Longitudinal Joint Forming in PCC Pavements, MLR-00-05, Construction Report, 2003

In conventional construction practices, a longitudinal joint is sawed in a PCC (Portland Cement Concrete) pavement to control concrete shrinkage cracking between two lanes of traffic. Sawing a joint in hardened concrete is an expensive and time consuming operation. The longitudinal joint is not a working joint (in comparison to a transverse joint) as it is typically tied with a tie bar at 30 inch spacing. The open joint reservoir, left by the saw blade, typically is filled or sealed with a durable crack sealant to keep incompressibles and water from getting into the joint reservoir. An experimental joint forming knife has been developed. It is installed under the paving machine to form the longitudinal joint in the wet concrete as a part of the paving process. Through this research method, forming a very narrow longitudinal joint during the paving process, two conventional paving operations can be eliminated. Joint forming eliminates the need of the joint sawing operation in the hard concrete, and as the joint that is formed does not leave a wide-open reservoir, but only a hairline crack, it does not need the joint filling or sealing operation. Therefore, the two conventional longitudinal joint sawing and sealing operations are both being eliminated by this innovation. A laboratory scale prototype joint forming knife was built and tested, initially forming joints in small concrete beams. The results were positive so the method was proposed for field testing. Initial field tests were done in the construction season of 2001, limited to one paving contractor. A number of modifications were made to the knife throughout the field tests. About 3000 feet of longitudinal joint was formed in 2001. Additional testing was done in the 2002 construction season, working with the same contractor. About 150,000 feet of longitudinal joint was formed in 2002. Evaluations of the formed joints were done to determine longitudinal joint hairline crack development rate and appearance. Additional tests will be done in the next construction season to improve or perfect the longitudinal joint forming technique.

Fluxo gênico em soja na Região Oeste do Paraná

Este trabalho teve o objetivo de avaliar o fluxo gênico em soja, na Região Oeste do Paraná. Foram semeados cinco círculos concêntricos, com a cultivar CD 219RR, que contém o gene CP4 EPSPS. Os círculos foram espaçados em 50 cm, com círculo interno de diâmetro de 50 cm. Externamente a estes, foi semeada a cultivar CD 211 (convencional), também em cinco círculos concêntricos, espaçados em 1 m. As plantas da cultivar CD 211 foram colhidas e trilhadas individualmente, e as sementes semeadas novamente no campo. Após a emergência, foram obtidas 151.772 plântulas, as quais, com 15 dias, foram pulverizadas com 900 g ha-1 de i.a. de glifosato. Após uma semana, plantas sobreviventes foram submetidas à análise de PCR, para verificar a presença do gene CP4 EPSPS. A taxa de fecundação cruzada foi de 0,61, 0,29, 0,23, 0,22 e 0,23% respectivamente a 1, 2, 3, 4 e 5 m de distância das plantas geneticamente modificadas.

Spatial learning by rats across visually disconnected environments

Two spatial tasks were designed to test specific properties of spatial representation in rats. In the first task, rats were trained to locate an escape hole at a fixed position in a visually homogeneous arena. This arena was connected with a periphery where a full view of the room environment existed. Therefore, rats were dependent on their memory trace of the previous position in the periphery to discriminate a position within the central region. Under these experimental conditions, the test animals showed a significant discrimination of the training position without a specific local view. In the second task, rats were trained in a radial maze consisting of tunnels that were transparent at their distal ends only. Because the central part of the maze was non-transparent, rats had to plan and execute appropriate trajectories without specific visual feedback from the environment. This situation was intended to encourage the reliance on prospective memory of the non-visited arms in selecting the following move. Our results show that acquisition performance was only slightly decreased compared to that shown in a completely transparent maze and considerably higher than in a translucent maze or in darkness. These two series of experiments indicate (1) that rats can learn about the relative position of different places with no common visual panorama, and (2) that they are able to plan and execute a sequence of visits to several places without direct visual feed-back about their relative position.

Wind Loads on Dynamic Message Cabinets and Behavior of Supporting Trusses, TR-612, 2013

Large Dynamic Message Signs (DMSs) have been increasingly used on freeways, expressways and major arterials to better manage the traffic flow by providing accurate and timely information to drivers. Overhead truss structures are typically employed to support those DMSs allowing them to provide wider display to more lanes. In recent years, there is increasing evidence that the truss structures supporting these large and heavy signs are subjected to much more complex loadings than are typically accounted for in the codified design procedures. Consequently, some of these structures have required frequent inspections, retrofitting, and even premature replacement. Two manufacturing processes are primarily utilized on truss structures - welding and bolting. Recently, cracks at welding toes were reported for the structures employed in some states. Extremely large loads (e.g., due to high winds) could cause brittle fractures, and cyclic vibration (e.g., due to diurnal variation in temperature or due to oscillations in the wind force induced by vortex shedding behind the DMS) may lead to fatigue damage, as these are two major failures for the metallic material. Wind and strain resulting from temperature changes are the main loads that affect the structures during their lifetime. The American Association of State Highway and Transportation Officials (AASHTO) Specification defines the limit loads in dead load, wind load, ice load, and fatigue design for natural wind gust and truck-induced gust. The objectives of this study are to investigate wind and thermal effects in the bridge type overhead DMS truss structures and improve the current design specifications (e.g., for thermal design). In order to accomplish the objective, it is necessary to study structural behavior and detailed strain-stress of the truss structures caused by wind load on the DMS cabinet and thermal load on the truss supporting the DMS cabinet. The study is divided into two parts. The Computational Fluid Dynamics (CFD) component and part of the structural analysis component of the study were conducted at the University of Iowa while the field study and related structural analysis computations were conducted at the Iowa State University. The CFD simulations were used to determine the air-induced forces (wind loads) on the DMS cabinets and the finite element analysis was used to determine the response of the supporting trusses to these pressure forces. The field observation portion consisted of short-term monitoring of several DMS Cabinet/Trusses and long-term monitoring of one DMS Cabinet/Truss. The short-term monitoring was a single (or two) day event in which several message sign panel/trusses were tested. The long-term monitoring field study extended over several months. Analysis of the data focused on trying to identify important behaviors under both ambient and truck induced winds and the effect of daily temperature changes. Results of the CFD investigation, field experiments and structural analysis of the wind induced forces on the DMS cabinets and their effect on the supporting trusses showed that the passage of trucks cannot be responsible for the problems observed to develop at trusses supporting DMS cabinets. Rather the data pointed toward the important effect of the thermal load induced by cyclic (diurnal) variations of the temperature. Thermal influence is not discussed in the specification, either in limit load or fatigue design. Although the frequency of the thermal load is low, results showed that when temperature range is large the restress range would be significant to the structure, especially near welding areas where stress concentrations may occur. Moreover stress amplitude and range are the primary parameters for brittle fracture and fatigue life estimation. Long-term field monitoring of one of the overhead truss structures in Iowa was used as the research baseline to estimate the effects of diurnal temperature changes to fatigue damage. The evaluation of the collected data is an important approach for understanding the structural behavior and for the advancement of future code provisions. Finite element modeling was developed to estimate the strain and stress magnitudes, which were compared with the field monitoring data. Fatigue life of the truss structures was also estimated based on AASHTO specifications and the numerical modeling. The main conclusion of the study is that thermal induced fatigue damage of the truss structures supporting DMS cabinets is likely a significant contributing cause for the cracks observed to develop at such structures. Other probable causes for fatigue damage not investigated in this study are the cyclic oscillations of the total wind load associated with the vortex shedding behind the DMS cabinet at high wind conditions and fabrication tolerances and induced stresses due to fitting of tube to tube connections.

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T-cell clones in long-term melanoma survivors.

Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive immune response to cancers. This CTL response is often insufficient because of functional impairment, tumor escape mechanisms, or inhibitory tumor microenvironment. However, little is known about the fate of given tumor-specific CTL clones in cancer patients. Studies in patients with favorable outcomes may be very informative. In this longitudinal study, we tracked, quantified, and characterized functionally defined antigen-specific T-cell clones ex vivo, in peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE-A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor lytic capabilities persisted in peripheral blood over more than 10 years, with quantitative variations correlating with the clinical course. These clones were also found in emerging metastases, and, in one patient, circulating clonal T cells displayed a fully differentiated effector phenotype at the time of relapse. Longevity, tumor homing, differentiation phenotype, and quantitative adaptation to the disease phases suggest the contribution of the tracked tumor-reactive clones in the tumor control of these long-term metastatic survivor patients. Focusing research on patients with favorable outcomes may help to identify parameters that are crucial for an efficient antitumor response and to optimize cancer immunotherapy.

Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.

Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.

East 1 St Street Interchange and I-35 Widening, From MP 94.3 to Oralabor Road, Polk County, Iowa, Project # IM-035-4(140)92--13-77, Environmental Assessment and Section 4(f) De Minimis Impact Finding, 2015

From Proposed Action: "The proposed action consists of reconstructing the East 1st Street/I-35 interchange with a Diverging Diamond interchange, widening I-35 from four (4) lanes to six (6) lanes, and widening East 1st Street from four (4) lanes to five (5) lanes from Delaware Avenue to Frisk Drive. The project also proposes to reconstruct the intersections of East 1st Street/Creekview Drive and East 1st Street/Frisk Drive."

Formation of a direct arterial blood supply to the anterior pituitary gland following complete or partial interruption of the hypophyseal portal vessels

If regions of the anterior pituitary gland received systemic blood via a direct arterial blood supply these regions would escape hypothalamic regulation and thus be a sequela in endocrine disorders. Since, in the untreated rat, all of the blood supply to the anterior pituitary gland is via the hypophyseal portal vessels, we hypothesized that partial interruption of the portal vessels could provoke the establishment of a direct arterial blood supply (arteriogenesis). We utilized the injection of polystyrene microspheres (15 or 9 micron diameter) into the left ventricle of the heart to test this hypothesis. Microspheres are trapped in the first capillary plexus they reach since they are too large to traverse the capillaries. No microspheres reached the anterior pituitary gland of control rats, a finding consistent with the fact that the anterior pituitary gland receives all of its blood supply via the hypophyseal portal blood vessels. Microspheres were observed in the primary portal capillary plexus in the infundibulum (median eminence), infundibular stalk (pituitary stalk), and infundibular process (pars nervosa), the first capillary plexus which they reached. A lesion of the medial basal hypothalamus (MBH) which destroyed the long portal vessels did not result in arteriogenesis since few, if any, microspheres were observed in the anterior pituitary gland. We confirmed, using vascular casts, that these lesions resulted in the long-term destruction of the primary portal capillaries in the infundibulum and of the long portal vessels. In MBH-lesioned animals it appears that all of the blood supply of the anterior pituitary gland is via short portal vessels arising from the infundibular stem and process.(ABSTRACT TRUNCATED AT 250 WORDS)

Road Safety Audit for the US 61/Harrison Street and West Locust Street Intersection in Davenport-Scott County, Iowa, 2008

On the October 7 and 8, 2008, a road safety audit was conducted for the intersection of US 61/Harrison Street and West Locust Street in Davenport, Iowa. US 61/Harrison Street is a one-way street and a principal arterial route through Davenport, with three southbound lanes. Locust Street is a four-lane, two-way minor arterial running across the city from west to east. The last major improvement at this intersection was implemented approximately 20 years ago. The Iowa Department of Transportation requested a safety audit of this intersection in response to a high incidence of crashes at the location over the past several years, in view of the fact that no major improvements are anticipated for this intersection in the immediate future. The road safety audit team discussed current conditions at the intersection and reviewed the last seven years of crash data. The team also made daytime and nighttime field visits to the intersection to examine field conditions and observe traffic flow and crossing guard operations with younger pedestrians. After discussing key issues, the road safety audit team drew conclusions and suggested possible enforcement, engineering, public information, and educational strategies for mitigation.

Tolerogenic dendritic cells and their role in induction of immune tolerance

Les cellules dendritiques sont des cellules du système immunitaire qui permettent d'instruire les lymphocytes T, autres cellules de ce système, pour mettre en place une réponse immunitaire adaptée afin de combattre et vaincre une infection. Ces cellules dendritiques vont reconnaître des motifs spécifiquement exprimés par des pathogènes par l'intermédiaire de récepteurs exprimés à leur surface. En détectant ces molécules, elles vont s'activer et subir diverses modifications pour pouvoir activer les lymphocytes T. Elles vont alors interagir avec les lymphocytes Τ et transférer les informations nécessaires pour que ces cellules s'activent à leur tour et produisent différentes protéines de façon à éliminer le pathogène. En fonction du type de pathogène, les informations transférées entre les cellules dendritiques et les lymphocytes seront différentes de manière à produire la réponse immunitaire la mieux adaptée pour supprimer l'élément infectieux. Dans le corps, les cellules dendritiques circulent continuellement afin de détecter les éléments étrangers. Quand elles reconnaissent une protéine étrangère, elles la phagocytent, c'est-à-dire qu'elles la mangent afin de pouvoir la présenter aux lymphocytes T. Mais quand elles phagocytent un élément étranger, elles peuvent également prendre des éléments du soi, comme par exemple quand elles phagocytent une cellule infectée par un virus. Les cellules dendritiques doivent alors être capables de différentier les molécules du soi et du non-soi de façon à ne pas induire une réponse en présentant un antigène du soi aux lymphocytes T. D'autant plus que lors de leur développement, les lymphocytes Τ qui sont capables de reconnaître le soi sont éliminés mais ce système n'est pas parfait et donc certains lymphocytes Τ auto-reactifs peuvent se trouver dans le corps. Il existe ainsi d'autres mécanismes en périphérie du site de développement pour inhiber ces lymphocytes Τ auto-reactifs. Ce sont les mécanismes de tolérance. Quand les lymphocytes Τ induisent une réponse aux antigènes du soi, cela résulte à des maladies auto-immunes. Dans mon projet de recherche, nous avons travaillé avec des lignées de cellules dendritiques, c'est-à-dire des cellules dendritiques semblables à celles que l'on peut trouver in vivo mais qui sont immortalisées, elles peuvent donc être cultiver et manipuler in vitro. Nous avons génétiquement modifiées ces lignées cellulaires pour qu'elles expriment des molécules immunosuppressives afin d'étudier comment induire une tolérance immunitaire, c'est-à-dire si l'expression de ces molécules permet d'éviter de générer une réponse immunitaire. Pour cela, nous avons utilisé des modèles murins de tumeurs et de maladies auto-immunes. Nous avons démontré que ces lignées de cellules dendritiques peuvent être un grand outil de recherche pour étudier les bénéfices de différentes molécules immuno-modulatrices afin d'induire une tolérance immunitaire à différents antigènes. - Les cellules dendritiques sont responsables de l'induction des réponses immunitaires adaptatives. Suite à une infection microbienne, les cellules dendritiques s'activent, elles induisent l'expression de molécules de costimulation à leur surface, sécrètent des cytokines et induisent la différentiation des cellules Τ effectrices et mémoires. De plus, les cellules dendritiques ont un rôle important dans l'induction et la maintenance de la tolérance immunitaire au niveau du thymus et en périphérie, en induisant l'anergie, la délétion ou la conversion des cellules Τ naïves en cellules régulatrices. Dans notre groupe, une nouvelle lignée de cellules dendritiques appelée MuTu a été crée par la culture de cellules dendritiques tumorales isolées à partir d'une rate d'une souris transgénique, dans laquelle l'expression de l'oncogène SV40 et du GFP sont sous le contrôle du promoteur CD1 le, et sont ainsi spécifiquement exprimés dans les cellules dendritiques. Ces nouvelles lignées appartiennent au sous-type des cellules dendritiques conventionnelles exprimant CD8a. Elles ont conservé leur capacité d'augmenter l'expression des marqueurs de costimulation à leur surface ainsi que le production de cytokines en réponse à des ligands des récepteurs Toll, ainsi que leur capacité à présenter des antigènes associés aux molécules du complexe majeur d'histocompatibilité (CMH) de classe I ou II pour activer la prolifération et la différentiation des lymphocytes T. En utilisant un système de transduction de lentivirus de seconde génération, ces nouvelles lignées de cellules dendritiques ont été génétiquement modifiées pour sur-exprimer des molécules immunosuppressives (IL-10, TGFP latent, TGFp actif, Activin A, Arginase 1, IDO, B7DC et CTLA4). Ces lignées permettent d'étudier de manière reproductible le rôle de ces molécules potentiellement tolérogènes sur les réponses immunitaires in vitro et in vivo. Ces lignées potentiellement tolérogènes ont été testées, tout d'abord, in vitro, pour leur capacité à inhiber l'activation des cellules dendritiques, à bloquer la prolifération des cellules Τ ou à modifier leur polarisation. Nos résultats démontrent qu'en réponse à une stimulation, la sur-expression des molécules costimulatrices et la sécrétion de molécules pro- inflammatoires est réduite quand les cellules dendritiques sur-expriment l'IL-10. La sur¬expression de TGFp sous sa forme active induit le développement de cellules régulatrices CD4+ CD25+ Foxp3+ et bloque la réponse CD8 cytotoxique tandis que la sur-expression de CTLA4 à la surface des cellules dendritiques inhibe une réponse Thl et induit des lymphocytes Τ anergiques. Ces lignées ont également été utilisées pour étudier l'induction de tolérance in vivo. Tout d'abord, nous avons étudié l'induction de tolérance dans un modèle de développement de tumeurs. En effet, quand les lignées tumorales sont transférées dans les lignées de souris C57BL/6, elles sont reconnues comme du non-soi du à l'expression de l'oncogène SV40 et du GFP et sont éliminées. Ce mécanisme d'élimination a été étudié en utilisant une lignée de cellules dendritiques modifiée pour exprimer la luciférase et qui a permis de suivre le développement des tumeurs par de l'imagerie in vivo dans des animaux vivants. Ces lignées de cellules dendritiques MuTu sont éliminées dans la souris C57BL/6 par les lymphocytes CD8 et l'action cytotoxique de la perforine. Après plusieurs injections, les cellules dendritiques sur-exprimant CTLA4 ou l'actif TGFp peuvent casser cette réponse immunitaire inhérente aux antigènes de la lignée et induire le développement de la tumeur dans la souris C57BL/6. Le développement tumoral a pu être suivi en mesurant la bioluminescence émise par des cellules dendritiques modifiées pour exprimer à la fois l'actif TGFp et la luciférase. Ces tumeurs ont pu se développer grâce à la mise en place d'un microenvironnement suppressif pour échapper à l'immunité en recrutant des cellules myéloïde suppressives, des lymphocytes CD4 régulateurs et en induisant l'expression d'une molécule inhibitrice PD-1 à la surface des lymphocytes CD8 infiltrant la tumeur. Dans un deuxième temps, ces lignées tolérogènes ont également été testées dans un modèle murin de maladies auto-immunes, appelé l'encéphalomyélite auto-immune expérimental (EAE), qui est un modèle pour la sclérose en plaques. L'EAE a été induite dans la souris par le transfert de cellules de ganglions prélevées d'une souris donneuse préalablement immunisée avec une protéine du système nerveux central, la glycoprotéine myéline oligodendrocyte (MOG) émulsifiée dans de l'adjuvant complet de Freund. La vaccination des souris donneuses et receveuses avec les cellules sur-exprimant l'actif TGFP préalablement chargées avec la protéine MOG bloque l'induction de l'EAE. Nous sommes actuellement en train de définir les mécanismes qui permettent de protéger la souris du développement de la maladie auto-immune. Dans cette étude, nous avons ainsi démontré la possibilité d'induire la tolérance in vivo et in vitro à différents antigènes en utilisant nos nouvelles lignées de cellules dendritiques et en les modifiant pour exprimer des molécules immunosuppressives. En conséquence, ces nouvelles lignées de cellules dendritiques représentent un outil pour explorer les bénéfices de différentes molécules ayant des propriétés immuno-modulatrices pour manipuler le système immunitaire vers un phénotype tolérogène. - Dendritic cells (DC) are widely recognized as potent inducers of the adaptive immune responses. Importantly, after microbial infections, DC become activated, induce co- stimulation, secrete cytokines and induce effector and memory Τ cells. DC furthermore play an important role in inducing and maintaining central and peripheral tolerance by inducing anergy, deletion or commitment of antigen-specific naïve Τ cells into regulatory Τ cells. In our group, stable MuTu DC lines were generated by culture of splenic DC tumors from transgenic mice expressing the SV40 large Τ oncogene and the GFP under DC-specific CDllc promoter. These transformed DC belong to the CD8a+ conventional DC subtype and have fully conserved their capacity to upregulate co-stimulatory markers and produce cytokines after activation with Toll Like Receptors-ligands, and to present Major Histocompatibility class-I or MHCII-restricted antigens to activate Τ cell expansion and differentiation. Using a second- generation lentiviral transduction system, these newly developed MuTu DC lines were genetically modified to overexpress immunosuppressive molecules (IL-10, latent TGFp, active TGFp, Activin A, Arginase 1, IDO, B7DC and CTLA4). This allows to reproducibly investigate the role of these potentially tolerogenic molecules on in vitro and in vivo immune responses. These potentially tolerogenic DC were tested in vitro for their ability to inhibit DC activation, to prevent Τ cell proliferation and to modify Τ cell polarization. Our results show that the upregulation of costimulatory molecules and the secretion of pro-inflammatory cytokines were reduced upon stimulation of DC overexpressing IL-10. The overexpression of active TGFP induced the development of CD4+ CD25+ Foxp3+ regulatory Τ cells and inhibited the cytotoxic CD8 Τ cell response as shown by using the OT-II Τ cell system whereas the surface expression of CTLA-4 on DC prevented the Thl response and prompted an anergic antigen-specific Τ cell response. These MuTu DC lines were also used in vivo in order to study the induction of tolerance. First we addressed the induction of tolerance in a model of tumorogenesis. The adoptively transferred tumor cell lines were cleared in C57BL/6 mice due to the foreign expression of SV40 LargeT and GFP. The mechanism of clearance of MuTu DC line into C57BL/6 mice was investigated by using luciferase-expressing DC line. These DC line allowed to follow, by in vivo imaging, the tumor development in living animals and determined that MuTu DC lines were eliminated in a perforin-mediated CD8 Τ cell dependent and CD4 Τ cell independent response. After multiple injections, DC overexpressing CTLA4 or active TGFp could break the immune response to these inherent antigens and induced DC tumorogenesis in wild type mice. The tumor outgrowth in C57BL/6 mice was nicely observed by double-transduced DC lines to express both luciferase and active TGFp. actTGFp-DC tumor was shown to recruit myeloid-derived suppressor cells, induce CD4+ CD25+ Foxp3+ regulatory Τ cells and induce the expression of the inhibitory receptor PD-1 on tumor- infiltrating CD8+ Τ cells in order to escape tumor immunity. Tolerogenic DC lines were also tested for the induction of tolerance in a murine model of autoimmune disease, the experimental autoimmune encephalitis (EAE) model for human multiple sclerosis. EAE was induced in C57BL/6 mice by the adoptive transfer of lymph node cells isolated from donor mice previously immunized by a protein specific to the central nervous system, the myelin oligodendrocyte glycoprotein (MOG) emulsified in the complete freund adjuvant. The vaccination of donor and recipient mice with MOG-pulsed actTGFP-DC line prevented EAE induction. We are still investigating how the active TGFP protect mice from EAE development. We generated tolerogenic DC lines inducing tolerance in vitro and in vivo. Thereby these MuTu DC lines represent a great tool to explore the benefits of various immuno-modulatory molecules to manipulate the immune system toward a tolerogenic phenotype.

Anti-angiogenic therapies in cancer: achievements and open questions.

The approval in 2004 of bevacizumab (Avastin), a neutralizing monoclonal antibody directed against vascular endothelial growth factor (VEGF) as the first anti-angiogenic systemic drug to treat cancer patients validated the notion introduced 33 years earlier by Dr. Judah Folkman, that inhibition of tumor angiogenesis might be a valid approach to control tumor growth. Anti-angiogenic therapy was greeted in the clinic a major step forward in cancer treatment. At the same time this success recently boosted the field to the quest for new anti-angiogenic targets and drugs. In spite of this success, however, some old questions in the field have remained unanswered and new ones have emerged. They include the identification for surrogate markers of angiogenesis and anti-angiogenesis, the understanding about how anti-angiogenic therapy and chemotherapy synergize, the characterization of the biological consequences of sustained suppression of angiogenesis on tumor biology and normal tissue homeostasis, and the mechanisms of tumor escape from anti-angiogenesis. In this review we summarize some of these outstanding questions, and highlight future challenges in clinical, translational and experimental research in anti-angiogenic therapy that need to be addressed in order to improve current treatments and to design new drugs.

Dissociation between components of spatial memory in rats after recovery from the effects of retrohippocampal lesions

A series of 4 experiments examined the performance of rats with retrohippocampal lesions on a spatial water-maze task. The animals were trained to find and escape onto a hidden platform after swimming in a large pool of opaque water. The platform was invisible and could not be located using olfactory cues. Successful escape performance required the rats to develop strategies of approaching the correct location with reference solely to distal extramaze cues. The lesions encompassed the entire rostro-caudal extent of the lateral and medial entorhinal cortex, and included parts of the pre- and para-subiculum, angular bundle and subiculum. Groups ECR 1 and 2 sustained only partial damage of the subiculum, while Group ECR+S sustained extensive damage. These groups were compared with sham-lesion and unoperated control groups. In Expt 1A, a profound deficit in spatial localisation was found in groups ECR 1 and ECR+S, the rats receiving all training postoperatively. In Expt 1B, these two groups showed hyperactivity in an open-field. In Expt 2, extensive preoperative training caused a transitory saving in performance of the spatial task by group ECR 2, but comparisons with the groups of Expt 1A revealed no sustained improvement, except on one measure of performance in a post-training transfer test. All rats were then given (Expt 3) training on a cueing procedure using a visible platform. The spatial deficit disappeared but, on returning to the normal hidden platform procedure, it reappeared. Nevertheless, a final transfer test, during which the platform was removed from the apparatus, revealed a dissociation between two independent measures of performance: the rats with ECR lesions failed to search for the hidden platform but repeatedly crossed its correct location accurately during traverses of the entire pool. This partial recovery of performance was not (Expt 4) associated with any ability to discriminate between two locations in the pool. The apparently selective recovery of aspects of spatial memory is discussed in relation to O'Keefe and Nadel's (1978) spatial mapping theory of hippocampal function. We propose a modification of the theory in terms of a dissociation between procedural and declarative subcomponents of spatial memory. The declarative component is a flexible access system in which information is stored in a form independent of action. It is permanently lost after the lesion. The procedural component is "unmasked" by the retrohippocampal lesion giving rise to the partial recovery of spatial localisation performance.

U.S. 61 From Memorial Park Road in Burlington North to 1 Mile North of IA 78 in Louisa County. Des Moines & Louisa County, Iowa NHS-061-2(50) - 19-58, 2015

Iowa Department of Transportation (Iowa DOT) has re-initiated planning and preliminary design studies to improve U.S. 61 from Memorial Park Road in Burlington north to 1-mile north of IA 78 in Louisa County. The proposed project consists of improving approximately 18 miles of roadway from 2-lanes to 4-lanes and evaluating a potential bypass around Mediapolis.

Life events in conversion disorder: Role of timing and nature of events

Aims: To compare the frequency of life events in the year preceding illness onset in a series of Conversion Disorder (CD) patients, with those of a matched control group and to characterize the nature of those events in terms of "escape" potential. Traditional models of CD hypothesise that relevant stressful experiences are "converted" into physical symptoms to relieve psychological pressure, and that the resultant disability allows "escape" from the stressor, providing some advantage to the individual. Methods: The Life Events and Difficulties Schedule (LEDS) is a validated semi-structured interview designed to minimise recall and interviewer bias through rigorous assessment and independent rating of events. An additional "escape" rating was developed. Results: In the year preceding onset in 25 CD patients (mean age 38.9 years ± 8) and a similar matched period in 13 controls (mean age 36.2 years ± 10), no significant difference was found in the proportion of subjects having ≥ 1 severe event (CD 64%, controls 38%; p=0.2). In the last month preceding onset, a higher number of patients experienced ≥1 severe events than controls (52% vs 15%, odds ratio 5.95 (CI: 1.09-32.57)). Patients were twice as much more likely to have a severe escape events than controls, in the month preceding onset (44% vs 7%, odds ratio 9.43 (CI: 1.06-84.04). Conclusion: Preliminary data from this ongoing study suggest that the time frame (preceding month) and the nature ("escape") of the events may play an important role in identifying key events related to CD onset.