Peroxisome proliferator-activated receptors (PPARs) in skin health, repair and disease.

Peroxisome proliferator-activated receptors, PPARalpha, PPARbeta/delta and PPARgamma, are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. While they are best known as transcriptional regulators of lipid and glucose metabolism, evidence has also accumulated for their importance in skin homeostasis. The three PPAR isotypes are expressed in rodent and human skin. Various cell culture and in vivo approaches suggest that PPARalpha contributes to fetal skin development, to epidermal barrier maturation and to sebocyte activity. PPARbeta/delta regulates sebocyte differentiation, promotes hair follicle growth and has pro-differentiating effects in keratinocytes in normal and inflammatory conditions. In contrast, the role of PPARgamma appears to be rather minor in keratinocytes, whereas its activity is required for sebaceous gland differentiation. Importantly, PPARalpha and beta/delta are instrumental in skin repair after an injury, each of them playing specific roles. Due to their collective diverse functions in skin biology, PPARs represent a major research target for the understanding and treatment of many skin diseases, such as benign epidermal tumors, papillomas, acne vulgaris and psoriasis.

Effective Structural Concrete Repair, Volume 1 of 3, Repair of Impact Damaged Prestressed Concrete Beams with CFRP, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Effective Structural Concrete Repair, Volume 2 of 3, Use of FRP to Prevent Chloride Penetration in Bridge Columns, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Effective Structural Concrete Repair, Volume 3 of 3, Evaluation of Repair Materials for Use in Patching Damaged Concrete, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Low-Cost Rural Surface Alternatives: Literature Review and Recommendations, TR-632, 2013

Freezing and thawing action induces damage to unbound gravel roads in Iowa resulting in maintenance costs for secondary road departments. Some approaches currently used by County Engineers to deal with this problem include temporarily spreading rock on the affected areas, lowering or improving drainage ditches, tiling, bridging the area with stone and geosynthetic covered by a top course of aggregate or gravel, coring boreholes and filling them with calcium chloride to melt lenses and provide drainage, and re-grading the crown to a slope of 4% to 6% to maximize spring drainage. However, most of these maintenance solutions are aimed at dealing with conditions after they occur. This study was tasked with identifying alternative approaches in the literature to mitigate the problem. An annotated bibliographic record of literature on the topic of frost-heave and thaw-weakening of gravel roads was generated and organized by topic, and all documents were assessed in terms of a suitable rating for mitigating the problem in Iowa. Over 300 technical articles were collected and selected down to about 150 relevant articles for a full assessment. The documents collected have been organized in an electronic database, which can be used as a tool by practitioners to search for information regarding the various repair and mitigation solutions, measurement technologies, and experiences that have been documented by selected domestic and international researchers and practitioners. Out of the 150+ articles, 71 articles were ranked as highly applicable to conditions in Iowa. The primary mitigation methods identified in this study included chemical and mechanical stabilization; scarification, blending, and recompaction; removal and replacement; separation, and reinforcement; geogrids and cellular confinement; drainage control and capillary barriers, and use of alternative materials. It is recommended that demonstration research projects be established to examine a range of construction methods and materials for treating granular surfaced roadways to mitigate frost-heave and thaw-weakening problems. Preliminary frost-susceptibility test results from ASTM D5916 are included for a range of Iowa materials.

Evaluation of an International Barrier Corporation Barrier, HR-532, 1990

In 1986, the Iowa DOT installed 700 feet of International Barrier Corporation (IBC) barrier between the 1-235 eastbound off ramp and the adjacent eastbound loop on ramp at 8th Street in West Des Moines. It is a 3 foot 6 inch high sand-filled galvanized sheet metal barrier. The bid price on this project was $130 per lineal foot. It was evaluated annually for four years. During this time, there have been no severe accidents where vehicles hit the barrier. There are scrapes and dents indicating minor accidents. The barrier has performed very well and required no maintenance. Due to its initial cost, the IBC barrier is not as cost-effective as portland cement concrete barrier rails.

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17 day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, cav-1, cav-2 and cav-3. While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of eNOS (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes.

The blood-brain barrier: cellular basis.

Perfusion experiments with horseradish peroxidase have established that the morphological substrate of the blood-brain barrier is represented by microvascular endothelial cells. They are characterized by complexly arranged tight junctions and a very low rate of transcytotic vesicular transport. They express transport enzymes, carrier systems and brain endothelial cell-specific molecules of unknown function not expressed by any other endothelial cell population. These blood-brain barrier properties are not intrinsic to these cells but are inducible by the surrounding brain tissue. Type I astrocytes injected into the anterior eye chamber of the rat or onto the chick chorioallantoic membrane are able to induce a host-derived angiogenesis and some blood-brain barrier properties in endothelial cells of non-neural origin. Recently we have shown that this cellular interaction is due to the secretion of a soluble astrocyte derived factor(s). Astrocytes are also implicated in the maintenance, functional regulation and the repair of the blood-brain barrier. Complex interactions between other constituents of the microenvironment surrounding the endothelial cells, such as the basement membrane, pericytes, nerve endings, microglial cells and the extracellular fluid, take place and are required for the proper functioning of the blood-brain barrier, which in addition is regionally different as reflected by endothelial cell heterogeneity.

Data collection and criticality analysis for cost effective maintenance during the life cycle of a flue gas line

Työn tarkoituksena oli kerätä käyttövarmuustietoa savukaasulinjasta kahdelta suomalaiselta sellutehtaalta niiden käyttöönotosta aina tähän päivään asti. Käyttövarmuustieto koostuu luotettavuustiedoista sekä kunnossapitotiedoista. Kerätyn tiedon avulla on mahdollista kuvata tarkasti laitoksen käyttövarmuutta seuraavilla tunnusluvuilla: suunnittelemattomien häiriöiden lukumäärä ja korjausajat, laitteiden seisokkiaika, vikojen todennäköisyys ja korjaavan kunnossapidon kustannukset suhteessa savukaasulinjan korjaavan kunnossapidon kokonaiskustannuksiin. Käyttövarmuustiedon keräysmetodi on esitelty. Savukaasulinjan kriittisten laitteiden määrittelyyn käytetty metodi on yhdistelmä kyselytutkimuksesta ja muunnellusta vian vaikutus- ja kriittisyysanalyysistä. Laitteiden valitsemiskriteerit lopulliseen kriittisyysanalyysiin päätettiin käyttövarmuustietojen sekä kyselytutkimuksen perusteella. Kriittisten laitteiden määrittämisen tarkoitus on löytää savukaasulinjasta ne laitteet, joiden odottamaton vikaantuminen aiheuttaa vakavimmat seuraukset savukaasulinjan luotettavuuteen, tuotantoon, turvallisuuteen, päästöihin ja kustannuksiin. Tiedon avulla rajoitetut kunnossapidon resurssit voidaan suunnata oikein. Kriittisten laitteiden määrittämisen tuloksena todetaan, että kolme kriittisintä laitetta savukaasulinjassa ovat molemmille sellutehtaille yhteisesti: savukaasupuhaltimet, laahakuljettimet sekä ketjukuljettimet. Käyttövarmuustieto osoittaa, että laitteiden luotettavuus on tehdaskohtaista, mutta periaatteessa samat päälinjat voidaan nähdä suunnittelemattomien vikojen todennäköisyyttä esittävissä kuvissa. Kustannukset, jotka esitetään laitteen suunnittelemattomien kunnossapitokustannusten suhteena savukaasulinjan kokonaiskustannuksiin, noudattelevat hyvin pitkälle luotettavuuskäyrää, joka on laskettu laitteen seisokkiajan suhteena käyttötunteihin. Käyttövarmuustiedon keräys yhdistettynä kriittisten laitteiden määrittämiseen mahdollistavat ennakoivan kunnossapidon oikean kohdistamisen ja ajoittamisen laitteiston elinaikana siten, että luotettavuus- ja kustannustehokkuusvaatimukset saavutetaan.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.

The importance of the Hedgehog signaling pathway at the level of the blood-brain barrier

La barrière hémato-encéphalique (BHE) protège le système nerveux central (SNC) en contrôlant le passage des substances sanguines et des cellules immunitaires. La BHE est formée de cellules endothéliales liées ensemble par des jonctions serrées et ses fonctions sont maintenues par des astrocytes, celles ci sécrétant un nombre de facteurs essentiels. Une analyse protéomique de radeaux lipidiques de cellules endothéliales de la BHE humaine a identifié la présence de la voie de signalisation Hedgehog (Hh), une voie souvent liées à des processus de développement embryologique ainsi qu’au niveau des tissus adultes. Suite à nos expériences, j’ai déterminé que les astrocytes produisent et secrètent le ligand Sonic Hh (Shh) et que les cellules endothéliales humaines en cultures primaires expriment le récepteur Patched (Ptch)-1, le co-récepteur Smoothened (Smo) et le facteur de transcription Gli-1. De plus, l’activation de la voie Hh augmente l’étanchéité des cellules endothéliales de la BHE in vitro. Le blocage de l’activation de la voie Hh en utilisant l’antagoniste cyclopamine ainsi qu’en utilisant des souris Shh déficientes (-/-) diminue l’expression des protéines de jonctions serrées, claudin-5, occcludin, et ZO-1. La voie de signalisation s’est aussi montrée comme étant immunomodulatoire, puisque l’activation de la voie dans les cellules endothéliales de la BHE diminue l’expression de surface des molécules d’adhésion ICAM-1 et VCAM-1, ainsi que la sécrétion des chimiokines pro-inflammatoires IL-8/CXCL8 et MCP-1/CCL2, créant une diminution de la migration des lymphocytes CD4+ à travers une monocouche de cellules endothéliales de la BHE. Des traitements avec des cytokines pro-inflammatoires TNF-α and IFN-γ in vitro, augmente la production de Shh par les astrocytes ainsi que l’expression de surface de Ptch-1 et de Smo. Dans des lésions actives de la sclérose en plaques (SEP), où la BHE est plus perméable, les astrocytes hypertrophiques augmentent leur expression de Shh. Par contre, les cellules endothéliales de la BHE n’augmentent pas leur expression de Ptch-1 ou Smo, suggérant une dysfonction dans la voie de signalisation Hh. Ces résultats montrent que la voie de signalisation Hh promeut les propriétés de la BHE, et qu’un environnement d’inflammation pourrait potentiellement dérégler la BHE en affectant la voie de signalisation Hh des cellules endothéliales.

Abdominal aortic aneurysm follow-up after endovascular repair in a canine model with non-invasive vascular elastography

Le traitement chirurgical des anévrismes de l'aorte abdominale est de plus en plus remplacé par la réparation endovasculaire de l’anévrisme (« endovascular aneurysm repair », EVAR) en utilisant des endoprothèses (« stent-grafts », SGs). Cependant, l'efficacité de cette approche moins invasive est compromise par l'incidence de l'écoulement persistant dans l'anévrisme, appelé endofuites menant à une rupture d'anévrisme si elle n'est pas détectée. Par conséquent, une surveillance de longue durée par tomodensitométrie sur une base annuelle est nécessaire ce qui augmente le coût de la procédure EVAR, exposant le patient à un rayonnement ionisants et un agent de contraste néphrotoxique. Le mécanisme de rupture d'anévrisme secondaire à l'endofuite est lié à une pression du sac de l'anévrisme proche de la pression systémique. Il existe une relation entre la contraction ou l'expansion du sac et la pressurisation du sac. La pressurisation résiduelle de l'anévrisme aortique abdominale va induire une pulsation et une circulation sanguine à l'intérieur du sac empêchant ainsi la thrombose du sac et la guérison de l'anévrisme. L'élastographie vasculaire non-invasive (« non-invasive vascular elastography », NIVE) utilisant le « Lagrangian Speckle Model Estimator » (LSME) peut devenir une technique d'imagerie complémentaire pour le suivi des anévrismes après réparation endovasculaire. NIVE a la capacité de fournir des informations importantes sur l'organisation d'un thrombus dans le sac de l'anévrisme et sur la détection des endofuites. La caractérisation de l'organisation d'un thrombus n'a pas été possible dans une étude NIVE précédente. Une limitation de cette étude était l'absence d'examen tomodensitométrique comme étalon-or pour le diagnostic d'endofuites. Nous avons cherché à appliquer et optimiser la technique NIVE pour le suivi des anévrismes de l'aorte abdominale (AAA) après EVAR avec endoprothèse dans un modèle canin dans le but de détecter et caractériser les endofuites et l'organisation du thrombus. Des SGs ont été implantés dans un groupe de 18 chiens avec un anévrisme créé dans l'aorte abdominale. Des endofuites de type I ont été créés dans 4 anévrismes, de type II dans 13 anévrismes tandis qu’un anévrisme n’avait aucune endofuite. L'échographie Doppler (« Doppler ultrasound », DUS) et les examens NIVE ont été réalisés avant puis à 1 semaine, 1 mois, 3 mois et 6 mois après l’EVAR. Une angiographie, une tomodensitométrie et des coupes macroscopiques ont été réalisées au moment du sacrifice. Les valeurs de contrainte ont été calculées en utilisant l`algorithme LSME. Les régions d'endofuite, de thrombus frais (non organisé) et de thrombus solide (organisé) ont été identifiées et segmentées en comparant les résultats de la tomodensitométrie et de l’étude macroscopique. Les valeurs de contrainte dans les zones avec endofuite, thrombus frais et organisé ont été comparées. Les valeurs de contrainte étaient significativement différentes entre les zones d'endofuites, les zones de thrombus frais ou organisé et entre les zones de thrombus frais et organisé. Toutes les endofuites ont été clairement caractérisées par les examens d'élastographie. Aucune corrélation n'a été trouvée entre les valeurs de contrainte et le type d'endofuite, la pression de sac, la taille des endofuites et la taille de l'anévrisme.

An illustration of the modelling of cost and efficacy data from a clinical trial

Health care providers, purchasers and policy makers need to make informed decisions regarding the provision of cost-effective care. When a new health care intervention is to be compared with the current standard, an economic evaluation alongside an evaluation of health benefits provides useful information for the decision making process. We consider the information on cost-effectiveness which arises from an individual clinical trial comparing the two interventions. Recent methods for conducting a cost-effectiveness analysis for a clinical trial have focused on the net benefit parameter. The net benefit parameter, a function of costs and health benefits, is positive if the new intervention is cost-effective compared with the standard. In this paper we describe frequentist and Bayesian approaches to cost-effectiveness analysis which have been suggested in the literature and apply them to data from a clinical trial comparing laparoscopic surgery with open mesh surgery for the repair of inguinal hernias. We extend the Bayesian model to allow the total cost to be divided into a number of different components. The advantages and disadvantages of the different approaches are discussed. In January 2001, NICE issued guidance on the type of surgery to be used for inguinal hernia repair. We discuss our example in the light of this information. Copyright © 2003 John Wiley & Sons, Ltd.

Improving aircraft maintenance, repair, and overhaul: A novel text mining approach

Aircraft Maintenance, Repair and Overhaul (MRO) feedback commonly includes an engineer’s complex text-based inspection report. Capturing and normalizing the content of these textual descriptions is vital to cost and quality benchmarking, and provides information to facilitate continuous improvement of MRO process and analytics. As data analysis and mining tools requires highly normalized data, raw textual data is inadequate. This paper offers a textual-mining solution to efficiently analyse bulk textual feedback data. Despite replacement of the same parts and/or sub-parts, the actual service cost for the same repair is often distinctly different from similar previously jobs. Regular expression algorithms were incorporated with an aircraft MRO glossary dictionary in order to help provide additional information concerning the reason for cost variation. Professional terms and conventions were included within the dictionary to avoid ambiguity and improve the outcome of the result. Testing results show that most descriptive inspection reports can be appropriately interpreted, allowing extraction of highly normalized data. This additional normalized data strongly supports data analysis and data mining, whilst also increasing the accuracy of future quotation costing. This solution has been effectively used by a large aircraft MRO agency with positive results.