Iowa Research with Chem-Crete Bitumen: Final Report Iowa Highway Research Board Project HR-226, June 1986

With the spiraling cost of construction, coupled with inflation, engineers must develop and research new techniques to better utilize the public's dollar. One area i n which these new technologies must be researched is in the field of highway construction; more specifically, asphalt products. There are areas within the state of Iowa which do not have Class I aggregate readily available for asphalt concrete road construction. The cost of transporting higher quality aggregate specified in the "Standard Specifications for Highway and Bridge construction"' for construction projects is escalating on a yearly basis. Many counties will be squeezed out of the construction of new roadways if an alternative to the high costs is not identified. The same high costs will curtail adequate upkeep on the existing paved system and will result in decreased serviceability. For this reason, a product is needed to better utilize the local aggregates for road construction and maintenance. There i s a product on the market which the promoters claim will improve the prer?nt asphalt to such a degree as to "upgrade deficient aggregates" to the level they can be used in today's standard construction techniques. This product is "Chem-Crete Bitumen," a'kpecially refined asphalt" that was promoted by Chem-Crete Corporation of Menlo Park, California. Chemkrete Technologies, Inc. of Wickliffe, Ohio; a wholly owned subsidiary of the Lubrizol Corporation has since purchased the U.S.

Load Ratings For Secondary Bridges Final Report Highway Research Advisory Board Project HR-239, May 1991

Load Rating: . , :Evaluation of the capacity of a bridge to carry vehicle Inventory Rating: Lbad level which can safely utilize the bridge for an indefinite period of time Operating Rating: Absolute maximum permissible load level for the bridge A load rating states the load in tons which a vehicle can impose on a bridge. Changes in guidelines, standards, and customary uses of bridges require analyses of bridges to be updated and re-evaluated. In this report, twenty-two secondary bridge standards for three types of bridges are rated for the AASHTO HS20-44 vehicle configuration and three typical Iowa legal vehicles

Rapid Improvement In Health-Related Quality Of Life In Gouty Arthritis Patients Treated With Canakinumab (Acz885) Compared To Triamcinolone Acetonide

Background : Canakinumab, a fully human anti-IL-1b antibody has been shown to control inflammation in gouty arthritis. This study evaluated changes in health-related quality of life (HRQoL) in patients treated with canakinumab or triamcinolone acetonide (TA).Methods : An 8-wk, dose-ranging, active controlled, single-blind study in patients (_18 to _80 years) with acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150mg sc or TA 40mg im. HRQoL was assessed using patient reported outcomes evaluating PCS and MCS, and subscale scores of SF-36_ [acute version 2]) and functional disability (HAQ-DI_).Results : In canakinumab 150mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved in 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) and at 8 wks improved to 86.1 and 86.6 (mean increases of 44.6 and 50.6); these were higher than levels seen in the general US population. TA group, showed less improvement in 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain). Functional disability scores, measured by the HAQ-DI_ decreased in both treatment groups (Table 1).Conclusions : Gouty arthritis patients treated with canakinumab showed a rapid improvement in physical and mental well-being based on SF-36_ scores. In contrast to the TA group, patients treated with canakinumab showed improvement in 7 days in physical function and bodily pain approaching levels of the general population.Disclosure statement : U.A., A.F., V.M., D.R., P.S. and K.S. are employees and shareholders of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support and consultancy fees from Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and EnzymeRx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultation fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Engineering Study for Reducing Sign Vandalism Final Report Highway Research Advisory Board Projec HR 246, June 1992

Sign vandalism has traditionally been a vexing problem for Iowa counties. The extent of the cost and incidence of these acts have never been fully ascertained, but a 1990 survey indicated that they cost Iowa counties more than 1.5 million dollars annually. In 1990, the Iowa Legislature recognized the seriousness of the problem and strengthened the existing sign vandalism law by increasing the penalty for illegal possession of a traffic control device from a simple to a serious misdemeanor. However, the courts must be willing to prosecute vandals to the magnitude provided in the Iowa Code. An educational campaign begun in 1987 involving over 200 Iowa school districts to educate students on the seriousness of the problem evidently did not have the effect of dramatically reducing the overall cost of sign vandalism in Iowa. This study sought to define the scope of the problem and possibly offer some effective countermeasures to combat sign vandalism and theft in Iowa.

Erosion Control for Highway Applications, Phase I: Review and Synthesis of Literature, Final Report, TR-464, May 2002

The project described herein has led to a convenient, computer-based expert system for identifying and evaluating potentially effective erosion- and sedimentation-control measures for use in roadway construction throughout Iowa and elsewhere in the Midwest. The expert system is intended to be an accessible and efficient practical resource to aid state, county, and municipal engineers in the selection of the best management practices for preventing unwanted erosion and sedimentation at roadway construction sites, during and after construction.

Field Evaluation of Timber Preservation Treatments for Highway Applications Final Report, December 2007

Timber material repair and replacement cost for timber bridges is a considerable expense to highway agencies in Iowa, especially to county road departments. To address these needs, the objectives of this investigation was to study the field effectiveness of various treatment alternatives used on Iowa roadway projects and to determine if the current specifications and testing are adequate for providing proper wood preservation. To satisfy the research needs, the project scope involved a literature review, identification of metrics, questionnaire survey of Iowa counties, onsite inspections, and a review of current specifications and testing procedures. Based on the preservative information obtained, the following general conclusions were made: Copper naphthenate is recommended as the plant-applied preservative treatment for timber bridges. Best Management Practices should be followed to ensure quality treatment of timber materials. Bridge maintenance programs need to be developed and implemented. The Iowa Department of Transportation specifications for preservative treatment are the regulating specification for bridges constructed with state or federal funding in Iowa and are also recommended for all other bridges.

Precast Concrete Elements for Accelerated Bridge Construction Final Report Volume 2. Laboratory Testing, Field Testing, and Evaluation of a Precast Concrete Bridge: Madison County Bridge, January 2009

The importance of rapid construction technologies has been recognized by the Federal Highway Administration (FHWA) and the Iowa DOT Office of Bridges and Structures. Recognizing this a two-lane single-span precast box girder bridge was constructed in 2007 over a stream. The bridge’s precast elements included precast cap beams and precast box girders. Precast element fabrication and bridge construction were observed, two precast box girders were tested in the laboratory, and the completed bridge was field tested in 2007 and 2008.

Precast Concrete Elements for Accelerated Bridge Construction Final Report Volume 3. Laboratory Testing, Field Testing, and Evaluation of a Precast Concrete Bridge: Black Hawk County,v January 2009

The importance of rapid construction technologies has been recognized by the Federal Highway Administration (FHWA) and the Iowa DOT Office of Bridges and Structures. Black Hawk County (BHC) has developed a precast modified beam-in-slab bridge (PMBISB) system for use with accelerated construction. A typical PMBISB is comprised of five to six precast MBISB panels and is used on low volume roads, on short spans, and is installed and fabricated by county forces. Precast abutment caps and a precast abutment backwall were also developed by BHC for use with the PMBISB. The objective of the research was to gain knowledge of the global behavior of the bridge system in the field, to quantify the strength and behavior of the individual precast components, and to develop a more time efficient panel-to-panel field connection. Precast components tested in the laboratory include two precast abutment caps, three different types of deck panel connections, and a precast abutment backwall. The abutment caps and backwall were tested for behavior and strength. The three panel-to-panel connections were tested in the lab for strength and were evaluated based on cost and constructability. Two PMBISB were tested in the field to determine stresses, lateral distribution characteristics, and overall global behavior.

Evaluation of the Buena Vista IBRD Bridge: A Furthering of Accelerated Bridge Construction in Iowa, February 2012

The need to construct bridges that last longer, are less expensive, and take less time to build has increased. The importance of accelerated bridge construction (ABC) technologies has been realized by the Federal Highway Administration (FHWA) and the Iowa Department of Transportation (DOT) Office of Bridges and Structures. This project is another in a series of ABC bridge projects undertaken by the Iowa DOT. Buena Vista County, Iowa, with the assistance of the Iowa Department of Transportation (DOT) and the Bridge Engineering Center (BEC) at Iowa State University, constructed a two-lane single-span precast box girder bridge, using rapid construction techniques. The design involved the use of precast, pretensioned components for the bridge superstructure, substructure, and backwalls. This application and demonstration represents an important step in the development and advancement of these techniques in Iowa as well as nationwide. Prior funding for the design and construction of this bridge (including materials) was obtained through the FHWA Innovative Bridge Research and Deployment (IBRD) Program. The Iowa Highway Research Board (IHRB) provided additional funding to test and evaluate the bridge. This project directly addresses the IBRD goal of demonstrating (and documenting) the effectiveness of innovative materials and construction techniques for the construction of new bridge structures. Evaluation of performance was formulated through comparisons with design assumptions and recognized codes and standards including American Association of State Highway and Transportation Officials (AASHTO) specifications.

Iowa State Highway Map, January 1, 2010

State highway map of Iowa for 2010, produced by Iowa Department of Transportation.

Étude du mécanisme de transport des cations par la Na, K-ATPase et de son implication dans la migraine familiale hémiplégique de type 2

Résumé La Na,K-ATPase est une protéine transmembranaire, présente dans toutes les cellules de mammifères et indispensable à la viabilité cellulaire. Elle permet le maintien des gradients sodiques et potassiques à l'origine du potentiel membranaire en transportant 3 Na+ en dehors de la cellule contre 2 K+, grâce à l'énergie fournie par l'hydrolyse d'une molécule d'ATP. Le potentiel membranaire est indispensable au maintien de l'excitabilité cellulaire et à la transmission de l'influx nerveux. Il semblerait que la Na,K-ATPase soit liée à l'hypertension et à certains troubles neurologiques comme la Migraine Familiale Hémiplégique (1VIFH). La MFH est une forme de migraine avec aura, qui se caractérise par une hémiparésie. Cette forme de migraine est très rare. Elle se transmet génétiquement sur un mode autosomique dominant. Plusieurs mutations localisées dans le gène de la Na,K-ATPase ont été identifiées durant ces 3 dernières années. C'est la première fois qu'une maladie génétique est associée au gène de la Na,K-ATPase. La compréhension du fonctionnement de cette protéine peut donner des informations sur les mécanismes conduisant à ces pathologies. On sait que la fonction d'une protéine est liée à sa structure. L'étude de sa fonction nécessite donc l'étude de sa structure. Alors que la structure de la SERCA a été déterminée à haute résolution, par cristallographie, celle de la Na,K-ATPase ne l'est toujours pas. Mais ces 2 ATPases présentent une telle homologie qu'un modèle de la Na,K-ATPase a pu être élaboré à partir de la structure de la SERCA. Les objectifs de cette étude sont d'une part, de comprendre le contrôle de l'accessibilité du K+ extracellulaire àses sites de liaison. Pour cela, nous avons ciblé cette étude sur la 2ìème et la 31eme boucle extracellulaire, qui relient respectivement les segments transmembranaires (STM) 3-4 et 5-6. Le choix s'est porté sur ces 2 boucles car elles bordent le canal des cations formés des 4ième' Sième et 6'ème hélices. D'autre part, nous avons également essayer de comprendre les effets des mutations, liées à la Migraine Familiale Hémiplégique de type 2 (MFH2), sur la fonctionnalité de la Na,K-ATPase. Alors que les STM et les domaines cytoplasmiques sont relativement proches entre la Na,KATPase et la SERCA, les boucles extracellulaires présentent des différences. Le modèle n'est donc pas une approche fiable pour déterminer la structure et la fonction des régions extracellulaires. Nous avons alors utilisé une approche fonctionnelle faisant appel à la mutation dirigée puis à l'étude de l'activité fonctionnelle de la Na,K ATPase par électrophysiologie sur des ovocytes de Xenopus. En conclusion, nous pouvons dire que la troisième boucle extracellulaire participerait à la structure de la voie d'entrée des cations et que la deuxième boucle extracellulaire semble impliquée dans le contrôle de l'accessibilité des ions K+àses sites de liaison. Concernant les mutations associées à la MFH2, nos résultats ont montré une forte diminution de l'activité fonctionnelle de la pompe Na,K, inférieure aux conditions physiologiques de fonctionnement, et pour une des mutations nous avons observés une diminution de l'affmité apparente au K+ externe. Nous poumons faire l'hypothèse que l'origine pathologique de la migraine est liée à une diminution de l'activité de la pompe à Na+. Summary The Na,K-ATPase is a transmembrane protein, present in all mammalian cells and is necessary for the viability of the cells. It maintains the gradients of Na+ and K+ involved in the membrane potential, by transporting 3Na+ out the cell, and 2K+ into the cell, using the energy providing from one ATP molecule hydrolysis. The membrane potential is necessary for the cell excitability and for the transmission of the nervous signal. Some evidence show that Na,K-ATPase is involved in hypertension and neurological disorders like the Familial Hemiplegic Migraine (FHM). La FHM is a rare form of migraine characterised by aura and hemiparesis and an autosomal dominant transmission. Several mutations linked to the Na,KATPase gene have been identified during these 3 last years. It's the first genetic disorder associated with the Na,K-ATPase gene. Understand the function of this protein is important to elucidate the mechanisms implicated in these pathologies. The function of a protein is linked with its structure. Thus, to know the function of a protein, we need to know its structure. While the Ca-ATPase (SERCA) has been crystallised with a high resolution, the structure of the Na,K-ATPase is not known. Because of the great homology between these 2 ATPases, a model of the Na,K-ATPase was realised by comparing with the structure of the SERCA. The aim of this study is on one side, understand the control of the extracellular K+ accessibility to their binding sites. Because of theirs closed proximity with the cation pathway, located between the 4th, 5th and 6th helices, we have targeted this study on the 2nd and the 3rd extracellular loops linking respectively the transmembrane segment (TMS) 3 and 4, and the TMS 5 and 6. And on the other side, we have tried to understand the functional effects of mutations linked with the Familial Hemiplegic Migraine Type 2 (FHM2). In contrast with the transmembrane segments and the cytoplasmic domains, the extracellular loops show lots of difference between Na,K-ATPase and SERCA, the model is not a good approach to know the structure and the function of the extracellular loops. Thus, we have used a functional approach consisting in directed mutagenesis and the study of the functional activity of the Na,K-ATPase by electrophysiological techniques with Xenopus oocytes. In conclusion, we have demonstrated that the third extracellular loop could participate in the structure of the entry of the cations pathway and that the second extracellular loop could control the K+ accessibility to their binding sites. Concerning the mutations associated with the FHM2, our results showed a strong decrease in the functional activity of the Na,K-pump under physiological conditions and for one of mutations, induce a decrease in the apparent external K+ affinity. We could make the hypothesis that the pathogenesis of migraine is related to the decrease in Na,K-pump activity. Résumé au large publique De la même manière que l'assemblage des mots forme des phrases et que l'assemblage des phrases forme des histoires, l'assemblage des cellules forme des organes et l'ensemble des organes constitue les êtres vivants. La fonction d'une cellule dans le corps humain peut se rapprocher de celle d'une usine hydroélectrique. La matière première apportée est l'eau, l'usine électrique va ensuite convertir l'eau en énergie hydraulique pour fournir de l'électricité. Le fonctionnement de base d'une cellule suit le même processus. La cellule a besoin de matières premières (oxygène, nutriments, eau...) pour produire une énergie sous forme chimique, l'ATP. Cette énergie est utilisée par exemple pour contracter les muscles et permet donc à l'individu de se déplacer. Morphologiquement la cellule est une sorte de petit sac rempli de liquide (milieu intracellulaire) baignant elle-même dans le liquide (milieu extracellulaire) composant le corps humain (un adulte est constitué environ de 65 % d'eau). La composition du milieu intracellulaire est différente de celle du milieu extracellulaire. Cette différence doit être maintenue pour que l'organisme fonctionne correctement. Une des différences majeures est la quantité de sodium. En effet il y a beaucoup plus de sodium à l'extérieur qu'à l'intérieur de la cellule. Bien que l'intérieur de la cellule soit isolé de l'extérieur par une membrane, le sodium arrive à passer à travers cette membrane, ce qui a tendance à augmenter la quantité de sodium dans la cellule et donc à diminuer sa différence de concentration entre le milieu extracellulaire et le milieu intracellulaire. Mais dans les membranes, il existe des pompes qui tournent et dont le rôle est de rejeter le sodium de la cellule. Ces pompes sont des protéines connues sous le nom de pompe à sodium ou Na,K-ATPase. On lui attribue le nom de Na,K-ATPase car en réalité elle rejette du sodium (Na) et en échange elle fait entrer dans la cellule du potassium (K), et pour fonctionner elle a besoin d'énergie (ATP). Lorsque les pompes à sodium ne fonctionnent pas bien, cela peut conduire à des maladies. En effet la Migraine Familiale Hémiplégique de type 2, est une migraine très rare qui se caractérise par l'apparition de la paralysie de la moitié d'un corps avant l'apparition du mal de tête. C'est une maladie génétique (altération qui modifie la fonction d'une protéine) qui touche la pompe à sodium située dans le cerveau. On a découvert que certaines altérations (mutations) empêchent les pompes à sodium de fonctionner correctement. On pense alors que le développement des migraines est en partie dû au fait que ces pompes fonctionnent moins bien. Il est important de bien connaître la fonction de ces pompes car cela permet de comprendre des mécanismes pouvant conduire à certaines maladies, comme les migraines. En biologie, la fonction d'une protéine est étudiée à travers sa structure. C'est pourquoi l'objectif de cette thèse a été d'étudier la structure de la Na,K-ATPase afin de mieux comprendre son mécanisme d'action.

Evaluation of uptake and transport of ultrasmall superparamagnetic iron oxide nanoparticles by human brain-derived endothelial cells.

Aim: Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NPs) are under development for imaging and drug delivery; however, their interaction with human blood-brain barrier models is not known. Materials & Methods: The uptake, reactive oxygen species production and transport of USPIO-NPs across human brain-derived endothelial cells as models of the blood-brain tumor barrier were evaluated for either uncoated, oleic acid-coated or polyvinylamine-coated USPIO-NPs. Results: Reactive oxygen species production was observed for oleic acid-coated and polyvinylamine-coated USPIO-NPs. The uptake and intracellular localization of the iron oxide core of the USPIO-NPs was confirmed by transmission electron microscopy. However, while the uptake of these USPIO-NPs by cells was observed, they were neither released by nor transported across these cells even in the presence of an external dynamic magnetic field. Conclusion: USPIO-NP-loaded filopodia were observed to invade the polyester membrane, suggesting that they can be transported by migrating angiogenic brain-derived endothelial cells.

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.

Rapid fluidic exchange microsystem for recording of fast ion channel kinetics in Xenopus oocytes.

We present a new lab-on-a-chip system for electrophysiological measurements on Xenopus oocytes. Xenopus oocytes are widely used host cells in the field of pharmacological studies and drug development. We developed a novel non-invasive technique using immobilized non-devitellinized cells that replaces the traditional "two-electrode voltage-clamp" (TEVC) method. In particular, rapid fluidic exchange was implemented on-chip to allow recording of fast kinetic events of exogenous ion channels expressed in the cell membrane. Reducing fluidic exchange times of extracellular reagent solutions is a great challenge with these large millimetre-sized cells. Fluidic switching is obtained by shifting the laminar flow interface in a perfusion channel under the cell by means of integrated poly-dimethylsiloxane (PDMS) microvalves. Reagent solution exchange times down to 20 ms have been achieved. An on-chip purging system allows to perform complex pharmacological protocols, making the system suitable for screening of ion channel ligand libraries. The performance of the integrated rapid fluidic exchange system was demonstrated by investigating the self-inhibition of human epithelial sodium channels (ENaC). Our results show that the response time of this ion channel to a specific reactant is about an order of magnitude faster than could be estimated with the traditional TEVC technique.