FESTA. D2.4 Data analysis and modelling

The chapter of the handbook and the deliverable on data analysis will provide guidance and general principles for - pre-testing to check the usability of the system and the feasibility of the evaluation process, - controlling the consistency of the chain and the precision with different sampling schemes, - modelling the impact for each indicators and for an integrated evaluation including a systemic and multidisciplinary interpretation of the effects, - integrating and controlling the quality of space-time data from various sources (numerical, video, questionnaires), - selecting the appropriate statistical techniques for data processing, PI estimation and hypothesis testing in accordance to the list of indicators and experimental design, - scaling up from experimental data and identified models to population and network level. Experimentalists stress the role and importance of a preliminary field test in FOT. Three main objectives have been defined to make a preliminary diagnosis of usability of the systems and to check the relevance and feasibility of the evaluation process. These preliminary tests are very important for the practical deployment of the FOT as well as for the overall scientific evaluation process. Recommendations about the monitoring of local and global consistency of the chain of operations from the database extraction to the hypothesis testing are given, especially to ensure the validation of the calculation of the Performance indicators. Integration of the outputs of the different analysis and hypothesis testing requires a kind of meta-model and the competences of a multidisciplinary evaluation team, specially for interpretation of the system impact and secondary effects (behavioural adaptation, learning process, long-term retroaction, …). In cooperation with WP2.2, methods for data quality control have been defined. Four types of checks have been defined to complement the information of the data base in order to prepare the data for the analysis. Statistical methods have been described for three steps of the chain: data processing, PI calculation and hypothesis testing. They belong either to exploratory data analysis or to inferential analysis. Special attention has been given to the precision of the estimates of the effects or impacts of the system on the Performance indicators by stressing the importance of controlled randomisation and application of mixed regression models. Scaling-up relies upon the potential to extrapolate from the PIs to estimates of the impact at an aggregated level. Three approaches have been defined to carry out the scaling up process from direct estimations to simulation models with the related assumptions. Models and methodologies for scaling up results on traffic flow, environmental effects (e.g. PM10, CO2, Noise emissions in db) and traffic safety have been collected

Multisystem involvement, defective lysosomes, and impaired autophagy in a novel rat model of Nephropathic Cystinosis

Recessive mutations in the CTNS gene encoding the lysosomal transporter cystinosin cause cystinosis, a lysosomal storage disease leading to kidney failure and multisystem manifestations. A Ctns knock-out mouse model recapitulates features of cystinosis, but the delayed onset of kidney manifestations, phenotype variability, and strain effects limit its use for mechanistic and drug development studies. To provide a better model for cystinosis, we generated a Ctns knock-out rat model using CRISPR/Cas9 technology. The Ctns-/- rats display progressive cystine accumulation and crystal formation in multiple tissues including kidney, liver and thyroid. They show an early onset and progressive loss of urinary solutes, indicating generalized proximal tubule dysfunction, with development of typical swan-neck lesions, tubulointerstitial fibrosis and kidney failure, and decreased survival. The Ctns-/- rats also present crystals in the cornea, and bone and liver defects, like in patients. Mechanistically, the loss of cystinosin induces a phenotype switch associating abnormal proliferation and dedifferentiation, loss of apical receptors and transporters, and defective lysosomal activity and autophagy in the cells. Primary cultures of proximal tubule cells derived from the Ctns-/- rat kidneys confirmed the key changes caused by cystine overload, including reduced endocytic uptake, increased proliferation and defective lysosomal dynamics and autophagy. The novel Ctns-/- rat model and derived proximal tubule cell system provide invaluable tools to investigate the pathogenesis of cystinosis and to accelerate drug discovery

The Copper-Responsive RicR Regulon Contributes to Mycobacterium tuberculosis Virulence

ABSTRACT As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance in vitro and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity in vivo or that this regulon is also important for resistance against Cu-independent mechanisms of host defense. IMPORTANCE Mycobacterium tuberculosis is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of M. tuberculosis is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth, M. tuberculosis has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high‐fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high‐fat diet consumption and aging are only now beginning to be elucidated. In this review we discuss the potential role for age‐related metabolic disturbances serving as an important basis for deleterious perturbations in the aging brain. These data not only have important implications for understanding the basis of brain aging, but also may be important to the development of therapeutic interventions which promote successful brain aging.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bruce Keller, Annadora J.. State University of Louisiana; Estados UnidosFil: Morrison, Christopher D.. State University of Louisiana; Estados UnidosFil: Fernandez Kim, Sun Ok. State University of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University of Louisiana; Estados UnidosFil: Zhang, Le. State University of Louisiana; Estados UnidosFil: Dasuri, Kalavathi. State University of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University of Louisiana; Estados Unido

Volume 05

Introduction from Dean Dr. Charles Ross The Tallis House as an Extension of Emily Tallis in McEwan\u27s Atonement by Ian Karamarkovich Graphic Design by Jessica Cox Graphic Design by Kyle Fowlkes Graphic Design by Allison Pawlowski Incorporating Original Research in The Classroom: A Case Study Analyzing the Influence of the Chesapeake Bay on Local Temperatures by Kaitlin Major, Carrie Dunham and Dr. Kelsey Scheitlin Graphic Design by Kathryn Grayson Graphic Design by Ashley Johnson Facing the Music: Environmental Impact Assessment of Building A Concert Hall on North Campus by Jennifer Nehrt, Kelsey Stolzenbach And Dr. Kelsey Scheitlin Art by Kristin McQuarrie Art by Sara Nelson Art by Melisa Michelle Prosocial Behavior as a Result of Prosocial Music by Jessica Sudlow Graphic Design by Perry Bason Graphic Design by Danielle Dmuchawski Graphic Design by Mariah Asbell Graphic Design by Matthew Sakach Identifying Pathogenic Salmonella Serotypes Isolated from Prince Edward County, VA Waterways via Mutiplex PCR Analysis by Timothy Smith, Jr. Art by Annaliese Troxell Art by T. Dane Summerell Development of Salicylidene Anilines for Application in the High School Laboratory by Sarah Ganrude Graphic Design by Malina Rutherford Graphic Design by Hannah Hopper, and Matthew Sakach Because That\u27s What Daddies Do: Effects of Fathering Patterns on Son\u27s Self and Gender Identities by John Berry, Jr. Graphic Design by James Early Graphic Design by Colleen Festa The Influence of Tropical Cyclones on Chesapeake Bay Dead Zones by Chelsea D. Taylor and Dr. Kelsey Scheitlin Graphic Design by Michelle Maddox Graphic Design by Kaitlyn Smith Graphic Design by Sarah Schu Graphic Design by Perry Bason, Cabell Edmunds, Katherine Grayson, Matthew Sakach, and Kayla Torna

Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose

<p>Abstract</p> <p>Background</p> <p>To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus.</p> <p>Methods</p> <p>Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity.</p> <p>Results</p> <p>Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean ± SEM HOMA2-IR values of 1.0 ± 0.1, 1.6 ± 0.2 and 2.5 ± 0.3 and Matsuda insulin sensitivity index values of 15.6 ± 2.0, 8.8 ± 1.2 and 6.0 ± 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 ± 80.7 (NFG), 684.0 ± 57.3 (IFG) and 188.3 ± 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison).</p> <p>Conclusion</p> <p>These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.</p

Selection of Reserves for Woodland Caribou Using an Optimization Approach

Habitat protection has been identified as an important strategy for the conservation of woodland caribou (Rangifer tarandus). However, because of the economic opportunity costs associated with protection it is unlikely that all caribou ranges can be protected in their entirety. We used an optimization approach to identify reserve designs for caribou in Alberta, Canada, across a range of potential protection targets. Our designs minimized costs as well as three demographic risk factors: current industrial footprint, presence of white-tailed deer (Odocoileus virginianus), and climate change. We found that, using optimization, 60% of current caribou range can be protected (including 17% in existing parks) while maintaining access to over 98% of the value of resources on public lands. The trade-off between minimizing cost and minimizing demographic risk factors was minimal because the spatial distributions of cost and risk were similar. The prospects for protection are much reduced if protection is directed towards the herds that are most at risk of near-term extirpation

X-ray fluorescence analysis of superalloy leach liquors using a thin-film technique

"The U.S. Bureau of Mines has developed a thin-film x-ray fluorescence technique to rapidly determine cu, ni, CO, fe, and cr in superalloy leach liquors. Total analysis time per sample was less than 15 min, as opposed to several hours for traditional wet chemical methods. Precision and accuracy were checked by replicate analyses of solutions similar in composition to leach liquors, whose analyte concentrations were well known. Coefficients of variation for all elements were found to be less than 2 pct. With the exception of the results for fe, all relative errors of estimation were also found to be less than 2 pct. Bulk liquids are not introduced into the spectrometer; thus, the potential for damage to the instrument by leakage of corrosive liquids is eliminated." - NIOSHTIC-2NIOSHTIC no. 1000725