Relationship between Speed and Lateral Position on Curves, September 2012

Excessive speed is often cited as a primary driver factor in crashes, particularly rural two-lane crashes. It has also been suggested that speed plays a significant role in crashes on curves. However, the relationship between speed and crashes on curves is not well documented because it is difficult to determine driver speed after the fact when investigating a crash. One method to begin documenting this relationship is to explore the relationship between lateral position and speed as a crash surrogate. For this study, the researchers collected speed and lateral position data for three rural two-lane curves. The relationship between lateral position and speed was assessed by comparing the odds of a near-lane crossing for vehicles traveling 5 or more mph over the advisory speed to those for vehicles traveling below that threshold.

Toolbox of Countermeasures for Rural Two-Lane Curves, June 2012

The Federal Highway Administration (FHWA) estimates that 58 percent of roadway fatalities are lane departures, while 40 percent of fatalities are single-vehicle run-off-road (SVROR) crashes. Addressing lane-departure crashes is therefore a priority for national, state, and local roadway agencies. Horizontal curves are of particular interest because they have been correlated with increased crash occurrence. This toolbox was developed to assist agencies address crashes at rural curves. The main objective of this toolbox is to summarize the effectiveness of various known curve countermeasures. While education, enforcement, and policy countermeasures should also be considered, they were not included given the toolbox focuses on roadway-based countermeasures. Furthermore, the toolbox is geared toward rural two-lane curves. The research team identified countermeasures based on their own research, through a survey of the literature, and through discussions with other professionals. Coverage of curve countermeasures in this toolbox is not necessarily comprehensive. For each countermeasure covered, this toolbox includes the following information: description, application, effectiveness, advantages, and disadvantages.

Machine learning analysis and modeling of interest rate curves

The present research deals with the review of the analysis and modeling of Swiss franc interest rate curves (IRC) by using unsupervised (SOM, Gaussian Mixtures) and supervised machine (MLP) learning algorithms. IRC are considered as objects embedded into different feature spaces: maturities; maturity-date, parameters of Nelson-Siegel model (NSM). Analysis of NSM parameters and their temporal and clustering structures helps to understand the relevance of model and its potential use for the forecasting. Mapping of IRC in a maturity-date feature space is presented and analyzed for the visualization and forecasting purposes.

MEPDG Work Plan Task No. 8: Validation of Pavement Performance Curves for the Mechanistic-Empirical Pavement Design Guide, 2009

The objective of this research is to determine whether the nationally calibrated performance models used in the Mechanistic-Empirical Pavement Design Guide (MEPDG) provide a reasonable prediction of actual field performance, and if the desired accuracy or correspondence exists between predicted and monitored performance for Iowa conditions. A comprehensive literature review was conducted to identify the MEPDG input parameters and the MEPDG verification/calibration process. Sensitivities of MEPDG input parameters to predictions were studied using different versions of the MEPDG software. Based on literature review and sensitivity analysis, a detailed verification procedure was developed. A total of sixteen different types of pavement sections across Iowa, not used for national calibration in NCHRP 1-47A, were selected. A database of MEPDG inputs and the actual pavement performance measures for the selected pavement sites were prepared for verification. The accuracy of the MEPDG performance models for Iowa conditions was statistically evaluated. The verification testing showed promising results in terms of MEPDG’s performance prediction accuracy for Iowa conditions. Recalibrating the MEPDG performance models for Iowa conditions is recommended to improve the accuracy of predictions. ****************** Large File**************************

Qualitative and quantitative analysis of thalamo-cortical axons in the somatosensory cortex of normal and barrelless mice

Résumé Les rongeurs utilisent leurs moustaches (vibrisses) pour explorer le milieu environnant. Chaque moustache est mue par un système des muscles. Les récepteurs situés à sa base transmettent les informations au système nerveux central. La transmission vers l'écorce se fait via trois neurones de relais qui se trouvent au niveau du ganglion trigéminé, du tronc cérébral et du thalamus. La représentation corticale d'une vibrisse est une concentration des axones thalamo-corticaux (ATC) autour desquelles s'organisent leurs cibles, les cellules de la couche IV. La structure peut être identifiée histologiquement en coupes tangentielles et porte le nom de « barrel » (« tonneau »). Cette correspondance vibrisse - barrel fait de ce système un model idéal pour étudier l'influence de l'activité périphérique sur l'établissement et le maintien des cartes somatotopiques. Notre laboratoire dispose d'une souche de souris qui a subi une mutation spontanée pour le gène codant l'adenylyl cyclase I (ACI). Cette enzyme membranaire catalyse la formation de l'AMPc et joue un rôle important dans le guidage axonal, la libération des neurotransmetteurs et l'intégration des signaux postsynaptiques. Nous avons démontré dans un premier temps que cette souris adulte ne développe pas de barrels. Cela est dû à un manque d'organisation des ATC et aussi des cellules de la couche IV. De plus, les résultats électrophysiologiques montrent que les informations venant des vibrisses adjacentes ne sont pas intégrées d'une manière normale. Dans ce travail de thèse, j'ai analysé la morphologie des ATC révélés individuellement avec de la biocytine. L'analyse quantitative des ATC a mis en évidence les points suivants: 1. Les axones de la souris normale (NOR) quittent le thalamus, traversent la capsule interne et la substance blanche sous-corticale et pénètrent dans le cortex somato-sensoriel primaire. A l'intérieur de l'écorce ils traversent au maximum 3 colonnes corticales adjacentes dont une contient le barrel cible. En passant à travers les couches VI et V, ces axones arborisent et convergent progressivement vers le barrel dans lequel ils forment une riche arborisation. Un petit nombre des branches « errantes », pleines de boutons synaptiques, pénètrent dans les barrels voisins. Deux axones NOR provenant de corps cellulaires très proches dans le thalamus peuvent avoir un cheminement très divergent lors de la traversée de la capsule interne et de la substance blanche sous-corticale mais, à leur entrée dans le cortex, ils sont distants d'au maximum 2 colonnes corticales de la colonne qui contient le barrel cible et ils convergent progressivement vers ce barrel. 2. Les axones de la souris mutante (BRL) ont le même trajet sous-cortical que les axones NOR, mais leur entrée dans le cortex somato-sensoriel primaire est aléatoire. A l'interface entre la substance blanche sous-corticale et le cortex, l'axone principal se divise rapidement en troncs axonaux qui traversent les couches VI et V d'une manière divergente pour arriver dans la couche IV. Cela contraste beaucoup avec la trajectoire des NOR qui convergent graduellement vers leur barrel cible. Le nombre de branches radiales que les axones BRL utilisent pour entrer dans le cortex et dans la couche IV est double par rapport aux axones NOR. Parmi ces branches, seules quelques-unes donnent des arborisations, les autres ne sont pas développées et leur morphologie est semblable à celle des branches formées par les axones de la souris normale lors du développement. Deux axones BRL issus de corps cellulaires proches dans le thalamus peuvent avoir une trajectoire très divergente jusqu'à leur entrée dans la couche IV, mais à ce niveau ils sont réorientés pour se retrouver et faire un nombre maximal de branches et boutons synaptiques dans la même région corticale. Dans un cas extrême, un des axones observés est entré dans le cortex à la limite entre l'aire somatosensorielle primaire et secondaire et a parcouru une distance de 2 mm pour retrouver son partenaire thalamique et donner avec celui-ci un nombre maximal de branches dans la même région de la couche IV. 3. Les mesures quantitatives ont montré que les arborisations corticales des axones NOR ont une longueur moyenne de 18mm et sont formées par 200 segments qui portent 1200 boutons synaptiques. Par rapport à la souris NOR, les axones BRL ont en moyenne la même longueur, le même nombre de segments et boutons synaptiques, mais donnent deux fois plus de branches radiales. La surface tangentielle occupée par les arborisations BRL dans la couche IV est 2 fois plus grande que celle des NOR. Cela signifie que les 1000 boutons synaptiques qui caractérisent les arborisations NOR et BRL dans la couche IV sont disséminés sur une surface tangentielle double chez les derniers, et donc que la densité des boutons par unité de surface corticale est en moyenne plus faible. En effet, l'augmentation de la surface corticale tangentielle des BRL est due aux surfaces de faible et moyenne densité synaptique (0 - 8 boutons / 400pn2) qui augmentent 2 fois tandis que les surfaces de haute densité synaptiques (8 - 64 boutons / 4001.tm2) sont les mêmes. Nous émettons l'hypothèse selon laquelle, durant le développement, les ATC de la souris BRL divergent et forment un nombre exubérant de branches. Grâce à cette divergence et aux branches supranuméraires, ils trouvent l'endroit de l'écorce où se trouvent leurs voisins thalamiques et arborisent abondamment dans cette région. Cependant, le déficit en AGI ne leurs permet pas par la suite, sous influence de l'activité périphérique, de retirer les branches qui se trouvent dans les endroits inappropriés de l'écorce, avec de possibles conséquences sur la discrimination tactile.

Toolbox of Countermeasures for Rural Two-Lane Curves [updated], TR-579, October 2013

The Federal Highway Administration (FHWA) estimates that 58 percent of roadway fatalities are lane departures, while 40 percent of fatalities are single-vehicle run-off-road (SVROR) crashes. Addressing lane-departure crashes is therefore a priority for national, state, and local roadway agencies. Horizontal curves are of particular interest because they have been correlated with increased crash occurrence. This toolbox was developed to assist agencies address crashes at rural curves. The main objective of this toolbox is to summarize the effectiveness of various known curve countermeasures. While education, enforcement, and policy countermeasures should also be considered, they were not included given the toolbox focuses on roadway-based countermeasures. Furthermore, the toolbox is geared toward rural two-lane curves. The research team identified countermeasures based on their own research, through a survey of the literature, and through discussions with other professionals. Coverage of curve countermeasures in this toolbox is not necessarily comprehensive. For each countermeasure covered, this toolbox includes the following information: description, application, effectiveness, advantages, and disadvantages.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

Prevalence of normal weight obesity in Switzerland: effect of various definitions

BACKGROUND: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI < 25 kg/m(2)), but its prevalence in the general population is unknown. AIM OF THE STUDY: To assess the prevalence of NWO in Switzerland according to different cut points used to define excess body fat. METHODS: Cross-sectional study including 3,213 women and 2,912 men aged 35-75 years. Body fat was assessed by bioelectrical impedance analysis and prevalence of NWO was assessed using four previously published definitions for excess body fat. RESULTS: Percent body fat increased with age: in men, the values (mean +/- SD) were 20.2 +/- 5.4, 23.0 +/- 5.4, 26.3 +/- 5.2 and 28.2 +/- 4.6 for age groups 35-44, 45-54, 55-64 and 65-75 years, respectively; the corresponding values for women were 29.9 +/- 7.8, 33.1 +/- 7.4, 36.7 +/- 7.5 and 39.6 +/- 6.9. In men, prevalence of NWO was <1% irrespective of the definition used. Conversely, in women, a 1- to 20-fold difference (from 1.4 to 27.8%) in NWO prevalence was found. The prevalence of NWO increased with age when age-independent cut points were used in women, but not in men. CONCLUSIONS: Prevalence of NWO is low in the general population and higher in women than in men. The prevalence is highly dependent on the criteria used to define excess body fat, namely in women. The use of gender- and age-specific cut points to define excess body fat is better than fixed or gender-specific only cut points.

Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered.

CTLA-4 is a critical negative regulator of T cell responses and CTLA-4-deficient (CTLA-4(-/-)) mice die of a lymphproliferative disease. Nevertheless, RAG-2-deficient mice reconstituted with a mixture of CTLA-4(-/-) and normal (CTLA-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their T cells do not express CTLA-4. Using such mixed chimeras, we analyzed the role of CTLA-4 in specific T cell responses to lymphocytic choriomeningitis virus, Leishmania major and mouse mammary tumor virus, which cause acute, chronic and persistent infections, respectively. The populations of antigen-specific CTLA-4(-/-)CD4(+) and CTLA-4(-/-)CD8(+) T cells became activated, expanded and contracted indistinguishably from CTLA-4(+/+)CD4(+) and CTLA-4(+/+)CD8(+) T cells after infection with all three pathogens. Thus, CTLA-4 is not involved in the down-regulation of specific T cell responses and peripheral deletion in a T cell-autonomous fashion.

Increased titers of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients with reduced H-ficolin levels but normal MASP-2 activity.

BACKGROUND AND AIMS: Mannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA. METHODS: ASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA. RESULTS: In CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p<0.001 and p=0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p=0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p=0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients. CONCLUSIONS: Our results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development.

P16 Mediated Suppression Of Telomerase In Normal And Malignant Human Breast Cells.

Summary The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.