that results in impaired clonogenicity in vitro and tumorigenicity in vivo. Importantly, inhibition of OXPHOS but not of glycolysis abolishes GBM cell clonogenicity. Our observations suggest that gliomaspheres depend on OXPHOS for their energy production and survival and that IMP2 expression provides a key mechanism to ensure OXPHOS maintenance by delivering respiratory chain subunit-encoding mRNAs to mitochondria and contributing to complex I and complex IV assembly.

Homeostasis and in vivo effector function of antigen-specific CD4+CD25+ regulatory T cells in experimental transplantation.

CD4+CD25+ regulatory T cells (Tregs) play a critical role in the prevention of autoimmune diseases as well as in the induction and maintenance of dominant tolerance in transplantation models. While their suppressive function has been extensively studied in vitro, their homeostasis and mechanisms of immunoregulation still remain to be clarifi ed in vivo. Using a murine adoptive transfer and skin allograft model, we analysed the expansion, effector function and traffi cking of effector T cells in the presence or absence of donor-specifi c Tregs. Although hyporesponsive to allogeneic and polyclonal stimulation in vitro, transferred Tregs survived and expanded, in response to an allograft in vivo. When co-transferred with naive CD4+CD25- effector T cells, they specifi cally prevented donor but not 3rd party allograft rejection by inhibiting the production of effector cytokines rather than the proliferation of effector T cells in response to alloantigens. The co-transfer of donor-specifi c Tregs did not affect the homing of effector T cells towards the graft draining lymph nodes, but it markedly reduced the infi ltration of the allograft by these pathogenic cells. Furthermore, in recipients where donor-specifi c transplantation tolerance was induced, Tregs preferentially accumulated in the allograft draining lymph nodes and within the grafted skin itself. Taken together, our results suggest that the suppression of graft rejection is an active process that involves the persistent presence of Tregs at the site of antigenic challenge.

Annual Report of the Iowa Highway Research Board Research and Development Activities FY 2009

The Highway Division of the Iowa Department of Transportation (Iowa DOT) engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; and second, to identify and implement improved engineering and management practices. This report, entitled ―Iowa Highway Research Board Research and Development Activities FY2009‖ is submitted in compliance with Sections 310.36 and 312.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund, respectively. It is a report of the status of research and development projects in progress on June 30, 2009. It is also a report on projects completed during the fiscal year beginning July 1, 2008 and ending June 30, 2009. Detailed information on each of the research and development projects mentioned in this report is available from the Research and Technology Bureau, Highway Division, Iowa Department of Transportation. All approved reports are also online for viewing at: www.iowadot.gov/operationsresearch/reports.aspx.

Status Report Midwest Regional Rail Passenger Initiative and Passenger Rail Service in Iowa February 1, 2010

This report fulfills the requirements of the following Code of Iowa sections: Section 327J.3(1): “The director may expend moneys from the fund to pay the costs associated with the initiation, operation, and maintenance of rail passenger service. The director shall report by February 1 of each year to the legislative services agency concerning the status of the fund including anticipated expenditures for the following fiscal year.” Section 327J.3(5): "The director shall report annually to the general assembly concerning the development and operation of the midwest regional rail system and the state's passenger rail service."

Office of Location and Environment Manual, August 2009

This manual captures the experience of practitioners in the Iowa Department of Transportation’s (Iowa DOT’s) Office of Location and Environment (OLE). It also documents the need for coordinated project development efforts during the highway project planning, or location study phase and engineering design. The location study phase establishes: * The definition of, and need for, the highway improvement project * The range of alternatives and many key attributes of the project’s design * The recommended alternative, its impacts, and the agreed-to conditions for project approval The location study process involves developing engineering alternatives, collecting engineering and environmental data, and completing design refinements to accomplish functional designs. The items above also embody the basic content required for projects compliant with the National Environmental Policy Act (NEPA) of 19691, which directs federal agencies to use a systematic, interdisciplinary approach during the planning process whenever proposed actions (or “projects”) have the potential for environmental impacts. In doing so, NEPA requires coordination with stakeholders, review, comment, and public disclosure. Are location studies and environmental studies more about the process or the documents? If properly conducted, they concern both—unbiased and reasonable processes with quality and timely documents. In essence, every project is a story that needs to be told. Engineering and environmental regulations and guidance, as documented in this manual, will help project staff and managers become better storytellers.