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Sample records for biochemical confounders nfr

  1. A cytoplasmic protein, NfrC, is required for bacteriophage N4 adsorption.

    PubMed Central

    Kiino, D R; Licudine, R; Wilt, K; Yang, D H; Rothman-Denes, L B

    1993-01-01

    At least four genes are required for irreversible adsorption of bacteriophage N4. nfrA and nfrB have been characterized previously and encode an outer membrane protein and inner membrane protein, respectively. The nfrC gene product is characterized in detail in this study. We have mapped the nfrD locus to min 52 on the Escherichia coli linkage map. Maxicell analysis of nfrC and a null allele (nfrC2) cloned into a high-copy-number plasmid shows its gene product to be 42 kDa in size. We determined the nfrC nucleotide sequence which predicts a gene product of 42 kDa. Western blots (immunoblots) of Escherichia coli proteins after cellular fractionation show NfrC to be a cytoplasmic protein which is required for irreversible bacteriophage N4 adsorption, an event occurring at the cell surface. Images PMID:8226648

  2. Performance of a novel Viresolve NFR virus filter.

    PubMed

    Brough, Helene; Antoniou, Chris; Carter, Jeffrey; Jakubik, Jocelyn; Xu, Yuan; Lutz, Herbert

    2002-01-01

    Mammalian cell-expressed therapeutic proteins are particularly vulnerable to contamination by endogenous retrovirus-like particles (RVLPs). The Viresolve NFR filter was designed to meet the critical requirement of manufacturing a safe and virus-free therapeutic by retaining RVLPs by a minimum of six log reduction value (LRV). The NFR designation refers to retrovirus removal in a normal flow format. To qualify the product, we tested two model viruses: the 78 nm diameter phi6 bacteriophage and the 80-110 nm diameter Xenotropic Murine Leukemia Virus (X-MuLV). Robust retention was demonstrated over a wide range of process parameters. Viresolve NFR filters also retain other model adventitious viruses including 70-85 nm diameter Reovirus 3 (Reo3), 70-90 nm diameter Adenovirus 2 (Ad2), and 53 nm diameter PR772 by >6 LRV. In addition to these model viruses, the filter retains >7 LRV of both the mycoplasma Acholeplasma laidlawii and the bacterium Brevundimonas diminuta. Protein passage is shown to be consistently high (95-100%) for a variety of therapeutic protein products, including monoclonal antibodies. Characterization of the filter in specific applications is made simple by availability of ultralow surface area (5 cm(2)) disks, which are shown to scale linearly to the manufacturing scale pleated-filters. Viresolve NFR filters provide consistent water permeability performance (34-37 LMH/psi) and show very little plugging for all feedstocks evaluated. The Viresolve NFR filter incorporates Retropore, a unique asymmetric polyethersulfone membrane, the surface of which has been modified to minimize protein binding. PMID:12153313

  3. Identifiability, exchangeability and confounding revisited

    PubMed Central

    Greenland, Sander; Robins, James M

    2009-01-01

    In 1986 the International Journal of Epidemiology published "Identifiability, Exchangeability and Epidemiological Confounding". We review the article from the perspective of a quarter century after it was first drafted and relate it to subsequent developments on confounding, ignorability, and collapsibility. PMID:19732410

  4. Interpretational Confounding or Confounded Interpretations of Causal Indicators?

    ERIC Educational Resources Information Center

    Bainter, Sierra A.; Bollen, Kenneth A.

    2014-01-01

    In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

  5. Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

    ERIC Educational Resources Information Center

    Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

    2016-01-01

    A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

  6. The Small GTPase ROP6 Interacts with NFR5 and Is Involved in Nodule Formation in Lotus japonicus1[C][W][OA

    PubMed Central

    Ke, Danxia; Fang, Qing; Chen, Chunfen; Zhu, Hui; Chen, Tao; Chang, Xiaojun; Yuan, Songli; Kang, Heng; Ma, Lian; Hong, Zonglie; Zhang, Zhongming

    2012-01-01

    Nod Factor Receptor5 (NFR5) is an atypical receptor-like kinase, having no activation loop in the protein kinase domain. It forms a heterodimer with NFR1 and is required for the early plant responses to Rhizobium infection. A Rho-like small GTPase from Lotus japonicus was identified as an NFR5-interacting protein. The amino acid sequence of this Rho-like GTPase is closest to the Arabidopsis (Arabidopsis thaliana) ROP6 and Medicago truncatula ROP6 and was designated as LjROP6. The interaction between Rop6 and NFR5 occurred both in vitro and in planta. No interaction between Rop6 and NFR1 was observed. Green fluorescent protein-tagged ROP6 was localized at the plasma membrane and cytoplasm. The interaction between ROP6 and NFR5 appeared to take place at the plasma membrane. The expression of the ROP6 gene could be detected in vascular tissues of Lotus roots. After inoculation with Mesorhizobium loti, elevated levels of ROP6 expression were found in the root hairs, root tips, vascular bundles of roots, nodule primordia, and young nodules. In transgenic hairy roots expressing ROP6 RNA interference constructs, Rhizobium entry into the root hairs did not appear to be affected, but infection thread growth through the root cortex were severely inhibited, resulting in the development of fewer nodules per plant. These data demonstrate a role of ROP6 as a positive regulator of infection thread formation and nodulation in L. japonicus. PMID:22434040

  7. Sensitivity analysis for interactions under unmeasured confounding.

    PubMed

    Vanderweele, Tyler J; Mukherjee, Bhramar; Chen, Jinbo

    2012-09-28

    We develop a sensitivity analysis technique to assess the sensitivity of interaction analyses to unmeasured confounding. We give bias formulas for sensitivity analysis for interaction under unmeasured confounding on both additive and multiplicative scales. We provide simplified formulas in the case in which either one of the two factors does not interact with the unmeasured confounder in its effects on the outcome. An interesting consequence of the results is that if the two exposures of interest are independent (e.g., gene-environment independence), even under unmeasured confounding, if the estimate of the interaction is nonzero, then either there is a true interaction between the two factors or there is an interaction between one of the factors and the unmeasured confounder; an interaction must be present in either scenario. We apply the results to two examples drawn from the literature.

  8. The product of the nitrogen fixation regulatory gene nfrX of Azotobacter vinelandii is functionally and structurally homologous to the uridylyltransferase encoded by glnD in enteric bacteria.

    PubMed Central

    Contreras, A; Drummond, M; Bali, A; Blanco, G; Garcia, E; Bush, G; Kennedy, C; Merrick, M

    1991-01-01

    We sequenced the nitrogen fixation regulatory gene nfrX from Azotobacter vinelandii, mutations in which cause a Nif- phenotype, and found that it encodes a 105-kDa protein (NfrX), the N terminus of which is highly homologous to that of the uridylyltransferase-uridylyl-removing enzyme encoded by glnD in Escherichia coli. In vivo complementation experiments demonstrate that the glnD and nfrX products are functionally interchangeable. A vinelandii nfrX thus appears to encode a uridylyltransferase-uridylyl-removing enzyme, and in this paper we report the first sequence of such a protein. The Nif- phenotype of nfrX mutants can be suppressed by a second mutation in a recently identified nifL-like gene immediately upstream of nifA in A. vinelandii. NifL mediates nif regulation in response to the N status in A. vinelandii, presumably by inhibiting NifA activator function as occurs in Klebsiella pneumoniae; thus, one role of NfrX is to modify, either directly or indirectly, the activity of the nifL product. PMID:1683868

  9. The product of the nitrogen fixation regulatory gene nfrX of Azotobacter vinelandii is functionally and structurally homologous to the uridylyltransferase encoded by glnD in enteric bacteria.

    PubMed

    Contreras, A; Drummond, M; Bali, A; Blanco, G; Garcia, E; Bush, G; Kennedy, C; Merrick, M

    1991-12-01

    We sequenced the nitrogen fixation regulatory gene nfrX from Azotobacter vinelandii, mutations in which cause a Nif- phenotype, and found that it encodes a 105-kDa protein (NfrX), the N terminus of which is highly homologous to that of the uridylyltransferase-uridylyl-removing enzyme encoded by glnD in Escherichia coli. In vivo complementation experiments demonstrate that the glnD and nfrX products are functionally interchangeable. A vinelandii nfrX thus appears to encode a uridylyltransferase-uridylyl-removing enzyme, and in this paper we report the first sequence of such a protein. The Nif- phenotype of nfrX mutants can be suppressed by a second mutation in a recently identified nifL-like gene immediately upstream of nifA in A. vinelandii. NifL mediates nif regulation in response to the N status in A. vinelandii, presumably by inhibiting NifA activator function as occurs in Klebsiella pneumoniae; thus, one role of NfrX is to modify, either directly or indirectly, the activity of the nifL product.

  10. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  11. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application.

  12. Modeling confounding by half-sibling regression

    PubMed Central

    Schölkopf, Bernhard; Hogg, David W.; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-01-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as “half-sibling regression,” is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  13. Resting-state FMRI confounds and cleanup

    PubMed Central

    Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

    2013-01-01

    The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

  14. Confounding Effect in Clinical Research of Otolaryngology and Its Control.

    PubMed

    Yu, Yong-qiang; Huang, Dong-yan; Armijo Olivo, Susan; Yang, Huai-an; Bambanini, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Constantinescu, Gabriela; Qian Yu, Jason; Zhang, Ming

    2015-06-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect. PMID:26149004

  15. Confounding Effect in Clinical Research of Otolaryngology and Its Control.

    PubMed

    Yu, Yong-qiang; Huang, Dong-yan; Armijo Olivo, Susan; Yang, Huai-an; Bambanini, Yagesh; Sonnenberg, Lyn; Clark, Brenda; Constantinescu, Gabriela; Qian Yu, Jason; Zhang, Ming

    2015-06-01

    Confounding effect is a critical issue in clinical research of otolaryngology because it can distort the research's conclusion. In this review, we introduce the definition of confounding effect, the methods of verifying and controlling the effect. Confounding effect can be prevented by research's design, and adjusted by data analysis. Clinicians would be aware and cautious about confounding effect in their research. They would be able to set up a research's design in which appropriate methods have been applied to prevent this effect.They would know how to adjust confounding effect after data collection. It is important to remember that sometimes it is impossible to eliminate confounding effect completely, and statistical method is not a master key. Solid research knowledge and critical thinking of our brain are the most important in controlling confounding effect.

  16. Still another confounded face in the crowd.

    PubMed

    Purcell, Dean G; Stewart, Alan L

    2010-11-01

    Experiments using schematic faces developed by Öhman (Öhman, Lundqvist, & Esteves, 2001) seem to document an anger-superiority effect, although we have come to question these experiments. Our work shows that the low-level features of these schematic faces interact with the face's surround to produce effects that have been attributed to facial affect. Using relatively neutral faces that preserved the feature and surround spatial relationships of angry and happy schematic faces, we produced reaction times (RTs) that were indistinguishable from those found with angry and happy faces. We also found that the target face's position within the crowd determined the magnitude of the advantage for angry faces as well as for relatively affect-neutral faces. Removing the facial surround reduces the advantage for angry faces, largely by improving performance on happy faces. There was an apparent small advantage for angry features without a surround. Öhman faces avoid the problems associated with modified grayscale faces only to introduce an equally troubling confound.

  17. The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

    PubMed Central

    Smith, Eric G.

    2015-01-01

    Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is

  18. Environmental confounding in gene-environment interaction studies.

    PubMed

    Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar

    2013-07-01

    We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.

  19. Transposon Mutagenesis of the Plant-Associated Bacillus amyloliquefaciens ssp. plantarum FZB42 Revealed That the nfrA and RBAM17410 Genes Are Involved in Plant-Microbe-Interactions

    PubMed Central

    Dietel, Kristin; Beator, Barbara; Dolgova, Olga; Fan, Ben; Bleiss, Wilfrid; Ziegler, Jörg; Schmid, Michael; Hartmann, Anton; Borriss, Rainer

    2014-01-01

    Bacillus amyloliquefaciens ssp. plantarum FZB42 represents the prototype of Gram-positive plant growth promoting and biocontrol bacteria. In this study, we applied transposon mutagenesis to generate a transposon library, which was screened for genes involved in multicellular behavior and biofilm formation on roots as a prerequisite of plant growth promoting activity. Transposon insertion sites were determined by rescue-cloning followed by DNA sequencing. As in B. subtilis, the global transcriptional regulator DegU was identified as an activator of genes necessary for swarming and biofilm formation, and the DegU-mutant of FZB42 was found impaired in efficient root colonization. Direct screening of 3,000 transposon insertion mutants for plant-growth-promotion revealed the gene products of nfrA and RBAM_017140 to be essential for beneficial effects exerted by FZB42 on plants. We analyzed the performance of GFP-labeled wild-type and transposon mutants in the colonization of lettuce roots using confocal laser scanning microscopy. While the wild-type strain heavily colonized root surfaces, the nfrA mutant did not colonize lettuce roots, although it was not impaired in growth in laboratory cultures, biofilm formation and swarming motility on agar plates. The RBAM17410 gene, occurring in only a few members of the B. subtilis species complex, was directly involved in plant growth promotion. None of the mutant strains were affected in producing the plant growth hormone auxin. We hypothesize that the nfrA gene product is essential for overcoming the stress caused by plant response towards bacterial root colonization. PMID:24847778

  20. Methodological problems with population cancer studies: The forgotten confounding factors

    PubMed Central

    Blaylock, Russell L.

    2015-01-01

    Among clinical physicians it is the population study that is considered to be the “gold standard” of medical evidence concerning acceptable treatments. As new information comes to light concerning the many variables and confounding factors that can affect such studies, many older studies lose much of their original impact. While newer population studies take into consideration a far greater number of confounding factors many are still omitted and a number of these omitted factors can have profound effects on interpretation and validity of the study. In this editorial, I will discuss some of the omitted confounding factors and demonstrate how they can alter the interpretation of these papers and their clinical application. PMID:26097772

  1. Air Pollution and Autism Spectrum Disorders: Causal or Confounded?

    PubMed

    Weisskopf, Marc G; Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L

    2015-12-01

    In the last decade, several studies have examined the association between perinatal exposure to ambient air pollution and risk of autism spectrum disorder (ASD). These studies have largely been consistent, with associations seen with different aspects of air pollution, including hazardous air toxics, ozone, particulate, and traffic-related pollution. Confounding by socioeconomic status (SES) and place of residence are of particular concern, as these can be related to ASD case ascertainment and other potential causal risk factors for ASD. While all studies take steps to address this concern, residual confounding is difficult to rule out. Two recent studies of air pollution and ASD, however, present findings that strongly argue against residual confounding, especially for factors that do not vary over relatively short time intervals. These two studies, conducted in communities around the USA, found a specific association with air pollution exposure during the 3rd, but not the 1st, trimester, when both trimesters were modeled simultaneously. In this review, we discuss confounding possibilities and then explain-with the aid of directed acyclic graphs (DAGs)-why an association that is specific to a particular time window, when multiple exposure windows are simultaneously assessed, argues against residual confounding by (even unmeasured) non-time-varying factors. In addition, we discuss why examining ambient air pollution concentration as a proxy for personal exposure helps avoid confounding by personal behavior differences, and the implications of measurement error in using ambient concentrations as a proxy for personal exposures. Given the general consistency of findings across studies and the exposure-window-specific associations recently reported, the overall evidence for a causal association between air pollution and ASD is increasingly compelling.

  2. Causal diagrams and multivariate analysis III: confound it!

    PubMed

    Jupiter, Daniel C

    2015-01-01

    This commentary concludes my series concerning inclusion of variables in multivariate analyses. We take up the issues of confounding and effect modification and summarize the work we have thus far done. Finally, we provide a rough algorithm to help guide us through the maze of possibilities that we have outlined.

  3. The Threshold of Embedded M Collider Bias and Confounding Bias

    ERIC Educational Resources Information Center

    Kelcey, Benjamin; Carlisle, Joanne

    2011-01-01

    Of particular import to this study, is collider bias originating from stratification on retreatment variables forming an embedded M or bowtie structural design. That is, rather than assume an M structural design which suggests that "X" is a collider but not a confounder, the authors adopt what they consider to be a more reasonable position and…

  4. Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy

    PubMed Central

    Brogly, Susan B; Hahn, Kristen A; Diaz, Sonia Hernandez; Werler, Martha

    2016-01-01

    Prenatal opioid agonist therapy with methadone or buprenorphine prevents maternal illicit opioid use and withdrawal and improves pregnancy outcomes compared to heroin use alone. Historically, methadone has been the first-line opioid agonist therapy for pregnant opioid dependent women; in recent years buprenorphine has become first-line treatment for some opioid dependent pregnant women. While there is some evidence of better outcomes in neonates exposed to buprenorphine vs. methadone, the effect of confounding from differences in women who use buprenorphine and methadone has not been carefully examined in most studies. This review explores mechanisms by which confounding can arise in measuring associations between prenatal buprenorphine vs. methadone exposure on neonatal outcomes using a graphical approach, directed acyclic graphs. The goal of this paper is to facilitate better understanding of the factors influencing neonatal abstinence syndrome and accurate assessment of the comparative safety of opioid agonist therapies on the neonate. PMID:27547489

  5. A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

    PubMed

    Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

    2016-09-10

    When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:27139250

  6. Air pollutants and health outcomes: Assessment of confounding by influenza

    NASA Astrophysics Data System (ADS)

    Thach, Thuan-Quoc; Wong, Chit-Ming; Chan, King-Pan; Chau, Yuen-Kwan; Neil Thomas, G.; Ou, Chun-Quan; Yang, Lin; Peiris, Joseph S. M.; Lam, Tai-Hing; Hedley, Anthony J.

    2010-04-01

    We assessed confounding of associations between short-term effects of air pollution and health outcomes by influenza using Hong Kong mortality and hospitalization data for 1996-2002. Three measures of influenza were defined: (i) intensity: weekly proportion of positive influenza viruses, (ii) epidemic: weekly number of positive influenza viruses ≥4% of the annual number for ≥2 consecutive weeks, and (iii) predominance: an epidemic period with co-circulation of respiratory syncytial virus <2% of the annual positive isolates for ≥2 consecutive weeks. We examined effects of influenza on associations between nitrogen dioxide (NO 2), sulfur dioxide (SO 2), particulate matter with aerodynamic diameter ≤10 μm (PM 10) and ozone (O 3) and health outcomes including all natural causes mortality, cardiorespiratory mortality and hospitalization. Generalized additive Poisson regression model with natural cubic splines was fitted to control for time-varying covariates to estimate air pollution health effects. Confounding with influenza was assessed using an absolute difference of >0.1% between unadjusted and adjusted excess risks (ER%). Without adjustment, pollutants were associated with positive ER% for all health outcomes except asthma and stroke hospitalization with SO 2 and stroke hospitalization with O 3. Following adjustment, changes in ER% for all pollutants were <0.1% for all natural causes mortality, but >0.1% for mortality from stroke with NO 2 and SO 2, cardiac or heart disease with NO 2, PM 10 and O 3, lower respiratory infections with NO 2 and O 3 and mortality from chronic obstructive pulmonary disease with all pollutants. Changes >0.1% were seen for acute respiratory disease hospitalization with NO 2, SO 2 and O 3 and acute lower respiratory infections hospitalization with PM 10. Generally, influenza does not confound the observed associations of air pollutants with all natural causes mortality and cardiovascular hospitalization, but for some pollutants

  7. Postglacial hillslope development in paraglacial tributary catchments (ESF-NFR SedyMONT-Norway Project, SedyMONT, Topo-Europe)

    NASA Astrophysics Data System (ADS)

    Laute, Katja; Beylich, Achim A.; Hansen, Louise; Vatne, Geir

    2010-05-01

    Topography and landforms of different spatial scales are generated by different operating processes and are characterized by different variables, evolved over different time periods. Changes in climate affect Earth surface systems and shapes Earth surface processes around the world and seem to have major impacts on sediment dynamics, especially in cold climate environments. Understanding climate and landform development from a Holocene to contemporary time perspective can contribute to document change of the Earth surface systems as well as to detect responsible processes for climatic and topographic change. Analyzing postglacial hillslope development and studying sediment transport within two small deglaciated, subarctic valley systems in Western Norway will improve the understanding of the complex response of mountain landscape formation. The innovative approach of this PhD research project is the combination of knowledge on Holocene process rates with data on subrecent to contemporary sedimentary fluxes, -budgets and process rates using different advanced methods and techniques. The PhD project is part of the NFR funded SedyMONT-Norway Project within the ESF EUROCORES TOPO-EUROPE SedyMONT (Timescales of sediment dynamics, climate and topographic change in mountain landscapes) Programme. Research is carried out within the Erdalen and Bødalen catchments of the Nordfjord valley-fjord system (inner Nordfjord, Western Norway). Both valleys can be described as steep U-shaped and glacier-fed tributary valleys. The runoff regime is complex with a high variability of discharge over the year. Instrumentation in both catchments includes an automatic weather station as well as five stationary stations for continuous and year-round monitoring of runoff, fluvial suspended sediment and solute transport. The main aims of the PhD project are to analyse (i) the spatial distribution of hillslopes, their contemporary structure, controls and current process rates, (ii) the

  8. Arsenic cancer risk confounder in southwest Taiwan data set.

    PubMed

    Lamm, Steven H; Engel, Arnold; Penn, Cecilia A; Chen, Rusan; Feinleib, Manning

    2006-07-01

    Quantitative analysis for the risk of human cancer from the ingestion of inorganic arsenic has been based on the reported cancer mortality experience in the blackfoot disease (BFD) -endemic area of southwest Taiwan. Linear regression analysis shows that arsenic as the sole etiologic factor accounts for only 21% of the variance in the village standardized mortality ratios for bladder and lung cancer. A previous study had reported the influence of confounders (township, BFD prevalence, and artesian well dependency) qualitatively, but they have not been introduced into a quantitative assessment. In this six-township study, only three townships (2, 4, and 6) showed a significant positive dose-response relationship with arsenic exposure. The other three townships (0, 3, and 5) demonstrated significant bladder and lung cancer risks that were independent of arsenic exposure. The data for bladder and lung cancer mortality for townships 2, 4, and 6 fit an inverse linear regression model (p < 0.001) with an estimated threshold at 151 microg/L (95% confidence interval, 42 to 229 microg/L) . Such a model is consistent with epidemiologic and toxicologic literature for bladder cancer. Exploration of the southwest Taiwan cancer mortality data set has clarified the dose-response relationship with arsenic exposure by separating out township as a confounding factor. Key words: arsenic, blackfoot disease, bladder cancer, cancer risk, confounder, dose-response relationship, southwest Taiwan, threshold model.

  9. Resting-state fMRI confounds and cleanup.

    PubMed

    Murphy, Kevin; Birn, Rasmus M; Bandettini, Peter A

    2013-10-15

    The goal of resting-state functional magnetic resonance imaging (fMRI) is to investigate the brain's functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain "at rest" as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of fMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state fMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO₂ concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state fMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state fMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline.

  10. [Bias and confounding: pharmacoepidemiological study using administrative database].

    PubMed

    Nojiri, Shuko

    2015-01-01

    The provision of health care frequently creates digitalized data such as hospital-based electronic data, medication prescription records, and claims data collectively termed "administrative database research". The data source and analytical opportunities for study create risks that can lead to misinterpretation or bias the results. This review serves as an introduction to the concept of bias and confounding to help researchers conduct methodologically sound pharmacoepidemiologic research projects using administrative databases. Beyond general considerations for observational study, there are several unique issues related to database research that should be addressed. The risks of uninterpretable or biased results can be minimized by: providing a robust description of the data tables used; focusing on why and how they were created; measuring and reporting the accuracy of diagnostic and procedural codes used; and properly accounting for any time-dependent nature of variables. The hallmark of good research is rigorously careful analysis and interpretation. The promise for value of real world evidence using databases in medical decision making must be balanced against concerns related to observational inherited limitations for bias and confounding. Researchers should aim to avoid bias in the design of a study, adjust for confounding, and discuss the effects of residual bias on the results. PMID:26028416

  11. Confounding and heterogeneity in genetic association studies with admixed populations.

    PubMed

    Liu, Jinghua; Lewinger, Juan Pablo; Gilliland, Frank D; Gauderman, W James; Conti, David V

    2013-02-15

    Association studies among admixed populations pose many challenges including confounding of genetic effects due to population substructure and heterogeneity due to different patterns of linkage disequilibrium (LD). We use simulations to investigate controlling for confounding by indicators of global ancestry and the impact of including a covariate for local ancestry. In addition, we investigate the use of an interaction term between a single-nucleotide polymorphism (SNP) and local ancestry to capture heterogeneity in SNP effects. Although adjustment for global ancestry can control for confounding, additional adjustment for local ancestry may increase power when the induced admixture LD is in the opposite direction as the LD in the ancestral population. However, if the induced LD is in the same direction, there is the potential for reduced power because of overadjustment. Furthermore, the inclusion of a SNP by local ancestry interaction term can increase power when there is substantial differential LD between ancestry populations. We examine these approaches in genome-wide data using the University of Southern California's Children's Health Study investigating asthma risk. The analysis highlights rs10519951 (P = 8.5 × 10(-7)), a SNP lacking any evidence of association from a conventional analysis (P = 0.5).

  12. Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

    PubMed Central

    Migliore, Enrica; Zugna, Daniela; Galassi, Claudia; Merletti, Franco; Gagliardi, Luigi; Rasero, Laura; Trevisan, Morena; Rusconi, Franca; Richiardi, Lorenzo

    2015-01-01

    Background Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding. Methods We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy. Results The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07–1.47] to 1.10 [0.94–1.30] in the first, and from 1.26 [1.08–1.47] to 1.10 [0.93–1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children. Conclusion The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding. PMID:26305473

  13. Possible confounding factors on cerebral diffusion tensor imaging measurements

    PubMed Central

    Nenonen, Miina; Hakulinen, Ullamari; Brander, Antti; Ohman, Juha; Dastidar, Prasun

    2015-01-01

    Background Diffusion tensor imaging (DTI) is prone to numerous systemic confounding factors that should be acknowledged to avoid false conclusions. Purpose To investigate the possible effects of age, gender, smoking, alcohol consumption, and education on cerebral DTI parameters in a generally healthy homogenous sample with no neurological or psychiatric diseases. Material and Methods Forty (n = 40) subjects (mean age, 40.3 years; SD, 12.3) underwent brain DTI with 3 T magnetic resonance imaging (MRI). At enrolment, all the subjects were interviewed with respect to general health, education, history of smoking, and alcohol consumption. Studied DTI parameters included: (i) fractional anisotropy (FA); and (ii) apparent diffusion coefficient (ADC). Region-of-interest (ROI)-based measurements were estimated at 13 anatomical locations bilaterally on the axial images, except for the corpus callosum in which the ROIs were placed on the sagittal images. Circular ROI measurements were mainly used. Freehand ROI method was used with the forceps minor, uncinate fasciculus, and thalamus. Intra-observer variability and repeatability were assessed. Results The most consistent finding was that aging decreased FA values in the frontal brain regions. Regarding the other confounding factors, the results were discontinuous and no concrete conclusions could be drawn from these findings. In general, intra-observer repeatability of the DTI measurement was considered relatively good. Conclusion Age should be noted as considerable confounding factors in ROI-based DTI analysis. More research on the effects of gender, smoking, alcohol consumption, and education is needed. PMID:25793107

  14. The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

    PubMed Central

    Källén, Bengt

    2012-01-01

    In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes. PMID:22190949

  15. Negative Confounding by Essential Fatty Acids in Methylmercury Neurotoxicity Associations

    PubMed Central

    Choi, Anna L; Mogensen, Ulla B.; Bjerve, Kristian S.; Debes, Frodi; Weihe, Pal; Grandjean, Philippe; Budtz-Jørgensen, Esben

    2014-01-01

    Background Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. Methods We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. Results A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (−18.9, 95% confidence interval [CI] = −36.3, −1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (−22.0, 95% confidence interval [CI] = −39.4, −4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (−1.94, 95% CI = −3.39, −0.49). Conclusions Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure. PMID:24561639

  16. Confounding Impacts of Iron Reduction on Arsenic Retention

    SciTech Connect

    Tufano, K.J.; Fendorf, S.

    2009-05-26

    A transition from oxidizing to reducing conditions has long been implicated to increase aqueous As concentrations, for which reductive dissolution of iron (hydr)oxides is commonly implicated as the primary culprit. Confounding our understanding of processes controlling As retention, however, is that reductive transformation of ferrihydrite has recently been shown to promote As retention rather than release. To resolve the role iron phases have in regulating arsenic concentrations, here we examine As desorption from ferrihydrite-coated sands presorbed with As(lll); experiments were performed at circumneutral pH under Fe-reducing conditions with the dissimilatory iron reducing bacterium Shewanella putrefaciens strain CN-32 over extended time periods. We reveal that with the initial phase of iron reduction, ferrihydrite undergoes transformation to secondary phases and increases As(lll) retention (relative to abiotic controls). However, with increased reaction time, cessation of the phase transitions and ensuing reductive dissolution result in prolonged release of As(III) to the aqueous phase. Our results suggest that As(lll) retention during iron reduction is temporally dependent on secondary precipitation of iron phases; during transformation to secondary phases, particularly magnetite, As(lll) retention is enhanced even relative to oxidized systems. However, conditions that retard secondary transformation (more stable iron oxides or limited iron reducing bacterial activity), or prolonged anaerobiosis, will lead to both the dissolution of ferric (hydr)oxides and release of As(lll) to the aqueous phase.

  17. Smoking and Hormesis as Confounding Factors in Radiation Pulmonary Carcinogenesis

    PubMed Central

    Sanders, Charles L.; Scott, Bobby R.

    2008-01-01

    Confounding factors in radiation pulmonary carcinogenesis are passive and active cigarette smoke exposures and radiation hormesis. Significantly increased lung cancer risk from ionizing radiation at lung doses < 1 Gy is not observed in never smokers exposed to ionizing radiations. Residential radon is not a cause of lung cancer in never smokers and may protect against lung cancer in smokers. The risk of lung cancer found in many epi-demiological studies was less than the expected risk (hormetic effect) for nuclear weapons and power plant workers, shipyard workers, fluoroscopy patients, and inhabitants of high-dose background radiation. The protective effect was noted for low- and mixed high- and low-linear energy transfer (LET) radiations in both genders. Many studies showed a protection factor (PROFAC) > 0.40 (40% avoided) against the occurrence of lung cancer. The ubiquitous nature of the radiation hormesis response in cellular, animal, and epidemio-logical studies negates the healthy worker effect as an explanation for radiation hormesis. Low-dose radiation may stimulate DNA repair/apoptosis and immunity to suppress and eliminate cigarette-smoke-induced transformed cells in the lung, reducing lung cancer occurrence in smokers. PMID:18648572

  18. Adhesion: a confounding bias in murine cervical heterotopic heart transplantation

    PubMed Central

    Yang, Jinghui; Chen, Qi; Liu, Fang; Fu, Zhiren; Wang, Quanxing

    2015-01-01

    Tissue adhesion is a common postsurgical phenomenon among the human population. This complication also occurs in murine transplant models. In this study, we investigated the impact of adhesion on murine cervical heterotopic heart transplantation by using sodium hyaluronate (SH) as an anti-adhesive agent. Our study revealed that SH administration produced no significant effect on histological change, TNF-α, IFN-γ, MCP-1, IL-2, IL-6 and IL-10 expression, CD4+ T, CD8+ T, or neutrophil and macrophage counts. Our findings suggest that SH was biocompatible and non-immunogenic. Later, we observed that adhesion not only affected the survival of the graft without mediating rejection, but was closely related to the severity of rejection as manifested by larger and more severe adhesion formation in total-allomismatched and MHC class II-allomismatched murine cardiac allografts. Therefore, we inferred that using the murine cervical heterotopic heart transplant model may lead to an exaggerated p-value in statistical significance testing which could mislead experimenters in considering that the results are more significant than the fact. To the best of our knowledge, this study is the first demonstration that proves that adhesion was a confounding bias in the murine cervical heterotopic heart transplant model and highlights the possibilities for improvement in future use. PMID:26550450

  19. Confounding variables in the environmental toxicology of arsenic.

    PubMed

    Gebel, T

    2000-04-01

    Arsenic is one of the most important global environmental toxicants. For example, in regions of West Bengal and Inner Mongolia, more than 100000 persons are chronically exposed to well water often strongly contaminated with As. Unfortunately, a toxicologically safe risk assessment and standard setting, especially for long-term and low-dose exposures to arsenic, is not possible. One reason is that the key mechanism of arsenic's tumorigenicity still is not elucidated. Experimental data indicate that either DNA repair inhibition or DNA methylation status alteration may be causal explanations. Moreover, when comparing epidemiological data, it cannot be ruled out that the susceptibility to arsenic's carcinogenicity may be different between Mexican and Taiwanese people. Some other studies indicate that some Andean populations do not develop skin cancer after long-term exposure to As. It is not known yet how this resistance could be mediated. Finally, the situation is even more complicated when taking into consideration that there are several compounds suspected to modulate the chronic environmental toxicity of arsenic, variables that may either enhance or suppress the in vivo genotoxicity and carcinogenicity of the metalloid. Among them are nutritional factors like selenium and zinc as well as drinking water co-contaminants like antimony. Further, yet unidentified factors influencing the body burden and/or the excretion of arsenic are possibly prevailing: preliminary data from own human biomonitoring studies showed a peaking of As in urine samples of non-exposed people which was not caused by elevated exposure to As through seafood consumption. The relevance of these putative confounding variables cannot be finally evaluated yet. Further experimental as well as epidemiological studies are needed to answer these questions. This would help to conduct a toxicologically improved risk assessment, especially for low-dose and long-term exposures to arsenic.

  20. Packet Randomized Experiments for Eliminating Classes of Confounders

    PubMed Central

    Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.

    2014-01-01

    Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088

  1. Eliminating a Confounding Factor in Power Law Parameter Interpretation

    NASA Astrophysics Data System (ADS)

    Karst, N.; Dralle, D.; Thompson, S. E.

    2015-12-01

    Power law models of the form y = -axb are used to represent a wide range of phenomena in the physical, biological and social sciences. Power laws are well known to display a "scale-free property", meaning that the value of the exponent b is independent of the unit of measurement (the "scale") of the state variable x. While this makes estimation of the exponent robust, it raises significant estimation challenges for the linear multiplier a. Specifically, if both the multiplier a and exponent b are allowed to vary when undertaking an empirical fitting procedure, then physical units used to measure x induce a formal (i.e., entirely nonphysical) dependence between a and b, because the fitted value of a will contain a (potentially large) multiplicative factor that varies depending on the scale of x. This is problematic for two reasons: (i) if a is to be empirically estimated, but admits a physical interpretation, then the scale-dependent factor can confound the physically meaningful value (ii) the formal relationship between a and b due to the scaling of the relationship obscures any true relationship between the parameters and could motivate a spurious interpretation of their co-variation. To correct this issue, we present a technique to remove the formal correlation between a and b, and demonstrate an application of the technique in the context of streamflow recession analysis, where the falling limb of the hydrograph is modeled using a simple power law relationship, dq/dt = -aqb. Following the decorrelation of (a, b) recession parameter pairs, physically intuitive seasonal patterns, greatly obscured in the original data, are clearly found.

  2. Confounding by dietary pattern of the inverse association between alcohol consumption and type 2 diabetes risk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as ...

  3. Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

  4. A method for assessing the potential for confounding applied to ionic strength in central Appalachian streams.

    PubMed

    Suter, Glenn W; Cormier, Susan M

    2013-02-01

    Causal relationships derived from field data are potentially confounded by variables that are correlated with both the cause and its effect. The present study presents a method for assessing the potential for confounding and applies it to the relationship between ionic strength and impairment of benthic invertebrate assemblages in central Appalachian streams. The method weighs all available evidence for and against confounding by each potential confounder. It identifies 10 types of evidence for confounding, presents a qualitative scoring system, and provides rules for applying the scores. Twelve potential confounders were evaluated: habitat, organic enrichment, nutrients, deposited sediments, pH, selenium, temperature, lack of headwaters, catchment area, settling ponds, dissolved oxygen, and metals. One potential confounder, low pH, was found to be biologically significant and eliminated by removing sites with pH < 6. Other potential confounders were eliminated based on the weight of evidence. This method was found to be useful and defensible. It could be applied to other environmental assessments that use field data to develop causal relationships, including contaminated site remediation or management of natural resources.

  5. Structural confounding of area-level deprivation and segreation: an empirical example

    EPA Science Inventory

    The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

  6. Bed Sharing, SIDS Research, and the Concept of Confounding: A Review for Public Health Nurses.

    PubMed

    Keys, Elizabeth M; Rankin, James A

    2015-01-01

    Confounding is an important concept for public health nurses (PHNs) to understand when considering the results of epidemiological research. The term confounding is derived from Latin, confundere, which means to "mix-up" or "mix together". Epidemiologists attempt to derive a cause and effect relationship between two variables traditionally known as the exposure and disease (e.g., smoking and lung cancer). Confounding occurs when a third factor, known as a confounder, leads to an over- or underestimate of the magnitude of the association between the exposure and disease. An understanding of confounding will facilitate critical appraisal of epidemiological research findings. This knowledge will enable PHNs to strengthen their evidence-based practice and better prepare them for policy development and implementation. In recent years, researchers and clinicians have examined the relationship between bed sharing and sudden infant death syndrome (SIDS). The discussion regarding the risk of bed sharing and SIDS provides ample opportunity to discuss the various aspects of confounding. The purpose of this article is to use the bed sharing and SIDS literature to assist PHNs to understand confounding and to apply this knowledge when appraising epidemiological research. In addition, strategies that are used to control confounding are discussed.

  7. Breast milk and cognitive development—the role of confounders: a systematic review

    PubMed Central

    Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

    2013-01-01

    Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously

  8. From bad to worse: collider stratification amplifies confounding bias in the "obesity paradox".

    PubMed

    Banack, Hailey R; Kaufman, Jay S

    2015-10-01

    Smoking is often identified as a confounder of the obesity-mortality relationship. Selection bias can amplify the magnitude of an existing confounding bias. The objective of the present report is to demonstrate how confounding bias due to cigarette smoking is increased in the presence of collider stratification bias using an empirical example and directed acyclic graphs. The empirical example uses data from the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of 15,792 men and women in the United States. Poisson regression models were used to examine the confounding effect of smoking. In the total ARIC study population, smoking produced a confounding bias of <3 percentage points. This result was obtained by comparing the incidence rate ratio (IRR) for obesity from a model adjusted for smoking was 1.07 (95 % CI 1.00, 1.15) with one that did not adjust for smoking was 1.10 (95 % CI 1.03, 1.18). However, among smokers with CVD, the obesity IRR was 0.89 (95 % CI 0.81, 0.99), while among non-smokers with CVD the obesity IRR was 1.20 (95 % CI 1.03, 1.41). The empirical and graphical explanations presented suggest that the magnitude of the confounding bias induced by smoking is greater in the presence of collider stratification bias.

  9. Biochemical transformation of coals

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  10. Biochemical transformation of coals

    DOEpatents

    Lin, M.S.; Premuzic, E.T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

  11. NFR TRIGA package design review report

    SciTech Connect

    Clements, M.D.

    1994-08-26

    The purpose of this document is to compile, present and document the formal design review of the NRF TRIGA packaging. The contents of this document include: the briefing meeting presentations, package description, design calculations, package review drawings, meeting minutes, action item lists, review comment records, final resolutions, and released drawings. This design review required more than two meeting to resolve comments. Therefore, there are three meeting minutes and two action item lists.

  12. Event-related potential indices of congruency sequence effects without feature integration or contingency learning confounds.

    PubMed

    Larson, Michael J; Clayson, Peter E; Kirwan, C Brock; Weissman, Daniel H

    2016-06-01

    The congruency effect in Stroop-like tasks (i.e., increased response time and reduced accuracy in incongruent relative to congruent trials) is often smaller when the previous trial was incongruent as compared to congruent. This congruency sequence effect (CSE) is thought to reflect cognitive control processes that shift attention to the target and/or modulate the response engendered by the distracter differently after incongruent relative to congruent trials. The neural signatures of CSEs are therefore usually attributed to cognitive control processes that minimize distraction from irrelevant stimuli. However, CSEs in previous functional neuroimaging studies were ubiquitously confounded with feature integration and/or contingency learning processes. We therefore investigated whether a neural CSE can be observed without such confounds in a group of healthy young adults (n = 56). To this end, we combined a prime-probe task that lacks such confounds with high-density ERPs to identify, for the first time, the neural time course of confound-minimized CSEs. Replicating recent behavioral findings, we observed strong CSEs in this task for mean response time and mean accuracy. Critically, conceptually replicating prior ERP results from confounded tasks, we also observed a CSE in both the parietal conflict slow potential (conflict SP) and the frontomedial N450. These findings indicate for the first time that neural CSEs as indexed by ERPs can be observed without the typical confounds. More broadly, the present study provides a confound-minimized protocol that will help future researchers to better isolate the neural bases of control processes that minimize distraction from irrelevant stimuli. PMID:26854028

  13. Adjusting effect estimates for unmeasured confounding with validation data using propensity score calibration

    PubMed Central

    Stürmer, Til; Schneeweiss, Sebastian; Avorn, Jerry; Glynn, Robert J

    2006-01-01

    Often important confounders are not available in studies. Sensitivity analyses based on the relation of single, but not multiple, unmeasured confounders with an exposure of interest in a separate validation study have been proposed. The authors controlled for measured confounding in the main cohort using propensity scores (PS) and addressed unmeasured confounding by estimating two additional PS in a validation study. The ‘error-prone’ PS exclusively used information available in the main cohort. The ‘gold-standard’ PS additionally included covariates available only in the validation study. Based on these two PS in the validation study, regression calibration was applied to adjust regression coefficients. This propensity score calibration (PSC) adjusts for unmeasured confounding in cohort studies with validation data under certain, usually untestable, assumptions. PSC was used to assess nonsteroidal antiinflammatory drugs (NSAID) and 1-year mortality in a large cohort of elderly. ‘Traditional’ adjustment resulted in a relative risk (RR) in NSAID users of 0.80 (95% confidence interval: 0.77–0.83) compared to an unadjusted RR of 0.68 (0.66–0.71). Application of PSC resulted in a more plausible RR of 1.06 (1.00–1.12). Until validity and limitations of PSC have been assessed in different settings, the method should be seen as a sensitivity analysis. PMID:15987725

  14. Sensitivity analysis for unmeasured confounding in principal stratification settings with binary variables

    PubMed Central

    Schwartz, Scott; Li, Fan; Reiter, Jerome P.

    2016-01-01

    Within causal inference, principal stratification (PS) is a popular approach for dealing with intermediate variables, that is, variables affected by treatment that also potentially affect the response. However, when there exists unmeasured confounding in the treatment arms—as can happen in observational studies—causal estimands resulting from PS analyses can be biased. We identify the various pathways of confounding present in PS contexts and their effects for PS inference. We present model-based approaches for assessing the sensitivity of complier average causal effect estimates to unmeasured confounding in the setting of binary treatments, binary intermediate variables, and binary outcomes. These same approaches can be used to assess sensitivity to unknown direct effects of treatments on outcomes because, as we show, direct effects are operationally equivalent to one of the pathways of unmeasured confounding. We illustrate the methodology using a randomized study with artificially introduced confounding and a sensitivity analysis for an observational study of the effects of physical activity and body mass index on cardiovascular disease. PMID:22362635

  15. Assessment and indirect adjustment for confounding by smoking in cohort studies using relative hazards models.

    PubMed

    Richardson, David B; Laurier, Dominique; Schubauer-Berigan, Mary K; Tchetgen Tchetgen, Eric; Cole, Stephen R

    2014-11-01

    Workers' smoking histories are not measured in many occupational cohort studies. Here we discuss the use of negative control outcomes to detect and adjust for confounding in analyses that lack information on smoking. We clarify the assumptions necessary to detect confounding by smoking and the additional assumptions necessary to indirectly adjust for such bias. We illustrate these methods using data from 2 studies of radiation and lung cancer: the Colorado Plateau cohort study (1950-2005) of underground uranium miners (in which smoking was measured) and a French cohort study (1950-2004) of nuclear industry workers (in which smoking was unmeasured). A cause-specific relative hazards model is proposed for estimation of indirectly adjusted associations. Among the miners, the proposed method suggests no confounding by smoking of the association between radon and lung cancer--a conclusion supported by adjustment for measured smoking. Among the nuclear workers, the proposed method suggests substantial confounding by smoking of the association between radiation and lung cancer. Indirect adjustment for confounding by smoking resulted in an 18% decrease in the adjusted estimated hazard ratio, yet this cannot be verified because smoking was unmeasured. Assumptions underlying this method are described, and a cause-specific proportional hazards model that allows easy implementation using standard software is presented.

  16. Assessment and Indirect Adjustment for Confounding by Smoking in Cohort Studies Using Relative Hazards Models

    PubMed Central

    Richardson, David B.; Laurier, Dominique; Schubauer-Berigan, Mary K.; Tchetgen, Eric Tchetgen; Cole, Stephen R.

    2014-01-01

    Workers' smoking histories are not measured in many occupational cohort studies. Here we discuss the use of negative control outcomes to detect and adjust for confounding in analyses that lack information on smoking. We clarify the assumptions necessary to detect confounding by smoking and the additional assumptions necessary to indirectly adjust for such bias. We illustrate these methods using data from 2 studies of radiation and lung cancer: the Colorado Plateau cohort study (1950–2005) of underground uranium miners (in which smoking was measured) and a French cohort study (1950–2004) of nuclear industry workers (in which smoking was unmeasured). A cause-specific relative hazards model is proposed for estimation of indirectly adjusted associations. Among the miners, the proposed method suggests no confounding by smoking of the association between radon and lung cancer—a conclusion supported by adjustment for measured smoking. Among the nuclear workers, the proposed method suggests substantial confounding by smoking of the association between radiation and lung cancer. Indirect adjustment for confounding by smoking resulted in an 18% decrease in the adjusted estimated hazard ratio, yet this cannot be verified because smoking was unmeasured. Assumptions underlying this method are described, and a cause-specific proportional hazards model that allows easy implementation using standard software is presented. PMID:25245043

  17. EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE TREATMENT EFFECT.

    PubMed

    Handorf, Elizabeth A; Bekelman, Justin E; Heitjan, Daniel F; Mitra, Nandita

    2013-01-01

    Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general adjustment formula for loglinear models of mean cost and explore special cases under plausible assumptions about the distribution of the unmeasured confounder. We assess the performance of the adjustment by simulation, in particular, examining robustness to a key assumption of conditional independence between the unmeasured and measured covariates given the treatment indicator. We apply our method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder cancer cohort. We evaluate the costs for radical cystectomy vs. combined radiation/chemotherapy, and find that the significance of the treatment effect is sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders. PMID:24587844

  18. Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

    USGS Publications Warehouse

    Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

    2015-01-01

    In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

  19. EVALUATING COSTS WITH UNMEASURED CONFOUNDING: A SENSITIVITY ANALYSIS FOR THE TREATMENT EFFECT

    PubMed Central

    Handorf, Elizabeth A.; Bekelman, Justin E.; Heitjan, Daniel F.; Mitra, Nandita

    2014-01-01

    Estimates of the effects of treatment on cost from observational studies are subject to bias if there are unmeasured confounders. It is therefore advisable in practice to assess the potential magnitude of such biases. We derive a general adjustment formula for loglinear models of mean cost and explore special cases under plausible assumptions about the distribution of the unmeasured confounder. We assess the performance of the adjustment by simulation, in particular, examining robustness to a key assumption of conditional independence between the unmeasured and measured covariates given the treatment indicator. We apply our method to SEER-Medicare cost data for a stage II/III muscle-invasive bladder cancer cohort. We evaluate the costs for radical cystectomy vs. combined radiation/chemotherapy, and find that the significance of the treatment effect is sensitive to plausible unmeasured Bernoulli, Poisson and Gamma confounders. PMID:24587844

  20. Biochemical Engineering Fundamentals

    ERIC Educational Resources Information Center

    Bailey, J. E.; Ollis, D. F.

    1976-01-01

    Discusses a biochemical engineering course that is offered as part of a chemical engineering curriculum and includes topics that influence the behavior of man-made or natural microbial or enzyme reactors. (MLH)

  1. Biochemical Education in Leisure.

    ERIC Educational Resources Information Center

    Tayyab, Saad

    1994-01-01

    Presents two alternative teaching approaches to ensure that students become active participants of learning in the biochemistry classroom. Diagrams and rules are provided for using educational playing cards and creating a biochemical comic book. (ZWH)

  2. Distinguishing prostate cancer from benign confounders via a cascaded classifier on multi-parametric MRI

    NASA Astrophysics Data System (ADS)

    Litjens, G. J. S.; Elliott, R.; Shih, N.; Feldman, M.; Barentsz, J. O.; Hulsbergen-van de Kaa, C. A.; Kovacs, I.; Huisman, H. J.; Madabhushi, A.

    2014-03-01

    Learning how to separate benign confounders from prostate cancer is important because the imaging characteristics of these confounders are poorly understood. Furthermore, the typical representations of the MRI parameters might not be enough to allow discrimination. The diagnostic uncertainty this causes leads to a lower diagnostic accuracy. In this paper a new cascaded classifier is introduced to separate prostate cancer and benign confounders on MRI in conjunction with specific computer-extracted features to distinguish each of the benign classes (benign prostatic hyperplasia (BPH), inflammation, atrophy or prostatic intra-epithelial neoplasia (PIN). In this study we tried to (1) calculate different mathematical representations of the MRI parameters which more clearly express subtle differences between different classes, (2) learn which of the MRI image features will allow to distinguish specific benign confounders from prostate cancer, and (2) find the combination of computer-extracted MRI features to best discriminate cancer from the confounding classes using a cascaded classifier. One of the most important requirements for identifying MRI signatures for adenocarcinoma, BPH, atrophy, inflammation, and PIN is accurate mapping of the location and spatial extent of the confounder and cancer categories from ex vivo histopathology to MRI. Towards this end we employed an annotated prostatectomy data set of 31 patients, all of whom underwent a multi-parametric 3 Tesla MRI prior to radical prostatectomy. The prostatectomy slides were carefully co-registered to the corresponding MRI slices using an elastic registration technique. We extracted texture features from the T2-weighted imaging, pharmacokinetic features from the dynamic contrast enhanced imaging and diffusion features from the diffusion-weighted imaging for each of the confounder classes and prostate cancer. These features were selected because they form the mainstay of clinical diagnosis. Relevant features for

  3. Race and Socioeconomic Status as Confounding Variables in the Accurate Diagnosis of Alcoholism.

    ERIC Educational Resources Information Center

    Luepnitz, Roy R.; And Others

    1982-01-01

    Studied the incidence of bias related to race and socioeconomic status which could confound the diagnosis of alcoholism. Graduate psychology students made a diagnosis based on videotapes. Results indicated lower socioeconomic class individuals were more often diagnosed correctly for alcoholism, and Blacks were diagnosed alcoholic more often than…

  4. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes.

    PubMed

    Mardinoglu, Adil; Boren, Jan; Smith, Ulf

    2016-01-12

    Type 2 diabetes (T2D) is associated with dysbiosis of the gut microbiota, though diabetes treatment regimens, including metformin, may confound the results. Forslund et al. (2015) identify distinct disease and drug signatures and highlight the importance of adjusting for treatment when investigating how T2D influences the human gut microbiome. PMID:26771114

  5. Controlling Time-Dependent Confounding by Health Status and Frailty: Restriction Versus Statistical Adjustment

    PubMed Central

    McGrath, Leah J.; Ellis, Alan R.; Brookhart, M. Alan

    2015-01-01

    Nonexperimental studies of preventive interventions are often biased because of the healthy-user effect and, in frail populations, because of confounding by functional status. Bias is evident when estimating influenza vaccine effectiveness, even after adjustment for claims-based indicators of illness. We explored bias reduction methods while estimating vaccine effectiveness in a cohort of adult hemodialysis patients. Using the United States Renal Data System and linked data from a commercial dialysis provider, we estimated vaccine effectiveness using a Cox proportional hazards marginal structural model of all-cause mortality before and during 3 influenza seasons in 2005/2006 through 2007/2008. To improve confounding control, we added frailty indicators to the model, measured time-varying confounders at different time intervals, and restricted the sample in multiple ways. Crude and baseline-adjusted marginal structural models remained strongly biased. Restricting to a healthier population removed some unmeasured confounding; however, this reduced the sample size, resulting in wide confidence intervals. We estimated an influenza vaccine effectiveness of 9% (hazard ratio = 0.91, 95% confidence interval: 0.72, 1.15) when bias was minimized through cohort restriction. In this study, the healthy-user bias could not be controlled through statistical adjustment; however, sample restriction reduced much of the bias. PMID:25868551

  6. Adjusting for unmeasured confounding due to either of two crossed factors with a logistic regression model.

    PubMed

    Li, Li; Brumback, Babette A; Weppelmann, Thomas A; Morris, J Glenn; Ali, Afsar

    2016-08-15

    Motivated by an investigation of the effect of surface water temperature on the presence of Vibrio cholerae in water samples collected from different fixed surface water monitoring sites in Haiti in different months, we investigated methods to adjust for unmeasured confounding due to either of the two crossed factors site and month. In the process, we extended previous methods that adjust for unmeasured confounding due to one nesting factor (such as site, which nests the water samples from different months) to the case of two crossed factors. First, we developed a conditional pseudolikelihood estimator that eliminates fixed effects for the levels of each of the crossed factors from the estimating equation. Using the theory of U-Statistics for independent but non-identically distributed vectors, we show that our estimator is consistent and asymptotically normal, but that its variance depends on the nuisance parameters and thus cannot be easily estimated. Consequently, we apply our estimator in conjunction with a permutation test, and we investigate use of the pigeonhole bootstrap and the jackknife for constructing confidence intervals. We also incorporate our estimator into a diagnostic test for a logistic mixed model with crossed random effects and no unmeasured confounding. For comparison, we investigate between-within models extended to two crossed factors. These generalized linear mixed models include covariate means for each level of each factor in order to adjust for the unmeasured confounding. We conduct simulation studies, and we apply the methods to the Haitian data. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892025

  7. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes.

    PubMed

    Mardinoglu, Adil; Boren, Jan; Smith, Ulf

    2016-01-12

    Type 2 diabetes (T2D) is associated with dysbiosis of the gut microbiota, though diabetes treatment regimens, including metformin, may confound the results. Forslund et al. (2015) identify distinct disease and drug signatures and highlight the importance of adjusting for treatment when investigating how T2D influences the human gut microbiome.

  8. Assessing Mediation Using Marginal Structural Models in the Presence of Confounding and Moderation

    ERIC Educational Resources Information Center

    Coffman, Donna L.; Zhong, Wei

    2012-01-01

    This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW…

  9. Confounds in Assessing the Associations between Biliteracy and English Language Proficiency

    ERIC Educational Resources Information Center

    Proctor, C. Patrick; Silverman, Rebecca D.

    2011-01-01

    It has long been theorized, if not exhaustively researched, that bilingualism and biliteracy are beneficial in promoting linguistic and academic gains; but the operationalization of these constructs is confounding. In the current study, the authors worked with 118 Spanish-English bilingual Latina/o students and investigated whether Spanish-English…

  10. An education gradient in health, a health gradient in education, or a confounded gradient in both?

    PubMed

    Lynch, Jamie L; von Hippel, Paul T

    2016-04-01

    There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health.

  11. Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

    PubMed Central

    DeMaris, Alfred

    2014-01-01

    Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

  12. Measures of Biochemical Sociology

    ERIC Educational Resources Information Center

    Snell, Joel; Marsh, Mitchell

    2008-01-01

    In a previous article, the authors introduced a new sub field in sociology that we labeled "biochemical sociology." We introduced the definition of a sociology that encompasses sociological measures, psychological measures, and biological indicators Snell & Marsh (2003). In this article, we want to demonstrate a research strategy that would assess…

  13. Biochemical Education in Brazil.

    ERIC Educational Resources Information Center

    Vella, F.

    1988-01-01

    Described are discussions held concerning the problems of biochemical education in Brazil at a meeting of the Sociedade Brazileira de Bioquimica in April 1988. Also discussed are other visits that were made to universities in Brazil. Three major recommendations to improve the state of biochemistry education in Brazil are presented. (CW)

  14. Biochemical upgrading of oils

    DOEpatents

    Premuzic, E.T.; Lin, M.S.

    1999-01-12

    A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed. 121 figs.

  15. Nanoparticles as biochemical sensors

    PubMed Central

    El-Ansary, Afaf; Faddah, Layla M

    2010-01-01

    There is little doubt that nanoparticles offer real and new opportunities in many fields, such as biomedicine and materials science. Such particles are small enough to enter almost all areas of the body, including cells and organelles, potentially leading to new approaches in nanomedicine. Sensors for small molecules of biochemical interest are of critical importance. This review is an attempt to trace the use of nanomaterials in biochemical sensor design. The possibility of using nanoparticles functionalized with antibodies as markers for proteins will be elucidated. Moreover, capabilities and applications for nanoparticles based on gold, silver, magnetic, and semiconductor materials (quantum dots), used in optical (absorbance, luminescence, surface enhanced Raman spectroscopy, surface plasmon resonance), electrochemical, and mass-sensitive sensors will be highlighted. The unique ability of nanosensors to improve the analysis of biochemical fluids is discussed either through considering the use of nanoparticles for in vitro molecular diagnosis, or in the biological/biochemical analysis for in vivo interaction with the human body. PMID:24198472

  16. Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

    PubMed Central

    Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

    2015-01-01

    We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

  17. Histopathological baseline levels and confounding factors in common sole (Solea solea) for marine environmental risk assessment.

    PubMed

    Cuevas, N; Zorita, I; Costa, P M; Larreta, J; Franco, J

    2015-09-01

    Liver and gonad histopathology, biometric parameters and hepatic metal bioaccumulation were assessed monthly over a one-year period in common soles from the Basque continental shelf, in order to determine baseline levels and confounding factors within biomonitoring studies. Biometric parameters and hepatic metal bioaccumulation varied according to season and gender. Accordingly, hepatic histopathological traits presented seasonal variations related to the reproductive cycle. However, the hepatic histopathological index showed that seasonality and gender were not significant confounding factors. Conversely, the gonad histopathological index was modulated by season and gender. As for organ comparison, the liver endured more severe histopathological damage than the gonad. In brief, the sampling period and gender may not affect the estimation of hepatic histopathological indices for biomonitoring purposes. Nonetheless, due to different sensitivities to environmental 'noise' variables, the sampling period and gender differentiation should be thoroughly considered for the assessment of gonad histopathology, biometrics and metal bioaccumulation. PMID:26364682

  18. In vivo measurement of 241Am in the lungs confounded by activity deposited in other organs.

    PubMed

    Lobaugh, Megan L; Spitz, Henry B; Glover, Samuel E

    2015-01-01

    Radioactive material deposited in multiple organs of the body is likely to confound a result of an in vivo measurement performed over the lungs, the most frequently monitored organ for occupational exposure. The significance of this interference was evaluated by measuring anthropometric torso phantoms containing lungs, liver, skeleton, and axillary lymph nodes, each with a precisely known quantity of 241Am uniformly distributed in the organs. Arrays of multiple high-resolution germanium detectors were positioned over organs within the torso phantom containing 241Am or over proximal organs without activity to determine the degree of measurement confounding due to photons emitted from other source organs. A set of four mathematical response functions describes the measured count rate with detectors positioned over each of the relevant organs and 241Am contained in the measured organ or one of the other organs selected as a confounder. Simultaneous solution of these equations by matrix algebra, where the diagonal terms of the matrix are calibration factors for a direct measurement of activity in an organ and the off-diagonal terms reflect the contribution (i.e., interference or cross-talk) produced by 241Am in a confounding organ, yields the activity deposited in each of the relevant organs. The matrix solution described in this paper represents a method for adjusting a result of 241Am measured directly in one organ for interferences that may arise from 241Am deposited elsewhere and represents a technically valid procedure to aid in evaluating internal dose based upon in vivo measurements for those radioactive materials known to deposit in multiple organs.

  19. In vivo measurement of 241Am in the lungs confounded by activity deposited in other organs.

    PubMed

    Lobaugh, Megan L; Spitz, Henry B; Glover, Samuel E

    2015-01-01

    Radioactive material deposited in multiple organs of the body is likely to confound a result of an in vivo measurement performed over the lungs, the most frequently monitored organ for occupational exposure. The significance of this interference was evaluated by measuring anthropometric torso phantoms containing lungs, liver, skeleton, and axillary lymph nodes, each with a precisely known quantity of 241Am uniformly distributed in the organs. Arrays of multiple high-resolution germanium detectors were positioned over organs within the torso phantom containing 241Am or over proximal organs without activity to determine the degree of measurement confounding due to photons emitted from other source organs. A set of four mathematical response functions describes the measured count rate with detectors positioned over each of the relevant organs and 241Am contained in the measured organ or one of the other organs selected as a confounder. Simultaneous solution of these equations by matrix algebra, where the diagonal terms of the matrix are calibration factors for a direct measurement of activity in an organ and the off-diagonal terms reflect the contribution (i.e., interference or cross-talk) produced by 241Am in a confounding organ, yields the activity deposited in each of the relevant organs. The matrix solution described in this paper represents a method for adjusting a result of 241Am measured directly in one organ for interferences that may arise from 241Am deposited elsewhere and represents a technically valid procedure to aid in evaluating internal dose based upon in vivo measurements for those radioactive materials known to deposit in multiple organs. PMID:25437522

  20. Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

    PubMed

    Blanes-Vidal, Victoria; Schwartz, Joel

    2016-01-01

    Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias.

  1. Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

    PubMed

    Blanes-Vidal, Victoria; Schwartz, Joel

    2016-01-01

    Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias. PMID:27046778

  2. Mediation Analysis With Intermediate Confounding: Structural Equation Modeling Viewed Through the Causal Inference Lens

    PubMed Central

    De Stavola, Bianca L.; Daniel, Rhian M.; Ploubidis, George B.; Micali, Nadia

    2015-01-01

    The study of mediation has a long tradition in the social sciences and a relatively more recent one in epidemiology. The first school is linked to path analysis and structural equation models (SEMs), while the second is related mostly to methods developed within the potential outcomes approach to causal inference. By giving model-free definitions of direct and indirect effects and clear assumptions for their identification, the latter school has formalized notions intuitively developed in the former and has greatly increased the flexibility of the models involved. However, through its predominant focus on nonparametric identification, the causal inference approach to effect decomposition via natural effects is limited to settings that exclude intermediate confounders. Such confounders are naturally dealt with (albeit with the caveats of informality and modeling inflexibility) in the SEM framework. Therefore, it seems pertinent to revisit SEMs with intermediate confounders, armed with the formal definitions and (parametric) identification assumptions from causal inference. Here we investigate: 1) how identification assumptions affect the specification of SEMs, 2) whether the more restrictive SEM assumptions can be relaxed, and 3) whether existing sensitivity analyses can be extended to this setting. Data from the Avon Longitudinal Study of Parents and Children (1990–2005) are used for illustration. PMID:25504026

  3. The determinants of actinic skin damage: problems of confounding among environmental and constitutional variables.

    PubMed

    Holman, C D; Evans, P R; Lumsden, G J; Armstrong, B K

    1984-09-01

    Constitutional and environmental determinants of actinic skin damage, assessed by cutaneous microtopography, were evaluated in 1,216 subjects attending the 1981 Busselton Health Survey in Western Australia. Increasing age, male sex, the tendency to burn on exposure to sunlight and outdoor occupation were found to have independent predictive value for the presence of actinic skin damage. Crude positive and inverse associations of actinic skin damage with several other factors were shown to arise from confounding. Effect measures for outdoor leisure pursuits and sunscreen use were underestimated due to inverse associations of these factors with older age, and inverse associations of high-exposure outdoor activities with poor skin response to sunlight. Associations of constitutional traits typical of fair individuals and sunscreen use with the tendency to burn resulted in overestimation of effect measures. Empirical relationships of actinic skin damage with certain leisure activities and with use of sunscreens were also confounded by sex. The results indicate a need for greater attention to confounding in nonexperimental skin cancer research.

  4. Automated isolation of translational efficiency bias that resists the confounding effect of GC(AT)-content.

    PubMed

    Raiford, Douglas W; Krane, Dan E; Doom, Travis E; Raymer, Michael L

    2010-01-01

    Genomic sequencing projects are an abundant source of information for biological studies ranging from the molecular to the ecological in scale; however, much of the information present may yet be hidden from casual analysis. One such information domain, trends in codon usage, can provide a wealth of information about an organism's genes and their expression. Degeneracy in the genetic code allows more than one triplet codon to code for the same amino acid, and usage of these codons is often biased such that one or more of these synonymous codons are preferred. Detection of this bias is an important tool in the analysis of genomic data, particularly as a predictor of gene expressivity. Methods for identifying codon usage bias in genomic data that rely solely on genomic sequence data are susceptible to being confounded by the presence of several factors simultaneously influencing codon selection. Presented here is a new technique for removing the effects of one of the more common confounding factors, GC(AT)-content, and of visualizing the search-space for codon usage bias through the use of a solution landscape. This technique successfully isolates expressivity-related codon usage trends, using only genomic sequence information, where other techniques fail due to the presence of GC(AT)-content confounding influences.

  5. Reporting phenotypes in mouse models when considering body size as a potential confounder.

    PubMed

    Oellrich, Anika; Meehan, Terrence F; Parkinson, Helen; Sarntivijai, Sirarat; White, Jacqueline K; Karp, Natasha A

    2016-01-01

    Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput phenotyping program whose goal is to collect phenotype data for a knockout mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation.

  6. Threats to internal validity in exercise science: a review of overlooked confounding variables.

    PubMed

    Halperin, Israel; Pyne, David B; Martin, David T

    2015-10-01

    Internal validity refers to the degree of control exerted over potential confounding variables to reduce alternative explanations for the effects of various treatments. In exercise and sports-science research and routine testing, internal validity is commonly achieved by controlling variables such as exercise and warm-up protocols, prior training, nutritional intake before testing, ambient temperature, time of testing, hours of sleep, age, and gender. However, a number of other potential confounding variables often do not receive adequate attention in sports physiology and performance research. These confounding variables include instructions on how to perform the test, volume and frequency of verbal encouragement, knowledge of exercise endpoint, number and gender of observers in the room, influence of music played before and during testing, and the effects of mental fatigue on performance. In this review the authors discuss these variables in relation to common testing environments in exercise and sports science and present some recommendations with the goal of reducing possible threats to internal validity.

  7. On the role of marginal confounder prevalence – implications for the high-dimensional propensity score algorithm

    PubMed Central

    Schuster, Tibor; Pang, Menglan; Platt, Robert W

    2016-01-01

    PURPOSE The high-dimensional propensity score algorithm attempts to improve control of confounding in typical treatment effect studies in pharmacoepidemiology and is increasingly being used for the analysis of large administrative databases. Within this multi-step variable selection algorithm, the marginal prevalence of non-zero covariate values is considered to be an indicator for a count variable's potential confounding impact. We investigate the role of the marginal prevalence of confounder variables on potentially caused bias magnitudes when estimating risk ratios in point exposure studies with binary outcomes. METHODS We apply the law of total probability in conjunction with an established bias formula to derive and illustrate relative bias boundaries with respect to marginal confounder prevalence. RESULTS We show that maximum possible bias magnitudes can occur at any marginal prevalence level of a binary confounder variable. In particular, we demonstrate that, in case of rare or very common exposures, low and high prevalent confounder variables can still have large confounding impact on estimated risk ratios. CONCLUSIONS Covariate pre-selection by prevalence may lead to sub-optimal confounder sampling within the high-dimensional propensity score algorithm. While we believe that the high-dimensional propensity score has important benefits in large-scale pharmacoepidemiologic studies, we recommend omitting the prevalence-based empirical identification of candidate covariates. PMID:25866189

  8. Progress in biochemical engineering.

    PubMed

    Böing, J T

    1976-07-01

    Biochemical engineering is one of the answers to some of the challenges of the present age: hunger, shortage in raw material and energy supply and contamination of environment. Its contribution to the solution of these problems is the industrial production of protein, the use of raw materials (incl. waste products) not used up to now, the accomplishment of chemical reactions at ambient temperatures as well as the degradation or utilization of widely different waste materials.

  9. Confronting ‘confounding by health system use’ in Medicare Part D: Comparative effectiveness of propensity score approaches to confounding adjustment

    PubMed Central

    Polinski, Jennifer M.; Schneeweiss, Sebastian; Glynn, Robert J.; Lii, Joyce; Rassen, Jeremy

    2012-01-01

    Purpose Under Medicare Part D, patient characteristics influence plan choice, which in turn influences Part D coverage gap entry. We compared pre-defined propensity score (PS) and high-dimensional propensity score (hdPS) approaches to address such ‘confounding by health system use’ in assessing whether coverage gap entry is associated with cardiovascular events or death. Methods We followed 243,079 Medicare patients aged 65+ with linked prescription, medical, and plan-specific data in 2005–2007. Patients reached the coverage gap and were followed until an event or year’s end. Exposed patients were responsible for drug costs in the gap; unexposed patients (patients with non-Part D drug insurance and Part D patients receiving a low-income subsidy (LIS)) received financial assistance. Exposed patients were 1:1 PS- or hdPS-matched to unexposed patients. The PS model included 52 predefined covariates; the hdPS model added 400 empirically identified covariates. Hazard ratios for death and any of five cardiovascular outcomes were compared. In sensitivity analyses, we explored residual confounding using only LIS patients in the unexposed group. Results In unadjusted analyses, exposed patients had no greater hazard of death (HR=1.00; 95% CI, 0.84–1.20) or other outcomes. PS- (HR=1.29;0.99–1.66) and hdPS- (HR=1.11;0.86–1.42) matched analyses showed elevated but non-significant hazards of death. In sensitivity analyses, the PS analysis showed a protective effect (HR=0.78;0.61–0.98), while the hdPS analysis (HR=1.06;0.82–1.37) confirmed the main hdPS findings. Conclusion Although the PS-matched analysis suggested elevated though non-significant hazards of death among patients with no financial assistance during the gap, the hdPS analysis produced lower estimates that were stable across sensitivity analyses. PMID:22552984

  10. The effect of clozapine on premature mortality: an assessment of clinical monitoring and other potential confounders.

    PubMed

    Hayes, Richard D; Downs, Johnny; Chang, Chin-Kuo; Jackson, Richard G; Shetty, Hitesh; Broadbent, Matthew; Hotopf, Matthew; Stewart, Robert

    2015-05-01

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes. PMID:25154620

  11. A powerful and efficient set test for genetic markers that handles confounders

    PubMed Central

    Listgarten, Jennifer; Lippert, Christoph; Kang, Eun Yong; Xiang, Jing; Kadie, Carl M.; Heckerman, David

    2013-01-01

    Motivation: Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger datasets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects—one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured Genetic Analysis Workshop 14 data demonstrates that our method successfully corrects for population structure and family relatedness, whereas application of our method to a 15 000 individual Crohn’s disease case–control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.com. Contact: jennl@microsoft.com or lippert@microsoft.com or heckerma@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23599503

  12. The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders

    PubMed Central

    Hayes, Richard D.; Downs, Johnny; Chang, Chin-Kuo; Jackson, Richard G.; Shetty, Hitesh; Broadbent, Matthew; Hotopf, Matthew; Stewart, Robert

    2015-01-01

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007–2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2–0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes. PMID:25154620

  13. Is the inverse association between selenium and bladder cancer due to confounding by smoking?

    PubMed

    Beane Freeman, Laura E; Karagas, Margaret R; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T; Colt, Joanne S; Jackson, Brian; Hosain, G M Monawar; Cantor, Kenneth P; Silverman, Debra T

    2015-04-01

    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

  14. A comparison of confounding adjustment methods with an application to early life determinants of childhood obesity

    PubMed Central

    Kleinman, Ken; Gillman, Matthew W.

    2014-01-01

    We implemented 6 confounding adjustment methods: 1) covariate-adjusted regression, 2) propensity score (PS) regression, 3) PS stratification, 4) PS matching with two calipers, 5) inverse-probability-weighting, and 6) doubly-robust estimation to examine the associations between the BMI z-score at 3 years and two separate dichotomous exposure measures: exclusive breastfeeding versus formula only (N = 437) and cesarean section versus vaginal delivery (N = 1236). Data were drawn from a prospective pre-birth cohort study, Project Viva. The goal is to demonstrate the necessity and usefulness, and approaches for multiple confounding adjustment methods to analyze observational data. Unadjusted (univariate) and covariate-adjusted linear regression associations of breastfeeding with BMI z-score were −0.33 (95% CI −0.53, −0.13) and −0.24 (−0.46, −0.02), respectively. The other approaches resulted in smaller N (204 to 276) because of poor overlap of covariates, but CIs were of similar width except for inverse-probability-weighting (75% wider) and PS matching with a wider caliper (76% wider). Point estimates ranged widely, however, from −0.01 to −0.38. For cesarean section, because of better covariate overlap, the covariate-adjusted regression estimate (0.20) was remarkably robust to all adjustment methods, and the widths of the 95% CIs differed less than in the breastfeeding example. Choice of covariate adjustment method can matter. Lack of overlap in covariate structure between exposed and unexposed participants in observational studies can lead to erroneous covariate-adjusted estimates and confidence intervals. We recommend inspecting covariate overlap and using multiple confounding adjustment methods. Similar results bring reassurance. Contradictory results suggest issues with either the data or the analytic method. PMID:25171142

  15. Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors

    PubMed Central

    Schiekirka, Sarah; Feufel, Markus A.; Herrmann-Lingen, Christoph; Raupach, Tobias

    2015-01-01

    Background and objective: Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors. Methods: We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the “grey literature”. Results are presented as a narrative review. Results: We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards. Conclusion: The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors. PMID:26421003

  16. Identification of pim kinases as novel targets for PJ34 with confounding effects in PARP biology.

    PubMed

    Antolín, Albert A; Jalencas, Xavier; Yélamos, José; Mestres, Jordi

    2012-12-21

    Small molecules are widely used in chemical biology without complete knowledge of their target profile, at risk of deriving conclusions that ignore potential confounding effects from unknown off-target interactions. The prediction and further experimental confirmation of novel affinities for PJ34 on Pim1 (IC(50) = 3.7 μM) and Pim2 (IC(50) = 16 μM) serine/threonine kinases, together with their involvement in many of the processes relevant to PARP biology, questions the appropriateness of using PJ34 as a chemical tool to probe the biological role of PARP1 and PARP2 at the high micromolar concentrations applied in most studies. PMID:23025350

  17. Bounds on potential risks and causal risk differences under assumptions about confounding parameters.

    PubMed

    Chiba, Yasutaka; Sato, Tosiya; Greenland, Sander

    2007-12-10

    Nonparametric bounds on causal effects in observational studies are available under deterministic potential-outcome models. We derive narrower bounds by adding assumptions regarding bias due to confounding. This bias is defined as the difference between the expectation of potential outcomes for the exposed group and that for the unexposed group. We show that crude effect measures bound causal effects under the given assumptions. We then derive bounds for randomized studies with noncompliance, which are given by the per protocol effect. With perfect compliance in one treatment group, the direction of effect becomes identifiable under our assumptions. Although the assumptions are not themselves identifiable, they are nonetheless reasonable in some situations.

  18. Subliminal psychodynamic activation: an experiment controlling for major possible confounding influences outlined by Fudin.

    PubMed

    Gustafson, R; Källmén, H

    1991-08-01

    40 and 48 subjects participated in two separate experiments aimed at reproducing the subliminal psychodynamic activation (SPA) phenomenon and taking into account the major methodological critique by Fudin (1986, 1990). Subjects were first exposed either to a full or one of all possible partial symbiotic messages and then to their anagram equivalents. Confounding and irrelevant influences were controlled; the results indicate that only the full symbiotic message improved motor performance. This strongly suggests that subjects encode the meaning of the full message and supports an interpretation in terms of an alleviation of an internal symbiotic conflict leading to a state of calmness conducive to improved motor performance. PMID:1945681

  19. Child welfare clients have higher risks for teenage childbirths: which are the major confounders?

    PubMed Central

    Vinnerljung, Bo; Hjern, Anders

    2016-01-01

    Background: Aiming to support effective social intervention strategies targeting high-risk groups for teenage motherhood, this study examined to what extent the elevated crude risks of teenage childbirth among child welfare groups were attributable to the uneven distribution of adverse individual and family background factors. Methods: Comprehensive longitudinal register data for more than 700 000 Swedish females born 1973–1989 (including around 29 000 child welfare clients) were analysed by means of binary logistic regression. The Karlson/Holm/Breen-method was used to decompose each confounding factor’s relative contribution to the difference between crude and adjusted odds ratios (ORs). Results: Elevated crude risks for teenage childbirth are to a large extent attributable to selection on observables. Girls’ school failure was the most potent confounder, accounting for 28–35% of the difference between crude and adjusted ORs. Conclusion: As in majority populations, girls’ school failure was a strong risk factor for teenage childbirth among former child welfare children. At least among pre-adolescents, promoting school performance among children in the child welfare system seems to be a viable intervention path. PMID:27085195

  20. On the causal interpretation of race in regressions adjusting for confounding and mediating variables.

    PubMed

    VanderWeele, Tyler J; Robinson, Whitney R

    2014-07-01

    We consider several possible interpretations of the "effect of race" when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person's life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the effect of race (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (eg, skin color), parental physical phenotype, genetic background, and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects.

  1. On causal interpretation of race in regressions adjusting for confounding and mediating variables

    PubMed Central

    VanderWeele, Tyler J.; Robinson, Whitney R.

    2014-01-01

    We consider several possible interpretations of the “effect of race” when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person’s life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the “effect of race” (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (e.g. skin color), parental physical phenotype, genetic background and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects. PMID:24887159

  2. Limitations of individual causal models, causal graphs, and ignorability assumptions, as illustrated by random confounding and design unfaithfulness.

    PubMed

    Greenland, Sander; Mansournia, Mohammad Ali

    2015-10-01

    We describe how ordinary interpretations of causal models and causal graphs fail to capture important distinctions among ignorable allocation mechanisms for subject selection or allocation. We illustrate these limitations in the case of random confounding and designs that prevent such confounding. In many experimental designs individual treatment allocations are dependent, and explicit population models are needed to show this dependency. In particular, certain designs impose unfaithful covariate-treatment distributions to prevent random confounding, yet ordinary causal graphs cannot discriminate between these unconfounded designs and confounded studies. Causal models for populations are better suited for displaying these phenomena than are individual-level models, because they allow representation of allocation dependencies as well as outcome dependencies across individuals. Nonetheless, even with this extension, ordinary graphical models still fail to capture distinctions between hypothetical superpopulations (sampling distributions) and observed populations (actual distributions), although potential-outcome models can be adapted to show these distinctions and their consequences.

  3. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  4. Non-Chemical Distant Cellular Interactions as a potential confounder of cell biology experiments.

    PubMed

    Farhadi, Ashkan

    2014-01-01

    Distant cells can communicate with each other through a variety of methods. Two such methods involve electrical and/or chemical mechanisms. Non-chemical, distant cellular interactions may be another method of communication that cells can use to modify the behavior of other cells that are mechanically separated. Moreover, non-chemical, distant cellular interactions may explain some cases of confounding effects in Cell Biology experiments. In this article, we review non-chemical, distant cellular interactions studies to try to shed light on the mechanisms in this highly unconventional field of cell biology. Despite the existence of several theories that try to explain the mechanism of non-chemical, distant cellular interactions, this phenomenon is still speculative. Among candidate mechanisms, electromagnetic waves appear to have the most experimental support. In this brief article, we try to answer a few key questions that may further clarify this mechanism.

  5. Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.

    PubMed

    Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

    2012-03-01

    Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. PMID:22243869

  6. Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

    PubMed

    Landau, Anne M; Kouassi, Edouard; Siegrist-Johnstone, Rosmarie; Desbarats, Julie

    2007-02-15

    Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model. PMID:17230468

  7. Duration perception of emotional stimuli: Using evaluative conditioning to avoid sensory confounds.

    PubMed

    Kliegl, Katrin M; Watrin, Luc; Huckauf, Anke

    2015-01-01

    It has been found that emotional pictures are estimated to last longer than neutral ones. However, emotional and neutral stimuli often differ in their physical characteristics, too. Since this might also affect time perception, we present a method disentangling a possible confounding regarding the processing of physically different stimulus material. In the evaluative condition paradigm, participants, at first, learnt the association of neutral images with a certain Landolt ring and of emotional images with another Landolt ring with a different gap position. The conditioned Landolt rings were subsequently used in a temporal bisection task. In two experiments, the results revealed a temporal overestimation of Landolt rings conditioned with emotional pictures compared to neutral pictures showing that the temporal overestimation of emotional stimuli cannot be attributed to perceptual differences between neutral and emotional stimuli. The method provides the potential for investigating emotional effects on various perceptual processes.

  8. How helpers help: disentangling ecological confounds from the benefits of cooperative breeding.

    PubMed

    Wright, Jonathan; Russell, Andrew F

    2008-05-01

    Evolutionary explanations for helping in cooperative breeding systems usually require a positive effect of helping on the fitness of the breeders being assisted. However, such helper effects have proven surprisingly difficult to quantify. Cockburn et al. (this issue) apply detailed statistical analyses to long-term field data on the enigmatic superb fairy-wren. They show that it is possible to disentangle the complex web of ecological and evolutionary interactions that confound so many studies. Whilst fairy-wren helpers may not increase nest productivity, they do increase future survival of breeding females. This study points the way for future statistical explorations of long-term data in other cooperative birds and mammals.

  9. Parietal and bi-occipital lobe infarction confounded by ethanol-induced optic neuropathy.

    PubMed

    Tornatore, C W; Townsend, J C; Selvin, G J

    1991-08-01

    A frequent occurrence in geriatric and chronically ill patients is the exhibition of several simultaneously occurring and confounding health problems. This paper reports the case of a 61-year-old-white male who presented with an extensive history of multiple brain infarcts, hemiparesis, personality changes and varied visual complaints. Tests in the neurooptometric work-up for this patient included static automated perimetry, stereoacuity and optokinetic nystagmus evaluation. The results were suggestive of multiple cerebrovascular accidents which included the right and left occipital lobes as well as the right parietal lobe. This clinical picture was complicated by the presence of nutritional or ethanol-induced optic neuropathy. Emphasis was placed on a detailed sequential history of events and a complete neurological and optometric evaluation to ascertain the multiple foci of cortical infarction. Corroboration of clinical findings was obtained by computerized axial tomography (CT scan).

  10. Can Jurors Recognize Missing Control Groups, Confounds, and Experimenter Bias in Psychological Science?

    PubMed Central

    McAuliff, Bradley D.; Kovera, Margaret Bull; Nunez, Gabriel

    2010-01-01

    This study examined the ability of jury-eligible community members (N = 248) to detect internal validity threats in psychological science presented during a trial. Participants read a case summary in which an expert testified about a study that varied in internal validity (valid, missing control group, confound, and experimenter bias) and ecological validity (high, low). Ratings of expert evidence quality and expert credibility were higher for the valid versus missing control group versions only. Internal validity did not influence verdict or ratings of plaintiff credibility and no differences emerged as a function of ecological validity. Expert evidence quality, expert credibility, and plaintiff credibility were positively correlated with verdict. Implications for the scientific reasoning literature and for trials containing psychological science are discussed. PMID:18587635

  11. Temperature: a prolonged confounding factor on cholinesterase activity in the tropical reef fish Acanthochromis polyacanthus.

    PubMed

    Botté, Emmanuelle S; Smith-Keune, Carolyn; Jerry, Dean R

    2013-09-15

    Cholinesterase activity usually decreases in fish exposed to anticholinesterase compounds such as organophosphate and carbamate pesticides. Here we show that tropical reef fish Acanthochromis polyacanthus (or spiny damsel) also exhibits a decrease in ChE activity when exposed to elevated temperature from 28°C to 32°C or 34°C after 4 days. We further demonstrate that the decline persists even after 7 days of recovery at control temperature. This is the first report of a drop in ChE activity in fish as temperature increases. Our results strongly suggest the need for long-term monitoring of water temperature in the field prior to sampling A. polyacanthus for toxicology studies, as temperature is a prolonged and confounding factor for ChE activity in this species.

  12. Missing variables: how exclusion of human resources policy information confounds research connecting health and business outcomes.

    PubMed

    Lynch, Wendy D; Sherman, Bruce W

    2014-01-01

    When corporate health researchers examine the effects of health on business outcomes or the effect of health interventions on health and business outcomes, results will necessarily be confounded by the corporate environment(s) in which they are studied. In this research setting, most studies control for factors traditionally identified in public health, such as demographics and health status. Nevertheless, often overlooked is the extent to which company policies can also independently impact health care cost, work attendance, and productivity outcomes. With changes in employment and benefits practices resulting from health care reform, including incentives and plan design options, consideration of these largely neglected variables in research design has become increasingly important. This commentary summarizes existing knowledge regarding the implications of policy variations in research outcomes and provides a framework for incorporating them into future employer-based research.

  13. Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.

    PubMed

    Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

    2012-03-01

    Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set.

  14. Can jurors recognize missing control groups, confounds, and experimenter bias in psychological science?

    PubMed

    McAuliff, Bradley D; Kovera, Margaret Bull; Nunez, Gabriel

    2009-06-01

    This study examined the ability of jury-eligible community members (N = 248) to detect internal validity threats in psychological science presented during a trial. Participants read a case summary in which an expert testified about a study that varied in internal validity (valid, missing control group, confound, and experimenter bias) and ecological validity (high, low). Ratings of expert evidence quality and expert credibility were higher for the valid versus missing control group versions only. Internal validity did not influence verdict or ratings of plaintiff credibility and no differences emerged as a function of ecological validity. Expert evidence quality, expert credibility, and plaintiff credibility were positively correlated with verdict. Implications for the scientific reasoning literature and for trials containing psychological science are discussed.

  15. Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

    PubMed Central

    Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

    2015-01-01

    Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

  16. Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia.

    PubMed

    Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

    2016-01-01

    Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent "time effects" in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.

  17. PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances

    PubMed Central

    Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V.

    2016-01-01

    Motivation: Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. Results: We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. Availability and Implementation: miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile. Contact: z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics

  18. Measurement confounding affects the extent to which verbal IQ explains social gradients in mortality

    PubMed Central

    Chapman, Benjamin; Fiscella, Kevin; Duberstein, Paul; Kawachi, Ichiro; Muennig, Peter

    2016-01-01

    Background IQ is thought to explain social gradients in mortality. IQ scores are based roughly equally on Verbal IQ (VIQ) and Performance IQ tests. VIQ tests, however, are suspected to confound true verbal ability with socioeconomic status (SES), raising the possibility that associations between SES and IQ scores might be overestimated. We examined, first, whether two of the most common types of VIQ tests exhibited differential item functioning (DIF) favouring persons of higher SES and/or majority race/ethnicity. Second, we assessed what impact, if any, this had on estimates of the extent to which VIQ explains social gradients in mortality. Methods Data from the General Social Survey-National Death Index cohort, a US population representative dataset, was used. Item response theory models queried social-factor DIF on the Thorndike Verbal Intelligence Scale and Wechsler Adult Intelligence Scales, Revised Similarities test. Cox models examined mortality associations among SES and VIQ scores corrected and uncorrected for DIF. Results When uncorrected for DIF, VIQ was correlated with income, education, occupational prestige and race, with correlation coefficients ranging between |0.12| and |0.43|. After correcting for DIF, correlations ranged from |0.06| to |0.16|. Uncorrected VIQ scores explained 11–40% of the Relative Index of Inequalities in mortality for social factors, while DIF-corrected scores explained 2–29%. Conclusions Two of the common forms of VIQ tests appear confound verbal intelligence with SES. Since these tests appear in most IQ batteries, circumspection may be warranted in estimating the amount of social inequalities in mortality attributable to IQ. PMID:24729404

  19. Sediment organic matter content as a confounding factor in toxicity tests with Chironomus tentans

    SciTech Connect

    Lacey, R.; Watzin, M.C.; McIntosh, A.W.

    1999-02-01

    Physicochemical characteristics of sediment unrelated to contaminant levels and bioavailability may influence the outcome of toxicity tests. In particular, sediment organic matter content has the potential to be a confounding factor in toxicity tests using the midge larva Chironomus tentans because the larvae are infaunal and feed on organic matter in the sediments. To examine the possibility, the authors conducted a series of tests using formulated sediments with varying organic matter contents following the standard US Environmental Protection Agency (US EPA) 10-day C. tentans growth and survival protocol. Formulated sediments made with peat moss, {alpha}-cellulose, and maple leaves were tested. An organic-rich natural sediment diluted with formulated sediment to achieve a range of organic matter contents was also examined. In a final experiment, sediments containing each of the four organic matter sources at the same concentration were tested against one another. Survival was not greatly affected by concentration of organic matter, except at the lowest concentrations in natural sediment, where survival dipped below 70%. In experiments using peat moss, {alpha}-cellulose, and maple leaves, significant differences in C. tentans growth were found at different organic matter concentrations. In contrast, concentration of organic matter in the natural sediment dilution series had little effect on growth, perhaps because much of this material was highly refractory. In the comparison experiment, growth differed significantly among the four sediments, with best growth achieved with {alpha}-cellulose and leaves. These results suggest that both organic matter quantity and quality can be confounding factors in toxicity tests using C. tentans.

  20. An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

    SciTech Connect

    Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

    2007-07-01

    We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extent to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.

  1. A method for controlling complex confounding effects in the detection of adverse drug reactions using electronic health records

    PubMed Central

    Li, Ying; Salmasian, Hojjat; Vilar, Santiago; Chase, Herbert; Friedman, Carol; Wei, Ying

    2014-01-01

    Objective Electronic health records (EHRs) contain information to detect adverse drug reactions (ADRs), as they contain comprehensive clinical information. A major challenge of using comprehensive information involves confounding. We propose a novel data-driven method to identify ADR signals accurately by adjusting for confounders. Materials and methods We focused on two serious ADRs, rhabdomyolysis and pancreatitis, and used information in 264 155 unique patient records. We identified an ADR using established criteria, selected potential confounders, and then used penalized logistic regressions to estimate confounder-adjusted ADR associations. A reference standard was created to evaluate and compare the precision of the proposed method and four others. Results Precision was 83.3% for rhabdomyolysis and 60.8% for pancreatitis when using the proposed method, and we identified several drug safety signals that are interesting for further clinical review. Discussion The proposed method effectively estimated ADR associations after adjusting for confounders. A main cause of error was probably due to the nature of the dataset in that a substantial number of patients had a single visit only and, therefore, it was not possible to determine correctly the appropriate sequence of events for them. It is likely that performance will be improved with use of EHR data that contain more longitudinal records. Conclusions This data-driven method is effective in controlling for confounding, resulting in either a higher or similar precision when compared with four comparators, has the unique ability to provide insight into confounders for each specific medication–ADR pair, and can be easily adapted to other EHR systems. PMID:23907285

  2. External Adjustment Sensitivity Analysis for Unmeasured Confounding: An Application to Coronary Stent Outcomes, Pennsylvania 2004–2008

    PubMed Central

    Huesch, Marco D

    2013-01-01

    Background Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. Objective To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Data Sources/Study Setting Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004–2005 followed up for death through 3 years. Study Design Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. Principal Findings DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Conclusions Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. PMID:23206261

  3. Accounting for uncertainty in confounder and effect modifier selection when estimating average causal effects in generalized linear models.

    PubMed

    Wang, Chi; Dominici, Francesca; Parmigiani, Giovanni; Zigler, Corwin Matthew

    2015-09-01

    Confounder selection and adjustment are essential elements of assessing the causal effect of an exposure or treatment in observational studies. Building upon work by Wang et al. (2012, Biometrics 68, 661-671) and Lefebvre et al. (2014, Statistics in Medicine 33, 2797-2813), we propose and evaluate a Bayesian method to estimate average causal effects in studies with a large number of potential confounders, relatively few observations, likely interactions between confounders and the exposure of interest, and uncertainty on which confounders and interaction terms should be included. Our method is applicable across all exposures and outcomes that can be handled through generalized linear models. In this general setting, estimation of the average causal effect is different from estimation of the exposure coefficient in the outcome model due to noncollapsibility. We implement a Bayesian bootstrap procedure to integrate over the distribution of potential confounders and to estimate the causal effect. Our method permits estimation of both the overall population causal effect and effects in specified subpopulations, providing clear characterization of heterogeneous exposure effects that may vary considerably across different covariate profiles. Simulation studies demonstrate that the proposed method performs well in small sample size situations with 100-150 observations and 50 covariates. The method is applied to data on 15,060 US Medicare beneficiaries diagnosed with a malignant brain tumor between 2000 and 2009 to evaluate whether surgery reduces hospital readmissions within 30 days of diagnosis.

  4. Accounting for Uncertainty in Confounder and Effect Modifier Selection when Estimating Average Causal Effects in Generalized Linear Models

    PubMed Central

    Wang, Chi; Dominici, Francesca; Parmigiani, Giovanni; Zigler, Corwin Matthew

    2015-01-01

    Summary Confounder selection and adjustment are essential elements of assessing the causal effect of an exposure or treatment in observational studies. Building upon work by Wang et al. (2012) and Lefebvre et al. (2014), we propose and evaluate a Bayesian method to estimate average causal effects in studies with a large number of potential confounders, relatively few observations, likely interactions between confounders and the exposure of interest, and uncertainty on which confounders and interaction terms should be included. Our method is applicable across all exposures and outcomes that can be handled through generalized linear models. In this general setting, estimation of the average causal effect is different from estimation of the exposure coefficient in the outcome model due to non-collapsibility. We implement a Bayesian bootstrap procedure to integrate over the distribution of potential confounders and to estimate the causal effect. Our method permits estimation of both the overall population causal effect and effects in specified subpopulations, providing clear characterization of heterogeneous exposure effects that may vary considerably across different covariate profiles. Simulation studies demonstrate that the proposed method performs well in small sample size situations with 100 to 150 observations and 50 covariates. The method is applied to data on 15060 US Medicare beneficiaries diagnosed with a malignant brain tumor between 2000 and 2009 to evaluate whether surgery reduces hospital readmissions within thirty days of diagnosis. PMID:25899155

  5. With a careful look: still no low-level confound to face pop-out.

    PubMed

    Hershler, Orit; Hochstein, Shaul

    2006-09-01

    In this issue of Vision Research, VanRullen, R. (2006). On second glance: Still no high-level pop-out effect for faces. Vision Research, in press. challenges our earlier Vision Research paper, "At first sight: A high-level pop-out effect for faces" (Hershler, O., & Hochstein, S. (2005). At first sight: A high-level pop-out effect for faces. Vision Research, 45, 1707-1724). In that paper, we showed that faces pop-out from a great variety of heterogeneous distractors. This search must have been based on a holistic combination of facial features, since it could not have relied on any single low-level distinguishing feature-each of which was present in at least some of the distractors. VanRullen implies that the pop-out effect is not limited to faces, is not holistic, and is due to a low-level confound, namely that the "low-level" Fourier amplitude spectrum may differentiate between faces and other categories. We now show that he fails to substantiate all three claims. His first experiment replicates our own and shows once again that faces do indeed pop-out, while other objects, such as cars, do not. The claim regarding the non-holistic nature of face search is based on a failure to differentiate between holistic processing for face detection and for individual face identification. His central claim is that the Fourier amplitude spectrum is processed low-level and could be used for face pop-out. However, changing the amplitude spectrum may well affect high-level representations as well. For example, his demonstration uses hybrid images which are extremely fuzzy, rendering them difficult to identify. More importantly, this claim would lead to the conclusion that targets with a non-face phase spectrum and only a face amplitude spectrum would pop-out among distractors with different amplitude spectra. We demonstrate that this is, of course, not the case and that the Fourier amplitude is not the hoped for "low-level confound". Until another such "hidden" low level feature

  6. Alcoholic myopathy: biochemical mechanisms.

    PubMed

    Preedy, V R; Paice, A; Mantle, D; Dhillon, A S; Palmer, T N; Peters, T J

    2001-08-01

    Between one- and two-thirds of all alcohol abusers have impairment of muscle function that may be accompanied by biochemical lesions and/or the presence of a defined myopathy characterised by selective atrophy of Type II fibres. Perturbations in protein metabolism are central to the effects on muscle and account for the reductions in muscle mass and fibre diameter. Ethanol abuse is also associated with abnormalities in carbohydrate (as well as lipid) metabolism in skeletal muscle. Ethanol-mediated insulin resistance is allied with the inhibitory effects of ethanol on insulin-stimulated carbohydrate metabolism. It acutely impairs insulin-stimulated glucose and lipid metabolism, although it is not known whether it has an analogous effect on insulin-stimulated protein synthesis. In alcoholic cirrhosis, insulin resistance occurs with respect to carbohydrate metabolism, although the actions of insulin to suppress protein degradation and stimulate amino acid uptake are unimpaired. In acute alcohol-dosing studies defective rates of protein synthesis occur, particularly in Type II fibre-predominant muscles. The relative amounts of mRNA-encoding contractile proteins do not appear to be adversely affected by chronic alcohol feeding, although subtle changes in muscle protein isoforms may occur. There are also rapid and sustained reductions in total (largely ribosomal) RNA in chronic studies. Loss of RNA appears to be related to increases in the activities of specific muscle RNases in these long-term studies. However, in acute dosing studies (less than 1 day), the reductions in muscle protein synthesis are not due to overt loss of total RNA. These data implicate a role for translational modifications in the initial stages of the myopathy, although changes in transcription and/or protein degradation may also be superimposed. These events have important implications for whole-body metabolism.

  7. Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

    PubMed

    Charron, L; Geffard, O; Chaumot, A; Coulaud, R; Queau, H; Geffard, A; Dedourge-Geffard, O

    2013-12-01

    The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

  8. Platelets confound the measurement of extracellular miRNA in archived plasma

    PubMed Central

    Mitchell, Adam J.; Gray, Warren D.; Hayek, Salim S.; Ko, Yi-An; Thomas, Sheena; Rooney, Kim; Awad, Mosaab; Roback, John D.; Quyyumi, Arshed; Searles, Charles D.

    2016-01-01

    Extracellular miRNAs are detectable in biofluids and represent a novel class of disease biomarker. Although many studies have utilized archived plasma for miRNA biomarker discovery, the effects of processing and storage have not been rigorously studied. Previous reports have suggested plasma samples are commonly contaminated by platelets, significantly confounding the measurement of extracellular miRNA, which was thought to be easily addressed by additional post-thaw plasma processing. In a case-control study of archived plasma, we noted a significant correlation between miRNA levels and platelet counts despite post-thaw processing. We thus examined the effects of a single freeze/thaw cycle on microparticles (MPs) and miRNA levels, and show that a single freeze/thaw cycle of plasma dramatically increases the number of platelet-derived MPs, contaminates the extracellular miRNA pool, and profoundly affects the levels of miRNAs detected. The measurement of extracellular miRNAs in archived samples is critically dependent on the removal of residual platelets prior to freezing plasma samples. Many previous clinical studies of extracellular miRNA in archived plasma should be interpreted with caution and future studies should avoid the effects of platelet contamination. PMID:27623086

  9. The Scalp Confounds Near-Infrared Signal from Rat Brain Following Innocuous and Noxious Stimulation

    PubMed Central

    He, Ji-Wei; Liu, Hanli; Peng, Yuan Bo

    2015-01-01

    Functional near-infrared imaging (fNIRI) is a non-invasive, low-cost and highly portable technique for assessing brain activity and functions. Both clinical and experimental evidence suggest that fNIRI is able to assess brain activity at associated regions during pain processing, indicating a strong possibility of using fNIRI-derived brain activity pattern as a biomarker for pain. However, it remains unclear how, especially in small animals, the scalp influences fNIRI signal in pain processing. Previously, we have shown that the use of a multi-channel system improves the spatial resolution of fNIRI in rats (without the scalp) during pain processing. Our current work is to investigate a scalp effect by comparing with new data from rats with the scalp during innocuous or noxious stimulation (n = 6). Results showed remarkable stimulus-dependent differences between the no-scalp and intact-scalp groups. In conclusion, the scalp confounded the fNIRI signal in pain processing likely via an autonomic mechanism; the scalp effect should be a critical factor in image reconstruction and data interpretation. PMID:26426058

  10. Choroidal abnormalities and masquerade syndromes confounding the diagnosis of laser-induced eye injuries

    NASA Astrophysics Data System (ADS)

    Hacker, Henry D.; Zwick, Harry; Brown, Jeremiah, Jr.; Dicks, Ronald; Cheramie, Rachel; Stuck, Bruce E.

    2005-04-01

    The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.

  11. Detection rates of geckos in visual surveys: Turning confounding variables into useful knowledge

    USGS Publications Warehouse

    Lardner, Bjorn; Rodda, Gordon H.; Yackel Adams, Amy A.; Savidge, Julie A.; Reed, Robert N.

    2016-01-01

    Transect surveys without some means of estimating detection probabilities generate population size indices prone to bias because survey conditions differ in time and space. Knowing what causes such bias can help guide the collection of relevant survey covariates, correct the survey data, anticipate situations where bias might be unacceptably large, and elucidate the ecology of target species. We used negative binomial regression to evaluate confounding variables for gecko (primarily Hemidactylus frenatus and Lepidodactylus lugubris) counts on 220-m-long transects surveyed at night, primarily for snakes, on 9,475 occasions. Searchers differed in gecko detection rates by up to a factor of six. The worst and best headlamps differed by a factor of at least two. Strong winds had a negative effect potentially as large as those of searchers or headlamps. More geckos were seen during wet weather conditions, but the effect size was small. Compared with a detection nadir during waxing gibbous (nearly full) moons above the horizon, we saw 28% more geckos during waning crescent moons below the horizon. A sine function suggested that we saw 24% more geckos at the end of the wet season than at the end of the dry season. Fluctuations on a longer timescale also were verified. Disturbingly, corrected data exhibited strong short-term fluctuations that covariates apparently failed to capture. Although some biases can be addressed with measured covariates, others will be difficult to eliminate as a significant source of error in longterm monitoring programs.

  12. Wrist actigraphy for scratch detection in the presence of confounding activities.

    PubMed

    Feuerstein, Johanna; Austin, Daniel; Sack, Robert; Hayes, Tamara L

    2011-01-01

    Scratching is a symptom of many dermatological disorders, especially atopic dermatitis. For the development of anti-itch medications, there is a need for objective measures of scratching. Wrist actigraphy (monitoring wrist and hand movements with micro-accelerometers) is a promising method for assessing scratching; however, currently available technology has a limited capacity to discriminate scratching from other similar movements. In this study, we investigated methods to improve the specificity of actigraphy for scratch detection on movement data collected from subjects using the PAM-RL actigraph. A k-means cluster analysis was used to differentiate scratching from walking and restless sleep, which are potential confounds for nighttime scratching. Features used in the analysis include variance, peak frequency, autocorrelation value at one lag, and number of counts above 0.01 g's. The k-means cluster analysis exhibited a high sensitivity (0.90 ± 0.10) and specificity for walking (0.98 ± 0.05) and restless sleep (0.88 ± 0.06), respectively, demonstrating the separability of these activities. This work indicates that the features described here can be used to develop a classifier that discriminates scratch from other activities. The described method of scratch detection shows promise as an objective method for assessing scratching movements in clinical trials and longitudinal studies of scratch. PMID:22255131

  13. Measuring oxidative stress: the confounding effect of lipid concentration in measures of lipid peroxidation.

    PubMed

    Pérez-Rodríguez, Lorenzo; Romero-Haro, Ana A; Sternalski, Audrey; Muriel, Jaime; Mougeot, Francois; Gil, Diego; Alonso-Alvarez, Carlos

    2015-01-01

    Lipid peroxidation products are widely used as markers of oxidative damage in the organism. To properly interpret the information provided by these markers, it is necessary to know potential sources of bias and control confounding factors. Here, we investigated the relationship between two indicators of lipid mobilization (circulating levels of triglycerides and cholesterol) and two common markers of oxidative damage (plasma levels of malondialdehyde and hydroperoxides; the latter estimated from the d-ROMs assay kit). The following five avian species were studied: red-legged partridge (Alectoris rufa), zebra finch (Taeniopygia guttata), spotless starling (Sturnus unicolor), marsh harrier (Circus aeroginosus), and Montagu's harrier (Circus pygargus). In all cases, plasma triglyceride levels positively and significantly correlated with lipid peroxidation markers, explaining between 8% and 34% of their variability. Plasma cholesterol, in contrast, showed a significant positive relationship only among spotless starling nestlings and a marginally significant association in zebra finches. These results indicate that lipid peroxidation marker levels covary with circulating lipid levels. We discuss the potential causes and implications of this covariation and recommend that future studies that measure oxidative damage using lipid peroxidation markers report both raw and relative levels (i.e., corrected for circulating triglycerides). Whether the observed pattern also holds for other tissues and in other taxa would deserve further research.

  14. Influence of potentially confounding factors on sea urchin porewater toxicity tests

    USGS Publications Warehouse

    Carr, R.S.; Biedenbach, J.M.; Nipper, M.

    2006-01-01

    The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

  15. Reproductive and socioeconomic determinants of child survival: confounded, interactive, and age-dependent effects.

    PubMed

    Kost, K; Amin, S

    1992-01-01

    Studies of infant and child mortality have evolved to distinguish between two sets of explanatory variables-factors related to reproductive or maternal characteristics and socioeconomic factors, generally described as characteristics of the family or household. Almost all multivariate analyses include variables from each of these two sets, but there has been little consideration of the relationship between them. We examine how these two sets of variables jointly affect mortality. We test first for confounded effects by examining socioeconomic effects while excluding and then including reproductive variables in nested multivariate models. Next, we look for age-dependent effects among the explanatory variables and find that reproductive and socioeconomic factors affect mortality at differing ages of children. Finally, we examine interactive effects of the two sets of variables. We conclude that the higher mortality observed among the low status groups is not a result of greater concentration of poor reproductive patterns in those groups. Instead, higher status groups probably have more resources available for combating the negative effects of the same high-risk reproductive patterns. PMID:1514117

  16. Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

    PubMed Central

    Kuuranne, Tiia; Saugy, Martial; Baume, Norbert

    2014-01-01

    In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module. PMID:24764553

  17. The confounding complexity of innate immune receptors within and between teleost species.

    PubMed

    Wcisel, Dustin J; Yoder, Jeffrey A

    2016-06-01

    Teleost genomes encode multiple multigene families of immunoglobulin domain-containing innate immune receptors (IIIRs) with unknown function and no clear mammalian orthologs. However, the genomic organization of IIIR gene clusters and the structure and signaling motifs of the proteins they encode are similar to those of mammalian innate immune receptor families such as the killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LILRs), Fc receptors, triggering receptors expressed on myeloid cells (TREMs) and CD300s. Teleost IIIRs include novel immune-type receptors (NITRs); diverse immunoglobulin domain containing proteins (DICPs); polymeric immunoglobulin receptor-like proteins (PIGRLs); novel immunoglobulin-like transcripts (NILTs) and leukocyte immune-type receptors (LITRs). The accumulation of genomic sequence data has revealed that IIIR gene clusters in zebrafish display haplotypic and gene content variation. This intraspecific genetic variation, as well as significant interspecific variation, frequently confounds the identification of definitive orthologous IIIR sequences between teleost species. Nevertheless, by defining which teleost lineages encode (and do not encode) different IIIR families, predictions can be made about the presence (or absence) of specific IIIR families in each teleost lineage. It is anticipated that further investigations into available genomic resources and the sequencing of a variety of multiple teleost genomes will identify additional IIIR families and permit the modeling of the evolutionary origins of IIIRs. PMID:26997203

  18. A causal examination of the effects of confounding factors on multimetric indices

    USGS Publications Warehouse

    Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

    2013-01-01

    The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

  19. Influence of potentially confounding factors on sea urchin porewater toxicity tests.

    PubMed

    Carr, R S; Biedenbach, J M; Nipper, M

    2006-11-01

    The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment.

  20. Assessing confounding, effect modification, and thresholds in the association between ambient particles and daily deaths.

    PubMed Central

    Schwartz, J

    2000-01-01

    I examined the relationship between daily deaths and airborne particles in 10 U.S. cities with varying climatic conditions and seasons in which particle concentrations were high. Airborne particles were associated with significant increases in daily deaths [0.67% increase for a 10 microg/m(3) increase in particles; 95% confidence interval (CI), 0.52-0.81%]. This association was the same in summer and winter. To examine potential confounding by other pollutants, I regressed city- and season-specific effect sizes against the relationship between airborne particles and other pollutants. Controlling for other pollutants did not substantially (or significantly) change the estimated effect of airborne particles. Socioeconomic differences between cities likewise did not modify the effect. The increase in daily deaths that occurred out of hospitals (0.89% per 10 microg/m(3); CI, 0.67-1.10%) was substantially greater than the increase in deaths in hospitals (0. 49%; CI, 0.31-0.68%). This is consistent with results previously reported in Philadelphia, Pennsylvania, and suggests that the particle-associated deaths are not just being brought forward by a few days. It is also consistent with recent animal and human studies of the mechanisms of particle toxicity. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:10856032

  1. Is it patience or motivation? On motivational confounds in intertemporal choice tasks.

    PubMed

    Paglieri, Fabio; Addessi, Elsa; Sbaffi, Agnese; Tasselli, Maria Isabella; Delfino, Alexia

    2015-01-01

    Intertemporal choices create a tension between amount maximization, which would favor the larger and later option (LL), and delay minimization, which would promote the smaller and sooner reward (SS). Two common interpretations of intertemporal choice behavior are discussed: looking at LL responses as indicative of self-control, and using intertemporal choices to assess delay aversion. We argue that both interpretations need to take into account motivational confounds, in order to be warranted by data. In intertemporal choices with prepotent, salient stimuli (e.g., food amounts, typically used with nonhuman primates), LL responses could also be indicative of failed inhibition of a "go for more" impulsive response-the opposite of self-control. Similarly, intertemporal choices can be used to measure delay aversion only with respect to the subject's baseline motivation to maximize the reinforcer in question, and this baseline is not always assessed in current experimental protocols. This concern is especially crucial in comparing intertemporal choices across different groups or manipulation. We focus in particular on the effects of reward types on intertemporal choices, presenting two experimental studies where the difference in behavior with monetary versus food rewards is the product of different baseline motivation, rather than variations in delay aversion. We conclude discussing the implications of these and other similar recent findings, which are far-reaching. PMID:25545635

  2. Task differences confound sex differences in receiver permissiveness in túngara frogs.

    PubMed

    Bernal, Ximena E; Rand, A Stanley; Ryan, Michael J

    2009-04-01

    In many mating systems, both sexes respond to the same sexual signal. In frogs, males typically call in response to advertisement calls, while females approach male calls in choosing a mate. The costs of signal detection errors are expected to differ between the sexes. Missed opportunities are costly for males because ignoring a signal results in failing to compete with rivals for mates, while their cost for misidentification is lower (time and energy displaying to the incorrect target). By contrast, for females, the cost of misidentification is high (mating with incorrect species or low-quality partner), while their cost for missed opportunity is lower because the operational sex ratio puts females at a premium. Consequently, females should be more selective in their response to signal variation than males. We report that presumed sexual differences in selectivity in túngara frogs (Physalaemus pustulosus) are task-specific rather than sex-specific. As predicted, male túngara frogs are less selective in their vocal responses than are females in their phonotactic responses. Males exhibiting phonotaxis to the same calls, however, are as selective as females, and are significantly more selective than when they respond vocally to the same calls. Our study shows that apparent differences between the sexes emerge from differences in the behaviours themselves and are not intrinsic to each sex. Analogous behavioural differences might confound sex differences in other systems; thus, we suggest consideration of the behavioural plasticity of sex as well as its stereotypy. PMID:19141428

  3. Isolating Cognitive and Neurologic HIV Effects in Substance-Dependent, Confounded Cohorts: A Pilot Study

    PubMed Central

    Byrd, Desiree A.; Robinson-Papp, Jessica; Mindt, Monica Rivera; Mintz, Letty; Elliott, Kathryn; Lighty, Quenesha; Morgello, Susan

    2013-01-01

    Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p <.05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories. PMID:23446056

  4. Platelets confound the measurement of extracellular miRNA in archived plasma.

    PubMed

    Mitchell, Adam J; Gray, Warren D; Hayek, Salim S; Ko, Yi-An; Thomas, Sheena; Rooney, Kim; Awad, Mosaab; Roback, John D; Quyyumi, Arshed; Searles, Charles D

    2016-01-01

    Extracellular miRNAs are detectable in biofluids and represent a novel class of disease biomarker. Although many studies have utilized archived plasma for miRNA biomarker discovery, the effects of processing and storage have not been rigorously studied. Previous reports have suggested plasma samples are commonly contaminated by platelets, significantly confounding the measurement of extracellular miRNA, which was thought to be easily addressed by additional post-thaw plasma processing. In a case-control study of archived plasma, we noted a significant correlation between miRNA levels and platelet counts despite post-thaw processing. We thus examined the effects of a single freeze/thaw cycle on microparticles (MPs) and miRNA levels, and show that a single freeze/thaw cycle of plasma dramatically increases the number of platelet-derived MPs, contaminates the extracellular miRNA pool, and profoundly affects the levels of miRNAs detected. The measurement of extracellular miRNAs in archived samples is critically dependent on the removal of residual platelets prior to freezing plasma samples. Many previous clinical studies of extracellular miRNA in archived plasma should be interpreted with caution and future studies should avoid the effects of platelet contamination. PMID:27623086

  5. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity.

    PubMed

    Tompuri, Tuomo T

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor.

  6. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity

    PubMed Central

    Tompuri, Tuomo T.

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor. PMID:26321958

  7. Do digestive contents confound body mass as a measure of relative condition in nestling songbirds?

    USGS Publications Warehouse

    Streby, Henry M.; Peterson, Sean M.; Lehman, Justin A.; Kramer, Gunnar R.; Vernasco, Ben J.; Andersen, David E.

    2014-01-01

    Relative nestling condition, typically measured as nestling mass or as an index including nestling mass, is commonly purported to correlate with fledgling songbird survival. However, most studies directly investigating fledgling survival have found no such relationship. We weighed feces and stomach contents of nestling golden-winged warblers (Vermivora chrysoptera) to investigate the potential contribution of variation in digestive contents to differences in nestling mass. We estimated that the mass of a seventh-day (near fledging) nestling golden-winged warbler varies by 0.65 g (approx. 9% of mean nestling mass) depending on the contents of the nestling's digestive system at the time of weighing, and that digestive contents are dissimilar among nestlings at any moment the brood is removed from the nest for weighing. Our conservative estimate of within-individual variation in digestive contents equals 72% and 24% of the mean within-brood and population-wide range in nestling mass, respectively. Based on our results, a substantive but typically unknown amount of the variation in body mass among nestlings is confounded by differences in digestive contents. We conclude that short-term variation in digestive contents likely precludes the use of body mass, and therefore any mass-dependent index, as a measure of relative nestling condition or as a predictor of survival in golden-winged warblers and likely in many other songbirds of similar size.

  8. A Course in... Biochemical Engineering.

    ERIC Educational Resources Information Center

    Ng, Terry K-L.; And Others

    1988-01-01

    Describes a chemical engineering course for senior undergraduates and first year graduate students in biochemical engineering. Discusses five experiments used in the course: aseptic techniques, dissolved oxygen measurement, oxygen uptake by yeast, continuous sterilization, and cultivation of microorganisms. (MVL)

  9. Treatment Confounded Missingness: A Comparison of Methods for Addressing Censored or Truncated Data in School Reform Evaluations. CRESST Report 832

    ERIC Educational Resources Information Center

    Rickles, Jordan H.; Hansen, Mark; Wang, Jia

    2013-01-01

    In this paper we examine ways to conceptualize and address potential bias that can arise when the mechanism for missing outcome data is at least partially associated with treatment assignment, an issue we refer to as treatment confounded missingness (TCM). In discussing TCM, we bring together concepts from the methodological literature on missing…

  10. Are We Missing Something Pertinent? A Bias Analysis of Unmeasured Confounding in the Firearm-Suicide Literature.

    PubMed

    Miller, M; Swanson, S A; Azrael, D

    2016-01-01

    Despite the magnitude and consistency of risk estimates in the peer-reviewed literature linking firearm availability and suicide, inferring causality has been questioned on the theoretical basis that existing studies may have failed to account for the possibility that members of households with firearms differ from members of households without firearms in important ways related to suicide risk. The current bias analysis directly addresses this concern by describing the salient characteristics that such an unmeasured confounder would need to possess in order to yield the associations between firearm availability and suicide observed in the literature when, in fact, the causal effect is null. Four US studies, published between 1992 and 2003, met our eligibility criteria. We find that any such unmeasured confounder would need to possess an untenable combination of characteristics, such as being not only 1) as potent a suicide risk factor as the psychiatric disorders most tightly linked to suicide (e.g., major depressive and substance use disorders) but also 2) an order of magnitude more imbalanced across households with versus without firearms than is any known risk factor. No such confounder has been found or even suggested. The current study strongly suggests that unmeasured confounding alone is unlikely to explain the association between firearms and suicide.

  11. Interpretational Confounding Is Due to Misspecification, Not to Type of Indicator: Comment on Howell, Breivik, and Wilcox (2007)

    ERIC Educational Resources Information Center

    Bollen, Kenneth A.

    2007-01-01

    R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal…

  12. Natural genetic variability of the neuronal nicotinic acetylcholine receptor subunit genes in mice: Consequences and confounds.

    PubMed

    Wilking, Jennifer A; Stitzel, Jerry A

    2015-09-01

    Recent human genetic studies have identified genetic variants in multiple nicotinic acetylcholine receptor (nAChR) subunit genes that are associated with risk for nicotine dependence and other smoking-related measures. Genetic variability also exists in the nAChR subunit genes in mice. Most studies on mouse nAChR subunit gene variability to date have focused on Chrna4, the gene that encodes the α4 nAChR subunit and Chrna7, the gene that encodes the α7 nAChR subunit. However, genetic variability exists for all nAChR genes in mice. In this review, we will describe what is known about nAChR subunit gene polymorphisms in mice and how it relates to variability in nAChR expression and function in brain. The relationship between nAChR genetic variability in mice and the effects of nicotine on several behavioral and physiological measures also will be discussed. In addition, an overview of the contribution of other genetic variation to nicotine sensitivity in mice will be provided. Finally, the potential for natural genetic variability to confound and/or modify the results of studies that utilize genetically engineered mice will be considered. As an example of the ability of a natural genetic variant to modify the effect of an engineered mutation, data will be presented that demonstrate that the effect of Chrna5 deletion on oral nicotine intake is dependent upon naturally occurring variant alleles of Chrna4. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25498233

  13. Comorbidity of intellectual disability confounds ascertainment of autism: implications for genetic diagnosis.

    PubMed

    Polyak, Andrew; Kubina, Richard M; Girirajan, Santhosh

    2015-10-01

    While recent studies suggest a converging role for genetic factors towards risk for nosologically distinct disorders including autism, intellectual disability (ID), and epilepsy, current estimates of autism prevalence fail to take into account the impact of comorbidity of these disorders on autism diagnosis. We aimed to assess the effect of comorbidity on the diagnosis and prevalence of autism by analyzing 11 years (2000-2010) of special education enrollment data on approximately 6.2 million children per year. We found a 331% increase in the prevalence of autism from 2000 to 2010 within special education, potentially due to a diagnostic recategorization from frequently comorbid features such as ID. The decrease in ID prevalence equaled an average of 64.2% of the increase of autism prevalence for children aged 3-18 years. The proportion of ID cases potentially undergoing recategorization to autism was higher (P = 0.007) among older children (75%) than younger children (48%). Some US states showed significant negative correlations between the prevalence of autism compared to that of ID while others did not, suggesting state-specific health policy to be a major factor in categorizing autism. Further, a high frequency of autistic features was observed when individuals with classically defined genetic syndromes were evaluated for autism using standardized instruments. Our results suggest that current ascertainment practices are based on a single facet of autism-specific clinical features and do not consider associated comorbidities that may confound diagnosis. Longitudinal studies with detailed phenotyping and deep molecular genetic analyses are necessary to completely understand the cause of this complex disorder.

  14. Confounding environmental colour and distribution shape leads to underestimation of population extinction risk.

    PubMed

    Fowler, Mike S; Ruokolainen, Lasse

    2013-01-01

    The colour of environmental variability influences the size of population fluctuations when filtered through density dependent dynamics, driving extinction risk through dynamical resonance. Slow fluctuations (low frequencies) dominate in red environments, rapid fluctuations (high frequencies) in blue environments and white environments are purely random (no frequencies dominate). Two methods are commonly employed to generate the coloured spatial and/or temporal stochastic (environmental) series used in combination with population (dynamical feedback) models: autoregressive [AR(1)] and sinusoidal (1/f) models. We show that changing environmental colour from white to red with 1/f models, and from white to red or blue with AR(1) models, generates coloured environmental series that are not normally distributed at finite time-scales, potentially confounding comparison with normally distributed white noise models. Increasing variability of sample Skewness and Kurtosis and decreasing mean Kurtosis of these series alter the frequency distribution shape of the realised values of the coloured stochastic processes. These changes in distribution shape alter patterns in the probability of single and series of extreme conditions. We show that the reduced extinction risk for undercompensating (slow growing) populations in red environments previously predicted with traditional 1/f methods is an artefact of changes in the distribution shapes of the environmental series. This is demonstrated by comparison with coloured series controlled to be normally distributed using spectral mimicry. Changes in the distribution shape that arise using traditional methods lead to underestimation of extinction risk in normally distributed, red 1/f environments. AR(1) methods also underestimate extinction risks in traditionally generated red environments. This work synthesises previous results and provides further insight into the processes driving extinction risk in model populations. We must let

  15. Improved estimation of controlled direct effects in the presence of unmeasured confounding of intermediate variables.

    PubMed

    Kaufman, Sol; Kaufman, Jay S; MacLehose, Richard F; Greenland, Sander; Poole, Charles

    2005-06-15

    Adjusting for a causal intermediate is a common analytic strategy for estimating an average causal direct effect (ACDE). The ACDE is the component of the total exposure effect that is not relayed through the specified intermediate. Even if the total effect is unconfounded, the usual ACDE estimate may be biased when an unmeasured variable affects the intermediate and outcome variables. Using linear programming optimization to compute non-parametric bounds, we develop new ACDE estimators for binary measured variables in this causal structure, and use root mean square confounding bias (RMSB) to compare their performance with the usual stratified estimator in simulated distributions of target populations comprised of the 64 possible potential response types as well as distributions of target populations restricted to subsets of 18 or 12 potential response types defined by monotonicity or no-interactions assumptions of unit-level causal effects. We also consider target population distributions conditioned on fixed outcome risk among the unexposed, or fixed true ACDE in one stratum of the intermediate. Results show that a midpoint estimator constructed from the optimization bounds has consistently lower RMSB than the usual stratified estimator both unconditionally and conditioned on any risk in the unexposed. When conditioning on true ACDE, this midpoint estimator performs more poorly only when conditioned on an extreme true ACDE in one stratum of the intermediate, yet outperforms the stratified estimator in the other stratum when interaction is permitted. An alternate 'limit-modified crude' estimator can never perform less favourably than the stratified estimator, and often has lower RMSB. PMID:15742358

  16. Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis

    PubMed Central

    Walne, Amanda J.; Collopy, Laura; Cardoso, Shirleny; Ellison, Alicia; Plagnol, Vincent; Albayrak, Canan; Albayrak, Davut; Kilic, Sara Sebnem; Patıroglu, Turkan; Akar, Haluk; Godfrey, Keith; Carter, Tina; Marafie, Makia; Vora, Ajay; Sundin, Mikael; Vulliamy, Thomas; Tummala, Hemanth; Dokal, Inderjeet

    2016-01-01

    Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. By whole exome and targeted sequencing, we identified biallelic variants in genes that are not associated with dyskeratosis congenita in 17 individuals from 12 families. Specifically, these were homozygous variants in USB1 (8 families), homozygous missense variants in GRHL2 (2 families) and identical compound heterozygous variants in LIG4 (2 families). All patients had multiple somatic features of dyskeratosis congenita but not the characteristic short telomeres. Our case series shows that biallelic variants in USB1, LIG4 and GRHL2, the genes mutated in poikiloderma with neutropenia, LIG4/Dubowitz syndrome and the recently recognized ectodermal dysplasia/short stature syndrome, respectively, cause features that overlap with dyskeratosis congenita. Strikingly, these genes also overlap in their biological function with the known dyskeratosis congenita genes that are implicated in telomere maintenance and DNA repair pathways. Collectively, these observations demonstrate the marked overlap of dyskeratosis congenita with four other genetic syndromes, confounding accurate diagnosis and subsequent management. This has important implications for establishing a genetic diagnosis when a new patient presents in the clinic. Patients with clinical features of dyskeratosis congenita need to have genetic analysis of USB1, LIG4 and GRHL2 in addition to the classical dyskeratosis congenita genes and telomere length measurements. PMID:27612988

  17. Timing of human preimplantation embryonic development is confounded by embryo origin

    PubMed Central

    Kirkegaard, K.; Sundvall, L.; Erlandsen, M.; Hindkjær, J.J.; Knudsen, U.B.; Ingerslev, H.J.

    2016-01-01

    STUDY QUESTION To what extent do patient- and treatment-related factors explain the variation in morphokinetic parameters proposed as embryo viability markers? SUMMARY ANSWER Up to 31% of the observed variation in timing of embryo development can be explained by embryo origin, but no single factor elicits a systematic influence. WHAT IS KNOWN ALREADY Several studies report that culture conditions, patient characteristics and treatment influence timing of embryo development, which have promoted the perception that each clinic must develop individual models. Most of the studies have, however, treated embryos from one patient as independent observations, and only very few studies that evaluate the influence from patient- and treatment-related factors on timing of development or time-lapse parameters as predictors of viability have controlled for confounding, which implies a high risk of overestimating the statistical significance of potential correlations. STUDY DESIGN, SIZE, DURATION Infertile patients were prospectively recruited to a cohort study at a hospital fertility clinic from February 2011 to May 2013. Patients aged <38 years without endometriosis were eligible if ≥8 oocytes were retrieved. Patients were included only once. All embryos were monitored for 6 days in a time-lapse incubator. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1507 embryos from 243 patients were included. The influence of fertilization method, BMI, maternal age, FSH dose and number of previous cycles on timing of t2-t5, duration of the 2- and 3-cell stage, and development of a blastocoel (tEB) and full blastocoel (tFB) was tested in multivariate, multilevel linear regression analysis. Predictive parameters for live birth were tested in a logistic regression analysis for 223 single transferred blastocysts, where time-lapse parameters were investigated along with patient and embryo characteristics. MAIN RESULTS AND THE ROLE OF CHANCE Moderate intra-class correlation coefficients

  18. Prostate-Specific Antigen Velocity Before and After Elimination of Factors That Can Confound the Prostate-Specific Antigen Level

    SciTech Connect

    Park, Jessica J.; Chen, Ming-Hui; Loffredo, Marian; D'Amico, Anthony V.

    2012-03-01

    Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y. Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders. Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09). Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels.

  19. Biochemical and histological methodologies for assessing vitamin A status in human populations

    SciTech Connect

    Underwood, B.A.

    1990-01-01

    In recent years, new biochemical and histological methodologies have been developed for assessing vitamin A nutritional status in humans at subclinical levels of nutriture. Insensitive static blood levels no longer are the only practical assessment parameter. Some of the newer functional methodologies require additional testing of their sensitivity and specificity under a variety of conditions existing in human populations and that frequently are associated with an inadequate vitamin A status. Some of these conditions could confound the interpretation when only a single assessment method is applied.

  20. BEST: Biochemical Engineering Simulation Technology

    SciTech Connect

    Not Available

    1996-01-01

    The idea of developing a process simulator that can describe biochemical engineering (a relatively new technology area) was formulated at the National Renewable Energy Laboratory (NREL) during the late 1980s. The initial plan was to build a consortium of industrial and U.S. Department of Energy (DOE) partners to enhance a commercial simulator with biochemical unit operations. DOE supported this effort; however, before the consortium was established, the process simulator industry changed considerably. Work on the first phase of implementing various fermentation reactors into the chemical process simulator, ASPEN/SP-BEST, is complete. This report will focus on those developments. Simulation Sciences, Inc. (SimSci) no longer supports ASPEN/SP, and Aspen Technology, Inc. (AspenTech) has developed an add-on to its ASPEN PLUS (also called BioProcess Simulator [BPS]). This report will also explain the similarities and differences between BEST and BPS. ASPEN, developed by the Massachusetts Institute of Technology for DOE in the late 1970s, is still the state-of-the-art chemical process simulator. It was selected as the only simulator with the potential to be easily expanded into the biochemical area. ASPEN/SP, commercially sold by SimSci, was selected for the BEST work. SimSci completed work on batch, fed-batch, and continuous fermentation reactors in 1993, just as it announced it would no longer commercially support the complete ASPEN/SP product. BEST was left without a basic support program. Luckily, during this same time frame, AspenTech was developing a biochemical simulator with its version of ASPEN (ASPEN PLUS), which incorporates most BEST concepts. The future of BEST will involve developing physical property data and models appropriate to biochemical systems that are necessary for good biochemical process design.

  1. Hematologic and Biochemical Biologic Variation in Laboratory Cats.

    PubMed

    Trumel, Catherine; Monzali, Céline; Geffré, Anne; Concordet, Didier V; Hourqueig, Louise; Braun, Jean-Pierre D; Bourgès-Abella, Nathalie H

    2016-01-01

    The biologic variation associated with a clinical pathology result is important to consider before reference intervals (RI) are used. Most available RI are population-based RI, in which the analytical variability, interindividual variability, and intraindividual variability are confounded. In addition, when the intraindividual variability is considerably less than the interindividual variability, a population-based RI is insufficiently sensitive to detect changes in a subject over time. Here we determined the biologic variation and reference change value (RCV) of hematologic and biochemical variables in laboratory cats. Blood specimens from 14 (7 females and 7 males) overnight-fasted laboratory cats sampled 7 times (days 1, 2, 7, 14, 31, 42, and 100) were analyzed regarding hematology and biochemistry variables. For each variable, analytical, intraindividual, and interindividual coefficients of variation were estimated prior to calculation of the index of individuality and the RCV. RBC variables (count, Hgb, Hct, MCV, MCH, MCHC, and RBC distribution width) and 5 biochemical analytes (cholesterol, creatinine, triglycerides, ALP, and calcium) exhibited marked individuality, therefore indicating that subject-based reference intervals or RCV would be preferable when monitoring these variables in laboratory cats. Population-based RI were shown to be adequate for glucose and sodium, and both types of population and individual RI were similarly efficient for albumin, total protein, urea, ALT, AST, creatine kinase, chloride, carbon dioxide, iron, magnesium, inorganic phosphate, and potassium and reticulocyte, WBC, neutrophil, lymphocyte, monocyte, eosinophil, and platelet counts. The RCV determined in the present study provide a valuable tool for monitoring hematologic and biochemical variables in healthy laboratory cats. PMID:27657703

  2. Circadian Clocks: Unexpected Biochemical Cogs

    PubMed Central

    Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie

    2015-01-01

    A circadian oscillation can be reconstituted in vitro from three proteins that cycles with a period of ~24 h. Two recent studies provide surprising biochemical answers to why this remarkable oscillator has such a long time constant and how it can switch effortlessly between alternating enzymatic modes. PMID:26439342

  3. Ultrasound Elastography and MR Elastography for Assessing Liver Fibrosis: Part 2, Diagnostic Performance, Confounders, and Future Directions

    PubMed Central

    Tang, An; Cloutier, Guy; Szeverenyi, Nikolaus M.; Sirlin, Claude B.

    2016-01-01

    OBJECTIVE The purpose of the article is to review the diagnostic performance of ultrasound and MR elastography techniques for detection and staging of liver fibrosis, the main current clinical applications of elastography in the abdomen. CONCLUSION Technical and instrument-related factors and biologic and patient-related factors may constitute potential confounders of stiffness measurements for assessment of liver fibrosis. Future developments may expand the scope of elastography for monitoring liver fibrosis and predict complications of chronic liver disease. PMID:25905762

  4. Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

    PubMed

    Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

    2008-12-01

    A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence.

  5. Distinguishing benign confounding treatment changes from residual prostate cancer on MRI following laser ablation

    NASA Astrophysics Data System (ADS)

    Litjens, G.; Huisman, H.; Elliott, R.; Shih, N.; Feldman, M.; Viswanath, S.; Fütterer, J.; Bomers, J.; Madabhushi, A.

    2014-03-01

    Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. However, very little is known about the specific effects of LITT within the ablation zone and the surrounding normal tissue regions. For instance, it is important to be able to assess the extent of residual cancer within the prostate following LITT, which may be masked by thermally induced benign necrotic changes. Fortunately LITT is MRI compatible and hence this allows for quantitatively assessing LITT induced changes via multi-parametric MRI. Of course definite validation of any LITT induced changes on MRI requires confirmation via histopathology. The aim of this study was to quantitatively assess and distinguish the imaging characteristics of prostate cancer and benign confounding treatment changes following LITTon 3 Tesla multi-parametric MRI by carefully mapping the treatment related changes from the ex vivo surgically resected histopathologic specimens onto the pre-operative in vivo imaging. A better understanding of the imaging characteristics of residual disease and successfully ablated tissue might lead to improved treatment monitoring and as such patient prognosis. A unique clinical trial at the Radboud University Medical Center, in which 3 patients underwent a prostatectomy after LITT treatment, yielded ex-vivo histopathologic specimens along with pre- and post-LITT MRI. Using this data we (1) identified the computer extracted MRI signatures associated with treatment effects including benign necrotic changes and residual disease and (2) subsequently evaluated the computer extracted MRI features previously identified in distinguishing LITT induced changes in the ablated area relative to the residual disease. Towards this end first a pathologist annotated the ablated area and the residual disease on the ex-vivo histology and then we transferred the annotations to the post-LITT MRI using semi-automatic elastic registration. The

  6. Examining the Relationship between Heavy Alcohol Use and Assaults: With Adjustment for the Effects of Unmeasured Confounders

    PubMed Central

    Liang, Wenbin; Chikritzhs, Tanya

    2015-01-01

    Background. Experimental studies suggest that alcohol can lead to aggression in laboratory settings; however, it is impossible to test the causal relationship between alcohol use and real-life violence among humans in randomized clinical trials. Objectives. (i) To examine the relationship between heavy alcohol use and assaults in a population based study; (ii) to demonstrate the proxy outcome method, as a means of controlling the effects of unknown/unmeasured confounders in observational studies. Methods. This study used data collected from three waves of the National Survey on Drug Use and Health (NSDUH). The effects of heavy alcohol use on assault were measured using multivariable logistic regressions in conjunction with the proxy outcome method. Results. Application of the proxy outcome method indicated that effect sizes of heavy alcohol use on the risk of assault were overestimated in the standard models. After adjusting for the effects of unknown/unmeasured confounders, the risk of assault remained 43% and 63% higher (P < 0.05) among participants who consumed 5+ drinks/day for 5–8 days/month and 9–30 days/month, respectively. Conclusions. Even after adjustment for unknown/unmeasured confounders the association between heavy alcohol use and risk of violence remained significant. These findings support the hypothesis that heavy alcohol use can cause violence. PMID:26380283

  7. Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications

    PubMed Central

    Hak, E; Verheij, T.; Grobbee, D; Nichol, K; Hoes, A

    2002-01-01

    Randomised allocation of vaccine or placebo is the preferred method to assess the effects of the vaccine on clinical outcomes relevant to the individual patient. In the absence of phase 3 trials using clinical end points, notably post-influenza complications, alternative non-experimental designs to evaluate vaccine effects or safety are often used. The application of these designs may, however, lead to invalid estimates of vaccine effectiveness or safety. As patients with poor prognosis are more likely to be immunised, selection for vaccination is confounded by patient factors that are also related to clinical end points. This paper describes several design and analytical methods aimed at limiting or preventing this confounding by indication in non-experimental studies. In short, comparison of study groups with similar prognosis, restriction of the study population, and statistical adjustment for dissimilarities in prognosis are important tools and should be considered. Only if the investigator is able to show that confounding by indication is sufficiently controlled for, results of a non-experimental study may be of use to direct an evidence based vaccine policy. PMID:12461118

  8. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

  9. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction—Having Your Cake and Eating It Two

    PubMed Central

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L.; Haneuse, Sebastien

    2016-01-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis—in which detailed high-quality confounding data are obtained among a small subsample—can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake. PMID:27285260

  10. Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction-Having Your Cake and Eating It Two.

    PubMed

    Spiegelman, Donna; Rivera-Rodriguez, Claudia L; Haneuse, Sebastien

    2016-07-01

    In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis-in which detailed high-quality confounding data are obtained among a small subsample-can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake.

  11. Biochemical Engineering. Part II: Process Design

    ERIC Educational Resources Information Center

    Atkinson, B.

    1972-01-01

    Describes types of industrial techniques involving biochemical products, specifying the advantages and disadvantages of batch and continuous processes, and contrasting biochemical and chemical engineering. See SE 506 318 for Part I. (AL)

  12. Connecting Biochemical Photosynthesis Models with Crop Models to Support Crop Improvement

    PubMed Central

    Wu, Alex; Song, Youhong; van Oosterom, Erik J.; Hammer, Graeme L.

    2016-01-01

    The next advance in field crop productivity will likely need to come from improving crop use efficiency of resources (e.g., light, water, and nitrogen), aspects of which are closely linked with overall crop photosynthetic efficiency. Progress in genetic manipulation of photosynthesis is confounded by uncertainties of consequences at crop level because of difficulties connecting across scales. Crop growth and development simulation models that integrate across biological levels of organization and use a gene-to-phenotype modeling approach may present a way forward. There has been a long history of development of crop models capable of simulating dynamics of crop physiological attributes. Many crop models incorporate canopy photosynthesis (source) as a key driver for crop growth, while others derive crop growth from the balance between source- and sink-limitations. Modeling leaf photosynthesis has progressed from empirical modeling via light response curves to a more mechanistic basis, having clearer links to the underlying biochemical processes of photosynthesis. Cross-scale modeling that connects models at the biochemical and crop levels and utilizes developments in upscaling leaf-level models to canopy models has the potential to bridge the gap between photosynthetic manipulation at the biochemical level and its consequences on crop productivity. Here we review approaches to this emerging cross-scale modeling framework and reinforce the need for connections across levels of modeling. Further, we propose strategies for connecting biochemical models of photosynthesis into the cross-scale modeling framework to support crop improvement through photosynthetic manipulation. PMID:27790232

  13. Abnormal liver function and central obesity associate with work-related fatigue among the Taiwanese workers

    PubMed Central

    Lin, Yu-Cheng; Chen, Jong-Dar; Chen, Chao-Jen

    2008-01-01

    AIM: To examine the associations between objective health indicators and high need for recovery (NFR) after work, one of the subjective presentations of work related-fatigue, among apparently healthy workers in modern workplaces. METHODS: From October to December, 2007, an annual health examination was performed for the workers from an electronics manufacturing factory in Taiwan. Health records of 1216 workers with a relatively homogeneous socioeconomic status were used for analysis. The health checkups included personal and NFR scale questionnaires, physical examinations, blood tests for biochemistry and hematology. The workers within the top tertile NFR score were defined as high-NFR workers. RESULTS: After adjusted for potential confounders, the workers with elevated alanine aminotransferase (ALT) and central obesity had a significantly higher NFR after work, with increased risks of 1.4-fold [95% confidence interval (CI) = 1.01-2.0] and 1.8-fold (95% CI = 1.2-2.7), respectively. Shiftworkers had a 2.0-fold (95% CI = 1.5-2.6) increased risk for high-NFR. The associations between high-NFR and lipid profiles, blood sugar, hematology indexes or blood pressure were insignificant after controlling for confounders. CONCLUSION: For apparently healthy workers, high NFR after work is not simply a subjective experience. Objective health measures, such as elevated ALT and increased waist circumference, should be carefully evaluated for the apparently healthy workers having a higher NFR after work. PMID:19030209

  14. Biochemical adaptation to ocean acidification.

    PubMed

    Stillman, Jonathon H; Paganini, Adam W

    2015-06-01

    The change in oceanic carbonate chemistry due to increased atmospheric PCO2  has caused pH to decline in marine surface waters, a phenomenon known as ocean acidification (OA). The effects of OA on organisms have been shown to be widespread among diverse taxa from a wide range of habitats. The majority of studies of organismal response to OA are in short-term exposures to future levels of PCO2 . From such studies, much information has been gathered on plastic responses organisms may make in the future that are beneficial or harmful to fitness. Relatively few studies have examined whether organisms can adapt to negative-fitness consequences of plastic responses to OA. We outline major approaches that have been used to study the adaptive potential for organisms to OA, which include comparative studies and experimental evolution. Organisms that inhabit a range of pH environments (e.g. pH gradients at volcanic CO2 seeps or in upwelling zones) have great potential for studies that identify adaptive shifts that have occurred through evolution. Comparative studies have advanced our understanding of adaptation to OA by linking whole-organism responses with cellular mechanisms. Such optimization of function provides a link between genetic variation and adaptive evolution in tuning optimal function of rate-limiting cellular processes in different pH conditions. For example, in experimental evolution studies of organisms with short generation times (e.g. phytoplankton), hundreds of generations of growth under future conditions has resulted in fixed differences in gene expression related to acid-base regulation. However, biochemical mechanisms for adaptive responses to OA have yet to be fully characterized, and are likely to be more complex than simply changes in gene expression or protein modification. Finally, we present a hypothesis regarding an unexplored area for biochemical adaptation to ocean acidification. In this hypothesis, proteins and membranes exposed to the

  15. Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

    SciTech Connect

    Fayerweather, W.E.

    2007-07-01

    The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimated by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.

  16. Smoking and degree of occupational exposure: are internal analyses in cohort studies likely to be confounded by smoking status

    SciTech Connect

    Siemiatycki, J.; Wacholder, S.; Dewar, R.; Wald, L.; Begin, D.; Richardson, L.; Rosenman, K.; Gerin, M.

    1988-01-01

    Occupational cohort studies are usually carried out without the benefit of information on smoking habits of cohort members. One common approach to avoid confounding bias related to smoking habits is to carry out an internal analysis, comparing workers with different degrees of occupational exposure. The premise behind this approach is that within a cohort there is unlikely to be correlation between degree of exposure and smoking habits. If this were untrue, smoking could confound the disease-exposure relationships. Our purpose was to verify the premise. The study sample consisted of 857 French-Canadian men born between 1910 and 1930, with 11 or fewer years of education, and interviewed around 1980 in the context of an occupational cancer case-control study. For each man we had information on smoking habits, job history, and a history of the chemicals he was exposed to in each of his jobs. We computed two indices of the dirtiness of workers' job histories: one based on the job titles held by the man and a second based on the degree of exposures to workplace substances. There was no correlation between these indices of job dirtiness and smoking history. We also examined the smoking-exposure relationship among the subsets of men who had been occupationally exposed to ten especially noticeable substances. Within the subsets, there was no indication of a consistent difference among the smoking subgroups in level or duration of exposure to these index substances. These findings do not support the view that nonsmokers sought out cleaner job environments than smokers; they imply that internal analyses of dose-response in cohort studies are unlikely to be seriously confounded by smoking habits.

  17. [Time-dependent confounding in the estimation of treatment effects in randomised trials with multimodal therapies--an illustration of the problem of time-dependent confounding by causal graphs].

    PubMed

    Zietemann, V D; Schuster, T; Duell, T H G

    2015-01-01

    Biased effect estimates induced by unconsidered confounding variables are a known problem in observational studies. Selection bias, resulting from non-random sampling of study participants, is widely recognised as a problem in case-control and cross-sectional studies. In contrast, possible bias in randomised controlled trials (RCTs) is mostly ignored. This paper illustrates, by applying directed acyclic graphs (DAGs), possible bias in the effect estimates of first-line therapy, caused by subsequent changes in therapy (time-dependent confounding). Possible selection bias, induced by not only random loss to follow-up, will be explained as well using DAGs. Underlying assumptions of standard methods usually used to analyse RCTs (like intention-to-treat, per-protocol) are shown and it is explained why effect estimates may be biased in RCTs, if only these conventional methods are used. Adequate statistical methods (causal inference models as marginal structural models and structural nested models) exist. Higher documentary efforts, however, are necessary, because any changes in medication, loss to follow-up as well as reasons for such changes need to be documented in detail as required by these advanced statistical methods. Nevertheless, causal inference models should become standard along side the currently applied standard methods, especially in studies with high non-compliance due to changes in therapy and substantial loss to follow-up. Possible bias cannot be excluded if similar results are obtained from both methods. However, study results should be interpreted with caution if they differ between both approaches.

  18. Biochemical Markers of Myocardial Damage

    PubMed Central

    2016-01-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  19. Biochemical Markers of Myocardial Damage.

    PubMed

    Bodor, Geza S

    2016-04-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  20. Ordering events of biochemical evolution.

    PubMed

    Cunchillos, C; Lecointre, G

    2007-05-01

    Metabolic pathways exhibit structures resulting from an evolutionary process. Pathways have been inherited through time with modification, from the earliest periods of life. It is possible to compare the structure of pathways as done in comparative anatomy, i.e. for inferring ancestral pathways or parts of it (ancestral enzymatic functions), using standard phylogenetic reconstruction. Thus a phylogenetic tree of pathways provides a relative ordering of the rise of enzymatic functions. It even becomes possible to order the birth of each complete pathway in time. This particular "DNA-free" conceptual approach to evolutionary biochemistry is reviewed, gathering all the justifications given for it. Then, the method of assigning a given pathway to a time span of biochemical development is revisited. The previous method used an implicit "clock" of metabolic development that is difficult to justify. We develop a new clock-free approach, using functional biochemical arguments. Results of the two methods are not significantly different; our method is just more precise. This suggests that the clock assumed in the first method does not provoke any important artefact in describing the development of biochemical evolution. It is just unnecessary to postulate it. As a result, most of the amino acid metabolic pathways develop forwards, confirming former models of amino acid catabolism evolution, but not those for amino acid anabolism. The order of appearance of sectors of universal cellular metabolism is: (1) amino acid catabolism, (2) amino acid anabolism and closure of the urea cycle, (3) glycolysis and glycogenesis, (4) closure of the pentose-phosphate cycle, (5) closure of the Krebs cycle and fatty acids metabolism, (6) closure of the Calvin cycle.

  1. Biochemical structure of Calendula officinalis.

    PubMed

    Korakhashvili, A; Kacharava, T; Kiknavelidze, N

    2007-01-01

    Calendula officinalis is a well known medicinal herb. It is common knowledge that its medicinal properties are conditioned on biologically active complex substances of Carotin (Provitamin A), Stearin, Triterpiniod, Plavonoid, Kumarin, macro and micro compound elements. Because of constant need in raw material of Calendula officinalis, features of its ontogenetic development agro-biological qualities in various eco regions of Georgia were investigated. The data of biologically active compounds, biochemical structure and the maintenance both in flowers and in others parts of plant is presented; the pharmacological activity and importance in medicine was reviewed. PMID:17921550

  2. High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions.

    PubMed

    Chu, Tianjiao; Yeniterzi, Suveyda; Yatsenko, Svetlana A; Dunkel, Mary; Shaw, Patricia A; Bunce, Kimberly D; Peters, David G

    2016-01-01

    Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV) was used to determine the "Genomic Variants Frequency" (GVF) for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC) for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically. PMID:27249650

  3. High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions

    PubMed Central

    Chu, Tianjiao; Yeniterzi, Suveyda; Yatsenko, Svetlana A.; Dunkel, Mary; Shaw, Patricia A.; Bunce, Kimberly D.; Peters, David G.

    2016-01-01

    Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV) was used to determine the “Genomic Variants Frequency” (GVF) for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC) for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically. PMID:27249650

  4. Vector Encoding in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Potter, Garrett; Sun, Bo

    Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

  5. Interpersonal discrimination and depressive symptomatology: examination of several personality-related characteristics as potential confounders in a racial/ethnic heterogeneous adult sample

    PubMed Central

    2013-01-01

    Background Research suggests that reports of interpersonal discrimination result in poor mental health. Because personality characteristics may either confound or mediate the link between these reports and mental health, there is a need to disentangle its role in order to better understand the nature of discrimination-mental health association. We examined whether hostility, anger repression and expression, pessimism, optimism, and self-esteem served as confounders in the association between perceived interpersonal discrimination and CESD-based depressive symptoms in a race/ethnic heterogeneous probability-based sample of community-dwelling adults. Methods We employed a series of ordinary least squares regression analyses to examine the potential confounding effect of hostility, anger repression and expression, pessimism, optimism, and self-esteem between interpersonal discrimination and depressive symptoms. Results Hostility, anger repression, pessimism and self-esteem were significant as possible confounders of the relationship between interpersonal discrimination and depressive symptoms, together accounting for approximately 38% of the total association (beta: 0.1892, p < 0.001). However, interpersonal discrimination remained a positive predictor of depressive symptoms (beta: 0.1176, p < 0.001). Conclusion As one of the first empirical attempts to examine the potential confounding role of personality characteristics in the association between reports of interpersonal discrimination and mental health, our results suggest that personality-related characteristics may serve as potential confounders. Nevertheless, our results also suggest that, net of these characteristics, reports of interpersonal discrimination are associated with poor mental health. PMID:24256578

  6. Disentangling the confounding effects of PAR and air temperature on net ecosystem exchange in time and scale

    NASA Astrophysics Data System (ADS)

    yang, Z.; Chen, J.; Becker, R.; Chu, H.; Xie, J.; Shao, C.

    2013-12-01

    Net ecosystem exchange of CO2 (NEE) in temperate forests is modulated by microclimatic factors. The effects of those factors differ at different time scales and during different time periods. Some of them are correlated across a number of time scales, so their effects on NEE are confounded by each other. PAR and air temperature (Ta) are among the two most important drivers of NEE in temperate forests, and among the two most correlated microclimatic factors. PAR and Ta have similar daily, seasonal, and annual cycles. Their influence on NEE is confounded by each other and entangled together especially at those scales. In this study, we tried to disentangle the confounding effects of them on NEE at different time scales and during different time periods. To accomplish this objective, we applied the innovative spectral analysis techniques including Continuous Wavelet Transformation (CWT), Cross Wavelet Transformation (XWT), Wavelet Coherent (WTC), and Partial Wavelet Coherence (PWC) on seven years time series (2004-2010) of PAR, Ta and NEE from the Ohio Oak Openings site (N 41.5545°, W 83.8438°), USA for spectral analysis. We found that PAR is the major driver at short time scales (e.g. semidiurnal and daily) and Ta is the major driver at long time scales (e.g. seasonal and annual). At daily scale during growing seasons, PAR is anti-phase with NEE with no time delay while Ta lagged PAR about 2-3 hours, which could be explained by the strong dependence of photosynthesis on PAR and a 2-3 hours lags of the daily course of Ta to PAR. At daily scale during non-growing season, NEE has little variation and thus neither Ta nor PAR has high common wavelet power and significant coherence with NEE. At annual scale, Ta is anti-phase with NEE and PAR leads NEE about 34 days, which could be explained by the strong dependence of LAI dynamics on Ta and the lag between the LAI/biomass development and the progress of sunlight. We also found that NEE distributes most of its variation

  7. In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain.

    PubMed

    Hackett, Mark J; Britz, Carter J; Paterson, Phyllis G; Nichol, Helen; Pickering, Ingrid J; George, Graham N

    2015-02-18

    Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into

  8. Biochemical Analysis of Protein SUMOylation

    PubMed Central

    Alontaga, Aileen Y.; Bobkova, Ekaterina; Chen, Yuan

    2012-01-01

    SUMOylation, the covalent attachment of Small Ubiquitin-like MOdifier (SUMO) polypeptides to other proteins, is among the most important post-translational modifications that regulate the functional properties of a large number of proteins. SUMOylation is broadly involved in cellular processes such as gene transcription, hormone response, signal transduction, DNA repair and nuclear transport. SUMO modification has also been implicated in the pathogenesis of human diseases, such as cancer, neurodegenerative disorders and viral infection. Attachment of a SUMO protein to another protein is carried out in multiple steps catalyzed by three enzymes. This unit describes and discusses the in vitro biochemical methods used for investigating each step of the SUMOylation process. In addition, a high throughput screening protocol is included for the identification of inhibitors of SUMOylation. PMID:22870855

  9. Biochemical markers of acute pancreatitis.

    PubMed

    Matull, W R; Pereira, S P; O'Donohue, J W

    2006-04-01

    Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in "idiopathic" acute recurrent pancreatitis.

  10. Hyponatraemia: biochemical and clinical perspectives.

    PubMed Central

    Gill, G.; Leese, G.

    1998-01-01

    Hyponatraemia is a common bio-chemical abnormality, occurring in about 15% of hospital inpatients. It is often associated with severe illness and relatively poor outcome. Pathophysiologically, hyponatraemia may be spurious, dilutional, depletional or redistributional. Particularly difficult causes and concepts of hyponatraemia are the syndrome of inappropriate antidiuresis and the sick cell syndrome, which are discussed here in detail. Therapy should always be targeted at the underlying disease process. 'Hyponatraemic symptoms' are of doubtful importance, and may be more related to water overload and/or the causative disease, than to hyponatraemia per se. Artificial elevation of plasma sodium by saline infusion carries the risk of induction of osmotic demyelination (central pontine myelinolysis). PMID:10211323

  11. Diagnosis of hyperandrogenism: biochemical criteria.

    PubMed

    Stanczyk, Frank Z

    2006-06-01

    Biochemical derangements in ovarian, adrenal, and peripheral androgen production and metabolism play an important role in underlying causes of hyperandrogenism. Specific diagnostic serum markers such as testosterone (total) and dehydroepiandrosterone sulfate (DHEAS), respectively, may be helpful in the diagnosis of ovarian and adrenal hyperandrogenism, respectively. Validated immunoassays or mass spectrometry assays should be used to quantify testosterone, DHEAS and other principal androgens. Free testosterone measurements, determined by equilibrium dialysis or the calculated method, are advocated for routine evaluation of more subtle forms of hyperandrogenism. The skin, with its pilosebaceous units (PSUs), is an important site of active androgen production. A key regulator in PSUs is 5alpha-reductase, which transforms testosterone or androstenedione to dihydrotestosterone (DHT). DHT in blood is not effective in indicating the presence of hyperandrogenism. However, distal metabolites of DHT have been shown to be good markers of clinical manifestations of hirsutism, acne and alopecia. Assays for these peripheral markers need improvement for routine clinical testing. PMID:16772150

  12. Soil acidification as a confounding factor on metal phytotoxicity in soils spiked with copper-rich mine wastes.

    PubMed

    Ginocchio, Rosanna; De la Fuente, Luz María; Sánchez, Pablo; Bustamante, Elena; Silva, Yasna; Urrestarazu, Paola; Rodríguez, Patricio H

    2009-10-01

    Pollution of soil with mine wastes results in both Cu enrichment and soil acidification. This confounding effect may be very important in terms of phytotoxicity, because pH is a key parameter influencing Cu solubility in soil solution. Laboratory toxicity tests were used to assess the effect of acidification by acidic mine wastes on Cu solubility and on root elongation of barley (Hordeum vulgare L.). Three contrasting substrates (two soils and a commercial sand) and two acidic, Cu-rich mine wastes (oxidized tailings [OxT] and smelter dust [SmD]) were selected as experimental materials. Substrates were spiked with a fixed amount of either SmD or OxT, and the pH of experimental mixtures was then modified in the range of 4.0 to 6.0 and 7.0 using PIPES (piperazine-1,4-bis(2-ethanesulfonic acid)), MES (2-(N-morpholino)ethanesulfonic acid), and MOPS (3-(N-Morpholino)-propanesulfonic acid) buffers. Chemical (pore-water Cu and pH) and toxicological (root length of barley plants) parameters were determined for experimental mixtures. Addition of SmD and OxT to substrates resulted in acidification (0.11-1.16 pH units) and high levels of soluble Cu and Zn. Neutralization of experimental mixtures with MES (pH 6.0) and MOPS (pH 7.0) buffers resulted in a marked decrease in soluble Cu and Zn, but the intensity of the effect was substrate-dependent. Adjustment of soil pH above the range normally considered to be toxic to plants (pH in water extract, > 5.5) significantly reduced metal toxicity in barley, but phytotoxicity was not completely eliminated. The present results stress the importance of considering confounding effects on derivation of toxicity thresholds to plants when using laboratory phytotoxicity tests. PMID:19480535

  13. When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment.

    PubMed

    Wilkening, Jennifer L; Ray, Chris; Varner, Johanna

    2016-01-01

    Measurement of stress hormone metabolites in fecal samples has become a common method to assess physiological stress in wildlife populations. Glucocorticoid metabolite (GCM) measurements can be collected noninvasively, and studies relating this stress metric to anthropogenic disturbance are increasing. However, environmental characteristics (e.g., temperature) can alter measured GCM concentration when fecal samples cannot be collected immediately after defecation. This effect can confound efforts to separate environmental factors causing predeposition physiological stress in an individual from those acting on a fecal sample postdeposition. We used fecal samples from American pikas (Ochotona princeps) to examine the influence of environmental conditions on GCM concentration by (1) comparing GCM concentration measured in freshly collected control samples to those placed in natural habitats for timed exposure, and (2) relating GCM concentration in samples collected noninvasively throughout the western United States to local environmental characteristics measured before and after deposition. Our timed-exposure trials clarified the spatial scale at which exposure to environmental factors postdeposition influences GCM concentration in pika feces. Also, fecal samples collected from occupied pika habitats throughout the species' range revealed significant relationships between GCM and metrics of climate during the postdeposition period (maximum temperature, minimum temperature, and precipitation during the month of sample collection). Conversely, we found no such relationships between GCM and metrics of climate during the predeposition period (prior to the month of sample collection). Together, these results indicate that noninvasive measurement of physiological stress in pikas across the western US may be confounded by climatic conditions in the postdeposition environment when samples cannot be collected immediately after defecation. Our results reiterate the importance

  14. Biochemical values in free-ranging white rhinoceros (Ceratotherium simum) in Kruger National Park, South Africa.

    PubMed

    Mathebula, Nomkhosi; Miller, Michele; Buss, Peter; Joubert, Jennifer; Martin, Laura; Kruger, Marius; Hofmeyr, Markus; Olea-Popelka, Francisco

    2012-09-01

    Biochemical panels were analyzed on 181 individual free-ranging white rhinoceros (Ceratotherium simum) from Kruger National Park, South Africa. These animals were immobilized between July 2006 and May 2010 for management purposes. Serum and heparinized plasma samples were analyzed using an in-house chemistry analyser (ABAXIS VetScan2). The objectives of this study were to establish biochemical references ranges for Kruger National Park's population of white rhinoceros; to assess differences in values obtained using sera or plasma; and to assess differences in values between gender and different age categories. Significant differences between plasma and serum values were found in most measured parameters except minerals (calcium and magnesium). Because all animals appeared clinically healthy at the time of blood collection, it is hypothesized that choice of anticoagulant may affect certain parameters. Comparison between age categories and gender also resulted in significant differences in a few measured parameters. Identifying differences are important when establishing baseline reference ranges for wildlife populations to allow accurate monitoring of trends that may change over time. The paucity of data on normal biochemical ranges for free-ranging white rhinoceros demonstrates the value of this study and importance of evaluating potential confounding variables.

  15. Biochemical transformation of solid carbonaceous material

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    2001-09-25

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  16. Serum Biochemical Phenotypes in the Domestic Dog.

    PubMed

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  17. Serum Biochemical Phenotypes in the Domestic Dog

    PubMed Central

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  18. Interpretation: a confounding factor.

    PubMed

    Gupta, Mohit

    2016-01-01

    With reference to the article "Passive euthanasia in India: a critique", authored by Ms Rohini Shukla and published online on August 5, 2015, I would like to make a few comments and highlight the following points. First, the author notes that Section 309 IPC has been decriminalised. This is not so since there has neither been any amendment to the IPC, nor has any ordinance been passed regarding the matter. Attempting suicide is still an offence in India. Second, the author observes that withholding life support is an act of omission and withdrawing life support is an act of commission and the terms have been used interchangeably by the Hon'ble Court, although there is a subtle difference between the two terms.

  19. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration

    PubMed Central

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0–20 years, 21–40 years, 41–60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0–20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p < 0.001 and r = -0.42, p < 0.001 respectively. Epithelial TFIs (mean ± SD) of years 2013/2014, 2011/2012, 2009/2010 and 2008 were 852.60 ± 432.46, 353.04 ± 127.12, 209.24 ± 55.57 and 429.22 ± 188.75 respectively. Generally, TFIs reduced with storage duration (r = -0.42, p < 0.001). Our findings agree that age-related telomere attrition occurs in normal somatic tissues, and suggest that an age-based reference can be established for telomere studies on FFPE tissues. We also showed that FFPE tissues archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  20. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration.

    PubMed

    Kong, Po-Lian; Looi, Lai-Meng; Lau, Tze-Pheng; Cheah, Phaik-Leng

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0-20 years, 21-40 years, 41-60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0-20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p < 0.001 and r = -0.42, p < 0.001 respectively. Epithelial TFIs (mean ± SD) of years 2013/2014, 2011/2012, 2009/2010 and 2008 were 852.60 ± 432.46, 353.04 ± 127.12, 209.24 ± 55.57 and 429.22 ± 188.75 respectively. Generally, TFIs reduced with storage duration (r = -0.42, p < 0.001). Our findings agree that age-related telomere attrition occurs in normal somatic tissues, and suggest that an age-based reference can be established for telomere studies on FFPE tissues. We also showed that FFPE tissues archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  1. Biochemical Characterization of Indole Prenyltransferases

    PubMed Central

    Yu, Xia; Liu, Yan; Xie, Xiulan; Zheng, Xiao-Dong; Li, Shu-Ming

    2012-01-01

    The putative prenyltransferase gene ACLA_031240 belonging to the dimethylallyltryptophan synthase superfamily was identified in the genome sequence of Aspergillus clavatus and overexpressed in Escherichia coli. The soluble His-tagged protein EAW08391 was purified to near homogeneity and used for biochemical investigation with diverse aromatic substrates in the presence of different prenyl diphosphates. It has shown that in the presence of dimethylallyl diphosphate (DMAPP), the recombinant enzyme accepted very well simple indole derivatives with l-tryptophan as the best substrate. Product formation was also observed for tryptophan-containing cyclic dipeptides but with much lower conversion yields. In contrast, no product formation was detected in the reaction mixtures of l-tryptophan with geranyl or farnesyl diphosphate. Structure elucidation of the enzyme products by NMR and MS analyses proved unequivocally the highly regiospecific regular prenylation at C-5 of the indole nucleus of the simple indole derivatives. EAW08391 was therefore termed 5-dimethylallyltryptophan synthase, and it filled the last gap in the toolbox of indole prenyltransferases regarding their prenylation positions. Km values of 5-dimethylallyltryptophan synthase were determined for l-tryptophan and DMAPP at 34 and 76 μm, respectively. Average turnover number (kcat) at 1.1 s−1 was calculated from kinetic data of l-tryptophan and DMAPP. Catalytic efficiencies of 5-dimethylallyltryptophan synthase for l-tryptophan at 25,588 s−1·m−1 and for other 11 simple indole derivatives up to 1538 s−1·m−1 provided evidence for its potential usage as a catalyst for chemoenzymatic synthesis. PMID:22123822

  2. Environment- and eye-centered inhibitory cueing effects are both observed after a methodological confound is eliminated

    PubMed Central

    He, Tao; Ding, Yun; Wang, Zhiguo

    2015-01-01

    Inhibition of return (IOR), typically explored in cueing paradigms, is a performance cost associated with previously attended locations and has been suggested as a crucial attentional mechanism that biases orientation towards novelty. In their seminal IOR paper, Posner and Cohen (1984) showed that IOR is coded in spatiotopic or environment-centered coordinates. Recent studies, however, have consistently reported IOR effects in both spatiotopic and retinotopic (eye-centered) coordinates. One overlooked methodological confound of all previous studies is that the spatial gradient of IOR is not considered when selecting the baseline for estimating IOR effects. This methodological issue makes it difficult to tell if the IOR effects reported in previous studies were coded in retinotopic or spatiotopic coordinates, or in both. The present study addresses this issue with the incorporation of no-cue trials to a modified cueing paradigm in which the cue and target are always intervened by a gaze-shift. The results revealed that a) IOR is indeed coded in both spatiotopic and retinotopic coordinates, and b) the methodology of previous work may have underestimated spatiotopic and retinotopic IOR effects. PMID:26565380

  3. Cryptic confounding compounds: A brief consideration of the influences of anthropogenic contaminants on courtship and mating behavior

    PubMed Central

    Blocker, Tomica D.; Ophir, Alexander G.

    2012-01-01

    Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals, and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have, and promote caution when interpreting results where the potential for cryptic affects are possible. PMID:24244068

  4. Application of Mycobacterium Leprae-specific cellular and serological tests for the differential diagnosis of leprosy from confounding dermatoses.

    PubMed

    Freitas, Aline Araújo; Hungria, Emerith Mayra; Costa, Maurício Barcelos; Sousa, Ana Lúcia Osório Maroccolo; Castilho, Mirian Lane Oliveira; Gonçalves, Heitor Sá; Pontes, Maria Araci Andrade; Duthie, Malcolm S; Stefani, Mariane Martins Araújo

    2016-10-01

    Mycobacterium leprae-specific serological and cell-mediated-immunity/CMI test were evaluated for the differential diagnosis of multibacillary/MB, and paucibacillary/PB leprosy from other dermatoses. Whole-blood assay/WBA/IFNγ stimulated with LID-1 antigen and ELISA tests for IgG to LID-1 and IgM to PGL-I were performed. WBA/LID-1/IFNγ production was observed in 72% PB, 11% MB leprosy, 38% dermatoses, 40% healthy endemic controls/EC. The receiver operating curve/ROC for WBA/LID-1 in PB versus other dermatoses showed 72.5% sensitivity, 61.5% specificity and an area-under-the-curve/AUC=0.75; 74% positive predictive value/PPV, 59% negative predictive value/NPV. Anti PGL-I serology was positive in 67% MB, 8% PB leprosy, 6% of other dermatoses; its sensitivity for MB=66%, specificity=93%, AUC=0.89; PPV=91%, NPV=72%. Anti-LID-1 serology was positive in 87% MB, 7% PB leprosy, all other participants were seronegative; 87.5% sensitivity for MB, 100% specificity, AUC=0.97; PPV=100%, NPV=88%. In highly endemic areas anti-LID-1/PGL-I serology and WBA/LID-1-represent useful tools for the differential diagnosis of leprosy from other confounding dermatoses.

  5. Potential confounds in estimating trial-to-trial correlations between neuronal response and behavior using choice probabilities

    PubMed Central

    Maunsell, John H. R.

    2012-01-01

    Correlations between trial-to-trial fluctuations in the responses of individual sensory neurons and perceptual reports, commonly quantified with choice probability (CP), have been widely used as an important tool for assessing the contributions of neurons to behavior. These correlations are usually weak and often require a large number of trials for a reliable estimate. Therefore, working with measures such as CP warrants care in data analysis as well as rigorous controls during data collection. Here we identify potential confounds that can arise in data analysis and lead to biased estimates of CP, and suggest methods to avoid the bias. In particular, we show that the common practice of combining neuronal responses across different stimulus conditions with z-score normalization can result in an underestimation of CP when the ratio of the numbers of trials for the two behavioral response categories differs across the stimulus conditions. We also discuss the effects of using variable time intervals for quantifying neuronal response on CP measurements. Finally, we demonstrate that serious artifacts can arise in reaction time tasks that use varying measurement intervals if the mean neuronal response and mean behavioral performance vary over time within trials. To emphasize the importance of addressing these concerns in neurophysiological data, we present a set of data collected from V1 cells in macaque monkeys while the animals performed a detection task. PMID:22993262

  6. Fluctuating estuarine conditions are not confounding factors for the Comet assay assessment of DNA damage in the mussel Mytilus edulis.

    PubMed

    Singh, Rupika; Hartl, Mark G J

    2012-10-01

    The Comet assay is finding increasing application as a biomarker assay for the genotoxic potential of contaminants in field transplantation experiments involving mussels. Especially in estuaries, habitats that are of particular concern, environmental variables, such as salinity, can vary significantly. Although hinted at in the literature, there is a lack of clarification as to whether changes in salinity or emersion-induced hypoxia have the potential to alter background DNA damage in mussels, thus masking the extent of potential genotoxic effects following exposure to environmental contaminants. The present study exposed Mytilus edulis in the laboratory to static salinities (25, 50, 75, and 100 %) for 72 h. Mussels were also subjected to simulated tidal cycles, including periods of emersion, for 72 h. None of these treatments resulted in a significant change in the level of DNA damage expressed as % tail DNA. These experiments demonstrate that salinity, within the limits of the concentrations tested, and temporary emersion are not confounding factors for Comet assay data derived from M. edulis.

  7. Cryptic confounding compounds: A brief consideration of the influences of anthropogenic contaminants on courtship and mating behavior.

    PubMed

    Blocker, Tomica D; Ophir, Alexander G

    2013-06-01

    Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals, and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have, and promote caution when interpreting results where the potential for cryptic affects are possible.

  8. Rainfall and temperatures changes have confounding impacts on Phytophthora cinnamomi occurrence risk in the southwestern USA under climate change scenarios.

    PubMed

    Thompson, Sally E; Levin, Simon; Rodriguez-Iturbe, Ignacio

    2014-04-01

    Global change will simultaneously impact many aspects of climate, with the potential to exacerbate the risks posed by plant pathogens to agriculture and the natural environment; yet, most studies that explore climate impacts on plant pathogen ranges consider individual climatic factors separately. In this study, we adopt a stochastic modeling approach to address multiple pathways by which climate can constrain the range of the generalist plant pathogen Phytophthora cinnamomi (Pc): through changing winter soil temperatures affecting pathogen survival; spring soil temperatures and thus pathogen metabolic rates; and changing spring soil moisture conditions and thus pathogen growth rates through host root systems. We apply this model to the southwestern USA for contemporary and plausible future climate scenarios and evaluate the changes in the potential range of Pc. The results indicate that the plausible range of this pathogen in the southwestern USA extends over approximately 200,000 km(2) under contemporary conditions. While warming temperatures as projected by the IPCC A2 and B1 emissions scenarios greatly expand the range over which the pathogen can survive winter, projected reductions in spring rainfall reduce its feasible habitat, leading to spatially complex patterns of changing risk. The study demonstrates that temperature and rainfall changes associated with possible climate futures in the southwestern USA have confounding impacts on the range of Pc, suggesting that projections of future pathogen dynamics and ranges should account for multiple pathways of climate-pathogen interaction.

  9. Confounding dynamic risk taking propensity with a momentum prognostic strategy: the case of the Columbia Card Task (CCT)

    PubMed Central

    Markiewicz, Łukasz; Kubińska, Elżbieta; Tyszka, Tadeusz

    2015-01-01

    Figner et al. (2009) developed the Columbia Card Task (CCT) to measure risk-taking attitudes. This tool consists of two versions: in the COLD version the decision maker needs to state in advance how many cards (out of 32) they want to turn over (so called static risk taking), in the HOT version they have the possibility of turning over all 32 cards one-by-one until they decide to finish (dynamic risk taking). We argue that the HOT version confounds an individual’s willingness to accept risk with their beliefs in trend continuation vs. trend reversal in a prognostic task. In two experimental studies we show that people believing in trend continuation (momentum subjects) turn over more cards than those believing in trend reversal (contrarians) in the HOT version of the task. However, this is not the case in the COLD version. Thus, we provide evidence that, when considered as a dynamic risk propensity measure, the number of turned over cards in the HOT version of the CCT is a contaminated measure and reflects two phenomena: (1) risk preference and (2) the decision-maker’s belief in trend continuation. We speculate that other dynamic risk taking measures can also be biased by a momentum strategy. PMID:26300799

  10. Pulmonary impairment in a cotton textile factory in Nigeria: is lifetime alcohol intake with low cigarette smoking a confounding factor?

    PubMed

    Oleru, U G

    1987-01-01

    A study of 60 Nigerian workers who seldom smoked and who were exposed for 2-15 yr in the printing, dyeing, and maintenance sections of a cotton textile factory showed a 38% airway and 20% "probably airway" symptoms. The airway symptoms were significantly (p less than .005) associated with a decrement in spirometric lung function before and after adjustment for age, height, and duration of employment. The change in residual pulmonary function (PFT) per year of employment was three times higher for the subjects with airway symptoms than for subjects presenting no symptoms. Lifetime alcohol intake was significantly (.025 greater than p less than .01) negatively correlated with pulmonary function and obstructive and restrictive lung disease parameters. Together with body weight, alcohol bottle-years accounted for between 18 and 22% of the variation in lung function, in a forward and reverse stepwise regression analysis. When duration of employment was standardized, subjects with considerable alcohol intake had significantly (.025 greater than p less than .005) lower pulmonary function before and after adjustment for age and height. When the residual PFT was further adjusted for duration of employment, the subjects with higher alcohol intake had significantly (.01 greater than p less than .005) higher residual per year of employment. The subjects presenting airway symptoms had significantly (.05 greater than p less than .005) higher alcohol intake than those in other symptom categories. These data suggest that alcohol intake is a probable confounder in the observed airway and PFT changes.

  11. Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients is not confounded by age or receipt of booster-doses.

    PubMed

    Sheridan, Sarah L; Ware, Robert S; Grimwood, Keith; Lambert, Stephen B

    2015-09-22

    Several observational studies provide evidence that acellular pertussis vaccines (aP) are less protective against pertussis disease than highly effective whole-cell pertussis vaccines (wP), however, concerns have been raised that some of these findings may be confounded by age. By undertaking age-stratified and restricted analyses on a cohort of Australian children primed with either aP-only, wP-only or mixed pertussis vaccine schedules, we demonstrate that compared to aP the association of wP with increased protection from pertussis is not confounded by age, nor by aP booster-dose receipt.

  12. A Program on Biochemical and Biomedical Engineering.

    ERIC Educational Resources Information Center

    San, Ka-Yiu; McIntire, Larry V.

    1989-01-01

    Presents an introduction to the Biochemical and Biomedical Engineering program at Rice University. Describes the development of the academic and enhancement programs, including organizational structure and research project titles. (YP)

  13. Biochemical Lab Activity Supports Evolution Theory

    ERIC Educational Resources Information Center

    Dyman, Daniel J.

    1974-01-01

    Described is thin-layer chromatography (TLC), a technique that can be conveniently used in the laboratory to generate evidence supporting the principle that degrees of biochemical similarity reflect degrees of evolutionary relatedness among organisms. (Author/PEB)

  14. [Biochemical diagnostics of fatal opium intoxication].

    PubMed

    Papyshev, I P; Astashkina, O G; Tuchik, E S; Nikolaev, B S; Cherniaev, A L

    2013-01-01

    Biochemical diagnostics of fatal opium intoxication remains a topical problem in forensic medical science and practice. We investigated materials obtained in the course of forensic medical expertise of the cases of fatal opium intoxication. The study revealed significant differences between myoglobin levels in blood, urine, myocardium, and skeletal muscles. The proposed approach to biochemical diagnostics of fatal opium intoxication enhances the accuracy and the level of evidence of expert conclusions.

  15. Issues Relating to Confounding and Meta-analysis When Including Non-Randomized Studies in Systematic Reviews on the Effects of Interventions

    ERIC Educational Resources Information Center

    Valentine, Jeffrey C.; Thompson, Simon G.

    2013-01-01

    Background: Confounding caused by selection bias is often a key difference between non-randomized studies (NRS) and randomized controlled trials (RCTs) of interventions. Key methodological issues: In this third paper of the series, we consider issues relating to the inclusion of NRS in systematic reviews on the effects of interventions. We discuss…

  16. Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions

    PubMed Central

    Chase, Herbert

    2016-01-01

    Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs. PMID:27716785

  17. The essence of linkage-based imprinting detection: comparing power, type 1 error, and the effects of confounders in two different analysis approaches.

    PubMed

    Greenberg, David A; Monti, Maria Cristina; Feenstra, Bjarke; Zhang, Junying; Hodge, Susan E

    2010-05-01

    Imprinting is critical to understanding disease expression. It can be detected using linkage information, but the effects of potential confounders (heterogeneity, sex-specific penetrance, and sex-biased ascertainment) have not been explored. We examine power and confounders in two imprinting detection approaches, and we explore imprinting-linkage interaction. One method (PP) models imprinting by maximising lod scores w.r.t. parent-specific penetrances. The second (DRF) approximates imprinting by maximising lods over differential male-female recombination fractions. We compared power, type 1 error, and confounder effects in these two methods, using computer-simulated data. We varied heterogeneity, penetrance, family and dataset size, and confounders that might mimic imprinting. Without heterogeneity, PP had more imprinting-detecting power than DRF. PP's power increased when parental affectedness status was ignored, but decreased with heterogeneity. With heterogeneity, type 1 error increased dramatically for both methods. However, DRF's power also increased under heterogeneity, more than was attributable to inflated type 1 error. Sex-specific penetrance could increase false positives for PP but not for DRF. False positives did not increase on ascertainment through an affected "mother". For PP, non-penetrant individuals increased information, arguing against using affected-only methods. The high type 1 error levels under some circumstances means these methods must be used cautiously. PMID:20374235

  18. Confounding effect of EEG implantation surgery: Inadequacy of surgical control in a two hit model of temporal lobe epilepsy.

    PubMed

    Balzekas, Irena; Hernandez, Jose; White, Jacob; Koh, Sookyong

    2016-05-27

    In rodent models of epilepsy, EEG implantation surgery is an essential modality to evaluate electrographic seizures. The inflammatory consequences of EEG electrode-implantation and their resultant effects on seizure susceptibility are unclear. We evaluated electrode-implantation in a two-hit model of epileptogenesis in C57BL/6 mice that included brief, recurrent febrile seizures (FS) at P14 and kainic acid induced seizures (KA-SZ) at P28. During KA-SZ, latencies to first electrographic and behavioral seizures, seizure severity, and KA dose sensitivity were measured. Mice that received subdural screw electrode implants at P25 for EEG monitoring at P28 had significantly shorter latencies to seizures than sham mice, regardless of early life seizure experience. Electrode-implanted mice were sensitive to low dose KA as shown by high mortality rate at KA doses above 10mg/kg. We then directly compared electrode-implantation and KA-SZ in seizure naive CX3CR1(GFP/+) transgenic C57BL/6 mice, wherein microglia express green fluorescent protein (GFP), to determine if microglia activation related to surgery was associated with the increased seizure susceptibility in electrode-implanted mice from the two-hit model. Hippocampal microglia activation, as demonstrated by percent area GFP signal and GFP positive cell counts, prior to seizures was indistinguishable between electrode-implanted mice and controls, but was significantly greater in electrode-implanted mice following seizures. Electrode-implantation had a confounding priming effect on the inflammatory response to subsequent seizures. PMID:27095588

  19. Phenotypic variation as an indicator of pesticide stress in gudgeon: Accounting for confounding factors in the wild.

    PubMed

    Shinn, Cândida; Blanchet, Simon; Loot, Géraldine; Lek, Sovan; Grenouillet, Gaël

    2015-12-15

    The response of organisms to environmental stress is currently used in the assessment of ecosystem health. Morphological changes integrate the multiple effects of one or several stress factors upon the development of the exposed organisms. In a natural environment, many factors determine the patterns of morphological differentiation between individuals. However, few studies have sought to distinguish and measure the independent effect of these factors (genetic diversity and structure, spatial structuring of populations, physical-chemical conditions, etc.). Here we investigated the relationship between pesticide levels measured at 11 sites sampled in rivers of the Garonne river basin (SW France) and morphological changes of a freshwater fish species, the gudgeon (Gobio gobio). Each individual sampled was genotyped using 8 microsatellite markers and their phenotype characterized via 17 morphological traits. Our analysis detected a link between population genetic structure (revealed by a Bayesian method) and morphometry (linear discriminant analysis) of the studied populations. We then developed an original method based on general linear models using distance matrices, an extension of the partial Mantel test beyond 3 matrices. This method was used to test the relationship between contamination (toxicity index) and morphometry (PST of morphometric traits), taking into account (1) genetic differentiation between populations (FST), (2) geographical distances between sites, (3) site catchment area, and (4) various physical-chemical parameters for each sampling site. Upon removal of confounding effects, 3 of the 17 morphological traits studied were significantly correlated with pesticide toxicity, suggesting a response of these traits to the anthropogenic stress. These results underline the importance of taking into account the different sources of phenotypic variability between organisms when identifying the stress factors involved. The separation and quantification of

  20. Measuring rDNA diversity in eukaryotic microbial systems: how intragenomic variation, pseudogenes, and PCR artifacts confound biodiversity estimates.

    PubMed

    Thornhill, Daniel J; Lajeunesse, Todd C; Santos, Scott R

    2007-12-01

    Molecular approaches have revolutionized our ability to study the ecology and evolution of micro-organisms. Among the most widely used genetic markers for these studies are genes and spacers of the rDNA operon. However, the presence of intragenomic rDNA variation, especially among eukaryotes, can potentially confound estimates of microbial diversity. To test this hypothesis, bacterially cloned PCR products of the internal transcribed spacer (ITS) region from clonal isolates of Symbiodinium, a large genus of dinoflagellates that live in symbiosis with many marine protists and invertebrate metazoa, were sequenced and analysed. We found widely differing levels of intragenomic sequence variation and divergence in representatives of Symbiodinium clades A to E, with only a small number of variants attributed to Taq polymerase/bacterial cloning error or PCR chimeras. Analyses of 5.8S-rDNA and ITS2 secondary structure revealed that some variants possessed base substitutions and/or indels that destabilized the folded form of these molecules; given the vital nature of secondary structure to the function of these molecules, these likely represent pseudogenes. When similar controls were applied to bacterially cloned ITS sequences from a recent survey of Symbiodinium diversity in Hawaiian Porites spp., most variants (approximately 87.5%) possessed unstable secondary structures, had unprecedented mutations, and/or were PCR chimeras. Thus, data obtained from sequencing of bacterially cloned rDNA genes can substantially exaggerate the level of eukaryotic microbial diversity inferred from natural samples if appropriate controls are not applied. These considerations must be taken into account when interpreting sequence data generated by bacterial cloning of multicopy genes such as rDNA.

  1. Phenotypic variation as an indicator of pesticide stress in gudgeon: Accounting for confounding factors in the wild.

    PubMed

    Shinn, Cândida; Blanchet, Simon; Loot, Géraldine; Lek, Sovan; Grenouillet, Gaël

    2015-12-15

    The response of organisms to environmental stress is currently used in the assessment of ecosystem health. Morphological changes integrate the multiple effects of one or several stress factors upon the development of the exposed organisms. In a natural environment, many factors determine the patterns of morphological differentiation between individuals. However, few studies have sought to distinguish and measure the independent effect of these factors (genetic diversity and structure, spatial structuring of populations, physical-chemical conditions, etc.). Here we investigated the relationship between pesticide levels measured at 11 sites sampled in rivers of the Garonne river basin (SW France) and morphological changes of a freshwater fish species, the gudgeon (Gobio gobio). Each individual sampled was genotyped using 8 microsatellite markers and their phenotype characterized via 17 morphological traits. Our analysis detected a link between population genetic structure (revealed by a Bayesian method) and morphometry (linear discriminant analysis) of the studied populations. We then developed an original method based on general linear models using distance matrices, an extension of the partial Mantel test beyond 3 matrices. This method was used to test the relationship between contamination (toxicity index) and morphometry (PST of morphometric traits), taking into account (1) genetic differentiation between populations (FST), (2) geographical distances between sites, (3) site catchment area, and (4) various physical-chemical parameters for each sampling site. Upon removal of confounding effects, 3 of the 17 morphological traits studied were significantly correlated with pesticide toxicity, suggesting a response of these traits to the anthropogenic stress. These results underline the importance of taking into account the different sources of phenotypic variability between organisms when identifying the stress factors involved. The separation and quantification of

  2. Global climate change in large European rivers: long-term effects on macroinvertebrate communities and potential local confounding factors.

    PubMed

    Floury, Mathieu; Usseglio-Polatera, Philippe; Ferreol, Martial; Delattre, Cecile; Souchon, Yves

    2013-04-01

    Aquatic species living in running waters are widely acknowledged to be vulnerable to climate-induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple-stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long-term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979-2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979-1988 and 1999-2008) and to a lesser extent discharge reduction (-80 m(3) s(-1) ) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution-sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects.

  3. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer

    PubMed Central

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas HG

    2011-01-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician’s discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account. PMID:22263071

  4. Coping with confounds in multivoxel pattern analysis: what should we do about reaction time differences? A comment on Todd, Nystrom & Cohen 2013.

    PubMed

    Woolgar, Alexandra; Golland, Polina; Bode, Stefan

    2014-09-01

    Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to

  5. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  6. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify...

  7. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  8. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  9. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  10. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  11. Nonlinear biochemical signal processing via noise propagation

    NASA Astrophysics Data System (ADS)

    Kim, Kyung Hyuk; Qian, Hong; Sauro, Herbert M.

    2013-10-01

    Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how noise affects cellular phenotypes based on identifying a system's nonlinearities and noise propagations. We observe that such noise can simultaneously enhance sensitivities in one behavioral region while reducing sensitivities in another. Employing this novel phenomenon we designed three biochemical signal processing modules: (a) A gene regulatory network that acts as a concentration detector with both enhanced amplitude and sensitivity. (b) A non-cooperative positive feedback system, with a graded dose-response in the deterministic case, that serves as a bistable switch due to noise-induced ultra-sensitivity. (c) A noise-induced linear amplifier for gene regulation that requires no feedback. The methods developed in the present work allow one to understand and engineer nonlinear biochemical signal processors based on fluctuation-induced phenotypes.

  12. Nonlinear biochemical signal processing via noise propagation.

    PubMed

    Kim, Kyung Hyuk; Qian, Hong; Sauro, Herbert M

    2013-10-14

    Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how noise affects cellular phenotypes based on identifying a system's nonlinearities and noise propagations. We observe that such noise can simultaneously enhance sensitivities in one behavioral region while reducing sensitivities in another. Employing this novel phenomenon we designed three biochemical signal processing modules: (a) A gene regulatory network that acts as a concentration detector with both enhanced amplitude and sensitivity. (b) A non-cooperative positive feedback system, with a graded dose-response in the deterministic case, that serves as a bistable switch due to noise-induced ultra-sensitivity. (c) A noise-induced linear amplifier for gene regulation that requires no feedback. The methods developed in the present work allow one to understand and engineer nonlinear biochemical signal processors based on fluctuation-induced phenotypes.

  13. Reconfigurable neuromorphic computation in biochemical systems.

    PubMed

    Chiang, Hui-Ju Katherine; Jiang, Jie-Hong R; Fages, Francois

    2015-08-01

    Implementing application-specific computation and control tasks within a biochemical system has been an important pursuit in synthetic biology. Most synthetic designs to date have focused on realizing systems of fixed functions using specifically engineered components, thus lacking flexibility to adapt to uncertain and dynamically-changing environments. To remedy this limitation, an analog and modularized approach to realize reconfigurable neuromorphic computation with biochemical reactions is presented. We propose a biochemical neural network consisting of neuronal modules and interconnects that are both reconfigurable through external or internal control over the concentrations of certain molecular species. Case studies on classification and machine learning applications using the DNA strain displacement technology demonstrate the effectiveness of our design in both reconfiguration and autonomous adaptation. PMID:26736417

  14. Biochemical Removal of HAP Precursors From Coal

    SciTech Connect

    Olson, G.; Tucker, L.; Richards, J.

    1997-07-01

    This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

  15. Testosterone Deficiency - Establishing A Biochemical Diagnosis

    PubMed Central

    Krakowsky, Yonah

    2015-01-01

    Testosterone deficiency is a common and often unrecognized disorder impacting the lives of many men. Symptoms related to low testosterone are relatively non-specific and clinicians must therefore ensure that a patients’ symptomatology is supported by a biochemical profile suggestive of testosterone deficiency. There are many options available to determine a patient’s testosterone level and laboratories will vary in the type of biochemical assessment they provide. In assessing patients with suspected low testosterone, the presence of symptoms and a low total testosterone is usually sufficient to initiate therapy. In equivocal cases, measurement of free or bioavailable testosterone with a reliable assay can further clarify the clinical picture. By understanding the differences between total, free and bioavailable testosterone, and the accuracy and reliability of their measurement, clinicians can better interpret their patients’ biochemical testosterone profile.

  16. Biochemical Screening for in utero Drug Exposure.

    PubMed

    Wright, Tricia E

    2015-01-01

    Licit and illicit drug use is a common complication of pregnancy. Accurate information on drug use is difficult to obtain for many reasons as women fear self-disclosure or consenting for drug testing due to stigma, guilt, and fear of social and legal harm. As information about drug use is clinically very important, biochemical testing is an important adjunct to careful maternal history. In addition, research studies depend on accurate measures of exposure when reporting risks of a substance. This paper delineates available matrices for and methods of biochemical drug testing in pregnant women and neonates.

  17. Biochemical computation for spine structural plasticity

    PubMed Central

    Nishiyama, Jun; Yasuda, Ryohei

    2015-01-01

    The structural plasticity of dendritic spines is considered to be essential for various forms of synaptic plasticity, learning and memory. The process is mediated by a complex signaling network consisting of numerous species of molecules. Furthermore, the spatiotemporal dynamics of the biochemical signaling is regulated in a complicated manner due to geometrical restrictions from the unique morphology of the dendritic branches and spines. Recent advances in optical techniques have enabled the exploration of the spatiotemporal aspects of the signal regulations in spines and dendrites and have provided many insights into the principle of the biochemical computation that underlies spine structural plasticity. PMID:26139370

  18. Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

    NASA Astrophysics Data System (ADS)

    Yong, Chin-Khian

    2013-09-01

    A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

  19. Annual survival estimation of migratory songbirds confounded by incomplete breeding site-fidelity: Study designs that may help

    USGS Publications Warehouse

    Marshall, M.R.; Diefenbach, D.R.; Wood, L.A.; Cooper, R.J.

    2004-01-01

    Many species of bird exhibit varying degrees of site-fidelity to the previous year's territory or breeding area, a phenomenon we refer to as incomplete breeding site-fidelity. If the territory they occupy is located beyond the bounds of the study area or search area (i.e., they have emigrated from the study area), the bird will go undetected and is therefore indistinguishable from dead individuals in capture-mark-recapture studies. Differential emigration rates confound inferences regarding differences in survival between sexes and among species if apparent survival rates are used as estimates of true survival. Moreover, the bias introduced by using apparent survival rates for true survival rates can have profound effects on the predictions of population persistence through time, source/sink dynamics, and other aspects of life-history theory. We investigated four study design and analysis approaches that result in apparent survival estimates that are closer to true survival estimates. Our motivation for this research stemmed from a multi-year capture-recapture study of Prothonotary Warblers (Protonotaria citrea) on multiple study plots within a larger landscape of suitable breeding habitat where substantial inter-annual movements of marked individuals among neighboring study plots was documented. We wished to quantify the effects of this type of movement on annual survival estimation. The first two study designs we investigated involved marking birds in a core area and resighting them in the core as well as an area surrounding the core. For the first of these two designs, we demonstrated that as the resighting area surrounding the core gets progressively larger, and more "emigrants" are resighted, apparent survival estimates begin to approximate true survival rates (bias < 0.01). However, given observed inter-annual movements of birds, it is likely to be logistically impractical to resight birds on sufficiently large surrounding areas to minimize bias. Therefore

  20. Propensity Score-Based Approaches to Confounding by Indication in Individual Patient Data Meta-Analysis: Non-Standardized Treatment for Multidrug Resistant Tuberculosis

    PubMed Central

    Fox, Gregory J.; Benedetti, Andrea; Mitnick, Carole D.; Pai, Madhukar; Menzies, Dick

    2016-01-01

    Background In the absence of randomized clinical trials, meta-analysis of individual patient data (IPD) from observational studies may provide the most accurate effect estimates for an intervention. However, confounding by indication remains an important concern that can be addressed by incorporating individual patient covariates in different ways. We compared different analytic approaches to account for confounding in IPD from patients treated for multi-drug resistant tuberculosis (MDR-TB). Methods Two antibiotic classes were evaluated, fluoroquinolones—considered the cornerstone of effective MDR-TB treatment—and macrolides, which are known to be safe, yet are ineffective in vitro. The primary outcome was treatment success against treatment failure, relapse or death. Effect estimates were obtained using multivariable and propensity-score based approaches. Results Fluoroquinolone antibiotics were used in 28 included studies, within which 6,612 patients received a fluoroquinolone and 723 patients did not. Macrolides were used in 15 included studies, within which 459 patients received this class of antibiotics and 3,670 did not. Both standard multivariable regression and propensity score-based methods resulted in similar effect estimates for early and late generation fluoroquinolones, while macrolide antibiotics use was associated with reduced treatment success. Conclusions In this individual patient data meta-analysis, standard multivariable and propensity-score based methods of adjusting for individual patient covariates for observational studies yielded produced similar effect estimates. Even when adjustment is made for potential confounding, interpretation of adjusted estimates must still consider the potential for residual bias. PMID:27022741

  1. Confounding factors to predict the awakening effect-site concentration of propofol in target-controlled infusion based on propofol and fentanyl anesthesia.

    PubMed

    Chan, Shun-Ming; Lee, Meei-Shyuan; Lu, Chueng-He; Cherng, Chen-Hwan; Huang, Yuan-Shiou; Yeh, Chun-Chang; Kuo, Chan-Yang; Wu, Zhi-Fu

    2015-01-01

    We conducted a large retrospective study to investigate the confounding factors that predict Ce ROC under propofol-based TIVA with TCI. We recorded sex, age, height, weight, Ce LOC, Ce ROC, total propofol and fentanyl consumption dose, and anesthetic time. Simple linear regression models were used to identify potential predictors of Ce ROC, and multiple linear regression models were used to identify the confounding predictors of Ce ROC. We found that Ce ROC correlated with age, sex, Ce LOC, and both total fentanyl and propofol consumption dose. The prediction formula was: Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC + 0.04 (if fentanyl consumption > 150 μg; if not, ignore this value) + 0.07 × (1 or 2, according to the total propofol consumption dose, 1 for a propofol amount 1000-2000 mg and 2 for a propofol amount > 2000 mg). We simplified the formula further as Ce ROC = 0.87 - 0.06 × age + 0.18 × Ce LOC. In conclusion, Ce ROC can be predicted under TCI with propofol- and fentanyl-based TIVA. The confounding factors that predicted propofol Ce ROC are age, sex, Ce LOC, and total consumption dose of propofol and fentanyl.

  2. [COMPUTER TECHNOLOGY FOR ACCOUNTING OF CONFOUNDERS IN THE RISK ASSESSMENT IN COMPARATIVE STUDIES ON THE BASE OF THE METHOD OF STANDARDIZATION].

    PubMed

    Shalaumova, Yu V; Varaksin, A N; Panov, V G

    2016-01-01

    There was performed an analysis of the accounting of the impact of concomitant variables (confounders), introducing a systematic error in the assessment of the impact of risk factors on the resulting variable. The analysis showed that standardization is an effective method for the reduction of the shift of risk assessment. In the work there is suggested an algorithm implementing the method of standardization based on stratification, providing for the minimization of the difference of distributions of confounders in groups on risk factors. To automate the standardization procedures there was developed a software available on the website of the Institute of Industrial Ecology, UB RAS. With the help of the developed software by numerically modeling there were determined conditions of the applicability of the method of standardization on the basis of stratification for the case of the normal distribution on the response and confounder and linear relationship between them. Comparison ofresults obtained with the help of the standardization with statistical methods (logistic regression and analysis of covariance) in solving the problem of human ecology, has shown that obtaining close results is possible if there will be met exactly conditions for the applicability of statistical methods. Standardization is less sensitive to violations of conditions of applicability. PMID:27266034

  3. [COMPUTER TECHNOLOGY FOR ACCOUNTING OF CONFOUNDERS IN THE RISK ASSESSMENT IN COMPARATIVE STUDIES ON THE BASE OF THE METHOD OF STANDARDIZATION].

    PubMed

    Shalaumova, Yu V; Varaksin, A N; Panov, V G

    2016-01-01

    There was performed an analysis of the accounting of the impact of concomitant variables (confounders), introducing a systematic error in the assessment of the impact of risk factors on the resulting variable. The analysis showed that standardization is an effective method for the reduction of the shift of risk assessment. In the work there is suggested an algorithm implementing the method of standardization based on stratification, providing for the minimization of the difference of distributions of confounders in groups on risk factors. To automate the standardization procedures there was developed a software available on the website of the Institute of Industrial Ecology, UB RAS. With the help of the developed software by numerically modeling there were determined conditions of the applicability of the method of standardization on the basis of stratification for the case of the normal distribution on the response and confounder and linear relationship between them. Comparison ofresults obtained with the help of the standardization with statistical methods (logistic regression and analysis of covariance) in solving the problem of human ecology, has shown that obtaining close results is possible if there will be met exactly conditions for the applicability of statistical methods. Standardization is less sensitive to violations of conditions of applicability.

  4. A Course in Biochemical Engineering Fundamentals (Revisited).

    ERIC Educational Resources Information Center

    Bailey, J. E.; Ollis, D. F.

    1985-01-01

    Provides: (1) a glossary of terms used in biochemical engineering; (2) a list of key developments in the field; and (3) emphases placed in 15 topic areas in a course restructured on the basis of these developments. Topic areas include enzyme kinetics/applications, genetics and microbial control, transport phenomena, and others. (JN)

  5. Predictive biochemical assays for late radiation effects

    SciTech Connect

    Rubin, P.; Finkelstein, J.N.; Siemann, D.W.; Shapiro, D.L.; Van Houtte, P.; Penney, D.P.

    1986-04-01

    Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man has been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve.

  6. Biochemical Applications in the Analytical Chemistry Lab

    ERIC Educational Resources Information Center

    Strong, Cynthia; Ruttencutter, Jeffrey

    2004-01-01

    An HPLC and a UV-visible spectrophotometer are identified as instruments that helps to incorporate more biologically-relevant experiments into the course, in order to increase the students understanding of selected biochemistry topics and enhances their ability to apply an analytical approach to biochemical problems. The experiment teaches…

  7. 2009 Biochemical Conversion Platform Review Report

    SciTech Connect

    Ferrell, John

    2009-12-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the U.S. Department of Energy Biomass Program’s Biochemical Conversion platform review meeting, held on April 14-16, 2009, at the Sheraton Denver Downtown, Denver, Colorado.

  8. Biochemical Thermodynamics under near Physiological Conditions

    ERIC Educational Resources Information Center

    Mendez, Eduardo

    2008-01-01

    The recommendations for nomenclature and tables in Biochemical Thermodynamics approved by IUBMB and IUPAC in 1994 can be easily introduced after the chemical thermodynamic formalism. Substitution of the usual standard thermodynamic properties by the transformed ones in the thermodynamic equations, and the use of appropriate thermodynamic tables…

  9. Survey of Biochemical Education in Japanese Universities.

    ERIC Educational Resources Information Center

    Kagawa, Yasuo

    1995-01-01

    Reports findings of questionnaires sent to faculty in charge of biochemical education in medical schools and other programs from dentistry to agriculture. Total class hours have declined since 1984. New trends include bioethics and computer-assisted learning. Tables show trends in lecture hours, lecture content, laboratory hours, core subject…

  10. Biochemical Approaches to Improved Nitrogen Fixation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Improving symbiotic nitrogen fixation by legumes has emerged again as an important topic on the world scene due to the energy crisis and lack of access to nitrogen fertilizer in developing countries. We have taken a biochemical genomics approach to improving symbiotic nitrogen fixation in legumes. L...

  11. Kombucha tea fermentation: Microbial and biochemical dynamics.

    PubMed

    Chakravorty, Somnath; Bhattacharya, Semantee; Chatzinotas, Antonis; Chakraborty, Writachit; Bhattacharya, Debanjana; Gachhui, Ratan

    2016-03-01

    Kombucha tea, a non-alcoholic beverage, is acquiring significant interest due to its claimed beneficial properties. The microbial community of Kombucha tea consists of bacteria and yeast which thrive in two mutually non-exclusive compartments: the soup or the beverage and the biofilm floating on it. The microbial community and the biochemical properties of the beverage have so far mostly been described in separate studies. This, however, may prevent understanding the causal links between the microbial communities and the beneficial properties of Kombucha tea. Moreover, an extensive study into the microbial and biochemical dynamics has also been missing. In this study, we thus explored the structure and dynamics of the microbial community along with the biochemical properties of Kombucha tea at different time points up to 21 days of fermentation. We hypothesized that several biochemical properties will change during the course of fermentation along with the shifts in the yeast and bacterial communities. The yeast community of the biofilm did not show much variation over time and was dominated by Candida sp. (73.5-83%). The soup however, showed a significant shift in dominance from Candida sp. to Lachancea sp. on the 7th day of fermentation. This is the first report showing Candida as the most dominating yeast genus during Kombucha fermentation. Komagateibacter was identified as the single largest bacterial genus present in both the biofilm and the soup (~50%). The bacterial diversity was higher in the soup than in the biofilm with a peak on the seventh day of fermentation. The biochemical properties changed with the progression of the fermentation, i.e., beneficial properties of the beverage such as the radical scavenging ability increased significantly with a maximum increase at day 7. We further observed a significantly higher D-saccharic acid-1,4-lactone content and caffeine degradation property compared to previously described Kombucha tea fermentations. Our

  12. Kombucha tea fermentation: Microbial and biochemical dynamics.

    PubMed

    Chakravorty, Somnath; Bhattacharya, Semantee; Chatzinotas, Antonis; Chakraborty, Writachit; Bhattacharya, Debanjana; Gachhui, Ratan

    2016-03-01

    Kombucha tea, a non-alcoholic beverage, is acquiring significant interest due to its claimed beneficial properties. The microbial community of Kombucha tea consists of bacteria and yeast which thrive in two mutually non-exclusive compartments: the soup or the beverage and the biofilm floating on it. The microbial community and the biochemical properties of the beverage have so far mostly been described in separate studies. This, however, may prevent understanding the causal links between the microbial communities and the beneficial properties of Kombucha tea. Moreover, an extensive study into the microbial and biochemical dynamics has also been missing. In this study, we thus explored the structure and dynamics of the microbial community along with the biochemical properties of Kombucha tea at different time points up to 21 days of fermentation. We hypothesized that several biochemical properties will change during the course of fermentation along with the shifts in the yeast and bacterial communities. The yeast community of the biofilm did not show much variation over time and was dominated by Candida sp. (73.5-83%). The soup however, showed a significant shift in dominance from Candida sp. to Lachancea sp. on the 7th day of fermentation. This is the first report showing Candida as the most dominating yeast genus during Kombucha fermentation. Komagateibacter was identified as the single largest bacterial genus present in both the biofilm and the soup (~50%). The bacterial diversity was higher in the soup than in the biofilm with a peak on the seventh day of fermentation. The biochemical properties changed with the progression of the fermentation, i.e., beneficial properties of the beverage such as the radical scavenging ability increased significantly with a maximum increase at day 7. We further observed a significantly higher D-saccharic acid-1,4-lactone content and caffeine degradation property compared to previously described Kombucha tea fermentations. Our

  13. Structural and biochemical characterization of DSL ribozyme.

    PubMed

    Horie, Souta; Ikawa, Yoshiya; Inoue, Tan

    2006-01-01

    We recently reported on the molecular design and synthesis of a new RNA ligase ribozyme (DSL), whose active site was selected from a sequence library consisting of 30 random nucleotides set on a defined 3D structure of a designed RNA scaffold. In this study, we report on the structural and biochemical analyses of DSL. Structural analysis indicates that the active site, which consists of the selected sequence, attaches to the folded scaffold as designed. To see whether DSL resembles known ribozymes, a biochemical assay was performed. Metal-dependent kinetic studies suggest that the ligase requires Mg2+ ions. The replacement of Mg2+ with Co(NH3)6(3+) prohibits the reaction, indicating that DSL requires innersphere coordination of Mg2+ for a ligation reaction. The results show that DSL has requirements similar to those of previously reported catalytic RNAs.

  14. Thermodynamics of biochemical networks and duality theorems

    NASA Astrophysics Data System (ADS)

    De Martino, Daniele

    2013-05-01

    One interesting yet difficult computational issue has recently been posed in biophysics in regard to the implementation of thermodynamic constraints to complex networks. Biochemical networks of enzymes inside cells are among the most efficient, robust, differentiated, and flexible free-energy transducers in nature. How is the second law of thermodynamics encoded for these complex networks? In this article it is demonstrated that for chemical reaction networks in the steady state the exclusion (presence) of closed reaction cycles makes possible (impossible) the definition of a chemical potential vector. Interestingly, this statement is encoded in one of the key results in combinatorial optimization, i.e., the Gordan theorem of the alternatives. From a computational viewpoint, the theorem reveals that calculating a reaction's free energy and identifying infeasible loops in flux states are dual problems whose solutions are mutually exclusive, and this opens the way for efficient and scalable methods to perform the energy balance analysis of large-scale biochemical networks.

  15. Least squares estimation in stochastic biochemical networks.

    PubMed

    Rempala, Grzegorz A

    2012-08-01

    The paper presents results on the asymptotic properties of the least-squares estimates (LSEs) of the reaction constants in mass-action, stochastic, biochemical network models. LSEs are assumed to be based on the longitudinal data from partially observed trajectories of a stochastic dynamical system, modeled as a continuous-time, pure jump Markov process. Under certain regularity conditions on such a process, it is shown that the vector of LSEs is jointly consistent and asymptotically normal, with the asymptotic covariance structure given in terms of a system of ordinary differential equations (ODE). The derived asymptotic properties hold true as the biochemical network size (the total species number) increases, in which case the stochastic dynamical system converges to the deterministic mass-action ODE. An example is provided, based on synthetic as well as RT-PCR data from the retro-transcription network of the LINE1 gene.

  16. Construction and analysis of biochemical networks

    NASA Astrophysics Data System (ADS)

    Binns, Michael; Theodoropoulos, Constantinos

    2012-09-01

    Bioprocesses are being implemented for a range of different applications including the production of fuels, chemicals and drugs. Hence, it is becoming increasingly important to understand and model how they function and how they can be modified or designed to give the optimal performance. Here we discuss the construction and analysis of biochemical networks which are the first logical steps towards this goal. The construction of a reaction network is possible through reconstruction: extracting information from literature and from databases. This can be supplemented by reaction prediction methods which can identify steps which are missing from the current knowledge base. Analysis of biochemical systems generally requires some experimental input but can be used to identify important reactions and targets for enhancing the performance of the organism involved. Metabolic flux, pathway and metabolic control analysis can be used to determine the limits, capabilities and potential targets for enhancement respectively.

  17. Biochemical alterations during swimming induced stress.

    PubMed

    Aruj, N; Sharafatullah, T; Najam, R; Ahmed, S P; Ahmad, S I

    1994-07-01

    Stress can be defined as any stimulus that creates an imbalance in the internal environment. Hypothalamus has sensors that detect changes produced in the body. Stress can cause diseases by altering immune system, cardiovascular System neurotransmitter and neuroendocrine functions. Present study is designed to evaluate the effect of stress on few biochemical parameters during swimming induced stress. Significant changes have been observed especially in lipid profile. Corticosterone was also evaluated as reliable stress marker.

  18. Biochemical correlates of neurosensory changes in weightlessness

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Reschke, Millard F.

    1989-01-01

    The possible existence of a relationship between space motion sickness and chemical and biochemical variables measured in body fluids is studied. Clinical chemistry and endocrine measurements from blood and urine samples taken before and after Space Shuttle flights were analyzed along with the occurrence of SMS during flight and provocative testing before flight. Significant positive correlations were observed with serum chloride and significant negative correlations with serum phosphate, serum uric acid, and plasma thyroid stimulating hormone.

  19. Electronic modulation of biochemical signal generation

    NASA Astrophysics Data System (ADS)

    Gordonov, Tanya; Kim, Eunkyoung; Cheng, Yi; Ben-Yoav, Hadar; Ghodssi, Reza; Rubloff, Gary; Yin, Jun-Jie; Payne, Gregory F.; Bentley, William E.

    2014-08-01

    Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

  20. Electronic modulation of biochemical signal generation.

    PubMed

    Gordonov, Tanya; Kim, Eunkyoung; Cheng, Yi; Ben-Yoav, Hadar; Ghodssi, Reza; Rubloff, Gary; Yin, Jun-Jie; Payne, Gregory F; Bentley, William E

    2014-08-01

    Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

  1. Stoichiometric network theory for nonequilibrium biochemical systems.

    PubMed

    Qian, Hong; Beard, Daniel A; Liang, Shou-dan

    2003-02-01

    We introduce the basic concepts and develop a theory for nonequilibrium steady-state biochemical systems applicable to analyzing large-scale complex isothermal reaction networks. In terms of the stoichiometric matrix, we demonstrate both Kirchhoff's flux law sigma(l)J(l)=0 over a biochemical species, and potential law sigma(l) mu(l)=0 over a reaction loop. They reflect mass and energy conservation, respectively. For each reaction, its steady-state flux J can be decomposed into forward and backward one-way fluxes J = J+ - J-, with chemical potential difference deltamu = RT ln(J-/J+). The product -Jdeltamu gives the isothermal heat dissipation rate, which is necessarily non-negative according to the second law of thermodynamics. The stoichiometric network theory (SNT) embodies all of the relevant fundamental physics. Knowing J and deltamu of a biochemical reaction, a conductance can be computed which directly reflects the level of gene expression for the particular enzyme. For sufficiently small flux a linear relationship between J and deltamu can be established as the linear flux-force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits.

  2. [Biochemical antenatal screening for fetal anomalies.].

    PubMed

    Torfadóttir, G; Jónsson, J J

    2001-05-01

    Biochemical antenatal screening started 30 years ago. Initially, the goal was to detect neural tube defects by measuring a-fetoprotein in maternal serum (MS-AFP) and amniotic fluid (AF-AFP). The serendipitous discovery of an association between low AFP maternal serum concentration and chromosomal anomalies resulted in increased research interest in biochemical screening in pregnancy. Subsequently double, triple or quadruple tests in 2nd trimester of pregnancy became widely used in combination with fetal chromosome determination in at risk individuals. In Iceland, antenatal screening for chromosomal anomalies has essentially been based on fetal chromosome studies offered to pregnant women 35 years or older. This strategy needs to be revised. Recently first trimester biochemical screening based on maternal serum pregnancy associated plasma protein A (MS-PAPP-A) and free b-human chorionic gonadotropin (MS-free b-hCG) and multivariate risk assessment has been developed. This screening test can be improved if done in conjunction with nuchal translucency measurements in an early sonography scan. PMID:17018982

  3. Hydrogel-based piezoresistive biochemical microsensors

    NASA Astrophysics Data System (ADS)

    Guenther, Margarita; Schulz, Volker; Gerlach, Gerald; Wallmersperger, Thomas; Solzbacher, Florian; Magda, Jules J.; Tathireddy, Prashant; Lin, Genyao; Orthner, Michael P.

    2010-04-01

    This work is motivated by a demand for inexpensive, robust and reliable biochemical sensors with high signal reproducibility and long-term-stable sensitivity, especially for medical applications. Micro-fabricated sensors can provide continuous monitoring and on-line control of analyte concentrations in ambient aqueous solutions. The piezoresistive biochemical sensor containing a special biocompatible polymer (hydrogel) with a sharp volume phase transition in the neutral physiological pH range near 7.4 can detect a specific analyte, for example glucose. Thereby the hydrogel-based biochemical sensors are useful for the diagnosis and monitoring of diabetes. The response of the glucosesensitive hydrogel was studied at different regimes of the glucose concentration change and of the solution supply. Sensor response time and accuracy with which a sensor can track gradual changes in glucose was estimated. Additionally, the influence of various recommended sterilization methods on the gel swelling properties and on the mechano-electrical transducer of the pH-sensors has been evaluated in order to choose the most optimal sterilization method for the implantable sensors. It has been shown that there is no negative effect of gamma irradiation with a dose of 25.7 kGy on the hydrogel sensitivity. In order to achieve an optimum between sensor signal amplitude and sensor response time, corresponding calibration and measurement procedures have been proposed and evaluated for the chemical sensors.

  4. Biochemical reaction engineering for redox reactions.

    PubMed

    Wandrey, Christian

    2004-01-01

    Redox reactions are still a challenge for biochemical engineers. A personal view for the development of this field is given. Cofactor regeneration was an obstacle for quite some time. The first technical breakthrough was achieved with the system formate/formate dehydrogenase for the regeneration of NADH2. In cases where the same enzyme could be used for chiral reduction as well as for cofactor regeneration, isopropanol as a hydrogen source proved to be beneficial. The coproduct (acetone) can be removed by pervaporation. Whole-cell reductions (often yeast reductions) can also be used. By proper biochemical reaction engineering, it is possible to apply these systems in a continuous way. By cloning a formate dehydrogenase and an oxidoreductase "designer bug" can be obtained where formate is used instead of glucose as the hydrogen source. Complex sequences of redox reactions can be established by pathway engineering with a focus on gene overexpression or with a focus on establishing non-natural pathways. The success of pathway engineering can be controlled by measuring cytosolic metabolite concentrations. The optimal exploitation of such systems calls for the integrated cooperation of classical and molecular biochemical engineering.

  5. Development of histopathological indices in the digestive gland and gonad of mussels: integration with contamination levels and effects of confounding factors.

    PubMed

    Cuevas, Nagore; Zorita, Izaskun; Costa, Pedro M; Franco, Javier; Larreta, Joana

    2015-05-01

    Bivalve histopathology has become an important tool in aquatic toxicology, having been implemented in many biomonitoring programmes worldwide. However, there are various gaps in the knowledge of many sentinel organisms and the interference of confounding factors. This work aimed (i) to develop a detailed semi-quantitative histopathological index of the digestive gland and gonad of the Mytilus galloprovincialis mussel collected from five sites contaminated with distinct patterns of organic and inorganic toxicants along the Basque coast (SE Bay of Biscay) and (ii) to investigate whether seasonal variability and parasitosis act as confounding factors. A total of twenty-three histopathological alterations were analysed in the digestive gland and gonad following a weighed condition index approach. The alterations were integrated into a single value for a better understanding of the mussels' health status. The digestive gland was consistently more damaged than the gonad. Mussels from the most impacted sites endured the most significant deleterious effects showing inflammation-related alterations together with digestive tubule atrophy and necrosis. Neoplastic diseases were scarce, with only a few cases of fibromas (benign neoplasia). In contrast, in moderately or little impacted sites, contamination levels did not cause significant tissue damage. However, parasites contributed to overestimating the values of histopathological indices (i.e. more severe tissue damage) in mussels from little impacted sites, whilst the opposite occurred in mussels from highly polluted sites. Accordingly, inter-site differences were more pronounced in autumn when natural physiological responses of advanced maturation stages did not interfere in the histological response. In conclusion, although seasonal variability and parasitosis mask the response of histopathological indices, this biomonitoring approach may provide good sensitivity for assessing the health status of mussels if fluctuations

  6. 'Bigger data' on scale-dependent effects of invasive species on biodiversity cannot overcome confounded analyses: a comment on Stohlgren & Rejmánek (2014).

    PubMed

    Chase, Jonathan M; Powell, Kristin I; Knight, Tiffany M

    2015-08-01

    A recent study by Stohlgren & Rejmánek (SR: Stohlgren TJ, Rejmánek M. 2014 Biol. Lett. 10. (doi:10.1098/rsbl.2013.0939)) purported to test the generality of a recent finding of scale-dependent effects of invasive plants on native diversity; dominant invasive plants decreased the intercept and increased the slope of the species-area relationship. SR (2014) find little correlation between invasive species cover and the slopes and intercepts of SARs across a diversity of sites. We show that the analyses of SR (2014) are inappropriate because of confounding causality.

  7. Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

    PubMed Central

    Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

    2016-01-01

    Objectives Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Design Retrospective cohort study. Setting Finnish healthcare registers. Participants Women aged 45–64 years initiating statin use for primary prevention of cardiovascular disease in 2001–2004 (n=42 807). Outcomes Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. Results During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Conclusions Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events

  8. 'Bigger data' on scale-dependent effects of invasive species on biodiversity cannot overcome confounded analyses: a comment on Stohlgren & Rejmánek (2014).

    PubMed

    Chase, Jonathan M; Powell, Kristin I; Knight, Tiffany M

    2015-08-01

    A recent study by Stohlgren & Rejmánek (SR: Stohlgren TJ, Rejmánek M. 2014 Biol. Lett. 10. (doi:10.1098/rsbl.2013.0939)) purported to test the generality of a recent finding of scale-dependent effects of invasive plants on native diversity; dominant invasive plants decreased the intercept and increased the slope of the species-area relationship. SR (2014) find little correlation between invasive species cover and the slopes and intercepts of SARs across a diversity of sites. We show that the analyses of SR (2014) are inappropriate because of confounding causality. PMID:26246332

  9. Analytic Strategies to Adjust Confounding Using Exposure Propensity Scores and Disease Risk Scores: Nonsteroidal Antiinflammatory Drugs (NSAID) and Short-term Mortality in the Elderly

    PubMed Central

    Stürmer, Til; Schneeweiss, Sebastian; Brookhart, M. Alan; Rothman, Kenneth J; Avorn, Jerry; Glynn, Robert J

    2006-01-01

    Little is known about optimal application and behavior of exposure propensity scores (EPS) in small studies. Based on a cohort of 103,133 elderly Medicaid beneficiaries, the effect of nonsteroidal anti-inflammatory drug (NSAID) use on 1-year all-cause mortality was assessed based on the assumption that there is no protective effect, and the preponderance of any observed effect would be confounded. To study the comparative behavior of EPS, disease risk scores (DRS), and ‘traditional’ disease models, we randomly re-sampled 1,000 subcohorts of 10,000, 1,000 and 500 people. The number of variables was limited in disease models, but not EPS and DRS. Estimated EPS were used to adjust for confounding by matching, inverse probability of treatment weighting (IPTW), stratification, and modeling. The crude rate ratio (RR) of death for NSAID users was 0.68. ‘Traditional’ adjustment resulted in a RR of 0.80 (95% confidence interval:0.77–0.84). The RR closest to 1 was achieved by IPTW (0.85;0.82–0.88). With decreasing study size, estimates remained further from the null, which was most pronounced for IPTW (N=500: RR=0.72;0.26–1.68). In this setting, analytic strategies using EPS or DRS were not generally superior to ‘traditional’. Various ways to use EPS and DRS behaved differently with smaller study size. PMID:15840622

  10. The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.

    PubMed

    Lemire, Mathieu; Zaidi, Syed H E; Zanke, Brent W; Gallinger, Steven; Hudson, Thomas J; Cleary, Sean P

    2015-12-01

    Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p=10(-6); CD8+: p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced.

  11. Cesarean Section and Subsequent Stillbirth, Is Confounding by Indication Responsible for the Apparent Association? An Updated Cohort Analysis of a Large Perinatal Database

    PubMed Central

    Wood, Stephen; Ross, Sue; Sauve, Reg

    2015-01-01

    Background Several studies and a recent meta-analysis have suggested that previous Cesarean section may increase the risk of stillbirth in a subsequent pregnancy. Given the high rates of Cesarean section in contemporary obstetric practice, this is of considerable public health importance. We sought to evaluate the potential that this association is the result of residual confounding bias. Methods A large perinatal database (Alberta Perinatal Health Project) was searched to identify a matched set of first and second births from the years 1992–2006. Data on pregnancy outcomes, demographics and potential confounding factors were obtained. Results The cohort was comprised of 98538 matched first and second births. Multivariate analysis did not reveal an association between previous Cesarean section and stillbirth, OR = 1.38 (0.98, 1.93). Restricting the analysis to a low risk group further attenuated the association, OR = .99 (0.62, 1.52). Analysis of the risk by indication for Cesarean section found that the risk was not increased for previous dystocia, OR = .91 (0.53, 1.55) nor for breech presentation, OR = 1.06 (0.50, 2.28) but only for other indications including non reassuring fetal status and fetal distress, OR = 1.96 (1.29, 2.98). Conclusions The results of our cohort analysis suggest that previous Cesarean section does not cause an increased risk of stillbirth. PMID:26331274

  12. fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions

    PubMed Central

    Boubela, Roland N.; Kalcher, Klaudius; Huf, Wolfgang; Seidel, Eva-Maria; Derntl, Birgit; Pezawas, Lukas; Našel, Christian; Moser, Ewald

    2015-01-01

    Imaging the amygdala with functional MRI is confounded by multiple averse factors, notably signal dropouts due to magnetic inhomogeneity and low signal-to-noise ratio, making it difficult to obtain consistent activation patterns in this region. However, even when consistent signal changes are identified, they are likely to be due to nearby vessels, most notably the basal vein of rosenthal (BVR). Using an accelerated fMRI sequence with a high temporal resolution (TR = 333 ms) combined with susceptibility-weighted imaging, we show how signal changes in the amygdala region can be related to a venous origin. This finding is confirmed here in both a conventional fMRI dataset (TR = 2000 ms) as well as in information of meta-analyses, implying that “amygdala activations” reported in typical fMRI studies are likely confounded by signals originating in the BVR rather than in the amygdala itself, thus raising concerns about many conclusions on the functioning of the amygdala that rely on fMRI evidence alone. PMID:25994551

  13. An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data.

    PubMed

    Satterthwaite, Theodore D; Elliott, Mark A; Gerraty, Raphael T; Ruparel, Kosha; Loughead, James; Calkins, Monica E; Eickhoff, Simon B; Hakonarson, Hakon; Gur, Ruben C; Gur, Raquel E; Wolf, Daniel H

    2013-01-01

    Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed.

  14. [Metabolic correction: a biochemical option against diseases].

    PubMed

    Miranda-Massari, Jorge R; González, Michael J; Rodriguez-Gomez, José R; Duconge, Jorge; Allende-Vigo, Myriam Z; Jiménez Ramirez, Francisco J; Cintrón, Kenneth; Ricart, Carlos; Zaragoza-Urdaz, Rafael; Berdiel, Miguel Jabbar; Vázquez, Alex

    2015-01-01

    Human development and its physiology depends on a number of complex biochemical body processes, many of which are interactive and codependent. The speed and the degree in which many physiological reactions are completed depend on enzyme activity, which in turn depends on the bioavailability of co-factors and micronutrients such as vitamins and minerals. To achieve a healthy physiological state, organism need that biochemical reactions occur in a controlled and specific way at a particular speed and level or grade fully completed. To achieve this, is required an optimal metabolic balance. Factors such as, a particular genetic composition, inadequate dietary consumption patterns, traumas, diseases, toxins and environmental stress all of these factors rising demands for nutrients in order to obtain optimal metabolic balance. Metabolic correction is a biochemical and physiological concept that explains how improvements in cellular biochemistry of an organism can help the body achieve metabolic and physiological optimization. We summarize the contribution of several pioneers in understanding the role of micronutrients in health management. The concept of metabolic correction is becoming a significant term due to the presence of genetic variants that affect the speed of reactions of enzymes, causing metabolic alterations that enhance or promote the state/development of multiple diseases. Decline in the nutritional value of the food we eat, the increase in demand for certain nutrients caused by normal development, diseases and medications induce, usually, nutrients consumption. These nutritional deficiencies and insufficiencies are causing massive economic costs due to increased morbidity and mortality in our society. In summary, metabolic correction improves the enzymatic function, which favors the physiological normal functions, thus, contributing to improving health and the welfare of the human being. The purpose of this paper is to describe and introduce the concept

  15. Biochemical processing of heavy oils and residuum

    SciTech Connect

    Lin, M.S.; Premuzic, T.; Yablon, J.H.; Zhou, Wei-Min

    1995-05-01

    During the past several decades, the petroleum industry has adjusted gradually to accommodate the changes in market product demands, government regulations, and the quality and cost of feedstock crude oils. For example, the trends show that the demand for distillate fuels, such as diesel, as compared to gasoline are increasing. Air-quality standards have put additional demand on the processing of heavier and higher sulfur feed stocks. Thus, the 1990 Clean Air Act amendments require the industry to produce greater quantities of oxygenated gasoline, and lower sulfur diesel and reformulated gasoline. Biochemical technology may play an important role in responding to these demands on the petroleum industry.

  16. Biochemical Disincentives to Fertilizing Cellulosic Ethanol Crops

    NASA Astrophysics Data System (ADS)

    Gallagher, M. E.; Hockaday, W. C.; Snapp, S.; McSwiney, C.; Baldock, J.

    2010-12-01

    Corn grain biofuel crops produce the highest yields when the cropping ecosystem is not nitrogen (N)-limited, achieved by application of fertilizer. There are environmental consequences for excessive fertilizer application to crops, including greenhouse gas emissions, hypoxic “dead zones,” and health problems from N runoff into groundwater. The increase in corn acreage in response to demand for alternative fuels (i.e. ethanol) could exacerbate these problems, and divert food supplies to fuel production. A potential substitute for grain ethanol that could reduce some of these impacts is cellulosic ethanol. Cellulosic ethanol feedstocks include grasses (switchgrass), hardwoods, and crop residues (e.g. corn stover, wheat straw). It has been assumed that these feedstocks will require similar N fertilization rates to grain biofuel crops to maximize yields, but carbohydrate yield versus N application has not previously been monitored. We report the biochemical stocks (carbohydrate, protein, and lignin in Mg ha-1) of a corn ecosystem grown under varying N levels. We measured biochemical yield in Mg ha-1 within the grain, leaf and stem, and reproductive parts of corn plants grown at seven N fertilization rates (0-202 kg N ha-1), to evaluate the quantity and quality of these feedstocks across a N fertilization gradient. The N fertilization rate study was performed at the Kellogg Biological Station-Long Term Ecological Research Site (KBS-LTER) in Michigan. Biochemical stocks were measured using 13C nuclear magnetic resonance spectroscopy (NMR), combined with a molecular mixing model (Baldock et al. 2004). Carbohydrate and lignin are the main biochemicals of interest in ethanol production since carbohydrate is the ethanol feedstock, and lignin hinders the carbohydrate to ethanol conversion process. We show that corn residue carbohydrate yields respond only weakly to N fertilization compared to grain. Grain carbohydrate yields plateau in response to fertilization at

  17. Noise-induced metastability in biochemical networks.

    PubMed

    Biancalani, Tommaso; Rogers, Tim; McKane, Alan J

    2012-07-01

    Intracellular biochemical reactions exhibit a rich dynamical phenomenology which cannot be explained within the framework of mean-field rate equations and additive noise. Here, we show that the presence of metastable states and radically different time scales are general features of a broad class of autocatalytic reaction networks, and that this fact may be exploited to gain analytical results. The latter point is demonstrated by a treatment of the paradigmatic Togashi-Kaneko reaction, which has resisted theoretical analysis for the last decade.

  18. Thermal lens spectrometry in biochemical analysis.

    PubMed

    Martín-Biosca, Y; García-Alvarez-Coque, M C; Ramis-Ramos, G

    1994-07-01

    The photothermal spectroscopic techniques, with special emphasis on the thermal lens spectrometry (TLS), are introduced to the non-specialist in laser spectroscopy. The following topics are treated on an elementary basis: fundamentals and analytical characteristics, instrumentation, selectivity and multi-wavelength capability, the models describing the signal-concentration relationship, the sensitivity, background noise and limits of detection, the influence of light scattering and flow. Applications related to the fields of clinical and biochemical analysis and organic pollution are given. The thermal lens circular dichroism and the infrared TLS are also briefly outlined.

  19. Ecological risk assessment of impacted estuarine areas: integrating histological and biochemical endpoints in wild Senegalese sole.

    PubMed

    Gonçalves, Cátia; Martins, Marta; Costa, Maria H; Caeiro, Sandra; Costa, Pedro M

    2013-09-01

    The analysis of multiple biomarker responses is nowadays recognized as a valuable tool to circumvent potential confounding factors affecting biomonitoring studies and allows a better understanding of the mechanisms underlying exposure to natural mixtures of toxicants. For the purpose of an environmental risk assessment (ERA) in an impacted estuary in SW Europe (the Sado, Portugal), juvenile Solea senegalensis from commercial fishing areas were surveyed for histopathological liver alterations and biochemical biomarkers. Although the findings revealed moderate differences in the patterns of histopathological traits between urban/industrial- and agricultural-influenced areas within the same estuary, no significant distinction was found between the cumulative alterations in animals from the two sites. The overall level of histopathological injury was low and severe traits like neoplasms or pre-neoplastic foci were absent. While metallothionein induction and lipid peroxidation could relate to histopathological condition indices, the activity of anti-oxidant enzymes appeared to be impaired in animals collected off the estuary's heavy-industry belt (the most contaminated site), which may partially explain some degree of hepatic integrity loss. Overall, the results are consistent with low-moderate contamination of the estuary and indicate that oxidative stress is the most important factor accounting for differences between sites. The study highlights the need of integrating multiple biomarkers when multiple environmental stressors are involved and the advantages of surveying toxicity effects in field-collected, foraging, organisms.

  20. Biochemical Manifestation of HIV Lipodystrophy Syndrome

    PubMed Central

    Ihenetu, Kenneth; Mason, Darius

    2012-01-01

    Objectives Highly active anti-retroviral therapy (HAART), including protease inhibitors (PI) have led to dramatic improvements in the quality and quantity of life in patients with acquired immunodeficiency syndrome (AIDS). However, a significant number of AIDS patients on HAART develop characteristic changes in body fat redistribution referred to as lipodystrophy syndrome (LDS). Features of LDS include hypertrophy in the neck fat pad (buffalo hump), increased fat in the abdominal region (protease paunch), gynecomastia and loss of fat in the mid-face and extremities. Methods The aim of this paper is to review the current knowledge regarding this syndrome. This article reviews the published investigations on biochemical manifestation of HIV lipodystrophy syndrome. Results It is estimated that approximately 64% of patients treated with PI will experience this syndrome. Biochemically, these patients have increased triglycerides (Trig), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and extremely low high-density lipoprotein-cholesterol (HDL-C). Conclusions and Public Health Implications It is hoped that awareness of this syndrome would aid in early diagnosis and better patient management, possibly leading to a lower incidence of cardiovascular complications among these patients.

  1. Biochemical enzyme analysis in acute leukaemia.

    PubMed Central

    Drexler, H G; Gaedicke, G; Minowada, J

    1985-01-01

    This report summarises the current knowledge regarding the clinical utility of biochemical enzyme markers for both diagnostic and therapeutic purposes in acute leukaemia. The enzymes studied most extensively in this field are terminal deoxynucleotidyl transferase, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, and acid phosphatase, esterase, hexosaminidase isoenzymes. For each enzyme, the quantitative and qualitative characteristics in various immunologically defined subclasses of acute leukaemia are described. The quantitative evaluation of enzyme activities represents an adjunctive classification technique which should be incorporated into the multivariate analysis, the "multiple marker analysis." By qualitative characterisation pronounced heterogeneity of leukaemia subsets is uncovered. The application of 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase, and the potential usefulness of two other enzymes as targets for treatment with selective agents is discussed. The concept that gene products expressed at certain developmental stages of normal cells can similarly be detected in leukaemic cells (which therefore seem to be "frozen" or "arrested" at this particular maturation/differentiation stage) is supported by the results obtained in enzyme studies. Besides their practical clinical importance for classification and treatment of acute leukaemias, biochemical enzyme markers constitute a valuable research tool to disclose biological properties of leukaemic cells. PMID:2981904

  2. Biochemical basis for the biological clock

    NASA Technical Reports Server (NTRS)

    Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

    2002-01-01

    NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

  3. Biochemical responses of the Skylab crewman

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Rambaut, P. C.

    1974-01-01

    The biochemical investigations of the Skylab crewmen were designed to study the physiological changes that were observed on flight crews returning from previous space flight missions as well as to study those changes expected to result from prolonged weightless exposure. These studies can be divided into two broad categories. One category included routine blood studies similar to those used in clinical medical practice. The second included research-type endocrine analyses used to investigate more thoroughly the metabolic/endocrine responses to the space flight environment. The premission control values indicated that all Skylab crewmen were healthy and were free from biochemical abnormalities. The routine results during and after flight showed slight but significant changes in electrolytes, glucose, total protein, osmolality, uric acid, cholesterol, and creatinine. Plasma hormal changes included adrenocorticotrophic hormone, cortisol, angiotensin I, aldosterone, insulin, and thyroxine. The 24-hour urine analyses results revealed increased excretion of cortisol, catecholamines, antidiuretic hormone, and aldosterone as well as excretion of significant electrolyte and uric acid during the Skylab flights.

  4. Transient absolute robustness in stochastic biochemical networks.

    PubMed

    Enciso, German A

    2016-08-01

    Absolute robustness allows biochemical networks to sustain a consistent steady-state output in the face of protein concentration variability from cell to cell. This property is structural and can be determined from the topology of the network alone regardless of rate parameters. An important question regarding these systems is the effect of discrete biochemical noise in the dynamical behaviour. In this paper, a variable freezing technique is developed to show that under mild hypotheses the corresponding stochastic system has a transiently robust behaviour. Specifically, after finite time the distribution of the output approximates a Poisson distribution, centred around the deterministic mean. The approximation becomes increasingly accurate, and it holds for increasingly long finite times, as the total protein concentrations grow to infinity. In particular, the stochastic system retains a transient, absolutely robust behaviour corresponding to the deterministic case. This result contrasts with the long-term dynamics of the stochastic system, which eventually must undergo an extinction event that eliminates robustness and is completely different from the deterministic dynamics. The transiently robust behaviour may be sufficient to carry out many forms of robust signal transduction and cellular decision-making in cellular organisms. PMID:27581485

  5. The essence of linkage-based imprinting detection: Comparing power, type 1 error, and the effects of confounders in two different analysis approaches

    PubMed Central

    Greenberg, David A.; Monti, Maria Cristina; Feenstra, Bjarke; Zhang, Junying; Hodge, Susan E.

    2010-01-01

    Summary Background and goal The epigenetic phenomenon of imprinting is critical to understanding disease expression. However, it is hard to detect and can be species- and tissue-specific. One approach is to detect imprinting by taking advantage of linkage information. Although imprinting detection methods exist, the effects of potential confounders, such as heterogeneity, sex-specific penetrance, and differential sex-based ascertainment, have not been explored in depth. In this study we explored possible confounders using two different imprinting detection approaches. Our goal was to understand the essence of how imprinting and linkage interact and to elucidate the underlying issues in existing imprinting detection approaches. Methods One method (PP) models imprinting by maximizing lod scores with respect to parent-specific penetrances. The other method (DRF) approximates imprinting by maximizing two-point lods with respect to differential male-female recombination fractions. We compared power, type 1 error, and confounder effects in these two linkage-based imprinting detection methods using two-point linkage analysis for simplicity. We computer-simulated data, determining power and type 1 error for imprinting detection among datasets with detectable linkage. We generated data with and without imprinting, with and without heterogeneity, and with varying reduced penetrance, family and dataset size. We also examined non-imprinting situations that could mimic imprinting, e.g., sex-specific penetrances, and a scenario requiring a sex-specified affected parent for ascertainment. Results Without heterogeneity, PP had more imprinting-detecting power than DRF. Surprisingly, PP’s power increased when parental affectedness status was ignored, but decreased with heterogeneity. With heterogeneity, type 1 error could increase dramatically for both methods. However, DRF’s power also appeared to increase under heterogeneity, more than could be attributed to the inflated type

  6. Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)

    PubMed Central

    Loccisano, Anne E.; Morken, Nils-Halvdan; Yoon, Miyoung; Wu, Huali; McDougall, Robin; Maisonet, Mildred; Marcus, Michele; Kishi, Reiko; Miyashita, Chihiro; Chen, Mei-Huei; Hsieh, Wu-Shiun; Andersen, Melvin E.; Clewell, Harvey J.; Longnecker, Matthew P.

    2015-01-01

    Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, Mc

  7. Blowfly strike in sheep flocks as an example of the use of a time-space scan statistic to control confounding.

    PubMed

    Ward, M P

    2001-04-13

    The use of a time-space scan statistic--defined by a cylindrical window with a circular geographic base and height corresponding to time--was investigated as a method of detecting clustering in veterinary epidemiology whilst controlling confounding. The example data set consisted of farmer-recorded occurrence of body strike and breech strike between August 1998 and May 1999 in 26 sheep flocks located in two local government areas of southeastern Queensland, Australia. This information was derived from a questionnaire survey mailed to farmers. Potentially confounding factors included in the investigation were flock size (< or = median, > median), flock structure (proportion of lambs, wethers, ewes and rams), pesticide application for flystrike control (yes, no) and rainfall (< or = median, > median). The total sheep population within selected flocks was 92,660; 1012 (1.09%) and 518 (0.56%) cases of body strike and breech strike were reported in 16 and 10 flocks, respectively.Clustering analyses of body strike and breech strike were undertaken separately, because different predisposing factors are associated with these diseases. Significant clustering of body strike (28.76 degrees S, 151.82 degrees E) during March 1999 and breech strike (28.73 degrees S, 151.16 degrees E) between February and May 1999 was detected. Adjusting for flock structure, flock size, pesticide use and rainfall did not alter the most likely cluster of body strike identified--although the relative risk changed (> 10%) after adjusting for flock structure. Adjustment for flock structure and rainfall resulted in different clusters of breech strike being identified.

  8. A population-based study of edentulism in the US: does depression and rural residency matter after controlling for potential confounders?

    PubMed Central

    2014-01-01

    Background Oral health is an integral component of general health and well-being. While edentulism has been examined in relation to socioeconomic status, rural residency, chronic disease and mental health, no study that we know of has examined edentulism and these factors together. The objective of this study was to determine whether depression and rural residency were significantly associated with partial and full edentulism in US adults after controlling for potential confounders. Methods 2006 Behavioral Risk Factor Surveillance Survey (BRFSS) data were analyzed to identify factors associated with increased odds of partial or full edentulism. This year of BRFSS data was chosen for analysis because in this year the standardized and validated Personal Health Questionnaire-8 (PHQ-8) was used to measure current depression. This measure was part of the optional questions BRFSS asks, and in 2006 33 states and/or territories included them in their annual surveillance data collection. Bivariate and logistic regression analyses were performed on weighted BRFSS data. Results Logistic regression analysis using either full or partial edentulism as the dependent variable yielded that rural residency or living in a rural locale, low and/or middle socioeconomic status (SES), depression as measured by the PHQ-8, and African American race/ethnicity were all independent risk factors when controlling for these and a number of additional covariates. Conclusions This study adds to the epidemiological literature by assessing partial and full edentulism in the US utilizing data from the CDC’s Behavioral Risk Factor Surveillance System (BRFSS). Examining data collected through a large national surveillance system such as BRFSS allows for an analysis that incorporates an array of covariates not available from clinically-based data alone. This study demonstrated that current depression and rural residency are important factors related to partial and full edentulism after controlling for

  9. Accounting for genetic and environmental confounds in associations between parent and child characteristics: a systematic review of children-of-twins studies.

    PubMed

    McAdams, Tom A; Neiderhiser, Jenae M; Rijsdijk, Fruhling V; Narusyte, Jurgita; Lichtenstein, Paul; Eley, Thalia C

    2014-07-01

    Parental psychopathology, parenting style, and the quality of intrafamilial relationships are all associated with child mental health outcomes. However, most research can say little about the causal pathways underlying these associations. This is because most studies are not genetically informative and are therefore not able to account for the possibility that associations are confounded by gene-environment correlation. That is, biological parents not only provide a rearing environment for their child, but also contribute 50% of their genes. Any associations between parental phenotype and child phenotype are therefore potentially confounded. One technique for disentangling genetic from environmental effects is the children-of-twins (COT) method. This involves using data sets comprising twin parents and their children to distinguish genetic from environmental associations between parent and child phenotypes. The COT technique has grown in popularity in the last decade, and we predict that this surge in popularity will continue. In the present article we explain the COT method for those unfamiliar with its use. We present the logic underlying this approach, discuss strengths and weaknesses, and highlight important methodological considerations for researchers interested in the COT method. We also cover variations on basic COT approaches, including the extended-COT method, capable of distinguishing forms of gene-environment correlation. We then present a systematic review of all the behavioral COT studies published to date. These studies cover such diverse phenotypes as psychosis, substance abuse, internalizing, externalizing, parenting, and marital difficulties. In reviewing this literature, we highlight past applications, identify emergent patterns, and suggest avenues for future research.

  10. Polymorphisms in DNA-Repair Genes in a Cohort of Prostate Cancer Patients from Different Areas in Spain: Heterogeneity between Populations as a Confounding Factor in Association Studies

    PubMed Central

    Henríquez-Hernández, Luis Alberto; Valenciano, Almudena; Foro-Arnalot, Palmira; Álvarez-Cubero, María Jesús; Cozar, José Manuel; Suárez-Novo, José Francisco; Castells-Esteve, Manel; Ayala-Gil, Adriana; Fernández-Gonzalo, Pablo; Ferrer, Montse; Guedea, Ferrán; Sancho-Pardo, Gemma; Craven-Bartle, Jordi; Ortiz-Gordillo, María José; Cabrera-Roldán, Patricia; Herrera-Ramos, Estefanía; Lara, Pedro C.

    2013-01-01

    Background Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. Objective To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. Design, Setting, and Participants A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Outcome Measurements and Statistical Analysis Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. Results and Limitations We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. Conclusion Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of

  11. Morphologic, Genetic, and Biochemical Characterization of Helicobacter Magdeburgensis, a Novel Species Isolated from the Intestine of Laboratory Mice

    PubMed Central

    Traverso, Francisco Rivas; Bohr, Ulrich R. M.; Oyarzabal, Omar A.; Rohde, Manfred; Clarici, Alexandra; Wex, Thomas; Kuester, Doerthe; Malfertheiner, Peter; Fox, James G.; Backert, Steffen

    2015-01-01

    Background The presence of enterohepatic Helicobacter species (EHS) is commonly noted in mouse colonies. These infections often remain unrecognized but can cause severe health complications or more subtle host immune perturbations and therefore can confound the results of animal experiments. The aim of this study was to isolate and characterize a putative novel EHS that has previously been detected by PCR screening of specific-pathogen-free mice. Materials and Methods Biochemical analysis of enzyme activities (API campy), morphologic investigation (Gram-staining and electron microscopy) and genetic analyses (16SrRNA and 23SrRNA analyses, DNA fingerprinting, restriction fragment polymorphisms, and pulsed-field gel electrophoresis) were used to characterize isolated EHS. Genomic DNA fragments were sequenced to develop a species-specific PCR detection assay. Results Scanning electron microscopy revealed the presence of spiral-shaped EHS, which varied in length (2.5–6 µm) and contained single monopolar or single bipolar sheathed flagella. The bacteria were grown under anaerobic conditions, preferably on agar plates containing serum or blood. The 16SrRNA, genetic, and biochemical analyses indicated the identification of a novel EHS species, named Helicobacter magdeburgensis. We also examined the genome content using pulsed-field gel electrophoresis. Based on the pattern produced by two restriction enzymes, BamIII and KspI, the genome size was determined to be about 1.7–1.8 Mbp. Conclusion We isolated and characterized a novel EHS species, H. magdeburgensis, morphologically, biochemically, and genetically. These results are important for future studies on the prevalence and pathophysiologic relevance of such infections. Our PCR assay can be used to detect and discriminate H. magdeburgensis from other Helicobacter species. PMID:21083746

  12. Photoinduced biochemical activity of fullerene carboxylic acid

    SciTech Connect

    Tokuyama, Hidetoshi; Yamago, Shigeru; Nakamura, Eiichi; Shiraki, Takashi; Sugiura, Yukio

    1993-08-25

    Here we report the preparation of a water-miscible fullerene carboxylic acid (2) and its biological activity-cytotoxicity and G-selective DNA cleaving ability. What is truly remarkable is that the biological activity of C{sub 60} was observed only under irradiation with visible light and not in the dark, suggesting that fullerenes may serve as useful photosensitive biochemical probes. We have found, for the first time, that even low-energy visible light is surfficient to induce biological activity in fullerene derivatives. Among the numerous implications of the present findings, the most exciting prospect includes the use of fullerene derivatives for photodynamic therapy. 18 refs., 2 figs., 1 tab.

  13. Thin membrane sensor with biochemical switch

    NASA Technical Reports Server (NTRS)

    Case, George D. (Inventor); Worley, III, Jennings F. (Inventor)

    1994-01-01

    A modular biosensor system for chemical or biological agent detection utilizes electrochemical measurement of an ion current across a gate membrane triggered by the reaction of the target agent with a recognition protein conjugated to a channel blocker. The sensor system includes a bioresponse simulator or biochemical switch module which contains the recognition protein-channel blocker conjugate, and in which the detection reactions occur, and a transducer module which contains a gate membrane and a measuring electrode, and in which the presence of agent is sensed electrically. In the poised state, ion channels in the gate membrane are blocked by the recognition protein-channel blocker conjugate. Detection reactions remove the recognition protein-channel blocker conjugate from the ion channels, thus eliciting an ion current surge in the gate membrane which subsequently triggers an output alarm. Sufficiently large currents are generated that simple direct current electronics are adequate for the measurements. The biosensor has applications for environmental, medical, and industrial use.

  14. The biochemical basis of hereditary fructose intolerance.

    PubMed

    Bouteldja, Nadia; Timson, David J

    2010-04-01

    Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

  15. Peter Hochachka: adventures in biochemical adaptation.

    PubMed

    Somero, George N; Suarez, Raul K

    2005-01-01

    Peter Hochachka was one of the most creative forces in the field of comparative physiology during the past half-century. His career was truly an exploratory adventure, in both intellectual and geographic senses. His broad comparative studies of metabolism in organisms as diverse as trout, tunas, oysters, squid, turtles, locusts, hummingbirds, seals, and humans revealed the adaptable features of enzymes and metabolic pathways that provide the biochemical bases for diverse lifestyles and environments. In its combined breadth and depth, no other corpus of work better illustrates the principle of "unity in diversity" that marks comparative physiology. Through his publications, his stimulating mentorship, his broad editorial services, and his continuous-and highly infectious-enthusiasm for his field, Peter Hochachka served as one of the most influential leaders in the transformation of comparative physiology.

  16. Biochemical pathways in seed oil synthesis.

    PubMed

    Bates, Philip D; Stymne, Sten; Ohlrogge, John

    2013-06-01

    Oil produced in plant seeds is utilized as a major source of calories for human nutrition, as feedstocks for non-food uses such as soaps and polymers, and can serve as a high-energy biofuel. The biochemical pathways leading to oil (triacylglycerol) synthesis in seeds involve multiple subcellular organelles, requiring extensive lipid trafficking. Phosphatidylcholine plays a central role in these pathways as a substrate for acyl modifications and likely as a carrier for the trafficking of acyl groups between organelles and membrane subdomains. Although much has been clarified regarding the enzymes and pathways responsible for acyl-group flux, there are still major gaps in our understanding. These include the identity of several key enzymes, how flux between alternative pathways is controlled and the specialized cell biology leading to biogenesis of oil bodies that store up to 80% of carbon in seeds.

  17. [Biochemical complications of experimental vesico-sigmoidostomy].

    PubMed

    Nuñez, R; Blesa, E; Ramos, S; Morillo, M; Ortega, L; Requena, F; Cardesa, J J

    1987-03-01

    Three experimental models of vesico-sigmoidostomy are studied (model-1, end to side V-S plus urethral ligation, model-2, end to end V-S, in "Y of Rous" plus urethral ligation and model-3, vesico-sigmoidoplasty), with aim of reproducing chemical imbalance observed in human subjects with ureterosigmoidostomy. Authors have evaluated clinical biochemical (serum acido-base balance, Cl, Na+, K+, BUN, creatinine, ammonia and albumin), and histologic variables in the first, third and fifth month after operation in 225 rats. Animal of model-1 presented more frequently than model-2 and model-3, alterations (hyperchloraemic acidosis, uraemia, hyperammonemia and hypoalbumin) as well as affectation of upper urinary system for acute or chronic pyelonephritis.

  18. Droplet microfluidics in (bio)chemical analysis.

    PubMed

    Basova, Evgenia Yu; Foret, Frantisek

    2015-01-01

    Droplet microfluidics may soon change the paradigm of performing chemical analyses and related instrumentation. It can improve not only the analysis scale, possibility for sensitivity improvement, and reduced consumption of chemical and biological reagents, but also the speed of performing a variety of unit operations. At present, microfluidic platforms can reproducibly generate monodisperse droplet populations at kHz or higher rates with droplet sizes suitable for high-throughput experiments, single-cell detection or even single molecule analysis. In addition to being used as microreactors with volume in the micro- to femtoliter range, droplet based systems have also been used to directly synthesize particles and encapsulate biological entities for biomedicine and biotechnology applications. This minireview summarizes various droplet microfluidics operations and applications for (bio)chemical assays described in the literature during the past few years.

  19. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    PubMed Central

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  20. Hemoglobin variants: biochemical properties and clinical correlates.

    PubMed

    Thom, Christopher S; Dickson, Claire F; Gell, David A; Weiss, Mitchell J

    2013-03-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.

  1. [Biochemical and immunological markers of autoimmune thyroiditis].

    PubMed

    Biktagirova, E M; Sattarova, L I; Vagapova, G R; Skibo, Y V; Chuhlovina, E N; Kravtsova, O A; Abramova, Z I

    2016-05-01

    Correlations between biochemical and immunological markers of programmed cell death (apoptosis), and the functional state of the thyroid gland (hyperthyroidism, euthyroidism, hypothyroidism) have been investigated in autoimmune thyroiditis (AT) (also known as chronic autoimmune thyroiditis). Annexin V, TRAIL and TNF-a, as well as DNA-hydrolyzing antibodies were used as the main markers. Increased levels of TRAIL were found in the serum of AT patients (hyperthyroidism>hypothyroidism>euthyroidism) compared with healthy individuals. The highest frequency of antibodies to denatured DNA (Abs-dDNA) had the highest frequency in AT patients (97%) compared with healthy controls. Among these patients, 75% had hyperthyroidism, 85% had hypothyroidism, and 84.7% had euthyroidism. Abs hydrolyzing activity demonstrated correlation dependence with symptoms of the thyroid dysfunction. PMID:27563001

  2. Biochemical Pharmacology of the Sigma-1 Receptor.

    PubMed

    Chu, Uyen B; Ruoho, Arnold E

    2016-01-01

    The sigma-1 receptor (S1R) is a 223 amino acid two transmembrane (TM) pass protein. It is a non-ATP-binding nonglycosylated ligand-regulated molecular chaperone of unknown three-dimensional structure. The S1R is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes with broad functions that regulate cellular calcium homeostasis and reduce oxidative stress. Several multitasking functions of the S1R are underwritten by chaperone-mediated direct (and indirect) interactions with ion channels, G-protein coupled receptors and cell-signaling molecules involved in the regulation of cell growth. The S1R is a promising drug target for the treatment of several neurodegenerative diseases related to cellular stress. In vitro and in vivo functional and molecular characteristics of the S1R and its interactions with endogenous and synthetic small molecules have been discovered by the use of pharmacologic, biochemical, biophysical, and molecular biology approaches. The S1R exists in monomer, dimer, tetramer, hexamer/octamer, and higher oligomeric forms that may be important determinants in defining the pharmacology and mechanism(s) of action of the S1R. A canonical GXXXG in putative TM2 is important for S1R oligomerization. The ligand-binding regions of S1R have been identified and include portions of TM2 and the TM proximal regions of the C terminus. Some client protein chaperone functions and interactions with the cochaperone 78-kDa glucose-regulated protein (binding immunoglobulin protein) involve the C terminus. Based on its biochemical features and mechanisms of chaperone action the possibility that the S1R is a member of the small heat shock protein family is discussed.

  3. Biochemically enhanced methane production from coal

    NASA Astrophysics Data System (ADS)

    Opara, Aleksandra

    For many years, biogas was connected mostly with the organic matter decomposition in shallow sediments (e.g., wetlands, landfill gas, etc.). Recently, it has been realized that biogenic methane production is ongoing in many hydrocarbon reservoirs. This research examined microbial methane and carbon dioxide generation from coal. As original contributions methane production from various coal materials was examined in classical and electro-biochemical bench-scale reactors using unique, developed facultative microbial consortia that generate methane under anaerobic conditions. Facultative methanogenic populations are important as all known methanogens are strict anaerobes and their application outside laboratory would be problematic. Additional testing examined the influence of environmental conditions, such as pH, salinity, and nutrient amendments on methane and carbon dioxide generation. In 44-day ex-situ bench-scale batch bioreactor tests, up to 300,000 and 250,000 ppm methane was generated from bituminous coal and bituminous coal waste respectively, a significant improvement over 20-40 ppm methane generated from control samples. Chemical degradation of complex hydrocarbons using environmentally benign reagents, prior to microbial biodegradation and methanogenesis, resulted in dissolution of up to 5% bituminous coal and bituminous coal waste and up to 25% lignite in samples tested. Research results confirm that coal waste may be a significant underutilized resource that could be converted to useful fuel. Rapid acidification of lignite samples resulted in low pH (below 4.0), regardless of chemical pretreatment applied, and did not generate significant methane amounts. These results confirmed the importance of monitoring and adjusting in situ and ex situ environmental conditions during methane production. A patented Electro-Biochemical Reactor technology was used to supply electrons and electron acceptor environments, but appeared to influence methane generation in a

  4. Biochemical diagnosis of neuroendocrine GEP tumor.

    PubMed Central

    Oberg, K.

    1997-01-01

    Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor

  5. Transcription fluctuation effects on biochemical oscillations.

    PubMed

    Nishino, Ryota; Sakaue, Takahiro; Nakanishi, Hiizu

    2013-01-01

    Some biochemical systems show oscillation. They often consist of feedback loops with repressive transcription regulation. Such biochemical systems have distinctive characteristics in comparison with ordinary chemical systems: i) numbers of molecules involved are small, ii) there are typically only a couple of genes in a cell with a finite regulation time. Due to the fluctuations caused by these features, the system behavior can be quite different from the one by deterministic rate equations, because the rate equations ignore molecular fluctuations and thus are exact only in the infinite molecular number limit. The molecular fluctuations on a free-running circadian system have been studied by Gonze et al. (2002) by introducing a scale parameter [Formula: see text] for the system size. They consider, however, only the first effect, assuming that the gene process is fast enough for the second effect to be ignored, but this has not been examined systematically yet. Here we study fluctuation effects due to the finite gene regulation time by introducing a new scale parameter [Formula: see text], which we take as the unbinding time of a nuclear protein from the gene. We focus on the case where the fluctuations due to small molecular numbers are negligible. In simulations on the same system studied by Gonze et al., we find the system is unexpectedly sensitive to the fluctuation in the transcription regulation; the period of oscillation fluctuates about 30 min even when the regulation time scale [Formula: see text] is around 30 s, that is even smaller than 1/1000 of its circadian period. We also demonstrate that the distribution width for the oscillation period and amplitude scales with [Formula: see text], and the correlation time scales with [Formula: see text] in the small [Formula: see text] regime. The relative fluctuations for the period are about half of that for the amplitude, namely, the periodicity is more stable than the amplitude.

  6. Pattern Selection by Dynamical Biochemical Signals

    PubMed Central

    Palau-Ortin, David; Formosa-Jordan, Pau; Sancho, José M.; Ibañes, Marta

    2015-01-01

    The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell

  7. Why Do Thin People Have Elevated All-Cause Mortality? Evidence on Confounding and Reverse Causality in the Association of Adiposity and COPD from the British Women’s Heart and Health Study

    PubMed Central

    Dale, Caroline; Nüesch, Eveline; Prieto-Merino, David; Choi, Minkyoung; Amuzu, Antoinette; Ebrahim, Shah; Casas, Juan P.; Davey-Smith, George

    2015-01-01

    Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women’s Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3 – 3.1 versus OR = 1.2; 95% CI 0.7 – 1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding. PMID:25884834

  8. Why do thin people have elevated all-cause mortality? Evidence on confounding and reverse causality in the association of adiposity and COPD from the British Women's Heart and Health Study.

    PubMed

    Dale, Caroline; Nüesch, Eveline; Prieto-Merino, David; Choi, Minkyoung; Amuzu, Antoinette; Ebrahim, Shah; Casas, Juan P; Davey-Smith, George

    2015-01-01

    Low adiposity has been linked to elevated mortality from several causes including respiratory disease. However, this could arise from confounding or reverse causality. We explore the association between two measures of adiposity (BMI and WHR) with COPD in the British Women's Heart and Health Study including a detailed assessment of the potential for confounding and reverse causality for each adiposity measure. Low BMI was found to be associated with increased COPD risk while low WHR was not (OR = 2.2; 95% CI 1.3-3.1 versus OR = 1.2; 95% CI 0.7-1.6). Potential confounding variables (e.g. smoking) and markers of ill-health (e.g. unintentional weight loss) were found to be higher in low BMI but not in low WHR. Women with low BMI have a detrimental profile across a broad range of health markers compared to women with low WHR, and women with low WHR do not appear to have an elevated COPD risk, lending support to the hypothesis that WHR is a less confounded measure of adiposity than BMI. Low adiposity does not in itself appear to increase the risk of respiratory disease, and the apparent adverse consequences of low BMI may be due to reverse causation and confounding.

  9. Biochemical Education in Thailand: Past, Present, and Future.

    ERIC Educational Resources Information Center

    Svasti, Jisnuson; Surarit, Rudee

    1991-01-01

    Traces the history of Thailand's biochemical education from its initial evolution from medicine to modern day. Discusses the following aspects of Thailand's modern biochemical education: biochemistry teaching at Thai schools, university departments and biochemistry courses, textbooks, degree programs, interplay between research and teaching, and…

  10. Biochemical indices associated with meditation practice: a literature review.

    PubMed

    Delmonte, M M

    1985-01-01

    Research findings on biochemical responsivity to meditation are reviewed. Although there are some contradictory and inconclusive outcomes, there is nevertheless sufficient evidence of interest to warrant further investigation of this area. However, in the meantime, there is no compelling basis to conclude that meditation practice is associated with special state or trait effects at the biochemical level.

  11. A Biochemical Approach to the Problem of Dyslexia.

    ERIC Educational Resources Information Center

    Baker, Sidney McDonald

    1985-01-01

    The paper presents the case of a sixth-grade boy, labeled dyslexic, who responded positively to a biochemical approach. Remedy of iron, zinc, and Vitamin B-6 deficiencies as well as an imbalance of fatty acids resulted in improvements in hair and skin and also in reading. A biochemical approach to behavior problems is proposed. (Author/CL)

  12. Simulation studies in biochemical signaling and enzyme reactions

    NASA Astrophysics Data System (ADS)

    Nelatury, Sudarshan R.; Vagula, Mary C.

    2014-06-01

    Biochemical pathways characterize various biochemical reaction schemes that involve a set of species and the manner in which they are connected. Determination of schematics that represent these pathways is an important task in understanding metabolism and signal transduction. Examples of these Pathways are: DNA and protein synthesis, and production of several macro-molecules essential for cell survival. A sustained feedback mechanism arises in gene expression and production of mRNA that lead to protein synthesis if the protein so synthesized serves as a transcription factor and becomes a repressor of the gene expression. The cellular regulations are carried out through biochemical networks consisting of reactions and regulatory proteins. Systems biology is a relatively new area that attempts to describe the biochemical pathways analytically and develop reliable mathematical models for the pathways. A complete understanding of chemical reaction kinetics is prohibitively hard thanks to the nonlinear and highly complex mechanisms that regulate protein formation, but attempting to numerically solve some of the governing differential equations seems to offer significant insight about their biochemical picture. To validate these models, one can perform simple experiments in the lab. This paper introduces fundamental ideas in biochemical signaling and attempts to take first steps into the understanding of biochemical oscillations. Initially, the two-pool model of calcium is used to describe the dynamics behind the oscillations. Later we present some elementary results showing biochemical oscillations arising from solving differential equations of Elowitz and Leibler using MATLAB software.

  13. Model-Based Design of Biochemical Microreactors

    PubMed Central

    Elbinger, Tobias; Gahn, Markus; Neuss-Radu, Maria; Hante, Falk M.; Voll, Lars M.; Leugering, Günter; Knabner, Peter

    2016-01-01

    Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P

  14. Model-Based Design of Biochemical Microreactors.

    PubMed

    Elbinger, Tobias; Gahn, Markus; Neuss-Radu, Maria; Hante, Falk M; Voll, Lars M; Leugering, Günter; Knabner, Peter

    2016-01-01

    Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P

  15. An empirical comparison of several clustered data approaches under confounding due to cluster effects in the analysis of complications of coronary angioplasty.

    PubMed

    Berlin, J A; Kimmel, S E; Ten Have, T R; Sammel, M D

    1999-06-01

    In the analysis of binary response data from many types of large studies, the data are likely to have arisen from multiple centers, resulting in a within-center correlation for the response. Such correlation, or clustering, occurs when outcomes within centers tend to be more similar to each other than to outcomes in other centers. In studies where there is also variability among centers with respect to the exposure of interest, analysis of the exposure-outcome association may be confounded, even after accounting for within-center correlations. We apply several analytic methods to compare the risk of major complications associated with two strategies, staged and combined procedures, for performing percutaneous transluminal coronary angioplasty (PTCA), a mechanical means of relieving blockage of blood vessels due to atherosclerosis. Combined procedures are used in some centers as a cost-cutting strategy. We performed a number of population-averaged and cluster-specific (conditional) analyses, which (a) make no adjustments for center effects of any kind; (b) make adjustments for the effect of center on only the response; or (c) make adjustments for both the effect of center on the response and the relationship between center and exposure. The method used for this third approach decomposes the procedure type variable into within-center and among-center components, resulting in two odds ratio estimates. The naive analysis, ignoring clusters, gave a highly significant effect of procedure type (OR = 1.6). Population average models gave marginally to very nonsignificant estimates of the OR for treatment type ranging from 1.6 to 1.2 with adjustment only for the effect of centers on response. These results depended on the assumed correlation structure. Conditional (cluster-specific) models and other methods that decomposed the treatment type variable into among- and within-center components all found no within-center effect of procedure type (OR = 1.02, consistently) and a

  16. PHA bioplastics, biochemicals, and energy from crops.

    PubMed

    Somleva, Maria N; Peoples, Oliver P; Snell, Kristi D

    2013-02-01

    Large scale production of polyhydroxyalkanoates (PHAs) in plants can provide a sustainable supply of bioplastics, biochemicals, and energy from sunlight and atmospheric CO(2). PHAs are a class of polymers with various chain lengths that are naturally produced by some microorganisms as storage materials. The properties of these polyesters make them functionally equivalent to many of the petroleum-based plastics that are currently in the market place. However, unlike most petroleum-derived plastics, PHAs can be produced from renewable feedstocks and easily degrade in most biologically active environments. This review highlights research efforts over the last 20 years to engineer the production of PHAs in plants with a focus on polyhydroxybutryrate (PHB) production in bioenergy crops with C(4) photosynthesis. PHB has the potential to be a high volume commercial product with uses not only in the plastics and materials markets, but also in renewable chemicals and feed. The major challenges of improving product yield and plant fitness in high biomass yielding C(4) crops are discussed in detail.

  17. Biochemical analysis of Phytolacca DOPA dioxygenase.

    PubMed

    Takahashi, Kana; Yoshida, Kazuko; Yura, Kei; Ashihara, Hiroshi; Sakuta, Masaaki

    2015-05-01

    The biochemical analysis of Phytolacca americana DOPA dioxygenases (PaDOD1 and PaDOD2) was carried out. The recombinant protein of PaDOD1 catalyzed the conversion of DOPA to betalamic acid, whereas DOD activity was not detected in PaDOD2 in vitro. While the reported motif conserved in DODs from betalain-producing plants was found in PaDOD1, a single amino acid residue alteration was detected in PaDOD2. A mutated PaDOD1 protein with a change of 177 Asn to Gly showed reduced specific activity compared with PaDOD1, while DOPA dioxygenase activity was not observed for a mutated PaDOD2 protein which had its conserved motif replaced with that of PaDOD. A three-dimensional (3D) structural model of PaDOD1 and PaDOD2 showed that the conserved motif in DODs was located in the N-terminal side of a loop, which was found close to the putative active site. The difference in stability of the loop may affect the enzymatic activity of PaDOD2. PMID:26058142

  18. Applied spectrophotometry: analysis of a biochemical mixture.

    PubMed

    Trumbo, Toni A; Schultz, Emeric; Borland, Michael G; Pugh, Michael Eugene

    2013-01-01

    Spectrophotometric analysis is essential for determining biomolecule concentration of a solution and is employed ubiquitously in biochemistry and molecular biology. The application of the Beer-Lambert-Bouguer Lawis routinely used to determine the concentration of DNA, RNA or protein. There is however a significant difference in determining the concentration of a given species (RNA, DNA, protein) in isolation (a contrived circumstance) as opposed to determining that concentration in the presence of other species (a more realistic situation). To present the student with a more realistic laboratory experience and also to fill a hole that we believe exists in student experience prior to reaching a biochemistry course, we have devised a three week laboratory experience designed so that students learn to: connect laboratory practice with theory, apply the Beer-Lambert-Bougert Law to biochemical analyses, demonstrate the utility and limitations of example quantitative colorimetric assays, demonstrate the utility and limitations of UV analyses for biomolecules, develop strategies for analysis of a solution of unknown biomolecular composition, use digital micropipettors to make accurate and precise measurements, and apply graphing software. PMID:23625877

  19. Biochemical analysis of Phytolacca DOPA dioxygenase.

    PubMed

    Takahashi, Kana; Yoshida, Kazuko; Yura, Kei; Ashihara, Hiroshi; Sakuta, Masaaki

    2015-05-01

    The biochemical analysis of Phytolacca americana DOPA dioxygenases (PaDOD1 and PaDOD2) was carried out. The recombinant protein of PaDOD1 catalyzed the conversion of DOPA to betalamic acid, whereas DOD activity was not detected in PaDOD2 in vitro. While the reported motif conserved in DODs from betalain-producing plants was found in PaDOD1, a single amino acid residue alteration was detected in PaDOD2. A mutated PaDOD1 protein with a change of 177 Asn to Gly showed reduced specific activity compared with PaDOD1, while DOPA dioxygenase activity was not observed for a mutated PaDOD2 protein which had its conserved motif replaced with that of PaDOD. A three-dimensional (3D) structural model of PaDOD1 and PaDOD2 showed that the conserved motif in DODs was located in the N-terminal side of a loop, which was found close to the putative active site. The difference in stability of the loop may affect the enzymatic activity of PaDOD2.

  20. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

    Mass, M.J.; Kaufman, D.G.

    1984-06-01

    Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. 94 references, 9 figures, 2 tables.

  1. Biochemical and Proteomic Characterization of Alkaptonuric Chondrocytes

    PubMed Central

    Braconi, Daniela; Bernardini, Giulia; Bianchini, Claretta; Laschi, Marcella; Millucci, Lia; Amato, Loredana; Tinti, Laura; Serchi, Tommaso; Chellini, Federico; Spreafico, Adriano; Santucci, Annalisa

    2012-01-01

    Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products which leads to the deposition of melanin-like pigments (ochronosis) in connective tissues. Although numerous case reports have described ochronosis in joints, little is known on the molecular mechanisms leading to such a phenomenon. For this reason, we characterized biochemically chondrocytes isolated from the ochronotic cartilage of AKU patients. Based on the macroscopic appearance of the ochronotic cartilage, two sub-populations were identified: cells coming from the black portion of the cartilage were referred to as “black” AKU chondrocytes, while those coming from the white portion were referred to as “white” AKU chondrocytes. Notably, both AKU chondrocytic types were characterized by increased apoptosis, NO release, and levels of pro-inflammatory cytokines. Transmission electron microscopy also revealed that intracellular ochronotic pigment deposition was common to both “white” and “black” AKU cells. We then undertook a proteomic and redox-proteomic analysis of AKU chondrocytes which revealed profound alterations in the levels of proteins involved in cell defence, protein folding, and cell organization. An increased post-translational oxidation of proteins, which also involved high molecular weight protein aggregates, was found to be particularly relevant in “black” AKU chondrocytes. J. Cell. Physiol. 227: 3333–3343, 2012. © 2011 Wiley Periodicals, Inc. PMID:22213341

  2. Biochemical markers in butadiene-exposed workers

    SciTech Connect

    Bechtold, W.E.; Hayes, R.B.; Thornton-Manning, J.R.; Henderson, R.F.

    1994-11-01

    1,3-Butadiene (BD) is used to manufacture a wide range of polymers and copolymers including styrene-butadiene rubber, polybutadiene, and acrylonitrile-butadiene-syrene resins. The carcinogenicity of BD has been determined in life-span inhalation studies in both Sprague-Dawley rats and B6C3F{sub 1} mice. Results suggest a marked species difference in the carcinogenic effects of BD. For example, female mice exposed to as low as 6.25 ppm BD exhibited increased alveolar/bronchiolar neoplasms. In contrast, BD was only a weak carcinogen in Sprague-Dawley rats. Rats were observed to have an increase only in mammary tumors after exposure to 1000 ppm. A biochemical study of highly exposed BD workers and unexposed controls is providing valuable information on BD metabolism in humans, and how this relates to the development of intermediate biologic effects. A group of heavily exposed workers were identified in a BD production facility in China. The purpose of this paper is to report the initial results from the sampling trip in the first quarter of 1994.

  3. Control analysis for autonomously oscillating biochemical networks.

    PubMed

    Reijenga, Karin A; Westerhoff, Hans V; Kholodenko, Boris N; Snoep, Jacky L

    2002-01-01

    It has hitherto not been possible to analyze the control of oscillatory dynamic cellular processes in other than qualitative ways. The control coefficients, used in metabolic control analyses of steady states, cannot be applied directly to dynamic systems. We here illustrate a way out of this limitation that uses Fourier transforms to convert the time domain into the stationary frequency domain, and then analyses the control of limit cycle oscillations. In addition to the already known summation theorems for frequency and amplitude, we reveal summation theorems that apply to the control of average value, waveform, and phase differences of the oscillations. The approach is made fully operational in an analysis of yeast glycolytic oscillations. It follows an experimental approach, sampling from the model output and using discrete Fourier transforms of this data set. It quantifies the control of various aspects of the oscillations by the external glucose concentration and by various internal molecular processes. We show that the control of various oscillatory properties is distributed over the system enzymes in ways that differ among those properties. The models that are described in this paper can be accessed on http://jjj.biochem.sun.ac.za.

  4. PHA bioplastics, biochemicals, and energy from crops.

    PubMed

    Somleva, Maria N; Peoples, Oliver P; Snell, Kristi D

    2013-02-01

    Large scale production of polyhydroxyalkanoates (PHAs) in plants can provide a sustainable supply of bioplastics, biochemicals, and energy from sunlight and atmospheric CO(2). PHAs are a class of polymers with various chain lengths that are naturally produced by some microorganisms as storage materials. The properties of these polyesters make them functionally equivalent to many of the petroleum-based plastics that are currently in the market place. However, unlike most petroleum-derived plastics, PHAs can be produced from renewable feedstocks and easily degrade in most biologically active environments. This review highlights research efforts over the last 20 years to engineer the production of PHAs in plants with a focus on polyhydroxybutryrate (PHB) production in bioenergy crops with C(4) photosynthesis. PHB has the potential to be a high volume commercial product with uses not only in the plastics and materials markets, but also in renewable chemicals and feed. The major challenges of improving product yield and plant fitness in high biomass yielding C(4) crops are discussed in detail. PMID:23294864

  5. Biochemical Plant Responses to Ozone 1

    PubMed Central

    Rosemann, Detlef; Heller, Werner; Sandermann, Heinrich

    1991-01-01

    Formation of the stilbenes pinosylvin and pinosylvin 3-methyl ether, as well as the activity of the biosynthetic enzyme stilbene synthase (pinosylvin-forming), were induced several hundred- to thousandfold in primary needles of 6-week-old pine (Pinus sylvestris L.) seedlings upon exposure to a single pulse of ozone of at least 0.15 microliters per liter. The seedlings required 4 hours of exposure as a minimum for the induction of stilbene biosynthesis when exposed to 0.2 microliters per liter ozone. Both stilbene synthase activity and stilbene accumulation increased with the duration of ozone treatment. The activity of phenylalanine ammonia-lyase and the activity of chalcone synthase, a key enzyme of the flavonoid pathway that uses the same substrates as stilbene synthase, were also stimulated about twofold by ozone. Stilbene biosynthesis appears to represent the first example of a dose-dependent biochemical response to ozone in a conifer species and may serve as a useful biomarker to study stress impacts on pine trees. PMID:16668544

  6. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1996-01-01

    A multiple capillary biochemical analyzer for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal to noise ratio.

  7. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1996-10-22

    A multiple capillary biochemical analyzer is disclosed for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal-to-noise ratio. 12 figs.

  8. Applied spectrophotometry: analysis of a biochemical mixture.

    PubMed

    Trumbo, Toni A; Schultz, Emeric; Borland, Michael G; Pugh, Michael Eugene

    2013-01-01

    Spectrophotometric analysis is essential for determining biomolecule concentration of a solution and is employed ubiquitously in biochemistry and molecular biology. The application of the Beer-Lambert-Bouguer Lawis routinely used to determine the concentration of DNA, RNA or protein. There is however a significant difference in determining the concentration of a given species (RNA, DNA, protein) in isolation (a contrived circumstance) as opposed to determining that concentration in the presence of other species (a more realistic situation). To present the student with a more realistic laboratory experience and also to fill a hole that we believe exists in student experience prior to reaching a biochemistry course, we have devised a three week laboratory experience designed so that students learn to: connect laboratory practice with theory, apply the Beer-Lambert-Bougert Law to biochemical analyses, demonstrate the utility and limitations of example quantitative colorimetric assays, demonstrate the utility and limitations of UV analyses for biomolecules, develop strategies for analysis of a solution of unknown biomolecular composition, use digital micropipettors to make accurate and precise measurements, and apply graphing software.

  9. Diagnosis of growth retardation by biochemical methods.

    PubMed

    Klopper, A

    1984-08-01

    The substances in the blood or urine of a pregnant woman which may give an indication of the state of fetal growth are examined. The drawback of measuring such substances is that the values are variable, making it difficult to distinguish between normal and abnormal. Variability arises from technical factors in measurements, from short-term changes of no significance and from the large spread of normal values from one individual to the next. Biochemical parameters of fetal growth can be applied in one of two ways: as screening tests or as control measures by serial assays to guide management. The criteria by which any test should be evaluated--sensitivity, specificity and relative risk--are examined. Particular substances whose measurement may be helpful are considered in terms of the steroids or proteins produced by the fetoplacental unit. The oestrogens, notably oestriol, hold pride of place among the steroids. Dynamic tests of steroid synthesis are also considered. The chief placental proteins of interest are chorionic gonadotrophin, placental lactogen and Schwangerschaftsprotein 1. It is concluded that the method to be recommended is to screen a whole obstetric population with assays of placental lactogen and to follow those with values below the normal limit with serial oestriol assays. PMID:6332704

  10. Management of a Septic Open Abdomen Patient with Spontaneous Jejunal Perforation after Emergent C/S with Confounding Factor of Mild Acute Pancreatitis

    PubMed Central

    Yetisir, Fahri; Sarer, Akgün Ebru; Acar, Hasan Zafer; Osmanoglu, Gokhan; Özer, Mehmet; Yaylak, Faik

    2016-01-01

    Introduction. We report the management of a septic Open Abdomen (OA) patient by the help of negative pressure therapy (NPT) and abdominal reapproximation anchor (ABRA) system in pregnant woman with spontaneous jejunal perforation after emergent cesarean section (C/S) with confounding factor of mild acute pancreatitis (AP). Presentation of Case. A 29-year-old and 34-week pregnant woman with AP underwent C/S. She was arrested after anesthesia induction and responded to cardiopulmonary resuscitation (CPR). There were only ash-colored serosanguinous fluid within abdomen during C/S. After C/S, she was transferred to intensive care unit (ICU) with vasopressor support. On postoperative 1st day, she underwent reoperation due to fecal fluid coming near the drainage. Leakage point could not be identified exactly and operation had to be deliberately abbreviated due to hemodynamic instability. NPT was applied. Two days later source control was provided by conversion of enteroatmospheric fistula (EAF) to jejunostomy. ABRA was added and OA was closed. No hernia developed at 10-month follow-up period. Conclusion. NPT application in septic OA patient may gain time to patient until adequate source control could be achieved. Using ABRA in conjunction with NPT increases the fascial closure rate in infected OA patient. PMID:27006853

  11. Management of a Septic Open Abdomen Patient with Spontaneous Jejunal Perforation after Emergent C/S with Confounding Factor of Mild Acute Pancreatitis.

    PubMed

    Yetisir, Fahri; Sarer, Akgün Ebru; Acar, Hasan Zafer; Osmanoglu, Gokhan; Özer, Mehmet; Yaylak, Faik

    2016-01-01

    Introduction. We report the management of a septic Open Abdomen (OA) patient by the help of negative pressure therapy (NPT) and abdominal reapproximation anchor (ABRA) system in pregnant woman with spontaneous jejunal perforation after emergent cesarean section (C/S) with confounding factor of mild acute pancreatitis (AP). Presentation of Case. A 29-year-old and 34-week pregnant woman with AP underwent C/S. She was arrested after anesthesia induction and responded to cardiopulmonary resuscitation (CPR). There were only ash-colored serosanguinous fluid within abdomen during C/S. After C/S, she was transferred to intensive care unit (ICU) with vasopressor support. On postoperative 1st day, she underwent reoperation due to fecal fluid coming near the drainage. Leakage point could not be identified exactly and operation had to be deliberately abbreviated due to hemodynamic instability. NPT was applied. Two days later source control was provided by conversion of enteroatmospheric fistula (EAF) to jejunostomy. ABRA was added and OA was closed. No hernia developed at 10-month follow-up period. Conclusion. NPT application in septic OA patient may gain time to patient until adequate source control could be achieved. Using ABRA in conjunction with NPT increases the fascial closure rate in infected OA patient. PMID:27006853

  12. Lung cancer mortality among nuclear workers of the Mayak facilities in the former Soviet Union. An updated analysis considering smoking as the main confounding factor.

    PubMed

    Kreisheimer, M; Sokolnikov, M E; Koshurnikova, N A; Khokhryakov, V F; Romanow, S A; Shilnikova, N S; Okatenko, P V; Nekolla, E A; Kellerer, A M

    2003-07-01

    A new analysis of lung cancer mortality in a cohort of male Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. The follow-up has been extended until 1999, moreover a new dosimetry system (DOSES2000) has been established. Particular emphasis has been given to a discrimination of the effects of external gamma-exposure and internal alpha-exposure due to incorporated plutonium. This study has also utilized and incorporated the information from a cohort of Mayak reactor workers, who were exposed only externally to gamma-rays. The influence of smoking as the main confounding factor for lung cancer has been studied. The baseline lung cancer mortality rate was not taken from national statistics but was derived from the cohort itself. The estimated excess relative risk for the plutonium alpha-rays was 0.23/Sv (95%CI: 0.16-0.31). The resulting risk coefficient for external gamma-ray exposure was very low with a statistically insignificant estimate of 0.058/Sv (95%CI: -0.072-0.20). The inferred relative risk for smokers was 16.5 (95%CI: 12.6-20.5).

  13. Associations of Milk Consumption and Vitamin B2 and Β12 Derived from Milk with Fitness, Anthropometric and Biochemical Indices in Children. The Healthy Growth Study

    PubMed Central

    Moschonis, George; van den Heuvel, Ellen G. H. M.; Mavrogianni, Christina; Singh-Povel, Cécile M.; Leotsinidis, Michalis; Manios, Yannis

    2016-01-01

    The benefits of dairy consumption seem to extend beyond its significant contribution to ensuring nutrient intake adequacy as indicated by the favourable associations with several health outcomes reported by different studies. The aims of the present study were to examine the associations of milk consumption with fitness, anthropometric and biochemical indices in children and further explore whether the observed associations are attributed to vitamins B2 and B12 derived from milk. A representative subsample of 600 children aged 9–13 years participating in the Healthy Growth Study was examined. Data were collected on children’s dietary intake, using 24 h recalls, as well as on fitness, anthropometric and biochemical indices. Regression analyses were performed for investigating the research hypothesis, adjusting for potential confounders and for B-vitamin status indices (i.e., plasma riboflavin, methylmalonic acid and total homocysteine concentrations), dietary calcium intake and plasma zinc concentrations that could possibly act as effect modifiers. Milk consumption was positively associated with the number of stages performed in the endurance run test (ERT) (β = 0.10; p = 0.017) and negatively with body mass index (BMI) (β = −0.10; p = 0.014), after adjusting for several potential confounders and effect modifiers. Dietary intakes of vitamin B2 and B12 derived from milk were also positively associated with the number of ERT stages (β = 0.10; p = 0.015 and β = 0.10; p = 0.014 respectively). In conclusion, higher intake of milk as well as vitamin B2 and B12 derived from milk were independently associated with higher cardiorespiratory fitness in Greek preadolescents. The key roles of these B-vitamins in substrate oxidation, energy production, haemoglobin synthesis and erythropoiesis could provide a basis for interpreting these associations. However, further research is needed to confirm this potential interpretation. PMID:27754376

  14. Biochemical genetics of largemouth bass. Final report

    SciTech Connect

    Phillipp, D.P.; Childers, W.F.; Whitt, G.S.

    1982-10-01

    Distinct biochemical genetic differences exist among largemouth bass (Micropterus salmoides) populations from different geographic regions. The level of genetic variation at 28 enzyme loci was determined for 90 bass populations throughout the United States through the use of vertical starch gel electrophoretic analyses. Allelic polymorphism was observed at 17 of these enzyme loci. Marked differences in allele frequencies at six of these loci exist among populations from the different geographic areas studied. Allele frequencies at two of these loci (isocitrate dehydrogenase-B and aspartate aminotransferase-B) can be used to quantitatively determine the contributions by each of the two recognized subspecies, M. s. salmoides and M. s. floridanus to the total gene pool of any population of largemouth bass. The current range of each subspecies and the extent of the range of intergradation has been redescribed. Furthermore, distinct north-south clinal distributions of the alleles at four of these loci (malate dehydrogenase-B, superoxide dismutase-A, isocitrate dehydrogenase-B and aspartate aminotransferase-B) indicate a possible involvement of these enzymes in the determination of the thermal tolerance/preference limits for this species. In vitro analyses of the different allelic isozymes at the malate dehydrogenase-B locus representing the northern and the southern phenotypes have revealed kinetic differences at temperatures which are encountered routinely in the environment, suggesting a possible mechanism for the genetic determination of thermal requirements. The results of these genetic analyses clearly indicate the need for incorporating sound genetic principles into current and future management programs.

  15. Genetically controlled food preference: biochemical mechanisms.

    PubMed Central

    Guarna, M M; Borowsky, R L

    1993-01-01

    Food choice is known to be correlated with genotype in the crustacean Gammarus palustris. Given a choice of Enteromorpha intestinalis (E) over Ulva lactuca (U), individuals homozygous for the Amy II.52 allele have a greater preference for E than do Amy II.55 homozygotes. To account for this correlation, we hypothesized that the proportions of saccharides released by the enzymatic action of Amy II.52 on E or Amy II.55 on U starches differ from and better stimulate feeding than those released by Amy II.52 on U and Amy II.55 on E starches. To test this, the two forms of amylase were purified by glycogen/ethanol precipitation and preparative PAGE. Their product distributions with each of the starches were determined by HPLC. Each amylase/starch combination gave different distributions of the main products: maltose, maltotriose, and maltotetraose. Feeding preference tests using artificial foods containing these sugars showed that the product distributions from Amy II.52/E starch or Amy II.55/U starch were preferred over those from Amy II.52/U or Amy II.55/E. Patterns of preferences for the artificial foods closely matched those observed in earlier experiments in which different genotypes fed on intact algae. Thus, genetic differences in feeding preferences can be understood in terms of variation in biochemical properties of a digestive enzyme. These results highlight a previously unappreciated role for digestive enzymes: in their capacity to modify the chemical nature of environmental stimuli prior to gustation, digestive enzymes can be viewed as having important chemosensory roles. PMID:7685121

  16. [INVESTIGATION OF BLOOD BIOCHEMICAL INDICES DURING BICYCLE ERGOMETRY].

    PubMed

    Davydov, B V; Stepanova, G P; Krivitsyna, Z A; Vorontsov, A L; Voronkov, Yu I

    2015-01-01

    Our investigations showed that physical work (bicycle ergometry) alters the biochemical status of male volunteers. On the 5th minute of bicycle endometry capillary blood looses significantly glucose and increases magnesium, phosphorus and particularly lactic acid. Creatine phosphokinase activity and trygliceride levels did not deviate much from baseline values. All the changes had a similar trend equally in the supine and sitting position. Therefore, biochemical investigations may complement essentially the physiological and neurophysiological tests of human adaptability to physical loads. The investigation utilized the dry chemistry technology of rapid biochemical diagnostics. PMID:26738302

  17. Nutritional status in pregnant adolescents: a systematic review of biochemical markers.

    PubMed

    Moran, Victoria Hall

    2007-04-01

    Adolescent pregnancy is a major public health challenge for many industrialized countries and is associated with significant medical, nutritional, social and economic risk for mothers and their infants. Despite this, relatively little is known about the nutritional status of this population. The aim of this paper was to conduct a systematic review of the current evidence relating to the biochemical markers of nutritional status of pregnant adolescents living in industrialized countries. Six papers were identified that fulfilled the inclusion criteria, the majority of which were conducted in the United States. The studies were of variable quality and most failed to control for potential confounders which may have strongly influenced the findings. Due to limited research, conclusions cannot be drawn about the zinc and calcium status of pregnant adolescents, and data on folate and vitamin B(12) status appeared conflicting. There was some consensus among studies, however, to suggest that indicators of anaemia and iron status were compromised in pregnant adolescents, particularly during the third trimester of pregnancy. Chronological age did not appear to influence nutritional status, although there was some evidence to suggest that increasing gynaecologic age may positively influence plasma ferritin levels. Current research is limited by sampling and measurement bias, and research is urgently required to address these limitations. Further consideration should also be made of the influence of the role of socio-economic support on pregnant adolescents' nutritional status. The achievement of improved nutrition in pregnancy among adolescents requires multidisciplinary collaborations of adolescent healthcare providers, academics, professional organizations, policymakers, industry and service users. Only once this is achieved can adolescent nutrition, and adolescent nutrition in pregnancy, be significantly and sustainably optimized.

  18. 40 CFR 158.2080 - Experimental use permit data requirements-biochemical pesticides.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements-biochemical pesticides. 158.2080 Section 158.2080 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2080 Experimental use permit data requirements—biochemical pesticides. (a) Sections...

  19. 40 CFR 158.2080 - Experimental use permit data requirements-biochemical pesticides.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements-biochemical pesticides. 158.2080 Section 158.2080 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2080 Experimental use permit data requirements—biochemical pesticides. (a) Sections...

  20. 40 CFR 158.2080 - Experimental use permit data requirements-biochemical pesticides.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements-biochemical pesticides. 158.2080 Section 158.2080 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2080 Experimental use permit data requirements—biochemical pesticides. (a) Sections...

  1. 40 CFR 158.2080 - Experimental use permit data requirements-biochemical pesticides.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements-biochemical pesticides. 158.2080 Section 158.2080 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2080 Experimental use permit data requirements—biochemical pesticides. (a) Sections...

  2. Distance to high-voltage power lines and risk of childhood leukemia--an analysis of confounding by and interaction with other potential risk factors.

    PubMed

    Pedersen, Camilla; Bräuner, Elvira V; Rod, Naja H; Albieri, Vanna; Andersen, Claus E; Ulbak, Kaare; Hertel, Ole; Johansen, Christoffer; Schüz, Joachim; Raaschou-Nielsen, Ole

    2014-01-01

    We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73). We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance. PMID:25259740

  3. Observed effects of “distributional learning” may not relate to the number of peaks. A test of “dispersion” as a confounding factor

    PubMed Central

    Wanrooij, Karin; Boersma, Paul; Benders, Titia

    2015-01-01

    Distributional learning of speech sounds is learning from simply being exposed to frequency distributions of speech sounds in one’s surroundings. In laboratory settings, the mechanism has been reported to be discernible already after a few minutes of exposure, in both infants and adults. These “effects of distributional training” have traditionally been attributed to the difference in the number of peaks between the experimental distribution (two peaks) and the control distribution (one or zero peaks). However, none of the earlier studies fully excluded a possibly confounding effect of the dispersion in the distributions. Additionally, some studies with a non-speech control condition did not control for a possible difference between processing speech and non-speech. The current study presents an experiment that corrects both imperfections. Spanish listeners were exposed to either a bimodal distribution encompassing the Dutch contrast /ɑ/∼/a/ or a unimodal distribution with the same dispersion. Before and after training, their accuracy of categorization of [ɑ]- and [a]-tokens was measured. A traditionally calculated p-value showed no significant difference in categorization improvement between bimodally and unimodally trained participants. Because of this null result, a Bayesian method was used to assess the odds in favor of the null hypothesis. Four different Bayes factors, each calculated on a different belief in the truth value of previously found effect sizes, indicated the absence of a difference between bimodally and unimodally trained participants. The implication is that “effects of distributional training” observed in the lab are not induced by the number of peaks in the distributions. PMID:26441719

  4. Biochemical observation during 28 days of space flight

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Kambaut, P. C.

    1975-01-01

    With the completion of the 28-day flight of Skylab 2, the sum of biochemical data on human reaction to the weightless environment was significantly extended both quantitatively and qualitatively. The biochemical studies were divided into two broad categories. One group included the more routine blood studies similar to those used in everyday medical practice. The second category encompassed those analyses used to investigate more thoroughly the endocrinological and fluid changes first seen in the crewmembers following the Gemini, Apollo, and Soviet missions. Significant biochemical changes were observed that varied in magnitude and direction, but all disappeared shortly after return to earth. Most of changes indicate successful adaptation by the body to the combined stresses of weightlessness. Results of the biochemical observation are presented in the form of data tables and graphs.

  5. Pleural, peritoneal and pericardial effusions – a biochemical approach

    PubMed Central

    Kopcinovic, Lara Milevoj; Culej, Jelena

    2014-01-01

    The pathological accumulation of serous fluids in the pleural, peritoneal and pericardial space occurs in a variety of conditions. Since patient management depends on right and timely diagnosis, biochemical analysis of extravascular body fluids is considered a valuable tool in the patient management process. The biochemical evaluation of serous fluids includes the determination of gross appearance, differentiation of transudative from exudative effusions and additional specific biochemical testing to assess the effusion etiology. This article summarized data from the most relevant literature concerning practice with special emphasis on usefulness of biochemical tests used for the investigation of pleural, peritoneal and pericardial effusions. Additionally, preanalytical issues concerning serous fluid analysis were addressed and recommendations concerning acceptable analytical practice in serous fluid analysis were presented. PMID:24627721

  6. 2011 Biomass Program Platform Peer Review: Biochemical Conversion

    SciTech Connect

    Pezzullo, Leslie

    2012-02-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the 2011 U.S. Department of Energy Biomass Program’s Biochemical Conversion Platform Review meeting.

  7. Rethinking glycolysis: on the biochemical logic of metabolic pathways.

    PubMed

    Bar-Even, Arren; Flamholz, Avi; Noor, Elad; Milo, Ron

    2012-05-17

    Metabolic pathways may seem arbitrary and unnecessarily complex. In many cases, a chemist might devise a simpler route for the biochemical transformation, so why has nature chosen such complex solutions? In this review, we distill lessons from a century of metabolic research and introduce new observations suggesting that the intricate structure of metabolic pathways can be explained by a small set of biochemical principles. Using glycolysis as an example, we demonstrate how three key biochemical constraints--thermodynamic favorability, availability of enzymatic mechanisms and the physicochemical properties of pathway intermediates--eliminate otherwise plausible metabolic strategies. Considering these constraints, glycolysis contains no unnecessary steps and represents one of the very few pathway structures that meet cellular demands. The analysis presented here can be applied to metabolic engineering efforts for the rational design of pathways that produce a desired product while satisfying biochemical constraints.

  8. CELLULAR, BIOCHEMICAL, AND MOLECULAR TECHNIQUES IN DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

    Cellular, molecular and biochemical approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The increasing interest in embryonic development as a model system for the study of gene expression has resulted in a cornucopia of i...

  9. Energy-based analysis of biochemical cycles using bond graphs

    PubMed Central

    Gawthrop, Peter J.; Crampin, Edmund J.

    2014-01-01

    Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks. PMID:25383030

  10. [Fifty years of cooperation--FEBS and Polish Biochemical Society].

    PubMed

    Barańska, Jolanta

    2014-01-01

    This year, the Federation of European Biochemical Societies (FEBS) celebrates its 50th anniversary. The Polish Biochemical Society, represented by the Society's President, Kazimierz Zakrzewski, was a founding member of the organization. The text presents a history of collaboration between FEBS and Polish Biochemical Society, the participation of Polish Biochemical Society members in different FEBS activities, as well as the role they played in running the Federation. Author describes FEBS Congresses which taken place in Warsaw, the first 3rd FEBS Meeting in 1966 and then 29th Congress in 2004. The profiles of Jakub Karol Parnas, the founding father of the Polish biochemistry and some crucial Presidents of the Society, are also presented. The text describes Parnas Conferences, organized jointly by Polish and Ukrainian Biochemical Societies from 1996, and growing from 2011 into three-nation event with participation of Ukrainian, Israeli and Polish scientists, largely due to significant help from FEBS. Summarizing the last few years, author judge the cooperation between the Federation and the Polish Biochemical Society as optimal.

  11. Energy-based analysis of biochemical cycles using bond graphs.

    PubMed

    Gawthrop, Peter J; Crampin, Edmund J

    2014-11-01

    Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks. PMID:25383030

  12. A method for zooming of nonlinear models of biochemical systems

    PubMed Central

    2011-01-01

    Background Models of biochemical systems are typically complex, which may complicate the discovery of cardinal biochemical principles. It is therefore important to single out the parts of a model that are essential for the function of the system, so that the remaining non-essential parts can be eliminated. However, each component of a mechanistic model has a clear biochemical interpretation, and it is desirable to conserve as much of this interpretability as possible in the reduction process. Furthermore, it is of great advantage if we can translate predictions from the reduced model to the original model. Results In this paper we present a novel method for model reduction that generates reduced models with a clear biochemical interpretation. Unlike conventional methods for model reduction our method enables the mapping of predictions by the reduced model to the corresponding detailed predictions by the original model. The method is based on proper lumping of state variables interacting on short time scales and on the computation of fraction parameters, which serve as the link between the reduced model and the original model. We illustrate the advantages of the proposed method by applying it to two biochemical models. The first model is of modest size and is commonly occurring as a part of larger models. The second model describes glucose transport across the cell membrane in baker's yeast. Both models can be significantly reduced with the proposed method, at the same time as the interpretability is conserved. Conclusions We introduce a novel method for reduction of biochemical models that is compatible with the concept of zooming. Zooming allows the modeler to work on different levels of model granularity, and enables a direct interpretation of how modifications to the model on one level affect the model on other levels in the hierarchy. The method extends the applicability of the method that was previously developed for zooming of linear biochemical models to

  13. Biochemical characterisation during seed development of oil palm (Elaeis guineensis).

    PubMed

    Kok, Sau-Yee; Namasivayam, Parameswari; Ee, Gwendoline Cheng-Lian; Ong-Abdullah, Meilina

    2013-07-01

    Developmental biochemical information is a vital base for the elucidation of seed physiology and metabolism. However, no data regarding the biochemical profile of oil palm (Elaeis guineensis Jacq.) seed development has been reported thus far. In this study, the biochemical changes in the developing oil palm seed were investigated to study their developmental pattern. The biochemical composition found in the seed differed significantly among the developmental stages. During early seed development, the water, hexose (glucose and fructose), calcium and manganese contents were present in significantly high levels compared to the late developmental stage. Remarkable changes in the biochemical composition were observed at 10 weeks after anthesis (WAA): the dry weight and sucrose content increased significantly, whereas the water content and hexose content declined. The switch from a high to low hexose/sucrose ratio could be used to identify the onset of the maturation phase. At the late stage, dramatic water loss occurred, whereas the content of storage reserves increased progressively. Lauric acid was the most abundant fatty acid found in oil palm seed starting from 10 WAA. PMID:23575803

  14. Maximizing the biochemical resolving power of fluorescence microscopy.

    PubMed

    Esposito, Alessandro; Popleteeva, Marina; Venkitaraman, Ashok R

    2013-01-01

    Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems. PMID:24204821

  15. Maximizing the Biochemical Resolving Power of Fluorescence Microscopy

    PubMed Central

    Esposito, Alessandro; Popleteeva, Marina; Venkitaraman, Ashok R.

    2013-01-01

    Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems. PMID:24204821

  16. Biochemical diagnosis in 3040 kidney stone formers in Argentina.

    PubMed

    Spivacow, Francisco Rodolfo; del Valle, Elisa Elena; Negri, Armando Luis; Fradinger, Erich; Abib, Anabella; Rey, Paula

    2015-08-01

    Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.

  17. Microstereolithography and its application to biochemical IC chip

    NASA Astrophysics Data System (ADS)

    Ikuta, Koji; Maruo, Shoji; Hasegawa, Tadahiro; Adachi, Takao

    2001-06-01

    The world's first micro stereo lithography, named IH process, was proposed and developed by the speaker in 1992. By now, several types of micro stereo lithography systems have been developed. Three-dimensional resolution of solidification has reached to 0.2 micron at present. These 3D micro fabrication processes using UV curable polymer gave a big impact on not only MEMS but also optics. The latest version of IH process enables us to make a movable micro mechanism without assemble process or sacrificial layer technique often used in silicon process. It is well known that the IH process is the mother of two-photon micro stereo lithography and its applications. Recently new micro chemical device named Biochemical IC Chip was proposed and developed by the speaker. This chip is based on the module IC chip-set like today's TTL family. IH process enable to make the biochemical IC including real three-dimensional micro fluid channels. Various kinds of Biochemical IC chips such as micro pump, switching valve, reactor, concentrator and detector have already been fabricated successfully. Basic performance of micro chemical devices constructed by the biochemical IC chips were demonstrated. The biochemical IC chips will open new bioscience and medicine based on innovative technology.

  18. Biochemical characterisation during seed development of oil palm (Elaeis guineensis).

    PubMed

    Kok, Sau-Yee; Namasivayam, Parameswari; Ee, Gwendoline Cheng-Lian; Ong-Abdullah, Meilina

    2013-07-01

    Developmental biochemical information is a vital base for the elucidation of seed physiology and metabolism. However, no data regarding the biochemical profile of oil palm (Elaeis guineensis Jacq.) seed development has been reported thus far. In this study, the biochemical changes in the developing oil palm seed were investigated to study their developmental pattern. The biochemical composition found in the seed differed significantly among the developmental stages. During early seed development, the water, hexose (glucose and fructose), calcium and manganese contents were present in significantly high levels compared to the late developmental stage. Remarkable changes in the biochemical composition were observed at 10 weeks after anthesis (WAA): the dry weight and sucrose content increased significantly, whereas the water content and hexose content declined. The switch from a high to low hexose/sucrose ratio could be used to identify the onset of the maturation phase. At the late stage, dramatic water loss occurred, whereas the content of storage reserves increased progressively. Lauric acid was the most abundant fatty acid found in oil palm seed starting from 10 WAA.

  19. Click Chemistry-Mediated Nanosensors for Biochemical Assays

    PubMed Central

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications. PMID:27217831

  20. Combined Biochemical and Serological Typing of Clinical Isolates of Klebsiella

    PubMed Central

    Rennie, R. P.; Duncan, I. B. R.

    1974-01-01

    In a series of 640 strains of Klebsiella isolated from clinical specimens over a 7-month period, there were sufficient biochemical differences between strains to allow a biochemical typing system to be established. Biochemical tests were done in solid media inoculated with a modified Steers inocula replicator. Biotypes were designated by a numerical coding system; 29 distinct biotypes were found among the 640 strains of Klebsiella. Serotyping of 270 of the strains was done by the Quellung reaction, and 40 capsular types were identified. Numerical biotypes and serotypes of strains appeared to vary independently. When used in conjunction, the two methods subdivided the strains into many more distinct types than either used alone. With the combined method over 100 types of Klebsiella were distinguished among the 270 isolates. PMID:4608362

  1. Hematologic and plasma biochemical values of hyacinth macaws (Anodorhynchus hyacinthinus).

    PubMed

    Kolesnikovas, Cristiane K M; Niemeyer, Claudia; Teixeira, Rodrigo H F; Nunes, Adauto L V; Rameh-de-Albuquerque, Luciana C; Sant'Anna, Sávio S; Catão-Dias, José L

    2012-09-01

    The hyacinth macaw (Anodorhyncus hyacinthinus), considered the largest psittacine bird species in the world, is an endangered species, with a remaining population of approximately 6500 birds in the wild. To establish hematologic and plasma biochemical reference ranges and to verify differences related to sex, samples from 29 hyacinth macaws (14 males, 15 females) were obtained from birds apprehended from illegal wildlife trade and subsequently housed at the Sorocaba Zoo, Brazil. No significant differences in hematologic or plasma biochemical values were found between females and males. Compared with published reference values, differences were found in mean concentrations of total red blood cell count, corpuscular volume, corpuscular hemoglobin level, total white blood cell count, aspartate aminotransferase level, creatine kinase concentration, alkaline phosphatase concentration, and phosphorus level. Baseline hematologic and plasma biochemical ranges were established, which may be useful as reference values for clinicians working with this endangered species in captivity or rehabilitation centers.

  2. Biochemical markers in oral submucous fibrosis: A review and update

    PubMed Central

    Kamath, V V; Satelur, K; Komali, Y

    2013-01-01

    Oral submucous fibrosis (OSMF) is a potentially malignant oral condition effectively linked to the causative habit of chewing areca nut. Since its first description in the 1950s, numerous epidemiological, biochemical, histological, and genetic studies have been reported. While most studies point out to the cause and effect of areca nut, co-additive factors are also implicated in the progression and malignant transformation of this condition. Biochemical investigations have concentrated on outlining such changes in the blood, serum or tissues of these patients and have given insights on the possible pathogenesis of OSMF. This article attempts to compile details of biochemical investigations in OSMF and summarize and infer on the findings. PMID:24348612

  3. Occurrence of bacteria and biochemical markers on public surfaces.

    PubMed

    Reynolds, Kelly A; Watt, Pamela M; Boone, Stephanie A; Gerba, Charles P

    2005-06-01

    From 1999-2003, the hygiene of 1061 environmental surfaces from shopping, daycare, and office environments, personal items, and miscellaneous activities (i.e., gymnasiums, airports, movie theaters, restaurants, etc.), in four US cities, was monitored. Samples were analyzed for fecal and total coliform bacteria, protein, and biochemical markers. Biochemical markers, i.e., hemoglobin (blood marker), amylase (mucus, saliva, sweat, and urine marker), and urea (urine and sweat marker) were detected on 3% (26/801); 15% (120/801), and 6% (48/801) of the surfaces, respectively. Protein (general hygiene marker) levels > or = 200 microg/10 cm2 were present on 26% (200/801) of the surfaces tested. Surfaces from children's playground equipment and daycare centers were the most frequently contaminated (biochemical markers on 36%; 15/42 and 46%; 25/54, respectively). Surfaces from the shopping, miscellaneous activities, and office environments were positive for biochemical markers with a frequency of 21% (69/333), 21% (66/308), and 11% (12/105), respectively). Sixty samples were analyzed for biochemical markers and bacteria. Total and fecal coliforms were detected on 20% (12/60) and 7% (4/ 60) of the surfaces, respectively. Half and one-third of the sites positive for biochemical markers were also positive for total and fecal coliforms, respectively. Artificial contamination of public surfaces with an invisible fluorescent tracer showed that contamination from outside surfaces was transferred to 86% (30/ 35) of exposed individual's hands and 82% (29/35) tracked the tracer to their home or personal belongings hours later. Results provide information on the relative hygiene of commonly encountered public surfaces and aid in the identification of priority environments where contaminant occurrence and risk of exposure may be greatest. Children's playground equipment is identified as a priority surface for additional research on the occurrence of and potential exposure to infectious

  4. Susceptibility to antibiotics and biochemical properties of Desulfovibrio desulfuricans strains.

    PubMed

    Dzierzewicz, Z; Cwalina, B; Jaworska-Kik, M; Weglarz, L; Wilczok, T

    2001-01-01

    Susceptibility to several antibiotics and biochemical properties of intestinal and soil strains of Desulfovibrio desulfuricans bacteria were investigated using the tests: ATB ANA, Sceptor Anaerobic MIC/ID and API ZYM. It was demonstrated that the D. desulfuricans strains were resistant to penicillin, cefoxitin, clindamycin, metronidazole, erythromycin, rifampicin and teicoplanin. The strains initially susceptible to imipenem became resistant to this drug following 72 h incubation with it. Of 25 analyzed antibiotics there was none that after 72 h action on the bacteria was effective in relation to all of the investigated strains. The differences in susceptibility of D. desulfuricans strains to antibiotics were not associated with the strains' biochemical properties. PMID:12197616

  5. Fast and simple spectral FLIM for biochemical and medical imaging.

    PubMed

    Popleteeva, Marina; Haas, Kalina T; Stoppa, David; Pancheri, Lucio; Gasparini, Leonardo; Kaminski, Clemens F; Cassidy, Liam D; Venkitaraman, Ashok R; Esposito, Alessandro

    2015-09-01

    Spectrally resolved fluorescence lifetime imaging microscopy (λFLIM) has powerful potential for biochemical and medical imaging applications. However, long acquisition times, low spectral resolution and complexity of λFLIM often narrow its use to specialized laboratories. Therefore, we demonstrate here a simple spectral FLIM based on a solid-state detector array providing in-pixel histrogramming and delivering faster acquisition, larger dynamic range, and higher spectral elements than state-of-the-art λFLIM. We successfully apply this novel microscopy system to biochemical and medical imaging demonstrating that solid-state detectors are a key strategic technology to enable complex assays in biomedical laboratories and the clinic.

  6. Physiological and molecular biochemical mechanisms of bile formation

    PubMed Central

    Reshetnyak, Vasiliy Ivanovich

    2013-01-01

    This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

  7. A biochemical strategy for simulation of endochondral and intramembranous ossification.

    PubMed

    Garzón-Alvarado, Diego A

    2014-01-01

    Following the assumption that parathyroid hormone related protein and Indian hedgehog form a biochemical regulatory loop for the endochondral process and bone morphogenetic protein 2 and Noggin in the intramembranous process, this paper implements these regulatory mechanisms. For this purpose, we use a set of reaction-diffusion equations that are widely used in morphogenesis, in which biochemical factors are assumed to be secreted by precursor cells, mesenchymal cells and chondrocytes, in endochondral and intramembranous ossification, respectively. The solution leads to the so-called Turing patterns, which represent these processes of ossification in a very approximate way.

  8. [Biochemical features of gallbladder bile in biliary tract diseases].

    PubMed

    Plotnikova, E Iu; Aleksandrova, A Iu; Beloborodova, E I; Didlovslaia, N A

    2007-06-01

    Sixty-two and 58 patients with hypo- and hypermotor biliary tract dysfunction (BTD), respectively, as well as 59 patients with chronic acalculous cholecystitis (CAC) and 63 with opisthorchiasis-complicated CAC were examined. A control group comprised 33 patients of the same sex and age. All the patients underwent fractional duodenal intubation, followed by clinical, biochemical, and serological bile studies. All the examinees were found to increased gallbladder bile lithogenicity, minor changes being observed in biliary tract dysfunction and more pronounced ones being in opisthorchiasis. A biochemical study of gallbladder bile, followed by its lithogenicity correction, is recommended in the treatment of different forms of BTD. PMID:17682480

  9. Overview of the DOE/SERI Biochemical Conversion Program

    SciTech Connect

    Wright, J D

    1986-09-01

    The Solar Energy Research Institute manages a program of research and development on the biochemical conversion of renewable lignocellulosic materials to liquid fuels for the Department of Energy's Biofuels and Municipal Waste Technology Division. The Biochemical Conversion Program is mission oriented so effort is concentrated on technologies which appear to have the greatest potential for being adopted by the private sector to economically convert lignocellulosic materials into high value liquid transportation fuels such as ethanol. The program is structured to supply the technology for such fuels to compete economically first as an octane booster or fuel additive, and, with additional improvements, as a neat fuel. 18 refs., 3 figs., 1 tab.

  10. The Biochemical Properties of Antibodies and Their Fragments.

    PubMed

    Hnasko, Robert M

    2015-01-01

    Immunoglobulins (Ig) or antibodies are powerful molecular recognition tools that can be used to identify minute quantities of a given target analyte. Their antigen-binding properties define both the sensitivity and selectivity of an immunoassay. Understanding the biochemical properties of this class of protein will provide users with the knowledge necessary to select the appropriate antibody composition to maximize immunoassay results. Here we define the general biochemical properties of antibodies and their similarities and differences, explain how these properties influence their functional relationship to an antigen target, and describe a method for the enzymatic fragmentation of antibodies into smaller functional parts.

  11. The Stereochemistry of Biochemical Molecules: A Subject to Revisit

    NASA Astrophysics Data System (ADS)

    Centelles, Josep J.; Imperial, Santiago

    2005-01-01

    Although Fischer’s convention for stereoisomers is useful for simple molecules, the stereochemistry of complex biochemical molecules is often poorly indicated in textbooks. This article reports on errors in stereochemistry of complex hydrosoluble vitamin B 12 molecule. Twenty-five popular biochemistry textbooks were examined for their treatment of the stereoisomery of vitamin B 12 . Mistakes, discrepancies, and oddities reported in vitamin B 12 are just an example of this problem. Biochemistry textbook authors and teachers should pay more attention to the stereoisomery of biochemical molecules to avoid students’ confusion.

  12. Study on color difference estimation method of medicine biochemical analysis

    NASA Astrophysics Data System (ADS)

    Wang, Chunhong; Zhou, Yue; Zhao, Hongxia; Sun, Jiashi; Zhou, Fengkun

    2006-01-01

    The biochemical analysis in medicine is an important inspection and diagnosis method in hospital clinic. The biochemical analysis of urine is one important item. The Urine test paper shows corresponding color with different detection project or different illness degree. The color difference between the standard threshold and the test paper color of urine can be used to judge the illness degree, so that further analysis and diagnosis to urine is gotten. The color is a three-dimensional physical variable concerning psychology, while reflectance is one-dimensional variable; therefore, the estimation method of color difference in urine test can have better precision and facility than the conventional test method with one-dimensional reflectance, it can make an accurate diagnose. The digital camera is easy to take an image of urine test paper and is used to carry out the urine biochemical analysis conveniently. On the experiment, the color image of urine test paper is taken by popular color digital camera and saved in the computer which installs a simple color space conversion (RGB -> XYZ -> L *a *b *)and the calculation software. Test sample is graded according to intelligent detection of quantitative color. The images taken every time were saved in computer, and the whole illness process will be monitored. This method can also use in other medicine biochemical analyses that have relation with color. Experiment result shows that this test method is quick and accurate; it can be used in hospital, calibrating organization and family, so its application prospect is extensive.

  13. MATLAB-Based Teaching Modules in Biochemical Engineering

    ERIC Educational Resources Information Center

    Lee, Kilho; Comolli, Noelle K.; Kelly, William J.; Huang, Zuyi

    2015-01-01

    Mathematical models play an important role in biochemical engineering. For example, the models developed in the field of systems biology have been used to identify drug targets to treat pathogens such as Pseudomonas aeruginosa in biofilms. In addition, competitive binding models for chromatography processes have been developed to predict expanded…

  14. Biochemical and Structural Studies of RNA Modification and Repair

    ERIC Educational Resources Information Center

    Chan, Chio Mui

    2009-01-01

    RNA modification, RNA interference, and RNA repair are important events in the cell. This thesis presents three projects related to these three fields. By using both biochemical and structural methods, we characterized enzymatic activities of pseudouridine synthase TruD, solved the structure of "A. aeolicus" GidA, and reconstituted a novel…

  15. Annelid Aminotransferase Activity--An Exercise in Basic Biochemical Skills.

    ERIC Educational Resources Information Center

    Teal, A. R.; Alcock, R. S.

    1978-01-01

    A practical exercise is described that allows students to investigate a specific problem using a variety of biochemical techniques. The need for a thorough understanding of the theoretical principles underlying these processes is emphasized. A program of private study and assessment is suggested to enable the progress of students to be followed.…

  16. Metstoich--Teaching Quantitative Metabolism and Energetics in Biochemical Engineering

    ERIC Educational Resources Information Center

    Wong, Kelvin W. W.; Barford, John P.

    2010-01-01

    Metstoich, a metabolic calculator developed for teaching, can provide a novel way to teach quantitative metabolism to biochemical engineering students. It can also introduce biochemistry/life science students to the quantitative aspects of life science subjects they have studied. Metstoich links traditional biochemistry-based metabolic approaches…

  17. Biosensors and bioelectronics on smartphone for portable biochemical detection.

    PubMed

    Zhang, Diming; Liu, Qingjun

    2016-01-15

    Smartphone has been widely integrated with sensors, such as test strips, sensor chips, and hand-held detectors, for biochemical detections due to its portability and ubiquitous availability. Utilizing built-in function modules, smartphone is often employed as controller, analyzer, and displayer for rapid, real-time, and point-of-care monitoring, which can significantly simplify design and reduce cost of the detecting systems. This paper presents a review of biosensors and bioelectronics on smartphone for portable biochemical detections. The biosensors and bioelectronics based on smartphone can mainly be classified into biosensors using optics, surface plasmon resonance, electrochemistry, and near-field communication. The developments of these biosensors and bioelectronics on smartphone are reviewed along with typical biochemical detecting cases. Sensor strategies, detector attachments, and coupling methods are highlighted to show designs of the compact, lightweight, and low-cost sensor systems. The performances and advantages of these designs are introduced with their applications in healthcare diagnosis, environment monitoring, and food evaluation. With advances in micro-manufacture, sensor technology, and miniaturized electronics, biosensor and bioelectronic devices on smartphone can be used to perform biochemical detections as common and convenient as electronic tag readout in foreseeable future.

  18. Parameter identifiability of power-law biochemical system models.

    PubMed

    Srinath, Sridharan; Gunawan, Rudiyanto

    2010-09-01

    Mathematical modeling has become an integral component in biotechnology, in which these models are frequently used to design and optimize bioprocesses. Canonical models, like power-laws within the Biochemical Systems Theory, offer numerous mathematical and numerical advantages, including built-in flexibility to simulate general nonlinear behavior. The construction of such models relies on the estimation of unknown case-specific model parameters by way of experimental data fitting, also known as inverse modeling. Despite the large number of publications on this topic, this task remains the bottleneck in canonical modeling of biochemical systems. The focus of this paper concerns with the question of identifiability of power-law models from dynamic data, that is, whether the parameter values can be uniquely and accurately identified from time-series data. Existing and newly developed parameter identifiability methods were applied to two power-law models of biochemical systems, and the results pointed to the lack of parametric identifiability as the root cause of the difficulty faced in the inverse modeling. Despite the focus on power-law models, the analyses and conclusions are extendable to other canonical models, and the issue of parameter identifiability is expected to be a common problem in biochemical system modeling. PMID:20197073

  19. Biochemical aspects of pressure tolerance in marine mammals.

    PubMed

    Castellini, Michael A; Rivera, Patricia M; Castellini, Judith M

    2002-11-01

    Some marine mammals can dive to depths approaching 2000 m. At these hydrostatic pressures (200 atm), some fish species show alterations in enzyme structure and function that make them pressure-tolerant. Do marine mammals also possess biochemical adaptations to withstand such pressures? In theory, biochemical alterations might occur at the control of enzymatic pathways, by impacting cell membrane fluidity changes or at a higher level, such as cellular metabolism. Studies of marine mammal tissues show evidence of all of these changes, but the results are not consistent across species or diving depth. This review discusses whether the elevated body temperature of marine mammals imparts pressure tolerance at the biochemical level, whether there are cell membrane structural differences in marine mammals and whether whole, living cells from marine mammals alter their metabolism when pressure stressed. We conclude that temperature alone is probably not protective against pressure and that cell membrane composition data are not conclusive. Whole cell studies suggest that marine mammals either respond positively to pressure or are not impacted by pressure. However, the range of tissue types and enzyme systems that have been studied is extremely limited and needs to be expanded before more general conclusions about how these mammals tolerate elevated pressures on a biochemical level can be drawn.

  20. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 2. MODEL EVALUATION

    EPA Science Inventory

    The multilayer biochemical dry deposition model (MLBC) described in the accompanying paper was tested against half-hourly eddy correlation data from six field sites under a wide range of climate conditions with various plant types. Modeled CO2, O3, SO2<...

  1. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... can be found in § 158.2000. (b) Each data table includes “use patterns” under which the individual... table and the test notes following the data table must be used to determine whether the data requirement... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Biochemical pesticides...

  2. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... can be found in § 158.2000. (b) Each data table includes “use patterns” under which the individual... table and the test notes following the data table must be used to determine whether the data requirement... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Biochemical pesticides...

  3. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... can be found in § 158.2000. (b) Each data table includes “use patterns” under which the individual... table and the test notes following the data table must be used to determine whether the data requirement... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticides...

  4. Biochemical Parameters of Orienteers Competing in a Long Distance Race.

    ERIC Educational Resources Information Center

    Mikan, Vladimir; And Others

    1992-01-01

    Measured important biochemical parameters in a group of orienteers two hours before beginning and immediately after an orienteering marathon. Found levels of dehydration. Suggests a drinking regimen which is designed for orienteering races. Concludes that no runner having kidney or liver abnormalities or changes in the urine should be allowed to…

  5. [Strategies for diagnosis and biochemical control of porphyrias].

    PubMed

    Brock, Axel; Rasmussen, Lars Melholt; Hertz, Jens Michael

    2014-02-17

    Porphyrias are rare, distinct and well characterized diseases due to impairment of one of the eight steps in the biosynthesis of haem, which is the functional group of haemoglobin, myoglobin and cytochromes, including the cytochrome P-450 family. The actual strategies for diagnosis and biochemical control of the five most common porphyrias are described.

  6. Classic and contemporary approaches to modeling biochemical reactions

    PubMed Central

    Chen, William W.; Niepel, Mario; Sorger, Peter K.

    2010-01-01

    Recent interest in modeling biochemical networks raises questions about the relationship between often complex mathematical models and familiar arithmetic concepts from classical enzymology, and also about connections between modeling and experimental data. This review addresses both topics by familiarizing readers with key concepts (and terminology) in the construction, validation, and application of deterministic biochemical models, with particular emphasis on a simple enzyme-catalyzed reaction. Networks of coupled ordinary differential equations (ODEs) are the natural language for describing enzyme kinetics in a mass action approximation. We illustrate this point by showing how the familiar Briggs-Haldane formulation of Michaelis-Menten kinetics derives from the outer (or quasi-steady-state) solution of a dynamical system of ODEs describing a simple reaction under special conditions. We discuss how parameters in the Michaelis-Menten approximation and in the underlying ODE network can be estimated from experimental data, with a special emphasis on the origins of uncertainty. Finally, we extrapolate from a simple reaction to complex models of multiprotein biochemical networks. The concepts described in this review, hitherto of interest primarily to practitioners, are likely to become important for a much broader community of cellular and molecular biologists attempting to understand the promise and challenges of “systems biology” as applied to biochemical mechanisms. PMID:20810646

  7. Physiologic and biochemical aspects of skeletal muscle denervation and reinnervation

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Mayer, R. F.

    1984-01-01

    Some of the physiologic and biochemical changes that occur in mammalian skeletal muscle following denervation and reinnervation are considered and some comparisons are made with changes observed following altered motor function. The nature of the trophic influence by which nerves control muscle properties are discussed, including the effects of choline acetyltransferase and acetylcholinesterase and the role of the acetylcholine receptor.

  8. Biochemical Engineering with Extensive Use of Personal Computers.

    ERIC Educational Resources Information Center

    Bungay, H. R.

    1986-01-01

    Describes a course in biochemical engineering fundamentals which relies heavily on the use of personal computers. The computers are used with interactive tutorials, problems that require computer simulations of differential equations, and homework assignments. A list of computer assignments and student term projects is included. (TW)

  9. Biochemical correlates in an animal model of depression

    SciTech Connect

    Johnson, J.O.

    1986-01-01

    A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action.

  10. The Stereochemistry of Biochemical Molecules: A Subject to Revisit

    ERIC Educational Resources Information Center

    Centelles, Josep J.; Imperial, Santiago

    2005-01-01

    Although Fischer's convention for stereoisomers is useful for simple molecules, the stereochemistry of complex biochemical molecules is often poorly indicated in textbooks. This article reports on errors in stereochemistry of complex hydrosoluble vitamin B12 molecule. Twenty-five popular biochemistry textbooks were examined for their treatment of…

  11. Know-how and know-why in biochemical engineering.

    PubMed

    von Stockar, U; Valentinotti, S; Marison, I; Cannizzaro, C; Herwig, C

    2003-08-01

    This contribution analyzes the position of biochemical engineering in general and bioprocess engineering particularly in the force fields between fundamental science and applications, and between academia and industry. By using culture technology as an example, it can be shown that bioprocess engineering has moved slowly but steadily from an empirical art concerned with mainly know-how to a science elucidating the know-why of culture behavior. Highly powerful monitoring tools enable biochemical engineers to understand and explain quantitatively the activity of cellular culture on a metabolic basis. Among these monitoring tools are not just semi-online analyses of culture broth by HPLC, GC and FIA, but, increasingly, also noninvasive methods such as midrange IR, Raman and capacitance spectroscopy, as well as online calorimetry. The detailed and quantitative insight into the metabolome and the fluxome that bioprocess engineers are establishing offers an unprecedented opportunity for building bridges between molecular biology and engineering biosciences. Thus, one of the major tasks of biochemical engineering sciences is not developing new know-how for industrial applications, but elucidating the know-why in biochemical engineering by conducting research on the underlying scientific fundamentals.

  12. Salvage Brachytherapy for Biochemically Recurrent Prostate Cancer following Primary Brachytherapy

    PubMed Central

    Lacy, John M.; Wilson, William A.; Bole, Raevti; Chen, Li; Meigooni, Ali S.; Rowland, Randall G.; Clair, William H. St.

    2016-01-01

    Purpose. In this study, we evaluated our experience with salvage brachytherapy after discovery of biochemical recurrence after a prior brachytherapy procedure. Methods and Materials. From 2001 through 2012 twenty-one patients treated by brachytherapy within University of Kentucky or from outside centers developed biochemical failure and had no evidence of metastases. Computed tomography (CT) scans were evaluated; patients who had an underseeded portion of their prostate were considered for reimplantation. Results. The majority of the patients in this study (61.9%) were low risk and median presalvage PSA was 3.49 (range 17.41–1.68). Mean follow-up was 61 months. At last follow-up after reseeding, 11/21 (52.4%) were free of biochemical recurrence. There was a trend towards decreased freedom from biochemical recurrence in low risk patients (p = 0.12). International Prostate Symptom Scores (IPSS) increased at 3-month follow-up visits but decreased and were equivalent to baseline scores at 18 months. Conclusions. Salvage brachytherapy after primary brachytherapy is possible; however, in our experience the side-effect profile after the second brachytherapy procedure was higher than after the first brachytherapy procedure. In this cohort of patients we demonstrate that approximately 50% oncologic control, low risk patients appear to have better outcomes than others. PMID:27092279

  13. Biochemical and physiological consequences of the Apollo flight diet.

    NASA Technical Reports Server (NTRS)

    Hander, E. W.; Leach, C. S.; Fischer, C. L.; Rummel, J.; Rambaut, P.; Johnson, P. C.

    1971-01-01

    Six male subjects subsisting on a typical Apollo flight diet for five consecutive days were evaluated for changes in biochemical and physiological status. Laboratory examinations failed to demonstrate any significant changes of the kind previously attributed to weightlessness, such as in serum electrolytes, endocrine values, body fluid, or hematologic parameters.

  14. BIOCHEMICAL INDICES OF EXPOSURE TO ENVIRONMENTAL ESTROGENS: A SPECIES COMPARISON

    EPA Science Inventory

    Existence of endocrine active substances in the aquatic environment has been clearly established in several studies. Exposure of organisms to both natural and synthetic xenoestrogens have been found to alter biochemical homeostatis and, in some cases, result in reproductive and d...

  15. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 1. MODEL FORMULATION

    EPA Science Inventory

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration ...

  16. Recommendations for terminology and databases for biochemical thermodynamics.

    PubMed

    Alberty, Robert A; Cornish-Bowden, Athel; Goldberg, Robert N; Hammes, Gordon G; Tipton, Keith; Westerhoff, Hans V

    2011-05-01

    Chemical equations are normally written in terms of specific ionic and elemental species and balance atoms of elements and electric charge. However, in a biochemical context it is usually better to write them with ionic reactants expressed as totals of species in equilibrium with each other. This implies that atoms of elements assumed to be at fixed concentrations, such as hydrogen at a specified pH, should not be balanced in a biochemical equation used for thermodynamic analysis. However, both kinds of equations are needed in biochemistry. The apparent equilibrium constant K' for a biochemical reaction is written in terms of such sums of species and can be used to calculate standard transformed Gibbs energies of reaction Δ(r)G'°. This property for a biochemical reaction can be calculated from the standard transformed Gibbs energies of formation Δ(f)G(i)'° of reactants, which can be calculated from the standard Gibbs energies of formation of species Δ(f)G(j)° and measured apparent equilibrium constants of enzyme-catalyzed reactions. Tables of Δ(r)G'° of reactions and Δ(f)G(i)'° of reactants as functions of pH and temperature are available on the web, as are functions for calculating these properties. Biochemical thermodynamics is also important in enzyme kinetics because apparent equilibrium constant K' can be calculated from experimentally determined kinetic parameters when initial velocities have been determined for both forward and reverse reactions. Specific recommendations are made for reporting experimental results in the literature.

  17. Accurate atom-mapping computation for biochemical reactions.

    PubMed

    Latendresse, Mario; Malerich, Jeremiah P; Travers, Mike; Karp, Peter D

    2012-11-26

    The complete atom mapping of a chemical reaction is a bijection of the reactant atoms to the product atoms that specifies the terminus of each reactant atom. Atom mapping of biochemical reactions is useful for many applications of systems biology, in particular for metabolic engineering where synthesizing new biochemical pathways has to take into account for the number of carbon atoms from a source compound that are conserved in the synthesis of a target compound. Rapid, accurate computation of the atom mapping(s) of a biochemical reaction remains elusive despite significant work on this topic. In particular, past researchers did not validate the accuracy of mapping algorithms. We introduce a new method for computing atom mappings called the minimum weighted edit-distance (MWED) metric. The metric is based on bond propensity to react and computes biochemically valid atom mappings for a large percentage of biochemical reactions. MWED models can be formulated efficiently as Mixed-Integer Linear Programs (MILPs). We have demonstrated this approach on 7501 reactions of the MetaCyc database for which 87% of the models could be solved in less than 10 s. For 2.1% of the reactions, we found multiple optimal atom mappings. We show that the error rate is 0.9% (22 reactions) by comparing these atom mappings to 2446 atom mappings of the manually curated Kyoto Encyclopedia of Genes and Genomes (KEGG) RPAIR database. To our knowledge, our computational atom-mapping approach is the most accurate and among the fastest published to date. The atom-mapping data will be available in the MetaCyc database later in 2012; the atom-mapping software will be available within the Pathway Tools software later in 2012.

  18. Uroncor consensus statement: Management of biochemical recurrence after radical radiotherapy for prostate cancer: From biochemical failure to castration resistance.

    PubMed

    López Torrecilla, José; Hervás, Asunción; Zapatero, Almudena; Gómez Caamaño, Antonio; Macías, Victor; Herruzo, Ismael; Maldonado, Xavier; Gómez Iturriaga, Alfonso; Casas, Francesc; González San Segundo, Carmen

    2015-01-01

    Management of patients who experience biochemical failure after radical radiotherapy with or without hormonal therapy is highly challenging. The clinician must not only choose the type of treatment, but also the timing and optimal sequence of treatment administration. When biochemical failure occurs, numerous treatment scenarios are possible, thus making it more difficult to select the optimal approach. Moreover, rapid and ongoing advances in treatment options require that physicians make decisions that could impact both survival and quality of life. The aim of the present consensus statement, developed by the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR), is to provide cancer specialists with the latest, evidence-based information needed to make the best decisions for the patient under all possible treatment scenarios. The structure of this consensus statement follows the typical development of disease progression after biochemical failure, with the most appropriate treatment recommendations given for each stage. The consensus statement is organized into three separate chapters, as follows: biochemical failure with or without local recurrence and/or metastasis; progression after salvage therapy; and treatment of castration-resistant patients. PMID:26109913

  19. National Bioenergy Center Biochemical Platform Integration Project: Quarterly Update #26, January - March 2010

    SciTech Connect

    Schell, D.

    2010-04-01

    January-March, 2010 edition of the National Bioenergy Center's Biochemical Platform Integration Project quarterly newsletter. Issue topics: understanding and improving sugar measurements in biomass hydrolysates; expansion of the NREL/DOE Biochemical Pilot Plant.

  20. ESTIMATING GASEOUS EXCHANGES BETWEEN THE ATMOSPHERE AND PLANTS USING A COUPLED BIOCHEMICAL DRY DEPOSITION MODEL

    EPA Science Inventory

    To study gaseous exchanges between the soil, biosphere and atmosphere, a biochemical model was coupled with the latest version of Meyers Multi-Layer Deposition Model. The biochemical model describes photosynthesis and respiration and their coupling with stomatal resistance for...

  1. Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.

    PubMed

    Sahebari, M; Nabavi, N; Salehi, M

    2014-10-01

    Notwithstanding that several original studies and some systematic reviews have been undertaken on the subject "correlation between serum values of vitamin D (VitD) and lupus disease activity," there is still no consensus on the importance of sectional measurement of serum VitD in the prediction of disease activity and important confounders in estimation of serum VitD. Medline, Web of Knowledge, and Scopus databases were searched from 1995 to 2013. The following medical subject heading (MeSH) terms and/or text words were used: "Vitamin D" OR "25OHD" OR "25(OH)D" combined with "systemic lupus erythematosus" OR "lupus" OR "SLE." References cited in the identified articles were also manually searched. Human studies in any language were included. Original research on this topic was also carried out on 82 lupus patients, considering important VitD confounders according to our systematic review and we included them in the meta-analysis. A total of 35 studies were registered for this study. Only 11 of these pointed to this correlation by Pearson test. The pooled Pearson correlation (r) of associations between disease activity and VitD was -0.365 (95% CI: -0.536, -0.165) with significant heterogeneity (p = 0.001 I (2 )= 93%). Sensitivity analysis resulted in no significant differences. The most important adjustable confounders considered by researchers were drugs, especially hydroxychloroquine, prednisolone and supplementary VitD, body mass index (BMI) and proteinuria or renal function. Only proteinuria was reported to influence VitD concentration strongly. BMI was another probable influencing factor. Our original research presented no correlation between VitD and SLEDAI (p = 0.68, r s = 0.003). This meta-analysis demonstrated that most of the studies on the relationship between VitD and lupus disease activity that found no correlation did not present the details of the statistics. However, analyzing 11 studies, most of which found a reverse correlation and

  2. Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.

    PubMed

    Sahebari, M; Nabavi, N; Salehi, M

    2014-10-01

    Notwithstanding that several original studies and some systematic reviews have been undertaken on the subject "correlation between serum values of vitamin D (VitD) and lupus disease activity," there is still no consensus on the importance of sectional measurement of serum VitD in the prediction of disease activity and important confounders in estimation of serum VitD. Medline, Web of Knowledge, and Scopus databases were searched from 1995 to 2013. The following medical subject heading (MeSH) terms and/or text words were used: "Vitamin D" OR "25OHD" OR "25(OH)D" combined with "systemic lupus erythematosus" OR "lupus" OR "SLE." References cited in the identified articles were also manually searched. Human studies in any language were included. Original research on this topic was also carried out on 82 lupus patients, considering important VitD confounders according to our systematic review and we included them in the meta-analysis. A total of 35 studies were registered for this study. Only 11 of these pointed to this correlation by Pearson test. The pooled Pearson correlation (r) of associations between disease activity and VitD was -0.365 (95% CI: -0.536, -0.165) with significant heterogeneity (p = 0.001 I (2 )= 93%). Sensitivity analysis resulted in no significant differences. The most important adjustable confounders considered by researchers were drugs, especially hydroxychloroquine, prednisolone and supplementary VitD, body mass index (BMI) and proteinuria or renal function. Only proteinuria was reported to influence VitD concentration strongly. BMI was another probable influencing factor. Our original research presented no correlation between VitD and SLEDAI (p = 0.68, r s = 0.003). This meta-analysis demonstrated that most of the studies on the relationship between VitD and lupus disease activity that found no correlation did not present the details of the statistics. However, analyzing 11 studies, most of which found a reverse correlation and

  3. The free energy cost of accurate biochemical oscillations

    PubMed Central

    Cao, Yuansheng; Wang, Hongli; Ouyang, Qi; Tu, Yuhai

    2015-01-01

    Oscillation is an important cellular process that regulates timing of different vital life cycles. However, in the noisy cellular environment, oscillations can be highly inaccurate due to phase fluctuations. It remains poorly understood how biochemical circuits suppress phase fluctuations and what is the incurred thermodynamic cost. Here, we study three different types of biochemical oscillations representing three basic oscillation motifs shared by all known oscillatory systems. In all the systems studied, we find that the phase diffusion constant depends on the free energy dissipation per period following the same inverse relation parameterized by system specific constants. This relationship and its range of validity are shown analytically in a model of noisy oscillation. Microscopically, we find that the oscillation is driven by multiple irreversible cycles that hydrolyze the fuel molecules such as ATP; the number of phase coherent periods is proportional to the free energy consumed per period. Experimental evidence in support of this general relationship and testable predictions are also presented. PMID:26566392

  4. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    NASA Astrophysics Data System (ADS)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  5. The free-energy cost of accurate biochemical oscillations

    NASA Astrophysics Data System (ADS)

    Cao, Yuansheng; Wang, Hongli; Ouyang, Qi; Tu, Yuhai

    2015-09-01

    Oscillations within the cell regulate the timing of many important life cycles. However, in this noisy environment, oscillations can be highly inaccurate owing to phase fluctuations. It remains poorly understood how biochemical circuits suppress these phase fluctuations and what is the incurred thermodynamic cost. Here, we study three different types of biochemical oscillation, representing three basic oscillation motifs shared by all known oscillatory systems. In all the systems studied, we find that the phase diffusion constant depends on the free-energy dissipation per period, following the same inverse relation parameterized by system-specific constants. This relationship and its range of validity are shown analytically in a model of noisy oscillation. Microscopically, we find that the oscillation is driven by multiple irreversible cycles that hydrolyse fuel molecules such as ATP; the number of phase coherent periods is proportional to the free energy consumed per period. Experimental evidence in support of this general relationship and testable predictions are also presented.

  6. Biochemical functionalization of peptide nanotubes with phage displayed peptides.

    PubMed

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering. PMID:27479451

  7. Biochemical markers in the assessment of bone disease

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.

    1997-01-01

    As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.

  8. Adult amphibian epidermal proteins: biochemical characterization and developmental appearance.

    PubMed

    Reeves, O R

    1975-08-01

    The keratin-like proteins (KLPs) from the epidermis of adult frogs of the species Xenopus laevis have been isolated and biochemically characterized by means of polyacrylamide gel electrophoresis, amino acid analysis, tryptic peptide mapping, amino-terminal end-group analysis and isoelectric focusing. One particular protein fraction of rather unusual amino acid composition found only in epidermal tissue was isolated in quantity by preparative gel electrophoresis and monospecific antibodies prepared against it. Using this anti-KLP antibody preparation it was possible to show that at least one kine of keratin-like protein characteristic of the adult epidermis first appears within the larval epidermis during metamorphosis. This is the first reported biochemical characterization of a tissue-specific protien from adult amphibian skin.

  9. Electrolyte-Gated Graphene Ambipolar Frequency Multipliers for Biochemical Sensing.

    PubMed

    Fu, Wangyang; Feng, Lingyan; Mayer, Dirk; Panaitov, Gregory; Kireev, Dmitry; Offenhäusser, Andreas; Krause, Hans-Joachim

    2016-04-13

    In this Letter, the ambipolar properties of an electrolyte-gated graphene field-effect transistor (GFET) have been explored to fabricate frequency-doubling biochemical sensor devices. By biasing the ambipolar GFETs in a common-source configuration, an input sinusoidal voltage at frequency f applied to the electrolyte gate can be rectified to a sinusoidal wave at frequency 2f at the drain electrode. The extraordinary high carrier mobility of graphene and the strong electrolyte gate coupling provide the graphene ambipolar frequency doubler an unprecedented unity gain, as well as a detection limit of ∼4 pM for 11-mer single strand DNA molecules in 1 mM PBS buffer solution. Combined with an improved drift characteristics and an enhanced low-frequency 1/f noise performance by sampling at doubled frequency, this good detection limit suggests the graphene ambipolar frequency doubler a highly promising biochemical sensing platform. PMID:26928906

  10. SABIO-RK--database for biochemical reaction kinetics.

    PubMed

    Wittig, Ulrike; Kania, Renate; Golebiewski, Martin; Rey, Maja; Shi, Lei; Jong, Lenneke; Algaa, Enkhjargal; Weidemann, Andreas; Sauer-Danzwith, Heidrun; Mir, Saqib; Krebs, Olga; Bittkowski, Meik; Wetsch, Elina; Rojas, Isabel; Müller, Wolfgang

    2012-01-01

    SABIO-RK (http://sabio.h-its.org/) is a web-accessible database storing comprehensive information about biochemical reactions and their kinetic properties. SABIO-RK offers standardized data manually extracted from the literature and data directly submitted from lab experiments. The database content includes kinetic parameters in relation to biochemical reactions and their biological sources with no restriction on any particular set of organisms. Additionally, kinetic rate laws and corresponding equations as well as experimental conditions are represented. All the data are manually curated and annotated by biological experts, supported by automated consistency checks. SABIO-RK can be accessed via web-based user interfaces or automatically via web services that allow direct data access by other tools. Both interfaces support the export of the data together with its annotations in SBML (Systems Biology Markup Language), e.g. for import in modelling tools.

  11. The application of information theory to biochemical signaling systems.

    PubMed

    Rhee, Alex; Cheong, Raymond; Levchenko, Andre

    2012-08-01

    Cell signaling can be thought of fundamentally as an information transmission problem in which chemical messengers relay information about the external environment to the decision centers within a cell. Due to the biochemical nature of cellular signal transduction networks, molecular noise will inevitably limit the fidelity of any messages received and processed by a cell's signal transduction networks, leaving it with an imperfect impression of its environment. Fortunately, Shannon's information theory provides a mathematical framework independent of network complexity that can quantify the amount of information that can be transmitted despite biochemical noise. In particular, the channel capacity can be used to measure the maximum number of stimuli a cell can distinguish based upon the noisy responses of its signaling systems. Here, we provide a primer for quantitative biologists that covers fundamental concepts of information theory, highlights several key considerations when experimentally measuring channel capacity, and describes successful examples of the application of information theoretic analysis to biological signaling.

  12. Electrolyte-Gated Graphene Ambipolar Frequency Multipliers for Biochemical Sensing.

    PubMed

    Fu, Wangyang; Feng, Lingyan; Mayer, Dirk; Panaitov, Gregory; Kireev, Dmitry; Offenhäusser, Andreas; Krause, Hans-Joachim

    2016-04-13

    In this Letter, the ambipolar properties of an electrolyte-gated graphene field-effect transistor (GFET) have been explored to fabricate frequency-doubling biochemical sensor devices. By biasing the ambipolar GFETs in a common-source configuration, an input sinusoidal voltage at frequency f applied to the electrolyte gate can be rectified to a sinusoidal wave at frequency 2f at the drain electrode. The extraordinary high carrier mobility of graphene and the strong electrolyte gate coupling provide the graphene ambipolar frequency doubler an unprecedented unity gain, as well as a detection limit of ∼4 pM for 11-mer single strand DNA molecules in 1 mM PBS buffer solution. Combined with an improved drift characteristics and an enhanced low-frequency 1/f noise performance by sampling at doubled frequency, this good detection limit suggests the graphene ambipolar frequency doubler a highly promising biochemical sensing platform.

  13. Genetic and biochemical dissection of the eucaryotic flagellum

    PubMed Central

    1984-01-01

    The axoneme is the basic functional unit of the eucaryotic flagellum. Periodic structures appended to its 9+2 microtubule core are responsible for generation of flagellar bending. An account of biochemical and genetic studies of flagellar-defective mutants of Chlamydomonas reinhardtii is presented. These studies provide insights into the complex molecular composition of the appended structures, their mode of assembly, and the way in which they interact to modulate flagellar function. PMID:6230366

  14. Molecular and biochemical pharmacology of the histamine H4 receptor

    PubMed Central

    Leurs, Rob; Chazot, Paul L; Shenton, Fiona C; Lim, Herman D; de Esch, Iwan JP

    2009-01-01

    The elucidation of the human genome has had a major impact on histamine receptor research. The identification of the human H4 receptor by several groups has been instrumental for a new appreciation of the role of histamine in the modulation of immune function. In this review, we summarize the historical developments and the molecular and biochemical pharmacology of the H4 receptor. PMID:19413568

  15. Current diagnostic guidelines for biochemical diagnosis of acromegaly.

    PubMed

    Ferone, D; Resmini, E; Bocca, L; Giusti, M; Barreca, A; Minuto, F

    2004-12-01

    Acromegaly is a rare and chronic disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH)-producing tumor of the pituitary. In the past, the diagnosis of acromegaly was established basically on physical changes, and only the patients with a severe clinical picture were brought to medical attention. The development of a radioimmunoassay for detecting GH allowed for the first time to confirm the diagnosis biochemically. Subsequently, methods for measuring insulin-like growth factor 1 (IGF-I) became available and added another important biochemical marker for the diagnosis and follow-up of these patients. Progressive improvements in assay methods have allowed for progressively better definitions of normality and, as a result, have permitted the diagnosis to be biochemically established in patients with only mild forms of the disease. Moreover, new potential markers of disease activity, such as other GH-dependent IGF system parameters, have been investigated and proposed in the diagnostic work-up and for monitoring the therapeutic outcome. Optimal assessment of disease activity, for both diagnostic and follow-up purposes, is mandatory. This subject has been strongly debated regarding proper cut-off values using highly sensitive GH assays as well as the problems linked to IGF system components measurement. Consequently, several consensus reports, as well as original studies, have been issued giving special attention to diagnostic procedures, cut-off revisions and definition of disease activity. The present review discuss principally the biochemical diagnosis of acromegaly based on these articles and on the experience collected in an endocrinological unit considered as reference center for pituitary diseases. PMID:15765030

  16. The energy costs of insulators in biochemical networks.

    PubMed

    Barton, John P; Sontag, Eduardo D

    2013-03-19

    Complex networks of biochemical reactions, such as intracellular protein signaling pathways and genetic networks, are often conceptualized in terms of modules--semiindependent collections of components that perform a well-defined function and which may be incorporated in multiple pathways. However, due to sequestration of molecular messengers during interactions and other effects, collectively referred to as retroactivity, real biochemical systems do not exhibit perfect modularity. Biochemical signaling pathways can be insulated from impedance and competition effects, which inhibit modularity, through enzymatic futile cycles that consume energy, typically in the form of ATP. We hypothesize that better insulation necessarily requires higher energy consumption. We test this hypothesis through a combined theoretical and computational analysis of a simplified physical model of covalent cycles, using two innovative measures of insulation, as well as a possible new way to characterize optimal insulation through the balancing of these two measures in a Pareto sense. Our results indicate that indeed better insulation requires more energy. While insulation may facilitate evolution by enabling a modular plug-and-play interconnection architecture, allowing for the creation of new behaviors by adding targets to existing pathways, our work suggests that this potential benefit must be balanced against the metabolic costs of insulation necessarily incurred in not affecting the behavior of existing processes. PMID:23528097

  17. Biochemical Markers of Bone Turnover Part I: Biochemistry and Variability

    PubMed Central

    2005-01-01

    With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies has markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. Part I of this article provides an overview of the basic biochemistry of bone markers, and sources of non-specific variability. Part II (to be published in a subsequent issue of this journal) will review the current evidence regarding the clinical use of biochemical markers of bone remodelling in metabolic and metastatic bone disease. PMID:16648882

  18. Design of a biochemical circuit motif for learning linear functions.

    PubMed

    Lakin, Matthew R; Minnich, Amanda; Lane, Terran; Stefanovic, Darko

    2014-12-01

    Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective. PMID:25401175

  19. Polyphenol oxidase as a biochemical seed defense mechanism

    PubMed Central

    Fuerst, E. Patrick; Okubara, Patricia A.; Anderson, James V.; Morris, Craig F.

    2014-01-01

    Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO), when wild oat (Avena fatua L.) caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea), non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems. PMID:25540647

  20. Inactivation of food-borne viruses using natural biochemical substances.

    PubMed

    Li, Dan; Baert, Leen; Uyttendaele, Mieke

    2013-08-01

    Food-borne viruses such as human Noroviruses (NoVs), hepatitis A virus (HAV), Rotaviruses (RoVs) are a public health concern worldwide. Biochemical substances, which occur naturally in plants, animals or microorganisms, might possess considerable antimicrobial properties. In this study, the reported effects of biochemical substances on food-borne viruses are reviewed. The biochemical substances are grouped into several categories including (i) polyphenols and proanthocyanins, (ii) saponin, (iii) polysaccharides, (iv) organic acids, (v) proteins and polypeptides, (vi) essential oils. Although not fully understood, the mechanism of action for the antiviral activity of the natural compounds is presented. Generally, it is thought to be the prevention of the viral attachment to host cells, either by causing damage on the viral capsids or change of the receptors on the cell membranes. It is recommended that further studies are undertaken not only on the wide-range screening for novel antiviral substances, but also on the mechanism in-depth as well as the exploration for their potential application in controlling virus contamination in foods or food processing. PMID:23628607

  1. How special is the biochemical function of native proteins?

    PubMed

    Skolnick, Jeffrey; Gao, Mu; Zhou, Hongyi

    2016-01-01

    Native proteins perform an amazing variety of biochemical functions, including enzymatic catalysis, and can engage in protein-protein and protein-DNA interactions that are essential for life. A key question is how special are these functional properties of proteins. Are they extremely rare, or are they an intrinsic feature? Comparison to the properties of compact conformations of artificially generated compact protein structures selected for thermodynamic stability but not any type of function, the artificial (ART) protein library, demonstrates that a remarkable number of the properties of native-like proteins are recapitulated. These include the complete set of small molecule ligand-binding pockets and most protein-protein interfaces. ART structures are predicted to be capable of weakly binding metabolites and cover a significant fraction of metabolic pathways, with the most enriched pathways including ancient ones such as glycolysis. Native-like active sites are also found in ART proteins. A small fraction of ART proteins are predicted to have strong protein-protein and protein-DNA interactions. Overall, it appears that biochemical function is an intrinsic feature of proteins which nature has significantly optimized during evolution. These studies raise questions as to the relative roles of specificity and promiscuity in the biochemical function and control of cells that need investigation.

  2. Weighting schemes in metabolic graphs for identifying biochemical routes.

    PubMed

    Ghosh, S; Baloni, P; Vishveshwara, S; Chandra, N

    2014-03-01

    Metabolism forms an integral part of all cells and its study is important to understand the functioning of the system, to understand alterations that occur in disease state and hence for subsequent applications in drug discovery. Reconstruction of genome-scale metabolic graphs from genomics and other molecular or biochemical data is now feasible. Few methods have also been reported for inferring biochemical pathways from these networks. However, given the large scale and complex inter-connections in the networks, the problem of identifying biochemical routes is not trivial and some questions still remain open. In particular, how a given path is altered in perturbed conditions remains a difficult problem, warranting development of improved methods. Here we report a comparison of 6 different weighting schemes to derive node and edge weights for a metabolic graph, weights reflecting various kinetic, thermodynamic parameters as well as abundances inferred from transcriptome data. Using a network of 50 nodes and 107 edges of carbohydrate metabolism, we show that kinetic parameter derived weighting schemes [Formula: see text] fare best. However, these are limited by their extent of availability, highlighting the usefulness of omics data under such conditions. Interestingly, transcriptome derived weights yield paths with best scores, but are inadequate to discriminate the theoretical paths. The method is tested on a system of Escherichia coli stress response. The approach illustrated here is generic in nature and can be used in the analysis for metabolic network from any species and perhaps more importantly for comparing condition-specific networks.

  3. Endothelial cells and cathepsins: Biochemical and biomechanical regulation.

    PubMed

    Platt, Manu O; Shockey, W Andrew

    2016-03-01

    Cathepsins are mechanosensitive proteases that are regulated not only by biochemical factors, but are also responsive to biomechanical forces in the cardiovascular system that regulate their expression and activity to participate in cardiovascular tissue remodeling. Their elastinolytic and collagenolytic activity have been implicated in atherosclerosis, abdominal aortic aneurysms, and in heart valve disease, all of which are lined by endothelial cells that are the mechanosensitive monolayer of cells that sense and respond to fluid shear stress as the blood flows across the surfaces of the arteries and valve leaflets. Inflammatory cytokine signaling is integrated with biomechanical signaling pathways by the endothelial cells to transcribe, translate, and activate either the cysteine cathepsins to remodel the tissue or to express their inhibitors to maintain healthy cardiovascular tissue structure. Other cardiovascular diseases should now be included in the study of the cysteine cathepsin activation because of the additional biochemical cues they provide that merges with the already existing hemodynamics driving cardiovascular disease. Sickle cell disease causes a chronic inflammation including elevated TNFα and increased numbers of circulating monocytes that alter the biochemical stimulation while the more viscous red blood cells due to the sickling of hemoglobin alters the hemodynamics and is associated with accelerated elastin remodeling causing pediatric strokes. HIV-mediated cardiovascular disease also occurs earlier in than the broader population and the influence of HIV-proteins and antiretrovirals on endothelial cells must be considered to understand these accelerated mechanisms in order to identify new therapeutic targets for prevention.

  4. How special is the biochemical function of native proteins?

    PubMed Central

    Skolnick, Jeffrey; Gao, Mu; Zhou, Hongyi

    2016-01-01

    Native proteins perform an amazing variety of biochemical functions, including enzymatic catalysis, and can engage in protein-protein and protein-DNA interactions that are essential for life. A key question is how special are these functional properties of proteins. Are they extremely rare, or are they an intrinsic feature? Comparison to the properties of compact conformations of artificially generated compact protein structures selected for thermodynamic stability but not any type of function, the artificial (ART) protein library, demonstrates that a remarkable number of the properties of native-like proteins are recapitulated. These include the complete set of small molecule ligand-binding pockets and most protein-protein interfaces. ART structures are predicted to be capable of weakly binding metabolites and cover a significant fraction of metabolic pathways, with the most enriched pathways including ancient ones such as glycolysis. Native-like active sites are also found in ART proteins. A small fraction of ART proteins are predicted to have strong protein-protein and protein-DNA interactions. Overall, it appears that biochemical function is an intrinsic feature of proteins which nature has significantly optimized during evolution. These studies raise questions as to the relative roles of specificity and promiscuity in the biochemical function and control of cells that need investigation. PMID:26962440

  5. Basic statistical recipes for the emergence of biochemical discernment.

    PubMed

    Michel, Denis

    2011-09-01

    An essential step towards understanding life would be to identify the very basic mechanisms responsible for the discerning behaviour of living biochemical systems, absent from randomly reacting chemical soups. One intuitively feels that this question goes beyond the particular nature of the biological molecules and should relate to general physical principles. The pre-eminent physicist Ludwig Boltzmann early envisioned life as a struggle for entropy, in concordance with the subsequent principle of self-organization out of equilibrium. Re-examination of elementary steady state biochemical systems from a statistical perspective supports this view and shows that sigmoidal responses arising from microstates elimination, are sufficient to explain innermost characteristics of life, including its capacity to convert random molecular interactions into accurate biological reactions. A primary operating strategy to achieve this goal is the introduction of time-irreversible transitions in molecular state conversion cycles by injection of free energy, which confers decisional capacity to single macromolecules. Selected examples from various fields of molecular biology such as enzymology and gene expression, are provided to show that these non-equilibrium steady state mechanisms remain important in contemporary biochemical systems. But in addition, information archiving allowed the emergence of the time-reversible counterparts of these mechanisms, mediated by evolutionary pre-organized macromolecular complexes capable of generating discernment in a non-dissipative manner.

  6. Modelling biochemical reaction systems by stochastic differential equations with reflection.

    PubMed

    Niu, Yuanling; Burrage, Kevin; Chen, Luonan

    2016-05-01

    In this paper, we gave a new framework for modelling and simulating biochemical reaction systems by stochastic differential equations with reflection not in a heuristic way but in a mathematical way. The model is computationally efficient compared with the discrete-state Markov chain approach, and it ensures that both analytic and numerical solutions remain in a biologically plausible region. Specifically, our model mathematically ensures that species numbers lie in the domain D, which is a physical constraint for biochemical reactions, in contrast to the previous models. The domain D is actually obtained according to the structure of the corresponding chemical Langevin equations, i.e., the boundary is inherent in the biochemical reaction system. A variant of projection method was employed to solve the reflected stochastic differential equation model, and it includes three simple steps, i.e., Euler-Maruyama method was applied to the equations first, and then check whether or not the point lies within the domain D, and if not perform an orthogonal projection. It is found that the projection onto the closure D¯ is the solution to a convex quadratic programming problem. Thus, existing methods for the convex quadratic programming problem can be employed for the orthogonal projection map. Numerical tests on several important problems in biological systems confirmed the efficiency and accuracy of this approach.

  7. Micro biochemical sensor based on SOI planar optical waveguide

    NASA Astrophysics Data System (ADS)

    Du, Yang; Dong, Ying

    2014-02-01

    A novel biochemical sensor based on planar optical waveguide is presented in this paper. The features of the sensor are as follows, the planar optical waveguide is made of SOI (Silicon-On-Insulator) material, a Mach Zehnder (M-Z) Interferometer structure is adopted as the sensing part, the sensor chip is fabricated using CMOS compatible technology and the size of the sensor chip is on the micron scale. Compared with the traditional biochemical sensors, this new type of sensor has such notable advantages as miniaturization, integration, high sensitivity and strong anti-interference capability, which provide the sensor with potential applications where traditional biochemical sensors cannot be used. At first, the benefits of SOI material comparing to other optical waveguide materials were analyzed in this paper. Then, according to the optical waveguide mode theory, M-Z interferometer waveguide was designed for the single mode behavior. By theoretical analysis of the radiation loss in the Y-junction of the planar waveguide interferometer, the relationship between the branch angle and the radiation loss was obtained. The power transfer function and the parametric equation of sensitivity of the M-Z interferometer were obtained through analysis of the waveguide structure. At last, the resolution of the effective refractive index and the characteristics of sensitivity of the sensor based on SOI M-Z Interferometer waveguide were simulated and analyzed by utilizing MATLAB software. As a result, the sensitivity of SOI M-Z Interferometer sensor can reach the order of 10-7 magnitude.

  8. Design of a biochemical circuit motif for learning linear functions

    PubMed Central

    Lakin, Matthew R.; Minnich, Amanda; Lane, Terran; Stefanovic, Darko

    2014-01-01

    Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective. PMID:25401175

  9. Effects of colchicine on parotid gland: structural and biochemical studies.

    PubMed

    Malberti, A I; González de Crosa, M

    1998-01-01

    The present study involves the analysis of structural, ultrastructural and biochemical modifications induced by colchicine (Col) in Guinea Pig parotid gland. The biochemical studies showed that the highest concentration of soluble proteins occurred 4 hs after colchicine injection. The curve of a-amylase activity in the gland showed an increase in enzyme activity over control at approximately 4 hs post-injection. At 8 hours the rise was even greater. The structural and ultrastructural analyses of the gland revealed that 4 hs post-injection colchicine exerts its maximum inhibitory effect on secretion. At this treatment time, the cytoplasm contained granules of various sizes and sharp outlines. Large areas of the cytoplasm exhibited material which resembled the granular content and seemed to result from the fusion of granules. No secretion was found in the lumen of the ducts. The inhibitory effect on secretion would be due to the disassembly of microtubules which would in turn impair transport of the granules to the apical surface of the membrane and eventual exocytosis. We herein propose that the effects of colchicine in the experimental conditions of this study would be largely reversible at 24 hours. At this time, structural, ultrastructural and biochemical features were similar to those of controls. PMID:11885456

  10. Effect of Different Psychoactive Substances on Serum Biochemical Parameters

    PubMed Central

    Sanli, Dilek Beker; Bilici, Rabia; Suner, Ozgur; Citak, Serhat; Kartkaya, Kazim; Mutlu, Fezan Sahin

    2015-01-01

    Background: Psychoactive substances affect mainly central nervous system and brain function causing changes in behavior. Objectives: The purpose of this study was to determine the effects of different psychoactive substances on serum biochemical parameters. Patients and Methods: The study included 324 drug dependents, and 69 controls. The patient group was determined according to DSM-IV (The diagnostic and statistical manual of mental disorders, fourth edition) criteria. All patients and control subjects were tested for routine biochemical parameters and urine toxicology parameters for psychoactive substance use. Cases and controls with accompanying diseases like diabetes, cancer, metabolic disorders etc. are excluded from the study. Moreover, an association between urine toxicology results and changes in biochemical parameters was evaluated for statistical significance. Results: There was a statistically significant difference in the Gamma-Glutamyl Transferase (GGT), uric acid, creatinine, urea, albumin, Aspartate Aminotransferase (AST) medians between the dependent and control groups (P < 0.05). We found a statistically significant difference in sodium and albumin levels between the opium-dependent and control groups (P < 0.05). In the benzodiazepin dependent group, we found a significant difference in GGT, urea, glucose, sodium, T protein, and AST levels (P < 0.05). Moreover, a statistically significant difference was observed in triglyceride and GGT levels between the ethyl glucuronide and control groups (P < 0.05). Conclusions: In psychoactive substance dependents, serum routine biochemistry parameters can be used to predict the need for intensive monitoring and treatment programs. PMID:26405680

  11. 40 CFR 180.1127 - Biochemical pesticide plant floral volatile attractant compounds: cinnamaldehyde, cinnamyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticide plant floral... From Tolerances § 180.1127 Biochemical pesticide plant floral volatile attractant compounds... biochemical pesticide plant floral volatile attractant compounds: cinnamaldehyde, cinnamyl alcohol,...

  12. 40 CFR 158.2070 - Biochemical pesticides product performance data requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides product... AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2070 Biochemical pesticides product performance data requirements. Product performance data must be developed...

  13. Discovering Reliable Sources of Biochemical Thermodynamic Data to Aid Students' Understanding

    ERIC Educational Resources Information Center

    Me´ndez, Eduardo; Cerda´, María F.

    2016-01-01

    Students of physical chemistry in biochemical disciplines need biochemical examples to capture the need, not always understood, of a difficult area in their studies. The use of thermodynamic data in the chemical reference state may lead to incorrect interpretations in the analysis of biochemical examples when the analysis does not include relevant…

  14. 40 CFR 158.2070 - Biochemical pesticides product performance data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides product... AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2070 Biochemical pesticides product performance data requirements. Product performance data must be developed...

  15. 40 CFR 158.2040 - Biochemical pesticides residue data requirements table.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides residue data... (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2040 Biochemical pesticides residue data requirements table. (a) General. Sections 158.100 through 158.130 describe how to...

  16. 40 CFR 158.2070 - Biochemical pesticides product performance data requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Biochemical pesticides product... AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2070 Biochemical pesticides product performance data requirements. Product performance data must be developed...

  17. 40 CFR 158.2070 - Biochemical pesticides product performance data requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Biochemical pesticides product... AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2070 Biochemical pesticides product performance data requirements. Product performance data must be developed...

  18. 40 CFR 158.2070 - Biochemical pesticides product performance data requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticides product... AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2070 Biochemical pesticides product performance data requirements. Product performance data must be developed...

  19. Simulation of Biochemical Pathway Adaptability Using Evolutionary Algorithms

    SciTech Connect

    Bosl, W J

    2005-01-26

    The systems approach to genomics seeks quantitative and predictive descriptions of cells and organisms. However, both the theoretical and experimental methods necessary for such studies still need to be developed. We are far from understanding even the simplest collective behavior of biomolecules, cells or organisms. A key aspect to all biological problems, including environmental microbiology, evolution of infectious diseases, and the adaptation of cancer cells is the evolvability of genomes. This is particularly important for Genomes to Life missions, which tend to focus on the prospect of engineering microorganisms to achieve desired goals in environmental remediation and climate change mitigation, and energy production. All of these will require quantitative tools for understanding the evolvability of organisms. Laboratory biodefense goals will need quantitative tools for predicting complicated host-pathogen interactions and finding counter-measures. In this project, we seek to develop methods to simulate how external and internal signals cause the genetic apparatus to adapt and organize to produce complex biochemical systems to achieve survival. This project is specifically directed toward building a computational methodology for simulating the adaptability of genomes. This project investigated the feasibility of using a novel quantitative approach to studying the adaptability of genomes and biochemical pathways. This effort was intended to be the preliminary part of a larger, long-term effort between key leaders in computational and systems biology at Harvard University and LLNL, with Dr. Bosl as the lead PI. Scientific goals for the long-term project include the development and testing of new hypotheses to explain the observed adaptability of yeast biochemical pathways when the myosin-II gene is deleted and the development of a novel data-driven evolutionary computation as a way to connect exploratory computational simulation with hypothesis

  20. A comparison of variant theories of intact biochemical systems. I. Enzyme-enzyme interactions and biochemical systems theory.

    PubMed

    Sorribas, A; Savageau, M A

    1989-06-01

    The need for a well-structured theory of intact biochemical systems becomes increasingly evident as one attempts to integrate the vast knowledge of individual molecular constituents, which has been expanding for several decades. In recent years, several apparently different approaches to the development of such a theory have been proposed. Unfortunately, the resulting theories have not been distinguished from each other, and this has led to considerable confusion with numerous duplications and rediscoveries. Detailed comparisons and critical tests of alternative theories are badly needed to reverse these unfortunate developments. In this paper we (1) characterize a specific system involving enzyme-enzyme interactions for reference in comparing alternative theories, and (2) analyze the reference system by applying the explicit S-system variant within biochemical systems theory (BST), which represents a fundamental framework based upon the power-law formalism and includes several variants. The results provide the first complete and rigorous numerical analysis within the power-law formalism of a specific biochemical system and further evidence for the accuracy of the explicit S-system variant within BST. This theory is shown to represent enzyme-enzyme interactions in a systematically structured fashion that facilitates analysis of complex biochemical systems in which these interactions play a prominent role. This representation also captures the essential character of the underlying nonlinear processes over a wide range of variation (on average 20-fold) in the independent variables of the system. In the companion paper in this issue the same reference system is analyzed by other variants within BST as well as by two additional theories within the same power-law formalism--flux-oriented and metabolic control theories. The results show how all these theories are related to one another.

  1. Biochemical thermodynamics and rapid-equilibrium enzyme kinetics.

    PubMed

    Alberty, Robert A

    2010-12-30

    Biochemical thermodynamics is based on the chemical thermodynamics of aqueous solutions, but it is quite different because pH is used as an independent variable. A transformed Gibbs energy G' is used, and that leads to transformed enthalpies H' and transformed entropies S'. Equilibrium constants for enzyme-catalyzed reactions are referred to as apparent equilibrium constants K' to indicate that they are functions of pH in addition to temperature and ionic strength. Despite this, the most useful way to store basic thermodynamic data on enzyme-catalyzed reactions is to give standard Gibbs energies of formation, standard enthalpies of formation, electric charges, and numbers of hydrogen atoms in species of biochemical reactants like ATP. This makes it possible to calculate standard transformed Gibbs energies of formation, standard transformed enthalpies of formation of reactants (sums of species), and apparent equilibrium constants at desired temperatures, pHs, and ionic strengths. These calculations are complicated, and therefore, a mathematical application in a computer is needed. Rapid-equilibrium enzyme kinetics is based on biochemical thermodynamics because all reactions in the mechanism prior to the rate-determining reaction are at equilibrium. The expression for the equilibrium concentration of the enzyme-substrate complex that yields products can be derived by applying Solve in a computer to the expressions for the equilibrium constants in the mechanism and the conservation equation for enzymatic sites. In 1979, Duggleby pointed out that the minimum number of velocities of enzyme-catalyzed reactions required to estimate the values of the kinetic parameters is equal to the number of kinetic parameters. Solve can be used to do this with steady-state rate equations as well as rapid-equilibrium rate equations, provided that the rate equation is a polynomial. Rapid-equilibrium rate equations can be derived for complicated mechanisms that involve several reactants

  2. [Biochemical diagnostics in acute pancreatitis recognition and outcome predicition].

    PubMed

    Olczyk, Paweł; Kozma, Ewa M; Olczyk, Krystyna; Komosińska-Vassev, Katarzyna

    2004-01-01

    Acute pancreatitis (AP) is a common disease associated with an improper activation of pancreatic zymogens leading to autodigestion of the gland and if excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis manifested by 20% of patients with acute pancreatitis is a life threatening disorder requiring subsequent management in intensive care unit. Unfortunately, none of biochemical tests presently used for laboratory assessment of acute pancreatitis at the early stage of the disease is able to estimate accurately: diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is based on evaluation of serum amylase and lipase activity due to easy availability and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine, procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness in the laboratory diagnosis of AP. The prediction of severity in acute pancreatitis using multifactorial scoring systems is cumbersome especially due to their complexity. On the other hand the biochemical method of choice, estimation of serum C reactive protein, is useless in the early phase of disease. Unfortunately, the computed tomography--the most accurate method in severity assessing--is not always available. Recent studies have brought some progress in severity predicting, such as phospholipase A2, cellular immunity markers, cytokines, activation peptides of trypsinogen and carboxypeptidase B, procalcitonine, pancreatitis associated protein and serum amyloid A. All these newly introduced biochemical methods allow to look optimistically into the future of laboratory diagnostics of the acute pancreatitis believing that the problem of diagnosing and predicting the AP severity will be solved. PMID:15850341

  3. Enabling intelligent readout of luminescent signals from nanoscale biochemical sensors

    NASA Astrophysics Data System (ADS)

    Yao, Lei; Yung, Ka Yi; Tripathi, Vijay; Chodavarapu, Vamsy; Cartwright, Alexander; Bright, Frank

    2009-02-01

    The development of intelligent miniaturized biochemical sensors has been an area of active research over the past several years. These microsensors and sensor microarrays are finding niche applications in point-of-care diagnostics, personal care, food safety, and environmental monitoring. Among these sensors, optical (luminescence) sensing holds a great promise towards implementing simple, specific, and highly sensitive biochemical sensors. It is generally understood that biochemical recognition elements that respond specifically to the target analytes play a critical role in the overall sensor operation. Aside from the recognition elements, signal detection and processing components are important to collect the information provided by recognition elements and output an easily understandable response. The signal processing component provides the best opportunity to incorporate intelligence to achieve low-power, adaptive, accurate, and reliable sensors. We deal with sensors that use sol-gel derived xerogels as recognition materials and Complementary Metal-Oxide Semiconductor (CMOS) integrated circuits for signal detection and processing. Xerogels are nano/microporous glasses that can be used to encapsulate luminophores, enzymes, and nanoparticles in their pores. In this Article, we will describe some of the emerging integrated sensor platforms that are based on monitoring the excited-state luminescence intensity and lifetimes of the luminophores housed in the xerogels. Specifically, we describe a CMOS imaging system for simultaneously monitoring xerogels sensor arrays. Next, we describe a non-linear phase luminometric system with enhanced and dynamically tunable sensitivity and improved signal-to-noise performance. Finally, we will describe time-based signal processing that could enable the direct measurement of excited state fluorescence lifetimes. This time-to-digital converter requires simple circuit implementation and can be used to measure lifetimes that are on

  4. [Biochemical diagnostics in acute pancreatitis recognition and outcome predicition].

    PubMed

    Olczyk, Paweł; Kozma, Ewa M; Olczyk, Krystyna; Komosińska-Vassev, Katarzyna

    2004-01-01

    Acute pancreatitis (AP) is a common disease associated with an improper activation of pancreatic zymogens leading to autodigestion of the gland and if excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis manifested by 20% of patients with acute pancreatitis is a life threatening disorder requiring subsequent management in intensive care unit. Unfortunately, none of biochemical tests presently used for laboratory assessment of acute pancreatitis at the early stage of the disease is able to estimate accurately: diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is based on evaluation of serum amylase and lipase activity due to easy availability and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine, procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness in the laboratory diagnosis of AP. The prediction of severity in acute pancreatitis using multifactorial scoring systems is cumbersome especially due to their complexity. On the other hand the biochemical method of choice, estimation of serum C reactive protein, is useless in the early phase of disease. Unfortunately, the computed tomography--the most accurate method in severity assessing--is not always available. Recent studies have brought some progress in severity predicting, such as phospholipase A2, cellular immunity markers, cytokines, activation peptides of trypsinogen and carboxypeptidase B, procalcitonine, pancreatitis associated protein and serum amyloid A. All these newly introduced biochemical methods allow to look optimistically into the future of laboratory diagnostics of the acute pancreatitis believing that the problem of diagnosing and predicting the AP severity will be solved.

  5. Biochemical and Clinical Profile in Type 2 Diabetics with Depression

    PubMed Central

    Bodi, Akhil Venkata; Sudagani, Jaidev

    2016-01-01

    Introduction There were 72 million adults with Diabetes Mellitus (DM) in 2013 in the South East Asian region of which India is a part. This figure is expected to rise to more than 123 million by 2035. Some studies have also shown that there is an increased risk of depression in subjects with Type 2 Diabetes Mellitus (T2DM). The present study is an attempt to decipher whether there is any difference in the metabolic and clinical profile between patients having T2DM with depression and without depression. Aim To study the clinical and biochemical profile of subjects with T2DM and depression and compare a non-depressed diabetic cohort on the same parameters. Materials and Methods The cross-sectional study was conducted at a tertiary care teaching hospital in rural Andhra Pradesh. Patients with T2DM who fulfilled the inclusion and exclusion criteria and attending the outpatient clinic of the General Medicine department were the subjects of this study. The subjects with T2DM were categorized as depressed or non-depressed after administering the Patient Health Questionnare-9. Out of them 30 subjects with depression and 30 without depression were selected. Samples for blood were collected and analysed for glucose, urea, creatinine, lipid profile and glycated haemoglobin. Urine micro protein was estimated. Anthropometric measurements, blood pressure and chronic complications were recorded. Results The two groups were similar on most of the socio-demographic parameters, biochemical and many of the clinical parameters like age, waist circumference, glycated haemoglobin, lipid profile and insulin use. The Chi-square test for association between the categorical variables like use of insulin, gender predilection, exercise and complications with depression were not significant. Conclusion The study did not show any significant difference between the two groups in terms of the biochemical and clinical profile. PMID:27656433

  6. Synchronization in Biochemical Substance Exchange Between Two Cells

    NASA Astrophysics Data System (ADS)

    Mihailović, Dragutin T.; Balaž, Igor

    In this paper, Mihailović et al. [Mod. Phys. Lett. B 25 (2011) 2407-2417] introduce a simplified model of cell communication in a form of coupled difference logistic equations. Then we investigated stability of exchange of signaling molecules under variability of internal and external parameters. However, we have not touched questions about synchronization and effect of noise on biochemical substance exchange between cells. In this paper, we consider synchronization in intercellular exchange in dependence of environmental and cell intrinsic parameters by analyzing the largest Lyapunov exponent, cross sample entropy and bifurcation maps.

  7. Biochemical properties of ricin in immature castor seed.

    PubMed

    Chakravartula, Srinivas V S; Guttarla, Nagaraj

    2008-05-10

    The biochemical properties of ricin at different stages of seed i.e. from immature to mature seed were studied. Hemagglutination, SDS-PAGE and UV-spectrometry studies showed total absence of RCA protein in the immature seed. Interestingly, ricin extract on SDS-PAGE showed only one protein band with a molecular weight of 29,000 dalton corresponding to the molecular weight of A chain of ricin. Our results have shown that at immature seed level only the toxic moiety of ricin (A chain) is being synthesized first and gradually the RCA and B chain of ricin. PMID:18569697

  8. Biochemical and electrophysiological characteristics of mammalian GABA receptors.

    PubMed

    Enna, S J; Gallagher, J P

    1983-01-01

    The concept that GABA is a neurotransmitter in the mammalian CNS is supported by both electrophysiological and biochemical data. Whereas the electrophysiological studies are essential for demonstrating a specific functional response to GABA, the biochemical approach is useful for characterizing the molecular properties of this site. As a result of these studies the concept of the GABA receptor has progressed from a simple model of a single recognition site associated with a chloride channel to a more complex structure having a variety of interacting components. Thus, both electrophysiological and biochemical data support the existence of at least two pharmacologically distinct types of GABA receptors, based on the sensitivity to bicuculline. Also, anatomically, there appear to be two different types of receptors, those located postsynaptically on the soma or dendrites of a neighboring cell and those found presynaptically on GABAergic and other neurotransmitter terminals. From biochemical studies it appears that the GABA receptor may be composed of at least three distinct interacting components. One of these, the recognition site, may exist in two conformations, with one preferring agonists and the other having a higher affinity for antagonists. Ion channels may be considered a second component, with some of these regulating the passage of chloride ion, whereas others may be associated with calcium transport. The third major element of GABA receptors appears to be a benzodiazepine recognition site, although only a certain population of GABA receptors may be endowed with this property. In addition to these, the GABA receptor complex appears to contain substances that modulate the recognition site by influencing the availability of higher affinity binding proteins. It would appear therefore that changes affecting any one of these constituents can influence the characteristics of the others. While increasing the complexity of the system, this arrangement makes for a

  9. Morphological and biochemical characteristics of bacterial isolates degrading crude oil

    SciTech Connect

    Janiyani, K.L.; Wate, S.R.; Joshi, S.R. )

    1993-01-01

    A mixed bacterial culture developed by soil enrichment procedure using crude oil as a substrate was screened for individual bacterial species. Studies on morphological and biochemical characterization of eleven dominant bacterial isolates revealed that most of the cultures were gram-negative motile rods, and were catalase and oxidase positive. It was observed that four bacterial isolates were efficient in degrading pure hydrocarbons, model petroleum and crude oil. Identification of dominant bacterial cultures confirmed the isolates as Pseudomonas stutzeri, Pseudomonas aeruginoss, Bacillus cereus and Pseudomonas fluorescens. 28 refs., 8 tabs.

  10. Biochemical Effects of Ozone on Asthma During Postnatal Development

    PubMed Central

    Auten, Richard L.; Foster, W. Michael

    2011-01-01

    Background Ozone exposure during early life has the potential to contribute to the development of asthma as well as to exacerbate underlying allergic asthma. Scope of Review Developmentally regulated aspects of sensitivity to ozone exposure and downstream biochemical and cellular responses. Major Conclusions Developmental differences in antioxidant defense responses, respiratory physiology, and vulnerabilities to cellular injury during particular developmental stages all contribute to disparities in the health effects of ozone exposure between children and adults. General Significance Ozone exposure has the capacity to affect multiple aspects of the “effector arc” of airway hyperresponsiveness, ranging from initial epithelial damage and neural excitation to neural reprogramming during infancy. PMID:21276837

  11. Advances in Metabolic Engineering of Cyanobacteria for Photosynthetic Biochemical Production

    PubMed Central

    Lai, Martin C.; Lan, Ethan I.

    2015-01-01

    Engineering cyanobacteria into photosynthetic microbial cell factories for the production of biochemicals and biofuels is a promising approach toward sustainability. Cyanobacteria naturally grow on light and carbon dioxide, bypassing the need of fermentable plant biomass and arable land. By tapping into the central metabolism and rerouting carbon flux towards desirable compound production, cyanobacteria are engineered to directly convert CO2 into various chemicals. This review discusses the diversity of bioproducts synthesized by engineered cyanobacteria, the metabolic pathways used, and the current engineering strategies used for increasing their titers. PMID:26516923

  12. Laser induced fluorescence of biochemical for UV LIDAR application.

    PubMed

    Gupta, L; Sharma, R C; Razdan, A K; Maini, A K

    2014-05-01

    Laser induced fluorescence spectroscopy in the ultraviolet regime has been used for the detection of biochemical through a fiber coupled CCD detector from a distance of 2 m. The effect of concentration and laser excitation energy on the fluorescence spectra of nicotinamide adenine dinucleotide (NADH) has been investigated. The signature fluorescence peak of NADH was centred about 460 nm. At lower concentration Raman peak centred at 405 nm was also observed. The origin of this peak has been discussed. Detection limit with the proposed set up is found to be 1 ppm.

  13. [Correlation of some biochemical and coagulological parameters in carotid atherosclerosis].

    PubMed

    Akhvlediani, M V; Vorob'eva, E O; Emukhvari, M G; Sharashidze, N A; Kupreishvili, S B

    2009-11-01

    It has been established positive correlation of the degree of stenosis and intima-media thickness of carotid arteries with the following biochemical parameters: total cholesterol, LDL cholesterol, Apo-B, Lp(a), triglycerides, hs-C-reactive protein(CRP), interleukines (IL-1beta and IL-6), fibrinogen, D-dimers. Negative correlation was stated with respect to HDL cholesterol, Apo-A-1, protein C. Relation between the parameters of the blood lipid spectre, proteins and mediators of inflammation as well as those of hemostasis enables us to approach pathophysiological mechanisms of carotid atherosclerosis, define the processes of inflammation and atherosclerosis.

  14. Fibre optic system for biochemical and microbiological sensing

    NASA Astrophysics Data System (ADS)

    Penwill, L. A.; Slater, J. H.; Hayes, N. W.; Tremlett, C. J.

    2007-07-01

    This poster will discuss state-of-the-art fibre optic sensors based on evanescent wave technology emphasising chemophotonic sensors for biochemical reactions and microbe detection. Devices based on antibody specificity and unique DNA sequences will be described. The development of simple sensor devices with disposable single use sensor probes will be illustrated with a view to providing cost effective field based or point of care analysis of major themes such as hospital acquired infections or bioterrorism events. This presentation will discuss the nature and detection thresholds required, the optical detection techniques investigated, results of sensor trials and the potential for wider commercial application.

  15. Biochemical nature of cellulases from mutants of Trichoderma reesei

    SciTech Connect

    Montenecourt, B.S.; Kelleher, T.J.; Eveleigh, D.E.; Pettersson, L.G.

    1980-01-01

    The cellulases of two new mutants of T. reesei, RUT-NG14 and RUT-C30, have been examined with respect to the separation and biochemical characterization of the various components in the cellulase complex. The cellulase of both mutants has been shown to contain enhanced proportions of a cellobiohydrolase by quantitative immune precipitation. Application of ion-exchange high-pressure liquid chromatography protein separations affords a rapid (30 min) and simple method of separating and comparing cellulase components from potential high-yielding cellulase mutants.

  16. Advances in Metabolic Engineering of Cyanobacteria for Photosynthetic Biochemical Production.

    PubMed

    Lai, Martin C; Lan, Ethan I

    2015-01-01

    Engineering cyanobacteria into photosynthetic microbial cell factories for the production of biochemicals and biofuels is a promising approach toward sustainability. Cyanobacteria naturally grow on light and carbon dioxide, bypassing the need of fermentable plant biomass and arable land. By tapping into the central metabolism and rerouting carbon flux towards desirable compound production, cyanobacteria are engineered to directly convert CO₂ into various chemicals. This review discusses the diversity of bioproducts synthesized by engineered cyanobacteria, the metabolic pathways used, and the current engineering strategies used for increasing their titers. PMID:26516923

  17. Single-molecule detection: applications to ultrasensitive biochemical analysis

    NASA Astrophysics Data System (ADS)

    Castro, Alonso; Shera, E. Brooks

    1995-06-01

    Recent developments in laser-based detection of fluorescent molecules have made possible the implementation of very sensitive techniques for biochemical analysis. We present and discuss our experiments on the applications of our recently developed technique of single-molecule detection to the analysis of molecules of biological interest. These newly developed methods are capable of detecting and identifying biomolecules at the single-molecule level of sensitivity. In one case, identification is based on measuring fluorescence brightness from single molecules. In another, molecules are classified by determining their electrophoretic velocities.

  18. Parameter inference for biochemical systems that undergo a Hopf bifurcation.

    PubMed

    Kirk, Paul D W; Toni, Tina; Stumpf, Michael P H

    2008-07-01

    The increasingly widespread use of parametric mathematical models to describe biological systems means that the ability to infer model parameters is of great importance. In this study, we consider parameter inferability in nonlinear ordinary differential equation models that undergo a bifurcation, focusing on a simple but generic biochemical reaction model. We systematically investigate the shape of the likelihood function for the model's parameters, analyzing the changes that occur as the model undergoes a Hopf bifurcation. We demonstrate that there exists an intrinsic link between inference and the parameters' impact on the modeled system's dynamical stability, which we hope will motivate further research in this area.

  19. Biochemical and Hematological Evaluations of Bryonia Epigaea Tubers

    PubMed Central

    Sinha, B.N.; Sasmal, D.; Basu, S.P.

    1999-01-01

    Bryonia epigaea (cucurbitaceae) has been evaluated on various inflammatory models in rats in our laboratory. Ana anti-inflammatory drug(s) irrespective of its potency may not be devoid of undesirable effects on biochemical and hematological parameters. Alcoholic extract of Bryonia epigaaea (BE-Extract) at the dose of 50 mg/kg body weight, was administered to rats. Hepatotxic and nephrotoxic effects of BE-Extract were studies by measuring cholesterol, urea, uric acid, SGOT, SGPT and glucose levels in blood. Effects of BE-Extract on RBC count, WBC count, platelet count, hemoglobin content, clotting and bleeding time were also studied. PMID:22556913

  20. Rieger syndrome: a clinical, molecular, and biochemical analysis.

    PubMed

    Amendt, B A; Semina, E V; Alward, W L

    2000-10-01

    Rieger syndrome (RIEG 1; MIM 180500) is an autosomal dominant disorder of morphogenesis. It is a phenotypically heterogeneous disorder characterized by malformations of the eyes, teeth, and umbilicus. RIEG belongs to the Axenfeld-Rieger group of anomalies, which includes Axenfeld anomaly and Rieger anomaly (or Rieger eye malformation), which display ocular features only. Recently, mutations in the homeodomain transcription factor, PITX2, have been shown to be associated with Rieger syndrome. This review discusses the clinical manifestations of Rieger syndrome and how they correlate with the current molecular and biochemical studies on this human disorder. PMID:11092457

  1. Setbacks in blood substitutes research and development: a biochemical perspective.

    PubMed

    Alayash, Abdu I

    2010-06-01

    Recent setbacks in using Hb-based technology to develop oxygen carriers or blood substitutes may spur new and fundamentally different approaches for the development of a new generation of hemoglobin-based oxygen carriers (HBOCs). This article briefly details some underlying mechanisms that may have been responsible for the adverse-event profile associated with HBOCs, with a focus on the contribution of the author's laboratory toward identifying some of these biochemical pathways and some ways and means to control them. It is hoped that this will aid in the development of a safe and effective second generation of HBOCs.

  2. Laser induced fluorescence of biochemical for UV LIDAR application.

    PubMed

    Gupta, L; Sharma, R C; Razdan, A K; Maini, A K

    2014-05-01

    Laser induced fluorescence spectroscopy in the ultraviolet regime has been used for the detection of biochemical through a fiber coupled CCD detector from a distance of 2 m. The effect of concentration and laser excitation energy on the fluorescence spectra of nicotinamide adenine dinucleotide (NADH) has been investigated. The signature fluorescence peak of NADH was centred about 460 nm. At lower concentration Raman peak centred at 405 nm was also observed. The origin of this peak has been discussed. Detection limit with the proposed set up is found to be 1 ppm. PMID:24337816

  3. Biochemical and cultural characteristics of invasive Escherichia coli.

    PubMed Central

    Silva, R M; Toledo, M R; Trabulsi, L R

    1980-01-01

    The biochemical characteristics of 97 invasive Escherichia coli strains of different O serogroups were studied. Considered as a group, the behavior of the strains was quite variable. However, none of them decarboxylated lysine and all but seven strains, belonging to the O124 serogroup, were nonmotile. The growth of 25 strains obtained on MacConkey, salmonella-shigella, xylose-lysine-desoxycholate, and Hektoen enteric agars was compared. MacConkey and Hektoen enteric agars yielded the highest average growth for these strains, whereas salmonella-shigella agar had the lowest average counts. PMID:6991526

  4. Remote sensing of forest canopy and leaf biochemical contents

    NASA Technical Reports Server (NTRS)

    Peterson, David L.; Matson, Pamela A.; Card, Don H.; Aber, John D.; Wessman, Carol; Swanberg, Nancy; Spanner, Michael

    1988-01-01

    Recent research on the remote sensing of forest leaf and canopy biochemical contents suggests that the shortwave IR region contains this information; laboratory analyses of dry ground leaves have yielded reliable predictive relationships between both leaf nitrogen and lignin with near-IR spectra. Attention is given to the application of these laboratory techniques to a limited set of spectra from fresh, whole leaves of conifer species. The analysis of Airborne Imaging Spectrometer data reveals that total water content variations in deciduous forest canopies appear as overall shifts in the brightness of raw spectra.

  5. Biochemical analysis of the crude extract of Momordica charantia (L.).

    PubMed

    Dar, Ume Kalsoom; Owais, Farah; Ahmad, Manzoor; Rizwani, Ghazala H

    2014-11-01

    Momordica charantia (L.) commonly referred as bitter gourd, karela and balsam pear. Its fruit is used for the treatment of diabetes and related conditions amongst the indigenous populations of Asia, South America, India and East Africa. The study was conducted to find out the biochemical aspects of crude extract of whole fruit of M. charantia including seeds which includes blood test (Hemoglobin, RBC, Total leukocyte count, platelets count, HbA1C (Glycocylated heamoglobin Type A1C)), Lipid profile test and electrolyte balance. Hemoglobin (7.1±0.14), platelets count (827 ×109±1.95), Cholesterol level (111±2), HDL (high density lipoproteins) (20±1.22) at 10mg shows marked increase in values as compared to control. While 25 mg dose shows insignificant result. Electrolyte balance are found significant at 10mg and 25mg except bicarbonates (Na(+¬)=143±1.87, K-=3.45±0.35, Cl(-) =108±1.48). Another important property of M. charantia is the elevation of platelet counts, heamoglobin and specifically high-density lipoproteins (HDL). It also controls cholesterol, triglycerides, HDL, LDL and VLDL at low dosage (10mg). Further studies can be conducted to find out which phytochemical components acts on specific biochemical activity. PMID:26045386

  6. Investigation on energy conversion technology using biochemical reaction elements, 2

    NASA Astrophysics Data System (ADS)

    1994-03-01

    For measures taken for resource/energy and environmental issues, a study is made on utilization of microbial biochemical reaction. As a reaction system using chemical energy, cited is production of petroleum substitution substances and food/feed by CO2 fixation using hydrogen energy and hydrogen bacteria. As to photo energy utilization, regarded as promising are CO2 fixation using photo energy and microalgae, and production of hydrogen and useful carbon compound using photosynthetic organisms. As living organism/electric energy interconversion, cited is the culture of chemoautotrophic bacteria which fix CO2 using electric energy. For enhancing its conversion efficiency, it is important to develop a technology of gene manipulation of the bacteria and a system to use functional biochemical elements adaptable to the electrode reaction. With regard to utilization of the microorganism metabolic function, the paper presents emission of soluble nitrogen in the hydrosphere into the atmosphere using denitrifying bacteria, removal of phosphorus, reduction in environmental pollution caused by heavy metal dilute solutions, and recovery as resources, etc.

  7. The application of information theory to biochemical signaling systems

    PubMed Central

    Rhee, Alex; Cheong, Raymond; Levchenko, Andre

    2012-01-01

    Cell signaling can be thought of fundamentally as an information transmission problem in which chemical messengers relay information about the external environment to the decision centers within a cell. Due to the biochemical nature of cellular signal transduction networks, molecular noise will inevitably limit the fidelity of any messages received and processed by a cell’s signal transduction networks, leaving it with an imperfect impression of its environment. Fortunately, Shannon’s information theory provides a mathematical framework independent of network complexity that can quantify the amount of information that can be transmitted despite biochemical noise. In particular, the channel capacity can be used to measure the maximum number of stimuli a cell can distinguish based upon the noisy responses of its signaling systems. Here, we provide a primer for quantitative biologists that covers fundamental concepts of information theory, highlights several key considerations when experimentally measuring channel capacity, and describes successful examples of the application of information theoretic analysis to biological signaling. PMID:22872091

  8. DNA damaging and biochemical effects of potassium tetraborate

    PubMed Central

    Çelikezen, Fatih Çaglar; Turkez, Hasan; Togar, Basak; Izgi, Mehmet Sait

    2014-01-01

    Potassium tetraborate (PTB) is a product resulting from the controlled reaction of potassium hydroxide, water and boric acid (BA). It is used in many areas of industry such as disinfectant, detergent and treatment of contact lenses. PTB is one of the boron compounds which is most commonly used in many areas of industry although very limited information is available concerning its toxicity. Therefore, in this study, it is aimed to determine genetic and biochemical effects of PTB in human blood cell cultures (n=4). PTB was added into culture tubes at various concentrations (0-1280 µg/ml). Micronucleus (MN) and chromosomal aberration (CA) tests were performed for genotoxic damage influences estimation. In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative status (TOS) were examined to determine oxidative effects. The results indicated that all tested concentrations of PTB were found to be non-genotoxic. In addition, low concentrations (1.25, 2.5 and 5 µg/ml) of PTB caused increases of TAC levels. Furthermore, all concentrations of PTB were not changed the TOS levels in cultured human blood cells. Based on these results, in this study it has been reported for the first time that PTB is not genotoxic and it increases the antioxidant capacity in human peripheral blood lymphocytes. PMID:26417271

  9. Hepatic histological alterations and biochemical changes induced by sildenafil overdoses.

    PubMed

    Jarrar, Bashir Mahmoud; Almansour, Mansour Ibrahim

    2015-11-01

    Sildenafil is used for the treatment of erectile dysfunction and is helping millions of men around the world to achieve and maintain a long lasting erection. Fifty healthy male rabbits (Oryctolagus cuniculus) were used in the present study and exposed daily to sildenafil (0, 1, 3, 6, 9 mg/kg) for 5 days per week for 7 weeks to investigate the biochemical changes and alterations in the hepatic tissues induced by this drug overdosing. In comparison with respective control rabbits, sildenafil overdoses elevated significantly (p-value<0.05, ANOVA test) alanine aminotransferase (ALT), aspartate aminotransferase (AST), testosterone, follicular stimulating hormone and total protein, while creatinine and urea were lowered with no significant alteration was observed in uric acid and luteinizing hormone concentration. Also sildenafil provoked hepatocytes nuclear alterations, necrosis, hydropic degeneration, bile duct hyperplasia, Kupffer cells hyperplasia, inflammatory cells infiltration, hepatic vessels congestion and evident partial depletion of glycogen content. The results show that subchronic exposure to sildenafil overdoses exhibits significant biochemical and alterations in the hepatic tissues that might affect the functions of the liver and other vital organs. PMID:26639481

  10. Millisecond-Scale Biochemical Response to Change in Strain

    PubMed Central

    Bickham, Dale C.; West, Timothy G.; Webb, Martin R.; Woledge, Roger C.; Curtin, Nancy A.; Ferenczi, Michael A.

    2011-01-01

    Muscle fiber contraction involves the cyclical interaction of myosin cross-bridges with actin filaments, linked to hydrolysis of ATP that provides the required energy. We show here the relationship between cross-bridge states, force generation, and Pi release during ramp stretches of active mammalian skeletal muscle fibers at 20°C. The results show that force and Pi release respond quickly to the application of stretch: force rises rapidly, whereas the rate of Pi release decreases abruptly and remains low for the duration of the stretch. These measurements show that biochemical change on the millisecond timescale accompanies the mechanical and structural responses in active muscle fibers. A cross-bridge model is used to simulate the effect of stretch on the distribution of actomyosin cross-bridges, force, and Pi release, with explicit inclusion of ATP, ADP, and Pi in the biochemical states and length-dependence of transitions. In the simulation, stretch causes rapid detachment and reattachment of cross-bridges without release of Pi or ATP hydrolysis. PMID:22098743

  11. Characterizing autism spectrum disorders by key biochemical pathways

    PubMed Central

    Subramanian, Megha; Timmerman, Christina K.; Schwartz, Joshua L.; Pham, Daniel L.; Meffert, Mollie K.

    2015-01-01

    The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions. PMID:26483618

  12. How spatial heterogeneity shapes multiscale biochemical reaction network dynamics.

    PubMed

    Pfaffelhuber, Peter; Popovic, Lea

    2015-03-01

    Spatial heterogeneity in cells can be modelled using distinct compartments connected by molecular movement between them. In addition to movement, changes in the amount of molecules are due to biochemical reactions within compartments, often such that some molecular types fluctuate on a slower timescale than others. It is natural to ask the following questions: how sensitive is the dynamics of molecular types to their own spatial distribution, and how sensitive are they to the distribution of others? What conditions lead to effective homogeneity in biochemical dynamics despite heterogeneity in molecular distribution? What kind of spatial distribution is optimal from the point of view of some downstream product? Within a spatially heterogeneous multiscale model, we consider two notions of dynamical homogeneity (full homogeneity and homogeneity for the fast subsystem), and consider their implications under different timescales for the motility of molecules between compartments. We derive rigorous results for their dynamics and long-term behaviour, and illustrate them with examples of a shared pathway, Michaelis-Menten enzymatic kinetics and autoregulating feedbacks. Using stochastic averaging of fast fluctuations to their quasi-steady-state distribution, we obtain simple analytic results that significantly reduce the complexity and expedite simulation of stochastic compartment models of chemical reactions.

  13. Applications of biochemical processes in geothermal and other industries

    SciTech Connect

    Premuzic, E.T.; Lin, M.S.; Jin, J.Z.

    1994-06-01

    Laboratory studies aimed at the development of economically and technically feasible, and environmentally acceptable technology for the disposal of geothermal sludges and wastes have led to the development of biochemical processes which meet the above conditions. A pilot-scale plant has been constructed and used to identify process variables and optimize processing conditions. The total process is flexible and can be used in several modes of operation which include (1) solubilization and removal of many metals, including radionuclides, from brines and sludges; (2) selective removal of a few metals; (3) concentration of metals; (4) recovery of metals; and (5) recovery of salts. The end product is a silica-type material which meets regulatory requirements, while the aqueous phase meets drinking water standards and can be reinjected and/or used for irrigation. Preliminary engineering studies of the metal and salt recovery technologies have indicated that significant cost benefits could be obtained by means of combined processing. Recent accomplishments in the development of new biochemical technologies will be discussed in this paper.

  14. In vitro reparative dentin: a biochemical and morphological study.

    PubMed

    Teti, G; Salvatore, V; Ruggeri, A; Manzoli, L; Gesi, M; Orsini, G; Falconi, M

    2013-08-06

    In this study, starting from human dental pulp cells cultured in vitro, we simulated reparative dentinogenesis using a medium supplemented with different odontogenic inductors. The differentiation of dental pulp cells in odontoblast-like cells was evaluated by means of staining, and ultramorphological, biochemical and biomolecular methods. Alizarin red staining showed mineral deposition while transmission electron microscopy revealed a synthesis of extracellular matrix fibers during the differentiation process. Biochemical assays demonstrated that the differentiated phenotype expressed odontoblast markers, such as Dentin Matrix Protein 1 (DMP1) and Dentin Sialoprotein (DSP), as well as type I collagen. Quantitative data regarding the mRNA expression of DMP1, DSP and type I collagen were obtained by Real Time PCR. Immunofluorescence data demonstrated the various localizations of DSP and DMP1 during odontoblast differentiation. Based on our results, we obtained odontoblast-like cells which simulated the reparative dentin processes in order to better investigate the mechanism of odontoblast differentiation, and dentin extracellular matrix deposition and mineralization.

  15. Biochemical and functional characterization of Helicobacter pylori vesicles

    PubMed Central

    Olofsson, Annelie; Vallström, Anna; Petzold, Katja; Tegtmeyer, Nicole; Schleucher, Jürgen; Carlsson, Sven; Haas, Rainer; Backert, Steffen; Wai, Sun Nyunt; Gröbner, Gerhard; Arnqvist, Anna

    2010-01-01

    Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor to the vigour of infection and resulting virulence. H. pylori adheres primarily via binding of BabA adhesins to ABO/Lewis b (Leb) blood group antigens and the binding of SabA adhesins to sialyl-Lewis x/a (sLex/a) antigens. Similar to most Gram-negative bacteria, H. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often include virulence-associated factors. Here we biochemically characterized highly purified H. pylori vesicles. Major protein and phospholipid components associated with the vesicles were identified with mass spectroscopy and nuclear magnetic resonance. A subset of virulence factors present was confirmed by immunoblots. Additional functional and biochemical analysis focused on the vesicle BabA and SabA adhesins and their respective interactions to human gastric epithelium. Vesicles exhibit heterogeneity in their protein composition, which were specifically studied in respect to the BabA adhesin. We also demonstrate that the oncoprotein, CagA, is associated with the surface of H. pylori vesicles. Thus, we have explored mechanisms for intimate H. pylori vesicle–host interactions and found that the vesicles carry effector-promoting properties that are important to disease development. PMID:20659286

  16. Transient amplification limits noise suppression in biochemical networks

    NASA Astrophysics Data System (ADS)

    Dixon, John; Lindemann, Anika; McCoy, Jonathan H.

    2016-01-01

    Cell physiology is orchestrated, on a molecular level, through complex networks of biochemical reactions. The propagation of random fluctuations through these networks can significantly impact cell behavior, raising challenging questions about how network design shapes the cell's ability to suppress or exploit these fluctuations. Here, drawing on insights from statistical physics, fluid dynamics, and systems biology, we explore how transient amplification phenomena arising from network connectivity naturally limit a biochemical system's ability to suppress small fluctuations around steady-state behaviors. We find that even a simple system consisting of two variables linked by a single interaction is capable of amplifying small fluctuations orders of magnitude beyond the levels predicted by linear stability theory. We also find that adding additional interactions can promote further amplification, even when these interactions implement classic design strategies known to suppress fluctuations. These results establish that transient amplification is an essential factor determining baseline noise levels in stable intracellular networks. Significantly, our analysis is not bound to specific systems or interaction mechanisms: we find that noise amplification is an emergent phenomenon found near steady states in any network containing sufficiently strong interactions, regardless of its form or function.

  17. SERI Biochemical Conversion Program: FY 1986, annual report

    SciTech Connect

    Not Available

    1987-09-01

    The Biochemical Conversion Program is mission oriented; effort is concentrated on technologies that appear to have the greatest potential for being adopted by the private sector to economically convert lignocellulosic materials into high-value liquid transportation fuels, particularly ethanol. The goal of the program is to develop the technology base for the biochemical conversion of these renewable lignocellulosic resources into fuels. The program is structured to supply the technology for such fuels to compete economically first as an octane booster or fuel additive, and, with additional improvements, as a neat fuel. The objectives of the program are to improve the pretreatment, hydrolysis, and bioconversion processes through research so that ethanol can be produced economically from lignocellulosic biomass; develop technologies to convert the underutilized portions of the lignocellulosic feedstock (xylan and lignin) to high-value liquid transportation fuels; evaluate the performance of the emerging process technologies in the smallest possible scale integrated experiment to assess their readiness for scaleup and to better define research needs; and to transfer the technology to the private sector for rapid commercialization by involving industry in the research process at the earliest possible time.

  18. The human sunburn reaction: histologic and biochemical studies

    SciTech Connect

    Gilchrest, B.A.; Soter, N.A.; Stoff, J.S.; Mihm, M.C. Jr.

    1981-01-01

    The ultraviolet-induced erythema reaction was investigated histologically and biochemically in four subjects, utilizing suction blister aspirates, analyzed for histamine and prostaglandin E2 (PGE2), and Epon-embedded 1-mu skin biopsy sections from control skin and from irradiated skin at intervals for 72 hours after exposure to a Hanovia lamp. Major histologic alterations in the epidermis included dyskeratotic and vacuolated keratinocytes (sunburn cells), and disappearance of Langerhans cells. In the dermis the major changes were vascular, involving both the superficial and deep venular plexuses. Endothelial cell enlargement was first apparent within 30 minutes of irradiation, peaked at 24 hours, and persisted throughout the 72-hour study period. Mast cell degranulation and associated perivenular edema were first apparent at 1 hour and striking at the onset of erythema, 3 to 4 hours postirradiation; edema was absent and mast cells were again normal in number and granule content at 24 hours. Histamine levels rose approximately fourfold above control values immediately after the onset of erythema and returned to baseline within 24 hours. PGE2 levels were statistically elevated even before the onset of erythema and reached approximately 150% of the control value at 24 hours. These data provide the first evidence that histamine may mediate the early phase of the human sunburn reaction and increase our understanding of its complex histologic and biochemical sequelae.

  19. Structure and Biochemical Activities of Escherichia coli MgsA

    SciTech Connect

    Page, Asher N.; George, Nicholas P.; Marceau, Aimee H.; Cox, Michael M.; Keck, James L.

    2012-02-27

    Bacterial 'maintenance of genome stability protein A' (MgsA) and related eukaryotic enzymes play important roles in cellular responses to stalled DNA replication processes. Sequence information identifies MgsA enzymes as members of the clamp loader clade of AAA{sup +} proteins, but structural information defining the family has been limited. Here, the x-ray crystal structure of Escherichia coli MgsA is described, revealing a homotetrameric arrangement for the protein that distinguishes it from other clamp loader clade AAA{sup +} proteins. Each MgsA protomer is composed of three elements as follows: ATP-binding and helical lid domains (conserved among AAA{sup +} proteins) and a tetramerization domain. Although the tetramerization domains bury the greatest amount of surface area in the MgsA oligomer, each of the domains participates in oligomerization to form a highly intertwined quaternary structure. Phosphate is bound at each AAA{sup +} ATP-binding site, but the active sites do not appear to be in a catalytically competent conformation due to displacement of Arg finger residues. E. coli MgsA is also shown to form a complex with the single-stranded DNA-binding protein through co-purification and biochemical studies. MgsA DNA-dependent ATPase activity is inhibited by single-stranded DNA-binding protein. Together, these structural and biochemical observations provide insights into the mechanisms of MgsA family AAA{sup +} proteins.

  20. The propagation approach for computing biochemical reaction networks.

    PubMed

    Henzinger, Thomas A; Mateescu, Maria

    2013-01-01

    We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its next operator propagates mass values through this set of nodes. We propose an approximate implementation of the next operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.

  1. Drug resistance and biochemical characteristics of Salmonella from turkeys.

    PubMed Central

    Poppe, C; Kolar, J J; Demczuk, W H; Harris, J E

    1995-01-01

    A study was conducted to determine the antibiotic resistance and biochemical characteristics of 2690 Salmonella strains belonging to 52 serovars and isolated from environmental and feed samples from 270 turkey flocks in Canada. Resistance of the Salmonella strains to the aminoglycoside antibiotics varied widely; none of the strains were resistant to amikacin, 14.2% were resistant to neomycin, 25.8% were resistant to gentamicin, and 27.7% of the strains were resistant to kanamycin. Most strains (97.6%) were resistant to the aminocyclitol, spectinomycin. Regarding resistance to the beta-lactam antibiotics, 14.3% and 14.4% of the strains were resistant to ampicillin and carbenicillin, respectively, whereas only 5 (0.2%) of the strains were resistant to cephalothin. None of the strains were resistant to the fluoroquinolone ciprofloxacin or to polymyxin B. Resistance to chloramphenicol and nitrofurantoin was found in 2.4% and 7% of the strains, respectively. Only 1.7% of the strains were resistant to the trimethoprimsulfamethoxazole combination, whereas 58.1% were resistant to sulfisoxazole. Thirty-eight percent of the strains were resistant to tetracycline. Salmonella serovars differed markedly in their drug resistance profiles. Biochemical characterization of the Salmonella showed that the S. anatum, S. saintpaul and S. reading serovars could be divided into distinct biotypes. PMID:8548684

  2. Biochemical and pathogenic properties of Shewanella alga and Shewanella putrefaciens.

    PubMed

    Khashe, S; Janda, J M

    1998-03-01

    We characterized 49 strains of Shewanella spp. from clinical (n = 31) and nonhuman (n = 18) sources. Most Shewanella alga organisms (Gilardi biovar 2; Centers for Disease Control and Prevention [CDC] biotype 2) originated from clinical material (92%), failed to produce acid from carbohydrates other than D-ribose, and were biochemically and enzymatically fairly homogeneous. In contrast, Shewanella putrefaciens organisms (Gilardi biovars 1 and 3; CDC biotype 1) were more often associated with nonhuman sources (70%), were able to utilize a number of sugars (sucrose, L-arabinose, and maltose), and were found to exhibit wider variations in biochemical characteristics; three biotypes within S. putrefaciens were detected. Notable differences between the two species in enzymatic activity, determined with the API-ZYM system (bioMérieux, Hazelwood, Mo.), and cellular fatty acid profiles, determined by the MIDI system (Microbial ID Inc., Newark, Del.), were also detected. Pathogenicity studies of mice indicate that S. alga appears to be the more virulent species, possibly due to the production of a hemolytic substance.

  3. Biochemical oxygen demand sensor using Serratia marcescens LSY 4.

    PubMed

    Kim, M N; Kwon, H S

    1999-01-01

    A microbial biochemical oxygen demand (BOD) sensor consisting of Serratia marcescens LSY 4 and an oxygen electrode was prepared for estimation of the biochemical oxygen demand. The response of the BOD sensor was insensitive to pH in the range of pH 6.0-8.0, and the baseline drift of the signal was nearly absent even in unbuffered aqueous solution. Because heavy metal ions were precipitated from the phosphate buffer solution, unbuffered solution was used to investigate the effect of the concentration of heavy metal ions on the sensor response. Contrary to previous studies, not only Cu2+ and Ag+ but also Cd2+ and Zn2+ significantly decreased the response of the BOD sensor in unbuffered solution. Graft polymerization of sodium styrene sulfonate on the surface of the porous teflon membrane was carried out to absorb the heavy metal ions permeating through the membrane. Tolerance against Zn2+ was induced for S. marcescens LSY 4 to make the cells less sensitive to the presence of heavy metal ions. The membrane modification and the Zn2+ tolerance induction showed some positive effects in such a way that they reduced the inhibitory effects of Zn2+ and Cd2+ on the sensitivity of the BOD sensor. However, they had no effect on the protection of the cells against the interference of Cu2+ and Ag+ on the performance of the sensor.

  4. Biochemical Effects of Technetium-99-Pertechnetate on Microorganisms 1

    PubMed Central

    Gearing, Patrick; Van Baalen, Chase; Parker, Patrick L.

    1975-01-01

    The biochemical effects of technetium-99 as pertechnetate (TcO4−) were investigated in a variety of microorganisms (a nonsulfur purple bacterium, five blue-green algae, a protozoan, a diatom, two heterotrophic bacteria, a red alga and two green algae). Sensitivity to pertechnetate as measured by growth ranged from marked inhibition at 1 μg Tc/ml (nonsulfur purple bacterium) to no effect at 600 μg Tc ml (both green algae). No correlation between organism type and growth susceptibility to pertechnetate was apparent. The blue-green alga, Agmenellum quadruplicatum strain PR-6, bound technetium-99 to a level of 3 μg/mg dry weight cells (from medium containing 1.5 mm pertechnetate) in the light, but little or none in the dark; cell death occurred only with uptake. Addition of TcO4− to the medium caused a rapid but temporary increase in ATP levels of PR-6 (in the light only) and Tetrahymena pyriformis strain WH14. Respiration of organisms WH14 and Bacillus subtilis and photosynthesis of organism PR-6 were immediately slowed by the introduction of pertechnetate. Technetium as pertechnetate has a possible biochemical effect on cells, unrelated to its radioactivity or to a general oxidation effect. PMID:16659059

  5. Coarse-graining stochastic biochemical networks: adiabaticity and fast simulations

    SciTech Connect

    Nemenman, Ilya; Sinitsyn, Nikolai; Hengartner, Nick

    2008-01-01

    We propose a universal approach for analysis and fast simulations of stiff stochastic biochemical kinetics networks, which rests on elimination of fast chemical species without a loss of information about mesoscoplc, non-Poissonian fluctuations of the slow ones. Our approach, which is similar to the Born-Oppenhelmer approximation in quantum mechanics, follows from the stochastic path Integral representation of the cumulant generating function of reaction events. In applications with a small number of chemIcal reactions, It produces analytical expressions for cumulants of chemical fluxes between the slow variables. This allows for a low-dimensional, Interpretable representation and can be used for coarse-grained numerical simulation schemes with a small computational complexity and yet high accuracy. As an example, we derive the coarse-grained description for a chain of biochemical reactions, and show that the coarse-grained and the microscopic simulations are in an agreement, but the coarse-gralned simulations are three orders of magnitude faster.

  6. Biochemical composition of three species of unionid mussels after emersion

    USGS Publications Warehouse

    Greseth, Shari L.; Cope, W.G.; Rada, R.G.; Waller, D.L.; Bartsch, M.R.

    2003-01-01

    Freshwater mussels are emersed (exposed to air) during conservation activities such as surveys and relocations. Success of these activities depends upon the ability of mussels to survive emersion and to re-burrow in the substratum. We evaluated the acute sublethal effects of emersion on three species of unionid mussels [pocketbook, Lampsilis cardium (Rafinesque, 1820); pimpleback, Quadrula pustulosa pustulosa (I. Lea, 1831); spike, Elliptio dilatata (Rafinesque, 1820)] by measuring three biochemicals (carbohydrate, lipid, protein) indicative of biochemical function and energy storage. Mussels were acclimated in water at 25??C and exposed to five air temperatures (15, 20, 25, 35 and 45??C) for 15, 30 and 60 min. After emersion, mussels were returned to water at 25??C and observed for 14 days. Samples of mantle tissue were taken after the 14-day postexposure period and analysed for carbohydrate, lipid and protein. Three-way analysis of variance (ANOVA) did not reveal consistent trends in carbohydrate, lipid or protein concentrations due to sex of mussels, duration of emersion, air temperature or their interaction terms that indicated biological compensation to stress. Overall mean carbohydrate concentrations were greatest (range 447-615 mg/g dry wt) among the species, followed by protein (179-289 mg/g dry wt) and lipids (26.7-38.1 mg/g dry wt). These results have positive implications for conducting conservation activities, because emersion over the range of temperatures (15-35??C) and durations (15-60 min) examined did not appear acutely harmful to mussels.

  7. Specificity and completion time distributions of biochemical processes

    SciTech Connect

    Munsky, Brian; Nemenman, Ilya; Bel, Golan

    2009-01-01

    In order to produce specific complex structures from a large set of similar biochemical building blocks, many biochemical systems require high sensitivity to small molecular differences. The first and most common mqdel used to explain this high specificity is kinetic proofreading, which has been extended to a variety of systems from detection of DNA mismatch to cell signaling processes. While the specification properties of the kinetic proofreading model are well known and were studied in various contexts, very little is known about its temporal behavior. In this work, we study the dynamical properties of discrete stochastic two-branch kinetic proofreading schemes. Using the Laplace transform of the corresponding chemical master equation, we obtain an analytical solution for the completion time distribution. In particular we provide expressions for the specificity and the mean and the variance of the process completion times. We also show that, for a wide range of parameters a process distinguishing between two different products can be reduced to a much simpler three point process. Our results allow for the systematic study of the interplay between specificity and completion times as well as testing the validity of the kinetic proofreading model in biological systems.

  8. [INVITED] Tilted fiber grating mechanical and biochemical sensors

    NASA Astrophysics Data System (ADS)

    Guo, Tuan; Liu, Fu; Guan, Bai-Ou; Albert, Jacques

    2016-04-01

    The tilted fiber Bragg grating (TFBG) is a new kind of fiber-optic sensor that possesses all the advantages of well-established Bragg grating technology in addition to being able to excite cladding modes resonantly. This device opens up a multitude of opportunities for single-point sensing in hard-to-reach spaces with very controllable cross-sensitivities, absolute and relative measurements of various parameters, and an extreme sensitivity to materials external to the fiber without requiring the fiber to be etched or tapered. Over the past five years, our research group has been developing multimodal fiber-optic sensors based on TFBG in various shapes and forms, always keeping the device itself simple to fabricate and compatible with low-cost manufacturing. This paper presents a brief review of the principle, fabrication, characterization, and implementation of TFBGs, followed by our progress in TFBG sensors for mechanical and biochemical applications, including one-dimensional TFBG vibroscopes, accelerometers and micro-displacement sensors; two-dimensional TFBG vector vibroscopes and vector rotation sensors; reflective TFBG refractometers with in-fiber and fiber-to-fiber configurations; polarimetric and plasmonic TFBG biochemical sensors for in-situ detection of cell, protein and glucose.

  9. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration

    PubMed Central

    Calve, Sarah; Simon, Hans-Georg

    2012-01-01

    During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and fibronectin controls muscle cell behavior in vivo and in vitro. However, the influence of extracellular matrix (ECM) remodeling on tissue stiffness and the cellular response to mechanical variations during regeneration was unknown. By measuring the transverse stiffness of tissues in situ, we found undifferentiated regenerative blastemas were less stiff than differentiated stump muscle (13.3±1.6 vs. 16.6±1.2 kPa). To directly determine how ECM and stiffness combine to affect skeletal muscle fragmentation, migration, and fusion, we coated silicone-based substrates ranging from 2 to 100 kPa with matrices representative of transitional (tenascin-C and fibronectin) and differentiated environments (laminin and Matrigel). Using live-cell imaging, we found softer tenascin-C-coated substrates significantly enhanced migration and fragmentation of primary newt muscle cells. In contrast, stiffer substrates coated with laminin, Matrigel, or fibronectin increased differentiation while suppressing migration and fragmentation. These data support our in vivo observations that a transitional matrix of reduced stiffness regulates muscle plasticity and progenitor cell recruitment into the regenerative blastema. These new findings will enable the determination of how biochemical and mechanical cues from the ECM control genetic pathways that drive regeneration.—Calve, S., Simon, H.-G. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration. PMID:22415307

  10. IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN). Recommendations for nomenclature and tables in biochemical thermodynamics. Recommendations 1994.

    PubMed

    Alberty, R A

    1996-08-15

    Chemical equations are written in terms of specific ionic and elemental species and balance elements and charge, whereas biochemical equations are written in terms of reactants that often consist of species in equilibrium with each other and do not balance elements that are assumed fixed such as hydrogen at constant pH. Both kinds of reaction equations are needed in biochemistry. When the pH and the free concentrations of certain metal ions are specified, the apparent equilibrium constant K' for a biochemical reaction is written in terms of sums of species and can be used to calculate a standard transformed Gibbs energy of reaction deltarG'o. Transformed thermodynamic properties can be calculated directly from conventional thermodynamic properties of species. Calorimetry or the dependence of K' on temperature can be used to obtain the standard transformed enthalpy of reaction deltarH'o. Standard transformed Gibbs energies of formation deltafG'o(i) and standard transformed enthalpies of formation deltafH'o(i) for reactants (sums of species) can be calculated at various T, pH, pMg, and ionic strength (I) if sufficient information about the chemical reactions involved is available. These quantities can also be calculated from measurement if K' for a number of reactions under the desired conditions. Tables can be used to calculate deltafG'o and deltarH'o for many more reactions.

  11. Posttraumatic knee osteoarthritis following anterior cruciate ligament injury: Potential biochemical mediators of degenerative alteration and specific biochemical markers

    PubMed Central

    LI, HONG; CHEN, CHEN; CHEN, SHIYI

    2015-01-01

    As a common injury, anterior cruciate ligament (ACL) injury is unable to heal itself naturally, which possibly increases knee instability, accelerates the risk of joint degeneration and leads to knee osteoarthritis (OA) in the ACL-injured knee. Thus, ACL reconstruction using an autograft or allograft tendon is proposed to maintain the biomechanical stability of the knee joint. However, previous studies demonstrate that surgical management of ACL reconstruction failed to abrogate the development of OA completely, indicating that biochemical disturbance is responsible for the osteoarthritic changes observed following ACL injury. Inflammatory mediators are elevated subsequent to ACL injury or rupture, inducing matrix metalloproteinase production, proteoglycan degradation, collagen destruction, chondrocyte necrosis and lubricin loss. These potential biochemical mediators may aid in the development of effective biological management to reduce the onset of future posttraumatic OA. Furthermore, during the degenerative process of cartilage, there are a number of cartilage-specific biomarkers, which play a critical step in the loss of structural and functional integrity of cartilage. The present review illustrates several specific biomarkers in the ACL-injured knee joint, which may provide effective diagnostic and prognostic tools for investigating cartilage degenerative progression and future posttraumatic OA of ACL-injured patients. PMID:25798238

  12. Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase

    PubMed Central

    Lazarus, Hilary

    2016-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the Km of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.

  13. Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase

    PubMed Central

    Lazarus, Hilary

    2016-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the Km of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target. PMID:27631026

  14. Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase.

    PubMed

    Adedeji, Adeyemi O; Lazarus, Hilary

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5'-to-3' direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the Km of ATP for M-nsp13 is inversely proportional to the length of the 5' loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5' loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target. PMID:27631026

  15. Biochemical Mechanisms Controlling Terminal Electron Transfer in Geobacter sulfurreducens

    NASA Astrophysics Data System (ADS)

    Helmus, R.; Liermann, L. J.; Brantley, S. L.; Tien, M.

    2009-04-01

    The ability of Geobacter sulfurreducens to use a variety of metals as terminal electron acceptors (TEAs) for cellular respiration makes it attractive for use in bioremediation and implies its importance to mineral cycling in the environment. This study is aimed at understanding the biochemical mechanisms that allow Geobacter sulfurreducens to use soluble and insoluble iron and manganese forms as TEAs for cellular respiration and is the first of its kind to address the kinetics of manganese use as a TEA by G. sulfurreducens. First, G. sulfurreducens was conditioned to grow on various soluble and insoluble iron and manganese forms. G. sulfurreducens demonstrated enhanced growth rates when cultured using soluble TEAs compared with insoluble TEAs. However, the lower growth rate on insoluble iron compared with soluble iron was observed concomitantly with a 1-2 log lower cell density in stationary phase in insoluble iron cultures and a lower growth yield per electron donor used in log growth phase. Furthermore, the growth yield per electron was similar with both soluble and insoluble iron. These results suggest that the net amount of energy available for biomass production achieved from reducing insoluble iron is lower than with soluble iron, which may be due to a different biochemical mechanism catalyzing the electron transfer to TEA dependent upon the solubility of the TEA. One scenario consistent with this notion is that protein(s) in the outer membrane of G. sulfurreducens that transfers electrons to insoluble TEAs does so in a manner that uncouples electron flow from the proton pump in the cellular membrane, similar to what we have observed with Shewanella oneidensis MR-1. Both the growth rate and growth yield of G. sulfurreducens on insoluble manganese were higher than on insoluble iron, indicating that there is a difference in the flow of electrons to the TEA in these two situations. While the different redox potentials of these elements may affect these values

  16. Using Fermentation and Catalysis to Make Fuels and Products: Biochemical Conversion

    SciTech Connect

    2010-09-01

    Information about the Biomass Program's collaborative projects to improve processing routes for biochemical conversion, which entails breaking down biomass to make the carbohydrates available for conversion into sugars.

  17. Biochemical and histochemical studies of the sarcocyst of Sarcocystis fusiformis of buffalo Bubalus bubalis.

    PubMed

    Chaudhry, R K; Kushwah, H S; Shah, H L

    1986-10-01

    The glycogen content and activities of alkaline and acid phosphatases of sarcocysts of Sarcocystis fusiformis from naturally infected Indian water buffalo (Bubalus bubalis) were determined biochemically and histochemically.

  18. Structural and biochemical analysis of a bacterial glycosyltransferase

    PubMed Central

    Zhu, Fan; Wu, Ren; Zhang, Hua; Wu, Hui

    2014-01-01

    Summary Glycosyltransferases (GTs) are a large family of enzymes that specifically transfer sugar moieties to a diverse range of substrates. The process of bacterial glycosylation (such as biosynthesis of glycolipids, glycoproteins, and polysaccharides) has been studied extensively, yet the majority of GTs involved remains poorly characterized. Besides predicting enzymatic parameters of GTs, the resolution of three-dimensional structures of GTs can help to determine activity, donor sugar binding, and acceptor substrate binding sites. It also facilitates amino acid sequence-based structural modeling and biochemical characterization of their homologues. Here we describe a general procedure to accomplish expression and purification of soluble and active recombinant GTs. Enzymatic characterization, and crystallization of GTs, and data refinement for structural analysis are also covered in this protocol. PMID:23765651

  19. A biochemical and genetic study of Leishmania donovani pyruvate kinase.

    PubMed

    Sandoval, Will; Isea, Raúl; Rodriguez, Evelyn; Ramirez, Jose Luis

    2008-11-15

    Here we present a biochemical and molecular biology study of the enzyme pyruvate kinase (PYK) from the parasitic protozoa Leishmania donovani. The PYK gene was cloned, mutagenised and over expressed and its kinetic parameters determined. Like in other kinetoplastids, L. donovani PYK is allosterically stimulated by the effector fructose 2,6 biphosphate and not by fructose 1,6 biphosphate. When the putative effector binding site of L. donovani PYK was mutagenised, we obtained two mutants with extreme kinetic behavior: Lys453Leu, which retained a sigmoidal kinetics and was little affected by the effector; and His480Gln, which deployed a hyperbolic kinetics that was not changed by the addition of the effector. Molecular Dynamics (MD) studies revealed that the mutations not only altered the effector binding site of L. donovani PYK but also changed the folding of its domain C. PMID:18725273

  20. A general method for modeling biochemical and biomedical response

    NASA Astrophysics Data System (ADS)

    Ortiz, Roberto; Lerd Ng, Jia; Hughes, Tyler; Abou Ghantous, Michel; Bouhali, Othmane; Arredouani, Abdelilah; Allen, Roland

    2012-10-01

    The impressive achievements of biomedical science have come mostly from experimental research with human subjects, animal models, and sophisticated laboratory techniques. Additionally, theoretical chemistry has been a major aid in designing new drugs. Here we introduce a method which is similar to others already well known in theoretical systems biology, but which specifically addresses biochemical changes as the human body responds to medical interventions. It is common in systems biology to use first-order differential equations to model the time evolution of various chemical concentrations, and we as physicists can make a significant impact through designing realistic models and then solving the resulting equations. Biomedical research is rapidly advancing, and the technique presented in this talk can be applied in arbitrarily large models containing tens, hundreds, or even thousands of interacting species, to determine what beneficial effects and side effects may result from pharmaceuticals or other medical interventions.