Identification of optimal structural connectivity using functional connectivity and neural modeling.

The complex network dynamics that arise from the interaction of the brain's structural and functional architectures give rise to mental function. Theoretical models demonstrate that the structure-function relation is maximal when the global network dynamics operate at a critical point of state transition. In the present work, we used a dynamic mean-field neural model to fit empirical structural connectivity (SC) and functional connectivity (FC) data acquired in humans and macaques and developed a new iterative-fitting algorithm to optimize the SC matrix based on the FC matrix. A dramatic improvement of the fitting of the matrices was obtained with the addition of a small number of anatomical links, particularly cross-hemispheric connections, and reweighting of existing connections. We suggest that the notion of a critical working point, where the structure-function interplay is maximal, may provide a new way to link behavior and cognition, and a new perspective to understand recovery of function in clinical conditions.

Physiologically based pharmacokinetic modeling of arsenic in the mouse

A remarkable feature of the carcinogenicity of inorganic arsenic is that while human exposures to high concentrations of inorganic arsenic in drinking water are associated with increases in skin, lung, and bladder cancer, inorganic arsenic has not typically caused tumors in standard laboratory animal test protocols. Inorganic arsenic administered for periods of up to 2 yr to various strains of laboratory mice, including the Swiss CD-1, Swiss CR:NIH(S), C57Bl/6p53(+/-), and C57Bl/6p53(+/+), has not resulted in significant increases in tumor incidence. However, Ng et al. (1999) have reported a 40% tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. In order to investigate the potential role of tissue dosimetry in differential susceptibility to arsenic carcinogenicity, a physiologically based pharmacokinetic (PBPK) model for inorganic arsenic in the rat, hamster, monkey, and human (Mann et al., 1996a, 1996b) was extended to describe the kinetics in the mouse. The PBPK model was parameterized in the mouse using published data from acute exposures of B6C3F1 mice to arsenate, arsenite, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) and validated using data from acute exposures of C57Black mice. Predictions of the acute model were then compared with data from chronic exposures. There was no evidence of changes in the apparent volume of distribution or in the tissue-plasma concentration ratios between acute and chronic exposure that might support the possibility of inducible arsenite efflux. The PBPK model was also used to project tissue dosimetry in the C57Bl/6J study, in comparison with tissue levels in studies having shorter duration but higher arsenic treatment concentrations. The model evaluation indicates that pharmacokinetic factors do not provide an explanation for the difference in outcomes across the various mouse bioassays. Other possible explanations may relate to strain-specific differences, or to the different durations of dosing in each of the mouse studies, given the evidence that inorganic arsenic is likely to be active in the later stages of the carcinogenic process. [Authors]

Working with Iowans building a culture of conservation, Program Summary, November 2008

Over 94% of Iowa ’ s land is held in private ownership, and the programs of the Iowa Department of Agriculture and Land Stewardship Division of Soil Conservation (IDALS-DSC) have been established to work with these landowners. Over 90% of the landscape is used for agricultural production so much of our focus is in rural communities, but we haven’t overlooked the importance of land management in urban areas. It is crucial to understanding of both conservation and hydrology issues, that what happens on the landscape has immense consequences to the environmental health of our state and the quality of life we enjoy. IDALS-DSC is striving to integrate our programs with other agencies and local concerns to improve water and local concerns to improve water and soil quality throughout the state and nation.

Modeling the impact of lesions in the human brain.

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous ("resting-state") neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.

Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.

Although all brain cells bear in principle a comparable potential in terms of energetics, in reality they exhibit different metabolic profiles. The specific biochemical characteristics explaining such disparities and their relative importance are largely unknown. Using a modeling approach, we show that modifying the kinetic parameters of pyruvate dehydrogenase and mitochondrial NADH shuttling within a realistic interval can yield a striking switch in lactate flux direction. In this context, cells having essentially an oxidative profile exhibit pronounced extracellular lactate uptake and consumption. However, they can be turned into cells with prominent aerobic glycolysis by selectively reducing the aforementioned parameters. In the case of primarily oxidative cells, we also examined the role of glycolysis and lactate transport in providing pyruvate to mitochondria in order to sustain oxidative phosphorylation. The results show that changes in lactate transport capacity and extracellular lactate concentration within the range described experimentally can sustain enhanced oxidative metabolism upon activation. Such a demonstration provides key elements to understand why certain brain cell types constitutively adopt a particular metabolic profile and how specific features can be altered under different physiological and pathological conditions in order to face evolving energy demands.

Evaluation of occupational exposure: comparison of biological and environmental variabilities using physiologically based toxicokinetic modeling

PURPOSE: Few studies compare the variabilities that characterize environmental (EM) and biological monitoring (BM) data. Indeed, comparing their respective variabilities can help to identify the best strategy for evaluating occupational exposure. The objective of this study is to quantify the biological variability associated with 18 bio-indicators currently used in work environments. METHOD: Intra-individual (BV(intra)), inter-individual (BV(inter)), and total biological variability (BV(total)) were quantified using validated physiologically based toxicokinetic (PBTK) models coupled with Monte Carlo simulations. Two environmental exposure profiles with different levels of variability were considered (GSD of 1.5 and 2.0). RESULTS: PBTK models coupled with Monte Carlo simulations were successfully used to predict the biological variability of biological exposure indicators. The predicted values follow a lognormal distribution, characterized by GSD ranging from 1.1 to 2.3. Our results show that there is a link between biological variability and the half-life of bio-indicators, since BV(intra) and BV(total) both decrease as the biological indicator half-lives increase. BV(intra) is always lower than the variability in the air concentrations. On an individual basis, this means that the variability associated with the measurement of biological indicators is always lower than the variability characterizing airborne levels of contaminants. For a group of workers, BM is less variable than EM for bio-indicators with half-lives longer than 10-15 h. CONCLUSION: The variability data obtained in the present study can be useful in the development of BM strategies for exposure assessment and can be used to calculate the number of samples required for guiding industrial hygienists or medical doctors in decision-making.

Schedule of Debt Service and Coverage for Iowa State University of Science and Technology for the Academic Building Revenue Bond Funds for the year ended June 30, 2009

Schedule of Debt Service and Coverage for Iowa State University of Science and Technology for the Academic Building Revenue Bond Funds for the year ended June 30, 2009

Projectes de modelatge i simulació avançada de sistemes mitjançant l'entorn ARENA

RESUM En l’exercici de les funcions típiques de qualsevol activitat humana, l’home ha de prendre decisions d’un o altre tipus permanentment i aquesta situació porta afegit, per lo general risc i incertesa, el que compromet la qualitat i l’èxit de la decisió. Per ajudar i contrarestar aquesta situació, l’home ha desenvolupat a través del temps una diversitat d’eines que li permeten minimitzar el risc i la incertesa en la presa de decisions. La simulació és una d’aquestes eines. Mitjançant la seva aplicació no només s’aconsegueix la comesa anterior, sinó que també es minimitzen els costos involucrats en la decisió mitjançant un millor ús dels recursos, la disminució del temps emprat per a la seva realització i la minimització de les probabilitats de risc. Aquest projecte representa la continuació d’un primer estudi introductori de la simulació anomenat: Estudi i guia docent per a modelatge i simulació de sistemes mitjançant l’entorn ARENA [9]. Realitzat per l’alumna d’Enginyeria en Organització Industrial de la Universitat de Vic, Montse Carbonell Crosas, l’any 2008 i sota la codirecció del director d’aquest segon projecte, el professor Juli Ordeix Rigo. Aquest nou projecte s’inicia amb una primera part teòrica, continguda dins del primer volum, la qual reforça els conceptes teòrics referents a la simulació amb ARENA, ja vistos en l’anterior projecte. Complementant aquells considerats bàsics i els de més utilitat i finalitza introduint nous conceptes avançats. Els nous capítols de temàtica avançada, junt als primers més bàsics de la primera part són exercitats dins de la segona, formant el segon volum d’aquest projecte. El mateix requereix la participació activa de l’alumne, per tal de realitzar cadascun dels 89 exercicis pràctics que es plantegen i poder onsolidar l’aprenentatge teòric d’aquesta eina avançada de simulació fent consultes als apartats teòrics recomanats dins de cada exercici. La complexitat dels exercicis anirà augmentant gradualment i s’insisteix en seguir la metodologia presentada en el projecte per a realitzar-los tots de forma ordenada i ascendent. L’ alumne quan acabi la part pràctica, haurà consolidat tota la part teòrica i serà capaç d’exercir com analista per tal de generar els seus propis projecte de simulació.

State of Iowa Space Utilization and Building Study, October 9, 2000

Executive Summary Purposes of this Report: • Recommend the most logical and economical options to address state governmental space needs in the Polk County metropolitan area to the year 2010. • Include building size, location, phasing, financing, method of project delivery and estimated cost. • Develop a software tool to compare costs of leasing vs. ownership of space. Methodology: Identify: 1. Current amount and location of owned and leased space, by agency; 2. Types of space and whether best located on or off of the Capitol Complex; 3. Utilization of space, noting over-crowding and under-utilization; 4. Current number of workstations for full and part time employees, Personnel Employment Organization (PEO) workers, contractors, interns, etc.; and, 5. History of staff levels to assist in the prediction of staff growth. Scope: This report focuses on 10 state-owned buildings located on the Capitol Complex and 48 leased spaces in the Polk County metropolitan area. (See Figures 1 and 2.) • Due to a separate space study under way by the Legislature, implications of area and staff for the State Capitol building are included only for the Governor, Lieutenant Governor, Treasurer, Secretary of State, Auditor and the Department of Management. • Because it is largely a museum building that does not have office space available for other agencies, the area and staff of the Historical Building are not fully addressed. • Only the parking implications of the new Judicial Building are included in this study because the building space is under the jurisdiction of the Judicial Branch and not available for other agencies. Several state-owned buildings are not included in the scope of this report, generally because they have highly focused purposes, and their space is not available for assignment to other agencies. Several leased locations are not included for similar reasons, including leases that do not fall within the authority of the Department of General Services.

Fact Sheet: House and Building Fires, 2009

A fire can engulf a structure in a matter of minutes. Understanding the basic characteristics of fire and learning the proper safety practices can be the key to surviving a house or building fire.