Estimating parameters for generalized mass action models using constraint propagation.

As modern molecular biology moves towards the analysis of biological systems as opposed to their individual components, the need for appropriate mathematical and computational techniques for understanding the dynamics and structure of such systems is becoming more pressing. For example, the modeling of biochemical systems using ordinary differential equations (ODEs) based on high-throughput, time-dense profiles is becoming more common-place, which is necessitating the development of improved techniques to estimate model parameters from such data. Due to the high dimensionality of this estimation problem, straight-forward optimization strategies rarely produce correct parameter values, and hence current methods tend to utilize genetic/evolutionary algorithms to perform non-linear parameter fitting. Here, we describe a completely deterministic approach, which is based on interval analysis. This allows us to examine entire sets of parameters, and thus to exhaust the global search within a finite number of steps. In particular, we show how our method may be applied to a generic class of ODEs used for modeling biochemical systems called Generalized Mass Action Models (GMAs). In addition, we show that for GMAs our method is amenable to the technique in interval arithmetic called constraint propagation, which allows great improvement of its efficiency. To illustrate the applicability of our method we apply it to some networks of biochemical reactions appearing in the literature, showing in particular that, in addition to estimating system parameters in the absence of noise, our method may also be used to recover the topology of these networks.

Health consultation : Mid-America Tanning Company, Sergeant Bluff, Woodbury County, Iowa EPA facility ID: IAD085824688 (2005)

On June 23, 2004, the U.S. Environmental Protection Agency (EPA) announced its intention to remove the Mid-American Tanning Company site from the National Priorities List (NPL). The EPA is inviting public comment on the proposed de-listing of the site from the NPL. The Iowa Department of Public Health in cooperation with the Agency for Toxic Substances and Disease Registry (ATSDR) prepared this health consultation to review the current status of the Mid-America Tanning Company site and to provide an evaluation of any public health consequences of de-listing the site. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Health consultation : Silver City petroleum release and municipal wells, Silver City, Mills County, Iowa (2005)

A resident of Silver City, Iowa requested the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to evaluate the health impacts of a petroleum release in Silver City, Iowa, and the health impacts from the presence of chemicals detected in wells utilized as the source of municipal water for the citizens of Silver City and in the treated municipal water supply. This health consultation addresses exposure to residents of Silver City to organic chemicals within the groundwater and water supply and potential health effects at the levels of exposure. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Health consultation : jet gas spill site, Lowell, Henry County, Iowa (2004)

An attorney representing seven property owners in Lowell, Iowa, requested the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Jet Gas Spill Site. The attorney asked the IDPH to provide comments concerning the potential and likely health effects to her clients due to exposure from the spill. The specific issues to be addressed are listed in this health consultation. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Health consultation : Climbing Hill groundwater contaminiation site, Climbing Hill, Woodbury County, Iowa (2004)

The Iowa Department of Natural Resources (IDNR) asked the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Climbing Hill, Iowa, groundwater contamination site. IDNR wants to know if the site poses a public health hazard. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations. Climbing Hill is an unincorporated town in Woodbury County, Iowa, approximately 15 miles southeast of Sioux City. The town has approximately 120 residents. All of the residents and most businesses within the town use private wells to supply their drinking water. The local restaurant has an individual well that is classified as a public water supply system because it has the potential to serve more than 25 people in a day. Several wells in the town have become contaminated with gasoline and diesel fuel leaking from two underground storage tanks. All of the wells are roughly 75–80 feet deep (R. Cardinale, IDNR, Underground Storage Tank Section, personal communication, January 30, 2004).

Health consultation : Hills, Iowa perchlorate groundwater contamination site, Hills, Johnson County, EPA facility ID: IAN 000704368 (2004)

The U. S. Environmental Protection Agency (EPA) Region 7, as well as concerned citizens, asked the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to perform a health consultation for the Hills, Iowa Perchlorate Groundwater Contamination Site. Specifically, IDPH was asked to determine if EPA’s action of providing bottled water to residents whose private wells had concentrations of greater than 18 μg/L (micrograms per liter) or 18 parts per billion (ppb) perchlorate is protective of public health, and to address some community health concerns. The information included in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Health consultation : Rolfe aboveground storage tank petroleum bulk plant targeted brownfields assessment, Railroad Street and 300th Avenue, Rolfe, Pocahontas County, Iowa (2005)

The Iowa Department of Natural Resources (IDNR) has requested the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program evaluate future health impacts of exposures at a former aboveground storage tank site located in Rolfe, Iowa. The former aboveground storage tank site is located to the southwest of the intersection of Railroad Street and 300th Avenue in Rolfe, Iowa. This site is undergoing a Targeted Brownfields Assessment conducted by the Contaminated Sites Section of the IDNR. This health consultation addresses potential health risks to people from future exposure to the soil within the property boundary, and any health impacts resulting from contaminated groundwater beneath the site property. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions.

TWEAK (TNF homologue with weak apoptosis-inducing activity) and Fn14 (fibroblast growth factor-inducible protein 14) are members of the tumor necrosis factor (TNF) ligand and receptor super-families. Having observed that Xenopus Fn14 cross-reacts with human TWEAK, despite its relatively low sequence homology to human Fn14, we examined the conservation in tertiary fold and binding interfaces between the two species. Our results, combining NMR solution structure determination, binding assays, extensive site-directed mutagenesis and molecular modeling, reveal that, in addition to the known and previously characterized β-hairpin motif, the helix-loop-helix motif makes an essential contribution to the receptor/ligand binding interface. We further discuss the insight provided by the structural analyses regarding how the cysteine-rich domains of the TNF receptor super-family may have evolved over time. DATABASE: Structural data are available in the Protein Data Bank/BioMagResBank databases under the accession codes 2KMZ, 2KN0 and 2KN1 and 17237, 17247 and 17252. STRUCTURED DIGITAL ABSTRACT: TWEAK binds to hFn14 by surface plasmon resonance (View interaction) xeFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction) TWEAK binds to xeFn14 by surface plasmon resonance (View interaction) hFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction).

Quantitative multi-parameter mapping of R1, PD(*), MT, and R2(*) at 3T: a multi-center validation.

Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM) was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1 mm high-resolution maps of the longitudinal relaxation rate (R1 = 1/T1), effective proton density (PD(*)), magnetization transfer saturation (MT) and effective transverse relaxation rate (R2(*) = 1/T2(*)). MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV) for typical morphometric measures [i.e., gray matter (GM) probability maps used in voxel-based morphometry] and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1 and 8%, respectively, except for the inter-site CoV of R2(*) (<20%). The GM probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived GM probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

Fluorescence flow cytometer to determine urine particle reference intervals in doping control samples.

Background: Urine is still the matrix of choice to fight against doping, because it can be collected non-invasively during anti-doping tests. Most of the World Anti-Doping Agency's accredited laboratories have more than 20 years experience in analyzing this biological fluid and the majority of the compounds listed in the 2010 Prohibited List - International Standard are eliminated through the urinary apparatus. Storing and transporting urine samples for doping analyses does not include a specific protocol to prevent microbial and thermal degradation. The use of a rapid and reliable screening method could enable determine reference intervals for urine specimens in doping control samples and evaluate notably the prevalence of microbial contamination known to be responsible for the degradation of chemical substances in urine.Methods: The Sysmex(R) UF-500i is a recent urine flow cytometer analyzer capable of quantifying BACT and other urinary particles such as RBC, WBC, EC, DEBRIS, CAST, PATH. CAST, YLC, SRC as well as measuring urine conductivity. To determine urine anti-doping reference intervals, 501 samples received in our laboratory over a period of two months were submitted to an immediate examination. All samples were collected and then transported at room temperature. Analysis of variance was performed to test the effects of factors such as gender, test type [in-competition, out-of-competition] and delivery time.Results: The data obtained showed that most of the urine samples were highly contaminated with bacteria. The other urine particles were also very different according to the factors.Conclusions: The Sysmex(R) UF-500i was capable of providing a snapshot of urine particles present in the samples at the time of the delivery to the laboratory. These particles, BACT in particular, gave a good idea of the possible microbial degradation which had and/or could have occurred in the sample. This information could be used as the first quality control set up in WADA (World Anti-Doping Agency) accredited laboratories to determine if steroid profiles, endogenous and prohibited substances have possibly been altered. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Sharing Open Source License and Copyright Data with SPDX

Organizations across the globe are creating and distributing products that include open source software. To ensure compliance with the open source licenses, each company needs to evaluate exactly what open source licenses and copyrights are included - resulting in duplicated effort and redundancy. This talk will provide an overview of a new Software Package Data Exchange (SPDX) specification. This specification will provide a common format to share information about the open source licenses and copyrights that are included in any software package, with the goal of saving time and improving data accuracy. This talk will review the progress of the initiative; discuss the benefits to organizations using open source and share information on how you can contribute.

Factors that determine the evolution of high-growth businesses

The study herein discusses research aimed at elucidating the factors that contribute to a business' ability to maintain high growth. The database from the Iberian Balance Sheet Analysis System (SABI, from its initials in Spanish) was used to identify 250 industrial Catalonian businesses with high growth during 2004-2007. These companies participated in a survey on strategies and management practices; in 2013, they were re-analyzed to investigate the factors that contributed to continued growth for certain companies. Through diverse statistical techniques, business policies related to quality, innovation, internationalization and finance were shown to influence business growth and sustainability over time. High-growth businesses have been studied throughout the world, but this is the first study to investigate the evolution of businesses after a high-growth phase.

Paperikoneen lajinvaihdon säätötapojen vertailu

Työn tavoitteena oli vertailla paperikoneen lajinvaihdon säätötapoja. Vertailun kohteina olivat Metso Automationin IQGradeChange lajinvaihto-ohjelmisto ja operaattoreiden käsin tekemät lajinvaihdot. Kattavan tutkimusaineiston saamiseksi paperikoneen lajinvaihtodataa kerättiin seitsemän kuukauden ajan. Kerätyt lajinvaihdot käytiin läpi Matlab-ympäristössä lajinvaihtoaikojen selvittämiseksi. Lisäksi lajinvaihdoista laskettiin tuotannon muutokset ((t/h)/min) vanhan ja uudenlajin välillä, jotta päästiin selvyyteen lajinvaihdon laajuudesta ja eri lajinvaihtotapojen suorituskyvyistä. Koeajojaksona paperikoneelta kerättiin kaikkiaan 130 lajinvaihdon tiedot. Näistä lajinvaihdoista 58 tehtiin IQGradeChange lajinvaihto-ohjelmistolla ja 72 oli operaattoreiden käsin tekemiä lajinvaihtoja. Kerätyistä 130 lajinvaihdosta 27 kappaletta päättyi ratakatkoon. Yhtenä tehtävänä olikin tutkia katkoon päättyneitä lajinvaihtoja.

Stability of cognitive performance in children with mild intellectual disability.

AIM: Longitudinal studies that have examined cognitive performance in children with intellectual disability more than twice over the course of their development are scarce. We assessed population and individual stability of cognitive performance in a clinical sample of children with borderline to mild non-syndromic intellectual disability. METHOD: Thirty-six children (28 males, eight females; age range 3-19y) with borderline to mild intellectual disability (Full-scale IQ [FSIQ] 50-85) of unknown origin were examined in a retrospective clinical case series using linear mixed models including at least three assessments with standardized intelligence tests. RESULTS: Average cognitive performance remained remarkably stable over time (high population stability, drop of only 0.38 IQ points per year, standard error=0.39, p=0.325) whereas individual stability was at best moderate (intraclass correlation of 0.58), indicating that about 60% of the residual variation in FSIQ scores can be attributed to between-child variability. Neither sex nor socio-economic status had a statistically significant impact on FSIQ. INTERPRETATION: Although intellectual disability during childhood is a relatively stable phenomenon, individual stability of IQ is only moderate, likely to be caused by test-to-test reliability (e.g. level of child's cooperation, motivation, and attention). Therefore, clinical decisions and predictions should not rely on single IQ assessments, but should also consider adaptive functioning and previous developmental history.

EMS mutagenesis in mature seed-derived rice calli as a new method for rapidly obtaining tilling mutant populations.

Background: TILLING (Targeting Induced Local Lesions IN Genomes) is a reverse genetic method that combines chemical mutagenesis with high-throughput genome-wide screening for point mutation detection in genes of interest. However, this mutation discovery approach faces a particular problem which is how to obtain a mutant population with a sufficiently high mutation density. Furthermore, plant mutagenesis protocols require two successive generations (M1, M2) for mutation fixation to occur before the analysis of the genotype can begin. Results: Here, we describe a new TILLING approach for rice based on ethyl methanesulfonate (EMS) mutagenesis of mature seed-derived calli and direct screening of in vitro regenerated plants. A high mutagenesis rate was obtained (i.e. one mutation in every 451 Kb) when plants were screened for two senescence-related genes. Screening was carried out in 2400 individuals from a mutant population of 6912. Seven sense change mutations out of 15 point mutations were identified. Conclusions: This new strategy represents a significant advantage in terms of time-savings (i.e. more than eight months), greenhouse space and work during the generation of mutant plant populations. Furthermore, this effective chemical mutagenesis protocol ensures high mutagenesis rates thereby saving in waste removal costs and the total amount of mutagen needed thanks to the mutagenesis volume reduction.