The puzzles of the prokineticin 2 pathway in human reproduction.

Prokineticin, 1 (PROK1) and prokineticin 2 (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. MIT-1 was initially identified as a non-toxic constituent in the venom of the black mamba snake (Dendroaspis polylepis) (Joubert and Strydom, 1980) while Bv8 was identified in the skin secretion of the toad, Bombina variegate (Mollay et al., 1999). All three homologs stimulate gastrointestinal motility thus accounting for their family name "prokineticins" (Schweitz et al., 1990, 1999). However, since its initial description, both PROK1 and PROK2 have been found to regulate a dazzling array of biological functions throughout the body. In particular, PROK1 acts as a potent angiogenic mitogen on endocrine vascular epithelium, thus earning its other name, Endocrine gland-vascular endothelial factor (EG-VEGF) (LeCouter et al., 2002). In contrast, the PROK2 signaling pathway is a critical regulator of olfactory bulb morphogenesis and sexual maturation in mammals and this function is the focus of this review.

Final Report on the Portable Computerized Assessments of Sleepy Drivers in Operational Environments, June 29, 2011

Excessive daytime sleepiness underpins a large number of the reported motor vehicle crashes. Fair and accurate field measures are needed to identify at-risk drivers who have been identified as potentially driving in a sleep deprived state on the basis of erratic driving behavior. The purpose of this research study was to evaluate a set of cognitive tests that can assist Motor Vehicle Enforcement Officers on duty in identifying drivers who may be engaged in sleep impaired driving. Currently no gold standard test exists to judge sleepiness in the field. Previous research has shown that Psychomotor Vigilance Task (PVT) is sensitive to sleep deprivation. The first goal of the current study was to evaluate whether computerized tests of attention and memory, more brief than PVT, would be as sensitive to sleepiness effects. The second goal of the study was to evaluate whether objective and subjective indices of acute and cumulative sleepiness predicted cognitive performance. Findings showed that sleepiness effects were detected in three out of six tasks. Furthermore, PVT was the only task that showed a consistent slowing of both ‘best’, i.e. minimum, and ‘typical’ responses, median RT due to sleepiness. However, PVT failed to show significant associations with objective measures of sleep deprivation (number of hours awake). The findings indicate that sleepiness tests in the field have significant limitations. The findings clearly show that it will not be possible to set absolute performance thresholds to identify sleep-impaired drivers based on cognitive performance on any test. Cooperation with industry to adjust work and rest cycles, and incentives to comply with those regulations will be critical components of a broad policy to prevent sleepy truck drivers from getting on the road.

Quality Control/Quality Assurance Testing for Joint Density and Segregation of Asphalt Mixtures, TR-623, 2013

Longitudinal joint quality control/assurance is essential to the successful performance of asphalt pavements and it has received considerable amount of attention in recent years. The purpose of the study is to evaluate the level of compaction at the longitudinal joint and determine the effect of segregation on the longitudinal joint performance. Five paving projects with the use of traditional butt joint, infrared joint heater, edge restraint by milling and modified butt joint with the hot pinch longitudinal joint construction techniques were selected in this study. For each project, field density and permeability tests were made and cores from the pavement were obtained for in-lab permeability, air void and indirect tensile strength. Asphalt content and gradations were also obtained to determine the joint segregation. In general, this study finds that the minimum required joint density should be around 90.0% of the theoretical maximum density based on the AASHTO T166 method. The restrained-edge by milling and butt joint with the infrared heat treatment construction methods both create the joint density higher than this 90.0% limit. Traditional butt joint exhibits lower density and higher permeability than the criterion. In addition, all of the projects appear to have segregation at the longitudinal joint except for the edge-restraint by milling method.

Long-Life Concrete: How Long Will My Concrete Last? A Synthesis of Knowledge of Potential Durability of Concrete, TPF-5(159), 2013

There is an ongoing discussion about moving toward performance-based specifications for concrete pavements. This document seeks to move the discussion forward by outlining the needs and the challenges, and proposing some immediate actions. However, this approach may increase risk for all parties until performance requirements are agreed upon and, more importantly, how the requirements can be measured. A fundamental issue behind pavement construction activities is that the owner/designer needs to be assured that the concrete in place will survive for the intended period (assuming there are no changes in the environment or loading) and, therefore, that full payment should be made. At the same time, each party along the supply chain needs to be assured that the material being supplied to them is able to meet the required performance, as is the product/system they are delivering. The focus of this document is a discussion of the issues behind this need, and the technologies that are available, or still needed, to meet this need, particularly from the point of view of potential durability

Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

The Use of Abrasives in Winter Maintenance, TR-434, 2001

The use of abrasives in winter maintenance is a well-established practice. The sand or other abrasive is intended to increase friction between vehicles and the (often snow or ice covered) pavement. In many agencies (and in many Iowa Counties, the focus of this study) the use of sand is a standard part of winter maintenance. Yet very little information exists on the value of sanding as a winter maintenance procedure. Some studies suggest that friction gains from sanding are minimal. In addition, there are increasing environmental concerns about sanding. These concerns focus on air quality and stormwater quality issues. This report reviews the state of the practice of abrasive usage in Iowa Counties, and classifies that usage according to its effectiveness. Possible changes in practice (with respect to abrasive usage) are presented and discussed.

Prevalence and Distribution of Young Driver Distraction Errors in Naturalistic Driving, TPF-5(207), 2014

Naturalistic driving studies are the latest resource for gathering data associated with driver behavior. The University of Iowa has been studying teen driving using naturalistic methods since 2006. By instrumenting teen drivers’ vehicles with event-triggered video recorders (ETVR), we are able to record a 12-second video clip every time a vehicle exceeds a pre-set g-force threshold. Each of these video clips contains valuable data regarding the frequency and types of distractions present in vehicles driven by today’s young drivers. The 16-year old drivers who participated in the study had a distraction present in nearly half of the events that were captured. While a lot of attention has been given to the distractions associated with technology in the vehicle (cell phones, navigation devices, entertainment systems, etc.), the most frequent type of distraction coded was the presence of teen passengers engaging in conversation (45%). Cognitive distractions, such as singing along with the radio, were the second most common distraction. Cell phone use was the third most common distraction, detected in only 10% of the events containing distraction.

Development of an Improved Agricultural-Based Deicing Product, TR-581, 2010

Snow and ice removal on public streets is a critical part of the work of departments of transportation in northern U.S. states, including Iowa. Iowa is also a state rich in agricultural resources, some of which undergo industrial processes that generate a number of byproducts, e.g., in converting corn to ethanol or soy to biodiesel. It would be desirable to find those that, with a minimum of additional processing, can be used as a deicing compound, either alone or in combination with products currently in use. The focus of this work is therefore to investigate by-products from agricultural processes that may be suitable for use as deicing applications. This topic has been investigated in the past by others, with many patented products described in the literature. An initial screening was carried out to assess the potential acceptability of selected commercial products, as well as a glycerol developed for this project. Based on the variety of parameters tested, the product combination that shows the greatest promise for future application consists of 80% glycerol with 20% NaCl.

Maximizing the Use of Roadway Weather Information Systems: Final Report, TR-404, 1998

This project was proposed as Phase I of a 2-phase program to evaluate the present use of weather information by Iowa Department of Transportation (IaDOT) personnel, recommend revised procedures, and then implement the resulting recommendations. Midway through Phase I (evaluation phase) the FORETELL project was funded. This project is a multi-state venture that engages the National Weather Service (NWS) and the Forecast Systems Laboratory of the National Oceanic and Atmospheric Administration and proposes to supplant the current weather information-generation and distribution system with an advanced system based on state-of-the-art technologies. The focus of the present project was therefore refined to consider use of weather data by IaDOT personnel, and the training programs needed to more effectively use these data. Results of the survey revealed that two major areas - training of personnel on use of data from whatever source and more precise information of frost formation - are not addressed in the FORETELL project. These aspects have been the focus of the present project.

Evaluation of Gateway and Low-Cost Traffic-Calming Treatments for Major Routes in Small, Rural Communities, TR-523, 2007

Many rural communities have developed around highways or major county roads; as a result, the main street through small rural communities is often part of a high-speed rural highway. Highways and county roads are characterized by high speeds outside the city limits; they then transition into a reduced speed section through the rural community. Consequently, drivers passing through the community often enter at high speeds and maintain those speeds as they travel through the community. Traffic calming in small rural communities along major roadways is common in Europe, but the U.S. does not have experience with applying traffic-calming measures outside of major urban areas. The purpose of the project was to evaluate traffic-calming treatments on the major road through small Iowa communities using either single-measure low-cost or gateway treatments. The project was partially funded by the Iowa Highway Research Board (IHRB). The focus of the IHRB portion was to evaluate single-measure, low-cost, traffic-calming measures that are appropriate to major roads through small rural communities. Seven different low-cost traffic treatments were implemented and evaluated in five rural Iowa communities. The research evaluated the use of two gateway treatments in Union and Roland; five single-measure treatments (speed table, on-pavement “SLOW” markings, a driver speed feedback sign, tubular markers, and on-pavement entrance treatments) were evaluated in Gilbert, Slater, and Dexter.

Comparative modular analysis of gene expression in vertebrate development

The focus of my PhD research was the concept of modularity. In the last 15 years, modularity has become a classic term in different fields of biology. On the conceptual level, a module is a set of interacting elements that remain mostly independent from the elements outside of the module. I used modular analysis techniques to study gene expression evolution in vertebrates. In particular, I identified ``natural'' modules of gene expression in mouse and human, and I showed that expression of organ-specific and system-specific genes tends to be conserved between such distance vertebrates as mammals and fishes. Also with a modular approach, I studied patterns of developmental constraints on transcriptome evolution. I showed that none of the two commonly accepted models of the evolution of embryonic development (``evo-devo'') are exclusively valid. In particular, I found that the conservation of the sequences of regulatory regions is highest during mid-development of zebrafish, and thus it supports the ``hourglass model''. In contrast, events of gene duplication and new gene introduction are most rare in early development, which supports the ``early conservation model''. In addition to the biological insights on transcriptome evolution, I have also discussed in detail the advantages of modular approaches in large-scale data analysis. Moreover, I re-analyzed several studies (published in high-ranking journals), and showed that their conclusions do not hold out under a detailed analysis. This demonstrates that complex analysis of high-throughput data requires a co-operation between biologists, bioinformaticians, and statisticians.

Statistics in science and in society: From a state-of-the-art to a new research agenda

Statistics occupies a prominent role in science and citizens' daily life. This article provides a state-of-the-art of the problems associated with statistics in science and in society, structured along the three paradigms defined by Bauer, Allum and Miller (2007). It explores in more detail medicine and public understanding of science on the one hand, and risks and surveys on the other. Statistics has received a good deal of attention; however, very often handled in terms of deficit - either of scientists or of citizens. Many tools have been proposed to improve statistical literacy, the image of and trust in statistics, but with little understanding of their roots, with little coordination among stakeholders and with few assessments of impacts. These deficiencies represent as many new and promising directions in which the PUS research agenda could be expanded.

Phenotypic and molecular characterization of the onset of neuropathy in rodent models of diabetes mellitus

Abstract : The principal focus of this work was to study the molecular changes leading to the development of diabetic peripheral neuropathy (DPN). DPN is the most common complication associated with both type I and II diabetes mellitus (DM). This pathology is the leading cause of non-traumatic amputations. Even though the pathological and morphological changes underlying DPN are relatively well described, the implicated molecular mechanisms remain poorly understood. The following two approaches were developed to study the development of DPN in a rodent model of DM type I. As a first approach, we studied the implication of lipid metabolism in DPN phenotype, concentrating on Sterol Response Element Binding Protein (SREBP)-lc which is the key regulator of storage lipid metabolism. We showed that SREBP-1c was expressed in peripheral nerves and that its expression profile followed the expression of genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurium of peripheral nerves was dependant upon nutritional status and this expression was also perturbed in type I diabetes. In line with this, we showed that insulin elevated the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-1c promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type I diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of DPN. As a second approach, we performed a comprehensive analysis of the molecular changes associated with DPN in the Akital~1~+ mouse which is a model of spontaneous early-onset type I diabetes mellitus. This mouse expresses a mutated non-functional isoform of insulin, leading to hypoinsulinemia and hyperglycaemia. To determine the onset of DPN, weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Akital+/+ mice during the first three months of life. A decrease in MNCV was evident akeady one week after the onset of hyperglycemia. To explore the molecular changes associated with the development of DPN in these mice, we performed gene expression profiling using sciatic nerve endoneurium and dorsal root ganglia (DRG) isolated from early diabetic male Akita+/+ mice and sex-matched littermate controls. No major transcriptional changes were detected either in the DRG or in the sciatic nerve endoneurium. This experiment indicates that the phenotypic changes observed during the development of DPN are not correlated with major transcriptional alterations, but mainly with alterations at the protein level. Résumé Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1 c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita+/+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique. Résumé : Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita~~Z~+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique.

The future of leadership

The good news with regard to this (or any) chapter on the future of leadership is that there is one. There was a time when researchers called for a moratorium on new leadership theory and research (e.g., Miner, 1975) citing the uncertain future of the field. Then for a time there was a popular academic perspective that leadership did not really matter when it came to shaping organizational outcomes (Meindl & Ehrlich, 1987; Meindl, Ehrlich, & Dukerich, 1985; Pfeffer, 1977). That perspective was laid to rest by "realists" in the field (Day & Antonakis, 2012a) by means of empirical re-interpretation of the results used to support the position that leadership does not matter (Lieberson & O'Connor, 1972; Salancik & Pfeffer, 1977). Specifically, Day and Lord (1988) showed that when proper methodological concerns were addressed (e.g., controlling for industry and company size effects; incorporating appropriate time lags) that the impact of top-level leadership was considerable - explaining as much as 45% of the variance in measures of organizational performance. Despite some recent pessimistic sentiments about the "curiously unformed" state of leadership research and theory (Hackman & Wageman, 2007), others have argued that the field has continued to evolve and is potentially on the threshold of some significant breakthroughs (Day & Antonakis, 2012a). Leadership scholars have been re-energized by new directions in the field and research efforts have revitalized areas previously abandoned for apparent lack of consistency in findings (e.g., leadership trait theory). Our accumulated knowledge now allows us to explain the nature of leadership including its biological bases and other antecedents, and consequences with some degree of confidence. There are other comprehensive sources that review the extensive theoretical and empirical foundation of leadership (Bass, 2008; Day & Antonakis, 2012b) so that will not be the focus of the present chapter. Instead, we will take a future-oriented perspective in identifying particular areas within the leadership field that we believe offer promising perspectives on the future of leadership. Nonetheless, it is worthwhile as background to first provide an overview of how we see the leadership field changing over the past decade or so. This short chronicle will set the stage for a keener understanding of where the future contributions are likely to emerge. Overall, across nine major schools of leadership - trait, behavioural, contingency, contextual, relational, sceptics, information processing, New Leadership, biological and evolutionary - researchers have seen a resurgence in interest in one area, a high level of activity in at least four other areas, inactivity in three areas, and one that was modestly active in the previous decade but we think holds strong promise for the future (Gardner, Lowe, Moss, Mahoney, & Cogliser, 2010). We will next provide brief overviews of these nine schools and their respective levels of research activity (see Figure 1).

Development of MASH TL-3 Transition Between Guardrail and Portable Concrete Barriers, TPF-5(081), 2014

Often, road construction causes the need to create a work zone. In these scenarios, portable concrete barriers (PCBs) are typically installed to shield workers and equipment from errant vehicles as well as prevent motorists from striking other roadside hazards. For an existing W-beam guardrail system installed adjacent to the roadway and near the work zone, guardrail sections are removed in order to place the portable concrete barrier system. The focus of this research study was to develop a proper stiffness transition between W-beam guardrail and portable concrete barrier systems. This research effort was accomplished through development and refinement of design concepts using computer simulation with LS-DYNA. Several design concepts were simulated, and design metrics were used to evaluate and refine each concept. These concepts were then analyzed and ranked based on feasibility, likelihood of success, and ease of installation. The rankings were presented to the Technical Advisory Committee (TAC) for selection of a preferred design alternative. Next, a Critical Impact Point (CIP) study was conducted, while additional analyses were performed to determine the critical attachment location and a reduced installation length for the portable concrete barriers. Finally, an additional simulation effort was conducted in order to evaluate the safety performance of the transition system under reverse-direction impact scenarios as well as to select the CIP. Recommendations were also provided for conducting a Phase II study and evaluating the nested Midwest Guardrail System (MGS) configuration using three Test Level 3 (TL-3) full-scale crash tests according to the criteria provided in the Manual for Assessing Safety Hardware, as published by the American Association of Safety Highway and Transportation Officials (AASHTO).