Science.gov

Sample records for causality chemically induced

  1. Causality

    NASA Astrophysics Data System (ADS)

    Pearl, Judea

    2000-03-01

    Written by one of the pre-eminent researchers in the field, this book provides a comprehensive exposition of modern analysis of causation. It shows how causality has grown from a nebulous concept into a mathematical theory with significant applications in the fields of statistics, artificial intelligence, philosophy, cognitive science, and the health and social sciences. Pearl presents a unified account of the probabilistic, manipulative, counterfactual and structural approaches to causation, and devises simple mathematical tools for analyzing the relationships between causal connections, statistical associations, actions and observations. The book will open the way for including causal analysis in the standard curriculum of statistics, artifical intelligence, business, epidemiology, social science and economics. Students in these areas will find natural models, simple identification procedures, and precise mathematical definitions of causal concepts that traditional texts have tended to evade or make unduly complicated. This book will be of interest to professionals and students in a wide variety of fields. Anyone who wishes to elucidate meaningful relationships from data, predict effects of actions and policies, assess explanations of reported events, or form theories of causal understanding and causal speech will find this book stimulating and invaluable.

  2. Advances in forensic toxicology for establishing causality between Great Lakes epizootics and specific persistent toxic chemicals

    SciTech Connect

    Gilbertson, M.

    1997-09-01

    Populations of fish, wildlife, and humans in the Great Lakes basin have been injured during this century by exposures to organochlorine pollutants such as PCBs and dioxin. The evidence presented by scientists working on these outbreaks of chemically induced disease has been received with skepticism among officials, who have expressed a desire for a proven cause and effect before further costly regulatory and remedial action is taken. Scientists have adapted epidemiological criteria to infer causal relationships between the injury and exposures to specific chemicals. These forensic statements are different from traditional toxicological statements about potential effects. There is a priority need to institutionalize this methodology within governments to complement established risk assessment techniques.

  3. Chemical-Induced Vitiligo.

    PubMed

    Harris, John E

    2017-04-01

    Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. Because chemical-induced depigmentation is clinically and histologically indistinguishable from nonchemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as "chemical-induced vitiligo," rather than less accurate terms that have been previously used. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Chemical-gene interaction networks and causal reasoning for ...

    EPA Pesticide Factsheets

    Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrate chemical monitoring and biological effects data to evaluate risks associated with chemicals present in the environment. Here, we used prior knowledge about chemical-gene interactions to develop a knowledge assembly model for detected chemicals at five locations near the North Branch and Chisago wastewater treatment plants (WWTP) in the St. Croix River Basin, MN and WI. The assembly model was used to generate hypotheses about the biological impacts of the chemicals at each location. The hypotheses were tested using empirical hepatic gene expression data from fathead minnows exposed for 12 d at each location. Empirical gene expression data were also mapped to the assembly models to evaluate the likelihood of a chemical contributing to the observed biological responses using richness and concordance statistics. The prior knowledge approach was able predict the observed biological pathways impacted at one site but not the other. Atrazine was identified as a potential contributor to the observed gene expression responses at a location upstream of the North Branch WTTP. Four chemicals were identified as contributors to the observed biological responses at the effluent and downstream o

  5. The AOP framework and causality: Meeting chemical risk ...

    EPA Pesticide Factsheets

    Chemical safety assessments are expanding from a focus on a few chemicals (or chemical mixtures) to the broader “universe” of thousands, if not hundreds of thousands of substances that potentially could impact humans or the environment. This is exemplified in regulatory activities such as the REACH program in Europe, or the recent reauthorization of TSCA in the US, which require consideration of the potential impacts of a much greater number of chemicals than in the past. The data needed to address these types of legislated mandates cannot realistically be obtained solely through using the whole animal testing approaches historically employed for chemical risk assessment. Rather, there needs to be an increased emphasis on cost-effective tools that enable robust prediction of potential chemical impacts when empirical data are lacking. Concurrent with the realization that predictive methods will need to play an increasingly prominent role in regulatory toxicology has been the recent explosion in technology in the biological sciences enabling collection of large amounts of pathway-based molecular and biochemical data. For example, genomic techniques and high-throughput (robotic-based) in vitro testing enable the generation of knowledge concerning the effects of chemical perturbation on biological systems in an increasingly efficient and rapid manner. However, a pressing need stemming from these technological advances is the ability to actually apply th

  6. The AOP framework and causality: Meeting chemical risk ...

    EPA Pesticide Factsheets

    Chemical safety assessments are expanding from a focus on a few chemicals (or chemical mixtures) to the broader “universe” of thousands, if not hundreds of thousands of substances that potentially could impact humans or the environment. This is exemplified in regulatory activities such as the REACH program in Europe, or the recent reauthorization of TSCA in the US, which require consideration of the potential impacts of a much greater number of chemicals than in the past. The data needed to address these types of legislated mandates cannot realistically be obtained solely through using the whole animal testing approaches historically employed for chemical risk assessment. Rather, there needs to be an increased emphasis on cost-effective tools that enable robust prediction of potential chemical impacts when empirical data are lacking. Concurrent with the realization that predictive methods will need to play an increasingly prominent role in regulatory toxicology has been the recent explosion in technology in the biological sciences enabling collection of large amounts of pathway-based molecular and biochemical data. For example, genomic techniques and high-throughput (robotic-based) in vitro testing enable the generation of knowledge concerning the effects of chemical perturbation on biological systems in an increasingly efficient and rapid manner. However, a pressing need stemming from these technological advances is the ability to actually apply th

  7. Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: How can we delineate causal effects?

    PubMed

    Ponsonby, Anne-Louise; Symeonides, Christos; Vuillermin, Peter; Mueller, Jochen; Sly, Peter D; Saffery, Richard

    2016-07-01

    Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research example: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.

  8. Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?

    PubMed

    Teschke, Rolf; Schulze, Johannes; Eickhoff, Axel; Danan, Gaby

    2017-04-11

    Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available.

  9. Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?

    PubMed Central

    Teschke, Rolf; Schulze, Johannes; Eickhoff, Axel; Danan, Gaby

    2017-01-01

    Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available. PMID:28398242

  10. Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment.

    PubMed

    Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schwarzenboeck, Alexander; Schulze, Johannes; Eickhoff, Axel

    2014-01-27

    Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved.

  11. Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

    PubMed Central

    Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schwarzenboeck, Alexander; Schulze, Johannes; Eickhoff, Axel

    2014-01-01

    Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. PMID:24653791

  12. Laser Induced Surface Chemical Epitaxy

    DTIC Science & Technology

    1990-03-01

    Laser-Induced Surface Chemical Epitaxy ( LSCE ). The essential features of LSCE as applied to CdTe epitaxy involve: coadsorption of DMCd and DMTe on a GaAs...DIAGRAM OF THE LSCE PROCESS UHV environment 1M substra1e 9 /X Adsorbed thin film produced CH 3 -Cd-GH 3 CH 3 -Te-CH, by molecular beam source hv ’ CH...with Anneal W/// substraIe %/"/,’ Figure 1.1. Schematic of the LSCE process. (1-2) t I 2. EXPERIMENTAL APPROACH 2.1 Experimental Apparatus The

  13. Causality assessment methods in drug induced liver injury: strengths and weaknesses.

    PubMed

    García-Cortés, Miren; Stephens, Camilla; Lucena, M Isabel; Fernández-Castañer, Alejandra; Andrade, Raúl J

    2011-09-01

    Diagnosis of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. Several methods have been developed in order to facilitate hepatotoxicity causality assessments. These methods can be divided into three categories: (1) expert judgement, (2) probabilistic approaches, and (3) algorithms or scales. The last category is further divided into general and liver-specific scales. The Council for International Organizations of Medical Sciences (CIOMS) scale, also referred to as the Roussel Uclaf Causality Assessment Method (RUCAM), although cumbersome and difficult to apply by physicians not acquainted with DILI, is used by many expert hepatologists, researchers, and regulatory authorities to assess the probability of suspected causal agents. However, several limitations of this scale have been brought to light, indicating that a number of adjustments are needed. This review is a detailed timely criticism to alert the readers of the limitations and give insight into what would be needed to improve the scale. Instructions on how to approach DILI diagnosis in practice are provided, using CIOMS as an aid to emphasize the topics to be addressed when assessing DILI cases. Amendments of the CIOMS scale in the form of applying authoritative evidence-based criteria, a simplified scoring system and appropriate weighting given to individual parameters based on statistical evaluations with large databases will provide wider applicability in the clinical setting.

  14. A causal role for posterior medial frontal cortex in choice-induced preference change.

    PubMed

    Izuma, Keise; Akula, Shyam; Murayama, Kou; Wu, Daw-An; Iacoboni, Marco; Adolphs, Ralph

    2015-02-25

    After a person chooses between two items, preference for the chosen item will increase and preference for the unchosen item will decrease because of the choice made. In other words, we tend to justify or rationalize our past behavior by changing our attitude. This phenomenon of choice-induced preference change has been traditionally explained by cognitive dissonance theory. Choosing something that is disliked or not choosing something that is liked are both cognitively inconsistent and, to reduce this inconsistency, people tend to change their subsequently stated preference in accordance with their past choices. Previously, human neuroimaging studies identified posterior medial frontal cortex (pMFC) as a key brain region involved in cognitive dissonance. However, it remains unknown whether the pMFC plays a causal role in inducing preference change after cognitive dissonance. Here, we demonstrate that 25 min, 1 Hz repetitive transcranial magnetic stimulation applied over the pMFC significantly reduces choice-induced preference change compared with sham stimulation or control stimulation over a different brain region, demonstrating a causal role for the pMFC. Copyright © 2015 the authors 0270-6474/15/353598-09$15.00/0.

  15. Causal Correlation Functions and Fourier Transforms: Application in Calculating Pressure Induced Shifts

    NASA Technical Reports Server (NTRS)

    Ma, Q.; Tipping, R. H.; Lavrentieva, N. N.

    2012-01-01

    By adopting a concept from signal processing, instead of starting from the correlation functions which are even, one considers the causal correlation functions whose Fourier transforms become complex. Their real and imaginary parts multiplied by 2 are the Fourier transforms of the original correlations and the subsequent Hilbert transforms, respectively. Thus, by taking this step one can complete the two previously needed transforms. However, to obviate performing the Cauchy principal integrations required in the Hilbert transforms is the greatest advantage. Meanwhile, because the causal correlations are well-bounded within the time domain and band limited in the frequency domain, one can replace their Fourier transforms by the discrete Fourier transforms and the latter can be carried out with the FFT algorithm. This replacement is justified by sampling theory because the Fourier transforms can be derived from the discrete Fourier transforms with the Nyquis rate without any distortions. We apply this method in calculating pressure induced shifts of H2O lines and obtain more reliable values. By comparing the calculated shifts with those in HITRAN 2008 and by screening both of them with the pair identity and the smooth variation rules, one can conclude many of shift values in HITRAN are not correct.

  16. Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods, Quo Vadis?

    PubMed Central

    Eickhoff, Axel; Schulze, Johannes

    2013-01-01

    Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale. PMID:26357608

  17. Causal Induction from Continuous Event Streams: Evidence for Delay-Induced Attribution Shifts

    ERIC Educational Resources Information Center

    Buehner, Marc J.; May, Jon

    2009-01-01

    Contemporary theories of Human Causal Induction assume that causal knowledge is inferred from observable contingencies. While this assumption is well supported by empirical results, it fails to consider an important problem-solving aspect of causal induction in real time: In the absence of well structured learning trials, it is not clear whether…

  18. The AOP framework and causality: Meeting chemical risk assessment challenges in the 21st century

    EPA Science Inventory

    Chemical safety assessments are expanding from a focus on a few chemicals (or chemical mixtures) to the broader “universe” of thousands, if not hundreds of thousands of substances that potentially could impact humans or the environment. This is exemplified in ...

  19. The AOP framework and causality: Meeting chemical risk assessment challenges in the 21st century

    EPA Science Inventory

    Chemical safety assessments are expanding from a focus on a few chemicals (or chemical mixtures) to the broader “universe” of thousands, if not hundreds of thousands of substances that potentially could impact humans or the environment. This is exemplified in ...

  20. Causal effects of synthetic chemicals on mitochondrial deficits and diabetes pandemic.

    PubMed

    Park, Wook-Ha; Kang, Young-Chul; Piao, Ying; Pak, Daniel Hyungseok; Pak, Youngmi Kim

    2013-02-01

    It is generally accepted that mitochondrial deficits cause many common age-associated diseases including type 2 diabetes. However, it has not been understood what causes mitochondrial damages and how to interrupt the development of the diseases in patients. Recent epidemiologic studies demonstrated a positive correlation between serum concentrations of environmental pollutants and insulin resistance/diabetes. Emerging data strongly suggest that some synthetic pollutants disturb the signaling pathway critical for energy homeostasis and insulin action. The synthetic chemicals are possibly involved in pathogenesis of insulin resistance and diabetes as mitochondria-disturbing agents. In this review, we present a molecular scheme to address the contribution of environmental synthetic chemicals to this metabolic catastrophe. Efforts to identify synthetic chemicals with mitochondria-damaging activities may open a new era to develop effective therapeutic interventions against the worldwide-spreading metabolic disorder.

  1. Oscillatory hydrodynamic flow induced by chemical waves

    NASA Astrophysics Data System (ADS)

    Miike, Hidetoshi; Müller, Stefan C.; Hess, Benno

    1988-05-01

    Hydrodynamic flows in a reactive liquid induced by the propagation of waves of chemical activity are investigated for the ferroin-catalyzed Belousov-Zhabotinskii reaction in thin layers by microscope video imaging techniques. The motion of added polystyrene spheres is observed with laser light illumination. Oscillations in the hydrodynamic flow were detected in rotating spiral waves with an open liquid/gas interface.

  2. Previous knowledge can induce an illusion of causality through actively biasing behavior

    PubMed Central

    Yarritu, Ion; Matute, Helena

    2015-01-01

    It is generally assumed that the way people assess the relationship between a cause and an outcome is closely related to the actual evidence existing about the co-occurrence of these events. However, people's estimations are often biased, and this usually translates into illusions of causality. Some have suggested that such illusions could be the result of previous knowledge-based expectations. In the present research we explored the role that previous knowledge has in the development of illusions of causality. We propose that previous knowledge influences the assessment of causality by influencing the decisions about responding or not (i.e., presence or absence of the potential cause), which biases the information people are exposed to, and this in turn produces illusions congruent with such biased information. In a non-contingent situation in which participants decided whether the potential cause was present or absent (Experiment 1), the influence of expectations on participants' judgments was mediated by the probability of occurrence of the potential cause (determined by participants' responses). However, in an identical situation, except that the participants were not allowed to decide the occurrence of the potential cause (Experiment 2), only the probability of the cause was significant, not the expectations or the interaction. Together, these results support our hypothesis that knowledge-based expectations affect the development of causal illusions by the mediation of behavior, which biases the information received. PMID:25904883

  3. Previous knowledge can induce an illusion of causality through actively biasing behavior.

    PubMed

    Yarritu, Ion; Matute, Helena

    2015-01-01

    It is generally assumed that the way people assess the relationship between a cause and an outcome is closely related to the actual evidence existing about the co-occurrence of these events. However, people's estimations are often biased, and this usually translates into illusions of causality. Some have suggested that such illusions could be the result of previous knowledge-based expectations. In the present research we explored the role that previous knowledge has in the development of illusions of causality. We propose that previous knowledge influences the assessment of causality by influencing the decisions about responding or not (i.e., presence or absence of the potential cause), which biases the information people are exposed to, and this in turn produces illusions congruent with such biased information. In a non-contingent situation in which participants decided whether the potential cause was present or absent (Experiment 1), the influence of expectations on participants' judgments was mediated by the probability of occurrence of the potential cause (determined by participants' responses). However, in an identical situation, except that the participants were not allowed to decide the occurrence of the potential cause (Experiment 2), only the probability of the cause was significant, not the expectations or the interaction. Together, these results support our hypothesis that knowledge-based expectations affect the development of causal illusions by the mediation of behavior, which biases the information received.

  4. Laser Induced Chemical Liquid Phase Deposition (LCLD)

    SciTech Connect

    Nanai, Laszlo; Balint, Agneta M.

    2012-08-17

    Laser induced chemical deposition (LCLD) of metals onto different substrates attracts growing attention during the last decade. Deposition of metals onto the surface of dielectrics and semiconductors with help of laser beam allows the creation of conducting metal of very complex architecture even in 3D. In the processes examined the deposition occurs from solutions containing metal ions and reducing agents. The deposition happens in the region of surface irradiated by laser beam (micro reactors). Physics -chemical reactions driven by laser beam will be discussed for different metal-substrate systems. The electrical, optical, mechanical properties of created interfaces will be demonstrated also including some practical-industrial applications.

  5. Different biogenetic causal explanations and attitudes towards persons with major depression, schizophrenia and alcohol dependence: is the concept of a chemical imbalance beneficial?

    PubMed

    Speerforck, Sven; Schomerus, Georg; Pruess, Susanne; Angermeyer, Matthias C

    2014-10-01

    It is unclear whether different biogenetic causal beliefs affect stigmatization of mentally-ill patients differently. It has been argued that in particular believing in a 'chemical imbalance' as a cause of mental disorder might be associated with more tolerant attitudes. In a representative population survey in Germany (n=3642), using unlabelled case vignettes of persons with depression, schizophrenia, or alcohol dependence, we elicited agreement with three different biogenetic explanations of the illness: 'Chemical imbalance of the brain', 'brain disease' and 'heredity'. We further investigated emotional reactions as well as the desire for social distance. For each vignette condition we calculated linear regressions with each biogenetic explanation as independent and emotional reactions as well as social distance as dependent variable controlling for socio-demographic variables. Our cross-sectional study does not allow statements regarding causality and the explanatory power of our statistical models was low. 'Chemical imbalance of the brain' and 'brain disease' were both associated with a stronger desire for social distance in schizophrenia and depression, and with more social acceptance in alcohol dependence, whereas 'heredity' was not significantly associated with social distance in any of the investigated illnesses. All three biogenetic causal beliefs were associated with more fear in all three illnesses. Our study corroborates findings that biogenetic explanations have different effects in different disorders, and seem to be harmful in depression and schizophrenia. A particular de-stigmatizing potential of the causal belief 'chemical imbalance' could not be found. Implications for useful anti-stigma messages are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Study of chemical and radiation induced carcinogenesis

    SciTech Connect

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  7. CMB temperature anisotropy at large scales induced by a causal primordial magnetic field

    SciTech Connect

    Bonvin, Camille; Caprini, Chiara E-mail: camille.bonvin@cea.fr

    2010-05-01

    We present an analytical derivation of the Sachs Wolfe effect sourced by a primordial magnetic field. In order to consistently specify the initial conditions, we assume that the magnetic field is generated by a causal process, namely a first order phase transition in the early universe. As for the topological defects case, we apply the general relativistic junction conditions to match the perturbation variables before and after the phase transition which generates the magnetic field, in such a way that the total energy momentum tensor is conserved across the transition and Einstein's equations are satisfied. We further solve the evolution equations for the metric and fluid perturbations at large scales analytically including neutrinos, and derive the magnetic Sachs Wolfe effect. We find that the relevant contribution to the magnetic Sachs Wolfe effect comes from the metric perturbations at next-to-leading order in the large scale limit. The leading order term is in fact strongly suppressed due to the presence of free-streaming neutrinos. We derive the neutrino compensation effect dynamically and confirm that the magnetic Sachs Wolfe spectrum from a causal magnetic field behaves as l(l+1) C{sup B}{sub l}∝l{sup 2} as found in the latest numerical analyses.

  8. Water stress-induced xylem hydraulic failure is a causal factor of tree mortality in beech and poplar

    PubMed Central

    Barigah, Têtè Sévérien; Charrier, Olivia; Douris, Marie; Bonhomme, Marc; Herbette, Stéphane; Améglio, Thierry; Fichot, Régis; Brignolas, Frank; Cochard, Hervé

    2013-01-01

    Background and Aims Extreme water stress episodes induce tree mortality, but the physiological mechanisms causing tree death are still poorly understood. This study tests the hypothesis that a potted tree's ability to survive extreme monotonic water stress is determined by the cavitation resistance of its xylem tissue. Methods Two species were selected with contrasting cavitation resistance (beech and poplar), and potted juvenile trees were exposed to a range of water stresses, causing up to 100 % plant death. Key Results The lethal dose of water stress, defined as the xylem pressure inducing 50 % mortality, differed sharply across species (1·75 and 4·5 MPa in poplar and beech, respectively). However, the relationships between tree mortality and the degree of cavitation in the stems were similar, with mortality occurring suddenly when >90 % cavitation had occurred. Conclusions Overall, the results suggest that cavitation resistance is a causal factor of tree mortality under extreme drought conditions. PMID:24081280

  9. Causal and causally separable processes

    NASA Astrophysics Data System (ADS)

    Oreshkov, Ognyan; Giarmatzi, Christina

    2016-09-01

    The idea that events are equipped with a partial causal order is central to our understanding of physics in the tested regimes: given two pointlike events A and B, either A is in the causal past of B, B is in the causal past of A, or A and B are space-like separated. Operationally, the meaning of these order relations corresponds to constraints on the possible correlations between experiments performed in the vicinities of the respective events: if A is in the causal past of B, an experimenter at A could signal to an experimenter at B but not the other way around, while if A and B are space-like separated, no signaling is possible in either direction. In the context of a concrete physical theory, the correlations compatible with a given causal configuration may obey further constraints. For instance, space-like correlations in quantum mechanics arise from local measurements on joint quantum states, while time-like correlations are established via quantum channels. Similarly to other variables, however, the causal order of a set of events could be random, and little is understood about the constraints that causality implies in this case. A main difficulty concerns the fact that the order of events can now generally depend on the operations performed at the locations of these events, since, for instance, an operation at A could influence the order in which B and C occur in A’s future. So far, no formal theory of causality compatible with such dynamical causal order has been developed. Apart from being of fundamental interest in the context of inferring causal relations, such a theory is imperative for understanding recent suggestions that the causal order of events in quantum mechanics can be indefinite. Here, we develop such a theory in the general multipartite case. Starting from a background-independent definition of causality, we derive an iteratively formulated canonical decomposition of multipartite causal correlations. For a fixed number of settings and

  10. Standardization of Nomenclature and Causality Assessment in Drug-Induced Liver Injury: Summary of a Clinical Research Workshop

    PubMed Central

    Fontana, Robert J.; Seeff, Leonard B.; Andrade, Raúl J.; Björnsson, Einar; Day, Christopher P.; Serrano, Jose; Hoofnagle, Jay H.

    2013-01-01

    Idiosyncratic drug-induced liver injury (DILI) is an important but relatively infrequent cause of potentially severe acute and chronic liver injury. The aim of this clinical research workshop was to review and attempt to standardize the current nomenclature and terminology used in DILI research. Because DILI is a diagnosis of exclusion, selected elements of the medical history, laboratory tests, and previous reports were proposed to improve causality assessment. Definitions and diagnostic criteria regarding the onset of DILI, evolution of liver injury, risk factors, and mandatory testing versus optional testing for competing causes were reviewed. In addition, the role of intentional and inadvertent rechallenge, liver histology, and host genetic polymorphisms in establishing the diagnosis and prognosis of DILI were reviewed. Consensus was established regarding the need to develop a web-of-knowledge database that provides concise, reliable, and updated information on cases of liver injury due to drugs and herbal and dietary supplements. In addition, the need to develop drug-specific computerized causality assessment methods that are derived from prospectively phenotyped cases was a high priority. Proposed scales for grading DILI severity and assessing the likelihood of an agent causing DILI and written criteria for improving the reliability, accuracy, and reproducibility of expert opinion were reviewed. Finally, the unique challenges of assessing causality in children, patients with underlying liver disease, and subjects taking herbal and dietary supplements were discussed. Conclusion: Workshop participants concluded that multicenter referral networks enrolling patients with suspected DILI according to standardized methodologies are needed. These networks should also collect biological samples that may provide crucial insights into the mechanism(s) of DILI with the ultimate aim of preventing future cases of DILI. PMID:20564754

  11. Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury.

    PubMed

    Benesic, Andreas; Leitl, Alexandra; Gerbes, Alexander L

    2016-09-01

    Idiosyncratic drug-induced liver injury (iDILI) is a frequent cause of acute liver injury and a serious problem in late stage drug-development. Its diagnosis is one of the most challenging in hepatology, since it is done by exclusion and relies on expert opinion. Until now no reliable in vitro test exists to support the diagnosis of iDILI. In some instances it is impossible to determine the causative drug in polymedicated patients. To investigate if monocyte-derived hepatocyte-like (MH) cells might be a tool supporting clinical judgment for iDILI diagnosis and causality assessment. This prospective study included 54 patients with acute liver injury and intake of at least one drug. Thirty-one patients were diagnosed with iDILI based on causality likelihood. MH cells were generated from every patient and in vitro toxicity of the respective drugs was assessed by lactate-dehydrogenase release. The results from MH cells and RUCAM, the most widely used scoring system as methods to support clinical judgement were compared. MH cells showed enhanced toxicity in 29 of the 31 patients with iDILI, similar to RUCAM score. MH cells exhibited negative results in the 23 non-DILI cases, whereas RUCAM indicated possible iDILI in six cases. Analysis of the comedications also showed superior specificity of MH cells. No MH cell toxicity of the drugs showing toxicity in patients with iDILI was observed in MH cells of healthy donors. In this pilot study in vitro testing using MH cells derived from patients with acute liver injury was able to identify patients with iDILI with an excellent sensitivity and a higher specificity than RUCAM, the most widely used current causality assessment score. Therefore, MH cells could be useful to identify the causative drugs even in polymedicated patients by adding objective data to causality assessment. NCT02353455. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Chemically induced mouse models of intestinal inflammation.

    PubMed

    Wirtz, Stefan; Neufert, Clemens; Weigmann, Benno; Neurath, Markus F

    2007-01-01

    Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.

  13. The Bradford Hill criteria and zinc-induced anosmia: a causality analysis.

    PubMed

    Davidson, Terence M; Smith, Wendy M

    2010-07-01

    To apply the Bradford Hill criteria, which are widely used to establish causality between an environmental agent and disease, to evaluate the relationship between over-the-counter intranasal zinc gluconate therapy and anosmia. Patient and literature review applying the Bradford Hill criteria on causation. University of California, San Diego, Nasal Dysfunction Clinic. The study included 25 patients who presented to the University of California, San Diego, Nasal Dysfunction Clinic complaining of acute-onset anosmia after intranasal application of homeopathic zinc gluconate gel. Each of the 9 Bradford Hill criteria--strength of association, consistency, specificity, temporality, biological gradient (dose-response), biological plausibility, biological coherence, experimental evidence, and analogy--was applied to intranasal zinc gluconate therapy and olfactory dysfunction using published, peer-reviewed medical literature and reported clinical experiences. Clinical, biological, and experimental data support the Bradford Hill criteria to demonstrate that intranasal zinc gluconate therapy causes hyposmia and anosmia. The Bradford Hill criteria represent an important tool for scientifically determining cause between environmental exposure and disease. Increased Food and Drug Administration oversight of homeopathic medications is needed to monitor the safety of these popular remedies.

  14. Relativistic causality

    NASA Astrophysics Data System (ADS)

    Valente, Giovanni; Owen Weatherall, James

    2014-11-01

    Relativity theory is often taken to include, or to imply, a prohibition on superluminal propagation of causal processes. Yet, what exactly the prohibition on superluminal propagation amounts to and how one should deal with its possible violation have remained open philosophical problems, both in the context of the metaphysics of causation and the foundations of physics. In particular, recent work in philosophy of physics has focused on the causal structure of spacetime in relativity theory and on how this causal structure manifests itself in our most fundamental theories of matter. These topics were the subject of a workshop on "Relativistic Causality in Quantum Field Theory and General Relativity" that we organized (along with John Earman) at the Center for Philosophy of Science in Pittsburgh on April 5-7, 2013. The present Special Issue comprises contributions by speakers in that workshop as well as several other experts exploring different aspects of relativistic causality. We are grateful to the journal for hosting this Special Issue, to the journal's managing editor, Femke Kuiling, for her help and support in putting the issue together, and to the authors and the referees for their excellent work.

  15. Epidemiological causality.

    PubMed

    Morabia, Alfredo

    2005-01-01

    Epidemiological methods, which combine population thinking and group comparisons, can primarily identify causes of disease in populations. There is therefore a tension between our intuitive notion of a cause, which we want to be deterministic and invariant at the individual level, and the epidemiological notion of causes, which are invariant only at the population level. Epidemiologists have given heretofore a pragmatic solution to this tension. Causal inference in epidemiology consists in checking the logical coherence of a causality statement and determining whether what has been found grossly contradicts what we think we already know: how strong is the association? Is there a dose-response relationship? Does the cause precede the effect? Is the effect biologically plausible? Etc. This approach to causal inference can be traced back to the English philosophers David Hume and John Stuart Mill. On the other hand, the mode of establishing causality, devised by Jakob Henle and Robert Koch, which has been fruitful in bacteriology, requires that in every instance the effect invariably follows the cause (e.g., inoculation of Koch bacillus and tuberculosis). This is incompatible with epidemiological causality which has to deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore invariant only for the population.

  16. Chemically induced compaction bands in geomaterials

    NASA Astrophysics Data System (ADS)

    Stefanou, Ioannis; Sulem, Jean

    2013-04-01

    Compaction bands play an important role in oil production and may provide useful information on various geological processes. Various mechanisms can be involved at different scales: the micro scale (e.g. the grain scale), the meso scale (e.g. the Representative Element Volume) and the macro scale (e.g. the structure). Moreover, hydro-chemo-mechanical couplings might play an important role in triggering instabilities in the form of compaction bands. Compaction bands can be seen as an instability of the underneath mathematical problem leading to localization of deformation [1,2,3]. Here we explore the conditions of compaction banding in quartz-based geomaterials by considering the effect of chemical dissolution and precipitation [4,5]. In due course of the loading process grain crushing affects the residual strength, the porosity and the permeability of the material. Moreover, at the micro-level, grain crushing results in an increase of the grain specific surface, which accelerates the dissolution [6]. Consequently, the silica is removed more rapidly from the grain skeleton and the overall mechanical properties are degraded due to chemical factors. The proposed model accounts for these phenomena. In particular, the diffusion of the diluted in the water silica is considered through the mass balance equation of the porous medium. The reduction of the mechanical strength of the material is described through a macroscopic failure criterion with chemical softening. The grain size reduction is related to the total energy input [7]. A grain size and porosity dependent permeability law is adopted. These degradation mechanisms are coupled with the dissolution/precipitation reaction kinetics. The obtained hydro-chemo-mechanical model is used to investigate the conditions, the material parameters and the chemical factors inducing compaction bands formation. References [1] J.W. Rudnicki, and J.R. Rice. "Conditions for the Localization of Deformation in Pressure

  17. Differential Contribution of Bilateral Supplementary Motor Area to the Effective Connectivity Networks Induced by Task Conditions Using Dynamic Causal Modeling

    PubMed Central

    Tao, Zhongping; Zhang, Mu

    2014-01-01

    Abstract Functional imaging studies have indicated hemispheric asymmetry of activation in bilateral supplementary motor area (SMA) during unimanual motor tasks. However, the hemispherically special roles of bilateral SMAs on primary motor cortex (M1) in the effective connectivity networks (ECN) during lateralized tasks remain unclear. Aiming to study the differential contribution of bilateral SMAs during the motor execution and motor imagery tasks, and the hemispherically asymmetric patterns of ECN among regions involved, the present study used dynamic causal modeling to analyze the functional magnetic resonance imaging data of the unimanual motor execution/imagery tasks in 12 right-handed subjects. Our results demonstrated that distributions of network parameters underlying motor execution and motor imagery were significantly different. The variation was mainly induced by task condition modulations of intrinsic coupling. Particularly, regardless of the performing hand, the task input modulations of intrinsic coupling from the contralateral SMA to contralateral M1 were positive during motor execution, while varied to be negative during motor imagery. The results suggested that the inhibitive modulation suppressed the overt movement during motor imagery. In addition, the left SMA also helped accomplishing left hand tasks through task input modulation of left SMA→right SMA connection, implying that hemispheric recruitment occurred when performing nondominant hand tasks. The results specified differential and altered contributions of bilateral SMAs to the ECN during unimanual motor execution and motor imagery, and highlighted the contributions induced by the task input of motor execution/imagery. PMID:24606178

  18. Is Contrast Medium Osmolality a Causal Factor for Contrast-Induced Nephropathy?

    PubMed Central

    Bucher, Andreas M.; De Cecco, Carlo N.; Schoepf, U. Joseph; Meinel, Felix G.; Krazinski, Aleksander W.; Spearman, James V.; McQuiston, Andrew D.; Wang, Rui; Bucher, Judith; Vogl, Thomas J.; Katzberg, Richard W.

    2014-01-01

    The exact pathophysiology of contrast-induced nephropathy (CIN) is not fully clarified, yet the osmotic characteristics of contrast media (CM) have been a significant focus in many investigations of CIN. Osmotic effects of CM specific to the kidney include transient decreases in blood flow, filtration fraction, and glomerular filtration rate. Potentially significant secondary effects include an osmotically induced diuresis with a concomitant dehydrating effect. Clinical experiences that have compared the occurrence of CIN between the various classes of CM based on osmolality have suggested a much less than anticipated advantage, if any, with a lower osmolality. Recent animal experiments actually suggest that induction of a mild osmotic diuresis in association with iso-osmolar agents tends to offset potentially deleterious renal effects of high viscosity-mediated intratubular CM stagnation. PMID:24800254

  19. Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum.

    PubMed

    Wang, Jiabo; Ma, Zhijie; Niu, Ming; Zhu, Yun; Liang, Qingsheng; Zhao, Yanling; Song, Jingyuan; Bai, Zhaofang; Zhang, Yaming; Zhang, Ping; Li, Na; Meng, Yakun; Li, Qi; Qin, Lushan; Teng, Guangju; Cao, Junling; Li, Baosen; Chen, Shilin; Li, Yonggang; Zou, Zhengsheng; Zhou, Honghao; Xiao, Xiaohe

    2015-12-01

    Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.

  20. Chemical leukoderma induced by dimethyl sulfate*

    PubMed Central

    Gozali, Maya Valeska; Zhang, Jia-an; Yi, Fei; Zhou, Bing-rong; Luo, Dan

    2016-01-01

    Chemical leukoderma occurs due to the toxic effect of a variety of chemical agents. Mechanisms include either destruction or inhibition of melanocytes. We report two male patients (36 and 51 years old) who presented with multiple hypopigmented macules and patches on the neck, wrist, and legs after exposure to dimethyl sulfate in a chemical industry. Physical examination revealed irregular depigmentation macules with sharp edges and clear hyperpigmentation around the lesions. History of repeated exposure to a chemical agent can help the clinical diagnosis of chemical leukoderma. This diagnosis is very important for prognosis and therapeutic management of the disease.

  1. Theory-Based Causal Induction

    ERIC Educational Resources Information Center

    Griffiths, Thomas L.; Tenenbaum, Joshua B.

    2009-01-01

    Inducing causal relationships from observations is a classic problem in scientific inference, statistics, and machine learning. It is also a central part of human learning, and a task that people perform remarkably well given its notorious difficulties. People can learn causal structure in various settings, from diverse forms of data: observations…

  2. Causality between expansion of seismic cloud and maximum magnitude of induced seismicity in geothermal field

    NASA Astrophysics Data System (ADS)

    Mukuhira, Yusuke; Asanuma, Hiroshi; Ito, Takatoshi; Häring, Markus

    2016-04-01

    Occurrence of induced seismicity with large magnitude is critical environmental issues associated with fluid injection for shale gas/oil extraction, waste water disposal, carbon capture and storage, and engineered geothermal systems (EGS). Studies for prediction of the hazardous seismicity and risk assessment of induced seismicity has been activated recently. Many of these studies are based on the seismological statistics and these models use the information of the occurrence time and event magnitude. We have originally developed physics based model named "possible seismic moment model" to evaluate seismic activity and assess seismic moment which can be ready to release. This model is totally based on microseismic information of occurrence time, hypocenter location and magnitude (seismic moment). This model assumes existence of representative parameter having physical meaning that release-able seismic moment per rock volume (seismic moment density) at given field. Seismic moment density is to be estimated from microseismic distribution and their seismic moment. In addition to this, stimulated rock volume is also inferred by progress of microseismic cloud at given time and this quantity can be interpreted as the rock volume which can release seismic energy due to weakening effect of normal stress by injected fluid. Product of these two parameters (equation (1)) provide possible seismic moment which can be released from current stimulated zone as a model output. Difference between output of this model and observed cumulative seismic moment corresponds the seismic moment which will be released in future, based on current stimulation conditions. This value can be translated into possible maximum magnitude of induced seismicity in future. As this way, possible seismic moment can be used to have feedback to hydraulic stimulation operation in real time as an index which can be interpreted easily and intuitively. Possible seismic moment is defined as equation (1), where D

  3. Oralair(®): a causal treatment for grass pollen-induced allergic rhinoconjunctivitis.

    PubMed

    Köberlein, Juliane; Mösges, Ralph

    2013-01-01

    Grass pollen-induced allergic rhinoconjunctivitis is a common disease, comprising more than just the classic symptoms of nasal obstruction, sneezing, rhinorrhea and itchy, watery eyes. Sufferers deal with severe impairments in daily life. Allergic rhinoconjunctivitis is also considered an important risk factor in the development of asthma. Allergen avoidance, medication for symptomatic treatment and allergen-specific immunotherapy are cornerstones in therapeutic management, but immunotherapy is the only available treatment that is able to affect the natural course of allergy. In recent decades, clinical trials have investigated the efficacy and safety of subcutaneous immunotherapy. To date, efforts have been made to develop more convenient routes of administration. Substantial improvement may be achieved through the application of sublingual tablets. This article discusses the development process of immunotherapy and the clinical background of the Oralair(®) (Stallergènes, Hauts-de-Seine, France) five-grass pollen tablet. Furthermore, it outlines this tablet's efficacy and safety properties.

  4. In vitro antibacterial activity of sphaeropsidins and chemical derivatives toward Xanthomonas oryzae pv. oryzae, the causal agent of rice bacterial blight.

    PubMed

    Evidente, Antonio; Venturi, Vittorio; Masi, Marco; Degrassi, Giuliano; Cimmino, Alessio; Maddau, Lucia; Andolfi, Anna

    2011-12-27

    Sphaeropsidin A, the main phytotoxin produced by Diplodia cupressi, as well as the two natural analogues sphaeropsidins B and C and 14 derivatives obtained by chemical modifications were assayed for antibacterial activity against Xanthomonas oryzae pv. oryzae, Pseudomonas fuscovaginae, and Burkholderia glumae, the causal agents of severe bacterial rice diseases. The results showed a strong and specific activity of sphaeropsidin A against X. oryzae pv. oryzae, while no activity was observed against the other two pathogens. The results of structure-activity relationship studies showed that structural features important to impart this antibacterial activity are the presence of the C-7 carbonyl group and the hemiketalic lactone functionality. The C-13 vinyl group, the double bond of ring C, and/or the tertiary C-9 hydroxy group, as well as the pimarane arrangement of the tricylic carbon skeleton, were also important for the antibacterial activity. These findings may be useful in designing novel compounds for practical applications in agriculture.

  5. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  6. AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

    EPA Science Inventory

    Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

  7. AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

    EPA Science Inventory

    Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

  8. Chemical inducers of systemic immunity in plants.

    PubMed

    Gao, Qing-Ming; Kachroo, Aardra; Kachroo, Pradeep

    2014-04-01

    Systemic acquired resistance (SAR) is a highly desirable form of resistance that protects against a broad-spectrum of related or unrelated pathogens. SAR involves the generation of multiple signals at the site of primary infection, which arms distal portions against subsequent secondary infections. The last decade has witnessed considerable progress, and a number of chemical signals contributing to SAR have been isolated and characterized. The diverse chemical nature of these chemicals had led to the growing belief that SAR might involve interplay of multiple diverse and independent signals. However, recent results suggest that coordinated signalling from diverse signalling components facilitates SAR in plants. This review mainly discusses organized signalling by two such chemicals, glycerol-3-phoshphate and azelaic acid, and the role of basal salicylic acid levels in G3P-conferred SAR.

  9. Mechanisms of chemical-induced porphyrinopathies

    SciTech Connect

    Silbergeld, E.K. Fowler, B.A.

    1987-01-01

    This book contains 45 selections. Some of the titles are: Genetic Regulation of the Heme Pathway; Porphyrins in Urine as an Indication of Exposure to Chlorinated Hydrocarbons; Mechanisms of PCB-induced Porphyria and Yusho Disease; and Lead-Induced Abnormalities of Porphyrin Metabolism: The Relationship with Iron Deficiency.

  10. Airbag-induced chemical eye injury.

    PubMed

    Subash, Malavika; Manzouri, Bita; Wilkins, Mark

    2010-02-01

    Chemical injuries of the eye are a rare complication of airbag deployment and result from seepage of the chemical, causing inflation through vents in the airbag. We describe a severe case of bilateral alkali eye injury upon airbag contact in a road traffic accident. Delayed recognition and irrigation of the eyes exacerbated the injury with a resultant poor healing response of the left eye. Consequently, a left amniotic membrane graft was performed to promote corneal epithelial healing. The use of an amniotic membrane graft in the acute period after a chemical keratitis is unusual and reflects the severity of the corneal injuries sustained by this patient. This case illustrates the vision-threatening risk of alkali keratitis secondary to airbag deployment and highlights the importance of early recognition and management.

  11. Klotho ameliorates chemically induced endoplasmic reticulum (ER) stress signaling.

    PubMed

    Banerjee, Srijita; Zhao, Yanhua; Sarkar, Partha S; Rosenblatt, Kevin P; Tilton, Ronald G; Choudhary, Sanjeev

    2013-01-01

    Both endoplasmic reticulum (ER) stress, a fundamental cell response associated with stress-initiated unfolded protein response (UPR), and loss of Klotho, an anti-aging hormone linked to NF-κB-induced inflammation, occur in chronic metabolic diseases such as obesity and type 2 diabetes. We investigated if the loss of Klotho is causally linked to increased ER stress. We treated human renal epithelial HK-2, alveolar epithelial A549, HEK293, and SH-SH-SY5Y neuroblastoma cells with ER stress-inducing agents, thapsigargin and/or tunicamycin. Effects of overexpression or siRNA-mediated knockdown of Klotho on UPR signaling was investigated by immunoblotting and Real-time PCR. Elevated Klotho levels in HK-2 cells decreased expression of ER stress markers phospho--IRE1, XBP-1s, BiP, CHOP, pJNK, and phospho-p38, all of which were elevated in response to tunicamycin and/or thapsigargin. Similar results were observed using A549 cells for XBP-1s, BiP, and CHOP in response to thapsigargin. Conversely, knockdown of Klotho in HEK 293 cells using siRNA caused further thapsigargin-induced increases in pIRE-1, XBP-1s, and BiP. Klotho overexpression in A549 cells blocked thapsigargin-induced caspase and PARP cleavage and improved cell viability. Our data indicate that Klotho has an important role in regulating ER stress and that loss of Klotho is causally linked to ER stress-induced apoptosis. Copyright © 2013 S. Karger AG, Basel.

  12. Laser-induced gas breakdown - Spectroscopic and chemical studies.

    NASA Technical Reports Server (NTRS)

    De Montgolfier, PH.; Dumont, P.; Mille, Y.; Villermaux, J.

    1972-01-01

    Discussion of the results of several experimental investigations on laser-induced gas breakdown. The experiments included time-resolved spectroscopy, direct detection of H atoms with a TiO2 probe, and chemical reactions; each of them provided insight into the behavior of the medium at different times. Chemical reactions and explosions have been initiated by the laser beam when a plasma was created. No primary multiphotonic absorption and no macroscopic chemical reactions were observed below the breakdown threshold.

  13. Laser-induced gas breakdown - Spectroscopic and chemical studies.

    NASA Technical Reports Server (NTRS)

    De Montgolfier, PH.; Dumont, P.; Mille, Y.; Villermaux, J.

    1972-01-01

    Discussion of the results of several experimental investigations on laser-induced gas breakdown. The experiments included time-resolved spectroscopy, direct detection of H atoms with a TiO2 probe, and chemical reactions; each of them provided insight into the behavior of the medium at different times. Chemical reactions and explosions have been initiated by the laser beam when a plasma was created. No primary multiphotonic absorption and no macroscopic chemical reactions were observed below the breakdown threshold.

  14. Simulating Chemical-Induced Injury Using Virtual Hepatic Tissues

    EPA Science Inventory

    Chemical-induced liver injury involves a dynamic sequence of events that span multiple levels of biological organization. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. It is dif...

  15. Simulating Chemical-Induced Injury Using Virtual Hepatic Tissues

    EPA Science Inventory

    Chemical-induced liver injury involves a dynamic sequence of events that span multiple levels of biological organization. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. It is dif...

  16. From the exposome to mechanistic understanding of chemical-induced adverse effects.

    PubMed

    Escher, Beate I; Hackermüller, Jörg; Polte, Tobias; Scholz, Stefan; Aigner, Achim; Altenburger, Rolf; Böhme, Alexander; Bopp, Stephanie K; Brack, Werner; Busch, Wibke; Chadeau-Hyam, Marc; Covaci, Adrian; Eisenträger, Adolf; Galligan, James J; Garcia-Reyero, Natalia; Hartung, Thomas; Hein, Michaela; Herberth, Gunda; Jahnke, Annika; Kleinjans, Jos; Klüver, Nils; Krauss, Martin; Lamoree, Marja; Lehmann, Irina; Luckenbach, Till; Miller, Gary W; Müller, Andrea; Phillips, David H; Reemtsma, Thorsten; Rolle-Kampczyk, Ulrike; Schüürmann, Gerrit; Schwikowski, Benno; Tan, Yu-Mei; Trump, Saskia; Walter-Rohde, Susanne; Wambaugh, John F

    2017-02-01

    The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. New Approach to Chemically Induced Silicon Oxidation

    DTIC Science & Technology

    1991-10-01

    Kim, C.H. Wolowodiuk, R.J. Jaccodine, F.A. Stevie , and P.M. Kohora, to be published in J. Electrochem. Society. 4. "Effect of NF3 Addition on Point...Defect Generation at the Oxidizing Interface", U.S. Kim, R.J. Jaccodine, F.A. Stevie , and T. Kook, to be published in J. Electrochem. Society. 5...Macfarlane, R.J. Jaccodine and F.A. Stevie , presented at the 180th Meeting of the Electro- chemical Society, Phoenix, AZ, October 13-18, 1991. 15

  18. [Extrapyramidal syndrome induced by chemical substances].

    PubMed

    Inoue, N

    1993-11-01

    Extrapyramidal signs are frequently observed in toxic diseases due to environmental and industrial chemical substances. The predominant manifestations are Parkinsonism and less frequently tremor. Parkinsonism has been described among the toxic diseases due to carbon monoxide, hydrogen sulfide, and hydrogen cyanide. In these diseases, Parkinsonism used to appear in the recovery stage from coma in the severe cases. This was also true in methyl alcohol poisoning. The extrapyramidal signs are usually symmetrical. Akinesia and rigidity are main features. Tremor is absent or mild. Levodopa and the other antiparkinsonian drugs are not so effective. Brain CT studies have revealed symmetrical low density areas in the globus pallidus and putamen. On the other hand, postural tremor is main neurological findings in the poisonings by inorganic mercury and tetraethyl lead. In general, tremor in the toxic disease is reported to be self-limited.

  19. Dynamic causal modelling revisited.

    PubMed

    Friston, K J; Preller, Katrin H; Mathys, Chris; Cagnan, Hayriye; Heinzle, Jakob; Razi, Adeel; Zeidman, Peter

    2017-02-17

    This paper revisits the dynamic causal modelling of fMRI timeseries by replacing the usual (Taylor) approximation to neuronal dynamics with a neural mass model of the canonical microcircuit. This provides a generative or dynamic causal model of laminar specific responses that can generate haemodynamic and electrophysiological measurements. In principle, this allows the fusion of haemodynamic and (event related or induced) electrophysiological responses. Furthermore, it enables Bayesian model comparison of competing hypotheses about physiologically plausible synaptic effects; for example, does attentional modulation act on superficial or deep pyramidal cells - or both? In this technical note, we describe the resulting dynamic causal model and provide an illustrative application to the attention to visual motion dataset used in previous papers. Our focus here is on how to answer long-standing questions in fMRI; for example, do haemodynamic responses reflect extrinsic (afferent) input from distant cortical regions, or do they reflect intrinsic (recurrent) neuronal activity? To what extent do inhibitory interneurons contribute to neurovascular coupling? What is the relationship between haemodynamic responses and the frequency of induced neuronal activity? This paper does not pretend to answer these questions; rather it shows how they can be addressed using neural mass models of fMRI timeseries.

  20. Using Chemical-Induced Gene Expression in Cultured Human Cells to Predict Chemical Toxicity.

    PubMed

    Liu, Ruifeng; Yu, Xueping; Wallqvist, Anders

    2016-11-21

    Chemical toxicity is conventionally evaluated in animal models. However, animal models are resource intensive; moreover, they face ethical and scientific challenges because the outcomes obtained by animal testing may not correlate with human responses. To develop an alternative method for assessing chemical toxicity, we investigated the feasibility of using chemical-induced genome-wide expression changes in cultured human cells to predict the potential of a chemical to cause specific organ injuries in humans. We first created signatures of chemical-induced gene expression in a vertebral-cancer of the prostate cell line for ∼15,000 chemicals tested in the US National Institutes of Health Library of Integrated Network-Based Cellular Signatures program. We then used the signatures to create naı̈ve Bayesian prediction models for chemical-induced human liver cholestasis, interstitial nephritis, and long QT syndrome. Detailed cross-validation analyses indicated that the models were robust with respect to false positives and false negatives in the samples we used to train the models and could predict the likelihood that chemicals would cause specific organ injuries. In addition, we performed a literature search for drugs and dietary supplements, not formally categorized as causing organ injuries in humans but predicted by our models to be most likely to do so. We found a high percentage of these compounds associated with case reports of relevant organ injuries, lending support to the idea that in vitro cell-based experiments can be used to predict the toxic potential of chemicals. We believe that this approach, combined with a robust technique to model human exposure to chemicals, may serve as a promising alternative to animal-based chemical toxicity assessment.

  1. Chemically Induced Surface Evolutions with Level Sets

    SciTech Connect

    2006-11-17

    ChISELS is used for the theoretical modeling of detailed surface chemistry and consomitant surface evolutions occurring during microsystem fabrication processes conducted at low pressures. Examples include physical vapor deposition (PVD), low pressure chemical vapor deposition (PECVD), and plasma etching. Evolving interfaces are represented using the level-set method and the evolution equations time integrated using a Semi-Lagrangian approach. A Ballistic transport model is employed to solve for the fluxes incident on each of the surface elements. Surface chemistry leading to etching or deposition is computed by either coupling to Surface Chemkin (a commercially available code) or by providing user defined subroutines. The computational meshes used are quad-trees (2-D) and oct-trees (3-D), constructed such that grid refinement is localized to regions near the surface interfaces. As the interface evolves, the mesh is dynamically reconstructed as needed for the grid to remain fine only around the interface. For parallel computation, a domain decomposition scheme with dynamic load balancing is used to distribute the computational work across processors.

  2. Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

    SciTech Connect

    Datskos, P.G.

    1999-04-05

    Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

  3. Morphological changes of amphiphilic molecular assemblies induced by chemical reactions.

    PubMed

    Nakagawa, Koh M; Noguchi, Hiroshi

    2015-02-04

    Shape transformations of amphiphilic molecular assemblies induced by chemical reactions are studied using coarse-grained molecular simulations. A binding reaction between hydrophilic and hydrophobic molecules is considered. It is found that the reaction induces transformation of an oil droplet to a tubular vesicle via bicelles and vesicles with discoidal arms. The discoidal arms close into vesicles, which are subsequently fused into the tubular vesicle. Under the chemical reaction, the bicelle-to-vesicle transition occurs at smaller sizes than in the absence of the hydrophobic molecules. It is revealed that the enhancement of this transition is due to embedded hydrophobic particles that reduce the membrane bending rigidity.

  4. Neuro-immune interactions in chemical-induced airway hyperreactivity.

    PubMed

    Devos, Fien C; Boonen, Brett; Alpizar, Yeranddy A; Maes, Tania; Hox, Valérie; Seys, Sven; Pollaris, Lore; Liston, Adrian; Nemery, Benoit; Talavera, Karel; Hoet, Peter H M; Vanoirbeek, Jeroen A J

    2016-08-01

    Asthma may be induced by chemical sensitisers, via mechanisms that are still poorly understood. This type of asthma is characterised by airway hyperreactivity (AHR) and little airway inflammation. Since potent chemical sensitisers, such as toluene-2,4-diisocyanate (TDI), are also sensory irritants, it is suggested that chemical-induced asthma relies on neuro-immune mechanisms.We investigated the involvement of transient receptor potential channels (TRP) A1 and V1, major chemosensors in the airways, and mast cells, known for their ability to communicate with sensory nerves, in chemical-induced AHR.In vitro intracellular calcium imaging and patch-clamp recordings in TRPA1- and TRPV1-expressing Chinese hamster ovarian cells showed that TDI activates murine TRPA1, but not TRPV1. Using an in vivo model, in which an airway challenge with TDI induces AHR in TDI-sensitised C57Bl/6 mice, we demonstrated that AHR does not develop, despite successful sensitisation, in Trpa1 and Trpv1 knockout mice, and wild-type mice pretreated with a TRPA1 blocker or a substance P receptor antagonist. TDI-induced AHR was also abolished in mast cell deficient Kit(Wsh) (/Wsh) mice, and in wild-type mice pretreated with the mast cell stabiliser ketotifen, without changes in immunological parameters.These data demonstrate that TRPA1, TRPV1 and mast cells play an indispensable role in the development of TDI-elicited AHR. Copyright ©ERS 2016.

  5. Causal reasoning with forces

    PubMed Central

    Wolff, Phillip; Barbey, Aron K.

    2015-01-01

    Causal composition allows people to generate new causal relations by combining existing causal knowledge. We introduce a new computational model of such reasoning, the force theory, which holds that people compose causal relations by simulating the processes that join forces in the world, and compare this theory with the mental model theory (Khemlani et al., 2014) and the causal model theory (Sloman et al., 2009), which explain causal composition on the basis of mental models and structural equations, respectively. In one experiment, the force theory was uniquely able to account for people's ability to compose causal relationships from complex animations of real-world events. In three additional experiments, the force theory did as well as or better than the other two theories in explaining the causal compositions people generated from linguistically presented causal relations. Implications for causal learning and the hierarchical structure of causal knowledge are discussed. PMID:25653611

  6. The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

  7. The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

  8. Chemically-induced Mouse Lung Tumors: Applications to ...

    EPA Pesticide Factsheets

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all three chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that available mouse lung tumor data should be considered for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism and relevan

  9. Chemically-induced mouse lung tumors: applications to ...

    EPA Pesticide Factsheets

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to discuss issues related to the use of mouse lung tumor data in human health assessments. Naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all these three environmental chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that data showing mouse lung tumors with chemical exposures can be relevant for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism

  10. Chemically-induced Mouse Lung Tumors: Applications to ...

    EPA Pesticide Factsheets

    A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all three chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that available mouse lung tumor data should be considered for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism and relevan

  11. Simple chemicals can induce maturation and apoptosis of dendritic cells

    PubMed Central

    Manome, H; Aiba, S; Tagami, H

    1999-01-01

    As is well known in the case of Langerhans cells, dendritic cells (DCs) play a crucial role in the initiation of immunity to simple chemicals such as noted in the contact hypersensitivity. Because DCs are scattered in non‐lymphoid organs as immature cells, they must be activated to initiate primary antigen‐specific immune reactions. Therefore, we hypothesized that some simple chemicals must affect the function of DCs. In this paper, we first demonstrated that human monocyte‐derived DCs responded to such simple chemicals as 2,4‐dinitrochlorobenzene (DNCB), 2,4,6‐trinitrochlorobenzene (TNCB), 2,4‐dinitrofluorobenzene (DNFB), NiCl2, MnCl2, CoCl2, SnCl2, and CdSO4 by augmenting their expression of CD86 or human leucocyte antigen‐DR (HLA‐DR), down‐regulating c‐Fms expression or increasing their production of tumour necrosis factor‐α (TNF‐α). In addition, the DCs stimulated with the chemicals demonstrated increased allogeneic T‐cell stimulatory function. Next, we found that, among these chemicals, only NiCl2 and CoCl2 induced apoptosis in them. Finally, we examined the effects of these chemicals on CD86 expression by three different macrophage subsets and DCs induced from the cultures of human peripheral blood monocytes in the presence of macrophage colony‐stimulating factor (M‐CSF), M‐CSF + interleukin‐4 (IL‐4), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and GM‐CSF + IL‐4, respectively. Among them, only DCs dramatically augmented their expression of CD86. These observations have revealed unique characteristics of DCs, which convert chemical stimuli to augmentation of their antigen presenting function, although their responses to different chemicals were not necessarily uniform in the phenotypic changes, cytokine production or in the induction of apoptosis. PMID:10594678

  12. Laser-induced chemical changes in art materials

    NASA Astrophysics Data System (ADS)

    Abraham, Margaret H.; Scheerer, Stefanie; Madden, Odile; Adar, Fran

    2001-10-01

    Lasers can induce subtle and not so subtle changes in material structure. We have found that certain pigments can undergo chemical and crystallographic changes and concomitant color shifts. Minerals and the related pigments may experience a loss of hydroxyl groups or other chemical reordering. The organic component of skeletal, keratinaceous, and cellulosic materials can be pyrolized, ablated, or etched. Polymers can discolor, undergo structural weakening, or be volatilized. A few of these processes have been investigated with regards to changes on ivory and bone, selected pigments and the removal of dye-based pen ink from porous substrates.

  13. Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction.

    PubMed

    Fu, Hai Ying; Sanada, Shoji; Matsuzaki, Takashi; Liao, Yulin; Okuda, Keiji; Yamato, Masaki; Tsuchida, Shota; Araki, Ryo; Asano, Yoshihiro; Asanuma, Hiroshi; Asakura, Masanori; French, Brent A; Sakata, Yasushi; Kitakaze, Masafumi; Minamino, Tetsuo

    2016-03-04

    Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane-resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. Doxorubicin activated the ER stress-initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment. © 2016 American Heart Association, Inc.

  14. Protective effect of silymarin against chemical-induced cardiotoxicity

    PubMed Central

    Razavi, Bibi Marjan; Karimi, Gholamreza

    2016-01-01

    Cardiac disorders remain one of the most important causes of death in the world. Oxidative stress has been suggested as one of the molecular mechanisms involved in drug-induced cardiac toxicity. Recently, several natural products have been utilized in different studies with the aim to protect the progression of oxidative stress-induced cardiac disorders. There is a large body of evidence that administration of antioxidants may be useful in ameliorating cardiac toxicity. Silymarin, a polyphenolic flavonoid has been shown to have utility in several cardiovascular disorders. In this review, various studies in scientific databases regarding the preventive effects of silymarin against cardiotoxicity induced by chemicals were introduced. Although there are many studies representing the valuable effects of silymarin in different diseases, the number of researches relating to the possible cardiac protective effects of silymarin against drugs induced toxicity is rather limited. Results of these studies show that silymarin has a broad spectrum of cardiac protective activity against toxicity induced by some chemicals including metals, environmental pollutants, oxidative agents and anticancer drugs. Further studies are needed to establish the utility of silymarin in protection against cardiac toxicity. PMID:27803777

  15. On the Chemical Mixing Induced by Internal Gravity Waves

    NASA Astrophysics Data System (ADS)

    Rogers, T. M.; McElwaine, J. N.

    2017-10-01

    Detailed modeling of stellar evolution requires a better understanding of the (magneto)hydrodynamic processes that mix chemical elements and transport angular momentum. Understanding these processes is crucial if we are to accurately interpret observations of chemical abundance anomalies, surface rotation measurements, and asteroseismic data. Here, we use two-dimensional hydrodynamic simulations of the generation and propagation of internal gravity waves in an intermediate-mass star to measure the chemical mixing induced by these waves. We show that such mixing can generally be treated as a diffusive process. We then show that the local diffusion coefficient does not depend on the local fluid velocity, but rather on the wave amplitude. We then use these findings to provide a simple parameterization for this diffusion, which can be incorporated into stellar evolution codes and tested against observations.

  16. Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes.

    PubMed

    Yang, Won-Mo; Jeong, Hyo-Jin; Park, Se-Whan; Lee, Wan

    2015-11-01

    Obesity increases intracellular lipid accumulation in key tissues or organs, which often leads to metabolic dysfunction and insulin resistance. Diets rich in saturated fatty acid (SFA) exacerbate obesity and hepatic steatosis, which accentuate the risk of insulin resistance and type 2 diabetes (T2DM). Although microRNAs (miRNAs) play a critical role in the regulation of gene expression, the implication of obesity-induced miRNAs in metabolic disorders particularly in the development of insulin resistance is largely unknown. Here, we investigated the implication of miR-15b, which is induced by SFA palmitate or obesity, in hepatic insulin resistance. Diet-induced obesity (DIO) in mice developed hyperglycemia and insulin resistance, accompanying with a reduction of insulin receptor (INSR) expression. Palmitate impaired insulin signaling as well as a decrease of INSR in hepatocytes. The expression of miR-15b was upregulated by DIO or palmitate in hepatocytes. Furthermore, the overexpression of miR-15b suppressed the protein expression of INSR through targeting INSR 3' untranslated region directly, resulting in an impairment of the insulin signaling and glycogen synthesis in hepatocytes. These results unveil a novel mechanism whereby miR-15b is linked causally to the pathogenesis of hepatic insulin resistance in SFA-induced obesity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Causality and persistence in ecological systems: a nonparametric spectral granger causality approach.

    PubMed

    Detto, Matteo; Molini, Annalisa; Katul, Gabriel; Stoy, Paul; Palmroth, Sari; Baldocchi, Dennis

    2012-04-01

    Abstract Directionality in coupling, defined as the linkage relating causes to their effects at a later time, can be used to explain the core dynamics of ecological systems by untangling direct and feedback relationships between the different components of the systems. Inferring causality from measured ecological variables sampled through time remains a formidable challenge further made difficult by the action of periodic drivers overlapping the natural dynamics of the system. Periodicity in the drivers can often mask the self-sustained oscillations originating from the autonomous dynamics. While linear and direct causal relationships are commonly addressed in the time domain, using the well-established machinery of Granger causality (G-causality), the presence of periodic forcing requires frequency-based statistics (e.g., the Fourier transform), able to distinguish coupling induced by oscillations in external drivers from genuine endogenous interactions. Recent nonparametric spectral extensions of G-causality to the frequency domain pave the way for the scale-by-scale decomposition of causality, which can improve our ability to link oscillatory behaviors of ecological networks to causal mechanisms. The performance of both spectral G-causality and its conditional extension for multivariate systems is explored in quantifying causal interactions within ecological networks. Through two case studies involving synthetic and actual time series, it is demonstrated that conditional G-causality outperforms standard G-causality in identifying causal links and their concomitant timescales.

  18. Chemical memory reactions induced bursting dynamics in gene expression.

    PubMed

    Tian, Tianhai

    2013-01-01

    Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

  19. Information thermodynamics on causal networks.

    PubMed

    Ito, Sosuke; Sagawa, Takahiro

    2013-11-01

    We study nonequilibrium thermodynamics of complex information flows induced by interactions between multiple fluctuating systems. Characterizing nonequilibrium dynamics by causal networks (i.e., Bayesian networks), we obtain novel generalizations of the second law of thermodynamics and the fluctuation theorem, which include an informational quantity characterized by the topology of the causal network. Our result implies that the entropy production in a single system in the presence of multiple other systems is bounded by the information flow between these systems. We demonstrate our general result by a simple model of biochemical adaptation.

  20. Precise excision of transposons and point mutations induced by chemicals.

    PubMed

    Rusina OYu; Mirskaya, E E; Andreeva, I V; Skavronskaya, A G

    1992-11-01

    The ability of 23 chemicals (carcinogens and non-carcinogens) to induce precise excision of Tn10 and point mutations was studied in experiments with a single strain. The mutation assay was shown to detect a wider spectrum of genotoxic agents than the assay of Tn10 precise excision. The latter was induced only by potent SOS mutagens, which is in accordance with data on the SOS dependence of the induction of precise excision of Tn10. The precise excision assay as an additional test contributing to the knowledge of particular features of the action of a tested mutagen is discussed. The induction of precise excision of Tn10 by pyrene (and its failure to induce point mutations in this strain) demonstrates the value of using the transposon excision assay in cases of 'problem' mutagens.

  1. Unraveling the mechanism of cell death induced by chemical fibrils

    PubMed Central

    Julien, Olivier; Kampmann, Martin; Bassik, Michael C.; Zorn, Julie A.; Venditto, Vincent J.; Shimbo, Kazutaka; Agard, Nicholas J.; Shimada, Kenichi; Rheingold, Arnold L.; Stockwell, Brent R.; Weissman, Jonathan S.

    2014-01-01

    We previously discovered a small-molecule inducer of cell death, named 1541, that non-covalently self-assembles into chemical fibrils (“chemi-fibrils”) and activates procaspase-3 in vitro. We report here that 1541-induced cell death is caused by the fibrillar, rather than the soluble form of the drug. An shRNA screen reveals that knockdown of genes involved in endocytosis, vesicle trafficking, and lysosomal acidification causes partial 1541 resistance. We confirm the role of these pathways using pharmacological inhibitors. Microscopy shows that the fluorescent chemi-fibrils accumulate in punctae inside cells that partially co-localize with lysosomes. Notably, the chemi-fibrils bind and induce liposome leakage in vitro, suggesting they may do the same in cells. The chemi-fibrils induce extensive proteolysis including caspase substrates, yet modulatory profiling reveals that chemi-fibrils form a distinct class from existing inducers of cell death. The chemi-fibrils share similarities to proteinaceous fibrils and may provide insight into their mechanism of cellular toxicity. PMID:25262416

  2. Extensin network formation in Vitis vinifera callus cells is an essential and causal event in rapid and H(2)O(2)-induced reduction in primary cell wall hydration.

    PubMed

    Pereira, Cristina Silva; Ribeiro, José M L; Vatulescu, Ada D; Findlay, Kim; MacDougall, Alistair J; Jackson, Phil A P

    2011-06-14

    Extensin deposition is considered important for the correct assembly and biophysical properties of primary cell walls, with consequences to plant resistance to pathogens, tissue morphology, cell adhesion and extension growth. However, evidence for a direct and causal role for the extensin network formation in changes to cell wall properties has been lacking. Hydrogen peroxide treatment of grapevine (Vitis vinifera cv. Touriga) callus cell walls was seen to induce a marked reduction in their hydration and thickness. An analysis of matrix proteins demonstrated this occurs with the insolubilisation of an abundant protein, GvP1, which displays a primary structure and post-translational modifications typical of dicotyledon extensins. The hydration of callus cell walls free from saline-soluble proteins did not change in response to H(2)O(2), but fully regained this capacity after addition of extensin-rich saline extracts. To assay the specific contribution of GvP1 cross-linking and other wall matrix proteins to the reduction in hydration, GvP1 levels in cell walls were manipulated in vitro by binding selected fractions of extracellular proteins and their effect on wall hydration during H(2)O(2) incubation assayed. This approach allowed us to conclude that a peroxidase-mediated formation of a covalently linked network of GvP1 is essential and causal in the reduction of grapevine callus wall hydration in response to H(2)O(2). Importantly, this approach also indicated that extensin network effects on hydration was only partially irreversible and remained sensitive to changes in matrix charge. We discuss this mechanism and the importance of these changes to primary wall properties in the light of extensin distribution in dicotyledons.

  3. Extensin network formation in Vitis vinifera callus cells is an essential and causal event in rapid and H2O2-induced reduction in primary cell wall hydration

    PubMed Central

    2011-01-01

    Background Extensin deposition is considered important for the correct assembly and biophysical properties of primary cell walls, with consequences to plant resistance to pathogens, tissue morphology, cell adhesion and extension growth. However, evidence for a direct and causal role for the extensin network formation in changes to cell wall properties has been lacking. Results Hydrogen peroxide treatment of grapevine (Vitis vinifera cv. Touriga) callus cell walls was seen to induce a marked reduction in their hydration and thickness. An analysis of matrix proteins demonstrated this occurs with the insolubilisation of an abundant protein, GvP1, which displays a primary structure and post-translational modifications typical of dicotyledon extensins. The hydration of callus cell walls free from saline-soluble proteins did not change in response to H2O2, but fully regained this capacity after addition of extensin-rich saline extracts. To assay the specific contribution of GvP1 cross-linking and other wall matrix proteins to the reduction in hydration, GvP1 levels in cell walls were manipulated in vitro by binding selected fractions of extracellular proteins and their effect on wall hydration during H2O2 incubation assayed. Conclusions This approach allowed us to conclude that a peroxidase-mediated formation of a covalently linked network of GvP1 is essential and causal in the reduction of grapevine callus wall hydration in response to H2O2. Importantly, this approach also indicated that extensin network effects on hydration was only partially irreversible and remained sensitive to changes in matrix charge. We discuss this mechanism and the importance of these changes to primary wall properties in the light of extensin distribution in dicotyledons. PMID:21672244

  4. A chemical chaperone induces inhomogeneous conformational changes in flexible proteins.

    PubMed

    Hamdane, Djemel; Velours, Christophe; Cornu, David; Nicaise, Magali; Lombard, Murielle; Fontecave, Marc

    2016-07-27

    Organic osmolytes also known as chemical chaperones are major cellular compounds that favor, by an unclear mechanism, protein's compaction and stabilization of the native state. Here, we have examined the chaperone effect of the naturally occurring trimethylamine N-oxide (TMAO) osmolyte on a loosely packed protein (LPP), known to be a highly flexible form, using an apoprotein mutant of the flavin-dependent RNA methyltransferase as a model. Thermal and chemical denaturation experiments showed that TMAO stabilizes the structural integrity of the apoprotein dramatically. The denaturation reaction is irreversible indicating that the stability of the apoprotein is under kinetic control. This result implies that the stabilization is due to a TMAO-induced reconfiguration of the flexible LPP state, which leads to conformational limitations of the apoprotein likely driven by favorable entropic contribution. Evidence for the conformational perturbation of the apoprotein had been obtained through several biophysical approaches notably analytical ultracentrifugation, circular dichroism, fluorescence spectroscopy, labelling experiments and proteolysis coupled to mass spectrometry. Unexpectedly, TMAO promotes an overall elongation or asymmetrical changes of the hydrodynamic shape of the apoprotein without alteration of the secondary structure. The modulation of the hydrodynamic properties of the protein is associated with diverse inhomogenous conformational changes: loss of the solvent accessible cavities resulting in a dried protein matrix; some side-chain residues initially buried become solvent exposed while some others become hidden. Consequently, the TMAO-induced protein state exhibits impaired capability in the flavin binding process. Our study suggests that the nature of protein conformational changes induced by the chemical chaperones may be specific to protein packing and plasticity. This could be an efficient mechanism by which the cell controls and finely tunes the

  5. Plasma membrane reorganization induced by chemical transformation in cultura

    SciTech Connect

    Packard, B.S.

    1984-04-01

    Induction of increased rigidity in the plasma membrane paralleling properties associated with a transformed state was suggested by two experiments. Fluorescence recovery after photobleaching (FRAP) indicated the induction of an environment in the plasma membrane where the synthetic fluorescent phospholipid collarein was immobile on the FRAP timescale. The other technique revealed the binding of epidermal growth factor (EGF) to a cryptic class of receptors which become accessible upon chemical transformation. These two lines of evidence are consistent with a reorganization of the plasma membrane induced by tumor promoters. 110 references, 38 figures, 4 tables.

  6. Chemical-induced DNA damage and human cancer risk.

    PubMed

    Poirier, Miriam C

    2012-10-01

    For more than 200 years human cancer induction has been known to be associated with a large variety of chemical exposures. Most exposures to chemical carcinogens occur as a result of occupation, pollution in the ambient environment, lifestyle choices, or pharmaceutical use. Scientific investigations have revealed that the majority of cancer causing chemicals, or chemical carcinogens, act through "genotoxic" or DNA damaging mechanisms, which involve covalent binding of the chemical to DNA (DNA adduct formation). Cancer-inducing exposures are typically frequent and/or chronic over years, and the accumulation of DNA damage or DNA adduct formation is considered to be a necessary requirement for tumor induction. Studies in animal models have indicated that the ability to reduce DNA damage will also result in reduction of tumor risk, leading to the hypothesis that individuals having the highest levels of DNA adducts may have an increased cancer risk, compared to individuals with the lowest levels of DNA adducts. Here we have reviewed twelve investigations showing 2- to 9-fold increased Relative Risks (RR) or Odds Ratios (OR) for cancer in (the 25% of) individuals having the highest DNA adduct levels, compared to (the 25% of) matched individuals with the lowest DNA adducts. These studies also provided preliminary evidence that multiple types of DNA adducts combined, or DNA adducts combined with other risk factors (such as infection or inflammation), may be associated with more than 10-fold higher cancer risks (RR = 34-60), compared to those found with a single carcinogen. Taken together the data suggest that a reduction in human DNA adduct level is likely to produce a reduction in human cancer risk.

  7. Causal Imprinting in Causal Structure Learning

    PubMed Central

    Taylor, Eric G.; Ahn, Woo-kyoung

    2012-01-01

    Suppose one observes a correlation between two events, B and C, and infers that B causes C. Later one discovers that event A explains away the correlation between B and C. Normatively, one should now dismiss or weaken the belief that B causes C. Nonetheless, participants in the current study who observed a positive contingency between B and C followed by evidence that B and C were independent given A, persisted in believing that B causes C. The authors term this difficulty in revising initially learned causal structures “causal imprinting.” Throughout four experiments, causal imprinting was obtained using multiple dependent measures and control conditions. A Bayesian analysis showed that causal imprinting may be normative under some conditions, but causal imprinting also occurred in the current study when it was clearly non-normative. It is suggested that causal imprinting occurs due to the influence of prior knowledge on how reasoners interpret later evidence. Consistent with this view, when participants first viewed the evidence showing that B and C are independent given A, later evidence with only B and C did not lead to the belief that B causes C. PMID:22859019

  8. Causal imprinting in causal structure learning.

    PubMed

    Taylor, Eric G; Ahn, Woo-Kyoung

    2012-11-01

    Suppose one observes a correlation between two events, B and C, and infers that B causes C. Later one discovers that event A explains away the correlation between B and C. Normatively, one should now dismiss or weaken the belief that B causes C. Nonetheless, participants in the current study who observed a positive contingency between B and C followed by evidence that B and C were independent given A, persisted in believing that B causes C. The authors term this difficulty in revising initially learned causal structures "causal imprinting." Throughout four experiments, causal imprinting was obtained using multiple dependent measures and control conditions. A Bayesian analysis showed that causal imprinting may be normative under some conditions, but causal imprinting also occurred in the current study when it was clearly non-normative. It is suggested that causal imprinting occurs due to the influence of prior knowledge on how reasoners interpret later evidence. Consistent with this view, when participants first viewed the evidence showing that B and C are independent given A, later evidence with only B and C did not lead to the belief that B causes C. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Bench-to-bedside review: Ventilation-induced renal injury through systemic mediator release--just theory or a causal relationship?

    PubMed

    Kuiper, Jan Willem; Vaschetto, Rosanna; Della Corte, Francesco; Plötz, Frans B; Groeneveld, A B Johan

    2011-08-16

    We review the current literature on the molecular mechanisms involved in the pathogenesis of acute kidney injury induced by plasma mediators released by mechanical ventilation. A comprehensive literature search in the PubMed database was performed and articles were identified that showed increased plasma levels of mediators where the increase was solely attributable to mechanical ventilation. A subsequent search revealed articles delineating the potential effects of each mediator on the kidney or kidney cells. Limited research has focused specifically on the relationship between mechanical ventilation and acute kidney injury. Only a limited number of plasma mediators has been implicated in mechanical ventilation-associated acute kidney injury. The number of mediators released during mechanical ventilation is far greater and includes pro- and anti-inflammatory mediators, but also mediators involved in coagulation, fibrinolysis, cell adhesion, apoptosis and cell growth. The potential effects of these mediators is pleiotropic and include effects on inflammation, cell recruitment, adhesion and infiltration, apoptosis and necrosis, vasoactivity, cell proliferation, coagulation and fibrinolysis, transporter regulation, lipid metabolism and cell signaling. Most research has focused on inflammatory and chemotactic mediators. There is a great disparity of knowledge of potential effects on the kidney between different mediators. From a theoretical point of view, the systemic release of several mediators induced by mechanical ventilation may play an important role in the pathophysiology of acute kidney injury. However, evidence supporting a causal relationship is lacking for the studied mediators.

  10. Pore pressure behavior at the shut-in phase and causality of large induced seismicity at Basel, Switzerland

    NASA Astrophysics Data System (ADS)

    Mukuhira, Y.; Dinske, C.; Asanuma, H.; Ito, T.; Häring, M. O.

    2017-01-01

    Induced seismicity with unexpectedly large magnitude often occurs after shut-in or end of stimulation, generating concerns at the end of stimulation. We investigated the physical mechanism of large-magnitude induced seismicity during shut-in following the hydraulic stimulation at Basel, Switzerland. Larger postinjection events occurred at the periphery of the seismic cloud. We estimated the pore pressure required to cause shear slip using Coulomb failure criteria from stress information, geometry of the fault planes of microseismic events, and a constant coefficient of friction. Time series analysis of pore pressure distribution indicated that pore pressure migrated to the far field even after shut-in. Redistribution of pore pressure at shut-in brought sufficient pore pressure increase to induce seismicity in the peripheral region. After shut-in, the pore pressure gradient away from the well lessened and eventually pressure became uniform. These observations suggest that the higher pore pressure, which remained in the vicinity of the injection point, shifted to the farthest field. Shut-in pressure migration caused uniform pore pressure distribution at the edge of the seismic zone. Shut-in pressure destabilized a large part of the fault located at the edge of the seismic cloud, resulting in the shear slip of a large section of the fault. Meanwhile, during stimulation, only some parts of the fault entered the critical state because of the pressure gradient. The resulting shear slip on that specific part causes moderate magnitude events at most.

  11. Chemical-induced disease relation extraction with various linguistic features

    PubMed Central

    Gu, Jinghang; Qian, Longhua; Zhou, Guodong

    2016-01-01

    Understanding the relations between chemicals and diseases is crucial in various biomedical tasks such as new drug discoveries and new therapy developments. While manually mining these relations from the biomedical literature is costly and time-consuming, such a procedure is often difficult to keep up-to-date. To address these issues, the BioCreative-V community proposed a challenging task of automatic extraction of chemical-induced disease (CID) relations in order to benefit biocuration. This article describes our work on the CID relation extraction task on the BioCreative-V tasks. We built a machine learning based system that utilized simple yet effective linguistic features to extract relations with maximum entropy models. In addition to leveraging various features, the hypernym relations between entity concepts derived from the Medical Subject Headings (MeSH)-controlled vocabulary were also employed during both training and testing stages to obtain more accurate classification models and better extraction performance, respectively. We demoted relation extraction between entities in documents to relation extraction between entity mentions. In our system, pairs of chemical and disease mentions at both intra- and inter-sentence levels were first constructed as relation instances for training and testing, then two classification models at both levels were trained from the training examples and applied to the testing examples. Finally, we merged the classification results from mention level to document level to acquire final relations between chemicals and diseases. Our system achieved promising F-scores of 60.4% on the development dataset and 58.3% on the test dataset using gold-standard entity annotations, respectively. Database URL: https://github.com/JHnlp/BC5CIDTask PMID:27052618

  12. Chemical-induced disease relation extraction with various linguistic features.

    PubMed

    Gu, Jinghang; Qian, Longhua; Zhou, Guodong

    2016-01-01

    Understanding the relations between chemicals and diseases is crucial in various biomedical tasks such as new drug discoveries and new therapy developments. While manually mining these relations from the biomedical literature is costly and time-consuming, such a procedure is often difficult to keep up-to-date. To address these issues, the BioCreative-V community proposed a challenging task of automatic extraction of chemical-induced disease (CID) relations in order to benefit biocuration. This article describes our work on the CID relation extraction task on the BioCreative-V tasks. We built a machine learning based system that utilized simple yet effective linguistic features to extract relations with maximum entropy models. In addition to leveraging various features, the hypernym relations between entity concepts derived from the Medical Subject Headings (MeSH)-controlled vocabulary were also employed during both training and testing stages to obtain more accurate classification models and better extraction performance, respectively. We demoted relation extraction between entities in documents to relation extraction between entity mentions. In our system, pairs of chemical and disease mentions at both intra- and inter-sentence levels were first constructed as relation instances for training and testing, then two classification models at both levels were trained from the training examples and applied to the testing examples. Finally, we merged the classification results from mention level to document level to acquire final relations between chemicals and diseases. Our system achieved promisingF-scores of 60.4% on the development dataset and 58.3% on the test dataset using gold-standard entity annotations, respectively. Database URL:https://github.com/JHnlp/BC5CIDTask.

  13. Chemically inducible expression of the PHB biosynthetic pathway in Arabidopsis.

    PubMed

    Kourtz, Lauralynn; Dillon, Kevin; Daughtry, Sean; Peoples, Oliver P; Snell, Kristi D

    2007-12-01

    Arabidopsis plants were transformed with a multi-gene construct for expression of the polyhydroxybutyrate (PHB) biosynthetic pathway containing a gene switch that can be activated by commercially available non-steroidal ecdysone analogs approved for use on some crops as pesticides. T(1) progeny of transgenic Arabidopsis plants were isolated and screened for PHB production in the presence of ecdysone analogs. T(2) progeny derived from selected T(1) lines were subjected to further analysis by comparing PHB production levels prior to treatment with inducing agent and 21 days after initiation of induction. Significant PHB production was delayed in many of the engineered plants until after induction. PHB levels of up to 14.3% PHB per unit dry weight were observed in young leaves harvested from engineered T(2) plants after applications of the commercial ecdysone analog Mimic. PHB in older leaves reached levels of up to 7% PHB per unit dry weight. This study represents a first step towards engineering a chemically inducible gene switch for PHB production in plants using inducing agents that are approved for field use.

  14. Causality in thought.

    PubMed

    Sloman, Steven A; Lagnado, David

    2015-01-03

    Causal knowledge plays a crucial role in human thought, but the nature of causal representation and inference remains a puzzle. Can human causal inference be captured by relations of probabilistic dependency, or does it draw on richer forms of representation? This article explores this question by reviewing research in reasoning, decision making, various forms of judgment, and attribution. We endorse causal Bayesian networks as the best normative framework and as a productive guide to theory building. However, it is incomplete as an account of causal thinking. On the basis of a range of experimental work, we identify three hallmarks of causal reasoning-the role of mechanism, narrative, and mental simulation-all of which go beyond mere probabilistic knowledge. We propose that the hallmarks are closely related. Mental simulations are representations over time of mechanisms. When multiple actors are involved, these simulations are aggregated into narratives.

  15. Causal density matrices

    NASA Astrophysics Data System (ADS)

    Engelhardt, Netta; Fischetti, Sebastian

    2017-06-01

    We define a new construct in quantum field theory—the causal density matrix—obtained from the singularity structure of correlators of local operators. This object provides a necessary and sufficient condition for a quantum field theory state to have a holographic semiclassical dual causal geometry. By exploiting the causal density matrix, we find that these dual causal geometries quite generally (even away from AdS /CFT ) exhibit features of quantum error correction. Within AdS /CFT , we argue that the "reduced" causal density matrix is the natural dual to the causal wedge. Our formalism is very well-suited to generalizations of holography beyond AdS /CFT or even gravity/QFT.

  16. Information Theoretic Causal Coordination

    DTIC Science & Technology

    2013-09-12

    his 1969 paper, Clive Granger , British economist and Nobel laureate, proposed a statistical def- inition of causality between stochastic processes. It...showed that the directed infor- mation, an information theoretic quantity, quantifies Granger causality . We also explored a more pessimistic setup...Final Technical Report Project Title: Information Theoretic Causal Coordination AFOSR Award Number: AF FA9550-10-1-0345 Reporting Period: July 15

  17. Multisource causal data mining

    NASA Astrophysics Data System (ADS)

    Woodley, Robert; Gosnell, Michael; Shallenberger, Kevin

    2012-06-01

    Analysts are faced with mountains of data, and finding that relevant piece of information is the proverbial needle in a haystack, only with dozens of haystacks. Analysis tools that facilitate identifying causal relationships across multiple data sets are sorely needed. 21st Century Systems, Inc. (21CSi) has initiated research called Causal-View, a causal datamining visualization tool, to address this challenge. Causal-View is built on an agent-enabled framework. Much of the processing that Causal-View will do is in the background. When a user requests information, Data Extraction Agents launch to gather information. This initial search is a raw, Monte Carlo type search designed to gather everything available that may have relevance to an individual, location, associations, and more. This data is then processed by Data- Mining Agents. The Data-Mining Agents are driven by user supplied feature parameters. If the analyst is looking to see if the individual frequents a known haven for insurgents he may request information on his last known locations. Or, if the analyst is trying to see if there is a pattern in the individual's contacts, the mining agent can be instructed with the type and relevance of the information fields to look at. The same data is extracted from the database, but the Data Mining Agents customize the feature set to determine causal relationships the user is interested in. At this point, a Hypothesis Generation and Data Reasoning Agents take over to form conditional hypotheses about the data and pare the data, respectively. The newly formed information is then published to the agent communication backbone of Causal- View to be displayed. Causal-View provides causal analysis tools to fill the gaps in the causal chain. We present here the Causal-View concept, the initial research into data mining tools that assist in forming the causal relationships, and our initial findings.

  18. dsRNA-induced gene silencing in Moniliophthora perniciosa, the causal agent of witches' broom disease of cacao.

    PubMed

    Caribé dos Santos, A C; Sena, J A L; Santos, S C; Dias, C V; Pirovani, C P; Pungartnik, C; Valle, R R; Cascardo, J C M; Vincentz, M

    2009-11-01

    The genome sequence of the hemibiotrophic fungus Moniliophthora perniciosa revealed genes possibly participating in the RNAi machinery. Therefore, studies were performed in order to investigate the efficiency of gene silencing by dsRNA. We showed that the reporter gfp gene stably introduced into the fungus genome can be silenced by transfection of in vitro synthesized gfpdsRNA. In addition, successful dsRNA-induced silencing of endogenous genes coding for hydrophobins and a peroxiredoxin were also achieved. All genes showed a silencing efficiency ranging from 18% to 98% when compared to controls even 28d after dsRNA treatment, suggesting systemic silencing. Reduction of GFP fluorescence, peroxidase activity levels and survival responses to H(2)O(2) were consistent with the reduction of GFP and peroxidase mRNA levels, respectively. dsRNA transformation of M. perniciosa is shown here to efficiently promote genetic knockdown and can thus be used to assess gene function in this pathogen.

  19. Granger causality revisited.

    PubMed

    Friston, Karl J; Bastos, André M; Oswal, Ashwini; van Wijk, Bernadette; Richter, Craig; Litvak, Vladimir

    2014-11-01

    This technical paper offers a critical re-evaluation of (spectral) Granger causality measures in the analysis of biological timeseries. Using realistic (neural mass) models of coupled neuronal dynamics, we evaluate the robustness of parametric and nonparametric Granger causality. Starting from a broad class of generative (state-space) models of neuronal dynamics, we show how their Volterra kernels prescribe the second-order statistics of their response to random fluctuations; characterised in terms of cross-spectral density, cross-covariance, autoregressive coefficients and directed transfer functions. These quantities in turn specify Granger causality - providing a direct (analytic) link between the parameters of a generative model and the expected Granger causality. We use this link to show that Granger causality measures based upon autoregressive models can become unreliable when the underlying dynamics is dominated by slow (unstable) modes - as quantified by the principal Lyapunov exponent. However, nonparametric measures based on causal spectral factors are robust to dynamical instability. We then demonstrate how both parametric and nonparametric spectral causality measures can become unreliable in the presence of measurement noise. Finally, we show that this problem can be finessed by deriving spectral causality measures from Volterra kernels, estimated using dynamic causal modelling.

  20. Causality and Composite Structure

    SciTech Connect

    Joglekar, Satish D.

    2007-10-03

    In this talk, we discuss the question of whether a composite structure of elementary particles, with a length scale 1/{lambda}, can leave observable effects of non-locality and causality violation at higher energies (but {<=}{lambda}); employing a model-independent approach based on Bogoliubov-Shirkov formulation of causality. We formulate a condition which must be fulfilled for the derived theory to be causal, if the fundamental theory is so; and analyze it to exhibit possibilities which fulfil and which violate the condition. We comment on how causality violating amplitudes can arise.

  1. Granger causality revisited

    PubMed Central

    Friston, Karl J.; Bastos, André M.; Oswal, Ashwini; van Wijk, Bernadette; Richter, Craig; Litvak, Vladimir

    2014-01-01

    This technical paper offers a critical re-evaluation of (spectral) Granger causality measures in the analysis of biological timeseries. Using realistic (neural mass) models of coupled neuronal dynamics, we evaluate the robustness of parametric and nonparametric Granger causality. Starting from a broad class of generative (state-space) models of neuronal dynamics, we show how their Volterra kernels prescribe the second-order statistics of their response to random fluctuations; characterised in terms of cross-spectral density, cross-covariance, autoregressive coefficients and directed transfer functions. These quantities in turn specify Granger causality — providing a direct (analytic) link between the parameters of a generative model and the expected Granger causality. We use this link to show that Granger causality measures based upon autoregressive models can become unreliable when the underlying dynamics is dominated by slow (unstable) modes — as quantified by the principal Lyapunov exponent. However, nonparametric measures based on causal spectral factors are robust to dynamical instability. We then demonstrate how both parametric and nonparametric spectral causality measures can become unreliable in the presence of measurement noise. Finally, we show that this problem can be finessed by deriving spectral causality measures from Volterra kernels, estimated using dynamic causal modelling. PMID:25003817

  2. Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells.

    PubMed

    Panth, Kranthi Marella; Leijenaar, Ralph T H; Carvalho, Sara; Lieuwes, Natasja G; Yaromina, Ala; Dubois, Ludwig; Lambin, Philippe

    2015-09-01

    The central hypothesis of "radiomics" is that imaging features reflect tumor phenotype and genotype. Until now only correlative studies have been performed. The main objective of our study is to determine whether a causal relationship exists between genetic changes and image features. The secondary objective is to assess whether the combination with radiotherapy (RT) influences these image features. HCT116 doxycycline (dox) inducible GADD34 cells were grown as xenografts in the flanks of NMRI-nu mice. GADD34 overexpression decreases hypoxic fraction. Radiomics analyses were performed on computed tomography images obtained at 40kVp and again at 80kVp for validation, before radiotherapy at a volume of 200mm(3), 4days post RT (10Gy) and 500mm(3). To select reproducible features test-retest experiments were performed at baseline. Gene induction and/or irradiation translated into significant changes in radiomics features. Post irradiation, 17 features for 40kVp and 9 features for 80kVp differed significantly between dox+ and dox- combined with RT. 8 and 4 of these features remained consistent for 40 and 80kVp, respectively. Radiomics is able to identify early effects of changed gene expression combined with radiation treatment in tumors with similar volumes which are not visible to human eye. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Granger causality for state-space models

    NASA Astrophysics Data System (ADS)

    Barnett, Lionel; Seth, Anil K.

    2015-04-01

    Granger causality has long been a prominent method for inferring causal interactions between stochastic variables for a broad range of complex physical systems. However, it has been recognized that a moving average (MA) component in the data presents a serious confound to Granger causal analysis, as routinely performed via autoregressive (AR) modeling. We solve this problem by demonstrating that Granger causality may be calculated simply and efficiently from the parameters of a state-space (SS) model. Since SS models are equivalent to autoregressive moving average models, Granger causality estimated in this fashion is not degraded by the presence of a MA component. This is of particular significance when the data has been filtered, downsampled, observed with noise, or is a subprocess of a higher dimensional process, since all of these operations—commonplace in application domains as diverse as climate science, econometrics, and the neurosciences—induce a MA component. We show how Granger causality, conditional and unconditional, in both time and frequency domains, may be calculated directly from SS model parameters via solution of a discrete algebraic Riccati equation. Numerical simulations demonstrate that Granger causality estimators thus derived have greater statistical power and smaller bias than AR estimators. We also discuss how the SS approach facilitates relaxation of the assumptions of linearity, stationarity, and homoscedasticity underlying current AR methods, thus opening up potentially significant new areas of research in Granger causal analysis.

  4. Granger causality for state-space models.

    PubMed

    Barnett, Lionel; Seth, Anil K

    2015-04-01

    Granger causality has long been a prominent method for inferring causal interactions between stochastic variables for a broad range of complex physical systems. However, it has been recognized that a moving average (MA) component in the data presents a serious confound to Granger causal analysis, as routinely performed via autoregressive (AR) modeling. We solve this problem by demonstrating that Granger causality may be calculated simply and efficiently from the parameters of a state-space (SS) model. Since SS models are equivalent to autoregressive moving average models, Granger causality estimated in this fashion is not degraded by the presence of a MA component. This is of particular significance when the data has been filtered, downsampled, observed with noise, or is a subprocess of a higher dimensional process, since all of these operations-commonplace in application domains as diverse as climate science, econometrics, and the neurosciences-induce a MA component. We show how Granger causality, conditional and unconditional, in both time and frequency domains, may be calculated directly from SS model parameters via solution of a discrete algebraic Riccati equation. Numerical simulations demonstrate that Granger causality estimators thus derived have greater statistical power and smaller bias than AR estimators. We also discuss how the SS approach facilitates relaxation of the assumptions of linearity, stationarity, and homoscedasticity underlying current AR methods, thus opening up potentially significant new areas of research in Granger causal analysis.

  5. Chemically induced magnetism in atomically precise gold clusters.

    PubMed

    Krishna, Katla Sai; Tarakeshwar, Pilarisetty; Mujica, Vladimiro; Kumar, Challa S S R

    2014-03-12

    Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Light-induced chemical vapour deposition painting with titanium dioxide

    NASA Astrophysics Data System (ADS)

    Halary-Wagner, E.; Bret, T.; Hoffmann, P.

    2003-03-01

    Light-induced chemical vapour deposits of titanium dioxide are obtained from titanium tetra-isopropoxide (TTIP) in an oxygen and nitrogen atmosphere with a long pulse (250 ns) 308 nm XeCl excimer laser using a mask projection set-up. The demonstrated advantages of this technique are: (i) selective area deposition, (ii) precise control of the deposited thickness and (iii) low temperature deposition, enabling to use a wide range of substrates. A revolving mask system enables, in a single reactor load, to deposit shapes of controlled heights, which overlap to build up a complex pattern. Interferential multi-coloured deposits are achieved, and the process limitations (available colours and resolution) are discussed.

  7. Chemical-gene interaction networks and causal reasoning for biological effects prediction and prioritization of contaminants for environmental monitoring and surveillance

    EPA Science Inventory

    Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrat...

  8. Chemical-gene interaction networks and causal reasoning for biological effects prediction and prioritization of contaminants for environmental monitoring and surveillance

    EPA Science Inventory

    Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrat...

  9. Protein's native state stability in a chemically induced denaturation mechanism.

    PubMed

    Olivares-Quiroz, L; Garcia-Colin, L S

    2007-05-21

    In this work, we present a generalization of Zwanzig's protein unfolding analysis [Zwanzig, R., 1997. Two-state models of protein folding kinetics. Proc. Natl Acad. Sci. USA 94, 148-150; Zwanzig, R., 1995. Simple model of protein folding kinetics. Proc. Natl Acad. Sci. USA 92, 9801], in order to calculate the free energy change Delta(N)(D)F between the protein's native state N and its unfolded state D in a chemically induced denaturation. This Extended Zwanzig Model (EZM) is both based on an equilibrium statistical mechanics approach and the inclusion of experimental denaturation curves. It enables us to construct a suitable partition function Z and to derive an analytical formula for Delta(N)(D)F in terms of the number K of residues of the macromolecule, the average number nu of accessible states for each single amino acid and the concentration C(1/2) where the midpoint of the N<==>D transition occurs. The results of the EZM for proteins where chemical denaturation follows a sigmoidal-type profile, as it occurs for the case of the T70N human variant of lysozyme (PDB code: T70N) [Esposito, G., et al., 2003. J. Biol. Chem. 278, 25910-25918], can be splitted into two lines. First, EZM shows that for sigmoidal denaturation profiles, the internal degrees of freedom of the chain play an outstanding role in the stability of the native state. On the other hand, that under certain conditions DeltaF can be written as a quadratic polynomial on concentration C(1/2), i.e., DeltaF approximately aC(1/2)(2)+bC(1/2)+c, where a,b,c are constant coefficients directly linked to protein's size K and the averaged number of non-native conformations nu. Such functional form for DeltaF has been widely known to fit experimental measures in chemically induced protein denaturation [Yagi, M., et al., 2003. J. Biol. Chem. 278, 47009-47015; Asgeirsson, B., Guojonsdottir, K., 2006. Biochim. Biophys. Acta 1764, 190-198; Sharma, S., et al., 2006. Protein Pept. Lett. 13(4), 323-329; Salem, M., et

  10. Assay to detect chemically induced DNA repair in rat spermatocytes

    SciTech Connect

    Working, P.K.; Butterworth, B.E.

    1984-01-01

    An in vivo/in vitro DNA repair assay has been developed to quantitate chemically induced unscheduled DNA synthesis (UDS) in rat spermatocytes utilizing autoradiography. Male Fischer-344 rats were treated by i.p. injection or gavage with a variety of genotoxic agents dissolved in dimethyl sulfoxide, corn oil, or water. At selected times after treatment, spermatocytes were isolated by trypsin digestion of testes and cultured for 24 hr in the presence of /sup 3/H-thymidine. The direct-acting genotoxicants methyl methanesulfonate (MMS) and ethyl methanesulfonate and the chemotherapeutic agent cyclophosphamide (CPA) produced positive UDS responses in spermatocyes isolated l hr after i.p. injection. Other known genotoxicants--including dimethylnitrosamine, aflatoxin B/sub 1/, 2-acetylaminofluorene, 2, 6-dinitrotoluene, and l,6-dinitropyrene--failed to induce UDS, even with routes of administration and at times of exposure known to produce a positive response in hepatocytes. These results demonstrate that the in vivo/in vitro spermatocyte DNA repair assay may be useful as a predictive screen for germ cell mutagens.

  11. Causal Learning Across Domains

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Gopnik, Alison

    2004-01-01

    Five studies investigated (a) children's ability to use the dependent and independent probabilities of events to make causal inferences and (b) the interaction between such inferences and domain-specific knowledge. In Experiment 1, preschoolers used patterns of dependence and independence to make accurate causal inferences in the domains of…

  12. Repeated Causal Decision Making

    ERIC Educational Resources Information Center

    Hagmayer, York; Meder, Bjorn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

  13. Causality in Classical Electrodynamics

    ERIC Educational Resources Information Center

    Savage, Craig

    2012-01-01

    Causality in electrodynamics is a subject of some confusion, especially regarding the application of Faraday's law and the Ampere-Maxwell law. This has led to the suggestion that we should not teach students that electric and magnetic fields can cause each other, but rather focus on charges and currents as the causal agents. In this paper I argue…

  14. Causality in Classical Electrodynamics

    ERIC Educational Resources Information Center

    Savage, Craig

    2012-01-01

    Causality in electrodynamics is a subject of some confusion, especially regarding the application of Faraday's law and the Ampere-Maxwell law. This has led to the suggestion that we should not teach students that electric and magnetic fields can cause each other, but rather focus on charges and currents as the causal agents. In this paper I argue…

  15. Agency, time, and causality

    PubMed Central

    Widlok, Thomas

    2014-01-01

    Cognitive Scientists interested in causal cognition increasingly search for evidence from non-Western Educational Industrial Rich Democratic people but find only very few cross-cultural studies that specifically target causal cognition. This article suggests how information about causality can be retrieved from ethnographic monographs, specifically from ethnographies that discuss agency and concepts of time. Many apparent cultural differences with regard to causal cognition dissolve when cultural extensions of agency and personhood to non-humans are taken into account. At the same time considerable variability remains when we include notions of time, linearity and sequence. The article focuses on ethnographic case studies from Africa but provides a more general perspective on the role of ethnography in research on the diversity and universality of causal cognition. PMID:25414683

  16. Agency, time, and causality.

    PubMed

    Widlok, Thomas

    2014-01-01

    Cognitive Scientists interested in causal cognition increasingly search for evidence from non-Western Educational Industrial Rich Democratic people but find only very few cross-cultural studies that specifically target causal cognition. This article suggests how information about causality can be retrieved from ethnographic monographs, specifically from ethnographies that discuss agency and concepts of time. Many apparent cultural differences with regard to causal cognition dissolve when cultural extensions of agency and personhood to non-humans are taken into account. At the same time considerable variability remains when we include notions of time, linearity and sequence. The article focuses on ethnographic case studies from Africa but provides a more general perspective on the role of ethnography in research on the diversity and universality of causal cognition.

  17. Quantum causal graph dynamics

    NASA Astrophysics Data System (ADS)

    Arrighi, Pablo; Martiel, Simon

    2017-07-01

    Consider a graph having quantum systems lying at each node. Suppose that the whole thing evolves in discrete time steps, according to a global, unitary causal operator. By causal we mean that information can only propagate at a bounded speed, with respect to the distance given by the graph. Suppose, moreover, that the graph itself is subject to the evolution, and may be driven to be in a quantum superposition of graphs—in accordance to the superposition principle. We show that these unitary causal operators must decompose as a finite-depth circuit of local unitary gates. This unifies a result on quantum cellular automata with another on reversible causal graph dynamics. Along the way we formalize a notion of causality which is valid in the context of quantum superpositions of time-varying graphs, and has a number of good properties. We discuss some of the implications for quantum gravity.

  18. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (Final Report)

    EPA Science Inventory

    EPA announced the release of the final report, Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment . This report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induc...

  19. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (Final Report)

    EPA Science Inventory

    EPA announced the release of the final report, Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment . This report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induc...

  20. Causal Networks or Causal Islands? The Representation of Mechanisms and the Transitivity of Causal Judgment

    ERIC Educational Resources Information Center

    Johnson, Samuel G. B.; Ahn, Woo-kyoung

    2015-01-01

    Knowledge of mechanisms is critical for causal reasoning. We contrasted two possible organizations of causal knowledge--an interconnected causal "network," where events are causally connected without any boundaries delineating discrete mechanisms; or a set of disparate mechanisms--causal "islands"--such that events in different…

  1. Causal Networks or Causal Islands? The Representation of Mechanisms and the Transitivity of Causal Judgment

    ERIC Educational Resources Information Center

    Johnson, Samuel G. B.; Ahn, Woo-kyoung

    2015-01-01

    Knowledge of mechanisms is critical for causal reasoning. We contrasted two possible organizations of causal knowledge--an interconnected causal "network," where events are causally connected without any boundaries delineating discrete mechanisms; or a set of disparate mechanisms--causal "islands"--such that events in different…

  2. Causality and headache triggers

    PubMed Central

    Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

    2013-01-01

    Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

  3. [The causal relationship].

    PubMed

    Glemain, P

    2000-09-01

    Only the controlled trial method, clinical equivalent to the experimental method, with its successive phases and randomization, is able to confirm a real causal relationship and quantify the risk of error (alpha). However, the study must have sufficient power and randomization must not have resulted in an unbalanced distribution of various parameters likely to influence the result. Other methods, particularly surveys and case studies, only provide presumptions of causality. This review article, illustrated by three examples from the urological literature, is designed to demonstrate the difficulties of establishing a causal relationship when possible biases and confounding factors are taken into account.

  4. Improving causal inferences in risk analysis.

    PubMed

    Cox, Louis Anthony Tony

    2013-10-01

    Recent headlines and scientific articles projecting significant human health benefits from changes in exposures too often depend on unvalidated subjective expert judgments and modeling assumptions, especially about the causal interpretation of statistical associations. Some of these assessments are demonstrably biased toward false positives and inflated effects estimates. More objective, data-driven methods of causal analysis are available to risk analysts. These can help to reduce bias and increase the credibility and realism of health effects risk assessments and causal claims. For example, quasi-experimental designs and analysis allow alternative (noncausal) explanations for associations to be tested, and refuted if appropriate. Panel data studies examine empirical relations between changes in hypothesized causes and effects. Intervention and change-point analyses identify effects (e.g., significant changes in health effects time series) and estimate their sizes. Granger causality tests, conditional independence tests, and counterfactual causality models test whether a hypothesized cause helps to predict its presumed effects, and quantify exposure-specific contributions to response rates in differently exposed groups, even in the presence of confounders. Causal graph models let causal mechanistic hypotheses be tested and refined using biomarker data. These methods can potentially revolutionize the study of exposure-induced health effects, helping to overcome pervasive false-positive biases and move the health risk assessment scientific community toward more accurate assessments of the impacts of exposures and interventions on public health.

  5. Epidemiological assessment of occupationally related, chemically induced sperm count suppression

    SciTech Connect

    Milby, T.H.; Whorton, D.

    1980-02-01

    Occupationally related, chemically induced sperm count suppression is a recently recognized problem, first brought to light in connection with the manufacture and formulation of dibromochloropropane (DBCP). The authors studied sperm count data from four occupational cohorts - two exposed to DBCP and two exposed to epichlorohydrin (ECH). In both DBCP cohorts there was a significant difference (alpha = 0.05) between sperm count distribution functions of the exposed group and of the non-exposed group. A much higher percentage of exposed men was oligospermic and the median sperm count for each exposed group was substantially lower than that for the respective non-exposed group. In the ECH cohorts there was no significant difference between sperm count data for the exposed group and for the non-exposed group. The authors concluded that exposure to DBCP, but not to ECH, was positively associated with detectable sperm count suppression. It is suggested that the key to identifying and assessing occupationally related sperm count suppression lies in the proper classification and interpretation of group sperm count data.

  6. Cell Adhesion Molecules in Chemically-Induced Renal Injury

    PubMed Central

    Prozialeck, Walter C.; Edwards, Joshua R.

    2007-01-01

    Cell adhesion molecules are integral cell-membrane proteins that maintain cell-cell and cell-substrate adhesion, and in some cases, act as regulators of intracellular signaling cascades. In the kidney, cell adhesion molecules such as the cadherins, the catenins, ZO-1, occludin and the claudins are essential for maintaining the epithelial polarity and barrier integrity that are necessary for the normal absorption/excretion of fluid and solutes. A growing volume of evidence indicates that these cell adhesion molecules are important early targets for a variety of nephrotoxic substances including metals, drugs, and venom components. In addition, it is now widely appreciated that molecules such as ICAM-1, the integrins and selectins play important roles in the recruitment of leukocytes and inflammatory responses that are associated with nephrotoxic injury. This review summarizes the results of recent in vitro and in vivo studies indicating that these cell adhesion molecules may be primary molecular targets in many types of chemically-induced renal injury. Some of the specific agents that are discussed include Cd, Hg, Bi, cisplatin, aminoglycoside antibiotics, S-(1,2-dichlorovinyl-L-cysteine) (DCVC) and various venom toxins. This review also includes a discussion of the various mechanisms by which these substances can affect cell adhesion molecules in the kidney. PMID:17316817

  7. Chemically induced skin carcinogenesis: Updates in experimental models (Review)

    PubMed Central

    NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  8. Photo-induced chemical reaction of trans-resveratrol.

    PubMed

    Zhao, Yue; Shi, Meng; Ye, Jian-Hui; Zheng, Xin-Qiang; Lu, Jian-Liang; Liang, Yue-Rong

    2015-03-15

    Photo-induced chemical reaction of trans-resveratrol has been studied. UV B, liquid state and sufficient exposure time are essential conditions to the photochemical change of trans-resveratrol. Three principal compounds, cis-resveratrol, 2,4,6-phenanthrenetriol and 2-(4-hydroxyphenyl)-5,6-benzofurandione, were successively generated in the reaction solution of trans-resveratrol (0.25 mM, 100% ethanol) under 100 μW cm(-2) UV B radiation for 4h. cis-Resveratrol, originated from isomerization of trans-resveratrol, resulted in 2,4,6-phenanthrenetriol through photocyclisation reaction meanwhile loss of 2 H. 2,4,6-Phenanthrenetriol played a role of photosensitizer producing singlet oxygen in the reaction pathway. The singlet oxygen triggered [4+2] cycloaddition reaction of trans-resveratrol, and then resulted in the generation of 2-(4-hydroxyphenyl)-5,6-benzofurandione through photorearrangement and oxidation reaction. The singlet oxygen reaction was closely related to the substrate concentration of trans-resveratrol in solution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Plastic Changes in Human Motor Cortical Output Induced by Random but not Closed-Loop Peripheral Stimulation: the Curse of Causality

    PubMed Central

    Brown, Kenneth I.; Williams, Elizabeth R.; de Carvalho, Felipe; Baker, Stuart N.

    2016-01-01

    Previous work showed that repetitive peripheral nerve stimulation can induce plastic changes in motor cortical output. Triggering electrical stimulation of central structures from natural activity can also generate plasticity. In this study, we tested whether triggering peripheral nerve stimulation from muscle activity would likewise induce changes in motor output. We developed a wearable electronic device capable of recording electromyogram (EMG) and delivering electrical stimulation under closed-loop control. This allowed paired stimuli to be delivered over longer periods than standard laboratory-based protocols. We tested this device in healthy human volunteers. Motor cortical output in relaxed thenar muscles was first assessed via the recruitment curve of responses to contralateral transcranial magnetic stimulation. The wearable device was then configured to record thenar EMG and stimulate the median nerve at the wrist (intensity around motor threshold, rate ~0.66 Hz). Subjects carried out normal daily activities for 4–7 h, before returning to the laboratory for repeated recruitment curve assessment. Four stimulation protocols were tested (9–14 subjects each): No Stim, no stimuli delivered; Activity, stimuli triggered by EMG activity above threshold; Saved, stimuli timed according to a previous Activity session in the same subject; Rest, stimuli given when EMG was silent. As expected, No Stim did not modify the recruitment curve. Activity and Rest conditions produced no significant effects across subjects, although there were changes in some individuals. Saved produced a significant and substantial increase, with average responses 2.14 times larger at 30% stimulator intensity above threshold. We argue that unavoidable delays in the closed loop feedback, due mainly to central and peripheral conduction times, mean that stimuli in the Activity paradigm arrived too late after cortical activation to generate consistent plastic changes. By contrast, stimuli

  10. Plastic Changes in Human Motor Cortical Output Induced by Random but not Closed-Loop Peripheral Stimulation: the Curse of Causality.

    PubMed

    Brown, Kenneth I; Williams, Elizabeth R; de Carvalho, Felipe; Baker, Stuart N

    2016-01-01

    Previous work showed that repetitive peripheral nerve stimulation can induce plastic changes in motor cortical output. Triggering electrical stimulation of central structures from natural activity can also generate plasticity. In this study, we tested whether triggering peripheral nerve stimulation from muscle activity would likewise induce changes in motor output. We developed a wearable electronic device capable of recording electromyogram (EMG) and delivering electrical stimulation under closed-loop control. This allowed paired stimuli to be delivered over longer periods than standard laboratory-based protocols. We tested this device in healthy human volunteers. Motor cortical output in relaxed thenar muscles was first assessed via the recruitment curve of responses to contralateral transcranial magnetic stimulation. The wearable device was then configured to record thenar EMG and stimulate the median nerve at the wrist (intensity around motor threshold, rate ~0.66 Hz). Subjects carried out normal daily activities for 4-7 h, before returning to the laboratory for repeated recruitment curve assessment. Four stimulation protocols were tested (9-14 subjects each): No Stim, no stimuli delivered; Activity, stimuli triggered by EMG activity above threshold; Saved, stimuli timed according to a previous Activity session in the same subject; Rest, stimuli given when EMG was silent. As expected, No Stim did not modify the recruitment curve. Activity and Rest conditions produced no significant effects across subjects, although there were changes in some individuals. Saved produced a significant and substantial increase, with average responses 2.14 times larger at 30% stimulator intensity above threshold. We argue that unavoidable delays in the closed loop feedback, due mainly to central and peripheral conduction times, mean that stimuli in the Activity paradigm arrived too late after cortical activation to generate consistent plastic changes. By contrast, stimuli delivered

  11. Causal networks in EIA

    SciTech Connect

    Perdicoulis, Anastassios . E-mail: tasso@utad.pt; Glasson, John . E-mail: jglasson@brookes.ac.uk

    2006-08-15

    Causal networks have been used in Environmental Impact Assessment (EIA) since its early days, but they appear to have a minimal use in modern practice. This article reviews the typology of causal networks in EIA as well as in other academic and professional fields, verifies their contribution to EIA against the principles and requirements of the process, and discusses alternative scenarios for their future in EIA.

  12. Obesity and infection: reciprocal causality.

    PubMed

    Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

    2015-01-01

    Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

  13. Chemically Induced Fires in Aircraft Electrical Circuitry by Glycol/ Water Solutions. Hazard Analysis and Elimination Methods

    DTIC Science & Technology

    1975-01-29

    DISCLOSURE# DISTRIBUTION STATEMENT A APPROVED FOR PUBLIC REL-EASE; DISTRIBUTION UNLIMITED, AD-AO08 896 CHEMICALLY INDUCED FIRES IN AIRCRAFT ELECTRICAL...January 1975 DISTRIBUTED BY: National Technical InfermatieM Service U. S. DEPARTMENT OF COMMERCE FZM-6345 12 9 04. 29 JANUARY 1975 Cf.) -- CHEMICALLY ...DYNAMICS FZM-6345 Fort Worth Division 29 JANUARY 1975 TITLE * CHEMICALLY INDUCED FIRES IN AIRCRAFT ELECTRICAL CIRCUITRY BY GLYCOL/WATER SOLUTIONS - HAZARD

  14. Differential Gene Expression in Chemically Induced Mouse Lung Adenomas1

    PubMed Central

    Yao, Ruisheng; Wang, Yian; Lubet, Ronald A; You, Ming

    2003-01-01

    Abstract Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS) was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60%) of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, α-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK), α-adaptin, α-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and α- and β-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240) and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of lung

  15. Determination whether the causal agent for mussel die-offs in the Mississippi River is of chemical or biological origin. Final report

    SciTech Connect

    Sparks, R.E.; Blodgett, K.D.; Durham, L.; Horner, R.

    1990-04-01

    Unexplained die-offs of freshwater mussels have occurred in the Mississippi River, including the water of Illinois, from 1982 to 1986. The research was directed at determining the cause, biological or chemical, of these massive die-offs. During the project, over 600 freshwater mussels were collected from the Illinois and Mississippi rivers. Sampling methodologies were developed to collect bacteria associated with various mussel organs and tissues, and the bacterial flora were characterized. This characterization of the bacterial flora of freshwater mussels provides a baseline for comparisons should mussel die-offs resume in the future.

  16. Causality discovery technology

    NASA Astrophysics Data System (ADS)

    Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

    2012-11-01

    Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

  17. Causal conditionals and counterfactuals

    PubMed Central

    Frosch, Caren A.; Byrne, Ruth M.J.

    2012-01-01

    Causal counterfactuals e.g., ‘if the ignition key had been turned then the car would have started’ and causal conditionals e.g., ‘if the ignition key was turned then the car started’ are understood by thinking about multiple possibilities of different sorts, as shown in six experiments using converging evidence from three different types of measures. Experiments 1a and 1b showed that conditionals that comprise enabling causes, e.g., ‘if the ignition key was turned then the car started’ primed people to read quickly conjunctions referring to the possibility of the enabler occurring without the outcome, e.g., ‘the ignition key was turned and the car did not start’. Experiments 2a and 2b showed that people paraphrased causal conditionals by using causal or temporal connectives (because, when), whereas they paraphrased causal counterfactuals by using subjunctive constructions (had…would have). Experiments 3a and 3b showed that people made different inferences from counterfactuals presented with enabling conditions compared to none. The implications of the results for alternative theories of conditionals are discussed. PMID:22858874

  18. Acoustic charge transport induced by the surface acoustic wave in chemical doped graphene

    NASA Astrophysics Data System (ADS)

    Zheng, Shijun; Zhang, Hao; Feng, Zhihong; Yu, Yuanyuan; Zhang, Rui; Sun, Chongling; Liu, Jing; Duan, Xuexin; Pang, Wei; Zhang, Daihua

    2016-10-01

    A graphene/LiNbO3 hybrid device is used to investigate the acoustic induced charge transport in chemical doped graphene. The chemical doping of graphene via its physisorption of gas molecules affects the surface acoustic wave (SAW) charge carrier transport in a manner different from electric field drift. That transport induces doping dependent macroscopic acoustoelectric current. The chemical doping can manipulate majority carriers and induces unique acoustoelectric features. The observation is explained by a classical relaxation model. Eventually the device based on acoustoelectric current is proved to outperform the common chemiresistor for chemicals. Our finding provides insight into acoustic charge carrier transport during chemical doping. The doping affects interaction of carriers with SAW phonon and facilitates the understanding of nanoscale acoustoelectric effect. The exploration inspires potential acoustoelectric application for chemical detection involving emerging 2D nanomaterials.

  19. Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed.

    PubMed

    Rasher, Douglas B; Hay, Mark E

    2014-02-22

    Many seaweeds and terrestrial plants induce chemical defences in response to herbivory, but whether they induce chemical defences against competitors (allelopathy) remains poorly understood. We evaluated whether two tropical seaweeds induce allelopathy in response to competition with a reef-building coral. We also assessed the effects of competition on seaweed growth and seaweed chemical defence against herbivores. Following 8 days of competition with the coral Porites cylindrica, the chemically rich seaweed Galaxaura filamentosa induced increased allelochemicals and became nearly twice as damaging to the coral. However, it also experienced significantly reduced growth and increased palatability to herbivores (because of reduced chemical defences). Under the same conditions, the seaweed Sargassum polycystum did not induce allelopathy and did not experience a change in growth or palatability. This is the first demonstration of induced allelopathy in a seaweed, or of competitors reducing seaweed chemical defences against herbivores. Our results suggest that the chemical ecology of coral-seaweed-herbivore interactions can be complex and nuanced, highlighting the need to incorporate greater ecological complexity into the study of chemical defence.

  20. Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed

    PubMed Central

    Rasher, Douglas B.; Hay, Mark E.

    2014-01-01

    Many seaweeds and terrestrial plants induce chemical defences in response to herbivory, but whether they induce chemical defences against competitors (allelopathy) remains poorly understood. We evaluated whether two tropical seaweeds induce allelopathy in response to competition with a reef-building coral. We also assessed the effects of competition on seaweed growth and seaweed chemical defence against herbivores. Following 8 days of competition with the coral Porites cylindrica, the chemically rich seaweed Galaxaura filamentosa induced increased allelochemicals and became nearly twice as damaging to the coral. However, it also experienced significantly reduced growth and increased palatability to herbivores (because of reduced chemical defences). Under the same conditions, the seaweed Sargassum polycystum did not induce allelopathy and did not experience a change in growth or palatability. This is the first demonstration of induced allelopathy in a seaweed, or of competitors reducing seaweed chemical defences against herbivores. Our results suggest that the chemical ecology of coral–seaweed–herbivore interactions can be complex and nuanced, highlighting the need to incorporate greater ecological complexity into the study of chemical defence. PMID:24403332

  1. Chemically and temperature-induced phase transformations of metal vanadates

    NASA Astrophysics Data System (ADS)

    Patridge, Christopher James

    Metal vanadates contain a diverse family of compounds due to the facile accessibility of different vanadium oxidation states and local coordination environments. Though these systems present a number of applications in catalysis and electronics, there may exist untapped physical phenomena that only reveal themselves when scaling these materials to nanoscale dimensions. Finite-size effects result from a number of factors including surface energy structural instabilities, nanostructure "self-purification," and physical constraints on mechanistic or conductive pathways. The MxV2O 5 bronze materials possess non-stoichiometry and this interesting property has hindered synthetic techniques to procure perfect crystalline material which is needed to expose the true physical properties. Through hydrothermal synthesis methods, pseudo one---dimensional nanostructures of Mx V2O5 display fascinating new properties and may be model systems for studying fundamentals associated with correlated electron dynamics in solid-state physics. Electron microscopy and powder X-ray diffraction reveal the near-perfect crystalline nanostructures. X-ray absorption spectroscopy studies show strong evidence for the localization of electron density and long-range crystal structure alignment of the nanowires. Single-nanowire electron transport measurements for the beta'-CuxV2O5 and the delta-KxV2O5 data shows novel temperature-induced reversible metal---insulator transition (MIT) near room temperature. The unprecedented magnitude (˜105) and discontinuous nature of the MIT suggests a mechanism closely associated with correlated electron motion. Additionally, the MIT can be induced by voltage ramping. The simultaneous temperature/voltage studies of single-nanowire transport support the existence of a critical threshold to overcome in order to facilitate instability in the insulating phase and transition to a metallic phase for the delta-KxV2O5 bronze. The MIT transition magnitudes of several

  2. Causal networks or causal islands? The representation of mechanisms and the transitivity of causal judgment

    PubMed Central

    Johnson, Samuel G. B.; Ahn, Woo-kyoung

    2014-01-01

    Knowledge of mechanisms is critical for causal reasoning. We contrasted two possible organizations of causal knowledge—an interconnected causal network, where events are causally connected without any boundaries delineating discrete mechanisms; or a set of disparate mechanisms—causal islands—such that events in different mechanisms are not thought to be related even when they belong to the same causal chain. To distinguish these possibilities, we used causal transitivity—the inference given A causes B and B causes C that A causes C. Specifically, causal chains schematized as one chunk or mechanism in semantic memory (e.g., exercising, becoming thirsty, drinking water) led to transitive causal judgments. On the other hand, chains schematized as multiple chunks (e.g., having sex, becoming pregnant, becoming nauseous) led to intransitive judgments despite strong intermediate links (Experiments 1–3). Normative accounts of causal intransitivity could not explain these intransitive judgments (Experiments 4–5). PMID:25556901

  3. Central nervous defects in two children of mothers exposed to chemicals in the reinforced plastics industry. Chance or a causal relation?

    PubMed

    Holmberg, P C

    1977-12-01

    With the use of a specially designed questionnaire, with the emphasis on occupational exposure to chemical agents at work, a case-referent study was started on 1 June 1976. The series comprised mothers of all children with central nervous defects notified to the Finnish Register of Congenital Malformations and their matched-pair referents. Information was gained by personal interview. By 1 March 1977 information had been gathered from 43 cases and their referents. Two case mothers had been employed in the reinforced plastics industry and had been exposed at work to a combination of styrene, polyester resin, organic peroxides, and acetone. When the number of fertile women in this industry is considered (some 250), along with the low rate of anencephaly and hydrochephalus in the general population--diagnoses made of the children of these case mothers (0.5/1,000 live births in Finland)--this occupational group is strongly overrepresented in the material. The paper is a more-detailed report regarding the two cases. Moreover a third case is mentioned in which the pregnant mother, a juvenile diabetic, had been exposed at home to styrene, polyester resin, and organic peroxides.

  4. Comparative chemical screening and genetic analysis reveal tentoxin as a new virulence factor in Cochliobolus miyabeanus, the causal agent of brown spot disease on rice.

    PubMed

    De Bruyne, Lieselotte; Van Poucke, Christof; Di Mavungu, Diana Jose; Zainudin, Nur Ain Izzati Mohd; Vanhaecke, Lynn; De Vleesschauwer, David; Turgeon, B Gillian; De Saeger, Sarah; Höfte, Monica

    2016-08-01

    Brown spot disease, caused by Cochliobolus miyabeanus, is currently considered to be one of the most important yield reducers of rice (Oryza sativa L.). Despite its agricultural importance, little is known about the virulence mechanisms deployed by the fungus. Therefore, we set out to identify novel virulence factors with a role in disease development. This article reports, for the first time, the production of tentoxin by C. miyabeanus as a virulence factor during brown spot disease and the identification of the non-ribosomal protein synthetase (NRPS) CmNps3, responsible for tentoxin biosynthesis. We compared the chemical compounds produced by C. miyabeanus strains differing in virulence ability using ultra-high-performance liquid chromatography (UHPLC) coupled to high-resolution Orbitrap mass spectrometry (HRMS). The production of tentoxin by a highly virulent strain was revealed by principal component analysis of the detected ions and confirmed by UHPLC coupled to tandem-quadrupole mass spectrometry (MS/MS). The corresponding NRPS was identified by in silico genome analysis and confirmed by gene deletion. Infection tests with wild-type and Cmnps3 mutants showed that tentoxin acts as a virulence factor and is correlated with chlorosis development during the second phase of infection. Although rice has previously been classified as a tentoxin-insensitive plant species, our data demonstrate that tentoxin production by C. miyabeanus affects symptom development. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  5. CD-REST: a system for extracting chemical-induced disease relation in literature.

    PubMed

    Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

    2016-01-01

    Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug-disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed fromhttp://clinicalnlptool.com/cdr The online CD-REST demonstration system is available athttp://clinicalnlptool.com/cdr/cdr.html. Database URL:http://clinicalnlptool.com/cdr;http://clinicalnlptool.com/cdr/cdr.html.

  6. Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis

    SciTech Connect

    Reynolds, S.H.; Stowers, S.J.; Patterson, R.M.; Maronpot, R.R.; Anderson, M.W.

    1988-06-01

    The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

  7. More discussions for granger causality and new causality measures.

    PubMed

    Hu, Sanqing; Cao, Yu; Zhang, Jianhai; Kong, Wanzeng; Yang, Kun; Zhang, Yanbin; Li, Xun

    2012-02-01

    Granger causality (GC) has been widely applied in economics and neuroscience to reveal causality influence of time series. In our previous paper (Hu et al., in IEEE Trans on Neural Netw, 22(6), pp. 829-844, 2011), we proposed new causalities in time and frequency domains and particularly focused on new causality in frequency domain by pointing out the shortcomings/limitations of GC or Granger-alike causality metrics and the advantages of new causality. In this paper we continue our previous discussions and focus on new causality and GC or Granger-alike causality metrics in time domain. Although one strong motivation was introduced in our previous paper (Hu et al., in IEEE Trans on Neural Netw, 22(6), pp. 829-844, 2011) we here present additional motivation for the proposed new causality metric and restate the previous motivation for completeness. We point out one property of conditional GC in time domain and the shortcomings/limitations of conditional GC which cannot reveal the real strength of the directional causality among three time series. We also show the shortcomings/limitations of directed causality (DC) or normalize DC for multivariate time series and demonstrate it cannot reveal real causality at all. By calculating GC and new causality values for an example we demonstrate the influence of one of the time series on the other is linearly increased as the coupling strength is linearly increased. This fact further supports reasonability of new causality metric. We point out that larger instantaneous correlation does not necessarily mean larger true causality (e.g., GC and new causality), or vice versa. Finally we conduct analysis of statistical test for significance and asymptotic distribution property of new causality metric by illustrative examples.

  8. Evaluating Causal Models.

    ERIC Educational Resources Information Center

    Watt, James H., Jr.

    Pointing out that linear causal models can organize the interrelationships of a large number of variables, this paper contends that such models are particularly useful to mass communication research, which must by necessity deal with complex systems of variables. The paper first outlines briefly the philosophical requirements for establishing a…

  9. Causal Premise Semantics

    ERIC Educational Resources Information Center

    Kaufmann, Stefan

    2013-01-01

    The rise of causality and the attendant graph-theoretic modeling tools in the study of counterfactual reasoning has had resounding effects in many areas of cognitive science, but it has thus far not permeated the mainstream in linguistic theory to a comparable degree. In this study I show that a version of the predominant framework for the formal…

  10. Causal Responsibility and Counterfactuals

    ERIC Educational Resources Information Center

    Lagnado, David A.; Gerstenberg, Tobias; Zultan, Ro'i

    2013-01-01

    How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in…

  11. Causality: Physics and Philosophy

    ERIC Educational Resources Information Center

    Chatterjee, Atanu

    2013-01-01

    Nature is a complex causal network exhibiting diverse forms and species. These forms or rather systems are physically open, structurally complex and naturally adaptive. They interact with the surrounding media by operating a positive-feedback loop through which, they adapt, organize and self-organize themselves in response to the ever-changing…

  12. Causal Responsibility and Counterfactuals

    ERIC Educational Resources Information Center

    Lagnado, David A.; Gerstenberg, Tobias; Zultan, Ro'i

    2013-01-01

    How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in…

  13. Causal Premise Semantics

    ERIC Educational Resources Information Center

    Kaufmann, Stefan

    2013-01-01

    The rise of causality and the attendant graph-theoretic modeling tools in the study of counterfactual reasoning has had resounding effects in many areas of cognitive science, but it has thus far not permeated the mainstream in linguistic theory to a comparable degree. In this study I show that a version of the predominant framework for the formal…

  14. The development of causal reasoning.

    PubMed

    Kuhn, Deanna

    2012-05-01

    How do inference rules for causal learning themselves change developmentally? A model of the development of causal reasoning must address this question, as well as specify the inference rules. Here, the evidence for developmental changes in processes of causal reasoning is reviewed, with the distinction made between diagnostic causal inference and causal prediction. Also addressed is the paradox of a causal reasoning literature that highlights the competencies of young children and the proneness to error among adults. WIREs Cogn Sci 2012, 3:327-335. doi: 10.1002/wcs.1160 For further resources related to this article, please visit the WIREs website.

  15. Spectroscopic Observation of Chemical Interaction Between Impact-induced Vapor Clouds and the Ambient Atmosphere

    NASA Technical Reports Server (NTRS)

    Sugita, S.; Heineck, J. T.; Schultz, P. H.

    2000-01-01

    Chemical reactions within impact-induced vapor clouds were observed in laboratory experiments using a spectroscopic method. The results indicate that projectile-derived carbon-rich vapor reacts intensively with atmospheric nitrogen.

  16. Enhanced chemical reactivity of graphene induced by mechanical strain.

    PubMed

    Bissett, Mark A; Konabe, Satoru; Okada, Susumu; Tsuji, Masaharu; Ago, Hiroki

    2013-11-26

    Control over chemical reactivity is essential in the field of nanotechnology. Graphene is a two-dimensional atomic sheet of sp(2) hybridized carbon with exceptional properties that can be altered by chemical functionalization. Here, we transferred single-layer graphene onto a flexible substrate and investigated the functionalization using different aryl diazonium molecules while applying mechanical strain. We found that mechanical strain can alter the structure of graphene, and dramatically increase the reaction rate, by a factor of up to 10, as well as increase the final degree of functionalization. Furthermore, we demonstrate that mechanical strain enables functionalization of graphene for both p- and n-type dopants, where unstrained graphene showed negligible reactivity. Theoretical calculations were also performed to support the experimental findings. Our findings offer a simple approach to control the chemical reactivity of graphene through the application of mechanical strain, allowing for a tuning of the properties of graphene.

  17. Causal Status and Coherence in Causal-Based Categorization

    ERIC Educational Resources Information Center

    Rehder, Bob; Kim, ShinWoo

    2010-01-01

    Research has documented two effects of interfeature causal knowledge on classification. A "causal status effect" occurs when features that are causes are more important to category membership than their effects. A "coherence effect" occurs when combinations of features that are consistent with causal laws provide additional…

  18. Causal Status and Coherence in Causal-Based Categorization

    ERIC Educational Resources Information Center

    Rehder, Bob; Kim, ShinWoo

    2010-01-01

    Research has documented two effects of interfeature causal knowledge on classification. A "causal status effect" occurs when features that are causes are more important to category membership than their effects. A "coherence effect" occurs when combinations of features that are consistent with causal laws provide additional…

  19. Chlorine Dioxide Induced Multiple Chemical Sensitivity: MMPI Validity Problems.

    ERIC Educational Resources Information Center

    Tentoni, Stuart C.

    This paper discusses Minnesota Multiphasic Personality Inventory (MMPI) data obtained from individuals exposed to chlorine dioxide in the workplace who developed Multiple Chemical Sensitivity Syndrome. The paper explores current research on chlorine dioxide exposed persons who were misdiagnosed on the basis of MMPI interpretations. Difficulties…

  20. Chlorine Dioxide Induced Multiple Chemical Sensitivity: MMPI Validity Problems.

    ERIC Educational Resources Information Center

    Tentoni, Stuart C.

    This paper discusses Minnesota Multiphasic Personality Inventory (MMPI) data obtained from individuals exposed to chlorine dioxide in the workplace who developed Multiple Chemical Sensitivity Syndrome. The paper explores current research on chlorine dioxide exposed persons who were misdiagnosed on the basis of MMPI interpretations. Difficulties…

  1. Causal Attributions in Young Children.

    ERIC Educational Resources Information Center

    Friedberg, Robert D.; Dalenberg, Constance J.

    1990-01-01

    Investigated the causal explanations children use to account for common experiences. In the study, 60 preschoolers watched videotaped puppet shows designed to elicit causal attributions. Most children predominantly used internal, unstable, and specific attributions. (CB)

  2. Causal Attributions in Young Children.

    ERIC Educational Resources Information Center

    Friedberg, Robert D.; Dalenberg, Constance J.

    1990-01-01

    Investigated the causal explanations children use to account for common experiences. In the study, 60 preschoolers watched videotaped puppet shows designed to elicit causal attributions. Most children predominantly used internal, unstable, and specific attributions. (CB)

  3. The development of causal categorization.

    PubMed

    Hayes, Brett K; Rehder, Bob

    2012-08-01

    Two experiments examined the impact of causal relations between features on categorization in 5- to 6-year-old children and adults. Participants learned artificial categories containing instances with causally related features and noncausal features. They then selected the most likely category member from a series of novel test pairs. Classification patterns and logistic regression were used to diagnose the presence of independent effects of causal coherence, causal status, and relational centrality. Adult classification was driven primarily by coherence when causal links were deterministic (Experiment 1) but showed additional influences of causal status when links were probabilistic (Experiment 2). Children's classification was based primarily on causal coherence in both cases. There was no effect of relational centrality in either age group. These results suggest that the generative model (Rehder, 2003a) provides a good account of causal categorization in children as well as adults. Copyright © 2012 Cognitive Science Society, Inc.

  4. Stress-induced chemical waves in sediment burial diagenesis.

    PubMed

    Wang, Yifeng; Budd, David A

    2012-02-21

    Lateral metre-scale periodic variations in porosity and composition are found in many dolomite strata. Such variations may embed important information about dolomite formation and transformation. Here we show that these variations could be fossilized chemical waves emerging from stress-mediated mineral-water interaction during sediment burial diagenesis. Under the overlying loading, crystals in higher porosity domains are subjected to a higher effective stress, causing pressure solution. The dissolved species diffuse to and precipitate in neighbouring lower porosity domains, further reducing the porosity. This positive feedback leads to lateral porosity and compositional patterning in dolomite. The pattern geometry depends on fluid flow regimes. In a diffusion-dominated case, the low- and high-porosity domains alternate spatially with no directional preference, while, in the presence of an advective flow, this alternation occurs only along the flow direction, propagating like a chemical wave. Our work provides a new perspective for interpreting diagenetic signatures in sedimentary rocks.

  5. Chemical processes induced by OH attack on nucleic acids

    NASA Astrophysics Data System (ADS)

    Kuwabara, Mikinori

    Recent studies concerning the chemical processes in nucleic acids starting with OH attack to produce free radicals and ending with the formation of stable products were reviewed. Using nucleosides, nucleotides and homopolynucleotides as model compounds, and DNA itself, free radicals produced by OH attack on nucleic acids have been mainly studied by a method combining ESR, spin trapping and high-performance liquid chromatography. For identification of final products in both base and sugar moieties of nucleic acids, mass and NMR spectroscopies combined with gas chromatography or high-performance liquid chromatography are usually employed. Kinetic measurements of structural alterations in the polynucleotides and DNA after OH attack have been made by a method combining electron-pulse irradiation and laser-light scattering. From these studies, the chemical reaction processes from the generation of free radicals in nucleic acids by OH attack, through the formation of unstable intermediates, to the formation of final products can be described.

  6. Chemically Induced Phase Transformation in Austenite by Focused Ion Beam

    NASA Astrophysics Data System (ADS)

    Basa, Adina; Thaulow, Christian; Barnoush, Afrooz

    2013-11-01

    A highly stable austenite phase in a super duplex stainless steel was subjected to a combination of different gallium ion doses at different acceleration voltages. It was shown that contrary to what is expected, an austenite to ferrite phase transformation occurred within the focused ion beam (FIB) milled regions. Chemical analysis of the FIB milled region proved that the gallium implantation preceded the FIB milling. High resolution electron backscatter diffraction analysis also showed that the phase transformation was not followed by the typical shear and plastic deformation expected from the martensitic transformation. On the basis of these observations, it was concluded that the change in the chemical composition of the austenite and the local increase in gallium, which is a ferrite stabilizer, results in the local selective transformation of austenite to ferrite.

  7. Laser Induced Chemical Vapor Deposition of Gallium Arsenide Films.

    DTIC Science & Technology

    1987-08-20

    be grown. The VPE processes can be subdivided into (a) the chloride and (b) the metalorganic chemical vapor deposition (MOCVD) processes. The... chloride VPE processes, utilizing 1= AsCl 3 -Ga-H 2 or HC1-Ga-AsH3 . are capable of producing epitazial layers with low carrier concentrations and high...electron mobilities. However. the chloride systems have not been successful for the growth of aluminum- containing III-V alloys because of the reactivity

  8. Shock-Induced Chemical Reactions in Condensed Matter.

    DTIC Science & Technology

    1982-08-01

    Technical, 4/1/78 - 6/30/82 Matter 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(s) S. CONTRACT OR GRANT NUMUER(e) George E. Duvall, Principal Investigator...CHEMICAL REACTIONS IN CONDENSED MATTER George E. Duvall, Principal Investigator Stephen A. Sheffield* Kendal M. OgilvieT 4 C. Robert Wilson Paul...Temperture," in Sixth Symposium (International on Detonation (Office of Naval Research, Arlington, 1976), ACR-Z21, p. 36. 24. G. Gamow , "Tentative

  9. Causal Discovery of Dynamic Systems

    ERIC Educational Resources Information Center

    Voortman, Mark

    2010-01-01

    Recently, several philosophical and computational approaches to causality have used an interventionist framework to clarify the concept of causality [Spirtes et al., 2000, Pearl, 2000, Woodward, 2005]. The characteristic feature of the interventionist approach is that causal models are potentially useful in predicting the effects of manipulations.…

  10. Causal Discovery of Dynamic Systems

    ERIC Educational Resources Information Center

    Voortman, Mark

    2010-01-01

    Recently, several philosophical and computational approaches to causality have used an interventionist framework to clarify the concept of causality [Spirtes et al., 2000, Pearl, 2000, Woodward, 2005]. The characteristic feature of the interventionist approach is that causal models are potentially useful in predicting the effects of manipulations.…

  11. Chemical products induce resistance to Xanthomonas perforans in tomato

    PubMed Central

    Itako, Adriana Terumi; Tolentino, João Batista; da Silva, Tadeu Antônio Fernandes; Soman, José Marcelo; Maringoni, Antonio Carlos

    2015-01-01

    The bacterial spot of tomato, caused by Xanthomonas spp., is a very important disease, especially in the hot and humid periods of the year. The chemical control of the disease has not been very effective for a number of reasons. This study aimed to evaluate, under greenhouse conditions, the efficacy of leaf-spraying chemicals (acibenzolar-S-methyl (ASM) (0.025 g.L−1), fluazinam (0.25 g.L−1), pyraclostrobin (0.08 g.L−1), pyraclostrobin + methiran (0.02 g.L−1 + 2.2 g.L−1), copper oxychloride (1.50 g.L−1), mancozeb + copper oxychloride (0.88 g.L−1 + 0.60 g.L−1), and oxytetracycline (0.40 g.L−1)) on control of bacterial spot. Tomatoes Santa Clara and Gisele cultivars were pulverized 3 days before inoculation with Xanthomonas perforans. The production of enzymes associated with resistance induction (peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, β-1,3-glucanase, and protease) was quantified from leaf samples collected 24 hours before and 24 hours after chemical spraying and at 1, 2, 4, 6, and 8 days after bacterial inoculation. All products tested controlled bacterial spot, but only ASM, pyraclostrobin, and pyraclostrobin + metiram increased the production of peroxidase in the leaves of the two tomato cultivars, and increased the production of polyphenol oxidase and β-1,3-glucanase in the Santa Clara cultivar. PMID:26413050

  12. Causal Responsibility and Counterfactuals

    PubMed Central

    Lagnado, David A; Gerstenberg, Tobias; Zultan, Ro'i

    2013-01-01

    How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in multiple agent contexts. We draw on the structural model account of actual causation (e.g., Halpern & Pearl, 2005) and its extension to responsibility judgments (Chockler & Halpern, 2004). We review the main theoretical and empirical issues that arise from this literature and propose a novel model of intuitive judgments of responsibility. This model is a function of both pivotality (whether an agent made a difference to the outcome) and criticality (how important the agent is perceived to be for the outcome, before any actions are taken). The model explains empirical results from previous studies and is supported by a new experiment that manipulates both pivotality and criticality. We also discuss possible extensions of this model to deal with a broader range of causal situations. Overall, our approach emphasizes the close interrelations between causality, counterfactuals, and responsibility attributions. PMID:23855451

  13. Causal responsibility and counterfactuals.

    PubMed

    Lagnado, David A; Gerstenberg, Tobias; Zultan, Ro'i

    2013-08-01

    How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in multiple agent contexts. We draw on the structural model account of actual causation (e.g., Halpern & Pearl, 2005) and its extension to responsibility judgments (Chockler & Halpern, 2004). We review the main theoretical and empirical issues that arise from this literature and propose a novel model of intuitive judgments of responsibility. This model is a function of both pivotality (whether an agent made a difference to the outcome) and criticality (how important the agent is perceived to be for the outcome, before any actions are taken). The model explains empirical results from previous studies and is supported by a new experiment that manipulates both pivotality and criticality. We also discuss possible extensions of this model to deal with a broader range of causal situations. Overall, our approach emphasizes the close interrelations between causality, counterfactuals, and responsibility attributions. Copyright © 2013 Cognitive Science Society, Inc.

  14. Proteomic Analyses of Cellular Events Mediating/Inhibiting Chemical-Induced Injury

    DTIC Science & Technology

    2009-07-21

    Electrophoresis 1999,20:3659-3669. 36. Teder P, Heldin P: Mechanism of impaired local hyaluronan turnover in bleomycin - induced lung injury in rat. Am J...5a. CONTRACT NUMBER Mediating/Inhibiting Chemical- Induced Injury FA9550-06-1-0083 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...used to induce lung injury in the rats over a 1.5 minute volatilization period using an IN-TOX jet nebulizer system. At a mean time of 42 minutes

  15. Chemical nociception in the jejunum induced by capsaicin

    PubMed Central

    Schmidt, B; Hammer, J; Holzer, P; Hammer, H F

    2004-01-01

    Background and aims: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. Methods: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 μg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). Results: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 μg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 μg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 μg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain

  16. Positive affect increases secondary control among causally uncertain individuals.

    PubMed

    Tobin, Stephanie J; George, Melanie P

    2015-01-01

    Secondary control (acceptance of and adjustment to negative events) is thought to promote positive affect. We examined the opposite path: could positive affect increase secondary control, particularly among individuals high in causal uncertainty, who stand to benefit from it the most? In two studies, participants completed a causal uncertainty scale, thought about a problem while listening to affect-inducing music or no music, and then completed items that assessed secondary control. In Study 1, the music induced positive or negative affect. In Study 2, the music induced affect that was high or low in activation and positive or negative in valence. In both studies, we found that positive affect-inducing music increased secondary control among high causal uncertainty participants. Furthermore, trait affect did not account for the effects of causal uncertainty, and music did not influence primary control. These findings show that secondary control can fluctuate as a function of state affect.

  17. Silicon Nitride Bioceramics Induce Chemically Driven Lysis in Porphyromonas gingivalis.

    PubMed

    Pezzotti, Giuseppe; Bock, Ryan M; McEntire, Bryan J; Jones, Erin; Boffelli, Marco; Zhu, Wenliang; Baggio, Greta; Boschetto, Francesco; Puppulin, Leonardo; Adachi, Tetsuya; Yamamoto, Toshiro; Kanamura, Narisato; Marunaka, Yoshinori; Bal, B Sonny

    2016-03-29

    Organisms of Gram-negative phylum bacteroidetes, Porphyromonas gingivalis, underwent lysis on polished surfaces of silicon nitride (Si3N4) bioceramics. The antibacterial activity of Si3N4 was mainly the result of chemically driven principles. The lytic activity, although not osmotic in nature, was related to the peculiar pH-dependent surface chemistry of Si3N4. A buffering effect via the formation of ammonium ions (NH4(+)) (and their modifications) was experimentally observed by pH microscopy. Lysis was confirmed by conventional fluorescence spectroscopy, and the bacteria's metabolism was traced with the aid of in situ Raman microprobe spectroscopy. This latter technique revealed the formation of peroxynitrite within the bacterium itself. Degradation of the bacteria's nucleic acid, drastic reduction in phenilalanine, and reduction of lipid concentration were observed due to short-term exposure (6 days) to Si3N4. Altering the surface chemistry of Si3N4 by either chemical etching or thermal oxidation influenced peroxynitrite formation and affected bacteria metabolism in different ways. Exploiting the peculiar surface chemistry of Si3N4 bioceramics could be helpful in counteracting Porphyromonas gingivalis in an alkaline pH environment.

  18. Interleukin 19 reduces inflammation in chemically induced experimental colitis.

    PubMed

    Matsuo, Yukiko; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Nishiyama, Kazuhiro; Yoshida, Natsuho; Ikeda, Yoshihito; Fujimoto, Yasuyuki; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2015-12-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice. Inflammatory responses in IL-19-deficient mice were assessed using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of acute colitis. IL-19 deficiency aggravated TNBS-induced colitis and compromised intestinal recovery in mice. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of interferon-gamma, IL-12 (p40), IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5. Using this model of induced colitis, our results revealed the immunopathological relevance of IL-19 as an anti-inflammatory cytokine in intestinal inflammation in mice.

  19. Chemically induced bidirectional differentiation of embryonal carcinoma cells in vitro.

    PubMed Central

    Speers, W. C.; Birdwell, C. R.; Dixon, F. J.

    1979-01-01

    N,N-dimethylacetamide, hexamethylene bisacetamide, and Polybrene induced rapid and extensive differentiation in vitro in an otherwise slowly differentiating subline of embryonal carcinoma cells. The type of differentiated cell induced was dependent on the spatial organization of the stem cells during drug treatment. In monalayer culture "epithelial" cells were produced exclusively. However, treatment of aggregated suspension cultures yielded predominantly "fibroblast-like" cells. The undifferentiated embryonal carcinoma cells and the two differentiated cell types were morphologically distinct when examined by light microscopy, scanning electron microscopy, and transmission electron microscopy; and they had differences in cell surface antigens. Both differential cell types produced large amounts of fibronectin, whereas the embryonal carcinoma cells produced only minimal amounts. This system provides a convenient way to induce relatively synchronous differentiation of embryonal carcinoma cells into specific differentiated cell types. Images Figure 5 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:507191

  20. CD-REST: a system for extracting chemical-induced disease relation in literature

    PubMed Central

    Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

    2016-01-01

    Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug–disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed from http://clinicalnlptool.com/cdr. The online CD-REST demonstration system is available at http://clinicalnlptool.com/cdr/cdr.html. Database URL: http://clinicalnlptool.com/cdr; http://clinicalnlptool.com/cdr/cdr.html PMID:27016700

  1. Nematicides induced changes in the chemical constituents of potato tubers.

    PubMed

    Marwaha, R S

    1988-01-01

    Changes in the chemical constitutents of potato tubers grown under different concentrations of 3 synthetic organic nematicides (carbofuran, aldicarb and phorate) and a natural plant product (sawdust) were investigated. There were no significant differences in the specific gravity, dry matter and starch content of tubers from different treatments. A significant increase in the content of non-reducing and total sugars was observed in all the treatments. Nematicidal treatments had significant effects on reducing sugars, true protein, free amino acids, orthodihydroxy phenols, beta-carotene and ascorbic acid. Application of nematicides reduced the content of total phenolic compounds which is a desirable change from a processing viewpoint. Potatoes grown under different nematicidal treatments can be processed into chips and French fries as they contain permissible levels of reducing sugars required for these forms of processing.

  2. Understanding clinical immunological testing in alleged chemically induced environmental illnesses.

    PubMed

    Salvaggio, J E

    1996-08-01

    Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged "multiple chemical sensitivity" and/or "environmental illness." According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental "immunotoxins" is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many

  3. Spin Manipulation in Graphene by Chemically Induced Pseudospin Polarization

    NASA Astrophysics Data System (ADS)

    Van Tuan, Dinh; Roche, Stephan

    2016-03-01

    Spin manipulation is one of the most critical challenges to realize spin-based logic devices and spintronic circuits. Graphene has been heralded as an ideal material to achieve spin manipulation, but so far new paradigms and demonstrators are limited. Here we show that certain impurities such as fluorine adatoms, which locally break sublattice symmetry without the formation of strong magnetic moment, could result in a remarkable variability of spin transport characteristics. The impurity resonance level is found to be associated with a long-range sublattice pseudospin polarization, which by locally decoupling spin and pseudospin dynamics provokes a huge spin lifetime electron-hole asymmetry. In the dilute impurity limit, spin lifetimes could be tuned electrostatically from 100 ps to several nanoseconds, providing a protocol to chemically engineer an unprecedented spin device functionality.

  4. Laser-induced chemical deposition from the gas phase

    NASA Astrophysics Data System (ADS)

    Teslenko, V. V.

    1990-02-01

    The results of the study of the chemical reactions involved in the deposition of various substances from the gas phase using the pulsed, quasi-continuous, and continuous laser radiation in the wavelength range 0.193-10.6 μm have been summarised. Particular attention has been paid to the deposition of inorganic substances, including non-metals (C, Si, Ge, etc.), metals (Cu, Au, Zn, Cd, Al, Cr, Mo, W, Ni), and a number of simple compounds. Detailed experimental data are given on the influence of the radiation parameters (wavelength, duration and spacing of the pulses, intensity of radiation, shape and position of the laser beam) and the nature of the reagents (hydrides, halides, carbonyls, alkyl organometallic compounds, etc.) on the rate of deposition and the composition of the deposit. The characteristics of photolytic deposition reactions and their possible applications have been examined. The bibliography contains 202 references.

  5. HCL or DCL chemical laser using laser induced chemistry

    SciTech Connect

    Merritt, J.A.

    1980-05-13

    A chemical HCL or DCL laser is obtained by irradiating CoCl2+H2/D2 in admixture with the P54 line of a CO2 laser. The irradiation is accomplished in a laser cavity provided with appropriate brewster windows, mirrors, and coupling means. The CoCl2 is mixed with H2 or D2 in a properly conditioned system without reacting. The irradiating by the P54 line of a CO2 laser dissociates the CoCl2 to form CO+2Cl* (Cl*-atom in an excited state). The Cl* atom then reacts with H2/D2 present to produce HCL or DCL in an excited vibrational state. The halogen containing molecule then lases.

  6. Spin Manipulation in Graphene by Chemically Induced Pseudospin Polarization.

    PubMed

    Van Tuan, Dinh; Roche, Stephan

    2016-03-11

    Spin manipulation is one of the most critical challenges to realize spin-based logic devices and spintronic circuits. Graphene has been heralded as an ideal material to achieve spin manipulation, but so far new paradigms and demonstrators are limited. Here we show that certain impurities such as fluorine adatoms, which locally break sublattice symmetry without the formation of strong magnetic moment, could result in a remarkable variability of spin transport characteristics. The impurity resonance level is found to be associated with a long-range sublattice pseudospin polarization, which by locally decoupling spin and pseudospin dynamics provokes a huge spin lifetime electron-hole asymmetry. In the dilute impurity limit, spin lifetimes could be tuned electrostatically from 100 ps to several nanoseconds, providing a protocol to chemically engineer an unprecedented spin device functionality.

  7. Altered Acer Rubrum Fecundity Induced By Chemical Climate Change

    NASA Astrophysics Data System (ADS)

    Deforest, J. L.; Peters, A.

    2014-12-01

    Red maple (Acer rubrum L.) is becoming the most dominating tree in North American eastern deciduous forests. Concurrently, human activities have altered the chemical climate of terrestrial ecosystems via acidic deposition, which increases the available of nitrogen (N), while decreasing phosphorus (P) availability. Once a minor forest component prior to European settlement, the abundance of red maple may be a symptom of the modern age. The current paradigm explaining red maple's rise to prominence concerns fire suppression that excludes competitors. However, this still does not explain why red maple is unique compared to other functionally similar trees. The objective of this study was to investigate the interactive influence of acid rain mitigation on the fecundity of red maple. Objectives were achieved by measuring flowering, seed production, germination, and growth from red maple on plots that have been experimentally manipulated to increase soil pH, P, or both in three unglaciated eastern deciduous hardwood forests. At least 50% of the red maple population is seed bearing in our control soils, however the median percent of seed-bearing trees declined to zero when mitigating soils from acidic deposition. This can be explained by the curious fact that red maple is polygamodioecious, or has labile sex-expression, in which an individual tree can change its sex-expression in response to the environment. Furthermore, seed-bearing trees in the mitigated plots grew less, produced less seeds, and germinated at lower rates than their counterparts in control soils. Our results provide evidence that chemical climate change could be the primary contributing factor accelerating the dominance of red maple in eastern North American forests. Our observations can provide a boarder conceptual framework for understanding how nutrient limitations can be applied beyond plant productivity towards explaining distribution changes in vegetation.

  8. A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

    PubMed Central

    Randhawa, Puneet Kaur; Singh, Kavinder; Singh, Nirmal

    2014-01-01

    Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD. PMID:25177159

  9. Analysis of DNA-protein complexes induced by chemical carcinogens

    SciTech Connect

    Costa, M. )

    1990-11-01

    DNA-protein complexes induced in intact cells by chromate have been isolated and compared with those formed by other agents such as cis-platinum. Actin has been identified as one of the major proteins that is complexed to the DNA by chromate based upon a number of criteria including, a molecular weight and isoelectric point identical to actin, positive reaction with actin polyclonal antibody, and proteolytic mapping. Chromate and cis-platinum both complex proteins of very similar molecular weight and isoelectric points and these complexes can be disrupted by exposure to chelating or reducing agents. These results suggest that the metal itself is participating in rather than catalyzing the formation of a DNA-protein complex. An antiserum which was raised to chromate-induced DNA-protein complexes reacted primarily with a 97,000 protein that could not be detected by silver staining. Western blots and slot blots were utilized to detect p97 DNA-protein complexes formed by cis-platinum, UV, formaldehyde, and chromate. Other work in this area, involving studying whether DNA-protein complexes are formed in actively transcribed DNA compared with genetically inactive DNA, is discussed. Methods to detect DNA-protein complexes, the stability and repair of these lesions, and characterization of DNA-protein complexes are reviewed. Nuclear matrix proteins have been identified as a major substrate for the formation of DNA-protein complexes and these findings are also reviewed.

  10. Quantum information causality.

    PubMed

    Pitalúa-García, Damián

    2013-05-24

    How much information can a transmitted physical system fundamentally communicate? We introduce the principle of quantum information causality, which states the maximum amount of quantum information that a quantum system can communicate as a function of its dimension, independently of any previously shared quantum physical resources. We present a new quantum information task, whose success probability is upper bounded by the new principle, and show that an optimal strategy to perform it combines the quantum teleportation and superdense coding protocols with a task that has classical inputs.

  11. Fast causal multicast

    NASA Technical Reports Server (NTRS)

    Birman, Kenneth P.; Schiper, Andre; Stephenson, Pat

    1990-01-01

    A new protocol is presented that efficiently implements a reliable, causally ordered multicast primitive and is easily extended into a totally ordered one. Intended for use in the ISIS toolkit, it offers a way to bypass the most costly aspects of ISIS while benefiting from virtual synchrony. The facility scales with bounded overhead. Measured speedups of more than an order of magnitude were obtained when the protocol was implemented within ISIS. One conclusion is that systems such as ISIS can achieve performance competitive with the best existing multicast facilities - a finding contradicting the widespread concern that fault-tolerance may be unacceptably costly.

  12. Causal Entropic Forces

    NASA Astrophysics Data System (ADS)

    Wissner-Gross, A. D.; Freer, C. E.

    2013-04-01

    Recent advances in fields ranging from cosmology to computer science have hinted at a possible deep connection between intelligence and entropy maximization, but no formal physical relationship between them has yet been established. Here, we explicitly propose a first step toward such a relationship in the form of a causal generalization of entropic forces that we find can cause two defining behaviors of the human “cognitive niche”—tool use and social cooperation—to spontaneously emerge in simple physical systems. Our results suggest a potentially general thermodynamic model of adaptive behavior as a nonequilibrium process in open systems.

  13. Learning a theory of causality.

    PubMed

    Goodman, Noah D; Ullman, Tomer D; Tenenbaum, Joshua B

    2011-01-01

    The very early appearance of abstract knowledge is often taken as evidence for innateness. We explore the relative learning speeds of abstract and specific knowledge within a Bayesian framework and the role for innate structure. We focus on knowledge about causality, seen as a domain-general intuitive theory, and ask whether this knowledge can be learned from co-occurrence of events. We begin by phrasing the causal Bayes nets theory of causality and a range of alternatives in a logical language for relational theories. This allows us to explore simultaneous inductive learning of an abstract theory of causality and a causal model for each of several causal systems. We find that the correct theory of causality can be learned relatively quickly, often becoming available before specific causal theories have been learned--an effect we term the blessing of abstraction. We then explore the effect of providing a variety of auxiliary evidence and find that a collection of simple perceptual input analyzers can help to bootstrap abstract knowledge. Together, these results suggest that the most efficient route to causal knowledge may be to build in not an abstract notion of causality but a powerful inductive learning mechanism and a variety of perceptual supports. While these results are purely computational, they have implications for cognitive development, which we explore in the conclusion.

  14. Surface chemical reactions induced by well-controlled molecular beams: translational energy and molecular orientation control.

    PubMed

    Okada, Michio

    2010-07-07

    I review our recent studies of chemical reactions on single-crystalline Cu and Si surfaces induced by hyperthermal oxygen molecular beams and by oriented molecular beams, respectively. Studies of oxide formation on Cu induced by hyperthermal molecular beams suggest that the translational energy of the incident molecules plays a significant role. The use of hyperthermal molecular beams enables us to open up new chemical reaction paths, and to develop new methods for the fabrication of thin films. Oriented molecular beams also demonstrate the possibility for controlling surface chemical reactions by varying the orientation of the incident molecules. The steric effects found on Si surfaces hint at new ways of achieving material fabrication on Si surfaces. Controlling the initial conditions of incoming molecules is a powerful tool for creating new materials on surfaces with well-controlled chemical reactions. © 2010 IOP Publishing Ltd

  15. Spider sedation induced by defensive chemicals of milliped prey*

    PubMed Central

    Carrel, James E.; Eisner, Thomas

    1984-01-01

    Wolf spiders (Lycosa spp.) show delayed induced sedation (total immobilization) of prolonged duration (in the order of days) after attacks upon millipeds (Glomeris marginata). The sedation is specifically attributable to glomerin and homoglomerin, two previously characterized quinazolinones present in the defensive secretion of Glomeris. Median sedative doses for the quinazolinones are in the range of 1-7 μg per spider, a fraction of the total (60-90 μg) present in the secretion of medium to full-grown millipeds. A sedative effect upon an invertebrate predator has not previously been demonstrated for an animal defense. Quinazolinones include the synthetic drug methaqualone (Quaalude), a potent human sedative. Images PMID:16593414

  16. Flow-Induced Control of Pattern Formation in Chemical Systems

    NASA Astrophysics Data System (ADS)

    Berenstein, Igal; Beta, Carsten

    Since Alan Turing's seminal paper in 1952, the study of spatio-temporal patterns that arise in systems of reacting and diffusing components has grown into an immense and vibrant realm of scientific research. This field includes not only chemical systems but spans many areas of science as diverse as cell and developmental biology, ecology, geosciences, or semiconductor physics. For several decades research in this field has concentrated on the vast variety of patterns that can emerge in reaction-diffusion systems and on the underlying instabilities. In the 1990s, stimulated by the pioneering work of Ott, Grebogi and Yorke, control of pattern formation arose as a new topical focus and gradually developed into an entire new field of research. On the one hand, research interests concentrated on control and suppression of undesired dynamical states, in particular on control of chaos. On the other hand, the design and engineering of particular space-time patterns became a major focus in this field that motivates ongoing scientific effort until today...

  17. Hygienic grooming is induced by contact chemicals in Drosophila melanogaster

    PubMed Central

    Yanagawa, Aya; Guigue, Alexandra M. A.; Marion-Poll, Frédéric

    2014-01-01

    In social insects, grooming is considered as a behavioral defense against pathogen and parasite infections since it contributes to remove microbes from their cuticle. However, stimuli which trigger this behavior are not well characterized yet. We examined if activating contact chemoreceptive sensilla could trigger grooming activities in Drosophila melanogaster. We monitored the grooming responses of decapitated flies to compounds known to activate the immune system, e.g., dead Escherichia coli (Ec) and lipopolysaccharides (LPS), and to tastants such as quinine, sucrose, and salt. LPS, quinine, and Ec were quite effective in triggering grooming movements when touching the distal border of the wings and the legs, while sucrose had no effect. Contact chemoreceptors are necessary and sufficient to elicit such responses, as grooming could not be elicited by LPS in poxn mutants deprived of external taste sensilla, and as grooming was elicited by light when a channel rhodopsin receptor was expressed in bitter-sensitive cells expressing Gr33a. Contact chemoreceptors distributed along the distal border of the wings respond to these tastants by an increased spiking activity, in response to quinine, Ec, LPS, sucrose, and KCl. These results demonstrate for the first time that bacterial compounds trigger grooming activities in D. melanogaster, and indicate that contact chemoreceptors located on the wings participate in the detection of such chemicals. PMID:25100963

  18. Transverse relaxation in the rotating frame induced by chemical exchange

    NASA Astrophysics Data System (ADS)

    Michaeli, Shalom; Sorce, Dennis J.; Idiyatullin, Djaudat; Ugurbil, Kamil; Garwood, Michael

    2004-08-01

    In the presence of radiofrequency irradiation, relaxation of magnetization aligned with the effective magnetic field is characterized by the time constant T1 ρ. On the other hand, the time constant T2 ρ characterizes the relaxation of magnetization that is perpendicular to the effective field. Here, it is shown that T2 ρ can be measured directly with Carr-Purcell sequences composed of a train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2 ρ characterizes the relaxation of the magnetization, which under adiabatic conditions remains approximately perpendicular to the time-dependent effective field. Theory is derived to describe the influence of chemical exchange on T2 ρ relaxation in the fast-exchange regime, with time constant defined as T2 ρ,ex . The derived theory predicts the rate constant R 2ρ, ex (=1/T 2ρ, ex) to be dependent on the choice of amplitude- and frequency-modulation functions used in the AFP pulses. Measurements of R2 ρ,ex of the water/ethanol exchanging system confirm the predicted dependence on modulation functions. The described theoretical framework and adiabatic methods represent new tools to probe exchanging systems.

  19. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    PubMed

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges

    PubMed Central

    Payne, Heather; Adamson, Andrew; Bahl, Amit; Borwell, Jonathan; Dodds, David; Heath, Catherine; Huddart, Robert; McMenemin, Rhona; Patel, Prashant; Peters, John L; Thompson, Andrew

    2013-01-01

    To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment-induced HC. There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria. The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette-Guérin, where the incidence has been reported as up to 30%. Mesna (2-mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment-related cystitis, but are not always effective. Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited. The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option. The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC. PMID:24000900

  1. Causal events enter awareness faster than non-causal events

    PubMed Central

    Wagemans, Johan; de-Wit, Lee

    2017-01-01

    Philosophers have long argued that causality cannot be directly observed but requires a conscious inference (Hume, 1967). Albert Michotte however developed numerous visual phenomena in which people seemed to perceive causality akin to primary visual properties like colour or motion (Michotte, 1946). Michotte claimed that the perception of causality did not require a conscious, deliberate inference but, working over 70 years ago, he did not have access to the experimental methods to test this claim. Here we employ Continuous Flash Suppression (CFS)—an interocular suppression technique to render stimuli invisible (Tsuchiya & Koch, 2005)—to test whether causal events enter awareness faster than non-causal events. We presented observers with ‘causal’ and ‘non-causal’ events, and found consistent evidence that participants become aware of causal events more rapidly than non-causal events. Our results suggest that, whilst causality must be inferred from sensory evidence, this inference might be computed at low levels of perceptual processing, and does not depend on a deliberative conscious evaluation of the stimulus. This work therefore supports Michotte’s contention that, like colour or motion, causality is an immediate property of our perception of the world. PMID:28149698

  2. Characterization of Chemically-Induced Bacterial Ghosts (BGs) Using Sodium Hydroxide-Induced Vibrio parahaemolyticus Ghosts (VPGs)

    PubMed Central

    Park, Hyun Jung; Oh, Sung; Vinod, Nagarajan; Ji, Seongmi; Noh, Han Byul; Koo, Jung Mo; Lee, Su Hyeong; Kim, Sei Chang; Lee, Ki-Sung; Choi, Chang Won

    2016-01-01

    Acellular bacterial ghosts (BGs) are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs) were generated by chemically-induced lysis and the method is based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH), acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid, and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, <50.0, 25.0, 6.25, 1.56, and 0.781 mg/mL. Except for boric acid, the lysis efficiency reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs appeared completely DNA-free, which was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS) extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells, as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened, or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however, the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS), anti-inflammatory cytokine (IL-10), and dual activities (IL-6) in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning electron

  3. [Chemical hazards induced by heavy metals refining processes].

    PubMed

    Gaweda, Ewa

    2003-01-01

    Processes of refining heavy metals consist in removing impurities, which can be found in metals produced on industrial scale. People involved in heavy metals refining processes are primarily exposed to metals (Pb, Cd, Cu), metalloids (As, Se) and metal compounds. Exposure to dusts (from 2 to 50% SiO2) and sulfuric acid is an additional hazard. The air concentrations of harmful chemical agents at heavy metals refining stations in two Polish Plants are presented. Several tens of workers employed in the processes of copper, lead, nickel sulfate, zinc, cadmium and silver production were examined. Concentrations of Cd, Ni, Se, Cu, Pb, Ag, As and Sb were determined by atomic absorption spectrometry (AAS) with a graphite tube, whereas Fe, ZnO oxide (as Zn), MgO (as Mg) and CaO (as Ca) by AAS with air-acetylene flame, and sulfuric acid by method described in PN-91/Z-04056/02. Lead concentrations in the samples collected in both Plants were often high (significantly exceeding Polish MAC values at some workstations). Arsenic concentrations ranged from very low in all processes in one Plant to very high, exceeding Polish MAC values, at some workstations in the other. In general, air concentrations of other agents were not high (fraction of MAC). The occurrence of antimony and magnesium oxide was not determined. The risk created by metals and metalloids at the workstations in two Plants was diversified. There is no need to determine Sb and MgO in further studies. Lead should be determined at all workstations, other agents can be determined at workstations with concentrations exceeding the determinability of relevant methods.

  4. Experimental test of nonlocal causality

    PubMed Central

    Ringbauer, Martin; Giarmatzi, Christina; Chaves, Rafael; Costa, Fabio; White, Andrew G.; Fedrizzi, Alessandro

    2016-01-01

    Explaining observations in terms of causes and effects is central to empirical science. However, correlations between entangled quantum particles seem to defy such an explanation. This implies that some of the fundamental assumptions of causal explanations have to give way. We consider a relaxation of one of these assumptions, Bell’s local causality, by allowing outcome dependence: a direct causal influence between the outcomes of measurements of remote parties. We use interventional data from a photonic experiment to bound the strength of this causal influence in a two-party Bell scenario, and observational data from a Bell-type inequality test for the considered models. Our results demonstrate the incompatibility of quantum mechanics with a broad class of nonlocal causal models, which includes Bell-local models as a special case. Recovering a classical causal picture of quantum correlations thus requires an even more radical modification of our classical notion of cause and effect. PMID:27532045

  5. Experimental test of nonlocal causality.

    PubMed

    Ringbauer, Martin; Giarmatzi, Christina; Chaves, Rafael; Costa, Fabio; White, Andrew G; Fedrizzi, Alessandro

    2016-08-01

    Explaining observations in terms of causes and effects is central to empirical science. However, correlations between entangled quantum particles seem to defy such an explanation. This implies that some of the fundamental assumptions of causal explanations have to give way. We consider a relaxation of one of these assumptions, Bell's local causality, by allowing outcome dependence: a direct causal influence between the outcomes of measurements of remote parties. We use interventional data from a photonic experiment to bound the strength of this causal influence in a two-party Bell scenario, and observational data from a Bell-type inequality test for the considered models. Our results demonstrate the incompatibility of quantum mechanics with a broad class of nonlocal causal models, which includes Bell-local models as a special case. Recovering a classical causal picture of quantum correlations thus requires an even more radical modification of our classical notion of cause and effect.

  6. Causal inference in public health.

    PubMed

    Glass, Thomas A; Goodman, Steven N; Hernán, Miguel A; Samet, Jonathan M

    2013-01-01

    Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.

  7. Redundant variables and Granger causality

    NASA Astrophysics Data System (ADS)

    Angelini, L.; de Tommaso, M.; Marinazzo, D.; Nitti, L.; Pellicoro, M.; Stramaglia, S.

    2010-03-01

    We discuss the use of multivariate Granger causality in presence of redundant variables: the application of the standard analysis, in this case, leads to under estimation of causalities. Using the un-normalized version of the causality index, we quantitatively develop the notions of redundancy and synergy in the frame of causality and propose two approaches to group redundant variables: (i) for a given target, the remaining variables are grouped so as to maximize the total causality and (ii) the whole set of variables is partitioned to maximize the sum of the causalities between subsets. We show the application to a real neurological experiment, aiming to a deeper understanding of the physiological basis of abnormal neuronal oscillations in the migraine brain. The outcome by our approach reveals the change in the informational pattern due to repetitive transcranial magnetic stimulations.

  8. Causal inference based on counterfactuals

    PubMed Central

    Höfler, M

    2005-01-01

    Background The counterfactual or potential outcome model has become increasingly standard for causal inference in epidemiological and medical studies. Discussion This paper provides an overview on the counterfactual and related approaches. A variety of conceptual as well as practical issues when estimating causal effects are reviewed. These include causal interactions, imperfect experiments, adjustment for confounding, time-varying exposures, competing risks and the probability of causation. It is argued that the counterfactual model of causal effects captures the main aspects of causality in health sciences and relates to many statistical procedures. Summary Counterfactuals are the basis of causal inference in medicine and epidemiology. Nevertheless, the estimation of counterfactual differences pose several difficulties, primarily in observational studies. These problems, however, reflect fundamental barriers only when learning from observations, and this does not invalidate the counterfactual concept. PMID:16159397

  9. Topological Causality in Dynamical Systems

    NASA Astrophysics Data System (ADS)

    Harnack, Daniel; Laminski, Erik; Schünemann, Maik; Pawelzik, Klaus Richard

    2017-09-01

    Determination of causal relations among observables is of fundamental interest in many fields dealing with complex systems. Since nonlinear systems generically behave as wholes, classical notions of causality assuming separability of subsystems often turn out inadequate. Still lacking is a mathematically transparent measure of the magnitude of effective causal influences in cyclic systems. For deterministic systems we found that the expansions of mappings among time-delay state space reconstructions from different observables not only reflect the directed coupling strengths, but also the dependency of effective influences on the system's temporally varying state. Estimation of the expansions from pairs of time series is straightforward and used to define novel causality indices. Mathematical and numerical analysis demonstrate that they reveal the asymmetry of causal influences including their time dependence, as well as provide measures for the effective strengths of causal links in complex systems.

  10. Chemically induced Jahn-Teller ordering on manganite surfaces.

    PubMed

    Gai, Zheng; Lin, Wenzhi; Burton, J D; Fuchigami, K; Snijders, P C; Ward, T Z; Tsymbal, Evgeny Y; Shen, J; Jesse, Stephen; Kalinin, Sergei V; Baddorf, Arthur P

    2014-07-24

    Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields and establish their coupling to electronic properties. Here we demonstrate that measuring the sub-30-pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunnelling microscopy allows the physical order parameter fields to be visualized in real space on the single-atom level. Here, this local crystallographic analysis is applied to the in-situ-grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level.

  11. Chemical modification of normal tissue damage induced by photodynamic therapy.

    PubMed Central

    Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

    1996-01-01

    One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

  12. Cell Therapy for Chemically Induced Ovarian Failure in Mice

    PubMed Central

    Terraciano, Paula; Durli, Isabel; Baggio, Melchiani; Kuhl, Cristiana Palma; Laurino, Claudia; Passos, Eduardo; Paz, Ana Helena; Cirne-Lima, Elizabeth

    2014-01-01

    Cell therapy has been linked to an unexplained return of ovarian function and fertility in some cancer survivors. Studies modeling this in mice have shown that cells transplantation generates donor-derived oocytes in chemotherapy-treated recipients. This study was conducted to further clarify the impact of cell transplantation from different sources on female reproductive function after chemotherapy using a preclinical mouse model. Methods. Female mice were administered 7.5 mg/kg cisplatin followed by cell transplantation (one week later) using GFP+ female cell donors. For cell tracking, adipose derived stem cell GFP+ (ADSC), female germline stem cell GFP+/MVH+ (FGSC), or ovary cell suspension GFP+ mice were transplanted into cisplatin-treated wild-type recipients. After 7 or 14 days animals were killed and histological analysis, IHQ for GFP cells, and ELISA for estradiol were performed. Results. Histological examinations showed that ADSC, ovary cell suspension, and FGSC transplant increase the number of follicles with apparent normal structure in the cells recipient group euthanized on day 7. Cell tracking showed GFP+ samples 7 days after transplant. Conclusion. These data suggest that intraovarian injection of ADSCs and FGSC into mice with chemotherapy-induced ovarian failure diminished the damage caused by cisplatin. PMID:25548574

  13. Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis.

    PubMed

    Carrasco-Torres, Gabriela; Monroy-Ramírez, Hugo Christian; Martínez-Guerra, Arturo Axayacatl; Baltiérrez-Hoyos, Rafael; Romero-Tlalolini, María de Los Ángeles; Villa-Treviño, Saúl; Sánchez-Chino, Xariss; Vásquez-Garzón, Verónica Rocío

    2017-01-01

    Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.

  14. Different chemical cues originating from a shared predator induce common defense responses in two prey species.

    PubMed

    Takahara, Teruhiko; Doi, Hideyuki; Kohmatsu, Yukihiro; Yamaoka, Ryohei

    2013-01-01

    In freshwater ecosystems, inducible defenses that involve behavioral or morphological changes in response to chemical cue detection are key phenomena in prey-predator interactions. Many species with different phylogenetic and ecological traits (e.g., general activity patterns and microhabitats) use chemical cues to avoid predators. We hypothesized that prey species with a shared predator, but having different ecological traits, would be adapted to detect different chemical cues from the predator. However, the proximate mechanisms by which prey use chemical cues to avoid predation remain little known. Here, we tested our hypothesis by using fractionated chemical components from predatory dragonfly nymphs (Lesser Emperor, Anax parthenope julius) to trigger anti-predator behavioral responses in two anuran tadpoles, the wrinkled frog Glandirana (Rana) rugosa and the Japanese tree frog Hyla japonica. Glandirana rugosa detected chemical cues that had either high or low hydrophobic properties, but H. japonica responded only to chemical cues with hydrophilic properties. During the normal behaviors of these tadpole species, G. rugosa remains immobile in benthic habitats, whereas H. japonica exhibits active swimming at the surface or in the middle of the water column. As we had hypothesized, these tadpole species, which have different general activity levels and microhabitats, detected different chemical cues that were exuded by their shared predator and responded by changing their activities to avoid predation. The specific chemical cues detected by each tadpole species are likely to have characteristics that optimize effective predator detection and encounter avoidance of the shared dragonfly predator.

  15. Force-induced chemical reactions on the metal centre in a single metalloprotein molecule.

    PubMed

    Zheng, Peng; Arantes, Guilherme M; Field, Martin J; Li, Hongbin

    2015-06-25

    Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of single-molecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions.

  16. One-Directional Fluidic Flow Induced by Chemical Wave Propagation in a Microchannel.

    PubMed

    Arai, Miyu; Takahashi, Kazuhiro; Hattori, Mika; Hasegawa, Takahiko; Sato, Mami; Unoura, Kei; Nabika, Hideki

    2016-05-26

    A one-directional flow induced by chemical wave propagation was investigated to understand the origin of its dynamic flow. A cylindrical injection port was connected with a straight propagation channel; the chemical wave was initiated at the injection port. Chemical waves propagated with a constant velocity irrespective of the channel width, indicating that the dynamics of the chemical waves were governed by a geometry-independent interplay between the chemical reaction and diffusion. In contrast, the velocity of the one-directional flow was dependent on the channel width. Furthermore, enlargement of the injection port volume increased the flow velocity and volume flux. These results imply that the one-directional flow in the microchannel is due to a hydrodynamic effect induced in the injection port. Spectroscopic analysis of a pH indicator revealed the simultaneous behavior between the pH increase near the injection port and the one-directional flow. Hence, we can conclude that the one-directional flow in the microchannel with chemical wave propagation was caused by a proton consumption reaction in the injection port, probably through liquid volume expansion by the reaction products and the reaction heat. It is a characteristic feature of the present system that the hydrodynamic flow started from the chemical wave initiation point and not the propagation wavefront, as observed for previous systems.

  17. The sexual inducer of Volvox carteri: purification, chemical characterization and identification of its gene

    PubMed Central

    Tschochner, H.; Lottspeich, F.; Sumper, M.

    1987-01-01

    The sexual inducer of Volvox carteri f. nagariensis is a glycoprotein and one of the most potent biological effector molecules known. It is synthesized by sperm cells and converts asexually growing males and females to the sexual pathway. Until now, large-scale production of the inducer was made impossible by an inherent biological `switch' mechanism, the spontaneous self-induction of asexually growing males. Here we describe a method overcoming this problem for the first time. Large-scale production and purification allowed a detailed chemical characterization of the inducer with respect to partial amino acid sequences and sugar composition. Chemically synthesized oligodeoxynucleotides corresponding to derived amino acid sequences were used to screen a genomic gene bank of V. carteri HK 10. A positive clone (Ind-28) was shown to encode the inducer gene by subcloning and sequencing. ImagesFig. 3. PMID:16453787

  18. Polish spaces of causal curves

    NASA Astrophysics Data System (ADS)

    Miller, Tomasz

    2017-06-01

    We propose and study a new approach to the topologization of spaces of (possibly not all) future-directed causal curves in a stably causal spacetime. It relies on parametrizing the curves ;in accordance; with a chosen time function. Thus obtained topological spaces of causal curves are separable and completely metrizable, i.e. Polish. The latter property renders them particularly useful in the optimal transport theory. To illustrate this fact, we explore the notion of a causal time-evolution of measures in globally hyperbolic spacetimes and discuss its physical interpretation.

  19. Causal Poisson bracket via deformation quantization

    NASA Astrophysics Data System (ADS)

    Berra-Montiel, Jasel; Molgado, Alberto; Palacios-García, César D.

    2016-06-01

    Starting with the well-defined product of quantum fields at two spacetime points, we explore an associated Poisson structure for classical field theories within the deformation quantization formalism. We realize that the induced star-product is naturally related to the standard Moyal product through an appropriate causal Green’s functions connecting points in the space of classical solutions to the equations of motion. Our results resemble the Peierls-DeWitt bracket that has been analyzed in the multisymplectic context. Once our star-product is defined, we are able to apply the Wigner-Weyl map in order to introduce a generalized version of Wick’s theorem. Finally, we include some examples to explicitly test our method: the real scalar field, the bosonic string and a physically motivated nonlinear particle model. For the field theoretic models, we have encountered causal generalizations of the creation/annihilation relations, and also a causal generalization of the Virasoro algebra for the bosonic string. For the nonlinear particle case, we use the approximate solution in terms of the Green’s function, in order to construct a well-behaved causal bracket.

  20. Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research

    PubMed Central

    Liu, Yewei; Yin, Ting; Feng, Yuanbo; Cona, Marlein Miranda; Huang, Gang; Liu, Jianjun; Song, Shaoli; Jiang, Yansheng; Xia, Qian; Swinnen, Johannes V.; Bormans, Guy; Himmelreich, Uwe; Oyen, Raymond

    2015-01-01

    Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-specific property. Chemical carcinogens can be classified upon their origins such as environmental pollutants, cooked meat derived carcinogens, N-nitroso compounds, food additives, antineoplastic agents, naturally occurring substances and synthetic carcinogens, etc. Carcinogen-induced models of primary cancers can be used to evaluate the diagnostic/therapeutic effects of candidate drugs, investigate the biological influential factors, explore preventive measures for carcinogenicity, and better understand molecular mechanisms involved in tumor initiation, promotion and progression. Among commonly adopted cancer models, chemically induced primary malignancies in mammals have several advantages including the easy procedures, fruitful tumor generation and high analogy to clinical human primary cancers. However, in addition to the time-consuming process, the major drawback of chemical carcinogenesis for translational research is the difficulty in noninvasive tumor burden assessment in small animals. Like human cancers, tumors occur unpredictably also among animals in terms of timing, location and the number of lesions. Thanks to the availability of magnetic resonance imaging (MRI) with various advantages such as ionizing-free scanning, superb soft tissue contrast, multi-parametric information, and utility of diverse contrast agents, now a workable solution to this bottleneck problem is to apply MRI for noninvasive detection, diagnosis and therapeutic monitoring on those otherwise

  1. Chemical inducible promotor used to obtain transgenic plants with a silent marker

    DOEpatents

    Chua, Nam-Hai; Aoyama, Takashi

    2000-01-01

    A chemically inducible promoter is described which may be used to transform plants with genes which are easily regulatable by adding plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one which is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

  2. Chemical inducible promoter used to obtain transgenic plants with a silent marker

    SciTech Connect

    Aoyama, Takashi; Zuo, Jianru; Chua, Nam-Hai

    2004-08-31

    A chemically inducible promoter is described that may be used to transform plants, including tobacco and lettuce, with genes which are easily regulatable by adding the plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one that is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

  3. Chemical inducible promotor used to obtain transgenic plants with a silent marker

    SciTech Connect

    Chua, N.H.; Aoyama, Takashi

    2000-05-16

    A chemically inducible promoter is described which may be used to transform plants with genes which are easily regulatable by adding plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

  4. An improved chemically inducible gene switch that functions in the monocotyledonous plant sugar cane.

    PubMed

    Kinkema, Mark; Geijskes, R Jason; Shand, Kylie; Coleman, Heather D; De Lucca, Paulo C; Palupe, Anthony; Harrison, Mark D; Jepson, Ian; Dale, James L; Sainz, Manuel B

    2014-03-01

    Chemically inducible gene switches can provide precise control over gene expression, enabling more specific analyses of gene function and expanding the plant biotechnology toolkit beyond traditional constitutive expression systems. The alc gene expression system is one of the most promising chemically inducible gene switches in plants because of its potential in both fundamental research and commercial biotechnology applications. However, there are no published reports demonstrating that this versatile gene switch is functional in transgenic monocotyledonous plants, which include some of the most important agricultural crops. We found that the original alc gene switch was ineffective in the monocotyledonous plant sugar cane, and describe a modified alc system that is functional in this globally significant crop. A promoter consisting of tandem copies of the ethanol receptor inverted repeat binding site, in combination with a minimal promoter sequence, was sufficient to give enhanced sensitivity and significantly higher levels of ethanol inducible gene expression. A longer CaMV 35S minimal promoter than was used in the original alc gene switch also substantially improved ethanol inducibility. Treating the roots with ethanol effectively induced the modified alc system in sugar cane leaves and stem, while an aerial spray was relatively ineffective. The extension of this chemically inducible gene expression system to sugar cane opens the door to new opportunities for basic research and crop biotechnology.

  5. The Cradle of Causal Reasoning: Newborns' Preference for Physical Causality

    ERIC Educational Resources Information Center

    Mascalzoni, Elena; Regolin, Lucia; Vallortigara, Giorgio; Simion, Francesca

    2013-01-01

    Perception of mechanical (i.e. physical) causality, in terms of a cause-effect relationship between two motion events, appears to be a powerful mechanism in our daily experience. In spite of a growing interest in the earliest causal representations, the role of experience in the origin of this sensitivity is still a matter of dispute. Here, we…

  6. The Cradle of Causal Reasoning: Newborns' Preference for Physical Causality

    ERIC Educational Resources Information Center

    Mascalzoni, Elena; Regolin, Lucia; Vallortigara, Giorgio; Simion, Francesca

    2013-01-01

    Perception of mechanical (i.e. physical) causality, in terms of a cause-effect relationship between two motion events, appears to be a powerful mechanism in our daily experience. In spite of a growing interest in the earliest causal representations, the role of experience in the origin of this sensitivity is still a matter of dispute. Here, we…

  7. The cradle of causal reasoning: newborns' preference for physical causality.

    PubMed

    Mascalzoni, Elena; Regolin, Lucia; Vallortigara, Giorgio; Simion, Francesca

    2013-05-01

    Perception of mechanical (i.e. physical) causality, in terms of a cause-effect relationship between two motion events, appears to be a powerful mechanism in our daily experience. In spite of a growing interest in the earliest causal representations, the role of experience in the origin of this sensitivity is still a matter of dispute. Here, we asked the question about the innate origin of causal perception, never tested before at birth. Three experiments were carried out to investigate sensitivity at birth to some visual spatiotemporal cues present in a launching event. Newborn babies, only a few hours old, showed that they significantly preferred a physical causality event (i.e. Michotte's Launching effect) when matched to a delay event (i.e. a delayed launching; Experiment 1) or to a non-causal event completely identical to the causal one except for the order of the displacements of the two objects involved which was swapped temporally (Experiment 3). This preference for the launching event, moreover, also depended on the continuity of the trajectory between the objects involved in the event (Experiment 2). These results support the hypothesis that the human system possesses an early available, possibly innate basic mechanism to compute causality, such a mechanism being sensitive to the additive effect of certain well-defined spatiotemporal cues present in the causal event independently of any prior visual experience. © 2013 Blackwell Publishing Ltd.

  8. Structural Equations and Causal Explanations: Some Challenges for Causal SEM

    ERIC Educational Resources Information Center

    Markus, Keith A.

    2010-01-01

    One common application of structural equation modeling (SEM) involves expressing and empirically investigating causal explanations. Nonetheless, several aspects of causal explanation that have an impact on behavioral science methodology remain poorly understood. It remains unclear whether applications of SEM should attempt to provide complete…

  9. Structural Equations and Causal Explanations: Some Challenges for Causal SEM

    ERIC Educational Resources Information Center

    Markus, Keith A.

    2010-01-01

    One common application of structural equation modeling (SEM) involves expressing and empirically investigating causal explanations. Nonetheless, several aspects of causal explanation that have an impact on behavioral science methodology remain poorly understood. It remains unclear whether applications of SEM should attempt to provide complete…

  10. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    SciTech Connect

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  11. Laser-induced fluorescence: quantitative analysis of atherosclerotic plaque chemical content in human aorta

    NASA Astrophysics Data System (ADS)

    Dai, Erbin; Wishart, David; Khoury, Samir; Kay, Cyril M.; Jugdutt, Bodh I.; Tulip, John; Lucas, Alexandra

    1996-05-01

    We have been studying laser-induced fluorescence as a technique for identification of selected changes in the chemical composition of atherosclerotic plaque. Formulae for quantification of chemical changes have been developed based upon analysis of fluorescence emission spectra using multiple regression analysis and the principal of least squares. The intima of human aortic necropsy specimens was injected with chemical compounds present in atherosclerotic plaque. Spectra recorded after injection of selected chemical components found in plaque (collagen I, III, IV, elastin and cholesterol) at varying concentrations (0.01 - 1.0 mg) were compared with saline injection. A single fiber system was used for both fluorescence excitation (XeCl excimer laser, 308 nm, 1.5 - 2.0 mJ/ pulse, 5 Hz) and fluorescence emission detection. Average spectra for each chemical have been developed and the wavelengths of peak emission intensity identified. Curve fitting analysis as well as multiple regression analysis were used to develop formulae for assessment of chemical content. Distinctive identifying average curves were established for each chemical. Excellent correlations were identified for collagen I, III, and IV, elastin, and cholesterol (R2 equals 0.92 6- 0.997). Conclusions: (1) Fluorescence spectra of human aortas were significantly altered by collagen I, collagen III, elastin and cholesterol. (2) Fluorescence spectroscopic analysis may allow quantitative assessment of atherosclerotic plaque chemical content in situ.

  12. Systematic trends in photonic reagent induced reactions in a homologous chemical family.

    PubMed

    Tibbetts, Katharine Moore; Xing, Xi; Rabitz, Herschel

    2013-08-29

    The growing use of ultrafast laser pulses to induce chemical reactions prompts consideration of these pulses as "photonic reagents" in analogy to chemical reagents. This work explores the prospect that photonic reagents may affect systematic trends in dissociative ionization reactions of a homologous family of halomethanes, much as systematic outcomes are often observed for reactions between homologous families of chemical reagents and chemical substrates. The experiments in this work with photonic reagents of varying pulse energy and linear spectral chirp reveal systematic correlations between observable ion yields and the following set of natural variables describing the substrate molecules: the ionization energy of the parent molecule, the appearance energy of each fragment ion, and the relative strength of carbon-halogen bonds in molecules containing two different halogens. The results suggest that reactions induced by photonic reagents exhibit systematic behavior analogous to that observed in reactions driven by chemical reagents, which provides a basis to consider empirical "rules" for predicting the outcomes of photonic reagent induced reactions.

  13. Sperm assays in man and other mammals as indicators of chemically induced testicular dysfunction

    SciTech Connect

    Wyrobek, A.J.

    1980-07-31

    Human sperm assays can be effective in identifying chemical agents that alter testicular function. Four human sperm assays are available - sperm density, motility, morphology, and the YFF test. Sperm assays have practical advantages over other approaches for assessing chemically induced changes in human testicular function, and they have been used in more than 60 different occupational, environmental, and drug-related chemical exposures. Studies of chemically induced sperm anomalies in other mammals have provided data on several hundred agents and encompass numerous species. The most widely used animal sperm assay is sperm morphology of mice. It is simple, quantitative, and sensitive to carcinogens, mutagens, and teratogens. The availability of both human and animal sperm assays provides a valuable link between human and animal studies which may be of potential benefit in assessing the heritable genetic risk associated with chemically induced sperm defects. Results from sperm assays may be used in conjunction with results from short term mutagenicity assays (those with definitive genetic endpoints) to identify those mutagens that may be active in the mammalian testes.

  14. Identification of Specific Pluripotent Stem Cell Death—Inducing Small Molecules by Chemical Screening

    PubMed Central

    Conesa, Celia; Doss, Michael Xavier; Antzelevitch, Charles; Sachinidis, Agapios; Sancho, Javier

    2012-01-01

    A potential application of embryonic and inducible pluripotent stem cells for the therapy of degenerative diseases involves pure somatic cells, free of tumorigenic undifferentiated embryonic and inducible pluripotent stem cells. In complex collections of chemicals with pharmacological potential we expect to find molecules able to induce specific pluripotent stem cell death, which could be used in some cell therapy settings to eliminate undifferentiated cells. Therefore, we have screened a chemical library of 1120 small chemicals to identify compounds that induce specifically apoptotic cell death in undifferentiated mouse embryonic stem cells (ESCs). Interestingly, three compounds currently used as clinically approved drugs, nortriptyline, benzethonium chloride and methylbenzethonium chloride, induced differential effects in cell viability in ESCs versus mouse embryonic fibroblasts (MEFs). Nortriptyline induced apoptotic cell death in MEFs but not in ESCs, whereas benzethonium and methylbenzethonium chloride showed the opposite effect. Nortriptyline, a tricyclic antidepressant, has also been described as a potent inhibitor of mitochondrial permeability transition, one of two major mechanisms involved in mitochondrial membrane permeabilization during apoptosis. Benzethonium chloride and methylbenzethonium chloride are quaternary ammonium salts used as antimicrobial agents with broad spectrum and have also been described as anticancer agents. A similar effect of benzethonium chloride was observed in human induced pluripotent stem cells (hiPSCs) when compared to both primary human skin fibroblasts and an established human fibroblast cell line. Human fibroblasts and hiPSCs were similarly resistant to nortriptyline, although with a different behavior. Our results indicate differential sensitivity of ESCs, hiPSCs and fibroblasts to certain chemical compounds, which might have important applications in the stem cell-based therapy by eliminating undifferentiated pluripotent

  15. Identification of specific pluripotent stem cell death--inducing small molecules by chemical screening.

    PubMed

    Conesa, Celia; Doss, Michael Xavier; Antzelevitch, Charles; Sachinidis, Agapios; Sancho, Javier; Carrodeguas, José Alberto

    2012-03-01

    A potential application of embryonic and inducible pluripotent stem cells for the therapy of degenerative diseases involves pure somatic cells, free of tumorigenic undifferentiated embryonic and inducible pluripotent stem cells. In complex collections of chemicals with pharmacological potential we expect to find molecules able to induce specific pluripotent stem cell death, which could be used in some cell therapy settings to eliminate undifferentiated cells. Therefore, we have screened a chemical library of 1120 small chemicals to identify compounds that induce specifically apoptotic cell death in undifferentiated mouse embryonic stem cells (ESCs). Interestingly, three compounds currently used as clinically approved drugs, nortriptyline, benzethonium chloride and methylbenzethonium chloride, induced differential effects in cell viability in ESCs versus mouse embryonic fibroblasts (MEFs). Nortriptyline induced apoptotic cell death in MEFs but not in ESCs, whereas benzethonium and methylbenzethonium chloride showed the opposite effect. Nortriptyline, a tricyclic antidepressant, has also been described as a potent inhibitor of mitochondrial permeability transition, one of two major mechanisms involved in mitochondrial membrane permeabilization during apoptosis. Benzethonium chloride and methylbenzethonium chloride are quaternary ammonium salts used as antimicrobial agents with broad spectrum and have also been described as anticancer agents. A similar effect of benzethonium chloride was observed in human induced pluripotent stem cells (hiPSCs) when compared to both primary human skin fibroblasts and an established human fibroblast cell line. Human fibroblasts and hiPSCs were similarly resistant to nortriptyline, although with a different behavior. Our results indicate differential sensitivity of ESCs, hiPSCs and fibroblasts to certain chemical compounds, which might have important applications in the stem cell-based therapy by eliminating undifferentiated pluripotent

  16. Cleavage enhancement of specific chemical bonds in DNA-Cisplatin complexes induced by X-rays

    NASA Astrophysics Data System (ADS)

    Zheng, Yi; Yao, Xiaobin; Luo, Xinglan; Fu, Xianzhi

    2014-04-01

    The chemical bond transformation of cisplatin-DNA complexes can be probed efficiently by XPS which provides a concomitant X-ray irradiation source as well. The presence to Pt could considerably increase formation of the SE induced by X-ray and that the further interaction of these LEE with DNA leads to the enhancement of bond cleavages.

  17. MICROWAVE-INDUCED RAPID CHEMICAL FUNCTIONALIZATION OF SINGLE-WALLED CARBON NANOTUBES (R830901)

    EPA Science Inventory


    Abstract

    The microwave-induced chemical functionalization of single-walled carbon nanotubes (SWNTs) is reported. The major advantage of this high-energy procedure is that it reduced the reaction time to the order of minutes and the number of steps in the reac...

  18. MICROWAVE-INDUCED RAPID CHEMICAL FUNCTIONALIZATION OF SINGLE-WALLED CARBON NANOTUBES (R830901)

    EPA Science Inventory


    Abstract

    The microwave-induced chemical functionalization of single-walled carbon nanotubes (SWNTs) is reported. The major advantage of this high-energy procedure is that it reduced the reaction time to the order of minutes and the number of steps in the reac...

  19. Imprint control of BaTiO3 thin films via chemically induced surface polarization pinning

    DOE PAGES

    Lee, Hyungwoo; Kim, Tae Heon; Patzner, Jacob J.; ...

    2016-02-22

    Surface-adsorbed polar molecules can significantly alter the ferroelectric properties of oxide thin films. Thus, fundamental understanding and controlling the effect of surface adsorbates are crucial for the implementation of ferroelectric thin film devices, such as ferroelectric tunnel junctions. Herein, we report an imprint control of BaTiO3 (BTO) thin films by chemically induced surface polarization pinning in the top few atomic layers of the water-exposed BTO films. Our studies based on synchrotron X-ray scattering and coherent Bragg rod analysis demonstrate that the chemically induced surface polarization is not switchable but reduces the polarization imprint and improves the bistability of ferroelectric phasemore » in BTO tunnel junctions. Here, we conclude that the chemical treatment of ferroelectric thin films with polar molecules may serve as a simple yet powerful strategy to enhance functional properties of ferroelectric tunnel junctions for their practical applications.« less

  20. Imprint Control of BaTiO3 Thin Films via Chemically Induced Surface Polarization Pinning.

    PubMed

    Lee, Hyungwoo; Kim, Tae Heon; Patzner, Jacob J; Lu, Haidong; Lee, Jung-Woo; Zhou, Hua; Chang, Wansoo; Mahanthappa, Mahesh K; Tsymbal, Evgeny Y; Gruverman, Alexei; Eom, Chang-Beom

    2016-04-13

    Surface-adsorbed polar molecules can significantly alter the ferroelectric properties of oxide thin films. Thus, fundamental understanding and controlling the effect of surface adsorbates are crucial for the implementation of ferroelectric thin film devices, such as ferroelectric tunnel junctions. Herein, we report an imprint control of BaTiO3 (BTO) thin films by chemically induced surface polarization pinning in the top few atomic layers of the water-exposed BTO films. Our studies based on synchrotron X-ray scattering and coherent Bragg rod analysis demonstrate that the chemically induced surface polarization is not switchable but reduces the polarization imprint and improves the bistability of ferroelectric phase in BTO tunnel junctions. We conclude that the chemical treatment of ferroelectric thin films with polar molecules may serve as a simple yet powerful strategy to enhance functional properties of ferroelectric tunnel junctions for their practical applications.

  1. The anti-nociceptive potential of tilmicosin against chemical-induced but not thermal-induced pain in mice.

    PubMed

    El-Mahmoudy, A; Gheith, I

    2016-03-01

    The aim of the present study was to assess the analgesic activity of the macrolide antibiotic tilmicosin at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, against chemical- and thermal-induced acute pains, using acetic acid-induced writhing, formalin-induced pain, hot-plate, and tail-flick models in mice. Tilmicosin showed a dose-dependent significant decrease in the number of writhes in the acetic acid-induced writhing test and significant decrease in hind paw-licking time in the late phase of the formalin test. However, it did not cause any significant changes in the reaction times to heat stimuli in the hot-plate and tail-flick models. In chemically-induced pains, both dose levels of tilmicosin showed significant effects compared to those of the corresponding standard peripheral analgesic, acetylsalicylic acid (200 mg/kg of body weight, subcutaneously) being 26.37±2.88 and 43.64±3.85% vs. 73.35±1.44% in acetic acid test; and 19.23±3.85 and 44.90±1.80% vs. 73.63±2.39% in the late phase of formalin test, respectively. These results may indicate that tilmicosin possesses a significant peripheral but not central analgesic potential that may be beneficial in symptomatic relief of pain when it is used in therapy, in addition to its well-established antibacterial effect.

  2. Causal Inference in Retrospective Studies.

    ERIC Educational Resources Information Center

    Holland, Paul W.; Rubin, Donald B.

    1988-01-01

    The problem of drawing causal inferences from retrospective case-controlled studies is considered. A model for causal inference in prospective studies is applied to retrospective studies. Limitations of case-controlled studies are formulated concerning relevant parameters that can be estimated in such studies. A coffee-drinking/myocardial…

  3. The Development of Causal Categorization

    ERIC Educational Resources Information Center

    Hayes, Brett K.; Rehder, Bob

    2012-01-01

    Two experiments examined the impact of causal relations between features on categorization in 5- to 6-year-old children and adults. Participants learned artificial categories containing instances with causally related features and noncausal features. They then selected the most likely category member from a series of novel test pairs.…

  4. Expert Causal Reasoning and Explanation.

    ERIC Educational Resources Information Center

    Kuipers, Benjamin

    The relationship between cognitive psychologists and researchers in artificial intelligence carries substantial benefits for both. An ongoing investigation in causal reasoning in medical problem solving systems illustrates this interaction. This paper traces a dialectic of sorts in which three different types of causal resaoning for medical…

  5. Commentary on Causal Prescriptive Statements

    ERIC Educational Resources Information Center

    Graesser, Arthur C.; Hu, Xiangen

    2011-01-01

    Causal prescriptive statements are valued in the social sciences when there is the goal of helping people through interventions. The articles in this special issue cover different methods for testing causal prescriptive statements. This commentary identifies both virtues and liabilities of these different approaches. We argue that it is extremely…

  6. Causal Inference and Developmental Psychology

    ERIC Educational Resources Information Center

    Foster, E. Michael

    2010-01-01

    Causal inference is of central importance to developmental psychology. Many key questions in the field revolve around improving the lives of children and their families. These include identifying risk factors that if manipulated in some way would foster child development. Such a task inherently involves causal inference: One wants to know whether…

  7. Causality in Solving Economic Problems

    ERIC Educational Resources Information Center

    Robinson, A. Emanuel; Sloman, Steven A.; Hagmayer, York; Hertzog, Christopher K.

    2010-01-01

    The role of causal beliefs in people's decisions when faced with economic problems was investigated. Two experiments are reported that vary the causal structure in prisoner's dilemma-like economic situations. We measured willingness to cooperate or defect and collected justifications and think-aloud protocols to examine the strategies that people…

  8. Causal Inference in Retrospective Studies.

    ERIC Educational Resources Information Center

    Holland, Paul W.; Rubin, Donald B.

    1988-01-01

    The problem of drawing causal inferences from retrospective case-controlled studies is considered. A model for causal inference in prospective studies is applied to retrospective studies. Limitations of case-controlled studies are formulated concerning relevant parameters that can be estimated in such studies. A coffee-drinking/myocardial…

  9. Causal Learning with Local Computations

    ERIC Educational Resources Information Center

    Fernbach, Philip M.; Sloman, Steven A.

    2009-01-01

    The authors proposed and tested a psychological theory of causal structure learning based on local computations. Local computations simplify complex learning problems via cues available on individual trials to update a single causal structure hypothesis. Structural inferences from local computations make minimal demands on memory, require…

  10. Commentary on Causal Prescriptive Statements

    ERIC Educational Resources Information Center

    Graesser, Arthur C.; Hu, Xiangen

    2011-01-01

    Causal prescriptive statements are valued in the social sciences when there is the goal of helping people through interventions. The articles in this special issue cover different methods for testing causal prescriptive statements. This commentary identifies both virtues and liabilities of these different approaches. We argue that it is extremely…

  11. Causal Inference and Developmental Psychology

    ERIC Educational Resources Information Center

    Foster, E. Michael

    2010-01-01

    Causal inference is of central importance to developmental psychology. Many key questions in the field revolve around improving the lives of children and their families. These include identifying risk factors that if manipulated in some way would foster child development. Such a task inherently involves causal inference: One wants to know whether…

  12. Causal Attributions of Shy Subjects.

    ERIC Educational Resources Information Center

    Teglasi, Hedwig; Hoffman, Mary Ann

    1982-01-01

    Causal attributions of shy students (N=36) were compared with those of a comparison group of students (N=36) in ten situations. Significant differences between the two groups emerged when explaining outcomes of situations considered to be problematic for shy individuals. Causal attributions may reflect realistic and situation-specific…

  13. How to Distinguish Conformational Selection and Induced Fit Based on Chemical Relaxation Rates

    PubMed Central

    2016-01-01

    Protein binding often involves conformational changes. Important questions are whether a conformational change occurs prior to a binding event (‘conformational selection’) or after a binding event (‘induced fit’), and how conformational transition rates can be obtained from experiments. In this article, we present general results for the chemical relaxation rates of conformational-selection and induced-fit binding processes that hold for all concentrations of proteins and ligands and, thus, go beyond the standard pseudo-first-order approximation of large ligand concentration. These results allow to distinguish conformational-selection from induced-fit processes—also in cases in which such a distinction is not possible under pseudo-first-order conditions—and to extract conformational transition rates of proteins from chemical relaxation data. PMID:27636092

  14. Effect of M-711 on experimental skin reactions induced by chemical mediators in rats.

    PubMed

    Shichinohe, K; Shimizu, M; Kurokawa, K

    1996-05-01

    We investigated the mechanism of anti-allergic action of Moku-boi-to (M-711) and effects on the skin reactions induced by chemical mediators as the model of allergic dermatitis. More than 20 mg/kg BW of M-711 significantly suppressed the enhancement of capillary permeability induced by histamine, LTC4, and anti-serum in the rat skin. Anti-histaminic effect of 40 mg/kg BW of M-711 was equipotent to same as the optimal doses of azelastine and diphenhydramine, respectively. As to anti-LTC4 action, 20 mg of M-711 was compared to the optimal dose of diphenhydramine. Those data showed that M-711 has the suppressive effects on the chemical mediators such as histamine and LTC4 and reduced the skin reaction induced by antigen-antibody response.

  15. A chemical-bond approach to doping, compensation and photo-induced degradation in amorphous silicon

    NASA Astrophysics Data System (ADS)

    Mueller, Gerhard; Kalbitzer, S.; Mannsperger, H.

    A model for the generalization of the doping theories of Street and Robertson is proposed. The basic idea is that during deposition of an Si:H film, a chemical equilibrium is established, relating the density of dangling-bond defects near mid-gap to the densities of electrons and holes in the conduction and valence band states. The appropriate chemical reaction formalism was developed. It is shown that the model allows doping, compensation, and photo-induced degradation to be treated within a single and unifying approach. The model can easily explain the existence of a low defect density in fully compensated material. By reducing the model to the intrinsic reactions (I-III), the bias-induced effects in p-i-n junctions and the photo-induced degradation in Si:H films are explained.

  16. On causality of extreme events

    PubMed Central

    2016-01-01

    Multiple metrics have been developed to detect causality relations between data describing the elements constituting complex systems, all of them considering their evolution through time. Here we propose a metric able to detect causality within static data sets, by analysing how extreme events in one element correspond to the appearance of extreme events in a second one. The metric is able to detect non-linear causalities; to analyse both cross-sectional and longitudinal data sets; and to discriminate between real causalities and correlations caused by confounding factors. We validate the metric through synthetic data, dynamical and chaotic systems, and data representing the human brain activity in a cognitive task. We further show how the proposed metric is able to outperform classical causality metrics, provided non-linear relationships are present and large enough data sets are available. PMID:27330866

  17. Paradoxical Behavior of Granger Causality

    NASA Astrophysics Data System (ADS)

    Witt, Annette; Battaglia, Demian; Gail, Alexander

    2013-03-01

    Granger causality is a standard tool for the description of directed interaction of network components and is popular in many scientific fields including econometrics, neuroscience and climate science. For time series that can be modeled as bivariate auto-regressive processes we analytically derive an expression for spectrally decomposed Granger Causality (SDGC) and show that this quantity depends only on two out of four groups of model parameters. Then we present examples of such processes whose SDGC expose paradoxical behavior in the sense that causality is high for frequency ranges with low spectral power. For avoiding misinterpretations of Granger causality analysis we propose to complement it by partial spectral analysis. Our findings are illustrated by an example from brain electrophysiology. Finally, we draw implications for the conventional definition of Granger causality. Bernstein Center for Computational Neuroscience Goettingen

  18. Structure and Strength in Causal Induction

    ERIC Educational Resources Information Center

    Griffiths, Thomas L.; Tenenbaum, Joshua B.

    2005-01-01

    We present a framework for the rational analysis of elemental causal induction--learning about the existence of a relationship between a single cause and effect--based upon causal graphical models. This framework makes precise the distinction between causal structure and causal strength: the difference between asking whether a causal relationship…

  19. Application of pulsed corona induced plasma chemical process to an industrial incinerator.

    PubMed

    Lee, Yong-Hwan; Jung, Won-Suk; Choi, Yu-Ri; Oh, Jong-Seok; Jang, Sung-Duck; Son, Yoon-Gyu; Cho, Moo-Hyun; Namkung, Won; Koh, Dong-Jun; Mok, Young-Sun; Chung, Jae-Woo

    2003-06-01

    Pulsed corona induced plasma chemical process (PPCP) has been investigated for the simultaneous removal of NO(x) (nitrogen oxides) and SO2 (sulfur dioxide) from the flue gas emission. It is one of the world's largest scales of PPCP for treating NO(x) and SO2 simultaneously. A PPCP unit equipped with an average 120 kW modulator has been installed and tested at an industrial incinerator with the gas flow rate of 42 000 m3/h. To improve the removal efficiency of SO2 and NO(x), ammonia (NH3) and propylene (C3H6) were used as chemical additives. It was observed that the pulsed corona induced plasma chemical process made significant NO(x) and SO2 conversion with reasonable electric power consumption. The ammonia injection was very effective in the enhancement of SO2 removal. NO removal efficiency was significantly improved by injecting a C3H6 additive. In the experiments, the removal efficiencies of SO2 and NO(x) were approximately 99 and 70%, respectively. The specific energy consumption during the normal operation was approximately 1.4 Wh/m3, and the nanopulse conversion efficiency of 64.3% was achieved with the pulsed corona induced plasma chemical process.

  20. Causal Rasch models

    PubMed Central

    Stenner, A. Jackson; Fisher, William P.; Stone, Mark H.; Burdick, Donald S.

    2013-01-01

    Rasch's unidimensional models for measurement show how to connect object measures (e.g., reader abilities), measurement mechanisms (e.g., machine-generated cloze reading items), and observational outcomes (e.g., counts correct on reading instruments). Substantive theory shows what interventions or manipulations to the measurement mechanism can be traded off against a change to the object measure to hold the observed outcome constant. A Rasch model integrated with a substantive theory dictates the form and substance of permissible interventions. Rasch analysis, absent construct theory and an associated specification equation, is a black box in which understanding may be more illusory than not. Finally, the quantitative hypothesis can be tested by comparing theory-based trade-off relations with observed trade-off relations. Only quantitative variables (as measured) support such trade-offs. Note that to test the quantitative hypothesis requires more than manipulation of the algebraic equivalencies in the Rasch model or descriptively fitting data to the model. A causal Rasch model involves experimental intervention/manipulation on either reader ability or text complexity or a conjoint intervention on both simultaneously to yield a successful prediction of the resultant observed outcome (count correct). We conjecture that when this type of manipulation is introduced for individual reader text encounters and model predictions are consistent with observations, the quantitative hypothesis is sustained. PMID:23986726

  1. Generalized Causal Mediation Analysis

    PubMed Central

    Albert, Jeffrey M.; Nelson, Suchitra

    2010-01-01

    Summary The goal of mediation analysis is to assess direct and indirect effects of a treatment or exposure on an outcome. More generally, we may be interested in the context of a causal model as characterized by a directed acyclic graph (DAG), where mediation via a specific path from exposure to outcome may involve an arbitrary number of links (or ‘stages’). Methods for estimating mediation (or pathway) effects are available for a continuous outcome and a continuous mediator related via a linear model, while for a categorical outcome or categorical mediator, methods are usually limited to two-stage mediation. We present a method applicable to multiple stages of mediation and mixed variable types using generalized linear models. We define pathway effects using a potential outcomes framework and present a general formula that provides the effect of exposure through any specified pathway. Some pathway effects are nonidentifiable and their estimation requires an assumption regarding the correlation between counterfactuals. We provide a sensitivity analysis to assess of the impact of this assumption. Confidence intervals for pathway effect estimates are obtained via a bootstrap method. The method is applied to a cohort study of dental caries in very low birth weight adolescents. A simulation study demonstrates low bias of pathway effect estimators and close-to-nominal coverage rates of confidence intervals. We also find low sensitivity to the counterfactual correlation in most scenarios. PMID:21306353

  2. History, causality, and sexology.

    PubMed

    Money, John

    2003-08-01

    In 1896, Krafft-Ebing published Psychopathia Sexualis. Popularly defined as hereditary weakness or taintedness in the family pedigree, degeneracy was called upon as a causal explanation for perversions of the sexual instinct. Although Krafft-Ebing accepted Karl Ulrichs proposal that homosexuality could be innate and probably located in the brain, he paid little attention to neuropathological sexology. Alfred Binet challenged Krafft-Ebing's orthodoxy by explaining fetishism in terms of associative learning, to which Krafft-Ebing's response was that only those with a hereditary taint would be vulnerable. Thus did the venerable nature-nurture antithesis maintain its rhetoric, even to the present day. Krafft-Ebing died too soon to meet the Freudian challenge of endopsychic determinism, and too soon also to encounter the idea of a developmental multivariate outcome of what I have termed the lovemap. Like other brain maps, for example the languagemap, the lovemap requires an intact human brain in which to develop. The personalized content of the lovemap has access to the brain by way of the special senses.

  3. Effect of a chemical chaperone, tauroursodeoxycholic acid, on HDM-induced allergic airway disease

    PubMed Central

    Siddesha, Jalahalli M.; Nakada, Emily M.; Mihavics, Bethany R.; Hoffman, Sidra M.; Rattu, Gurkiranjit K.; Chamberlain, Nicolas; Cahoon, Jonathon M.; Lahue, Karolyn G.; Daphtary, Nirav; Aliyeva, Minara; Chapman, David G.; Desai, Dhimant H.; Poynter, Matthew E.

    2016-01-01

    Endoplasmic reticulum (ER) stress-induced unfolded protein response plays a critical role in inflammatory diseases, including allergic airway disease. However, the benefits of inhibiting ER stress in the treatment of allergic airway disease are not well known. Herein, we tested the therapeutic potential of a chemical chaperone, tauroursodeoxycholic acid (TUDCA), in combating allergic asthma, using a mouse model of house dust mite (HDM)-induced allergic airway disease. TUDCA was administered during the HDM-challenge phase (preventive regimen), after the HDM-challenge phase (therapeutic regimen), or therapeutically during a subsequent HDM rechallenge (rechallenge regimen). In the preventive regimen, TUDCA significantly decreased HDM-induced inflammation, markers of ER stress, airway hyperresponsiveness (AHR), and fibrosis. Similarly, in the therapeutic regimen, TUDCA administration efficiently decreased HDM-induced airway inflammation, mucus metaplasia, ER stress markers, and AHR, but not airway remodeling. Interestingly, TUDCA administered therapeutically in the HDM rechallenge regimen markedly attenuated HDM-induced airway inflammation, mucus metaplasia, ER stress markers, methacholine-induced AHR, and airway fibrotic remodeling. These results indicate that the inhibition of ER stress in the lungs through the administration of chemical chaperones could be a valuable strategy in the treatment of allergic airway diseases. PMID:27154200

  4. The chemical cue tetrabromopyrrole from a biofilm bacterium induces settlement of multiple Caribbean corals

    PubMed Central

    Sneed, Jennifer M.; Sharp, Koty H.; Ritchie, Kimberly B.; Paul, Valerie J.

    2014-01-01

    Microbial biofilms induce larval settlement for some invertebrates, including corals; however, the chemical cues involved have rarely been identified. Here, we demonstrate the role of microbial biofilms in inducing larval settlement with the Caribbean coral Porites astreoides and report the first instance of a chemical cue isolated from a marine biofilm bacterium that induces complete settlement (attachment and metamorphosis) of Caribbean coral larvae. Larvae settled in response to natural biofilms, and the response was eliminated when biofilms were treated with antibiotics. A similar settlement response was elicited by monospecific biofilms of a single bacterial strain, Pseudoalteromonas sp. PS5, isolated from the surface biofilm of a crustose coralline alga. The activity of Pseudoalteromonas sp. PS5 was attributed to the production of a single compound, tetrabromopyrrole (TBP), which has been shown previously to induce metamorphosis without attachment in Pacific acroporid corals. In addition to inducing settlement of brooded larvae (P. astreoides), TBP also induced larval settlement for two broadcast-spawning species, Orbicella (formerly Montastraea) franksi and Acropora palmata, indicating that this compound may have widespread importance among Caribbean coral species. PMID:24850918

  5. "Head take you": causal attributions of mental illness in Jamaica.

    PubMed

    Arthur, Carlotta M; Whitley, Rob

    2015-02-01

    Causal attributions are a key factor in explanatory models of illness; however, little research on causal attributions of mental illness has been conducted in developing nations in the Caribbean, including Jamaica. Explanatory models of mental illness may be important in understanding illness experience and be a crucial factor in mental health service seeking and utilization. We explored causal attributions of mental illness in Jamaica by conducting 20 focus groups, including 16 community samples, 2 patient samples, and 2 samples of caregivers of patients, with a total of 159 participants. The 5 most commonly endorsed causal attributions of mental illness are discussed: (a) drug-related causes, including ganja (marijuana); (b) biological causes, such as chemical imbalance, familial transmission, and "blood"; (c) psychological causes, including stress and thinking too much; (d) social causes, such as relationship problems and job loss; and (e) spiritual or religious causes, including Obeah. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  6. The relationship between chemical-induced kidney weight increases and kidney histopathology in rats.

    PubMed

    Craig, Evisabel A; Yan, Zhongyu; Zhao, Q Jay

    2015-07-01

    The kidney is a major site of chemical excretion, which results in its propensity to exhibit chemically-induced toxicological effects at a higher rate than most other organs. Although the kidneys are often weighed in animal toxicity studies, the manner in which these kidney weight measurements are interpreted and the value of this information in predicting renal damage remains controversial. In this study we sought to determine whether a relationship exists between chemically-induced kidney weight changes and renal histopathological alterations. We also examined the relative utility of absolute and relative (kidney-to-body weight ratio) kidney weight in the prediction of renal toxicity. For this, data extracted from oral chemical exposure studies in rats performed by the National Toxicology Program were qualitatively and quantitatively evaluated. Our analysis showed a statistically significant correlation between absolute, but not relative, kidney weight and renal histopathology in chemically-treated rats. This positive correlation between absolute kidney weight and histopathology was observed even with compounds that statistically decreased terminal body weight. Also, changes in absolute kidney weight, which occurred at subchronic exposures, were able to predict the presence or absence of kidney histopathology at both subchronic and chronic exposures. Furthermore, most increases in absolute kidney weight reaching statistical significance (irrespective of the magnitude of change) were found to be relevant for the prediction of histopathological changes. Hence, our findings demonstrate that the evaluation of absolute kidney weight is a useful method for identifying potential renal toxicants. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Inducible interleukin-4-secreting cells provoked in mice during chemical sensitization.

    PubMed Central

    Dearman, R J; Ramdin, L S; Basketter, D A; Kimber, I

    1994-01-01

    It has been demonstrated previously that chemical contact and respiratory allergens differ with respect to the quality of immune responses they will provoke in mice. Trimellitic anhydride (TMA), a human respiratory allergen, induces in mice responses consistent with the preferential activation of Th2-type cells, resulting in the production of IgE anti-hapten antibody and an increase in the serum concentration of IgE. In contrast, oxazolone (OX), a potent contact allergen considered not to cause respiratory hypersensitivity, induces instead Th1-type responses in mice characterized by vigorous IgG2a antibody production and a failure to elicit IgE. In the present study we have extended these investigations and have examined the capacity of these chemicals to stimulate inducible interleukin-4 (IL-4) production by draining lymph node cells (LNC). IL-4 was measured in the supernatants of draining LNC cultured for various periods in the presence or absence of concanavalin A (Con A). Following primary topical exposure to the chemical allergens, Con A-stimulated LNC from OX-treated mice secreted significantly more IL-4 than did LNC from mice exposed to trimellitic anhydride (TMA). A different pattern of IL-4 secretion was observed following culture with Con A of LNC prepared from lymph nodes draining the sites of secondary exposure to these chemicals. In this case significantly higher concentrations of IL-4 were produced by TMA-treated mice. Detectable levels of IL-4 (> 300 pg/ml) were not found following culture of draining LNC from sensitized mice in the absence of Con A or following culture of LNC from naive mice with or without Con A. These data demonstrate that chemical allergens of different types stimulate discrete and changing patterns of inducible IL-4 synthesis consistent with the selective activation of Th-cell subpopulations. PMID:8039807

  8. Principal stratification in causal inference.

    PubMed

    Frangakis, Constantine E; Rubin, Donald B

    2002-03-01

    Many scientific problems require that treatment comparisons be adjusted for posttreatment variables, but the estimands underlying standard methods are not causal effects. To address this deficiency, we propose a general framework for comparing treatments adjusting for posttreatment variables that yields principal effects based on principal stratification. Principal stratification with respect to a posttreatment variable is a cross-classification of subjects defined by the joint potential values of that posttreatment variable tinder each of the treatments being compared. Principal effects are causal effects within a principal stratum. The key property of principal strata is that they are not affected by treatment assignment and therefore can be used just as any pretreatment covariate. such as age category. As a result, the central property of our principal effects is that they are always causal effects and do not suffer from the complications of standard posttreatment-adjusted estimands. We discuss briefly that such principal causal effects are the link between three recent applications with adjustment for posttreatment variables: (i) treatment noncompliance, (ii) missing outcomes (dropout) following treatment noncompliance. and (iii) censoring by death. We then attack the problem of surrogate or biomarker endpoints, where we show, using principal causal effects, that all current definitions of surrogacy, even when perfectly true, do not generally have the desired interpretation as causal effects of treatment on outcome. We go on to forrmulate estimands based on principal stratification and principal causal effects and show their superiority.

  9. Causal inference and developmental psychology.

    PubMed

    Foster, E Michael

    2010-11-01

    Causal inference is of central importance to developmental psychology. Many key questions in the field revolve around improving the lives of children and their families. These include identifying risk factors that if manipulated in some way would foster child development. Such a task inherently involves causal inference: One wants to know whether the risk factor actually causes outcomes. Random assignment is not possible in many instances, and for that reason, psychologists must rely on observational studies. Such studies identify associations, and causal interpretation of such associations requires additional assumptions. Research in developmental psychology generally has relied on various forms of linear regression, but this methodology has limitations for causal inference. Fortunately, methodological developments in various fields are providing new tools for causal inference-tools that rely on more plausible assumptions. This article describes the limitations of regression for causal inference and describes how new tools might offer better causal inference. This discussion highlights the importance of properly identifying covariates to include (and exclude) from the analysis. This discussion considers the directed acyclic graph for use in accomplishing this task. With the proper covariates having been chosen, many of the available methods rely on the assumption of "ignorability." The article discusses the meaning of ignorability and considers alternatives to this assumption, such as instrumental variables estimation. Finally, the article considers the use of the tools discussed in the context of a specific research question, the effect of family structure on child development.

  10. Ultrafast laser induced breakdown spectroscopy for high spatial resolution chemical analysis

    NASA Astrophysics Data System (ADS)

    Zorba, Vassilia; Mao, Xianglei; Russo, Richard E.

    2011-02-01

    Femtosecond laser induced breakdown spectroscopy (LIBS) was used to identify the spatial resolution limitations and assess the minimal detectable mass restrictions in laser-ablation based chemical analysis. The atomic emission of sodium (Na) and potassium (K) dopants in transparent dielectric Mica matrices was studied, to find that both these elements could be detected from 450 nm diameter ablation craters, full-width-at-half-maximum (FWHM). Under optimal conditions, mass as low as 220 ag was measured, demonstrating the feasibility of using laser-ablation based chemical analysis to achieve high spatial resolution elemental analysis in real-time and at atmospheric pressure conditions.

  11. THE EFFECT OF CHEMICAL CARCINOGENS ON VIRUS-INDUCED RABBIT PAPILLOMAS

    PubMed Central

    Rous, Peyton; Friedewald, William F.

    1944-01-01

    The application of methylcholanthrene and tar to virus-induced papillomas of the domestic rabbit caused them to become carcinomatous with great rapidity, and the malignant changes were frequently multiple. In bringing on the cancers the chemical agents acted in their specific capacity as carcinogens, not as ordinary stimulants of cell proliferation. The cancers derived from the virus-infected cells and were of the same types as arise from these elements spontaneously after a much longer time. The evidence would seem to indicate that the chemical carcinogens acted by way of the virus. PMID:19871385

  12. Identification of a second family of genes in Moniliophthora perniciosa, the causal agent of witches' broom disease in cacao, encoding necrosis-inducing proteins similar to cerato-platanins.

    PubMed

    Zaparoli, Gustavo; Cabrera, Odalys García; Medrano, Francisco Javier; Tiburcio, Ricardo; Lacerda, Gustavo; Pereira, Gonçalo Guimarães

    2009-01-01

    The hemibiotrophic basidiomycete Moniliophthora perniciosa is the causal agent of witches' broom disease in cacao. This is a dimorphic species, with monokaryotic hyphae during the biotrophic phase, which is converted to dikaryotic mycelia during the saprophytic phase. The infection in pod is characterized by the formation of hypertrophic and hyperplasic tissues in the biotrophic phase, which is followed by necrosis and complete degradation of the organ. We found at least five sequences in the fungal genome encoding putative proteins similar to cerato-platanin (CP)-like proteins, a novel class of proteins initially found in the phytopathogen Ceratocystis fimbriata. One M. perniciosa CP gene (MpCP1) was expressed in vitro and proved to have necrosis-inducing ability in tobacco and cacao leaves. The protein is present in solution as dimers and is able to recover necrosis activity after heat treatment. Transcription analysis ex planta showed that MpCP1 is more expressed in biotrophic-like mycelia than saprotrophic mycelia. The necrosis profile presented is different from that caused by M. perniciosa necrosis and ethylene-inducing proteins (MpNEPs), another family of elicitors expressed by M. perniciosa. Remarkably, a mixture of MpCP1 with MpNEP2 led to a synergistic necrosis effect very similar to that found in naturally infected plants. This is the first report of a basidiomycete presenting both NEP1-like proteins (NLPs) and CPs in its genome.

  13. Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation

    PubMed Central

    Ye, Wei; Wu, Hongqing; He, Xin; Wang, Lei; Zhang, Weimin; Li, Haohua; Fan, Yunfei; Tan, Guohui; Liu, Taomei; Gao, Xiaoxia

    2016-01-01

    Background Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. Methodology/Principal Findings A five-year-old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant–pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. Conclusions/Significance The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of

  14. Causal evolution of wave packets

    NASA Astrophysics Data System (ADS)

    Eckstein, Michał; Miller, Tomasz

    2017-03-01

    Drawing from the optimal transport theory adapted to the relativistic setting we formulate the principle of a causal flow of probability and apply it in the wave-packet formalism. We demonstrate that whereas the Dirac Hamiltonian impels a causal evolution of probabilities, even in the presence of interactions, the relativistic-Schrödinger model is acausal. We quantify the causality breakdown in the latter model and argue that, in contrast to the popular viewpoint, it is not related to the localization properties of the states.

  15. Human causal discovery from observational data.

    PubMed Central

    Hashem, A. I.; Cooper, G. F.

    1996-01-01

    Utilizing Bayesian belief networks as a model of causality, we examined medical students' ability to discover causal relationships from observational data. Nine sets of patient cases were generated from relatively simple causal belief networks by stochastic simulation. Twenty participants examined the data sets and attempted to discover the underlying causal relationships. Performance was poor in general, except at discovering the absence of a causal relationship. This work supports the potential for combining human and computer methods for causal discovery. PMID:8947621

  16. A chemical pollen suppressant inhibits auxin-induced growth in maize coleoptile sections

    SciTech Connect

    Vesper, M.J. ); Cross, J.W. )

    1990-05-01

    Chemical inhibitors of pollen development having a phenylcinnoline carboxylate structure were found to inhibit IAA- and 1-NAA-induced growth in maize coleoptile sections. The inhibitor (100 {mu}M) used in these experiments caused approx. 35% reduction in auxin-induced growth over the auxin concentration range of 0.3 to 100 {mu}M. Growth inhibition was noted as a lengthening of the latent period and a decrease in the rate of an auxin-induced growth response. An acid growth response to pH 5 buffer in abraded sections was not impaired. The velocity of basipetal transport of ({sup 3}H)IAA through the coleoptile sections also was not inhibited by the compound, nor was uptake of ({sup 3}H)IAA. Similarly, the inhibitor does not appear to alter auxin-induced H{sup +} secretion. We suggest that the agent targets some other process necessary for auxin-dependent growth.

  17. Polar/apolar chemical inducers of differentiation of transformed cells: strategies to improve therapeutic potential.

    PubMed Central

    Marks, P A; Breslow, R; Rifkind, R A; Ngo, L; Singh, R

    1989-01-01

    N,N'-Hexamethylenebisacetamide (HMBA) induces transformed cells to differentiate, accompanied by suppression of oncogenicity. Clinical trials have shown that HMBA can cause positive therapeutic responses in some cancer patients, but clinical efficacy may be limited, in part, by dose-related toxicity. Potential improvements in efficacy may be accomplished by changes in the chemical structure of inducing agents and by increasing the sensitivity of tumor cells to inducers of differentiation. We have previously described an approach to improving tumor cell responsiveness to inducing agents. Transformed cell lines that have acquired low levels of resistance to vincristine display a markedly increased sensitivity to HMBA. We now report on a series of hybrid polar/apolar compounds--some of which are as active as HMBA and several of which are significantly more active than HMBA in vitro--whose chemical structures make it likely that they have different pharmacokinetics. Vincristine-resistant murine erythroleukemia cells also are shown to have marked increased sensitivity to these hybrid polar/apolar compounds. Thus these findings suggest potentially useful strategies for the application of polar/apolar inducers of differentiation to the treatment of cancers. These studies also provide approaches to further understanding of the biological process of terminal differentiation. PMID:2762329

  18. Chemical Leucoderma Induced by Ear-ring Stoppers Made of Polyvinyl Chloride

    PubMed Central

    Sharma, Reena; Singal, Archana; Verma, Prashant; Grover, Chander

    2012-01-01

    We report a case of chemical leucoderma (CL) in a 15-year-old girl, who developed patterned depigmentation at the back of both ear lobules after contact with plastic ear-ring stoppers made of polyvinyl chloride (PVC) after continuous use for 6–7 months. Patch test with Indian standard series and cosmetic series was negative after 48 h, but she refused patch testing for extended duration as the possibility of induced depigmentation at the test site was unacceptable to her. To the best of our knowledge, this is the first report of plastic ear-ring stopper induced CL. PMID:23060712

  19. Fabrication of highly ultramicroporous carbon nanofoams by SF6-catalyzed laser-induced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Hattori, Yoshiyuki; Shuhara, Ai; Kondo, Atsushi; Utsumi, Shigenori; Tanaka, Hideki; Ohba, Tomonori; Kanoh, Hirofumi; Takahashi, Kunimitsu; Vallejos-Burgos, Fernando; Kaneko, Katsumi

    2016-05-01

    We have developed a laser-induced chemical vapor deposition (LCVD) method for preparing nanocarbons with the aid of SF6. This method would offer advantages for the production of aggregates of nanoscale foams (nanofoams) at high rates. Pyrolysis of the as-grown nanofoams induced the high surface area (1120 m2 g-1) and significantly enhanced the adsorption of supercritical H2 (16.6 mg g-1 at 77 K and 0.1 MPa). We also showed that the pyrolized nanofoams have highly ultramicroporous structures. The pyrolized nanofoams would be superior to highly microporous nanocarbons for the adsorption of supercritical gases.

  20. Protective effect of dieckol against chemical hypoxia-induced cytotoxicity in primary cultured mouse hepatocytes.

    PubMed

    Jeon, Yu Jin; Kim, Hyoung Seok; Song, Kyung-Sik; Han, Ho Jae; Park, Soo Hyun; Chang, Woochul; Lee, Min Young

    2015-04-01

    Hepatic ischemic injury is a major complication arising from liver surgery, transplantation, or other ischemic diseases, and both reactive oxygen species (ROS) and pro-inflammatory mediators play the role of key mediators in hepatic ischemic injury. In this study, we examined the effect of dieckol in chemical hypoxia-induced injury in mouse hepatocytes. Cell viability was significantly decreased after treatment with cobalt chloride (CoCl2), a well-known hypoxia mimetic agent in a time- and dose-dependent manner. Pretreatment with dieckol before exposure to CoCl2 significantly attenuated the CoCl2-induced decrease of cell viability. Additionally, pretreatment with dieckol potentiated the CoCl2-induced decrease of Bcl-2 expression and attenuated the CoCl2-induced increase in the expression of Bax and caspase-3. Treatment with CoCl2 resulted in an increased intracellular ROS generation, which is inhibited by dieckol or N-acetyl cysteine (NAC, a ROS scavenger), and p38 MAPK phosphorylation, which is also blocked by dieckol or NAC. In addition, dieckol and SB203580 (p38 MAPK inhibitor) increased the CoCl2-induced decrease of Bcl-2 expression and decreased the CoCl2-induced increase of Bax and caspase-3 expressions. CoCl2-induced decrease of cell viability was attenuated by pretreatment with dieckol, NAC, and SB203580. Furthermore, dieckol attenuated CoCl2-induced COX-2 expression. Similar to the effect of dieckol, NAC also blocked CoCl2-induced COX-2 expression. Additionally, CoCl2-induced decrease of cell viability was attenuated not only by dieckol and NAC but also by NS-398 (a selective COX-2 inhibitor). In conclusion, dieckol protects primary cultured mouse hepatocytes against CoCl2-induced cell injury through inhibition of ROS-activated p38 MAPK and COX-2 pathway.

  1. Cortisol influences the antipredator behavior induced by chemical alarm cues in the Frillfin goby.

    PubMed

    Barreto, Rodrigo Egydio; Barbosa-Júnior, Augusto; Urbinati, Elisabeth Criscuolo; Hoffmann, Anette

    2014-04-01

    We evaluated the effect of increased plasma cortisol levels on fish antipredator behavior induced by conspecific chemical alarm cues. The experimental model for the study was the Frillfin goby Bathygobius soporator. We first confirmed that the alarm substance induces typical defensive antipredator responses in Frillfin gobies and described their alarm substance cells (epidermal 'club' cells). Second, we confirmed that intraperitoneal cortisol implants increase plasma cortisol levels in this species. We then demonstrated that exogenous cortisol administration and subsequent exposure to an alarm substance decreased swimming activity to a greater extent than the activity prompted by either stimulus alone. In addition, cortisol did not abolish the sheltering response to the alarm chemical cue even though it decreased activity. As predators use prey movements to guide their first contact with the prey, a factor that decreases swimming activity clearly increases the probability of survival. Consequently, this observation indicates that cortisol helps improve the antipredator response in fish. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Noise induced oscillations and coherence resonance in a generic model of the nonisothermal chemical oscillator

    PubMed Central

    Simakov, David S. A.; Pérez-Mercader, Juan

    2013-01-01

    Oscillating chemical reactions are common in biological systems and they also occur in artificial non-biological systems. Generally, these reactions are subject to random fluctuations in environmental conditions which translate into fluctuations in the values of physical variables, for example, temperature. We formulate a mathematical model for a nonisothermal minimal chemical oscillator containing a single negative feedback loop and study numerically the effects of stochastic fluctuations in temperature in the absence of any deterministic limit cycle or periodic forcing. We show that noise in temperature can induce sustained limit cycle oscillations with a relatively narrow frequency distribution and some characteristic frequency. These properties differ significantly depending on the noise correlation. Here, we have explored white and colored (correlated) noise. A plot of the characteristic frequency of the noise induced oscillations as a function of the correlation exponent shows a maximum, therefore indicating the existence of autonomous stochastic resonance, i.e. coherence resonance. PMID:23929212

  3. Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts

    PubMed Central

    Lai, Pei-Lun; Lin, Hsuan; Chen, Shang-Fu; Yang, Shang-Chih; Hung, Kuo-Hsuan; Chang, Ching-Fang; Chang, Hsiang-Yi; Lu, Frank Leigh; Lee, Yi-Hsuan; Liu, Yu-Chuan; Huang, Hsiao-Chun; Lu, Jean

    2017-01-01

    Human mesenchymal stromal/stem cells (MSCs) are multipotent and currently undergoing hundreds of clinical trials for disease treatments. To date, no studies have generated induced MSCs from skin fibroblasts with chemicals or growth factors. Here, we established the first chemical method to convert primary human dermal fibroblasts into multipotent, induced MSC-like cells (iMSCs). The conversion method uses a defined cocktail of small molecules and growth factors, and it can achieve efficient conversion with an average rate of 38% in 6 days. The iMSCs have much higher clonogenicity than fibroblasts, and they can be maintained and expanded in regular MSC medium for at least 8 passages and further differentiated into osteoblasts, adipocytes, and chondrocytes. Moreover, the iMSCs can suppress LPS-mediated acute lung injury as effectively as bone marrow-derived mesenchymal stem cells. This finding may greatly benefit stem cell biology, cell therapy, and regenerative medicine. PMID:28303927

  4. Metabolomic assessment of induced and activated chemical defence in the invasive red alga Gracilaria vermiculophylla.

    PubMed

    Nylund, Göran M; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  5. Metabolomic Assessment of Induced and Activated Chemical Defence in the Invasive Red Alga Gracilaria vermiculophylla

    PubMed Central

    Nylund, Göran M.; Weinberger, Florian; Rempt, Martin; Pohnert, Georg

    2011-01-01

    In comparison with terrestrial plants the mechanistic knowledge of chemical defences is poor for marine macroalgae. This restricts our understanding in the chemically mediated interactions that take place between algae and other organisms. Technical advances such as metabolomics, however, enable new approaches towards the characterisation of the chemically mediated interactions of organisms with their environment. We address defence responses in the red alga Gracilaria vermiculophylla using mass spectrometry based metabolomics in combination with bioassays. Being invasive in the north Atlantic this alga is likely to possess chemical defences according to the prediction that well-defended exotics are most likely to become successful invaders in systems dominated by generalist grazers, such as marine macroalgal communities. We investigated the effect of intense herbivore feeding and simulated herbivory by mechanical wounding of the algae. Both processes led to similar changes in the metabolic profile. Feeding experiments with the generalist isopod grazer Idotea baltica showed that mechanical wounding caused a significant increase in grazer resistance. Structure elucidation of the metabolites of which some were up-regulated more than 100 times in the wounded tissue, revealed known and novel eicosanoids as major components. Among these were prostaglandins, hydroxylated fatty acids and arachidonic acid derived conjugated lactones. Bioassays with pure metabolites showed that these eicosanoids are part of the innate defence system of macroalgae, similarly to animal systems. In accordance with an induced defence mechanism application of extracts from wounded tissue caused a significant increase in grazer resistance and the up-regulation of other pathways than in the activated defence. Thus, this study suggests that G. vermiculophylla chemically deters herbivory by two lines of defence, a rapid wound-activated process followed by a slower inducible defence. By unravelling

  6. Modelling biological and chemically induced precipitation of calcium phosphate in enhanced biological phosphorus removal systems.

    PubMed

    Barat, R; Montoya, T; Seco, A; Ferrer, J

    2011-06-01

    The biologically induced precipitation processes can be important in wastewater treatment, in particular treating raw wastewater with high calcium concentration combined with Enhanced Biological Phosphorus Removal. Currently, there is little information and experience in modelling jointly biological and chemical processes. This paper presents a calcium phosphate precipitation model and its inclusion in the Activated Sludge Model No 2d (ASM2d). The proposed precipitation model considers that aqueous phase reactions quickly achieve the chemical equilibrium and that aqueous-solid change is kinetically governed. The model was calibrated using data from four experiments in a Sequencing Batch Reactor (SBR) operated for EBPR and finally validated with two experiments. The precipitation model proposed was able to reproduce the dynamics of amorphous calcium phosphate (ACP) formation and later crystallization to hydroxyapatite (HAP) under different scenarios. The model successfully characterised the EBPR performance of the SBR, including the biological, physical and chemical processes.

  7. Alignment of cylindrical colloids near chemically patterned substrates induced by critical Casimir torques.

    PubMed

    Labbé-Laurent, M; Tröndle, M; Harnau, L; Dietrich, S

    2014-04-07

    Recent experiments have demonstrated a fluctuation-induced lateral trapping of spherical colloidal particles immersed in a binary liquid mixture near its critical demixing point and exposed to chemically patterned substrates. Inspired by these experiments, we study this kind of effective interaction, known as the critical Casimir effect, for elongated colloids of cylindrical shape. This adds orientational degrees of freedom. When the colloidal particles are close to a chemically structured substrate, a critical Casimir torque acting on the colloids emerges. We calculate this torque on the basis of the Derjaguin approximation. The range of validity of the latter is assessed via mean-field theory. This assessment shows that the Derjaguin approximation is reliable in experimentally relevant regimes, so that we extend it to Janus particles endowed with opposing adsorption preferences. Our analysis indicates that critical Casimir interactions are capable of achieving well-defined, reversible alignments both of chemically homogeneous and of Janus cylinders.

  8. Fabrication of chemical templates via selective laser-induced desorption of hexadecanethiol self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Schröter, Anja; Mathieu, Mareike; Franzka, Steffen; Feydt, Jürgen; Irsen, Stephan; Hartmann, Nils

    2013-08-01

    A nonlinear photothermal laser patterning technique for rapid fabrication of chemical templates is demonstrated. Hexadecanethiol monolayers on Au-coated Si substrates are processed at λ = 532 nm, a 1/e2 spot diameter of d=2.8 μm and ambient conditions. Local laser irradiation at high laser powers and short irradiation times in the micro-/millisecond range induces desorption of thiol molecules. The laser-depleted areas are backfilled with mercaptohexadecanoic acid in order to build up chemical templates. Atomic force microscopy, scanning electron microscopy and scanning Auger electron spectroscopy are used for characterization of these templates. In agreement with a selective laser process, the results indicate the formation of flat chemical patterns with well-defined boundaries. Complementary condensation experiments demonstrate the functionality of the patterns as hydrophilic/hydrophobic templates. In particular, upon decreasing the temperature below the dew point, selective formation of water droplets on the backfilled areas is observed.

  9. Laser-induced chemical liquid phase deposition of copper from aqueous solutions without reducing agents

    SciTech Connect

    Kochemirovsky, V A; Tumkin, I I; Logunov, L S; Safonov, S V; Menchikov, Leonid G

    2012-08-31

    Laser-induced chemical liquid phase deposition of copper without a traditional reducing agent has been used for the first time to obtain conductive patterns on a dielectric surface having a reducing ability. It is shown that phenol-formaldehyde binder of the dielectric (glass fibre) can successfully play the role of a reducing agent in this process. The resulting copper sediments have low electrical resistance and good topology. (interaction of laser radiation with matter. laser plasmas)

  10. Study on chemical, UV and gamma radiation-induced grafting of 2-hydroxyethyl methacrylate onto chitosan

    NASA Astrophysics Data System (ADS)

    Casimiro, M. H.; Botelho, M. L.; Leal, J. P.; Gil, M. H.

    2005-04-01

    In the present study, 2-hydroxyethyl methacrylate has been grafted onto chitosan by using either chemical initiation, or photo-induction or gamma radiation-induced polymerisation, all under heterogeneous conditions. The evidence of grafting was provided by Fourier transform infrared spectroscopy and thermal analysis. The results concerning the effect of initiator concentration, initial monomer concentration and dose rate influencing on the yield of grafting reactions are presented. These suggest that gamma irradiation is the method that leads to higher yields of grafting.

  11. Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.

    PubMed

    Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

    2015-10-15

    Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Fluorescence Visualization of the Enteric Nervous Network in a Chemically Induced Aganglionosis Model

    PubMed Central

    Shimojima, Naoki; Morikawa, Yasuhide; Okano, Hideyuki; Kuroda, Tatsuo

    2016-01-01

    Gastrointestinal motility disorders, severe variants in particular, remain a therapeutic challenge in pediatric surgery. Absence of enteric ganglion cells that originate from neural crest cells is a major cause of dysmotility. However, the limitations of currently available animal models of dysmotility continue to impede the development of new therapeutics. Indeed, the short lifespan and/or poor penetrance of existing genetic models of dysmotility prohibit the functional evaluation of promising approaches, such as stem cell replacement strategy. Here, we induced an aganglionosis model using topical benzalkonium chloride in a P0-Cre/GFP transgenic mouse in which the neural crest lineage is labeled by green fluorescence. Pathological abnormalities and functional changes in the gastrointestinal tract were evaluated 2–8 weeks after chemical injury. Laparotomy combined with fluorescence microscopy allowed direct visualization of the enteric neural network in vivo. Immunohistochemical evaluation further confirmed the irreversible disappearance of ganglion cells, glial cells, and interstitial cell of Cajal. Remaining stool weight and bead expulsion time in particular supported the pathophysiological relevance of this chemically-induced model of aganglionosis. Interestingly, we show that chemical ablation of enteric ganglion cells is associated with a long lifespan. By combining genetic labeling of neural crest derivatives and chemical ablation of enteric ganglion cells, we developed a newly customized model of aganglionosis. Our results indicate that this aganglionosis model exhibits decreased gastrointestinal motility and shows sufficient survival for functional evaluation. This model may prove useful for the development of future therapies against motility disorders. PMID:26943905

  13. A crowdsourcing workflow for extracting chemical-induced disease relations from free text

    PubMed Central

    Li, Tong Shu; Bravo, Àlex; Furlong, Laura I.; Good, Benjamin M.; Su, Andrew I.

    2016-01-01

    Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505 F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available at https://github.com/SuLab/crowd_cid_relex Database URL: https://github.com/SuLab/crowd_cid_relex PMID:27087308

  14. Boundary terms for causal sets

    NASA Astrophysics Data System (ADS)

    Buck, Michel; Dowker, Fay; Jubb, Ian; Surya, Sumati

    2015-10-01

    We propose a family of boundary terms for the action of a causal set with a spacelike boundary. We show that in the continuum limit one recovers the Gibbons-Hawking-York boundary term in the mean. We also calculate the continuum limit of the mean causal set action for an Alexandrov interval in flat spacetime. We find that it is equal to the volume of the codimension-2 intersection of the two light-cone boundaries of the interval.

  15. [Causal analysis approaches in epidemiology].

    PubMed

    Dumas, O; Siroux, V; Le Moual, N; Varraso, R

    2014-02-01

    Epidemiological research is mostly based on observational studies. Whether such studies can provide evidence of causation remains discussed. Several causal analysis methods have been developed in epidemiology. This paper aims at presenting an overview of these methods: graphical models, path analysis and its extensions, and models based on the counterfactual approach, with a special emphasis on marginal structural models. Graphical approaches have been developed to allow synthetic representations of supposed causal relationships in a given problem. They serve as qualitative support in the study of causal relationships. The sufficient-component cause model has been developed to deal with the issue of multicausality raised by the emergence of chronic multifactorial diseases. Directed acyclic graphs are mostly used as a visual tool to identify possible confounding sources in a study. Structural equations models, the main extension of path analysis, combine a system of equations and a path diagram, representing a set of possible causal relationships. They allow quantifying direct and indirect effects in a general model in which several relationships can be tested simultaneously. Dynamic path analysis further takes into account the role of time. The counterfactual approach defines causality by comparing the observed event and the counterfactual event (the event that would have been observed if, contrary to the fact, the subject had received a different exposure than the one he actually received). This theoretical approach has shown limits of traditional methods to address some causality questions. In particular, in longitudinal studies, when there is time-varying confounding, classical methods (regressions) may be biased. Marginal structural models have been developed to address this issue. In conclusion, "causal models", though they were developed partly independently, are based on equivalent logical foundations. A crucial step in the application of these models is the

  16. Characterization of necrosis and ethylene-inducing proteins (NEP) in the basidiomycete Moniliophthora perniciosa, the causal agent of witches' broom in Theobroma cacao.

    PubMed

    Garcia, Odalys; Macedo, Joci A N; Tibúrcio, Ricardo; Zaparoli, Gustavo; Rincones, Johana; Bittencourt, Livia M C; Ceita, Geruza O; Micheli, Fabienne; Gesteira, Abelmon; Mariano, Andréa C; Schiavinato, Marlene A; Medrano, Francisco J; Meinhardt, Lyndel W; Pereira, Gonçalo A G; Cascardo, Júlio C M

    2007-04-01

    The hemibiotrophic basidiomycete Moniliophthora perniciosa causes witches' broom disease of Theobroma cacao. Analysis of the M. perniciosa draft genome led to the identification of three putative genes encoding necrosis and ethylene-inducing proteins (MpNEPs), which are apparently located on the same chromosome. MpNEP1 and 2 have highly similar sequences and are able to induce necrosis and ethylene emission in tobacco and cacao leaves. MpNEP1 is expressed in both biotrophic and saprotrophic mycelia, the protein behaves as an oligomer in solution and is very sensitive to temperature. MpNEP2 is expressed mainly in biotrophic mycelia, is present as a monomer in solution at low concentrations (<40 microM) and is able to recover necrosis activity after boiling. These differences indicate that similar NEPs can have distinct physical characteristics and suggest possible complementary roles during the disease development for both proteins. This is the first report of NEP1-like proteins in a basidiomycete.

  17. Causal Inference in Public Health

    PubMed Central

    Glass, Thomas A.; Goodman, Steven N.; Hernán, Miguel A.; Samet, Jonathan M.

    2014-01-01

    Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action’s consequences rather than the less precise notion of a risk factor’s causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world. PMID:23297653

  18. An introduction to causal inference.

    PubMed

    Pearl, Judea

    2010-02-26

    This paper summarizes recent advances in causal inference and underscores the paradigmatic shifts that must be undertaken in moving from traditional statistical analysis to causal analysis of multivariate data. Special emphasis is placed on the assumptions that underlie all causal inferences, the languages used in formulating those assumptions, the conditional nature of all causal and counterfactual claims, and the methods that have been developed for the assessment of such claims. These advances are illustrated using a general theory of causation based on the Structural Causal Model (SCM) described in Pearl (2000a), which subsumes and unifies other approaches to causation, and provides a coherent mathematical foundation for the analysis of causes and counterfactuals. In particular, the paper surveys the development of mathematical tools for inferring (from a combination of data and assumptions) answers to three types of causal queries: those about (1) the effects of potential interventions, (2) probabilities of counterfactuals, and (3) direct and indirect effects (also known as "mediation"). Finally, the paper defines the formal and conceptual relationships between the structural and potential-outcome frameworks and presents tools for a symbiotic analysis that uses the strong features of both. The tools are demonstrated in the analyses of mediation, causes of effects, and probabilities of causation.

  19. A mechanistic model for understanding root-induced chemical changes controlling phosphorus availability

    PubMed Central

    Devau, Nicolas; Le Cadre, Edith; Hinsinger, Philippe; Gérard, Frédéric

    2010-01-01

    Background and Aims Plant nutrition models do not properly account for the effects of root-induced chemical changes in the rhizosphere, e.g. pH changes, on the availability of nutrients such as phosphorus (P). As a result, they underestimate the actual P uptake, i.e. P bioavailability to the plant, in low-P soils. The present study aims at simulating root-induced chemical mechanisms controlling P nutrition in a P-limited soil. Methods In this work a mechanistic description for the adsorption of cations and anions by soil constituents (1pK-Triple Plane Model, ion-exchange and Nica–Donnan) was used to simulate changes induced by durum wheat (Triticum durum turgidum) in the P availability of the soil, as measured by water and CaCl2 extraction. Calcium (Ca) availability was also measured and simulated. Key Results The simulations were found to be in close agreement with experimental data. In the rhizosphere, the goodness-of-fit required to account for the measured uptake of Ca by plants, in addition to the measured uptake of P and root-induced alkalization, were satisfactory. Calcium uptake significantly increased P availability, as assessed through water extraction, by decreasing the promoting effect of Ca adsorption on P adsorption. The study thus enabled P and Ca availability to be related to their bioavailability for durum wheat under experimental conditions. It was also shown that P was primarily adsorbed onto Fe oxides and clay minerals (kaolinite and illite) depending on soil pH. The major source of P for durum wheat nutrition was P desorbed from goethite and kaolinite. Conclusions In addition to confirming the validity of our approach to model P availability, the present investigation suggested that in the studied soil, a novel root-induced chemical process was controlling P nutrition under P-deficient conditions, namely the uptake of Ca. PMID:20495198

  20. Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?

    PubMed

    Linnebank, M; Malessa, S; Moskau, S; Semmler, A; Pels, H; Klockgether, T; Schlegel, U

    2007-08-01

    Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment.

  1. An efficient two-tier causal protocol for mobile distributed systems.

    PubMed

    Dominguez, Eduardo Lopez; Pomares Hernandez, Saul E; Gomez, Gustavo Rodriguez; Medina, Maria Auxilio

    2013-01-01

    Causal ordering is a useful tool for mobile distributed systems (MDS) to reduce the non-determinism induced by three main aspects: host mobility, asynchronous execution, and unpredictable communication delays. Several causal protocols for MDS exist. Most of them, in order to reduce the overhead and the computational cost over wireless channels and mobile hosts (MH), ensure causal ordering at and according to the causal view of the Base Stations. Nevertheless, these protocols introduce certain disadvantage, such as unnecessary inhibition at the delivery of messages. In this paper, we present an efficient causal protocol for groupware that satisfies the MDS's constraints, avoiding unnecessary inhibitions and ensuring the causal delivery based on the view of the MHs. One interesting aspect of our protocol is that it dynamically adapts the causal information attached to each message based on the number of messages with immediate dependency relation, and this is not directly proportional to the number of MHs.

  2. Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation

    PubMed Central

    2010-01-01

    Background Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically) of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state. Results First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT) under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH). Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution). To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa)). The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size. Conclusion Water sorption leads to aggregation, inactivation

  3. Comparison Analysis: Granger Causality and New Causality and Their Applications to Motor Imagery.

    PubMed

    Hu, Sanqing; Wang, Hui; Zhang, Jianhai; Kong, Wanzeng; Cao, Yu; Kozma, Robert

    2016-07-01

    In this paper we first point out a fatal drawback that the widely used Granger causality (GC) needs to estimate the autoregressive model, which is equivalent to taking a series of backward recursive operations which are infeasible in many irreversible chemical reaction models. Thus, new causality (NC) proposed by Hu et al. (2011) is theoretically shown to be more sensitive to reveal true causality than GC. We then apply GC and NC to motor imagery (MI) which is an important mental process in cognitive neuroscience and psychology and has received growing attention for a long time. We study causality flow during MI using scalp electroencephalograms from nine subjects in Brain-computer interface competition IV held in 2008. We are interested in three regions: Cz (central area of the cerebral cortex), C3 (left area of the cerebral cortex), and C4 (right area of the cerebral cortex) which are considered to be optimal locations for recognizing MI states in the literature. Our results show that: 1) there is strong directional connectivity from Cz to C3/C4 during left- and right-hand MIs based on GC and NC; 2) during left-hand MI, there is directional connectivity from C4 to C3 based on GC and NC; 3) during right-hand MI, there is strong directional connectivity from C3 to C4 which is much clearly revealed by NC than by GC, i.e., NC largely improves the classification rate; and 4) NC is demonstrated to be much more sensitive to reveal causal influence between different brain regions than GC.

  4. Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant.

    PubMed

    Tjiurutue, Muvari Connie; Sandler, Hilary A; Kersch-Becker, Monica F; Theis, Nina; Adler, Lynn A

    2016-02-01

    Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics.

  5. Phytophthora megakarya and P. palmivora, Causal Agents of Black Pod Rot, Induce Similar Plant Defense Responses Late during Infection of Susceptible Cacao Pods

    PubMed Central

    Ali, Shahin S.; Shao, Jonathan; Lary, David J.; Strem, Mary D.; Meinhardt, Lyndel W.; Bailey, Bryan A.

    2017-01-01

    Phytophthora megakarya (Pmeg) and Phytophthora palmivora (Ppal) cause black pod rot of Theobroma cacao L. (cacao). Of these two clade 4 species, Pmeg is more virulent and is displacing Ppal in many cacao production areas in Africa. Symptoms and species specific sporangia production were compared when the two species were co-inoculated onto pod pieces in staggered 24 h time intervals. Pmeg sporangia were predominantly recovered from pod pieces with unwounded surfaces even when inoculated 24 h after Ppal. On wounded surfaces, sporangia of Ppal were predominantly recovered if the two species were simultaneously applied or Ppal was applied first but not if Pmeg was applied first. Pmeg demonstrated an advantage over Ppal when infecting un-wounded surfaces while Ppal had the advantage when infecting wounded surfaces. RNA-Seq was carried out on RNA isolated from control and Pmeg and Ppal infected pod pieces 3 days post inoculation to assess their abilities to alter/suppress cacao defense. Expression of 4,482 and 5,264 cacao genes was altered after Pmeg and Ppal infection, respectively, with most genes responding to both species. Neural network self-organizing map analyses separated the cacao RNA-Seq gene expression profiles into 24 classes, 6 of which were largely induced in response to infection. Using KEGG analysis, subsets of genes composing interrelated pathways leading to phenylpropanoid biosynthesis, ethylene and jasmonic acid biosynthesis and action, plant defense signal transduction, and endocytosis showed induction in response to infection. A large subset of genes encoding putative Pr-proteins also showed differential expression in response to infection. A subset of 36 cacao genes was used to validate the RNA-Seq expression data and compare infection induced gene expression patterns in leaves and wounded and unwounded pod husks. Expression patterns between RNA-Seq and RT-qPCR were generally reproducible. The level and timing of altered gene expression was

  6. Phytophthora megakarya and P. palmivora, Causal Agents of Black Pod Rot, Induce Similar Plant Defense Responses Late during Infection of Susceptible Cacao Pods.

    PubMed

    Ali, Shahin S; Shao, Jonathan; Lary, David J; Strem, Mary D; Meinhardt, Lyndel W; Bailey, Bryan A

    2017-01-01

    Phytophthora megakarya (Pmeg) and Phytophthora palmivora (Ppal) cause black pod rot of Theobroma cacao L. (cacao). Of these two clade 4 species, Pmeg is more virulent and is displacing Ppal in many cacao production areas in Africa. Symptoms and species specific sporangia production were compared when the two species were co-inoculated onto pod pieces in staggered 24 h time intervals. Pmeg sporangia were predominantly recovered from pod pieces with unwounded surfaces even when inoculated 24 h after Ppal. On wounded surfaces, sporangia of Ppal were predominantly recovered if the two species were simultaneously applied or Ppal was applied first but not if Pmeg was applied first. Pmeg demonstrated an advantage over Ppal when infecting un-wounded surfaces while Ppal had the advantage when infecting wounded surfaces. RNA-Seq was carried out on RNA isolated from control and Pmeg and Ppal infected pod pieces 3 days post inoculation to assess their abilities to alter/suppress cacao defense. Expression of 4,482 and 5,264 cacao genes was altered after Pmeg and Ppal infection, respectively, with most genes responding to both species. Neural network self-organizing map analyses separated the cacao RNA-Seq gene expression profiles into 24 classes, 6 of which were largely induced in response to infection. Using KEGG analysis, subsets of genes composing interrelated pathways leading to phenylpropanoid biosynthesis, ethylene and jasmonic acid biosynthesis and action, plant defense signal transduction, and endocytosis showed induction in response to infection. A large subset of genes encoding putative Pr-proteins also showed differential expression in response to infection. A subset of 36 cacao genes was used to validate the RNA-Seq expression data and compare infection induced gene expression patterns in leaves and wounded and unwounded pod husks. Expression patterns between RNA-Seq and RT-qPCR were generally reproducible. The level and timing of altered gene expression was

  7. Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin.

    PubMed

    Zhang, Shuihua; Ji, Guang; Liu, Jianwen

    2006-07-01

    Puerarin is a major isoflavonoid compound isolated from Pueraria lobata, an edible vine used widely for various medicinal purposes. It has been used for centuries in China to counteract alcohol intoxication. However, the effects of puerarin on chemical-induced liver fibrosis have not been reported. In the present study, we investigated the effects of puerarin on liver fibrosis in Wistar rats induced by alcohol plus carbon tetrachloride administration. Liver fibrosis was produced in rats by treatment with a mixture (50% alcohol, 8 g/kg per day; corn oil, 2 g/kg per day; pyrazole, 24 mg/kg per day; ig) once a day and by intraperitoneal injection of 0.25 ml/kg of a 25% solution of carbon tetrachloride in olive oil twice a week for 8 weeks. After 8 weeks, treatment with puerarin (0.4 and 0.8 g/kg ig, daily for 4 weeks) was conducted to examine its therapeutic effects. At the same time, the model group and treatment group continued to receive the chemical mixture, while the control group received saline instead of the chemical mixture. Upon pathological examination, the puerarin-treated rats significantly reversed the symptoms of liver fibrosis and other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with puerarin treatment, whereas no significant effect was discovered in the levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A significant increase in apoptosis of activated hepatic stellate cell (HSC) was found by flow cytometric analysis of the hepatic tissues. And the expression of bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all these results showed that puerarin could effectively reverse chemical-induced liver fibrosis in experimental rats, via the recovery of hepatic injury as well as the induction of apoptosis in activated HSC.

  8. NEP1 orthologs encoding necrosis and ethylene inducing proteins exist as a multigene family in Phytophthora megakarya, causal agent of black pod disease on cacao.

    PubMed

    Bae, Hanhong; Bowers, John H; Tooley, Paul W; Bailey, Bryan A

    2005-12-01

    Phvytophthora megakarya is a devastating oomycete pathogen that causes black pod disease in cacao. Phytophthora species produce a protein that has a similar sequence to the necrosis and ethylene inducing protein (Nep1) of Fusarium oxysporum. Multiple copies of NEP1 orthologs (PmegNEP) have been identified in P. megakarya and four other Phytophthora species (P. citrophthora, P. capsici, P. palmivora, and P. sojae). Genome database searches confirmed the existence of multiple copies of NEP1 orthologs in P. sojae and P. ramorum. In this study, nine different PmegNEP orthologs from P. megakarya strain Mk-1 were identified and analyzed. Of these nine orthologs, six were expressed in mycelium and in P. megakarya zoospore-infected cacao leaf tissue. The remaining two clones are either regulated differently, or are nonfunctional genes. Sequence analysis revealed that six PmegNEP orthologs were organized in two clusters of three orthologs each in the P. megakarya genome. Evidence is presented for the instability in the P. megakarya genome resulting from duplications, inversions, and fused genes resulting in multiple NEP1 orthologs. Traits characteristic of the Phytophthora genome, such as the clustering of NEP1 orthologs, the lack of CATT and TATA boxes, the lack of introns, and the short distance between ORFs were also observed.

  9. Modeling Smith-Lemli-Opitz syndrome with induced pluripotent stem cells reveals a causal role for Wnt/β-catenin defects in neuronal cholesterol synthesis phenotypes.

    PubMed

    Francis, Kevin R; Ton, Amy N; Xin, Yao; O'Halloran, Peter E; Wassif, Christopher A; Malik, Nasir; Williams, Ian M; Cluzeau, Celine V; Trivedi, Niraj S; Pavan, William J; Cho, Wonhwa; Westphal, Heiner; Porter, Forbes D

    2016-04-01

    Smith-Lemli-Opitz syndrome (SLOS) is a malformation disorder caused by mutations in DHCR7, which impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. SLOS results in cognitive impairment, behavioral abnormalities and nervous system defects, though neither affected cell types nor impaired signaling pathways are fully understood. Whether 7DHC accumulation or cholesterol loss is primarily responsible for disease pathogenesis is also unclear. Using induced pluripotent stem cells (iPSCs) from subjects with SLOS, we identified cellular defects that lead to precocious neuronal specification within SLOS derived neural progenitors. We also demonstrated that 7DHC accumulation, not cholesterol deficiency, is critical for SLOS-associated defects. We further identified downregulation of Wnt/β-catenin signaling as a key initiator of aberrant SLOS iPSC differentiation through the direct inhibitory effects of 7DHC on the formation of an active Wnt receptor complex. Activation of canonical Wnt signaling prevented the neural phenotypes observed in SLOS iPSCs, suggesting that Wnt signaling may be a promising therapeutic target for SLOS.

  10. Different Kinds of Causality in Event Cognition

    ERIC Educational Resources Information Center

    Radvansky, Gabriel A.; Tamplin, Andrea K.; Armendarez, Joseph; Thompson, Alexis N.

    2014-01-01

    Narrative memory is better for information that is more causally connected and occurs at event boundaries, such as a causal break. However, it is unclear whether there are common or distinct influences of causality. For the event boundaries that arise as a result of causal breaks, the events that follow may subsequently become more causally…

  11. The crystal structure of necrosis- and ethylene-inducing protein 2 from the causal agent of cacao's Witches' Broom disease reveals key elements for its activity.

    PubMed

    Zaparoli, Gustavo; Barsottini, Mario Ramos de Oliveira; de Oliveira, Juliana Ferreira; Dyszy, Fabio; Teixeira, Paulo José Pereira Lima; Barau, Joan Grande; Garcia, Odalys; Costa-Filho, Antonio José; Ambrosio, Andre Luis Berteli; Pereira, Gonçalo Amarante Guimarães; Dias, Sandra Martha Gomes

    2011-11-15

    The necrosis- and ethylene-inducing peptide 1 (NEP1)-like proteins (NLPs) are proteins secreted from bacteria, fungi and oomycetes, triggering immune responses and cell death in dicotyledonous plants. Genomic-scale studies of Moniliophthora perniciosa, the fungus that causes the Witches' Broom disease in cacao, which is a serious economic concern for South and Central American crops, have identified five members of this family (termed MpNEP1-5). Here, we show by RNA-seq that MpNEP2 is virtually the only NLP expressed during the fungus infection. The quantitative real-time polymerase chain reaction results revealed that MpNEP2 has an expression pattern that positively correlates with the necrotic symptoms, with MpNEP2 reaching its highest level of expression at the advanced necrotic stage. To improve our understanding of MpNEP2's molecular mechanism of action, we determined the crystallographic structure of MpNEP2 at 1.8 Å resolution, unveiling some key structural features. The implications of a cation coordination found in the crystal structure were explored, and we show that MpNEP2, in contrast to another previously described member of the NLP family, NLP(Pya) from Pythium aphanidermatum, does not depend on an ion to accomplish its necrosis- and electrolyte leakage-promoting activities. Results of site-directed mutagenesis experiments confirmed the importance of a negatively charged cavity and an unforeseen hydrophobic β-hairpin loop for MpNEP2 activity, thus offering a platform for compound design with implications for disease control. Electron paramagnetic resonance and fluorescence assays with MpNEP2 performed in the presence of lipid vesicles of different compositions showed no sign of interaction between the protein and the lipids, implying that MpNEP2 likely requires other anchoring elements from the membrane to promote cytolysis or send death signals.

  12. Chemical Etch Effects on Laser-Induced Surface Damage Growth in Fused Silica

    SciTech Connect

    Hrubesh, L W; Norton, M A; Molander, W A; Wegner, P J; Staggs, M; Demos, S G; Britten, J A; Summers, L J; Lindsey, E F; Kozlowski, M R

    2000-12-22

    We investigated chemical etching as a possible means to mitigate the growth of UV laser-induced surface damage on fused silica. The intent of this work is to examine the growth behavior of existing damage sites that have been processed to remove the UV absorbing, thermo-chemically modified material within the affected area. The study involved chemical etching of laser-induced surface damage sites on fused silica substrates, characterizing the etched sites using scanning electron microscopy (SEM) and laser fluorescence, and testing the growth behavior of the etched sites upon illumination with multiple pulses of 351nm laser light. The results show that damage sites that have been etched to depths greater than about 9 {micro}m have about a 40% chance for zero growth with 1000 shots at fluences of 6.8-9.4 J/cm{sup 2}. For the etched sites that grow, the growth rates are consistent with those for non-etched sites. There is a weak dependence of the total fluorescence emission with the etch depth of a site, but the total fluorescence intensity from an etched site is not well correlated with the propensity of the site to grow. Deep wet etching shows some promise for mitigating damage growth in fused silica, but fluorescence does not seem to be a good indicator of successful mitigation.

  13. On the Causality and K-Causality between Measures

    NASA Astrophysics Data System (ADS)

    Miller, Tomasz

    2017-03-01

    Drawing from our earlier works on the notion of causality for nonlocal phenomena, we propose and study the extension of the Sorkin--Woolgar relation $K^+$ onto the space of Borel probability measures on a given spacetime. We show that it retains its fundamental properties of transitivity and closedness. Furthermore, we list and prove several characterizations of this relation, including the `nonlocal' analogue of the characterization of $K^+$ in terms of time functions. This generalizes and casts new light on our earlier results concerning the causal precedence relation $J^+$ between measures.

  14. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe.

    PubMed

    Teschke, Rolf; Glass, Xaver; Schulze, Johannes; Eickhoff, Axel

    2012-03-01

    In 21 published case reports, the use of the herb Greater Celandine (GC) (Chelidonium majus L.) has been causally related to liver injury, but a variety of confounding variables were evident that might have offset causality. This study reanalyses causality levels in these cases with a liver-specific causality evaluation method. All 21 cases were submitted to the liver-specific, standardized, structured, quantitative and updated scale of the Council for International Organizations of Medical Sciences. This scale considers, among other items, latency period, course of alanine aminotransferase after treatment discontinuation, risk factors, comedication and alternative causes. Using this method for assessment, causality for GC was highly probable in two and probable in six cases, with lower causality grading in the remaining 13 cases. In these patients, causality for GC was possible in 10 cases and excluded in three cases. On the basis of the eight cases with highly probable and probable causality gradings, GC hepatotoxicity represents an idiosyncratic reaction of the metabolic type, whereas immunologic or obligatory hepatotoxic features are lacking. In some cases, alternative diagnoses and poor data quality were confounding variables that reduced causality levels. Confounding variables reduced causality levels for GC in reported cases of liver injury, but there is still striking evidence for herb-induced liver injury by GC with high causality gradings. GC hepatotoxicity is caused by an idiosyncratic reaction of the metabolic form, but there is uncertainty with respect to its culprit(s).

  15. Bayesian networks improve causal environmental ...

    EPA Pesticide Factsheets

    Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on value

  16. Histopathological image analysis of chemical-induced hepatocellular hypertrophy in mice.

    PubMed

    Asaoka, Yoshiji; Togashi, Yuko; Mutsuga, Mayu; Imura, Naoko; Miyoshi, Tomoya; Miyamoto, Yohei

    2016-04-01

    Chemical-induced hepatocellular hypertrophy is frequently observed in rodents, and is mostly caused by the induction of phase I and phase II drug metabolic enzymes and peroxisomal lipid metabolic enzymes. Liver weight is a sensitive and commonly used marker for detecting hepatocellular hypertrophy, but is also increased by a number of other factors. Histopathological observations subjectively detect changes such as hepatocellular hypertrophy based on the size of a hepatocyte. Therefore, quantitative microscopic observations are required to evaluate histopathological alterations objectively. In the present study, we developed a novel quantitative method for an image analysis of hepatocellular hypertrophy using liver sections stained with hematoxylin and eosin, and demonstrated its usefulness for evaluating hepatocellular hypertrophy induced by phenobarbital (a phase I and phase II enzyme inducer) and clofibrate (a peroxisomal enzyme inducer) in mice. The algorithm of this imaging analysis was designed to recognize an individual hepatocyte through a combination of pixel-based and object-based analyses. Hepatocellular nuclei and the surrounding non-hepatocellular cells were recognized by the pixel-based analysis, while the areas of the recognized hepatocellular nuclei were then expanded until they ran against their expanding neighboring hepatocytes and surrounding non-hepatocellular cells by the object-based analysis. The expanded area of each hepatocellular nucleus was regarded as the size of an individual hepatocyte. The results of this imaging analysis showed that changes in the sizes of hepatocytes corresponded with histopathological observations in phenobarbital and clofibrate-treated mice, and revealed a correlation between hepatocyte size and liver weight. In conclusion, our novel image analysis method is very useful for quantitative evaluations of chemical-induced hepatocellular hypertrophy. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. Inducers of chemical hypoxia act in a gender- and brain region-specific manner on primary astrocyte viability and cytochrome C oxidase.

    PubMed

    Roemgens, André; Singh, Shilpee; Beyer, Cordian; Arnold, Susanne

    2011-07-01

    Oxygen is the ultimate electron acceptor for mitochondrial respiration, a process catalyzed by cytochrome c oxidase (COX). In mammals, oxygen concentration regulates gene transcription of COX subunit IV isoforms. Here, we demonstrate that chemical hypoxia, i.e. inhibition of mitochondrial respiration by application of the COX inhibitors cobalt, cyanide, and azide, affects COX isoform IV-1 and IV-2 transcription in a gender- and brain region-specific way. After treatment with cyanide and cobalt, female cortical and mesencephalic astrocytes, respectively, revealed an up-regulation of COX IV-2 which was accompanied by increased ROS production and necrotic cell death. In male astrocytes, the ratio of COX IV-1/COX IV-2 was lowest after treatment with cobalt and paralleled by highest levels of ROS production and necrosis. These results support the view of a causal correlation of COX IV-2 transcription with cellular oxidative stress and cell death and highlight a gender specificity of these effects. By comparing three toxins, cobalt represented the most potent inducer of overall cell death and resembled most closely the previously observed effects of oxygen deprivation on decreasing the cox4i1/cox4i2 ratio. Overall, an increased sensitivity of male compared with female cell viability towards the toxins was detected. These regulatory responses might be causative for the known gender specificity of toxic and neurodegenerative processes in the brain.

  18. Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries.

    PubMed

    Hase, K; Kadota, S; Basnet, P; Takahashi, T; Namba, T

    1996-04-01

    Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the water extract of the seed of Celosia argentea, was investigated using chemical and immunological liver injury models. Celosian inhibited the elevation of serum enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))-induced liver injuries in rat. In addition, the hepatoprotective effect of celosian was also observed in this model of liver injury by histopathological findings. Moreover, celosian suppressed rises in GPT or mortality on fulminant hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or Propionibacterium acnes/LPS in mice. These findings suggested that celosian is an active component in protection against chemical and immunological hepatitis and the activity was found to be a dose dependent. Celosian showed a concentration dependent inhibitory effect on lipid peroxide (LPO) generation in vitro. Though celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha), it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver injury in D-galactosamine sensitized mice.

  19. Suppressive function of RKTG on chemical carcinogen-induced skin carcinogenesis in mouse.

    PubMed

    Xie, Xiaoduo; Zhang, Yixuan; Jiang, Yuhui; Liu, Weizhong; Ma, Hong; Wang, Zhenzhen; Chen, Yan

    2008-08-01

    Raf kinase trapping to Golgi (RKTG) is a newly characterized negative regulator of the Ras-Raf-MEK-ERK signaling pathway via sequestrating Raf-1 to the Golgi apparatus. However, little is known about the physiological functions of RKTG in mitogenic pathway and carcinogenesis. Here, we describe a suppressive role of RKTG in skin carcinogenesis by analyzing chemical carcinogen-induced tumorigenesis. Epidermis hyperplasia and proliferation are increased in RKTG-deficient mice (RKTG(-/-)) after acute treatment with 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Using a two-stage DMBA/TPA carcinogenesis protocol on mouse skin, the number and size of papillomas are increased in RKTG(-/-) mice, accompanied by shortened tumor latency and enhanced keratinocyte proliferation. The regression of the carcinogen-induced tumors is also prolonged in RKTG(-/-) mice. Consistently, the levels of Raf-1 and extracellular signal-regulated kinase phosphorylation in primary keratinocytes as well as skin tumors are elevated when RKTG is disrupted. Collectively, our results indicate that RKTG has a suppressive activity in chemical carcinogen-induced mitogenesis and tumor formation in mouse skin.

  20. Chemical cues induce consumer-specific defenses in a bloom-forming marine phytoplankton

    PubMed Central

    Long, Jeremy D.; Smalley, Gabriela W.; Barsby, Todd; Anderson, Jon T.; Hay, Mark E.

    2007-01-01

    Blooms of the phytoplankton Phaeocystis can comprise 85% of total production and generate major biogeochemical signals across broad oceanic regions. The success of Phaeocystis may result from its ability to change size by many orders of magnitude when it shifts from small cells of 4–6 μm to large colonies of up to 30,000 μm in diameter. Single cells are consumed by ciliates but not copepods, whereas colonies are consumed by copepods but not ciliates. We demonstrate that chemical cues associated with each of these grazers induce consumer-specific, but opposing, morphological transformations in the bloom-forming species Phaeocystis globosa. Chemical cues from grazing copepods suppress colony formation by a significant 60–90%, a response that should be adaptive because copepods feed four times more on colonies versus solitary cells. In contrast, chemical cues from grazing ciliates enhance colony formation by >25%, a response that should be adaptive because ciliates grow three times faster when fed solitary cells versus colonies. Because size-selective predation fundamentally alters community structure and ecosystem function, this chemically cued shift may redirect energy and nutrients from food webs supporting fisheries to those fueling detrital pathways, thus potentially altering ecosystem-level processes such as productivity, carbon storage, and nutrient release. PMID:17563379

  1. Effects of the extracts of Pycanthus angolensis against chemically induced acute hepatotoxicity.

    PubMed

    Achudume, A C; Ogunyemi, K E

    2007-09-15

    The efficacy of the extract of Pycnanthus Angolensis (PA) against Carbon Tetra-chloride (CCl4) induced hepatotoxicity was studied in rat. The study highlights information on the protective effect of PA extract as ethnomedical treatment of induced hepatotoxic injury. The dried powder of PA extract was administered orally at a dose of 300 mg/3 mL solution while liver injury was induced by carbon tetrachloride administered intraperitoneally at a dose of 0.67 mg kg(-1). Estimating the protein concentrations, saponins, alkaloid, glutathione and cholesterol levels monitored the hepato-protective activity. The result shows evidence of non-toxic response of PA extract against chemically induced hepatic damage. The antioxidant activities in the extract indicated its ability to protect against CCl4 induced hepatic injury in rat. The saponins and bile acids may have interacted with cholesterol in the liver to form unabsorbed complexes, which are excreted via faeces resulting in decrease level of cholesterol in the experimental animals.

  2. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells

    PubMed Central

    Biswas, Dhruba; Jiang, Peng

    2016-01-01

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming. PMID:26861316

  3. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

    PubMed

    Biswas, Dhruba; Jiang, Peng

    2016-02-06

    The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

  4. Laser Induced Breakdown Spectroscopy applications to meteorites: Chemical analysis and composition profiles

    NASA Astrophysics Data System (ADS)

    Dell'Aglio, M.; De Giacomo, A.; Gaudiuso, R.; Pascale, O. De; Senesi, G. S.; Longo, S.

    2010-12-01

    A fast procedure for chemical analysis of different meteorites is presented, based on LIBS (Laser Induced Breakdown Spectroscopy). The technique is applied to several test cases (Dhofar 019, Dhofar 461, Sahara 98222, Toluca, Sikhote Alin and Campo del Cielo) and can be useful for rapid meteorite identification providing geologists with specific chemical information for meteorite classification. Concentration profiles of Fe, Ni and Co are simultaneously detected across the Widmanstätten structure of the iron meteorite Toluca with a view to determining cooling rates. The LIBS analysis of meteorites is also used as a laboratory test for analogous studies on the respective parent bodies (Mars, asteroids) in space exploration missions where one clear advantage of the proposed technique is that no direct contact with the sample is required.

  5. Time evolution studies of laser induced chemical changes in InAs nanowire using Raman spectroscopy

    SciTech Connect

    Pal, Suparna; Aggarwal, R.; Kumari Gupta, Vandna; Ingale, Alka

    2014-07-07

    We report the study of time evolution of chemical changes on the surface of an InAs nanowire (NW) on laser irradiation in different power density regime, using Raman spectroscopy for a time span of 8–16 min. Mixture of metastable oxides like InAsO{sub 4,} As{sub 2}O{sub 3} are formed upon oxidation, which are reflected as sharp Raman peaks at ∼240–254 and 180–200 cm{sup −1}. Evidence of removal of arsenic layer by layer is also observed at higher power density. Position controlled laser induced chemical modification on a nanometer scale, without changing the core of the NW, can be useful for NW based device fabrication.

  6. Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces.

    PubMed

    Maeda, Satoshi; Harabuchi, Yu; Takagi, Makito; Taketsugu, Tetsuya; Morokuma, Keiji

    2016-10-01

    In this account, a technical overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chemical reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimolecular and multicomponent reactions and the latter to unimolecular isomerization and dissociation reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene molecule. Finally, possible applications of the AFIR method are discussed. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Causal reasoning with mental models.

    PubMed

    Khemlani, Sangeet S; Barbey, Aron K; Johnson-Laird, Philip N

    2014-01-01

    This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex.

  8. Causal reasoning with mental models

    PubMed Central

    Khemlani, Sangeet S.; Barbey, Aron K.; Johnson-Laird, Philip N.

    2014-01-01

    This paper outlines the model-based theory of causal reasoning. It postulates that the core meanings of causal assertions are deterministic and refer to temporally-ordered sets of possibilities: A causes B to occur means that given A, B occurs, whereas A enables B to occur means that given A, it is possible for B to occur. The paper shows how mental models represent such assertions, and how these models underlie deductive, inductive, and abductive reasoning yielding explanations. It reviews evidence both to corroborate the theory and to account for phenomena sometimes taken to be incompatible with it. Finally, it reviews neuroscience evidence indicating that mental models for causal inference are implemented within lateral prefrontal cortex. PMID:25389398

  9. Wormholes, baby universes, and causality

    SciTech Connect

    Visser, M. )

    1990-02-15

    In this paper wormholes defined on a Minkowski signature manifold are considered, both at the classical and quantum levels. It is argued that causality in quantum gravity may best be imposed by restricting the functional integral to include only causal Lorentzian spacetimes. Subject to this assumption, one can put very tight constraints on the quantum behavior of wormholes, their cousins the baby universes, and topology-changing processes in general. Even though topology-changing processes are tightly constrained, this still allows very interesting geometrical (rather than topological) effects. In particular, the laboratory construction of baby universes is {ital not} prohibited provided that the umbilical cord'' is never cut. Methods for relaxing these causality constraints are also discussed.

  10. Wormholes, baby universes, and causality

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    1990-02-01

    In this paper wormholes defined on a Minkowski signature manifold are considered, both at the classical and quantum levels. It is argued that causality in quantum gravity may best be imposed by restricting the functional integral to include only causal Lorentzian spacetimes. Subject to this assumption, one can put very tight constraints on the quantum behavior of wormholes, their cousins the baby universes, and topology-changing processes in general. Even though topology-changing processes are tightly constrained, this still allows very interesting geometrical (rather than topological) effects. In particular, the laboratory construction of baby universes is not prohibited provided that the ``umbilical cord'' is never cut. Methods for relaxing these causality constraints are also discussed.

  11. Causal analysis of academic performance.

    PubMed

    Rao, D C; Morton, N E; Elston, R C; Yee, S

    1977-03-01

    Maximum likelihood methods are presented to test for the relations between causes and effects in linear path diagrams, without assuming that estimates of causes are free of error. Causal analysis is illustrated by published data of the Equal Educational Opportunity Survey, which show that American schools do not significantly modify socioeconomic differences in academic performance and that little of the observed racial difference in academic performance is causal. For two races differing by 15 IQ points, the differential if social class were randomized would be only about 3 points. The principle is stressed that a racial effect in a causal system may be environmental and that its etiology can be studied only by analysis of family resemblance in hybrid populations.

  12. Matched designs and causal diagrams

    PubMed Central

    Mansournia, Mohammad A; Hernán, Miguel A; Greenland, Sander

    2013-01-01

    We use causal diagrams to illustrate the consequences of matching and the appropriate handling of matched variables in cohort and case-control studies. The matching process generally forces certain variables to be independent despite their being connected in the causal diagram, a phenomenon known as unfaithfulness. We show how causal diagrams can be used to visualize many previous results about matched studies. Cohort matching can prevent confounding by the matched variables, but censoring or other missing data and further adjustment may necessitate control of matching variables. Case-control matching generally does not prevent confounding by the matched variables, and control of matching variables may be necessary even if those were not confounders initially. Matching on variables that are affected by the exposure and the outcome, or intermediates between the exposure and the outcome, will ordinarily produce irremediable bias. PMID:23918854

  13. Systems Toxicology of Chemically Induced Liver and Kidney Injuries: Histopathology-Associated Gene Co-Expression Modules

    DTIC Science & Technology

    2016-01-04

    exposures and adverse histopathology assessments in Sprague–Dawley rats . We proposed a protocol for selecting gene modules associated with chemical-induced...for damage assessment, early inter- vention and treatment, and prediction of potential for recovery ( Parkes et al., 2012). Efforts in elucidating...organ-specific data on chemically induced gene expression changes coupled to graded histopathology assessments in male Sprague–Dawley rats (Igarashi

  14. A crowdsourcing workflow for extracting chemical-induced disease relations from free text.

    PubMed

    Li, Tong Shu; Bravo, Àlex; Furlong, Laura I; Good, Benjamin M; Su, Andrew I

    2016-01-01

    Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available athttps://github.com/SuLab/crowd_cid_relexDatabase URL:https://github.com/SuLab/crowd_cid_relex. © The Author(s) 2016. Published by Oxford University Press.

  15. Mesoherbivores reduce net growth and induce chemical resistance in natural seaweed populations.

    PubMed

    Toth, Gunilla B; Karlsson, Malin; Pavia, Henrik

    2007-05-01

    Herbivory on marine macroalgae (seaweeds) in temperate areas is often dominated by relatively small gastropods and crustaceans (mesoherbivores). The effects of these herbivores on the performance of adult seaweeds have so far been almost exclusively investigated under artificial laboratory conditions. Furthermore, several recent laboratory studies with mesoherbivores indicate that inducible chemical resistance may be as common in seaweeds as in vascular plants. However, in order to further explore and test the possible ecological significance of induced chemical resistance in temperate seaweeds, data are needed that address this issue in natural populations. We investigated the effect of grazing by littorinid herbivorous snails (Littorina spp.) on the individual net growth of the brown seaweed Ascophyllum nodosum in natural field populations. Furthermore, the capacity for induced resistance in the seaweeds was assessed by removing herbivores and assaying for relaxation of defences. We found that ambient densities of gastropod herbivores significantly reduced net growth by 45% in natural field populations of A. nodosum. Seaweeds previously exposed to grazing in the field were less consumed by gastropod herbivores in feeding bioassays. Furthermore, the concentration of phlorotannins (polyphenolics), which have been shown to deter gastropod herbivores, was higher in the seaweeds that were exposed to gastropod herbivores in the field. This field study corroborates earlier laboratory experiments and demonstrates that it is important to make sure that the lack of experimental field data on marine mesoherbivory does not lead to rash conclusions about the lack of significant effects of these herbivores on seaweed performance. The results strongly suggest that gastropods exert a significant selection pressure on the evolution of defensive traits in the seaweeds, and that brown seaweeds can respond to attacks by natural densities of these herbivores through increased

  16. Evaluation of a chemically inducible promoter for developing a within-plant refuge for resistance management.

    PubMed

    Bates, Sarah L; Cao, Jun; Zhao, Jian-Zhou; Earle, Elizabeth D; Roush, Richard T; Shelton, Anthony M

    2005-12-01

    Chemically inducible production of Bacillus thuringiensis (Bt) toxins in transgenic plants may provide considerable benefits in preventing or delaying the evolution of insect resistance to Bt crops by creating within-plant temporal refuges. We examined the effect of inducible cry1Ab expression on survival of different genotypes (RR, RS, and SS) of diamondback moth, Plutella xylostella (L.), in transgenic broccoli, Brassica oleracea L., plants transformed with a PR-1a/cry1Ab expression cassette. Spraying leaves of these plants with the inducer acibenzolar-s-methyl [= benzo (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester] (ASM) resulted in high levels of Bt toxin, and detached leaves from fully induced plants caused 100% mortality to all instars of P. xylostella SS and RS genotypes. When plants infested with larvae were treated with ASM, only a few larvae that were nearing completion of their development were able to survive the induction process. Signal transduction from ASM-treated leaves to new plant tissue also was evaluated using a larval assay. New foliage that emerged after plants were induced remained toxic to > or = 80% of RS larvae up to the fourth new leaf. In whole plant tests, however, induced plants remained protected from larval damage for > or = 3 wk. Uninduced PR-1a/cry1Ab plants seemed to produce low levels of Bt that were undetected by an enzyme-linked immunosorbent assay but that resulted in significant fitness costs for susceptible insects. The suitability of PR-1a/cry1Ab broccoli plants for insect resistance management and the requirements of an appropriate inducible promoter are discussed.

  17. Amniotic membrane traps and induces apoptosis of inflammatory cells in ocular surface chemical burn

    PubMed Central

    Liu, Ting; Zhai, Hualei; Xu, Yuanyuan; Dong, Yanling; Sun, Yajie; Zang, Xinjie

    2012-01-01

    Purpose Severe chemical burns can cause necrosis of ocular surface tissues following the infiltration of inflammatory cells. It has been shown that amniotic membrane transplantation (AMT) is an effective treatment for severe chemical burns, but the phenotypes of cells that infiltrate the amniotic membrane and the clinical significance of these cellular infiltrations have not previously been reported. The present work studies the inflammation cell traps and apoptosis inducing roles of the amniotic membrane after AMT in patients with acute chemical burns. Methods A total of 30 patients with acute alkaline burns were classified as having either moderate or severe burns. In all participants, AMT was performed within one week of his/her injury. After 7–9 days, the transplanted amniotic membranes were removed. Histopathological and immunohistochemical techniques were used for the examination and detection of infiltrating cells, and tests for the expression of CD (cluster of differentiation)15, CD68, CD3, CD20, CD57, CD31, CD147, and CD95 (Fas) were performed. A TUNEL (TdT-mediated dUTP nick end labeling) assay was used to confirm apoptosis of the infiltrating cells. Three patients with herpes simplex-induced keratitis who had undergone AMT to treat persistent epithelium defects were used as a control group. Amniotic membrane before transplantation was used as another control. Results After amniotic membrane transplantation, the number of infiltrating cells in patients with severe burns was significantly higher than in patients with moderate burns or in control patients (p<0.05). Among the severe burns patients, CD15 and CD68 were widely expressed in the infiltrating cells, and CD3, CD20, and CD57 were only found in a small number of cells. Occasionally, CD31-positive cells were found in the amniotic membranes. More cells that were CD147, Fas, and TUNEL positive were found in patients with severe burns than in patients with moderate burns or in control patients

  18. Reasoning about Causal Relationships: Inferences on Causal Networks

    PubMed Central

    Rottman, Benjamin Margolin; Hastie, Reid

    2013-01-01

    Over the last decade, a normative framework for making causal inferences, Bayesian Probabilistic Causal Networks, has come to dominate psychological studies of inference based on causal relationships. The following causal networks—[X→Y→Z, X←Y→Z, X→Y←Z]—supply answers for questions like, “Suppose both X and Y occur, what is the probability Z occurs?” or “Suppose you intervene and make Y occur, what is the probability Z occurs?” In this review, we provide a tutorial for how normatively to calculate these inferences. Then, we systematically detail the results of behavioral studies comparing human qualitative and quantitative judgments to the normative calculations for many network structures and for several types of inferences on those networks. Overall, when the normative calculations imply that an inference should increase, judgments usually go up; when calculations imply a decrease, judgments usually go down. However, two systematic deviations appear. First, people’s inferences violate the Markov assumption. For example, when inferring Z from the structure X→Y→Z, people think that X is relevant even when Y completely mediates the relationship between X and Z. Second, even when people’s inferences are directionally consistent with the normative calculations, they are often not as sensitive to the parameters and the structure of the network as they should be. We conclude with a discussion of productive directions for future research. PMID:23544658

  19. Changes in ultraweak luminescence from living fish induced by three chemicals

    SciTech Connect

    Wang Yingyan; Li Da ); Ma Yuqin; Li Shenxun; Zhang Yujing; Song Xueling )

    1991-03-01

    Ultraweak luminescence is a ubiquitous phenomenon in biological systems, which differs from bioluminescence of luciferin-luciferase. This low-intensity emission is inherently associated with the following important process such as oxidative metabolism, cell division, carcinogenesis, photosynthesis, and cell death. In general, ultraweak luminescence may be classified as two kinds, namely spontaneous and induced. Zebra fish is a recommended specimen for toxicity and toxicological test. The purpose of this, the changes before and after the treatment with three chemicals: uranium oxides, sodium azide or cyclophosphamide and their correlations between the dose and effect.

  20. Chemical patterning of Ag(111): Spatially confined oxide formation induced by electron beam irradiation

    SciTech Connect

    Guenther, S.; Reichelt, R.; Wintterlin, J.; Barinov, A.; Mentes, T. O.; Nino, M. A.; Locatelli, A.

    2008-12-08

    Low energy electron irradiation of a Ag(111) surface during NO{sub 2} adsorption at 300 K induces formation of Ag oxide. Using a spatially confined electron beam, small Ag{sub 2}O spots could be grown with a sharp, {approx}100 nm wide, boundary to the nonirradiated metallic surface. Since the structure size will mainly depend on the sharpness of the irradiating electron beam, this process has the potential of a single step nanostructuring process. Temperature treatment offers an easy way to manipulate the boundary between oxide and metallic silver by steering a chemical front.

  1. Metal-enhanced chemiluminescence: Radiating plasmons generated from chemically induced electronic excited states

    NASA Astrophysics Data System (ADS)

    Chowdhury, Mustafa H.; Aslan, Kadir; Malyn, Stuart N.; Lakowicz, Joseph R.; Geddes, Chris D.

    2006-04-01

    In this letter, we report the observation of metal-enhanced chemiluminescence. Silver Island films, in close proximity to chemiluminescence species, can significantly enhance luminescence intensities; a 20-fold increase in chemiluminescence intensity was observed as compared to an identical control sample containing no silver. This suggests the use of silver nanostructures in the chemiluminescence-based immunoassays used in the biosciences today, to improve signal and therefore analyte detectability. In addition, this finding suggests that surface plasmons can be directly excited by chemically induced electronically excited luminophores, a significant finding toward our understanding of fluorophore-metal interactions and the generation of surface plasmons.

  2. Chemical effects of F KVV Auger spectra induced by photon impact

    NASA Astrophysics Data System (ADS)

    Uda, M.; Maeda, K.; Koyama, A.; Sasa, Y.

    1984-03-01

    F KVV Auger emissions were measured with NaF, MgF2, A1F3, and Teflon [(CF2)n], which were induced by photoionization. Chemical effects were reflected in line broadening and change in intensity ratios of the spectra emitted from singly and doubly ionized initial states, |K1L0> and |K1L1>. Reduction in Auger peak intensities which originated from |K1L1> is in the order of the covalencies of the fluorides or the natural widths of F L shells. This is caused by the refilling of a F L-shell vacancy by one of the ligand electrons prior to Auger emission.

  3. Convection and mass-transport in laser-induced chemical vapor deposition

    NASA Technical Reports Server (NTRS)

    Patnaik, S.; Brown, R. A.

    1988-01-01

    Gas flow and energy and species transport in laser-induced chemical vapor deposition (LICVD) of amorphous silicon films by silane pyrolysis are analyzed by finite element analysis of a two-dimensional model for the process. Spatial nonuniformity of the deposited film is shown to result from diffusion controlled transport of products between the beam and substrate. Deposition profiles are affected by buoyancy-driven convection only at increased gas pressures. Horizontal orientation of the reactor with respect to gravity is optimal because the stagnation-like flow, that results adjacent to the substrate, enhances mixing, and smoothes the film profile.

  4. Laser-induced chemical vapour deposition of conductive and insulating thin films

    NASA Astrophysics Data System (ADS)

    Reisse, G.; Gaensicke, F.; Ebert, R.; Illmann, U.; Johansen, H.

    1992-01-01

    Investigations concerning the laser-induced chemical vapour deposition of Mo, W, Co and TiSi 2 conductive thin film structures from Mo(CO) 6, W(CO) 6, Co 2(CO) 8, TiCl 4 and SiH 4 using a direct writing method are presented. SiO 2 thin films were deposited from SiH 4 and N 2O in a large area deposition process stimulated by an excimer laser by using a parallel beam configuration.

  5. Effect of Lepidium meyenii (maca) on testicular function of mice with chemically and physically induced subfertility.

    PubMed

    Valdivia Cuya, M; Yarasca De La Vega, K; Lévano Sánchez, G; Vásquez Cavero, J; Temoche García, H; Torres Torres, L; Cruz Ornetta, V

    2016-10-01

    The aim of this study was to evaluate the effect of Lepidium meyenii (maca) in chemically and physically subfertile mice. After 35 days, the following groups of mice were evaluated: control, sham, chemical subfertility, chemical subfertility-maca-supplemented, physical subfertility, physical subfertility-maca-supplemented and maca-supplemented only. Motility (32.36% ± 5.34%) and sperm count (44.4 ± 5.37 × 10(6) /ml) in the chemically and physically subfertile mice (11.81% ± 4.06%, 17.34 ± 13.07 × 10(6) /ml) decreased compared to the control (75.53% ± 2.97% and 57.4 ± 19.6 10(6) /ml) and sham (53.5% ± 7.86% and 58.4 ± 14.10 10(6) /ml). Maca was able to reverse the deleterious effect of motility (76.36 ± 1.97) as well as sperm count (53.5 ± 9.18 × 10(6) /ml) on chemical subfertility. In contrast, maca did not reverse the effects of induced physical subfertility nor motility (18.78% ± 14.41%) or sperm count (20.17 ± 11.20 × 10(6) /ml). The percentage of sperm DNA fragmentation in the physically subfertile mice increased (11.1% ± 19.29%) compared to the control (0.84% ± 0.85%). However, in the physically subfertile group, maca decreased sperm DNA fragmentation (2.29% ± 2.30%) closer to the sham (1.04% ± 0.62%) and the control (0.84% ± 0.85%). The group supplemented only with maca showed 0.54% ± 0.50% of spermatozoa with DNA fragmentation. Yet, the differences observed were statistically not significant. In conclusion, it appears that maca activates the cytochrome P450 system after chemically induced subfertility. However, it does not reverse the low mitochondrial membrane potential in spermatozoa compromised in the physical subfertility group. © 2016 Blackwell Verlag GmbH.

  6. Herbal hepatotoxicity: challenges and pitfalls of causality assessment methods.

    PubMed

    Teschke, Rolf; Frenzel, Christian; Schulze, Johannes; Eickhoff, Axel

    2013-05-21

    The diagnosis of herbal hepatotoxicity or herb induced liver injury (HILI) represents a particular clinical and regulatory challenge with major pitfalls for the causality evaluation. At the day HILI is suspected in a patient, physicians should start assessing the quality of the used herbal product, optimizing the clinical data for completeness, and applying the Council for International Organizations of Medical Sciences (CIOMS) scale for initial causality assessment. This scale is structured, quantitative, liver specific, and validated for hepatotoxicity cases. Its items provide individual scores, which together yield causality levels of highly probable, probable, possible, unlikely, and excluded. After completion by additional information including raw data, this scale with all items should be reported to regulatory agencies and manufacturers for further evaluation. The CIOMS scale is preferred as tool for assessing causality in hepatotoxicity cases, compared to numerous other causality assessment methods, which are inferior on various grounds. Among these disputed methods are the Maria and Victorino scale, an insufficiently qualified, shortened version of the CIOMS scale, as well as various liver unspecific methods such as the ad hoc causality approach, the Naranjo scale, the World Health Organization (WHO) method, and the Karch and Lasagna method. An expert panel is required for the Drug Induced Liver Injury Network method, the WHO method, and other approaches based on expert opinion, which provide retrospective analyses with a long delay and thereby prevent a timely assessment of the illness in question by the physician. In conclusion, HILI causality assessment is challenging and is best achieved by the liver specific CIOMS scale, avoiding pitfalls commonly observed with other approaches.

  7. Herbal hepatotoxicity: Challenges and pitfalls of causality assessment methods

    PubMed Central

    Teschke, Rolf; Frenzel, Christian; Schulze, Johannes; Eickhoff, Axel

    2013-01-01

    The diagnosis of herbal hepatotoxicity or herb induced liver injury (HILI) represents a particular clinical and regulatory challenge with major pitfalls for the causality evaluation. At the day HILI is suspected in a patient, physicians should start assessing the quality of the used herbal product, optimizing the clinical data for completeness, and applying the Council for International Organizations of Medical Sciences (CIOMS) scale for initial causality assessment. This scale is structured, quantitative, liver specific, and validated for hepatotoxicity cases. Its items provide individual scores, which together yield causality levels of highly probable, probable, possible, unlikely, and excluded. After completion by additional information including raw data, this scale with all items should be reported to regulatory agencies and manufacturers for further evaluation. The CIOMS scale is preferred as tool for assessing causality in hepatotoxicity cases, compared to numerous other causality assessment methods, which are inferior on various grounds. Among these disputed methods are the Maria and Victorino scale, an insufficiently qualified, shortened version of the CIOMS scale, as well as various liver unspecific methods such as the ad hoc causality approach, the Naranjo scale, the World Health Organization (WHO) method, and the Karch and Lasagna method. An expert panel is required for the Drug Induced Liver Injury Network method, the WHO method, and other approaches based on expert opinion, which provide retrospective analyses with a long delay and thereby prevent a timely assessment of the illness in question by the physician. In conclusion, HILI causality assessment is challenging and is best achieved by the liver specific CIOMS scale, avoiding pitfalls commonly observed with other approaches. PMID:23704820

  8. Shock-induced hotspot formation and chemical reaction initiation in PETN containing a spherical void

    NASA Astrophysics Data System (ADS)

    Shan, Tzu-Ray; Thompson, Aidan P.

    2014-05-01

    We present results of reactive molecular dynamics simulations of hotspot formation and chemical reaction initiation in shock-induced compression of pentaerythritol tetranitrate (PETN) with the ReaxFF reactive force field. A supported shockwave is driven through a PETN crystal containing a 20 nm spherical void at a sub-threshold impact velocity of 2 km/s. Formation of a hotspot due to shock-induced void collapse is observed. During void collapse, NO2 is the dominant species ejected from the upstream void surface. Once the ejecta collide with the downstream void surface and the hotspot develops, formation of final products such as N2 and H2O is observed. The simulation provides a detailed picture of how void collapse and hotspot formation leads to initiation at sub-threshold impact velocities.

  9. Chemical state evolution in ferroelectric films during tip-induced polarization and electroresistive switching

    SciTech Connect

    Ievlev, Anton V.; Maksymovych, Petro; Trassin, Morgan; Seidel, Jan; Ramesh, Ramamoorthy; Kalinin, Sergei V.; Ovchinnikova, Olga S.

    2016-10-11

    Domain formation and ferroelectric switching is fundamentally inseparable from polarization screening, which on free surfaces can be realized via band bending and ionic adsorption. In the latter case, polarization switching is intrinsically coupled to the surface electrochemical phenomena, and the electrochemical stage can control kinetics and induce long-range interactions. However, despite extensive evidence towards the critical role of surface electrochemistry, little is known about the nature of the associated processes. Here we combine SPM tip induce polarization switching and secondary ion mass spectrometry to explore the evolution of chemical state of ferroelectric during switching. Surprisingly, we find that even pristine surfaces contain ions (e.g. Cl-) that are not anticipated based on chemistry of the system and processing. In the ferroelectric switching regime, we find surprising changes in surface chemistry, including redistribution of base cations. Finally, at higher voltages in the electroforming regime significant surface deformation was observed and associated with a strong ion intermixing.

  10. Chemical inducers of differentiation in a long-term renal cell line.

    PubMed Central

    Lever, J E

    1989-01-01

    The long-term renal epithelial cell line LLC-PK1 expresses at confluence several differentiated characteristics of renal proximal tubule including Na/glucose cotransport and several brush border membrane hydrolases. The differentiation-inducing chemical hexamethylene bisacetamide (HMBA) triggers a dramatic induction of Na+/glucose symport, trehalase and maltase, expressed as an increase in the number of cells in the culture that express the differentiated phenotype. Characteristics of the induction response are reviewed in terms of proposed mechanisms of inducer action. New evidence suggests that in addition to elevation of intracellular Na levels mediated by partial inhibition of the sodium pump, HMBA treatment also alters polyamine levels via effects on ornithine decarboxylase. These responses may be mediated by HMBA effects on protein kinase C activity. The possible role of polyamine fluctuations and DNA demethylation in mediating HMBA effects on differentiated gene expression is currently being investigated. Images FIGURE 2. FIGURE 3. PMID:2647478

  11. Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation.

    PubMed

    Rovira, Meritxell; Huang, Wei; Yusuff, Shamila; Shim, Joong Sup; Ferrante, Anthony A; Liu, Jun O; Parsons, Michael J

    2011-11-29

    Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.

  12. Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation

    PubMed Central

    Rovira, Meritxell; Huang, Wei; Yusuff, Shamila; Shim, Joong Sup; Ferrante, Anthony A.; Liu, Jun O.; Parsons, Michael J.

    2011-01-01

    Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis. PMID:22084084

  13. Chemical state evolution in ferroelectric films during tip-induced polarization and electroresistive switching

    SciTech Connect

    Ievlev, Anton V.; Maksymovych, Petro; Trassin, Morgan; Seidel, Jan; Ramesh, Ramamoorthy; Kalinin, Sergei V.; Ovchinnikova, Olga S.

    2016-10-11

    Domain formation and ferroelectric switching is fundamentally inseparable from polarization screening, which on free surfaces can be realized via band bending and ionic adsorption. In the latter case, polarization switching is intrinsically coupled to the surface electrochemical phenomena, and the electrochemical stage can control kinetics and induce long-range interactions. However, despite extensive evidence towards the critical role of surface electrochemistry, little is known about the nature of the associated processes. Here we combine SPM tip induce polarization switching and secondary ion mass spectrometry to explore the evolution of chemical state of ferroelectric during switching. Surprisingly, we find that even pristine surfaces contain ions (e.g. Cl-) that are not anticipated based on chemistry of the system and processing. In the ferroelectric switching regime, we find surprising changes in surface chemistry, including redistribution of base cations. Finally, at higher voltages in the electroforming regime significant surface deformation was observed and associated with a strong ion intermixing.

  14. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    SciTech Connect

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-11-15

    cultures were more sensitive to neurite outgrowth inhibitors, they also had a lower dynamic range for detecting chemical-induced neurite outgrowth inhibition and greater variability from culture-to-culture as compared to rat primary cortical cultures.

  15. A genetically encoded indicator for assaying bioactive chemicals that induce nuclear transport of glucocorticoid receptor.

    PubMed

    Kim, Sung Bae; Ozawa, Takeaki; Umezawa, Yoshio

    2005-12-15

    Glucocorticoids, the adrenal steroid hormones secreted during stress, are essential to homeostasis and metabolism in the human body. An impaired glucocorticoid signaling due to dysfunction of the glucocorticoid receptor (GR) by synthetic chemicals can cause diseases and disruptions of the homeostasis and metabolism. Here we demonstrate the development of a method for screening endocrine-disrupting chemicals and potent risk factors of human diseases based on the nuclear trafficking of the GR. We constructed a new assay using a pair of genetic indicators with the full length of the GR, split Renilla luciferase (RLuc), and split DnaE (a protein splicing element). The GR-containing fusion protein with C-terminal halves of DnaE and RLuc is localized in cytosol due to the cytosolic character of the GR, whereas the fusion protein with N-terminal halves of DnaE and RLuc stays in the nucleus due to the cofused nucleus localization signal. On being stimulated with a ligand, the GR is translocated into the cellular nucleus. Thus, a protein splicing occurs in the nucleus by an interaction between the splicing junctions of each DnaE fragment. The enzymatic activities from the reconstituted RLuc allow the ligand-dependent luminescence intensities. The feasibility of the method was evaluated by quantifying the hormonal activities of 20 different kinds of steroids and synthetic chemicals using the NIH 3T3 cells carrying the pair of indicators. The hormonal activities of tested ligands are discussed based on the chemical structure-activity relationship. We found that androgens, testosterone, and 19-nortestosterone weakly induce the nuclear transport of the GR. The current assay allows high-throughput screening of risk chemicals and drug candidates influential to a signal transduction pathway of the GR.

  16. Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents

    PubMed Central

    Dong, Jie; Yu, Xiaoqing; Porter, Dale W.; Battelli, Lori A.; Kashon, Michael L.

    2016-01-01

    Pulmonary fibrosis results from the excessive deposition of collagen fibers and scarring in the lungs with or without an identifiable cause. The mechanism(s) underlying lung fibrosis development is poorly understood, and effective treatment is lacking. Here we compared mouse lung fibrosis induced by pulmonary exposure to prototypical particulate (crystalline silica) or soluble chemical (bleomycin or paraquat) fibrogenic agents to identify the underlying mechanisms. Young male C57BL/6J mice were given silica (2 mg), bleomycin (0.07 mg), or paraquat (0.02 mg) by pharyngeal aspiration. All treatments induced significant inflammatory infiltration and collagen deposition, manifesting fibrotic foci in silica-exposed lungs or diffuse fibrosis in bleomycin or paraquat-exposed lungs on day 7 post-exposure, at which time the lesions reached their peaks and represented a junction of transition from an acute response to chronic fibrosis. Lung genomewide gene expression was analyzed, and differential gene expression was confirmed by quantitative RT-PCR, immunohistochemistry, and immunoblotting for representative genes to demonstrate their induced expression and localization in fibrotic lungs. Canonical signaling pathways, gene ontology, and upstream transcription networks modified by each agent were identified. In particular, these inducers elicited marked proliferative responses; at the same time, silica preferentially activated innate immune functions and the defense against foreign bodies, whereas bleomycin and paraquat boosted responses related to cell adhesion, platelet activation, extracellular matrix remodeling, and wound healing. This study identified, for the first time, the shared and unique genes, signaling pathways, and biological functions regulated by particulate and soluble chemical fibrogenic agents during lung fibrosis, providing insights into the mechanisms underlying human lung fibrotic diseases. PMID:26345256

  17. Renoprotective chemical constituents from an edible mushroom, Pleurotus cornucopiae in cisplatin-induced nephrotoxicity.

    PubMed

    Lee, Seoung Rak; Lee, Dahae; Lee, Hae-Jeung; Noh, Hyung Jun; Jung, Kiwon; Kang, Ki Sung; Kim, Ki Hyun

    2017-01-19

    Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.

  18. Chemical modifications of polymer films induced by high energy heavy ions

    NASA Astrophysics Data System (ADS)

    Zhu, Zhiyong; Sun, Youmei; Liu, Changlong; Liu, Jie; Jin, Yunfan

    2002-06-01

    Polymer films including polyethylene terephthalate (PET), polystyrene (PS) and polycarbonate (PC) were irradiated at room temperature with ions of 35 MeV/u 40Ar, 25 MeV/u 84Kr, 15.1 MeV/u 136Xe and 11.4 MeV/u 238U to fluences ranging from 9×10 9 to 5.5×10 12 ions/cm 2. The radiation-induced chemical changes of the materials were investigated by Fourier-transform infrared (FTIR) and ultraviolet/visible spectroscopies. It is found that the absorbance in the ultraviolet and visible range induced by all irradiations follows a linear relationship with fluence. The radiation-induced absorbance normalized to one particle increases slowly with increasing of electronic energy loss below about 8 keV/nm followed by a sharp increase up to about 15 keV/nm above which saturation is reached. FTIR measurements reveal that the materials suffer serious degradation through bond breaking. The absorbance of the typical infrared bands decays exponentially with increase of ion fluence and the bond-disruption cross-section shows a sigmoid variation with electronic energy loss. In PET loss of crystallinity is attributed to the configuration transformation of the ethylene glycol residue from trans into the gauche. Alkyne end groups are induced in all the materials above certain electronic energy loss threshold, which is found to be about 0.8 keV/nm for PS and 0.4 keV/nm for PC. The production cross-section of alkyne end group increases with increasing of electronic energy loss and shows saturation at high electronic energy loss values. It is concluded that not only the physical processes but also the chemical processes of the energy deposition determine the modification of polymer.

  19. Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2.

    PubMed

    Shearstone, Jeffrey R; Golonzhka, Olga; Chonkar, Apurva; Tamang, David; van Duzer, John H; Jones, Simon S; Jarpe, Matthew B

    2016-01-01

    Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC) 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2), elicits a dose and time dependent induction of γ-globin mRNA (HBG) and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB). Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq) of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene.

  20. Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2

    PubMed Central

    Golonzhka, Olga; Chonkar, Apurva; Tamang, David; van Duzer, John H.; Jones, Simon S.; Jarpe, Matthew B.

    2016-01-01

    Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC) 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2), elicits a dose and time dependent induction of γ-globin mRNA (HBG) and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB). Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq) of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene. PMID:27073918

  1. Causal discovery from medical textual data.

    PubMed Central

    Mani, S.; Cooper, G. F.

    2000-01-01

    Medical records usually incorporate investigative reports, historical notes, patient encounters or discharge summaries as textual data. This study focused on learning causal relationships from intensive care unit (ICU) discharge summaries of 1611 patients. Identification of the causal factors of clinical conditions and outcomes can help us formulate better management, prevention and control strategies for the improvement of health care. For causal discovery we applied the Local Causal Discovery (LCD) algorithm, which uses the framework of causal Bayesian Networks to represent causal relationships among model variables. LCD takes as input a dataset and outputs causes of the form variable Y causally influences variable Z. Using the words that occur in the discharge summaries as attributes for input, LCD output 8 purported causal relationships. The relationships ranked as most probable subjectively appear to be most causally plausible. PMID:11079942

  2. Causal discovery from medical textual data.

    PubMed

    Mani, S; Cooper, G F

    2000-01-01

    Medical records usually incorporate investigative reports, historical notes, patient encounters or discharge summaries as textual data. This study focused on learning causal relationships from intensive care unit (ICU) discharge summaries of 1611 patients. Identification of the causal factors of clinical conditions and outcomes can help us formulate better management, prevention and control strategies for the improvement of health care. For causal discovery we applied the Local Causal Discovery (LCD) algorithm, which uses the framework of causal Bayesian Networks to represent causal relationships among model variables. LCD takes as input a dataset and outputs causes of the form variable Y causally influences variable Z. Using the words that occur in the discharge summaries as attributes for input, LCD output 8 purported causal relationships. The relationships ranked as most probable subjectively appear to be most causally plausible.

  3. Aqueous suspension of anise "Pimpinella anisum" protects rats against chemically induced gastric ulcers.

    PubMed

    Al Mofleh, Ibrahim A; Alhaider, Abdulqader A; Mossa, Jaber S; Al-Soohaibani, Mohammed O; Rafatullah, Syed

    2007-02-21

    To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, "Pimpinella anisum L." on experimentally-induced gastric ulceration and secretion in rats. Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCl and indomethacin. Anti-secretory studies were undertaken using pylorus-ligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments. Anise significantly inhibited gastric mucosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension significantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration. Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties.

  4. Inducible and Selective Erasure of Memories in the Mouse Brain via Chemical-Genetic Manipulation

    PubMed Central

    Cao, Xiaohua; Wang, Huimin; Mei, Bing; An, Shuming; Yin, Liang; Wang, L. Phillip; Tsien, Joe Z.

    2010-01-01

    SUMMARY Rapid and selective erasures of certain types of memories in the brain would be desirable under certain clinical circumstances. By employing an inducible and reversible chemical-genetic technique, we find that transient αCaMKII overexpression at the time of recall impairs the retrieval of both newly formed one-hour object recognition memory and fear memories, as well as 1-month-old fear memories. Systematic analyses suggest that excessive αCaMKII activity-induced recall deficits are not caused by disrupting the retrieval access to the stored information but are, rather, due to the active erasure of the stored memories. Further experiments show that the recall-induced erasure of fear memories is highly restricted to the memory being retrieved while leaving other memories intact. Therefore, our study reveals a molecular genetic paradigm through which a given memory, such as new or old fear memory, can be rapidly and specifically erased in a controlled and inducible manner in the brain. PMID:18957226

  5. Contrasting roles of dietary selenium and selenoproteins in chemically induced hepatocarcinogenesis

    PubMed Central

    Gladyshev, Vadim N.

    2013-01-01

    Selenium (Se) has long been known for its cancer prevention properties, but the molecular basis remains unclear. The principal questions in assessing the effect of dietary Se in cancer are whether selenoproteins, small molecule selenocompounds, or both, are involved, and under which conditions and genotypes Se may be protective. In this study, we examined diethylnitrosamine-induced hepatocarcinogenesis in mice lacking a subset of selenoproteins due to expression of a mutant selenocysteine tRNA gene (Trsp A37G mice). To uncouple the effects of selenocompounds and selenoproteins, these animals were examined at several levels of dietary Se. Our analysis revealed that tumorigenesis in Trsp A37G mice maintained on the adequate Se diet was increased. However, in the control, wild-type mice, both Se deficiency and high Se levels protected against tumorigenesis. We further found that the Se-deficient diet induced severe neurological phenotypes in TrspA37G mice. Surprisingly, a similar phenotype could be induced in these mice at high dietary Se intake. Overall, our results show a complex role of Se in chemically induced hepatocarcinogenesis, which involves interaction among selenoproteins, selenocompounds and toxins, and depends on genotype and background of the animals. PMID:23389288

  6. Aqueous suspension of anise “Pimpinella anisum” protects rats against chemically induced gastric ulcers

    PubMed Central

    Al Mofleh, Ibrahim A; Alhaider, Abdulqader A; Mossa, Jaber S; Al-Soohaibani, Mohammed O; Rafatullah, Syed

    2007-01-01

    AIM: To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, “Pimpinella anisum L.” on experimentally-induced gastric ulceration and secretion in rats. METHODS: Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCl and indomethacin. Anti-secretory studies were undertaken using pylorus-ligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: Anise significantly inhibited gastric mu-cosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension significantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration. CONCLUSION: Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties. PMID:17373749

  7. A detection algorithm for drug-induced liver injury in medical information databases using the Japanese diagnostic scale and its comparison with the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method scale.

    PubMed

    Hanatani, Tadaaki; Sai, Kimie; Tohkin, Masahiro; Segawa, Katsunori; Kimura, Michio; Hori, Katsuhito; Kawakami, Junichi; Saito, Yoshiro

    2014-09-01

    Drug-induced liver injury (DILI) is one of the primary targets for pharmacovigilance using medical information databases (MIDs). Because of diagnostic complexity, a standardized method for identifying DILI using MIDs has not yet been established. We applied the Digestive Disease Week Japan 2004 (DDW-J) scale, a Japanese clinical diagnostic criteria for DILI, to a DILI detection algorithm, and compared it with the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale to confirm its consistency. Characteristics of DILI cases identified by the DDW-J algorithm were examined in two Japanese MIDs. Using an MID from the Hamamatsu University Hospital, we constructed a DILI detection algorithm on the basis of the DDW-J scale. We then compared the findings between the DDW-J and CIOMS/RUCAM scales. We examined the characteristics of DILI after antibiotic treatment in the Hamamatsu population and a second population that included data from 124 hospitals, which was derived from an MID from the Medical Data Vision Co., Ltd. We performed a multivariate logistic regression analysis to assess the possible DILI risk factors. The concordance rate was 79.4% between DILI patients identified by the DDW-J and CIOMS/RUCAM; the Spearman rank correlation coefficient was 0.952 (P < 0.0001). Men showed a significantly higher risk for DILI after antibiotic treatments in both MID populations. The DDW-J and CIOMS/RUCAM algorithms were equivalent for identifying the DILI cases, confirming the utility of our DILI detection method using MIDs. This study provides evidence supporting the use of MID analyses to improve pharmacovigilance. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Particulate Matter Physicochemistry and Toxicology: In Search of Causality-A Critical Perspective.

    PubMed

    Dreher, K L

    2000-01-01

    Results from epidemiology studies have shown statistical associations between ambient air particulate matter (PM) concentrations and mortality/morbidity, particularly among susceptible subpopulations. Although the epidemiology of ambient air PM is compelling, there remains considerable uncertainty in PM risk assessment, particularly with regard to identification of PM properties and mechanisms that are responsible for its observed adverse health effects. In addition, the biological mechanisms by which specific PM properties mediate their adverse health effects are currently not known. In vivo and in vitro toxicological studies have examined particles derived from a number of sources such as ambient air, combustion, and natural sources, as well as laboratory-derived surrogate particles, in order to identify the characteristics of particles that are responsible for their adverse health effects. These studies have identified a number of potential causal biogenic, physical, and chemical properties of PM. A number of PM physical and chemical properties have been found to elicit biological responses in animal models of disease, which has enhanced their plausibility as being properties responsible for PM-associated health effects. In vitro mechanistic studies have shown that PM derived from a variety of sources mediate their adverse biological effects by inducing an oxidative stress, which may alter intracellular signal transduction pathways that regulate a number of biological responses such as cell growth, stress response, apoptosis, and inflammation. The challenge of future PM toxicology research will be to demonstrate "biological plausibility and coherence" for potential causal PM properties.

  9. Nonlinear connectivity by Granger causality.

    PubMed

    Marinazzo, Daniele; Liao, Wei; Chen, Huafu; Stramaglia, Sebastiano

    2011-09-15

    The communication among neuronal populations, reflected by transient synchronous activity, is the mechanism underlying the information processing in the brain. Although it is widely assumed that the interactions among those populations (i.e. functional connectivity) are highly nonlinear, the amount of nonlinear information transmission and its functional roles are not clear. The state of the art to understand the communication between brain systems are dynamic causal modeling (DCM) and Granger causality. While DCM models nonlinear couplings, Granger causality, which constitutes a major tool to reveal effective connectivity, and is widely used to analyze EEG/MEG data as well as fMRI signals, is usually applied in its linear version. In order to capture nonlinear interactions between even short and noisy time series, a few approaches have been proposed. We review them and focus on a recently proposed flexible approach has been recently proposed, consisting in the kernel version of Granger causality. We show the application of the proposed approach on EEG signals and fMRI data.

  10. Causal Categories: Relativistically Interacting Processes

    NASA Astrophysics Data System (ADS)

    Coecke, Bob; Lal, Raymond

    2013-04-01

    A symmetric monoidal category naturally arises as the mathematical structure that organizes physical systems, processes, and composition thereof, both sequentially and in parallel. This structure admits a purely graphical calculus. This paper is concerned with the encoding of a fixed causal structure within a symmetric monoidal category: causal dependencies will correspond to topological connectedness in the graphical language. We show that correlations, either classical or quantum, force terminality of the tensor unit. We also show that well-definedness of the concept of a global state forces the monoidal product to be only partially defined, which in turn results in a relativistic covariance theorem. Except for these assumptions, at no stage do we assume anything more than purely compositional symmetric-monoidal categorical structure. We cast these two structural results in terms of a mathematical entity, which we call a causal category. We provide methods of constructing causal categories, and we study the consequences of these methods for the general framework of categorical quantum mechanics.

  11. Hypothesizing and Refining Causal Models,

    DTIC Science & Technology

    1984-12-01

    the purposes of this research, it was critica ! to be able to represent a sequence of events, in which the learning program would look for causal... tlc sense because tliv imply random behavior. This is an oversimplified, but usc^ul telcological assumption about the nature of dependences in designed

  12. Learning a Theory of Causality

    ERIC Educational Resources Information Center

    Goodman, Noah D.; Ullman, Tomer D.; Tenenbaum, Joshua B.

    2011-01-01

    The very early appearance of abstract knowledge is often taken as evidence for innateness. We explore the relative learning speeds of abstract and specific knowledge within a Bayesian framework and the role for innate structure. We focus on knowledge about causality, seen as a domain-general intuitive theory, and ask whether this knowledge can be…

  13. Identity, causality, and pronoun ambiguity.

    PubMed

    Sagi, Eyal; Rips, Lance J

    2014-10-01

    This article looks at the way people determine the antecedent of a pronoun in sentence pairs, such as: Albert invited Ron to dinner. He spent hours cleaning the house. The experiment reported here is motivated by the idea that such judgments depend on reasoning about identity (e.g., the identity of the he who cleaned the house). Because the identity of an individual over time depends on the causal-historical path connecting the stages of the individual, the correct antecedent will also depend on causal connections. The experiment varied how likely it is that the event of the first sentence (e.g., the invitation) would cause the event of the second (the house cleaning) for each of the two individuals (the likelihood that if Albert invited Ron to dinner, this would cause Albert to clean the house, versus cause Ron to clean the house). Decisions about the antecedent followed causal likelihood. A mathematical model of causal identity accounted for most of the key aspects of the data from the individual sentence pairs.

  14. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (External Review Draft)

    EPA Science Inventory

    This draft report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induced by chemical agents and radiation in humans, with a primary emphasis on leukemia and leukemia-inducing agents. It focuses on how mechanistic information on human l...

  15. DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

    EPA Science Inventory

    Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

  16. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (External Review Draft)

    EPA Science Inventory

    This draft report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induced by chemical agents and radiation in humans, with a primary emphasis on leukemia and leukemia-inducing agents. It focuses on how mechanistic information on human l...

  17. DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

    EPA Science Inventory

    Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

  18. Music and Spatial Task Performance: A Causal Relationship.

    ERIC Educational Resources Information Center

    Rauscher, Frances H.; And Others

    This research paper reports on testing the hypothesis that music and spatial task performance are causally related. Two complementary studies are presented that replicate and explore previous findings. One study of college students showed that listening to a Mozart sonata induces subsequent short-term spatial reasoning facilitation and tested the…

  19. p21 Expression and DNA ploidy in chemically-induced transitional cell carcinoma

    SciTech Connect

    Rhodes, S.W.

    1987-01-01

    Occupational and environmental exposure to chemical carcinogens and the incidence of bladder carcinoma suggest that biochemical indicators for individual risk, and early detection would be beneficial in facilitating timely intervention and cancer management. Further, such objective measures may provide a quantitative basis for determination of the biological potential of tumors and the development of end point markers in chemical risk assessment. In this study quantitative measures for biochemical alterations were developed for in situ measurement of the ras oncoprotein, p21, and DNA ploidy in tissue sections. These assays were then applied to an animal model in which transitional cell carcinoma was induced with N-butyl-N-(4-hydroxybutyl) nitrosamine, which primarily induced low grade tumors. Three measures of DNA ploidy were utilized: (A) 95th percentile of cellular DNA content (C value), (B) percent of cells with a DNA complement greater than 5.0C, and (C) mode. The 95th percentile C value was able to delineate normal and hyperplastic tissues from tumor tissues. The percent of cells with a DNA content greater than 5.0C was capable of differentiating invasive lesions from noninvasive lesions.

  20. Autologous, Noncultured Epidermal Cell Suspension Grafting in the Management of Mechanically and Chemically Induced Leukodermic Scars.

    PubMed

    Vyas, Nikki S; Lawrence, Kelsey L; Griffith, James L; Hamzavi, Iltefat H

    2015-01-01

    Melanocyte-keratinocyte transplant procedure (MKTP) successfully repigments postburn leukodermic scars. To further investigate the efficacy and limitations of MKTP for treatment of mechanically and chemically induced leukodermic scars. Ten patients with mechanically or chemically induced, depigmented or hypopigmented scars were preoperatively evaluated with Wood's light examination, treated with MKTP, and followed for at least 6 months, with monitoring of repigmentation and colour matching. Nine patients attended at least 6 months of follow-up. Six patients showed no fluorescence of scars under Wood's lamp. All patients whose lesions didn't fluoresce displayed less than 50% repigmentation, with 5 of 6 attaining 0% to 24%. Of the 3 patients displaying bright or some fluorescence, more than 95% repigmentation was achieved in 2 patients (skin phototypes V and VI), while less than 24% was attained for the third (skin phototype II). In this small case series, lack of fluorescence in leukodermic scars may be a useful negative prognostic indicator for MKTP, but additional trials are needed to verify that this is not due to melanocompetency. © The Author(s) 2015.

  1. Reactivity pattern of bromonucleosides induced by 2-hydroxypropyl radicals: photochemical, radiation chemical, and computational studies.

    PubMed

    Zdrowowicz, Magdalena; Chomicz, Lidia; Miloch, Justyna; Wiczk, Justyna; Rak, Janusz; Kciuk, Gabriel; Bobrowski, Krzysztof

    2015-06-04

    The bromonucleosides (BrdX's) 5-bromo-2'-deoxyuridine (BrdU), 5-bromo-2'-deoxycytidine (BrdC), 8-bromo-2'-deoxyadenosine (BrdA), and 5-bromo-2'-deoxyguanosine (BrdG) may substitute for ordinary nucleosides in DNA. As indicated by electron-stimulated desorption experiments, such a modified biopolymer is greater than 2-3-fold more sensitive to damage induced by excess electrons. The other major product of water radiolysis, the (•)OH radical, may form a number of other radicals in chemical reactions with the complex content of the cell. Thus, the well-proved BrdU-labeled DNA radiosensitivity may be, at least in part, related to secondary organic radicals. Therefore, in the current study, the propensity of BrdX's to damage induced by 2-hydroxypropyl radical (OHisop(•))-a prototype radical species-was investigated. The HPLC and LC-MS analyses revealed the formation of two major products from the brominated pyrimidine nucleosides, a native nucleoside and an adduct of BrdX and OHisop(•) , and only an adduct of BrdX from the bromopurine nucleosides. Quantum chemical calculations ascribed this evident difference between purines and pyrimidines to the electron transfer from OHisop(•) to BrdX that is especially favorable in pyrimidines.

  2. Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

    PubMed Central

    De Vooght, Vanessa; Schoofs, Liliane; Nemery, Benoit; Clynen, Elke; Hoet, Peter H. M.

    2015-01-01

    Introduction and Aim The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mice. Results Sixteen proteins were identified that were significantly up- or down-regulated in B lymphocytes of sensitized mice. Particularly differences in the expression of cyclophilin A, cofilin 1 and zinc finger containing CCHC domain protein 11 could be correlated to the function of B lymphocytes as initiators of T lymphocyte independent asthma-like responses. Conclusion This study revealed important alterations in the proteome of sensitized B cells in a mouse model of chemical-induced asthma, which will have an important impact on the B cell function. PMID:26398101

  3. Improving analytical methods for protein-protein interaction through implementation of chemically inducible dimerization

    PubMed Central

    Andersen, Tonni Grube; Nintemann, Sebastian J.; Marek, Magdalena; Halkier, Barbara A.; Schulz, Alexander; Burow, Meike

    2016-01-01

    When investigating interactions between two proteins with complementary reporter tags in yeast two-hybrid or split GFP assays, it remains troublesome to discriminate true- from false-negative results and challenging to compare the level of interaction across experiments. This leads to decreased sensitivity and renders analysis of weak or transient interactions difficult to perform. In this work, we describe the development of reporters that can be chemically induced to dimerize independently of the investigated interactions and thus alleviate these issues. We incorporated our reporters into the widely used split ubiquitin-, bimolecular fluorescence complementation (BiFC)- and Förster resonance energy transfer (FRET)- based methods and investigated different protein-protein interactions in yeast and plants. We demonstrate the functionality of this concept by the analysis of weakly interacting proteins from specialized metabolism in the model plant Arabidopsis thaliana. Our results illustrate that chemically induced dimerization can function as a built-in control for split-based systems that is easily implemented and allows for direct evaluation of functionality. PMID:27282591

  4. Investigation of the shock-induced chemical reaction (SICR) in Ni + Al nanoparticle mixtures.

    PubMed

    Xiong, Yongnan; Xiao, Shifang; Deng, Huiqiu; Zhu, Wenjun; Hu, Wangyu

    2017-07-21

    Molecular dynamics (MD) simulations are used to investigate the shock-compression response of Ni + Al spherical nanoparticles arranged in a NaCl-like structure. The deformation and reaction characteristics are studied from the particle level to the atomic scale at various piston velocities. Shock-induced chemical reactions (SICRs) occur during non-equilibrium processes, accompanied by a sharp rise in temperature and rapid mixing of atoms. The preferentially deformed Al particles form a high-speed mass flow relative to the Ni at the shock front, which impinges on the Ni particles, and mixing of Ni and Al atoms occurs immediately at the interface. The particle velocity dispersion (PVD) that appears at the shock front has important implications for the initiation of shock-induced chemical reactions. We show that dislocations are mainly generated at the beginning of particle deformation or at the shock front, and do not directly affect the occurrence of SICRs. The intimate contact of the molten Al and the amorphous Ni is found to be critical to the subsequent reactions for the extensive mixing of Ni and Al. We conclude that the mechanisms of SICRs involve mechanochemical processes near the shock front and subsequent interdiffusion processes.

  5. Imaging, chemical and spectroscopic studies of the methylation-induced decomposition of melanosomes.

    PubMed

    Kempf, Valerie R; Wakamatsu, Kazumasa; Ito, Shosuke; Simon, John D

    2010-01-01

    The morphological and chemical changes associated with the exposure of melanosomes to methyl iodide are assessed by a variety of analytical, imaging and spectroscopic methods. Scanning electron microscopy, light scattering and N(2) adsorption measurements all indicate significant changes in the morphology of the pigment following methylation. Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy and chemical degradation analysis reveals the methylation results in the introduction of ester groups into the pigment structures. Amino acid analysis further reveals that Arg, Cys, His, Ser and Tyr undergo methylation; the SS-NMR data provide additional evidence for the methylation of the sulfur of Cys. Methylation results in increased solubility of the melanosome; the absorption properties of the dissolved material are characterized by an absorption maximum at 225 nm, with a long tail throughout the UV-A and UV-B, indicating that the solubilized material is a combination of protein and pigment. The methylation-induced decomposition of the melanosomes provides new insights into both the observed increase in O-methyl derivatives of the indolic precursor to eumelanin in the urine of melanoma patients and how increased levels of biologic methylating agents in the brain induce symptoms that resemble Parkinson's disease.

  6. Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

    SciTech Connect

    Iwai, M.; Shimazu, T.

    1988-01-01

    The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCL/sub 4/) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine amino-transferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VHM) in CCl/sub 4/-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VHM stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl/sub 4/ injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve, possibly by affecting liver metabolism more than the blood flow change to the liver.

  7. C-1s NEXAFS spectroscopy reveals chemical fractionation of humic acid by cation-induced coagulation

    SciTech Connect

    Christl,I.; Kretzschmar, R.

    2007-01-01

    The influence of cation-induced coagulation on the chemical composition of dissolved and coagulated fractions of humic acid was investigated in batch coagulation experiments for additions of aluminum at pH 4 and 5, iron at pH 4, and calcium and lead at pH 6. The partitioning of organic carbon and metals was determined by analyzing total organic carbon and total metal contents of the dissolved phase. Both the dissolved and the coagulated humic acid fractions were characterized using synchrotron scanning transmission X-ray microscopy (STXM) and C-1s near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. Intensities of {pi}* transitions of carboxyl carbon and {sigma}* transitions of alkyl, O-alkyl, and carboxyl carbon decreased with increasing metal concentration for the dissolved humic acid fractions. This decrease was accompanied by an increase of the respective intensities in the coagulated fraction as shown for lead. Intensities of aromatic and phenolic carbon were affected to a larger extent only by aluminum and iron additions. The changes observed in the C-1s NEXAFS spectra coincided with an increasing removal of organic carbon from the dissolved phase with increasing total metal concentrations. We conclude that humic acid was chemically fractionated by cation-induced coagulation, which preferentially removed functional groups involved in metal-cation binding from solution.

  8. Modulatory activity of Brazilian red propolis on chemically induced dermal carcinogenesis.

    PubMed

    Pinheiro, Kariny Souza; Ribeiro, Danielle Rodrigues; Alves, Angela Valéria Farias; Pereira-Filho, Rose Nely; Oliveira, Clauberto Rodrigues de; Lima, Sônia Oliveira; Reis, Francisco Prado; Cardoso, Juliana Cordeiro; Albuquerque-Júnior, Ricardo Luiz Cavalcanti de

    2014-02-01

    To evaluate modulatory effects of a hydroalcoholic extract of Brazilian red propolis (HERP) on dermal carcinogenesis using a murine model. The HERP was used at concentrations of 10, 50 and 100 mg/kg (PROP10, PROP50 and PROP100, respectively) to modulate dermal carcinogenesis induced by the application of 9,10-dimetil-1,2-benzatraceno (DMBA) on the backs of animals. The chemical compounds identified in HERP included propyl gallate, catechin, epicatechin and formononetin. PROP100 treatment resulted in significantly decreased tumor multiplicity throughout the five weeks of tumor promotion (p<0.05), and this concentration also resulted in the highest frequency of verrucous tumors (p<0.05). All of the tumors that developed in DMBA-treated animals were regarded as squamous cell carcinomas and were either diagnosed as non-invasive verrucous carcinomas or invasive squamous cell carcinomas (SCCs). The average score for malignancy was significantly lower in the PROP100-treated group than the non-treated group (p<0.05), but there was no difference between the other groups (p>0.05). The oral administration of hydroalcoholic extract of Brazilian red propolis at a dose of 100 mg/kg had a significant modulatory effect on the formation, differentiation and progression of chemically induced squamous cell carcinoma in a murine experimental model.

  9. Evaluation of Maltose-Induced Chemical Degradation at the Interface of Bilayer Tablets.

    PubMed

    Matsuzaki, Naoya; Yamamoto, Yousuke; Murayama, Daisuke; Katakawa, Yoshifumi; Mimura, Hisashi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2017-01-01

    Fixed dose combination tablets consisting of mirabegron (MB) and solifenacin succinate (SS) were developed and formulated into bilayer tablets in the current study. The results of a chemical stability study showed that the original formulation for the tablets led to a significant increase of unknown degradants in the SS layer. Two compatibility studies were conducted to simulate the interface between the MB and SS layers, and the results revealed that the degradants only formed in the presence of both active pharmaceutical ingredients (APIs), and that the presence of maltose in the SS layer was critical to inducing degradation. High resolution mass spectroscopy coupled with high performance liquid chromatography was used to determine the chemical structures of the degradants, which were identified to MB derivatives bearing one or two sugar units. These findings therefore suggested that the degradation of the API could be attributed to the addition of sugar units from maltose to MB under the acidic conditions caused by SS. With this in mind, we developed a new formulation by replacing maltose with hydroxypropyl cellulose as a polymer-type binder. The results showed that this formulation suppressed the formation of the degradants. The results of this study have shown that chemical degradation can occur at the interface of bilayer tablets and that an alternative strategy is available to formulate more stable MB/SS bilayer tablets.

  10. Extraction of chemical-induced diseases using prior knowledge and textual information.

    PubMed

    Pons, Ewoud; Becker, Benedikt F H; Akhondi, Saber A; Afzal, Zubair; van Mulligen, Erik M; Kors, Jan A

    2016-01-01

    We describe our approach to the chemical-disease relation (CDR) task in the BioCreative V challenge. The CDR task consists of two subtasks: automatic disease-named entity recognition and normalization (DNER), and extraction of chemical-induced diseases (CIDs) from Medline abstracts. For the DNER subtask, we used our concept recognition tool Peregrine, in combination with several optimization steps. For the CID subtask, our system, which we named RELigator, was trained on a rich feature set, comprising features derived from a graph database containing prior knowledge about chemicals and diseases, and linguistic and statistical features derived from the abstracts in the CDR training corpus. We describe the systems that were developed and present evaluation results for both subtasks on the CDR test set. For DNER, our Peregrine system reached anF-score of 0.757. For CID, the system achieved anF-score of 0.526, which ranked second among 18 participating teams. Several post-challenge modifications of the systems resulted in substantially improvedF-scores (0.828 for DNER and 0.602 for CID). RELigator is available as a web service athttp://biosemantics.org/index.php/software/religator. © The Author(s) 2016. Published by Oxford University Press.

  11. Role of oxidative stress in chemical allergens induced skin cells activation.

    PubMed

    Corsini, Emanuela; Galbiati, Valentina; Nikitovic, Dragana; Tsatsakis, Aristidis M

    2013-11-01

    Allergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to chemical allergens. It describes the adverse effects that may results when exposure to a chemical elicits a T cell-mediated inflammatory skin disease. The ability of contact sensitizers to induce the oxidative stress pathway in keratinocytes and dendritic cells has been confirmed by several authors. Reactive oxygen species (ROS) can serve as essential second messengers mediating cellular responses resulting in immune cells activation. Oxidative stress may be the starter point, as it leads to the activation of transcription factors and signaling pathways, including NF-kB and p38 MAPK, which leads to the release of cytokines and chemokines. ROS are also involved in the activation of the NLRP3/NALP3 inflammasome, which is required to direct the proteolytic maturation of inflammatory cytokines such as IL-1β and IL-18, which are all integral to the process of dendritic cells mobilization, migration and functional maturation. Moreover, emerging evidence correlates ROS to changes in the constitution of the extracellular microenvironment found to facilitate ACD. The purpose of this review is to provide both conceptual and technical frameworks on the role of oxidative stress in chemical allergy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Basolateral potassium (IKCa) channel inhibition prevents increased colonic permeability induced by chemical hypoxia.

    PubMed

    Loganathan, A; Linley, J E; Rajput, I; Hunter, M; Lodge, J P A; Sandle, G I

    2011-01-01

    Major liver resection is associated with impaired intestinal perfusion and intestinal ischemia, resulting in decreased mucosal integrity, increased bacterial translocation, and an increased risk of postoperative sepsis. However, the mechanism by which ischemia impairs intestinal mucosal integrity is unclear. We therefore evaluated the role of Ca(2+)-sensitive, intermediate-conductance (IK(Ca)) basolateral potassium channels in enhanced intestinal permeability secondary to chemical hypoxia. The effects of chemical hypoxia induced by 100 μM dinitrophenol (DNP) and 5 mM deoxyglucose (DG) on basolateral IK(Ca) channel activity and whole cell conductance in intact human colonic crypts, and paracellular permeability (G(S)) in isolated colonic sheets, were determined by patch-clamp recording and transepithelial electrical measurements, respectively. DNP and DG rapidly stimulated IK(Ca) channels in cell-attached basolateral membrane patches and elicited a twofold increase (P = 0.004) in whole cell conductance in amphotericin B-permeabilized membrane patches, changes that were inhibited by the specific IK(Ca) channel blockers TRAM-34 (100 nM) and clotrimazole (CLT; 10 μM). In colonic sheets apically permeabilized with nystatin, DNP elicited a twofold increase (P = 0.005) in G(S), which was largely inhibited by the serosal addition of 50 μM CLT. We conclude that, in intestinal epithelia, chemical hypoxia increases G(S) through a mechanism involving basolateral IK(Ca) channel activation. Basolateral IK(Ca) channel inhibition may prevent or limit increased intestinal permeability during liver surgery.

  13. Artificially induced polyploidization in Humulus lupulus L. and its effect on morphological and chemical traits

    PubMed Central

    Trojak-Goluch, Anna; Skomra, Urszula

    2013-01-01

    Chemically induced polyploids were obtained by the colchicine treatment of shoot tips of Humulus lupulus L. ‘Sybilla’. Flow cytometry revealed that most of the treatments resulted in the production of tetraploids. The highest number of tetraploids was obtained when explants were immersed in 0.05% colchicine for 48 h. A field experiment was conducted to compare diploid and tetraploid plants and assess the effect of genome polyploidization on the morphological and chemical characteristics. Tetraploids showed significant differences in relation to diploids. They had thinner and shorter shoots. The influence of chromosome doubling was also reflected in the length, width and area of leaves. The length of female flowers in the tetraploids was significantly shorter than that observed in diploids. Tetraploids produced a diverse number of lupuline glands that were almost twice as large as those observed in diploids. The most distinct effect of genome polyploidization was a significant increase in the weight of cones and spindles. Contents of major chemical constituents of hop cones was little affected by ploidy level. Total essential oils were significantly lower than those in diploids. However there was a significant increase in the proportion of humulene, caryophyllene and farnesene, oils desired by the brewing industry. PMID:24399911

  14. Artificially induced polyploidization in Humulus lupulus L. and its effect on morphological and chemical traits.

    PubMed

    Trojak-Goluch, Anna; Skomra, Urszula

    2013-12-01

    Chemically induced polyploids were obtained by the colchicine treatment of shoot tips of Humulus lupulus L. 'Sybilla'. Flow cytometry revealed that most of the treatments resulted in the production of tetraploids. The highest number of tetraploids was obtained when explants were immersed in 0.05% colchicine for 48 h. A field experiment was conducted to compare diploid and tetraploid plants and assess the effect of genome polyploidization on the morphological and chemical characteristics. Tetraploids showed significant differences in relation to diploids. They had thinner and shorter shoots. The influence of chromosome doubling was also reflected in the length, width and area of leaves. The length of female flowers in the tetraploids was significantly shorter than that observed in diploids. Tetraploids produced a diverse number of lupuline glands that were almost twice as large as those observed in diploids. The most distinct effect of genome polyploidization was a significant increase in the weight of cones and spindles. Contents of major chemical constituents of hop cones was little affected by ploidy level. Total essential oils were significantly lower than those in diploids. However there was a significant increase in the proportion of humulene, caryophyllene and farnesene, oils desired by the brewing industry.

  15. Causal inference in obesity research.

    PubMed

    Franks, P W; Atabaki-Pasdar, N

    2017-03-01

    Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance, bias and confounding. Even data on the protective effects of weight loss from randomized controlled trials will be susceptible to confounding and bias if treatment assignment cannot be masked, which is usually the case with lifestyle and surgical interventions. Thus, whilst obesity is widely considered the major modifiable risk factor for many chronic diseases, its causes and consequences are often difficult to determine. Addressing this is important, as the prevention and treatment of any disease requires that interventions focus on causal risk factors. Disease prediction, although not dependent on knowing the causes, is nevertheless enhanced by such knowledge. Here, we provide an overview of some of the barriers to causal inference in obesity research and discuss analytical approaches, such as Mendelian randomization, that can help to overcome these obstacles. In a systematic review of the literature in this field, we found: (i) probable causal relationships between adiposity and bone health/disease, cancers (colorectal, lung and kidney cancers), cardiometabolic traits (blood pressure, fasting insulin, inflammatory markers and lipids), uric acid concentrations, coronary heart disease and venous thrombosis (in the presence of pulmonary embolism), (ii) possible causal relationships between adiposity and gray matter volume, depression and common mental disorders, oesophageal cancer, macroalbuminuria, end-stage renal disease, diabetic kidney disease, nuclear cataract and gall stone disease, and (iii) no evidence for causal relationships between adiposity and Alzheimer's disease, pancreatic cancer, venous thrombosis (in the absence of pulmonary embolism), liver function and periodontitis. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  16. Chemically induced enucleation of activated bovine oocytes: chromatin and microtubule organization and production of viable cytoplasts.

    PubMed

    Saraiva, Naiara Zoccal; Oliveira, Clara Slade; Leal, Cláudia Lima Verde; de Lima, Marina Ragagnin; Del Collado, Maite; Vantini, Roberta; Monteiro, Fabio Morato; Niciura, Simone Cristina Méo; Garcia, Joaquim Mansano

    2015-12-01

    As the standard enucleation method in mammalian nuclear transfer is invasive and damaging to cytoplast spatial organization, alternative procedures have been developed over recent years. Among these techniques, chemically induced enucleation (IE) is especially interesting because it does not employ ultraviolet light and reduces the amount of cytoplasm eliminated during the procedure. The objective of this study was to optimize the culture conditions with demecolcine of pre-activated bovine oocytes for chemically IE, and to evaluate nuclear and microtubule organization in cytoplasts obtained by this technique and their viability. In the first experiment, a negative effect on oocyte activation was verified when demecolcine was added at the beginning of the process, reducing activation rates by approximately 30%. This effect was not observed when demecolcine was added to the medium after 1.5 h of activation. In the second experiment, although a reduction in the number of microtubules was observed in most oocytes, these structures did not disappear completely during assessment. Approximately 50% of treated oocytes presented microtubule reduction at the end of the evaluation period, while 23% of oocytes were observed to exhibit the complete disappearance of these structures and 28% exhibited visible microtubules. These findings indicated the lack of immediate microtubule repolymerization after culture in demecolcine-free medium, a fact that may negatively influence embryonic development. However, cleavage rates of 63.6-70.0% and blastocyst yield of 15.5-24.2% were obtained in the final experiment, without significant differences between techniques, indicating that chemically induced enucleation produces normal embryos.

  17. Influence of exothermic chemical reactions on laser-induced shock waves.

    PubMed

    Gottfried, Jennifer L

    2014-10-21

    Differences in the excitation of non-energetic and energetic residues with a 900 mJ, 6 ns laser pulse (1064 nm) have been investigated. Emission from the laser-induced plasma of energetic materials (e.g. triaminotrinitrobenzene [TATB], cyclotrimethylene trinitramine [RDX], and hexanitrohexaazaisowurtzitane [CL-20]) is significantly reduced compared to non-energetic materials (e.g. sugar, melamine, and l-glutamine). Expansion of the resulting laser-induced shock wave into the air above the sample surface was imaged on a microsecond timescale with a high-speed camera recording multiple frames from each laser shot; the excitation of energetic materials produces larger heat-affected zones in the surrounding atmosphere (facilitating deflagration of particles ejected from the sample surface), results in the formation of additional shock fronts, and generates faster external shock front velocities (>750 m s(-1)) compared to non-energetic materials (550-600 m s(-1)). Non-explosive materials that undergo exothermic chemical reactions in air at high temperatures such as ammonium nitrate and magnesium sulfate produce shock velocities which exceed those of the inert materials but are less than those generated by the exothermic reactions of explosive materials (650-700 m s(-1)). The most powerful explosives produced the highest shock velocities. A comparison to several existing shock models demonstrated that no single model describes the shock propagation for both non-energetic and energetic materials. The influence of the exothermic chemical reactions initiated by the pulsed laser on the velocity of the laser-induced shock waves has thus been demonstrated for the first time.

  18. Modeling Drug- and Chemical-Induced Hepatotoxicity with Systems Biology Approaches

    PubMed Central

    Bhattacharya, Sudin; Shoda, Lisl K.M.; Zhang, Qiang; Woods, Courtney G.; Howell, Brett A.; Siler, Scott Q.; Woodhead, Jeffrey L.; Yang, Yuching; McMullen, Patrick; Watkins, Paul B.; Andersen, Melvin E.

    2012-01-01

    We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of “toxicity pathways” is described in the context of the 2007 US National Academies of Science report, “Toxicity testing in the 21st Century: A Vision and A Strategy.” Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity) – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular “virtual tissue” model of the liver lobule that combines molecular circuits in individual hepatocytes with cell–cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the aryl hydrocarbon receptor toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsym™) to understand drug-induced liver injury (DILI), the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological

  19. Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms

    SciTech Connect

    Borek, C.; Ong, A.; Mason, H.; Donahue, L.; Biaglow, J.E.

    1986-03-01

    Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. The authors examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo(a)pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 ..mu..M Na/sup 2/SeO/sup 3/ (selenium) or with 7 ..mu..M ..cap alpha..-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by and alternate complementary mechanism.

  20. Characterization of Chemically Induced Liver Injuries Using Gene Co-Expression Modules

    PubMed Central

    Tawa, Gregory J.; AbdulHameed, Mohamed Diwan M.; Yu, Xueping; Kumar, Kamal; Ippolito, Danielle L.; Lewis, John A.; Stallings, Jonathan D.; Wallqvist, Anders

    2014-01-01

    Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules) specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1) known biochemical pathways associated with liver injuries and 2) clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20%) genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects. PMID:25226513

  1. A quantum chemical study of HOCl-induced transformations of carbamazepine.

    PubMed

    Tandarić, Tana; Vrček, Valerije; Šakić, Davor

    2016-11-22

    The antiepileptic drug carbamazepine (CBZ) is one of the most persistent pharmaceuticals in the environment. Its chemical fate is influenced by the type of wastewater treatment. This study sets out to determine the degradation mechanism and products in the reaction between CBZ and hypochlorous acid (HOCl), which is the main chlorinating species in water. In the search for the most feasible pathways of HOCl-induced transformations of CBZ, a quantum chemical approach was employed. Chlorination and epoxidation of CBZ are two initial, competitive processes that result in two key intermediates: N-chloramide and 10,11-epoxide. The calculated free energy barriers (ΔG) for these reactions are 105.7 and 95.7 kJ mol(-1) resp., which is in agreement with the experimental energy barrier of 98.2 kJ mol(-1). All transformation products detected in chlorination experiments were located by computational models, and the reaction mechanism underlying their formation was described in detail. Different computational methods (density functional and ab initio theory) were applied, and the double hybrid B2-PLYPD functional was found to be superior in terms of efficiency and accuracy. Of special interest are oxoiminostilbene and formylacridine, which are the final products in the degradation cascade. Their exceptional thermodynamic stability, as predicted by quantum chemical methods, suggests that these structures should be considered as recalcitrants in chlorinated waters. Fruitful interplay between computational models and experimental data proves that the quantum chemical approach can be used as a predictive tool in environmental degradation studies.

  2. Herbivore-induced chemical and molecular responses of the kelps Laminaria digitata and Lessonia spicata

    PubMed Central

    Ritter, Andrés; Cabioch, Léa; Brillet-Guéguen, Loraine; Corre, Erwan; Cosse, Audrey; Dartevelle, Laurence; Duruflé, Harold; Fasshauer, Carina; Goulitquer, Sophie; Thomas, François; Correa, Juan A.; Potin, Philippe; Faugeron, Sylvain; Leblanc, Catherine

    2017-01-01

    chemical and molecular responses in kelp species, showing similar inducible responses upon specialist herbivores in their respective ecosystems. PMID:28253346

  3. Analysing connectivity with Granger causality and dynamic causal modelling.

    PubMed

    Friston, Karl; Moran, Rosalyn; Seth, Anil K

    2013-04-01

    This review considers state-of-the-art analyses of functional integration in neuronal macrocircuits. We focus on detecting and estimating directed connectivity in neuronal networks using Granger causality (GC) and dynamic causal modelling (DCM). These approaches are considered in the context of functional segregation and integration and--within functional integration--the distinction between functional and effective connectivity. We review recent developments that have enjoyed a rapid uptake in the discovery and quantification of functional brain architectures. GC and DCM have distinct and complementary ambitions that are usefully considered in relation to the detection of functional connectivity and the identification of models of effective connectivity. We highlight the basic ideas upon which they are grounded, provide a comparative evaluation and point to some outstanding issues.

  4. Formaldehyde and leukemia: an improbable causal relationship.

    PubMed

    Cole, Philip; Axten, Charles

    2004-10-01

    Formaldehyde has been the subject of numerous toxicological and epidemiological investigations for almost 25 years. Though most toxicology studies have focused on the effects of the chemical on the nasal tract and respiratory system, epidemiology investigations have been more extensive evaluating the association between formaldehyde and cancers not only of the nasal cavities, nasopharynx, and lung, but also of the brain, prostate, pancreas, and hematopoietic system. Recently, three studies have been published which report on the possible association between exposure to formaldehyde and an increased incidence of leukemia, specifically myeloid leukemia. The article summarizes the results of these three studies, evaluates the evidence for causality based on recognized epidemiologic criteria, and provides an assessment that the association between formaldehyde and the increased incidence of leukemia reported in these studies is not plausible.

  5. Study of permeability changes induced by external stimuli on chemically modified electrodes

    NASA Astrophysics Data System (ADS)

    Perera, Dingiri Mudiyanselage Neluni T.

    This research was focused on understanding how external stimuli affect the permeability of the chemically modified electrodes, and how the materials used in modifying the working electrodes respond to the changes in the surface charge. We adopted a voltammetric type electrochemical sensor to investigate the permeability effects induced by pH and organic solvents. The working electrodes used in this research were chemically modified with thioctic acid self assembled monolayer (TA SAM), track etched polycarbonate membranes (TEPCM) and PS-b-PMMA nanoporous films (polystyrene-block-polymethylmethacrylate). We studied the permeability behavior of each of the material upon application of external stimuli. In chapter 3, the permeability changes induced by change in surface charge of thioctic acid SAM was investigated. The surface charge of the monolayer was tuned by changing pH of the medium, which resulted in decrease of redox current of a negatively charged marker due to deprotonation of the surface --COOH groups of TA SAM. Decrease in redox current reflected a decrease in the reaction rate, and by using closed form equations the effective rate constants at several pKa values were extracted. In chapter 4, permeability changes induced by pH in TEPCM were investigated. We assessed the surface charge of these membranes via cyclic voltammetry generated for neutral and charged redox molecules. Limiting current of charged markers were affected by the surface charge induced by pH, where as the redox current for the neutral marker was not affected. Experimental redox currents were larger than the theoretical current, indicating that redox molecules preferentially distributed in a surface layer on the nanopore. Organic solvent induced permeability changes of PS-b-PMMA nanoporous films were investigated via electrochemical impedance spectroscopy and AFM. Higher response of pore resistance in the presence of organic solvents indicated either swelling of the nanoporous film or

  6. Relating Granger causality to long-term causal effects.

    PubMed

    Smirnov, Dmitry A; Mokhov, Igor I

    2015-10-01

    In estimation of causal couplings between observed processes, it is important to characterize coupling roles at various time scales. The widely used Granger causality reflects short-term effects: it shows how strongly perturbations of a current state of one process affect near future states of another process, and it quantifies that via prediction improvement (PI) in autoregressive models. However, it is often more important to evaluate the effects of coupling on long-term statistics, e.g., to find out how strongly the presence of coupling changes the variance of a driven process as compared to an uncoupled case. No general relationships between Granger causality and such long-term effects are known. Here, we pose the problem of relating these two types of coupling characteristics, and we solve it for a class of stochastic systems. Namely, for overdamped linear oscillators, we rigorously derive that the above long-term effect is proportional to the short-term effects, with the proportionality coefficient depending on the prediction interval and relaxation times. We reveal that this coefficient is typically considerably greater than unity so that small normalized PI values may well correspond to quite large long-term effects of coupling. The applicability of the derived relationship to wider classes of systems, its limitations, and its value for further research are discussed. To give a real-world example, we analyze couplings between large-scale climatic processes related to sea surface temperature variations in equatorial Pacific and North Atlantic regions.

  7. Relating Granger causality to long-term causal effects

    NASA Astrophysics Data System (ADS)

    Smirnov, Dmitry A.; Mokhov, Igor I.

    2015-10-01

    In estimation of causal couplings between observed processes, it is important to characterize coupling roles at various time scales. The widely used Granger causality reflects short-term effects: it shows how strongly perturbations of a current state of one process affect near future states of another process, and it quantifies that via prediction improvement (PI) in autoregressive models. However, it is often more important to evaluate the effects of coupling on long-term statistics, e.g., to find out how strongly the presence of coupling changes the variance of a driven process as compared to an uncoupled case. No general relationships between Granger causality and such long-term effects are known. Here, we pose the problem of relating these two types of coupling characteristics, and we solve it for a class of stochastic systems. Namely, for overdamped linear oscillators, we rigorously derive that the above long-term effect is proportional to the short-term effects, with the proportionality coefficient depending on the prediction interval and relaxation times. We reveal that this coefficient is typically considerably greater than unity so that small normalized PI values may well correspond to quite large long-term effects of coupling. The applicability of the derived relationship to wider classes of systems, its limitations, and its value for further research are discussed. To give a real-world example, we analyze couplings between large-scale climatic processes related to sea surface temperature variations in equatorial Pacific and North Atlantic regions.

  8. Chemopreventive effect of a mixture of Chinese Herbs (antitumor B) on chemically induced oral carcinogenesis.

    PubMed

    Wang, Yian; Yao, Ruisheng; Gao, Song; Wen, Weidong; Du, Yinqiu; Szabo, Eva; Hu, Ming; Lubet, Ronald A; You, Ming

    2013-01-01

    In this study, we evaluated chemopreventive efficacy of Antitumor B, a Chinese herbal mixture of six plants (Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus arvensis L., Dictamnus dasycarpus, and Dioscorea bulbifera) on the development of 4-nitroquinoline-1-oxide (4NQO) induced oral squamous cell carcinomas in A/J mice. Antitumor B, delivered through diet, inhibited 4NQO-induced oral cancer development by 59.19%. The reduction of cell proliferation appears to be associated with efficacy of Antitumor B against 4NQO-induced oral cancer in A/J mice. The expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (Tyr1173) were down-regulated by Antitumor B. Tissue distribution of Antitumor B was determined using obacunone, matrine, and maackiain as marker chemicals. We found significant amounts of obacunone, matrine, and maackiain in the blood after 1-wk treatment. The concentrations of these three compounds did not increase further at 18  wk, suggesting that plasma concentrations had reached a steady-state level at 1  wk. There was no significant body weight loss and there was no other obvious sign of toxicity in Antitumor B-treated mice. These results suggest that Antitumor B is a promising agent for human oral cancer chemoprevention.

  9. Label free high throughput screening for apoptosis inducing chemicals using time-lapse microscopy signal processing.

    PubMed

    Aftab, Obaid; Nazir, Madiha; Fryknäs, Mårten; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

    2014-09-01

    Label free time-lapse microscopy has opened a new avenue to the study of time evolving events in living cells. When combined with automated image analysis it provides a powerful tool that enables automated large-scale spatiotemporal quantification at the cell population level. Very few attempts, however, have been reported regarding the design of image analysis algorithms dedicated to the detection of apoptotic cells in such time-lapse microscopy images. In particular, none of the reported attempts is based on sufficiently fast signal processing algorithms to enable large-scale detection of apoptosis within hours/days without access to high-end computers. Here we show that it is indeed possible to successfully detect chemically induced apoptosis by applying a two-dimensional linear matched filter tailored to the detection of objects with the typical features of an apoptotic cell in phase-contrast images. First a set of recorded computational detections of apoptosis was validated by comparison with apoptosis specific caspase activity readouts obtained via a fluorescence based assay. Then a large screen encompassing 2,866 drug like compounds was performed using the human colorectal carcinoma cell line HCT116. In addition to many well known inducers (positive controls) the screening resulted in the detection of two compounds here reported for the first time to induce apoptosis.

  10. Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

    PubMed

    Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes

    2006-08-01

    Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.' Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia and proposes criteria that can be used in the assessment for classification of substances which induce such effects. An overview of the primary and secondary effects of haemolytic anaemia which can occur in rodent repeated dose toxicity studies is given. A detailed analysis of the toxicological significance of such effects is then performed and correlated with the general classification criteria used for this endpoint. This review intends to give guidance when carrying out an assessment for classification for this endpoint and to allow for better transparency in the decision-making process on when to classify based on the presence of haemolytic anaemia in repeated dose toxicity studies. The extended classification criteria for haemolytic anaemia outlined in this review were accepted by the EU Commission Working Group on the Classification and Labelling of Dangerous Substances in September 2004.

  11. Effect of measurement noise on Granger causality

    NASA Astrophysics Data System (ADS)

    Nalatore, Hariharan; N, Sasikumar; Rangarajan, Govindan

    2014-12-01

    Most of the signals recorded in experiments are inevitably contaminated by measurement noise. Hence, it is important to understand the effect of such noise on estimating causal relations between such signals. A primary tool for estimating causality is Granger causality. Granger causality can be computed by modeling the signal using a bivariate autoregressive (AR) process. In this paper, we greatly extend the previous analysis of the effect of noise by considering a bivariate AR process of general order p . From this analysis, we analytically obtain the dependence of Granger causality on various noise-dependent system parameters. In particular, we show that measurement noise can lead to spurious Granger causality and can suppress true Granger causality. These results are verified numerically. Finally, we show how true causality can be recovered numerically using the Kalman expectation maximization algorithm.

  12. Effect of measurement noise on Granger causality.

    PubMed

    Nalatore, Hariharan; Sasikumar, N; Rangarajan, Govindan

    2014-12-01

    Most of the signals recorded in experiments are inevitably contaminated by measurement noise. Hence, it is important to understand the effect of such noise on estimating causal relations between such signals. A primary tool for estimating causality is Granger causality. Granger causality can be computed by modeling the signal using a bivariate autoregressive (AR) process. In this paper, we greatly extend the previous analysis of the effect of noise by considering a bivariate AR process of general order p. From this analysis, we analytically obtain the dependence of Granger causality on various noise-dependent system parameters. In particular, we show that measurement noise can lead to spurious Granger causality and can suppress true Granger causality. These results are verified numerically. Finally, we show how true causality can be recovered numerically using the Kalman expectation maximization algorithm.

  13. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

    SciTech Connect

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin; Jeong, Jae-Hoon; Kang, Seongman; Lim, Young-Bin

    2014-07-25

    Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  14. Persistent phosphorylation at specific H3 serine residues involved in chemical carcinogen-induced cell transformation.

    PubMed

    Zhu, Xiaonian; Li, Daochuan; Zhang, Zhengbao; Zhu, Wei; Li, Wenxue; Zhao, Jian; Xing, Xiumei; He, Zhini; Wang, Shan; Wang, Fangping; Ma, Lu; Bai, Qing; Zeng, Xiaowen; Li, Jie; Gao, Chen; Xiao, Yongmei; Wang, Qing; Chen, Liping; Chen, Wen

    2017-05-01

    Identification of aberrant histone H3 phosphorylation during chemical carcinogenesis will lead to a better understanding of the substantial roles of histone modifications in cancer development. To explore whether aberrant H3 phosphorylation contributes to chemical carcinogenesis, we examined the dynamic changes of H3 phosphorylation at various residues in chemical carcinogen-induced transformed human cells and human cancers. We found that histone H3 phosphorylation at Ser10 (p-H3S10) and Ser28 (p-H3S28) was upregulated by 1.5-4.8 folds and 2.1-4.3 folds, respectively in aflatoxin B1 -transformed hepatocytes L02 cells (L02RT-AFB1 ), benzo(a)pyrene-transformed HBE cells (HBERT-BaP), and coke oven emissions-transformed HBE cells (HBERT-COE). The ectopic expression of histone H3 mutant (H3S10A or H3S28A) in L02 cells led to the suppression of an anchorage-independent cell growth as well as tumor formation in immunodeficient mice. In addition, an enhanced p-H3S10 was found in 70.6% (24/34) of hepatocellular carcinoma (HCC), and 70.0% (21/30) of primary lung cancer, respectively. Notably, we found that expression of H3 carrying a mutant H3S10A or H3S28A conferred to cells the ability to maintain a denser chromatin and resistance to induction of DNA damage and carcinogen-induced cell transformation. Particularly, we showed that introduction of a mutant H3S10A abolished the bindings of p-H3S10 to the promoter of DNA repair genes, PARP1 and MLH1 upon AFB1 treatment. Furthermore, we revealed that PP2A was responsible for dephosphorylation of p-H3S10. Taken together, these results reveal a key role of persistent H3S10 or H3S28 phosphorylation in chemical carcinogenesis through regulating gene transcription of DNA damage response (DDR) genes. © 2017 Wiley Periodicals, Inc.

  15. Compact Representations of Extended Causal Models

    DTIC Science & Technology

    2012-10-01

    models. A number of authors have suggested that an adequate account of actual causation must appeal not only to causal structure , but also to...about both causal structure and normality. Extended causal models are potentially very complex. In this paper, we show how it is possible to achieve...causation must be sensitive to considerations of normality, as well as to causal structure . In (Halpern & Hitchcock, 2011), we suggest a way of

  16. Investigating lipids as a source of chemical exchange-induced MRI frequency shifts.

    PubMed

    Shmueli, K; Dodd, S J; van Gelderen, P; Duyn, J H

    2017-04-01

    While magnetic susceptibility is a major contributor to NMR resonance frequency variations in the human brain, a substantial contribution may come from the chemical exchange of protons between water and other molecules. Exchange-induced frequency shifts fe have been measured in tissue and protein solutions, but relatively lipid-rich white matter (WM) has a larger fe than gray matter, suggesting that lipids could contribute. Galactocerebrosides (GC) are a prime candidate as they are abundant in WM and susceptible to exchange. To investigate this, fe was measured in a model of WM lipid membranes in the form of multilamellar vesicles (MLVs), consisting of a 1:2 molar ratio of GC and phospholipids (POPC), and in MLVs with POPC only. Chemical shift imaging with 15% volume fraction of dioxane, an internal reference whose protons are assumed not to undergo chemical exchange, was used to remove susceptibility-induced frequency shifts in an attempt to measure fe in MLVs at several lipid concentrations. Initial analysis of these measurements indicated a necessity to correct for small unexpected variations in dioxane concentration due to its effect on the water frequency shift. To achieve this, the actual dioxane concentration was inferred from spectral analysis and its additional contribution to fe was removed through separate experiments which showed that the water-dioxane frequency shift depended linearly on the dioxane concentration at low concentrations with a proportionality constant of -0.021 ± 0.002 ppb/mM in agreement with published experiments. Contrary to expectations and uncorrected results, for GC + POPC vesicles, the dependence of the corrected fe on GC concentration was insignificant (0.023 ± 0.037 ppb/mM; r(2)  = 0.085, p > 0.57), whereas for the POPC-only vesicles a small but significant linear increase with POPC concentration was found: 0.044 ± 0.008 ppb/mM (r(2)  = 0.877, p < 0.01). These findings suggest that the

  17. Distinguishing time-delayed causal interactions using convergent cross mapping

    PubMed Central

    Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

    2015-01-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

  18. The latent causal chain of industrial water pollution in China.

    PubMed

    Miao, Xin; Tang, Yanhong; Wong, Christina W Y; Zang, Hongyu

    2015-01-01

    The purpose of this paper is to discover the latent causal chain of industrial water pollution in China and find ways to cure the want on discharge of toxic waste from industries. It draws evidences from the past pollution incidents in China. Through further digging the back interests and relations by analyzing representative cases, extended theory about loophole derivations and causal chain effect is drawn. This theoretical breakthrough reflects deeper causality. Institutional defect instead of human error is confirmed as the deeper reason of frequent outbreaks of water pollution incidents in China. Ways for collaborative environmental governance are proposed. This paper contributes to a better understanding about the deep inducements of industrial water pollution in China, and, is meaningful for ensuring future prevention and mitigation of environmental pollution. It illuminates multiple dimensions for collaborative environmental governance to cure the stubborn problem.

  19. Causal Anomalies in Kaluza-Klein Gravity Theories

    NASA Astrophysics Data System (ADS)

    Rebouças, M. J.; Teixeira, A. F. F.

    Causal anomalies in two Kaluza-Klein gravity theories are examined, particularly as to whether these theories permit solutions in which the causality principle is violated. It is found that similarly to general relativity the field equations of the space-time-mass Kaluza-Klein (STM-KK) gravity theory do not exclude violation of causality of Gödel type, whereas the induced matter Kaluza-Klein (IM-KK) gravity rules out noncausal Gödel-type models. The induced matter version of general relativity is shown to be an efficient therapy for causal anomalies that occurs in a wide class of noncausal geometries. Perfect fluid and dust Gödel-type solutions of the STM-KK field equations are studied. It is shown that every Gödel-type perfect fluid solution is isometric to the unique dust solution of the STM-KK field equations. The question as to whether 5D Gödel-type noncausal geometries induce any physically acceptable 4D energy-momentum tensor is also addressed.

  20. Designing Effective Supports for Causal Reasoning

    ERIC Educational Resources Information Center

    Jonassen, David H.; Ionas, Ioan Gelu

    2008-01-01

    Causal reasoning represents one of the most basic and important cognitive processes that underpin all higher-order activities, such as conceptual understanding and problem solving. Hume called causality the "cement of the universe" [Hume (1739/2000). Causal reasoning is required for making predictions, drawing implications and…

  1. Exploring Individual Differences in Preschoolers' Causal Stance

    ERIC Educational Resources Information Center

    Alvarez, Aubry; Booth, Amy E.

    2016-01-01

    Preschoolers, as a group, are highly attuned to causality, and this attunement is known to facilitate memory, learning, and problem solving. However, recent work reveals substantial individual variability in the strength of children's "causal stance," as demonstrated by their curiosity about and preference for new causal information. In…

  2. Towards an Algebra for Analyzing Causal Relations.

    ERIC Educational Resources Information Center

    Ellett, Frederick S., Jr.; Ericson, David P.

    Correlation-based approaches to causal analysis contain too much irrelevant information that masks and modulates the true nature of causal processes in the world. Both causal modeling and path analysis/structural equations give the wrong answers for certain conceptions of causation, given certain assumptions about the "error" variables.…

  3. Constraints on Children's Judgments of Magical Causality

    ERIC Educational Resources Information Center

    Woolley, Jacqueline D.; Browne, Cheryl A.; Boerger, Elizabeth A.

    2006-01-01

    In 3 studies we addressed the operation of constraints on children's causal judgments. Our primary focus was whether children's beliefs about magical causality, specifically wishing, are constrained by features that govern the attribution of ordinary causality. In Experiment 1, children witnessed situations in which a confederate's wish appeared…

  4. Representing Personal Determinants in Causal Structures.

    ERIC Educational Resources Information Center

    Bandura, Albert

    1984-01-01

    Responds to Staddon's critique of the author's earlier article and addresses issues raised by Staddon's (1984) alternative models of causality. The author argues that it is not the formalizability of causal processes that is the issue but whether cognitive determinants of behavior are reducible to past stimulus inputs in causal structures.…

  5. Designing Effective Supports for Causal Reasoning

    ERIC Educational Resources Information Center

    Jonassen, David H.; Ionas, Ioan Gelu

    2008-01-01

    Causal reasoning represents one of the most basic and important cognitive processes that underpin all higher-order activities, such as conceptual understanding and problem solving. Hume called causality the "cement of the universe" [Hume (1739/2000). Causal reasoning is required for making predictions, drawing implications and…

  6. Constraints on Children's Judgments of Magical Causality

    ERIC Educational Resources Information Center

    Woolley, Jacqueline D.; Browne, Cheryl A.; Boerger, Elizabeth A.

    2006-01-01

    In 3 studies we addressed the operation of constraints on children's causal judgments. Our primary focus was whether children's beliefs about magical causality, specifically wishing, are constrained by features that govern the attribution of ordinary causality. In Experiment 1, children witnessed situations in which a confederate's wish appeared…

  7. Causal inference in economics and marketing.

    PubMed

    Varian, Hal R

    2016-07-05

    This is an elementary introduction to causal inference in economics written for readers familiar with machine learning methods. The critical step in any causal analysis is estimating the counterfactual-a prediction of what would have happened in the absence of the treatment. The powerful techniques used in machine learning may be useful for developing better estimates of the counterfactual, potentially improving causal inference.

  8. Expectations and Interpretations during Causal Learning

    ERIC Educational Resources Information Center

    Luhmann, Christian C.; Ahn, Woo-kyoung

    2011-01-01

    In existing models of causal induction, 4 types of covariation information (i.e., presence/absence of an event followed by presence/absence of another event) always exert identical influences on causal strength judgments (e.g., joint presence of events always suggests a generative causal relationship). In contrast, we suggest that, due to…

  9. Expectations and Interpretations During Causal Learning

    PubMed Central

    Luhmann, Christian C.; Ahn, Woo-kyoung

    2012-01-01

    In existing models of causal induction, 4 types of covariation information (i.e., presence/absence of an event followed by presence/absence of another event) always exert identical influences on causal strength judgments (e.g., joint presence of events always suggests a generative causal relationship). In contrast, we suggest that, due to expectations developed during causal learning, learners give varied interpretations to covariation information as it is encountered and that these interpretations influence the resulting causal beliefs. In Experiments 1A–1C, participants’ interpretations of observations during a causal learning task were dynamic, expectation based, and, furthermore, strongly tied to subsequent causal judgments. Experiment 2 demonstrated that adding trials of joint absence or joint presence of events, whose roles have been traditionally interpreted as increasing causal strengths, could result in decreased overall causal judgments and that adding trials where one event occurs in the absence of another, whose roles have been traditionally interpreted as decreasing causal strengths, could result in increased overall causal judgments. We discuss implications for traditional models of causal learning and how a more top-down approach (e.g., Bayesian) would be more compatible with the current findings. PMID:21534705

  10. Considerations on causality in pharmacovigilance.

    PubMed

    Edwards, I Ralph

    2012-01-01

    Causality has been a topic of debate by philosophers, scientists, lawyers and for centuries. It is essential to define as precisely as possible all steps in the logical chain of events, since each may strengthen or confound an argument. Almost always there are issues of missing and conflicting data that need to be addressed specifically. In pharmacovigilance, as in many other situations, there is not just one possible causation for an effect but several. Each must be evaluated in the given context for probability. There is also likely to be a causal chain of events to the adverse effect under consideration, and each must be considered. In an individual patient diagnosis the components of patient history, clinical findings and various laboratory test findings are combined to point to the probability of the patho-physiological diagnosis, which in turn is related to possible causes with a strength determined by the constellation of findings. The established Bradford-Hill criteria are valuable in considering all the possible causal factors. Pharmacoepidemiology allows for population incidences of causes for particular effects and therefore provides an a priori probability listing for competing possible causes, or at least of one possible cause against the background of all others in a control group. Since adverse effects of medicines are generally rare, it is not possible to exclude drug causation in an individual by reliance on epidemiological evidence alone, only to argue that the incidence is below a level determined by statistical power, of the study or studies combined. Other areas of society are concerned with the process of causal inference, and this is especially true in legal cases in which judgements are made on possible personal injury by drugs.

  11. An Introduction to Causal Inference

    DTIC Science & Technology

    2009-11-02

    University of California, Los Angeles,Computer Science Department,Los Angeles,CA,90095-1596 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...University of California, Los Angeles Computer Science Department Los Angeles, CA, 90095-1596, USA judea@cs.ucla.edu September 30, 2009 Abstract This paper...Introduction The questions that motivate most studies in the health, social and behavioral sciences are not associational but causal in nature. For example

  12. Two roads to noncommutative causality

    NASA Astrophysics Data System (ADS)

    Besnard, Fabien

    2015-08-01

    We review the physical motivations and the mathematical results obtained so far in the isocone-based approach to noncommutative causality. We also give a briefer account of the alternative framework of Franco and Eckstein which is based on Lorentzian spectral triples. We compare the two theories on the simple example of the product geometry of the Minkowski plane by the finite noncommutative space with algebra M2(C).

  13. THE CAUSAL ANALYSIS / DIAGNOSIS DECISION ...

    EPA Pesticide Factsheets

    CADDIS is an on-line decision support system that helps investigators in the regions, states and tribes find, access, organize, use and share information to produce causal evaluations in aquatic systems. It is based on the US EPA's Stressor Identification process which is a formal method for identifying causes of impairments in aquatic systems. CADDIS 2007 increases access to relevant information useful for causal analysis and provides methods and tools that practitioners can use to analyze their own data. The new Candidate Cause section provides overviews of commonly encountered causes of impairments to aquatic systems: metals, sediments, nutrients, flow alteration, temperature, ionic strength, and low dissolved oxygen. CADDIS includes new Conceptual Models that illustrate the relationships from sources to stressors to biological effects. An Interactive Conceptual Model for phosphorus links the diagram with supporting literature citations. The new Analyzing Data section helps practitioners analyze their data sets and interpret and use those results as evidence within the USEPA causal assessment process. Downloadable tools include a graphical user interface statistical package (CADStat), and programs for use with the freeware R statistical package, and a Microsoft Excel template. These tools can be used to quantify associations between causes and biological impairments using innovative methods such as species-sensitivity distributions, biological inferenc

  14. Modeling of causality with metamaterials

    NASA Astrophysics Data System (ADS)

    Smolyaninov, Igor I.

    2013-02-01

    Hyperbolic metamaterials may be used to model a 2 + 1-dimensional Minkowski space-time in which the role of time is played by one of the spatial coordinates. When a metamaterial is built and illuminated with a coherent extraordinary laser beam, the stationary pattern of light propagation inside the metamaterial may be treated as a collection of particle world lines, which represents a complete ‘history’ of this 2 + 1-dimensional space-time. While this model may be used to build interesting space-time analogs, such as metamaterial ‘black holes’ and a metamaterial ‘big bang’, it lacks causality: since light inside the metamaterial may propagate back and forth along the ‘timelike’ spatial coordinate, events in the ‘future’ may affect events in the ‘past’. Here we demonstrate that a more sophisticated metamaterial model may fix this deficiency via breaking the mirror and temporal (PT) symmetries of the original model and producing one-way propagation along the ‘timelike’ spatial coordinate. The resulting 2 + 1-dimensional Minkowski space-time appears to be causal. This scenario may be considered as a metamaterial model of the Wheeler-Feynman absorber theory of causality.

  15. THE CAUSAL ANALYSIS / DIAGNOSIS DECISION ...

    EPA Pesticide Factsheets

    CADDIS is an on-line decision support system that helps investigators in the regions, states and tribes find, access, organize, use and share information to produce causal evaluations in aquatic systems. It is based on the US EPA's Stressor Identification process which is a formal method for identifying causes of impairments in aquatic systems. CADDIS 2007 increases access to relevant information useful for causal analysis and provides methods and tools that practitioners can use to analyze their own data. The new Candidate Cause section provides overviews of commonly encountered causes of impairments to aquatic systems: metals, sediments, nutrients, flow alteration, temperature, ionic strength, and low dissolved oxygen. CADDIS includes new Conceptual Models that illustrate the relationships from sources to stressors to biological effects. An Interactive Conceptual Model for phosphorus links the diagram with supporting literature citations. The new Analyzing Data section helps practitioners analyze their data sets and interpret and use those results as evidence within the USEPA causal assessment process. Downloadable tools include a graphical user interface statistical package (CADStat), and programs for use with the freeware R statistical package, and a Microsoft Excel template. These tools can be used to quantify associations between causes and biological impairments using innovative methods such as species-sensitivity distributions, biological inferenc

  16. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    PubMed

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  17. Substrate induced modulation of electronic, magnetic and chemical properties of MoSe{sub 2} monolayer

    SciTech Connect

    Wasey, A. H. M. Abdul; Chakrabarty, Soubhik; Das, G. P.

    2014-04-15

    Monolayer of MoSe{sub 2}, having a typical direct band gap of ∼1.5 eV, is a promising material for optoelectronic and solar cell applications. When this 2D semiconductor is supported on transition metal substrates, such as Ni(111) and Cu(111), its electronic structure gets modulated. First principles density functional investigation shows the appearance of de-localized mid-gap states in the density of states. The work function of the semiconductor overlayer gets modified considerably, indicating n-type doping caused by the metal contacts. The charge transfer across the metal-semiconductor junction also significantly enhances the chemical reactivity of the MoSe{sub 2} overlayer, as observed by Hydrogen absorption. Furthermore, for Ni contact, there is a signature of induced magnetism in MoSe{sub 2} monolayer.

  18. High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation

    PubMed Central

    Sim, Kyoseung; Chen, Song; Li, Yuhang; Kammoun, Mejdi; Peng, Yun; Xu, Minwei; Gao, Yang; Song, Jizhou; Zhang, Yingchun; Ardebili, Haleh; Yu, Cunjiang

    2015-01-01

    Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated. PMID:26553110

  19. Decomposition of gaseous organic contaminants by surface discharge induced plasma chemical processing -- SPCP

    SciTech Connect

    Oda, Tetsuji; Yamashita, Ryuichi; Haga, Ichiro; Takahashi, Tadashi; Masuda, Senichi

    1996-01-01

    The decomposition performance of the surface induced plasma chemical processing (SPCP) for chlorofluorocarbon (83 ppm CFC-113 in air), acetone, trichloroethylene, and isopropylalcohol was experimentally examined. In every case, very high decomposition performance, more than 90 or 99% removal rate, is realized when the residence time is about 1 second and the input electric power for a 16 cm{sup 3} reactor is about 10 W. Acetone is the most stable compound and alcohol is most easily decomposed. The decomposed product-analysis by a GasChromato-MassSpectrometer has just started but very poor results are obtained. In fact, some portion of the isopropylalcohol may change to acetone which is worse than alcohol. The necessary energy to decompose one mol gas diluted in the air is calculated form the experiments. The necessary energy level for acetone and trichloroethylene is about one-tenth or one-fiftieth of that for chlorofluorocarbon.

  20. Elucidating chemical and morphological changes in tetrachloroauric solutions induced by X-ray photochemical reaction.

    PubMed

    Ma, Qing; Divan, Ralu; Mancini, Derrick C; Keane, Denis T

    2008-05-22

    Chemical and morphological changes induced by an X-ray photochemical reaction in tetrachloroauric solutions leading to Au(3+)-to-Au(0) reduction are monitored in real time by X-ray absorption spectroscopy and X-ray small angle scattering. Prior to metal precipitation, the intermediate state, also observed by other techniques, is unambiguously determined for the first time to be the reduction of Au(3+) to Au(1+), whose kinetics is strictly of the zeroth order. The morphological changes occur simultaneously in the solutions, that is, the gold complexes rearrange and aggregate, as unequivocally observed by the correlated changes in the Au L(3) emission and small angle scattering intensities. The experimental evidence indicates that the eventual metal precipitation is strongly influenced by the changing solution acidity under X-ray irradiation. Detailed local structure changes are also described.

  1. High Fidelity Tape Transfer Printing Based On Chemically Induced Adhesive Strength Modulation

    NASA Astrophysics Data System (ADS)

    Sim, Kyoseung; Chen, Song; Li, Yuhang; Kammoun, Mejdi; Peng, Yun; Xu, Minwei; Gao, Yang; Song, Jizhou; Zhang, Yingchun; Ardebili, Haleh; Yu, Cunjiang

    2015-11-01

    Transfer printing, a two-step process (i.e. picking up and printing) for heterogeneous integration, has been widely exploited for the fabrication of functional electronics system. To ensure a reliable process, strong adhesion for picking up and weak or no adhesion for printing are required. However, it is challenging to meet the requirements of switchable stamp adhesion. Here we introduce a simple, high fidelity process, namely tape transfer printing(TTP), enabled by chemically induced dramatic modulation in tape adhesive strength. We describe the working mechanism of the adhesion modulation that governs this process and demonstrate the method by high fidelity tape transfer printing several types of materials and devices, including Si pellets arrays, photodetector arrays, and electromyography (EMG) sensors, from their preparation substrates to various alien substrates. High fidelity tape transfer printing of components onto curvilinear surfaces is also illustrated.

  2. Heuristic model of chemically induced electron spin polarization in two dimensions

    NASA Astrophysics Data System (ADS)

    Adrian, Frank J.

    2010-11-01

    A heuristic model of chemically induced electron spin polarization (CIDEP) that breaks the polarization mechanism into its component steps, with each step governed by an appropriate solution of the diffusion equation, is extended from a three to a two-dimensional system. The required solution of the 2D diffusion equation is provided by a relatively simple analytic approximation to the usual infinite series solution. The model yields the polarization and its time development for weak to strong singlet-triplet mixing in the radical pairs, whereas previous models are limited to very weak or very strong mixing. Its results agree with a variational solution of an integral equation of Monchick and are encouraging for observation of CIDEP in dimensionally restricted systems. The method also may be applicable to other diffusion-controlled, spin-dependent chemistry in spatially restricted environments.

  3. Light induced chemical vapour deposition of titanium oxide thin films at room temperature

    NASA Astrophysics Data System (ADS)

    Halary, E.; Benvenuti, G.; Wagner, F.; Hoffmann, P.

    2000-02-01

    High resolution patterned deposition of titania is achieved by light induced chemical vapour deposition (LICVD), by imaging a mask onto a glass substrate. A long pulse XeCl Excimer laser (308 nm) provides, by perpendicular irradiation, the energy to convert titanium tetraisopropoxide (TTIP) vapour into titanium dioxide films, in an oxygen atmosphere, on unheated glass substrates. The amorphous titania deposits contain about 6% carbon contamination according to X-ray photoelectron spectroscopy (XPS) measurements. The deposition rate increases with increasing laser fluence until a maximum value is reached, then remains constant over a wide range, and finally decreases with further fluence increase due to titania ablation or thermal effects. The film thickness increases linearly with the number of pulses after a nucleation period. The strong influence of the laser pulse repetition rate on the growth rate and the thickness profile are reported.

  4. Effect of silicon resistivity on its porosification using metal induced chemical etching: morphology and photoluminescence studies

    NASA Astrophysics Data System (ADS)

    Saxena, Shailendra K.; Sahu, Gayatri; Kumar, Vivek; Sahoo, P. K.; Sagdeo, Pankaj R.; Kumar, Rajesh

    2015-03-01

    The structure and light-emitting properties of porous Si nanowires (Si NWs) fabricated by metal induced chemical etching (MIE) process on two different Si substrates of different resistivities have been investigated here. The surface morphological studies have been carried out using scanning electron microscopy. It is observed that porous Si containing well aligned Si NWs is formed from high resistivity (1-20 Ωcm) Si wafer, whereas interconnected pores or cheese-like structures are formed from low resistivity (0.2 Ωcm) Si wafers after MIE. An explanation for the different porosification processes has been proposed based on the initial doping level, where number of dopants seems to be playing an important role in the etching process. Visible photoluminescence (PL) has been observed from all the porous Si samples, that are attributed due to quantum confinement effect.

  5. Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier.

    PubMed

    Lin, Yu-Chun; Niewiadomski, Pawel; Lin, Benjamin; Nakamura, Hideki; Phua, Siew Cheng; Jiao, John; Levchenko, Andre; Inoue, Takafumi; Rohatgi, Rajat; Inoue, Takanari

    2013-07-01

    Primary cilia function as specialized compartments for signal transduction. The stereotyped structure and signaling function of cilia inextricably depend on the selective segregation of molecules in cilia. However, the fundamental principles governing the access of soluble proteins to primary cilia remain unresolved. We developed a methodology termed 'chemically inducible diffusion trap at cilia' to visualize the diffusion process of a series of fluorescent proteins ranging in size from 3.2 nm to 7.9 nm into primary cilia. We found that the interior of the cilium was accessible to proteins as large as 7.9 nm. The kinetics of ciliary accumulation of this panel of proteins was exponentially limited by their Stokes radii. Quantitative modeling suggests that the diffusion barrier operates as a molecular sieve at the base of cilia. Our study presents a set of powerful, generally applicable tools for the quantitative monitoring of ciliary protein diffusion under both physiological and pathological conditions.

  6. Chemical carcinogen-induced decreases in genomic 5-methyldeoxycytidine content of normal human bronchial epithelial cells

    SciTech Connect

    Wilson, V.L.; Smith, R.A.; Longoria, J.; Liotta, M.A.; Harper, C.M.; Harris, C.C.

    1987-05-01

    The genomic content of DNA 5-methyldeoxycytidine (m/sup 5/dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m/sup 5/dC content whereas the weakly carcinogenic and noncarcinogenic agents, benzo(e)pyrene and phenanthrene (respectively), did not. These reductions varied from 8% to 31% depending on the agent and the donor cells. The reduction is genomic m/sup 5/dC levels were concentration dependent for the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene. The authors speculate that carcinogen-induced perturbation of DNA m/sup 5/dC patterns may lead to heritable changes in gene expression and contribute to the molecular alterations involved in the initiation and the subsequent steps of the carcinogenesis process.

  7. Critical role of surface chemical modifications induced by length shortening on multi-walled carbon nanotubes-induced toxicity

    PubMed Central

    2012-01-01

    Given the increasing use of carbon nanotubes (CNT) in composite materials and their possible expansion to new areas such as nanomedicine which will both lead to higher human exposure, a better understanding of their potential to cause adverse effects on human health is needed. Like other nanomaterials, the biological reactivity and toxicity of CNT were shown to depend on various physicochemical characteristics, and length has been suggested to play a critical role. We therefore designed a comprehensive study that aimed at comparing the effects on murine macrophages of two samples of multi-walled CNT (MWCNT) specifically synthesized following a similar production process (aerosol-assisted CVD), and used a soft ultrasonic treatment in water to modify the length of one of them. We showed that modification of the length of MWCNT leads, unavoidably, to accompanying structural (i.e. defects) and chemical (i.e. oxidation) modifications that affect both surface and residual catalyst iron nanoparticle content of CNT. The biological response of murine macrophages to the two different MWCNT samples was evaluated in terms of cell viability, pro-inflammatory cytokines secretion and oxidative stress. We showed that structural defects and oxidation both induced by the length reduction process are at least as responsible as the length reduction itself for the enhanced pro-inflammatory and pro-oxidative response observed with short (oxidized) compared to long (pristine) MWCNT. In conclusion, our results stress that surface properties should be considered, alongside the length, as essential parameters in CNT-induced inflammation, especially when dealing with a safe design of CNT, for application in nanomedicine for example. PMID:23181604

  8. Chemically induced hepatotoxicity in human stem cell-induced hepatocytes compared with primary hepatocytes and HepG2.

    PubMed

    Kang, Seok-Jin; Lee, Hyuk-Mi; Park, Young-Il; Yi, Hee; Lee, Hunjoo; So, ByungJae; Song, Jae-Young; Kang, Hwan-Goo

    2016-10-01

    Stem cell-induced hepatocytes (SC-iHeps) have been suggested as a valuable model for evaluating drug toxicology. Here, human-induced pluripotent stem cells (QIA7) and embryonic stem cells (WA01) were differentiated into hepatocytes, and the hepatotoxic effects of acetaminophen (AAP) and aflatoxin B1 (AFB1) were compared with primary hepatocytes (p-Heps) and HepG2. In a cytotoxicity assay, the IC50 of SC-iHeps was similar to that in p-Heps and HepG2 in the AAP groups but different from that in p-Heps of the AFB1 groups. In a multi-parameter assay, phenotypic changes in mitochondrial membrane potential, calcium influx and oxidative stress were similar between QIA7-iHeps and p-Heps following AAP and AFB1 treatment but relatively low in WA01-iHeps and HepG2. Most hepatic functional markers (hepatocyte-specific genes, albumin/urea secretion, and the CYP450 enzyme activity) were decreased in a dose-dependent manner following AAP and AFB1 treatment in SC-iHeps and p-Heps but not in HepG2. Regarding CYP450 inhibition, the cell viability of SC-iHeps and p-Heps was increased by ketoconazole, a CYP3A4 inhibitor. Collectively, SC-iHeps and p-Heps showed similar cytotoxicity and hepatocyte functional effects for AAP and AFB1 compared with HepG2. Therefore, SC-iHeps have phenotypic characteristics and sensitivity to cytotoxic chemicals that are more similar to p-Heps than to HepG2 cells.

  9. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation—A Chemical Approach

    PubMed Central

    Genaro-Mattos, Thiago C.; Maurício, Ângelo Q.; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here—in association with its reported signaling effects—could be an explanation to its beneficial effects

  10. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    PubMed

    Genaro-Mattos, Thiago C; Maurício, Ângelo Q; Rettori, Daniel; Alonso, Antonio; Hermes-Lima, Marcelo

    2015-01-01

    Caffeic acid (CA) is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR) oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its beneficial effects

  11. Evolution of color vision loss induced by occupational exposure to chemicals.

    PubMed

    Gobba, F; Cavalleri, A

    2000-10-01

    The evolution of occupationally induced color vision loss was studied in workers exposed to various chemicals. Exposure was evaluated by biological monitoring or personal air samplers, and color vision using the Lanthony D-15 desaturated panel (D-15 d). The effect of short-term interruption of exposure was studied in 39 Styrene (St) exposed workers: at a first examination a dose-related color vision loss was disclosed; a re-test performed after one month's interruption of exposure did not show any improvement of the effect. The evolution during longer periods was studied in another group of 30 St workers. Exposure and color vision were evaluated, then a follow-up was done 12 months later: the exposure was unmodified or slightly decreased in 20 subjects, and D-15 d outcomes remained unchanged, while St levels had increased and color vision loss progressed in the other 10. Similar results were obtained in 33 PCE exposed dry-cleaners: no change in color perception was observed in 14 workers whose exposure decreased, while in the other 19 a rise in PCE levels was followed by a significant color vision worsening. In 21 Hg exposed workers whose mean urinary excretion of Hg was threefold the BEI proposed by ACGIH, a dose-related impairment in color perception was observed. 12 months after a marked reduction of exposure, an almost complete recovery of the impairment was observed. Our data show that an increase in exposure can induce a worsening in color vision loss. A short interruption in exposure did not reduce the effect. A more prolonged reduction of dose reversed color vision loss in Hg exposed workers, while in solvent-exposed individuals the progression deserves further evaluation. D-15 d proved a useful test for studies on the evolution of color perception in workers exposed to eye-toxic chemicals.

  12. Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.

    PubMed

    Xia, Tian; Korge, Paavo; Weiss, James N; Li, Ning; Venkatesen, M Indira; Sioutas, Constantinos; Nel, Andre

    2004-10-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .- generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than the particles themselves.

  13. Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity

    PubMed Central

    Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

    2004-01-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•− generation, decrease of membrane potential (ΔΨm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ΔΨm at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ΔΨm at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ΔΨm are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

  14. DNA damage induced by occupational and environmental exposure to miscellaneous chemicals.

    PubMed

    da Silva, Juliana

    Epidemiological studies for hazardous situations resulting from the risk of environmental and/or occupational exposure to miscellaneous chemicals present several difficulties. Biomonitoring of human populations can provide an early detection system for the initiation of cell dysregulation in the development of cancer, which would help develop an efficient prevention program. Recently, the cytokinesis-block micronucleus (CBMN) assay in lymphocyte cells has become an important tool for assessing DNA damage in exposed populations. This is the method of choice for population-based studies of occupational and/or environmental exposure to different agents. In this review, human populations exposed to coal, dyes, paints, organic solvents in a complex mixture, and others miscellaneous chemicals were analyzed. Data from 28 studies was evaluated in relation to the effect of complex mixture exposition on micronucleus (MN) frequency. Other biomarkers and the background factors were evaluated as well, such as gender, age, or smoking habit. Most of these studies (75%) showed a significant increase of micronucleated cells to exposed groups in relation to the control groups, besides chromosomal aberrations (CA), sister chromatid exchanging (SCE) and comet cells (comet assay). The studies from this review about miscellaneous chemicals exposures using CBMN assay have indicated some time and dose-dependent effects. Overall, the findings suggest that the responses resulting from exposure to complex mixtures are varied and complicated. However, they are also an important mechanism of DNA damage concerning disruption of metal ion homeostasis that may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently could induce cancer.

  15. Protection of PC12 cells from chemical ischemia induced oxidative stress by Fagonia arabica.

    PubMed

    Satpute, Ravindra M; Kashyap, Rajpal S; Deopujari, Jayant Y; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F

    2009-11-01

    Fagonia arabica (Zygophyllaceae) is an important Ayurvedic herb, grows throughout arid regions of India, has been widely used as a folk remedy by the indigenous people for its anti-inflammatory, analgesic and antipyretic effects. In the present study, antioxidant potential of F. arabica and the associated mechanism of antioxidant defence in rat pheochromocytoma (PC12) cells subjected to chemical ischemia was studied. Effect of total extract of F. arabica was studied for its antioxidant potential on the chemical ischemia induced PC12 cells. Alterations in the activities of cellular antioxidant enzymes (SOD, CAT, GSH-Px and GSH-R) were measured. Antioxidant potential of herb (ABTS), extent of lipid peroxidation (MDA and 4-HAE), total antioxidant status (TAS) and total glutathione (reduced, oxidized and their ratio) were evaluated. F. arabica scavenges the free radicals (ABTS(.)+), and showed a concentration dependent antioxidant activity, highest being at 1000 microg/ml. Its treatment with ischemic cells ameliorates the GSH and TAS levels and also helps the cells to restore the activities of the cellular antioxidative enzymes and also reduced the degree of lipid peroxidation. F. arabica scavenges the free radicals and attenuates oxidative stress mediated cell injury during ischemia.

  16. Chemical and explosive detection with long-wave infrared laser induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Jin, Feng; Trivedi, Sudhir B.; Yang, Clayton S.; Brown, Ei E.; Kumi-Barimah, Eric; Hommerich, Uwe H.; Samuels, Alan C.

    2016-05-01

    Conventional laser induced breakdown spectroscopy (LIBS) mostly uses silicon-based detectors and measures the atomic emission in the UV-Vis-NIR (UVN) region of the spectrum. It can be used to detect the elements in the sample under test, such as the presence of lead in the solder for electronics during RoHS compliance verification. This wavelength region, however, does not provide sufficient information on the bonding between the elements, because the molecular vibration modes emit at longer wavelength region. Measuring long-wave infrared spectrum (LWIR) in a LIBS setup can instead reveal molecular composition of the sample, which is the information sought in applications including chemical and explosive detection and identification. This paper will present the work and results from the collaboration of several institutions to develop the methods of LWIR LIBS for chemical/explosive/pharmaceutical material detection/identification, such as DMMP and RDX, as fast as using a single excitation laser pulse. In our latest LIBS setup, both UVN and LWIR spectra can be collected at the same time, allowing more accurate detection and identification of materials.

  17. Nanometer-resolved chemical analyses of femtosecond laser-induced periodic surface structures on titanium

    NASA Astrophysics Data System (ADS)

    Kirner, Sabrina V.; Wirth, Thomas; Sturm, Heinz; Krüger, Jörg; Bonse, Jörn

    2017-09-01

    The chemical characteristics of two different types of laser-induced periodic surface structures (LIPSS), so-called high and low spatial frequency LIPSS (HSFL and LSFL), formed upon irradiation of titanium surfaces by multiple femtosecond laser pulses in air (30 fs, 790 nm, 1 kHz), are analyzed by various optical and electron beam based surface analytical techniques, including micro-Raman spectroscopy, energy dispersive X-ray analysis, X-ray photoelectron spectroscopy, and Auger electron spectroscopy. The latter method was employed in a high-resolution mode being capable of spatially resolving even the smallest HSFL structures featuring spatial periods below 100 nm. In combination with an ion sputtering technique, depths-resolved chemical information of superficial oxidation processes was obtained, revealing characteristic differences between the two different types of LIPSS. Our results indicate that a few tens of nanometer shallow HSFL are formed on top of a ˜150 nm thick graded superficial oxide layer without sharp interfaces, consisting of amorphous TiO2 and partially crystallized Ti2O3. The larger LSFL structures with periods close to the irradiation wavelength originate from the laser-interaction with metallic titanium. They are covered by a ˜200 nm thick amorphous oxide layer, which consists mainly of TiO2 (at the surface) and other titanium oxide species of lower oxidation states underneath.

  18. Host Chemical Footprints Induce Host Sex Discrimination Ability in Egg Parasitoids

    PubMed Central

    Peri, Ezio; Frati, Francesca; Salerno, Gianandrea; Conti, Eric; Colazza, Stefano

    2013-01-01

    Trissolcus egg parasitoids, when perceiving the chemical footprints left on a substrate by pentatomid host bugs, adopt a motivated searching behaviour characterized by longer searching time on patches were signals are present. Once in contact with host chemical footprints, Trissolcus wasps search longer on traces left by associated hosts rather than non-associated species, and, in the former case, they search longer on traces left by females than males. Based on these evidences, we hypothesized that only associated hosts induce the ability to discriminate host sex in wasps. To test this hypothesis we investigated the ability of Trissolcus basalis, T. brochymenae, and Trissolcus sp. to distinguish female from male Nezara viridula, Murgantia histrionica, and Graphosoma semipunctatum footprints. These three pentatomid bugs were selected according to variable association levels. Bioassays were conducted on filter paper sheets, and on Brassica oleracea (broccoli) leaves. The results confirmed our hypothesis showing that wasps spent significantly more time on female rather than male traces left by associated hosts on both substrates. No differences were observed in the presence of traces left by non-associated hosts. The ecological consequences for parasitoid host location behaviour are discussed. PMID:24244417

  19. Extraction of chemical-induced diseases using prior knowledge and textual information

    PubMed Central

    Pons, Ewoud; Becker, Benedikt F.H.; Akhondi, Saber A.; Afzal, Zubair; van Mulligen, Erik M.; Kors, Jan A.

    2016-01-01

    We describe our approach to the chemical–disease relation (CDR) task in the BioCreative V challenge. The CDR task consists of two subtasks: automatic disease-named entity recognition and normalization (DNER), and extraction of chemical-induced diseases (CIDs) from Medline abstracts. For the DNER subtask, we used our concept recognition tool Peregrine, in combination with several optimization steps. For the CID subtask, our system, which we named RELigator, was trained on a rich feature set, comprising features derived from a graph database containing prior knowledge about chemicals and diseases, and linguistic and statistical features derived from the abstracts in the CDR training corpus. We describe the systems that were developed and present evaluation results for both subtasks on the CDR test set. For DNER, our Peregrine system reached an F-score of 0.757. For CID, the system achieved an F-score of 0.526, which ranked second among 18 participating teams. Several post-challenge modifications of the systems resulted in substantially improved F-scores (0.828 for DNER and 0.602 for CID). RELigator is available as a web service at http://biosemantics.org/index.php/software/religator. PMID:27081155

  20. Complex graph matrix representations and characterizations of proteomic maps and chemically induced changes to proteomes.

    PubMed

    Balasubramanian, Krishnan; Khokhani, Kanan; Basak, Subhash C

    2006-05-01

    We have presented a complex graph matrix representation to characterize proteomics maps obtained from 2D-gel electrophoresis. In this method, each bubble in a 2D-gel proteomics map is represented by a complex number with components which are charge and mass. Then, a graph with complex weights is constructed by connecting the vertices in the relative order of abundance. This yields adjacency matrices and distance matrices of the proteomics graph with complex weights. We have computed the spectra, eigenvectors, and other properties of complex graphs and the Euclidian/graph distance obtained from the complex graphs. The leading eigenvalues and eigenvectors and, likewise, the smallest eigenvalues and eigenvectors, and the entire graph spectral patterns of the complex matrices derived from them yield novel weighted biodescriptors that characterize proteomics maps with information of charge and masses of proteins. We have also applied these eigenvector and eigenvalue maps to contrast the normal cells and cells exposed to four peroxisome proliferators, namely, clofibrate, diethylhexyl phthalate (DEHP), perfluorodecanoic acid (PFDA), and perfluoroctanoic acid (PFOA). Our complex eigenspectra show that the proteomic response induced by DEHP differs from the corresponding responses of other three chemicals consistent with their chemical structures and properties.

  1. Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple Contaminated Aquatic Systems.

    PubMed

    Rotter, Stefanie; Gunold, Roman; Mothes, Sibylle; Paschke, Albrecht; Brack, Werner; Altenburger, Rolf; Schmitt-Jansen, Mechthild

    2015-08-18

    Aquatic ecosystems are often contaminated with large numbers of chemicals, which cannot be sufficiently addressed by chemical target analyses. Effect-directed analysis (EDA) enables the identification of toxicants in complex contaminated environmental samples. This study suggests pollution-induced community tolerance (PICT) as a confirmation tool for EDA to identify contaminants which actually impact on local communities. The effects of three phytotoxic compounds local periphyton communities, cultivated at a reference (R-site) and a polluted site (P-site), were assessed to confirm the findings of a former EDA study on sediments. The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N-phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and exposure concentrations were determined. Prometryn and PNA concentrations were significantly higher at the P-site, whereas TBT concentrations were in the same range at both sites. Periphyton communities differed in biomass, but algal class composition and diatom diversity were similar. Community tolerance of P-communities was significantly enhanced for prometryn, but not for PNA and TBT, confirming site-specific effects on local periphyton for prometryn only. Thus, PICT enables in situ effect confirmation of phytotoxic compounds at the community level and seems to be suitable to support confirmation and enhance ecological realism of EDA.

  2. Manifestation of the light-induced drift effect in chemically peculiar stellar atmospheres

    NASA Astrophysics Data System (ADS)

    Parkhomenko, A. I.; Shalagin, A. M.

    2013-02-01

    We have calculated the factor ( ν g - ν e )/ ν g in the temperature range T = 300-20 000 K for the ions Be+, Mg+, Ca+, C+ in atomic hydrogen and for the ions Mg+ in atomic argon using the known interaction potentials. Here ν e and ν g are the transport collision frequencies for excited- and ground-state particles respectively. Calculations have shown that at T = 10 000-20 000 K, typical temperatures of the atmospheres of chemically peculiar (CP) stars, the values | ν g - ν e |/ ν g ≈ 0.1-0.2 can be reached for ions. This causes the light-induced drift (LID) velocity of ions up to ˜0.1 cm/s in the atmospheres of CP stars with temperatures T < 10 000 K. Therefore the separation of chemical elements due to the LID of ions under the conditions of the atmospheres of such CP stars can be an order of magnitude more efficient in comparison with the separation caused by the radiation pressure. In the atmosphere of more hot stars (20 000 K > T > 10 000 K) it is possible to expect approximately identical magnitude of the LID effect and that of radiation pressure. In the very hot stars ( T >20 000 K) the LID effect is manifested very weakly.

  3. IR and UV laser-induced chemical vapor deposition: Chemical mechanism for a-Si:H and Cr (O,C) film formation

    NASA Astrophysics Data System (ADS)

    Hess, Peter

    The characteristic features of laser-induced chemical vapor deposition in the parallel and perpendicular laser beam/surface configurations are discussed. Low temperature chemical processing with directed and spatially localized energy deposition in the system is investigated. Results obtained for the deposition of hydrogenated amorphous silicon (a-Si:H) films in the parallel configuration employing CO 2 and KrFlasers and SiH 4 and Si 2H 6 as precursors are presented. As a second example, the growth of oxygen- and carbon-containing chromium films Cr(O,C) from chromium hexacarbonyl as the precursor using cw and pulse uv lasers is discussed. The chemical pathways leasing to film formation are investigated in detail.

  4. Glucose-induced cytosolic pH changes in beta-cells and insulin secretion are not causally related: studies in islets lacking the Na+/H+ exchangeR NHE1.

    PubMed

    Stiernet, Patrick; Nenquin, Myriam; Moulin, Pierre; Jonas, Jean-Christophe; Henquin, Jean-Claude

    2007-08-24

    The contribution of Na(+)/H(+) exchange (achieved by NHE proteins) to the regulation of beta-cell cytosolic pH(c), and the role of pH(c) changes in glucose-induced insulin secretion are disputed and were examined here. Using real-time PCR, we identified plasmalemmal NHE1 and intracellular NHE7 as the two most abundant NHE isoforms in mouse islets. We, therefore, compared insulin secretion, cytosolic free Ca(2+) ([Ca(2+)](c)) and pH(c) in islets from normal mice and mice bearing an inactivating mutation of NHE1 (Slc9A1-swe/swe). The experiments were performed in HCO(-)(3)/CO(2) or HEPES/NaOH buffers. PCR and functional approaches showed that NHE1 mutant islets do not express compensatory pH-regulating mechanisms. NHE1 played a greater role than HCO(-)(3)-dependent mechanisms in the correction of an acidification imposed by a pulse of NH(4)Cl. In contrast, basal pH(c) (in low glucose) and the alkalinization produced by high glucose were independent of NHE1. Dimethylamiloride, a classic blocker of Na(+)/H(+) exchange, did not affect pH(c) but increased insulin secretion in NHE1 mutant islets, indicating unspecific effects. In control islets, glucose similarly increased [Ca(2+)](c) and insulin secretion in HCO(-)(3) and HEPES buffer, although pH(c) changed in opposite directions. The amplification of insulin secretion that glucose produces when [Ca(2+)](c) is clamped at an elevated level by KCl was also unrelated to pH(c) and pH(c) changes. All effects of glucose on [Ca(2+)](c) and insulin secretion proved independent of NHE1. In conclusion, NHE1 protects beta-cells against strong acidification, but has no role in stimulus-secretion coupling. The changes in pH(c) produced by glucose involve HCO(-)(3)-dependent mechanisms. Variations in beta-cell pH(c) are not causally related to changes in insulin secretion.

  5. Cognition and causality, fiction and explanation.

    PubMed

    Spaulding, W D

    1995-09-01

    The debate about the causal efficacy of cognition involves two overlapping but different issues: (1) whether explanatory fictions improve upon the power and utility of nonfictional explanations of behavior, and (2) whether any explanation, either purely empirical or purely inferential, can describe proximal causality in behavioral functioning. The resolution of the first issue depends on the purpose to which the explanation is to be put. The resolution of the second issue depends on the larger paradigmatic context in which causality is understood. In modern biosystemic models of behavior, linear causality is important only as a special case of the multidirectional and reciprocal causality which characterizes complex self-regulating systems.

  6. Combinatorial electrostatic collision-induced dissociative chemical cross-linking reagents for probing protein surface topology.

    PubMed

    Liu, Fan; Goshe, Michael B

    2010-07-15

    To ascertain more information on protein domain orientation and complex structure associations using chemical cross-linking, we have developed a combination of electrostatic collision-induced dissociative cross-linking reagents that differentially react with protein surfaces which are effectively analyzed by liquid chromatography-tandem mass spectrometry using ion trap multistage collision-induced dissociation. Implementing our original design and methodology based on disuccinimidyl-succinamyl-aspartyl-proline (SuDP) (Soderblom, E. J.; Goshe, M. B. Anal. Chem 2006, 78, 8059-8068. Soderblom, E. J.; Bobay, B. G.; Cavanagh, J.; Goshe, M. B. Rapid Commun Mass Spectrom 2007, 21, 3395-3408.), disuccinimidyl-succinamyl-valyl-proline (SuVP) was synthesized. The SuDP and SuVP reagents are the same except for the valyl and aspartyl groups which provide a distinctive chemical feature to each reagent. When performing labeling reactions using various protein-to-cross-linker ratios at pH 7.5, the negatively charged SuDP and neutral SuVP were used to label bovine serum albumin and hemoglobin. After protein digestion, the resulting peptides were analyzed using four different ion trap LC/MS(3) acquisition methods incorporating multistage CID. The more polar BSA surface resulted in a number of unique interpeptide and intrapeptide cross-links for each reagent whereas the less polarized surface of hemoglobin produced similar results for both reagents. Based on the identification of dead-end products (i.e., a cross-link modification containing a hydrolyzed end) for each protein, the aminolysis reactivity of each modified lysyl side chain revealed a preference for reacting with each reagent according to its local electrostatic surface environment. Overall, combinatorial application of SuDP and SuVP chemical labeling produces a set of unique interpeptide, intrapeptide, and dead-end cross-linked products that provides protein structural information according to its electrostatic surface

  7. Assessing thalamocortical functional connectivity with Granger causality.

    PubMed

    Chen, Cheng; Maybhate, Anil; Israel, David; Thakor, Nitish V; Jia, Xiaofeng

    2013-09-01

    Assessment of network connectivity across multiple brain regions is critical to understanding the mechanisms underlying various neurological disorders. Conventional methods for assessing dynamic interactions include cross-correlation and coherence analysis. However, these methods do not reveal the direction of information flow, which is important for studying the highly directional neurological system. Granger causality (GC) analysis can characterize the directional influences between two systems. We tested GC analysis for its capability to capture directional interactions within both simulated and in vivo neural networks. The simulated networks consisted of Hindmarsh-Rose neurons; GC analysis was used to estimate the causal influences between two model networks. Our analysis successfully detected asymmetrical interactions between these networks ( , t -test). Next, we characterized the relationship between the "electrical synaptic strength" in the model networks and interactions estimated by GC analysis. We demonstrated the novel application of GC to monitor interactions between thalamic and cortical neurons following ischemia induced brain injury in a rat model of cardiac arrest (CA). We observed that during the post-CA acute period the GC interactions from the thalamus to the cortex were consistently higher than those from the cortex to the thalamus ( 1.983±0.278 times higher, p = 0.021). In addition, the dynamics of GC interactions between the thalamus and the cortex were frequency dependent. Our study demonstrated the feasibility of GC to monitor the dynamics of thalamocortical interactions after a global nervous system injury such as CA-induced ischemia, and offers preferred alternative applications in characterizing other inter-regional interactions in an injured brain.

  8. Assessing Thalamocortical Functional Connectivity with Granger Causality

    PubMed Central

    Israel, David; Thakor, Nitish V.; Jia, Xiaofeng

    2014-01-01

    Assessment of network connectivity across multiple brain regions is critical to understanding the mechanisms underlying various neurological disorders. Conventional methods for assessing dynamic interactions include cross-correlation and coherence analysis. However, these methods do not reveal the direction of information flow, which is important for studying the highly directional neurological system. Granger causality (GC) analysis can characterize the directional influences between two systems. We tested GC analysis for its capability to capture directional interactions within both simulated and in-vivo neural networks. The simulated networks consisted of Hindmarsh-Rose neurons; GC analysis was used to estimate the causal influences between two model networks. Our analysis successfully detected asymmetrical interactions between these networks (p<10−10, t-test). Next, we characterized the relationship between the “electrical synaptic strength” in the model networks and interactions estimated by GC analysis. We demonstrated the novel application of GC to monitor interactions between thalamic and cortical neurons following ischemia induced brain injury in a rat model of cardiac arrest (CA). We observed that during the post-CA acute period the GC interactions from the thalamus to the cortex were consistently higher than those from the cortex to the thalamus (1.983±0.278 times higher, p=0.021). In addition, the dynamics of GC interactions between the thalamus and the cortex were frequency dependent. Our study demonstrated the feasibility of GC to monitor the dynamics of thalamocortical interactions after a global nervous system injury such as CA-induced ischemia, and offers preferred alternative applications in characterizing other inter-regional interactions in an injured brain. PMID:23864221

  9. Near-field photochemical and radiation-induced chemical fabrication of nanopatterns of a self-assembled silane monolayer

    PubMed Central

    Hentschel, Carsten; Fontein, Florian; Stegemann, Linda; Hoeppener, Christiane; Fuchs, Harald; Hoeppener, Stefanie

    2014-01-01

    Summary A general concept for parallel near-field photochemical and radiation-induced chemical processes for the fabrication of nanopatterns of a self-assembled monolayer (SAM) of (3-aminopropyl)triethoxysilane (APTES) is explored with three different processes: 1) a near-field photochemical process by photochemical bleaching of a monomolecular layer of dye molecules chemically bound to an APTES SAM, 2) a chemical process induced by oxygen plasma etching as well as 3) a combined near-field UV-photochemical and ozone-induced chemical process, which is applied directly to an APTES SAM. All approaches employ a sandwich configuration of the surface-supported SAM, and a lithographic mask in form of gold nanostructures fabricated through colloidal sphere lithography (CL), which is either exposed to visible light, oxygen plasma or an UV–ozone atmosphere. The gold mask has the function to inhibit the photochemical reactions by highly localized near-field interactions between metal mask and SAM and to inhibit the radiation-induced chemical reactions by casting a highly localized shadow. The removal of the gold mask reveals the SAM nanopattern. PMID:25247126

  10. Chemical state evolution in ferroelectric films during tip-induced polarization and electroresistive switching

    DOE PAGES

    Ievlev, Anton V.; Maksymovych, Petro; Trassin, Morgan; ...

    2016-10-11

    Domain formation and ferroelectric switching is fundamentally inseparable from polarization screening, which on free surfaces can be realized via band bending and ionic adsorption. In the latter case, polarization switching is intrinsically coupled to the surface electrochemical phenomena, and the electrochemical stage can control kinetics and induce long-range interactions. However, despite extensive evidence towards the critical role of surface electrochemistry, little is known about the nature of the associated processes. Here we combine SPM tip induce polarization switching and secondary ion mass spectrometry to explore the evolution of chemical state of ferroelectric during switching. Surprisingly, we find that even pristinemore » surfaces contain ions (e.g. Cl-) that are not anticipated based on chemistry of the system and processing. In the ferroelectric switching regime, we find surprising changes in surface chemistry, including redistribution of base cations. Finally, at higher voltages in the electroforming regime significant surface deformation was observed and associated with a strong ion intermixing.« less

  11. Modeling of dual emission laser induced fluorescence for slurry thickness measurements in chemical mechanical polishing

    NASA Astrophysics Data System (ADS)

    Gray, Caprice; Rogers, Chris B.; Manno, Vincent P.; White, Robert D.

    2011-07-01

    Dual emission laser induced fluorescence (DELIF) is a technique for measuring the instantaneous thin fluid film thickness in dynamic systems. Two fluorophores within the system produce laser induced emissions that are filtered and captured by two cameras. The ratio of the images from these cameras is used to cancel the effect of the laser beam profile on the image intensity. The resultant intensity ratio can be calibrated to a fluid film thickness. The utilization of a 2-dye system when applied to Chemical Mechanical Polishing (CMP) is complicated by the fluorescence of the polymeric polishing pad and the light scattering particles in the polishing slurry. We have developed a model of DELIF for CMP with 1-dye employing the polishing pad as the second fluorophore. While scattering particles in the slurry decrease the overall intensity of the individual images, the contrast in the image ratio increases. Using the 1-dye DELIF system to measure thin slurry films, our model results indicate that a cubic calibration may be needed. However, experimental results suggest a linear calibration is achieved for slurry films between 0 and 133 μm thick with scattering coefficients as high as 8.66 mm-1 at a wavelength equal to 410 nm.

  12. Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis.

    PubMed

    Romualdo, Guilherme Ribeiro; Goto, Renata Leme; Henrique Fernandes, Ana Angélica; Cogliati, Bruno; Barbisan, Luis Fernando

    2016-10-01

    Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect.

  13. In-situ FT-IR monitoring of a solar flux induced chemical process

    SciTech Connect

    Markham, J.R.; Cosgrove, J.E.; Nelson, C.M.; Bonanno, A.S.; Schlief, R.E.; Stoy, M.A.; Glatzmaier, G.C.; Bingham, C.E.; Lewandowski, A.A.

    1997-08-01

    The capability to perform in-situ, on-line monitoring of processes induced by concentrated solar flux will enhance the development and utilization of solar technologies. Temperature measurements and chemical concentration measurements provide an understanding of the ongoing chemistry, process limits, and process reproducibility. A Fourier transform infrared (FT-IR) spectrometer was optically coupled to a quartz flow reactor at the High Flux Solar Furnace of the National Renewable Energy Laboratory in Golden, CO. In-situ emission/transmission spectroscopy was utilized to simultaneously monitor steam temperature and the concentration of formed hydrogen bromide during the solar flux induced reaction of steam and bromine. The photochemical process is being investigated for the production of industrial quantities of hydrogen and oxygen, where downstream electrolysis of the formed hydrogen bromide provides the hydrogen and regenerates bromine. Steam temperature was measured to increase upon the addition of bromine to the reactor. Gas temperature increases of 200 C to 400 C were observed. Hydrogen bromide concentrations up to ten percent of the reactor gas volume was measured. The FT-IR system provided quantitative information of two critical parameters of the measured process and serves to accelerate this technology area.

  14. Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis.

    PubMed

    Tho, L M; Libertini, S; Rampling, R; Sansom, O; Gillespie, D A

    2012-03-15

    Chk1 is a key regulator of DNA damage checkpoint responses and genome stability in eukaryotes. To better understand how checkpoint proficiency relates to cancer development, we investigated the effects of genetic ablation of Chk1 in the mouse skin on tumors induced by chemical carcinogens. We found that homozygous deletion of Chk1 immediately before carcinogen exposure strongly suppressed benign tumor (papilloma) formation, and that the few, small lesions that formed in the ablated skin always retained Chk1 expression. Remarkably, Chk1 deletion rapidly triggered spontaneous cell proliferation, γ-H2AX staining and apoptosis within the hair follicle, a principal site of origin for carcinogen-induced tumors. At later times, the ablated skin was progressively repopulated by non-recombined Chk1-expressing cells and ultimately normal sensitivity to tumor induction was restored when carcinogen treatment was delayed. In marked contrast, papillomas formed normally in Chk1 hemizygous skin but showed an increased propensity to progress to carcinoma. Thus, complete loss of Chk1 is incompatible with epithelial tumorigenesis, whereas partial loss of function (haploinsufficiency) fosters benign malignant tumor progression.

  15. Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line.

    PubMed

    Liu, Fang; Du, Ke-Jie; Fang, Zhen; You, Yong; Wen, Ge-Bo; Lin, Ying-Wu

    2015-05-01

    Uranium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium.

  16. Suppression of osteopontin inhibits chemically induced hepatic carcinogenesis by induction of apoptosis in mice

    PubMed Central

    Lee, Su-Hyung; Park, Jun-Won; Woo, Sang-Ho; Go, Du-Min; Kwon, Hyo-Jung; Jang, Ja-June; Kim, Dae-Yong

    2016-01-01

    Previous clinical reports have found elevated osteopontin (OPN) levels in tumor tissues to be indicative of greater malignancy in human hepatocellular carcinoma (HCC). However, the role of OPN on carcinogenesis and its underlying mechanism remain unclear. In the present study, we investigated the oncogenic role of OPN in diethylnitrosamine (DEN)-induced hepatic carcinogenesis in mice. The overall incidence of hepatic tumors at 36 weeks was significantly lower in OPN knockout (KO) mice than in wild-type (WT) mice. Apoptosis was significantly enhanced in OPN KO mice, and was accompanied by the downregulation of epidermal growth factor receptor (EGFR). In the in vitro study, OPN suppression also led to lower mRNA and protein levels of EGFR associated with the downregulation of c-Jun in Hep3B and Huh7 human HCC cells lines, which resulted in increased apoptotic cell death in both cell lines. Moreover, a positive correlation was clearly identified between the expression of OPN and EGFR in human HCC tissues. These data demonstrate that the OPN deficiency reduced the incidence of chemically induced HCC by suppressing EGFR-mediated anti-apoptotic signaling. An important implication of our findings is that OPN positively contributes to hepatic carcinogenesis. PMID:27888617

  17. Chemically induced hypoxia promotes differential outcomes over preadipocyte- or adipocyte-macrophage communication.

    PubMed

    Avila-George, K; Ramos-Olivares, K; Vasquez-Munoz, K; Villanueva-Morales, V; Reyes-Farias, M; Quintero, P; Garcia, L; Garcia-Diaz, D F

    2017-07-01

    Expansion of white adipose tissue induce insufficient vascularization, driving hypoxia and low-grade inflammation. Resident preadipocytes are thought to be involved. We evaluated the effects of hypoxia over preadipocytes and adipocytes, to determine which cellular type impacts the most over macrophages activation. 3T3-L1 cells were either differentiated, or maintained undifferentiated. Each group was subjected to the presence or absence of chemical hypoxia (200 μM CoCl2) for 24 h. Conditioned media were used as treatment for murine RAW264.7 macrophages for 24 h. Gene expression of HIF-1α and TNF-α, and the release of several markers were assessed. It was observed that culture media from hypoxic preadipocytes induced greater expression of inflammatory markers and NO release than culture media from hypoxic adipocytes, by macrophages. Gene expression correlated closer with inflammatory markers release specially on macrophages treated with conditioned media from preadipocytes. Hence, the present work highlights the importance of preadipocytes on inflammatory conditions in vitro.

  18. Ability of 13 chemical agents used in dental practice to induce sister-chromatid exchanges in Syrian hamster embryo cells.

    PubMed

    Miyachi, Takashi; Tsutsui, Takeki

    2005-09-01

    To evaluate the genotoxic potential of 13 chemical agents used in dental practice, the abilities of these agents to induce sister-chromatid exchanges (SCEs) were examined using Syrian hamster embryo (SHE) cells. Statistically significant increases in the frequencies of SCEs were observed in SHE cells treated with all seven of the chemical agents used as endodontic medicaments: p-chlorophenol, m-cresol, formaldehyde, guaiacol, hydrogen peroxide, p-phenolsulfonic acid, and sodium hypochlorite (P < 0.01; Student t test). Assessment of two chemical agents that are applied to the oral mucosa as antiseptics showed that SCEs were induced by iodine (P < 0.01), but not by chlorhexidine. Of three chemical agents that are used as dyes for disclosing dental plaque, erythrosine B had no effect on SCE induction, while acid fuchsin and basic fuchsin increased the SCE frequencies in SHE cells (P < 0.01). Glutaraldehyde, which is used as a disinfectant for dental instruments and impressions, also induced SCEs (P < 0.01). Because SCE assays are used as a sensitive indicator for evaluating genetic toxicity of chemicals, the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.

  19. Improving causality induction with category learning.

    PubMed

    Guo, Yi; Wang, Zhihong; Shao, Zhiqing

    2014-01-01

    Causal relations are of fundamental importance for human perception and reasoning. According to the nature of causality, causality has explicit and implicit forms. In the case of explicit form, causal-effect relations exist at either clausal or discourse levels. The implicit causal-effect relations heavily rely on empirical analysis and evidence accumulation. This paper proposes a comprehensive causality extraction system (CL-CIS) integrated with the means of category-learning. CL-CIS considers cause-effect relations in both explicit and implicit forms and especially practices the relation between category and causality in computation. In elaborately designed experiments, CL-CIS is evaluated together with general causality analysis system (GCAS) and general causality analysis system with learning (GCAS-L), and it testified to its own capability and performance in construction of cause-effect relations. This paper confirms the expectation that the precision and coverage of causality induction can be remarkably improved by means of causal and category learning.

  20. Improving Causality Induction with Category Learning

    PubMed Central

    Wang, Zhihong; Shao, Zhiqing

    2014-01-01

    Causal relations are of fundamental importance for human perception and reasoning. According to the nature of causality, causality has explicit and implicit forms. In the case of explicit form, causal-effect relations exist at either clausal or discourse levels. The implicit causal-effect relations heavily rely on empirical analysis and evidence accumulation. This paper proposes a comprehensive causality extraction system (CL-CIS) integrated with the means of category-learning. CL-CIS considers cause-effect relations in both explicit and implicit forms and especially practices the relation between category and causality in computation. In elaborately designed experiments, CL-CIS is evaluated together with general causality analysis system (GCAS) and general causality analysis system with learning (GCAS-L), and it testified to its own capability and performance in construction of cause-effect relations. This paper confirms the expectation that the precision and coverage of causality induction can be remarkably improved by means of causal and category learning. PMID:24883419

  1. Experimental verification of an indefinite causal order

    PubMed Central

    Rubino, Giulia; Rozema, Lee A.; Feix, Adrien; Araújo, Mateus; Zeuner, Jonas M.; Procopio, Lorenzo M.; Brukner, Časlav; Walther, Philip

    2017-01-01

    Investigating the role of causal order in quantum mechanics has recently revealed that the causal relations of events may not be a priori well defined in quantum theory. Although this has triggered a growing interest on the theoretical side, creating processes without a causal order is an experimental task. We report the first decisive demonstration of a process with an indefinite causal order. To do this, we quantify how incompatible our setup is with a definite causal order by measuring a “causal witness.” This mathematical object incorporates a series of measurements that are designed to yield a certain outcome only if the process under examination is not consistent with any well-defined causal order. In our experiment, we perform a measurement in a superposition of causal orders—without destroying the coherence—to acquire information both inside and outside of a “causally nonordered process.” Using this information, we experimentally determine a causal witness, demonstrating by almost 7 SDs that the experimentally implemented process does not have a definite causal order. PMID:28378018

  2. Causal capture effects in chimpanzees (Pan troglodytes).

    PubMed

    Matsuno, Toyomi; Tomonaga, Masaki

    2017-01-01

    Extracting a cause-and-effect structure from the physical world is an important demand for animals living in dynamically changing environments. Human perceptual and cognitive mechanisms are known to be sensitive and tuned to detect and interpret such causal structures. In contrast to rigorous investigations of human causal perception, the phylogenetic roots of this perception are not well understood. In the present study, we aimed to investigate the susceptibility of nonhuman animals to mechanical causality by testing whether chimpanzees perceived an illusion called causal capture (Scholl & Nakayama, 2002). Causal capture is a phenomenon in which a type of bistable visual motion of objects is perceived as causal collision due to a bias from a co-occurring causal event. In our experiments, we assessed the susceptibility of perception of a bistable stream/bounce motion event to a co-occurring causal event in chimpanzees. The results show that, similar to in humans, causal "bounce" percepts were significantly increased in chimpanzees with the addition of a task-irrelevant causal bounce event that was synchronously presented. These outcomes suggest that the perceptual mechanisms behind the visual interpretation of causal structures in the environment are evolutionarily shared between human and nonhuman animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Norms and customs: causally important or causally impotent?

    PubMed

    Jones, Todd

    2010-01-01

    In this article, I argue that norms and customs, despite frequently being described as being causes of behavior in the social sciences and ordinary conversation, cannot really cause behavior. Terms like "norms" and the like seem to refer to philosophically disreputable disjunctive properties. More problematically, even if they do not, or even if there can be disjunctive properties after all, I argue that norms and customs still cannot cause behavior. The social sciences would be better off without referring to properties like norms and customs as if they could be causal.

  4. CADDIS Volume 1. Stressor Identification: About Causal Assessment

    EPA Pesticide Factsheets

    An introduction to the history of our approach to causal assessment, A chronology of causal history and philosophy, An introduction to causal history and philosophy, References for the Causal Assessment Background section of Stressor Identification

  5. Voluntary action and causality in temporal binding.

    PubMed

    Cravo, Andre M; Claessens, Peter M E; Baldo, Marcus V C

    2009-10-01

    Previous studies have documented temporal attraction in perceived times of actions and their effects. While some authors argue that voluntary action is a necessary condition for this phenomenon, others claim that the causal relationship between action and effect is the crucial ingredient. In the present study, we investigate voluntary action and causality as the necessary and sufficient conditions for temporal binding. We used a variation of the launching effect proposed by Michotte, in which participants controlled the launch stimulus in some blocks. Volunteers reported causality ratings and estimated the interval between the two events. Our results show dissociations between causality ratings and temporal estimation. While causality ratings are not affected by voluntary action, temporal bindings were only found in the presence of both voluntary action and high causality. Our results indicate that voluntary action and causality are both necessary for the emergence of temporal binding.

  6. Distinguishing causal interactions in neural populations.

    PubMed

    Seth, Anil K; Edelman, Gerald M

    2007-04-01

    We describe a theoretical network analysis that can distinguish statistically causal interactions in population neural activity leading to a specific output. We introduce the concept of a causal core to refer to the set of neuronal interactions that are causally significant for the output, as assessed by Granger causality. Because our approach requires extensive knowledge of neuronal connectivity and dynamics, an illustrative example is provided by analysis of Darwin X, a brain-based device that allows precise recording of the activity of neuronal units during behavior. In Darwin X, a simulated neuronal model of the hippocampus and surrounding cortical areas supports learning of a spatial navigation task in a real environment. Analysis of Darwin X reveals that large repertoires of neuronal interactions contain comparatively small causal cores and that these causal cores become smaller during learning, a finding that may reflect the selection of specific causal pathways from diverse neuronal repertoires.

  7. Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells.

    PubMed

    Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin; Jeong, Jae-Hoon; Kang, Seongman; Lim, Young-Bin

    2014-07-25

    Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

  8. Laser induced sub-micron changes of the chemical composition of SiO2-based optical fibers

    NASA Astrophysics Data System (ADS)

    Fokine, Michael A.

    2003-11-01

    A method to create sub-micron changes of the chemical composition of silica based optical fibers is reviewed. The method is used to create thermally stable refractive index structures, Fiber Bragg gratings, which can be used e.g. as sensors operating at very high temperatures. The method is based on UV induced chemical reactions of the silica glass with in-diffused molecular hydrogen. A change in the chemical composition is attained after thermal treatment, and the mechanism is attributed to diffusion of hydrogen compounds within the glass.

  9. Chemical kinetic behavior of chlorogenic acid in protecting erythrocyte and DNA against radical-induced oxidation.

    PubMed

    Tang, You-Zhi; Liu, Zai-Qun

    2008-11-26

    As an abundant ingredient in coffee, chlorogenic acid (CGA) is a well-known antioxidant. Although some works have dealt with its radical-scavenging property, the present work investigated the protective effects of CGA on the oxidation of DNA and on the hemolysis of human erythrocytes induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) by means of chemical kinetics. The inhibition period (t(inh)) derived from the protective effect of CGA on erythrocyte and DNA was proportional to its concentration, t(inh) = (n/R(i))[CGA], where R(i) refers to the radical-initiation rate, and n indicates the number of radical-propagation chains terminated by CGA. It was found that the n of CGA to protect erythrocytes was 0.77, lower than that of vitamin E (2.0), but higher than that of vitamin C (0.19). Furthermore, CGA facilitated a mutual protective effect with VE and VC on AAPH-induced hemolysis by increasing n of VE and VC. CGA was also found to be a membrane-stabilizer to protect erythrocytes against hemin-induced hemolysis. Moreover, the n of CGA was only 0.41 in the process of protecting DNA. This fact revealed that CGA served as an efficient antioxidant to protect erythrocytes more than to protect DNA. Finally, the reaction between CGA and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS(+*)) or 2,2'-diphenyl-1-picrylhydrazyl (DPPH) revealed that CGA was able to trap radicals by reducing radicals more than by donating its hydrogen atoms to radicals.

  10. CGene: an R package for implementation of causal genetic analyses

    PubMed Central

    Lipman, Peter J; Lange, Christoph

    2011-01-01

    The excitement over findings from Genome-Wide Association Studies (GWASs) has been tempered by the difficulty in finding the location of the true causal disease susceptibility loci (DSLs), rather than markers that are correlated with the causal variants. In addition, many recent GWASs have studied multiple phenotypes – often highly correlated – making it difficult to understand which associations are causal and which are seemingly causal, induced by phenotypic correlations. In order to identify DSLs, which are required to understand the genetic etiology of the observed associations, statistical methodology has been proposed that distinguishes between a direct effect of a genetic locus on the primary phenotype and an indirect effect induced by the association with the intermediate phenotype that is also correlated with the primary phenotype. However, so far, the application of this important methodology has been challenging, as no user-friendly software implementation exists. The lack of software implementation of this sophisticated methodology has prevented its large-scale use in the genetic community. We have now implemented this statistical approach in a user-friendly and robust R package that has been thoroughly tested. The R package ‘CGene' is available for download at http://cran.r-project.org/. The R code is also available at http://people.hsph.harvard.edu/~plipman. PMID:21731061

  11. Conditional Granger causality and partitioned Granger causality: differences and similarities.

    PubMed

    Malekpour, Sheida; Sethares, William A

    2015-12-01

    Neural information modeling and analysis often requires a measurement of the mutual influence among many signals. A common technique is the conditional Granger causality (cGC) which measures the influence of one time series on another time series in the presence of a third. Geweke has translated this condition into the frequency domain and has explored the mathematical relationships between the time and frequency domain expressions. Chen has observed that in practice, the expressions may return (meaningless) negative numbers, and has proposed an alternative which is based on a partitioned matrix scheme, which we call partitioned Granger causality (pGC). There has been some confusion in the literature about the relationship between cGC and pGC; some authors treat them as essentially identical measures, while others have noted that some properties (such as the relationship between the time and frequency domain expressions) do not hold for the pGC. This paper presents a series of matrix equalities that simplify the calculation of the pGC. In this simplified expression, the essential differences and similarities between the cGC and the pGC become clear; in essence, the pGC is dependent on only a subset of the parameters in the model estimation, and the noise residuals (which are uncorrelated in the cGC) need not be uncorrelated in the pGC. The mathematical results are illustrated with a simulation, and the measures are applied to an EEG dataset.

  12. Reverse causal reasoning: applying qualitative causal knowledge to the interpretation of high-throughput data

    PubMed Central

    2013-01-01

    Background Gene expression profiling and other genome-scale measurement technologies provide comprehensive information about molecular changes resulting from a chemical or genetic perturbation, or disease state. A critical challenge is the development of methods to interpret these large-scale data sets to identify specific biological mechanisms that can provide experimentally verifiable hypotheses and lead to the understanding of disease and drug action. Results We present a detailed description of Reverse Causal Reasoning (RCR), a reverse engineering methodology to infer mechanistic hypotheses from molecular profiling data. This methodology requires prior knowledge in the form of small networks that causally link a key upstream controller node representing a biological mechanism to downstream measurable quantities. These small directed networks are generated from a knowledge base of literature-curated qualitative biological cause-and-effect relationships expressed as a network. The small mechanism networks are evaluated as hypotheses to explain observed differential measurements. We provide a simple implementation of this methodology, Whistle, specifically geared towards the analysis of gene expression data and using prior knowledge expressed in Biological Expression Language (BEL). We present the Whistle analyses for three transcriptomic data sets using a publically available knowledge base. The mechanisms inferred by Whistle are consistent with the expected biology for each data set. Conclusions Reverse Causal Reasoning yields mechanistic insights to the interpretation of gene expression profiling data that are distinct from and complementary to the results of analyses using ontology or pathway gene sets. This reverse engineering algorithm provides an evidence-driven approach to the development of models of disease, drug action, and drug toxicity. PMID:24266983

  13. Analysis of α-particle-induced chromosomal aberrations by chemically-induced PCC. Elaboration of dose-effect curves.

    PubMed

    Puig, Roser; Pujol, Mònica; Barrios, Leonardo; Caballín, María Rosa; Barquinero, Joan-Francesc

    2016-09-01

    In a similar way to high-dose exposures to low-LET radiations, cells show difficulties reaching mitosis after high-LET radiation exposure. For this reason, techniques have been proposed that are able to analyze chromosome aberrations in interphase by prematurely condensing the chromosomes (PCC-techniques). Few dose-effect curves for high-LET radiation types have been reported, and none for α-particles. The aim of this study was to evaluate, by chemically-induced PCC, the chromosome aberrations induced by several doses of α-particles. Monolayers of peripheral lymphocytes were exposed to an α-source of Americium-241 with a mean energy entering the cells of 2.7 MeV. Lymphocytes were exposed to 10 doses, from 0-2.5 Gy, and then cultured for 48 h. Colcemid and Calyculin-A were added at 24 and 1 h before harvesting, respectively. During microscope analysis, chromosome rings and extra chromosome pieces were scored in G2/M-PCC and M cells, while dicentric chromosomes were only scored in M cells. As the dose increased, fewer cells were able to reach mitosis and the proportion of G2/M-PCC cells increased. Chromosome rings were hardly observed in M cells when compared to G2/M-PCC cells. Extra fragments were more frequent than rings in both G2/M-PCC and M cells, but with lower frequencies than in G2/M-PCC cells. The distribution of dicentrics and extra fragments showed a clear overdispersion; this was not so evident for rings. The dose-effect curves obtained fitted very well to a linear model. Damaged cells after α-particle irradiation show more difficulties in reaching mitosis than cells exposed to γ-rays. After α-particle irradiation the frequency of all the chromosome aberrations considered increased linearly with the dose, and α-particles clearly produced more dicentrics and extra chromosome pieces with respect to γ-rays. After α-particle exposure, the existence of extra chromosome fragments in PCC cells seems to be a good candidate for use as a biomarker

  14. Determining molecular predictors of adverse drug reactions with causality analysis based on structure learning.

    PubMed

    Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua

    2014-01-01

    Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs.

  15. Determining molecular predictors of adverse drug reactions with causality analysis based on structure learning

    PubMed Central

    Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua

    2014-01-01

    Objective Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. Methods We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. Results CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. Conclusions The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs. PMID:24334612

  16. Local chemical reaction of benzene on Cu110 via STM-induced excitation.

    PubMed

    Komeda, T; Kim, Y; Fujita, Y; Sainoo, Y; Kawai, Maki

    2004-03-15

    We have investigated the mechanism of the chemical reaction of the benzene molecule adsorbed on Cu(110) surface induced by the injection of tunneling electrons using scanning tunneling microscopy (STM). With the dosing of tunneling electrons of the energy 2-5 eV from the STM tip to the molecule, we have detected the increase of the height of the benzene molecule by 40% in the STM image and the appearance of the vibration feature of the nu(C-H) mode in the inelastic tunneling spectroscopy (IETS) spectrum. It can be understood with a model in which the dissociation of C-H bonds occurs in a benzene molecule that induces a bonding geometry change from flat-lying to up-right configuration, which follows the story of the report of Lauhon and Ho on the STM-induced change of benzene on the Cu(100) surface. [L. J. Lauhon and W. Ho, J. Phys. Chem. A 104, 2463 (2000)]. The reaction probability shows a sharp rise at the sample bias voltage at 2.4 V, which saturates at 3.0 V, which is followed by another sharp rise at the voltage of 4.3 V. No increase of the reaction yield is observed for the negative sample voltage up to 5 eV. In the case of a fully deuterated benzene molecule, it shows the onset at the same energy of 2.4 eV, but the reaction probability is 10(3) smaller than the case of the normal benzene molecule. We propose a model in which the dehydrogenation of the benzene molecule is induced by the formation of the temporal negative ion due to the trapping of the electrons at the unoccupied resonant states formed by the pi orbitals. The existence of the resonant level close to the Fermi level ( approximately 2.4 eV) and multiple levels in less than approximately 5 eV from the Fermi level, indicates a fairly strong interaction of the Cu-pi(*) state of the benzene molecule. We estimated that the large isotope effect of approximately 10(3) can be accounted for with the Menzel-Gomer-Redhead (MGR) model with an assumption of a shallow potential curve for the excited state. (c

  17. Space and time in perceptual causality.

    PubMed

    Straube, Benjamin; Chatterjee, Anjan

    2010-01-01

    Inferring causality is a fundamental feature of human cognition that allows us to theorize about and predict future states of the world. Michotte suggested that humans automatically perceive causality based on certain perceptual features of events. However, individual differences in judgments of perceptual causality cast doubt on Michotte's view. To gain insights in the neural basis of individual difference in the perception of causality, our participants judged causal relationships in animations of a blue ball colliding with a red ball (a launching event) while fMRI-data were acquired. Spatial continuity and temporal contiguity were varied parametrically in these stimuli. We did not find consistent brain activation differences between trials judged as caused and those judged as non-caused, making it unlikely that humans have universal instantiation of perceptual causality in the brain. However, participants were slower to respond to and showed greater neural activity for violations of causality, suggesting that humans are biased to expect causal relationships when moving objects appear to interact. Our participants demonstrated considerable individual differences in their sensitivity to spatial and temporal characteristics in perceiving causality. These qualitative differences in sensitivity to time or space in perceiving causality were instantiated in individual differences in activation of the left basal ganglia or right parietal lobe, respectively. Thus, the perception that the movement of one object causes the movement of another is triggered by elemental spatial and temporal sensitivities, which themselves are instantiated in specific distinct neural networks.

  18. Independence and dependence in human causal reasoning.

    PubMed

    Rehder, Bob

    2014-07-01

    Causal graphical models (CGMs) are a popular formalism used to model human causal reasoning and learning. The key property of CGMs is the causal Markov condition, which stipulates patterns of independence and dependence among causally related variables. Five experiments found that while adult's causal inferences exhibited aspects of veridical causal reasoning, they also exhibited a small but tenacious tendency to violate the Markov condition. They also failed to exhibit robust discounting in which the presence of one cause as an explanation of an effect makes the presence of another less likely. Instead, subjects often reasoned "associatively," that is, assumed that the presence of one variable implied the presence of other, causally related variables, even those that were (according to the Markov condition) conditionally independent. This tendency was unaffected by manipulations (e.g., response deadlines) known to influence fast and intuitive reasoning processes, suggesting that an associative response to a causal reasoning question is sometimes the product of careful and deliberate thinking. That about 60% of the erroneous associative inferences were made by about a quarter of the subjects suggests the presence of substantial individual differences in this tendency. There was also evidence that inferences were influenced by subjects' assumptions about factors that disable causal relations and their use of a conjunctive reasoning strategy. Theories that strive to provide high fidelity accounts of human causal reasoning will need to relax the independence constraints imposed by CGMs.

  19. How prescriptive norms influence causal inferences.

    PubMed

    Samland, Jana; Waldmann, Michael R

    2016-11-01

    Recent experimental findings suggest that prescriptive norms influence causal inferences. The cognitive mechanism underlying this finding is still under debate. We compare three competing theories: The culpable control model of blame argues that reasoners tend to exaggerate the causal influence of norm-violating agents, which should lead to relatively higher causal strength estimates for these agents. By contrast, the counterfactual reasoning account of causal selection assumes that norms do not alter the representation of the causal model, but rather later causal selection stages. According to this view, reasoners tend to preferentially consider counterfactual states of abnormal rather than normal factors, which leads to the choice of the abnormal factor in a causal selection task. A third view, the accountability hypothesis, claims that the effects of prescriptive norms are generated by the ambiguity of the causal test question. Asking whether an agent is a cause can be understood as a request to assess her causal contribution but also her moral accountability. According to this theory norm effects on causal selection are mediated by accountability judgments that are not only sensitive to the abnormality of behavior but also to mitigating factors, such as intentionality and knowledge of norms. Five experiments are presented that favor the accountability account over the two alternative theories.

  20. Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

    PubMed

    Agarwal, R; Korman, N J; Mohan, R R; Feyes, D K; Jawed, S; Zaim, M T; Mukhtar, H

    1996-04-01

    Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.