Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major.

Metacaspases are cysteine peptidases that could play a role similar to caspases in the cell death programme of plants, fungi and protozoa. The human protozoan parasite Leishmania major expresses a single metacaspase (LmjMCA) harbouring a central domain with the catalytic dyad histidine and cysteine as found in caspases. In this study, we investigated the processing sites important for the maturation of LmjMCA catalytic domain, the cellular localization of LmjMCA polypeptides, and the functional role of the catalytic domain in the cell death pathway of Leishmania parasites. Although LmjMCA polypeptide precursor form harbours a functional mitochondrial localization signal (MLS), we determined that LmjMCA polypeptides are mainly localized in the cytoplasm. In stress conditions, LmjMCA precursor forms were extensively processed into soluble forms containing the catalytic domain. This domain was sufficient to enhance sensitivity of parasites to hydrogen peroxide by impairing the mitochondrion. These data provide experimental evidences of the importance of LmjMCA processing into an active catalytic domain and of its role in disrupting mitochondria, which could be relevant in the design of new drugs to fight leishmaniasis and likely other protozoan parasitic diseases.

Analysis of Markers for Recent Alcohol Consumption by Capillary Zone Electrophoresis and an Immunochemical Method

Le but de ce travail doctoral était le développement de méthodes analytiques pour la détermination dethyl glucuronide et dethyl sulfate. Ces deux substances sont des métabolites directs de lethanol qui peuvent être détectées pendant des heures jusqu'à des jours dans des fluides corporels, après que léthanol ait été complètement éliminé du corps humain. Ce sont donc des marqueurs de consommation récente d'alcool.La majorité des expériences ont été effectuées en utilisant l'électrophorèse capillaire. Il était envisagé de fournir des méthodes utilisables dans des laboratoires de routine. Des méthodes électrophorétiques ont été développées et optimisées pour la détermination dethyl sulfate dans le sérum et l'urine ainsi que pour lethyl glucuronide dans le sérum. Lethyl glucuronide urinaire a pu être déterminé par un immunoassay commerciale qui a en plus été adapté avec succès pour des échantillons de sérum. Avec toutes ces méthodes d'analyse il était possible d'observer les deux marqueurs de consommation d'alcool récente, même une consommation aussi basse qu'un verre de boissons alcooliques.Finalement, une étude englobant plus de 100 échantillons aété effectuée avec l'ambition de déterminer les valeurs de référence pour lethyl glucuronide dans le sérum et l'urine. De plus, la nécessité de normaliser les échantillons d'urine par rapport à la dilution a été investiguée. Grâce à cette étude des valeurs de cut-off et une base statistique pour l'interprétation probabiliste ont pu être proposées.

Chemical and physical composition of grain-type and food-type soybean for food processing

The objective of this work was to evaluate the chemical and physical characteristics of grains of soybean (Glycine max) cultivars for food processing. The soybean cultivars evaluated were: grain-type - BRS 133 and BRS 258; food-type - BRS 213 (null lipoxygenases), BRS 267 (vegetable-type) and BRS 216 (small grain size). BRS 267 and BRS 216 cultivars showed higher protein content, indicating that they could promote superior nutritional value. BRS 213 cultivar showed the lowest lipoxygenase activity, and BRS 267, the lowest hexanal content. These characteristics can improve soyfood flavor. After cooking, BRS 267 cultivar grains presented a higher content of aglycones (more biologically active form of isoflavones) and oleic acid, which makes it proper for functional foods and with better stability for processing, and also showed high content of fructose, glutamic acid and alanine, compounds related to the soybean mild flavor. Because of its large grain size, BRS 267 is suitable for tofu and edamame, while small-grain-sized BRS 216 is good for natto and for soybean sprouts production. BRS 216 and BRS 213 cultivars presented shorter cooking time, which may be effective for reducing processing costs.

Implementation of the Federal Highway Administration Final Rule on Work Zone Safety and Mobility, 2007

The Federal Highway Administration published the final rule updating 23 CFR 630 Subpart J in September 2004. The revised rule requires agencies using federal funding to address both safety and mobility in planning and construction of roadway improvements. The Iowa Department of Transportation (Iowa DOT) requested the assistance of the Center for Transportation and Research in developing guidance for a policy and procedures to comply with the final rule. This report describes an in-depth examination of current Iowa DOT project development processes for all types of improvements, including maintenance, as well as a detailed characterization of work zone impact considerations throughout project completion. To comply with both the letter and perceived intent of the final rule on safety and mobility, the report features a suggested work zone policy statement and suggested revisions in the Iowa DOT project development processes, including a definition of the key element: significant projects.

Towards a diffusion image processing validation and accuracy prediction framework

Validation is the main bottleneck preventing theadoption of many medical image processing algorithms inthe clinical practice. In the classical approach,a-posteriori analysis is performed based on someobjective metrics. In this work, a different approachbased on Petri Nets (PN) is proposed. The basic ideaconsists in predicting the accuracy that will result froma given processing based on the characterization of thesources of inaccuracy of the system. Here we propose aproof of concept in the scenario of a diffusion imaginganalysis pipeline. A PN is built after the detection ofthe possible sources of inaccuracy. By integrating thefirst qualitative insights based on the PN withquantitative measures, it is possible to optimize the PNitself, to predict the inaccuracy of the system in adifferent setting. Results show that the proposed modelprovides a good prediction performance and suggests theoptimal processing approach.

Evaluation of Work Zone Speed Reduction Measures, 2000

The Iowa Department of Transportation (DOT) has made improving work zone (WZ) safety a high priority. Managing vehicle speeds through work zones is perceived to be an important factor in achieving this goal. A number of speed reduction techniques are currently used by transportation agencies throughout the country to control speeds and reduce speed variation at work zones. The purpose of this project is to study these and other applicable work zone speed reduction strategies. Furthermore, this research explores transportation agencies' policies regarding managing speeds in long-term, short-term, and moving work zones. This report consists of three chapters. The first chapter, a literature review, examines the current speed reduction practices at work zones and provides a review of the relevant literature. The speed control strategies reviewed in this chapter range from posting regulatory and advisory speed limit signs to using the latest radar technologies to reduce speeds at work zones. The second chapter includes a short write-up for each identified speed control technique. The write-up includes a description, the results of any field tests, the benefits and the costs of the technology or technique. To learn more about other state policies regarding work zone speed reduction and management, the Center for Transportation Research and Education conducted a survey. The survey consists of six multipart questions. The third chapter provides summaries of the response to each question.

Molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease.

A crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein (GP) that is essential for virus-host cell attachment and entry. The maturation of the arenavirus GP precursor (GPC) critically depends on proteolytic processing by the cellular proprotein convertase (PC) subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P). Here we undertook a molecular characterization of the SKI-1/S1P processing of the GPCs of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and the pathogenic Lassa virus (LASV). Previous studies showed that the GPC of LASV undergoes processing in the endoplasmic reticulum (ER)/cis-Golgi compartment, whereas the LCMV GPC is cleaved in a late Golgi compartment. Herein we confirm these findings and provide evidence that the SKI-1/S1P recognition site RRLL, present in the SKI-1/S1P prodomain and LASV GPC, but not in the LCMV GPC, is crucial for the processing of the LASV GPC in the ER/cis-Golgi compartment. Our structure-function analysis revealed that the cleavage of arenavirus GPCs, but not cellular substrates, critically depends on the autoprocessing of SKI-1/S1P, suggesting differences in the processing of cellular and viral substrates. Deletion mutagenesis showed that the transmembrane and intracellular domains of SKI-1/S1P are dispensable for arenavirus GPC processing. The expression of a soluble form of the protease in SKI-I/S1P-deficient cells resulted in the efficient processing of arenavirus GPCs and rescued productive virus infection. However, exogenous soluble SKI-1/S1P was unable to process LCMV and LASV GPCs displayed at the surface of SKI-I/S1P-deficient cells, indicating that GPC processing occurs in an intracellular compartment. In sum, our study reveals important differences in the SKI-1/S1P processing of viral and cellular substrates.

Feasibility of Visualization and Simulation Applications to Improve Work Zone Safety and Mobility

Visualization is a relatively recent tool available to engineers for enhancing transportation project design through improved communication, decision making, and stakeholder feedback. Current visualization techniques include image composites, video composites, 2D drawings, drive-through or fly-through animations, 3D rendering models, virtual reality, and 4D CAD. These methods are used mainly to communicate within the design and construction team and between the team and external stakeholders. Use of visualization improves understanding of design intent and project concepts and facilitates effective decision making. However, visualization tools are typically used for presentation only in large-scale urban projects. Visualization is not widely accepted due to a lack of demonstrated engineering benefits for typical agency projects, such as small- and medium-sized projects, rural projects, and projects where external stakeholder communication is not a major issue. Furthermore, there is a perceived high cost of investment of both financial and human capital in adopting visualization tools. The most advanced visualization technique of virtual reality has only been used in academic research settings, and 4D CAD has been used on a very limited basis for highly complicated specialty projects. However, there are a number of less intensive visualization methods available which may provide some benefit to many agency projects. In this paper, we present the results of a feasibility study examining the use of visualization and simulation applications for improving highway planning, design, construction, and safety and mobility.

The Effect of the No-Passing Zone Sign on "Passing" Accidents, 1963

The No Passing Zone sign (Wl0-4) was designed in 1958 for the purpose of informing the driver contemplating a passing maneuver of hazardous sight conditions ahead. This warning sign, of pennent shape design, was placed on the left side of the road so as to be more conspicuous to the intended driver. During the two year period 1959-1960, the Wl0-4 signs were erected throughout the Iowa Primary Road System.

Iowa Study of No Passing Zone Signing, 1962

This report is compiled from data gathered by interviewing motorists to sample their opinion of Iowa's method of supplementing the yellow barrier line pavement marking of no passing zones on primary highways with yellow pennant shaped "No Passing Zone" signs mounted on the left shoulder of the highway. The effective designation of no passing zones is one form of control that can contribute to a reduction in the number of fatal high-speed head-on collisions resulting from passing in areas which do not afford sufficient sight distance of approaching traffic. It is the purpose of this report to present an evaluation of the Iowa "No Passing Zone" sign by individuals from all states who have traveled on Iowa's primary highways and who must obey the no passing zone restrictions and be warned by this sign of the presence of the zones. The "No Passing Zone" sign was formulated and approved by the Governor's Safety Committee a short time prior to the experimental erection of the signs. The Governor's Safety Committee adopted this sign as they felt that such a sign should be distinctive (not similar to any other type of sign) and easily visible to a driver attempting a passing maneuver.

Decision-theoretic reflections on processing a fingermark

A recent publication in this journal [Neumann et al., Forensic Sci. Int. 212 (2011) 32-46] presented the results of a field study that revealed the data provided by the fingermarks not processed in a forensic science laboratory. In their study, the authors were interested in the usefulness of this additional data in order to determine whether such fingermarks would have been worth submitting to the fingermark processing workflow. Taking these ideas as a starting point, this communication here places the fingermark in its context of a case brought before a court, and examines the question of processing or not processing a fingermark from a decision-theoretic point of view. The decision-theoretic framework presented provides an answer to this question in the form of a quantified expression of the expected value of information (EVOI) associated with the processed fingermark, which can then be compared with the cost of processing the mark.

Bayesian Markov-chain-Monte-Carlo inversion of time-lapse cross hole ground-penetrating radar data to characterize the vadose zone at the Arrenaes field site, Denmark

The ground-penetrating radar (GPR) geophysical method has the potential to provide valuable information on the hydraulic properties of the vadose zone because of its strong sensitivity to soil water content. In particular, recent evidence has suggested that the stochastic inversion of crosshole GPR traveltime data can allow for a significant reduction in uncertainty regarding subsurface van Genuchten-Mualem (VGM) parameters. Much of the previous work on the stochastic estimation of VGM parameters from crosshole GPR data has considered the case of steady-state infiltration conditions, which represent only a small fraction of practically relevant scenarios. We explored in detail the dynamic infiltration case, specifically examining to what extent time-lapse crosshole GPR traveltimes, measured during a forced infiltration experiment at the Arreneas field site in Denmark, could help to quantify VGM parameters and their uncertainties in a layered medium, as well as the corresponding soil hydraulic properties. We used a Bayesian Markov-chain-Monte-Carlo inversion approach. We first explored the advantages and limitations of this approach with regard to a realistic synthetic example before applying it to field measurements. In our analysis, we also considered different degrees of prior information. Our findings indicate that the stochastic inversion of the time-lapse GPR data does indeed allow for a substantial refinement in the inferred posterior VGM parameter distributions compared with the corresponding priors, which in turn significantly improves knowledge of soil hydraulic properties. Overall, the results obtained clearly demonstrate the value of the information contained in time-lapse GPR data for characterizing vadose zone dynamics.

The Dutung-Thaktote extensional fault zone and nappe structures documented by illite crystallinity and clay-mineral paragenesis in the Tethys Himalaya between Spiti river and Tso Morari, NW India

Numerous measurements by XRD of the Scherrer width at half-peak height (001 reflection of illite), coupled with analyses of clay-size assemblages, provide evidence for strong variations in the conditions of low temperature metamorphism in the Tethyan Himalaya metasediments between the Spiti river and the Tso Morari. Three sectors can be distinguished along the Spiti river-Tso Morari transect. In the SW, the Takling and Parang La area is characterised by a metamorphism around anchizone-epizone boundary conditions. Further north, in the Dutung area, the metamorphic grade abruptly decreases to weak diagenesis, with the presence of mixed-layered clay phases. At the end of the profile towards the NE, a progressive metamorphic increase up to greenschist facies is recorded, marked by the appearance of biotite and chloritoid. The combination of these data with the structural. observations permits to propose that a nappe stack has been crosscut by the younger Dutung-Thaktote extensional fault zone (DTFZ). The change in metamorphism across this zone helps to assess the displacements which occurred during synorogenic extension. In the SW and NE parts of the studied transect, a burial of 12 km has been estimated, assuming a geothermal gradient of 25 degrees C/km. In the SW part, this burial is due to the juxtaposition of the Shikar Beh and Mata nappes and in the NE part, solely to burial beneath the Mata nappe. In the central part of the profile, the effect of the DTFZ is to bring down diagenetic sediments in-between the two aforesaid metamorphic zones. The offset along the Dutung-Thaktote normal faults is estimated at 16 km.