Application of toxicogenomics to the endocrine disruption issue

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2419-2422 ◽  
Author(s):  
T. Shirai ◽  
Makoto Asamoto
Keyword(s):  
Gene Expression ◽  
Risk Management ◽  
Endocrine Disruption ◽  
Epidemiological Data ◽  
Risk Identification ◽  
Short Term ◽  
Carcinogenic Potential ◽  
Short Period ◽  
Genomic Scale ◽  
Active Substances

Toxicogenomics can be expected to be a useful method for detecting the carcinogenic potential of endocrine active substances (EASs) in the short term with the generation of understanding of mode-of-action and mechanisms when a reliable database with information about proteomics and informatics is established. At present, there are no concrete epidemiological data supporting any exogenous EAS contribution to hormone-related organ carcinogenesis in humans. However, with the establishment of appropriate animal models and analysis of genomic-scale gene expression, risk identification and evaluation should be facilitated within a relatively short period, and this approach eventually promises to contribute a great deal of risk management regarding EASs.

AhR Activation in Pharmaceutical Development: Applying Liver Gene Expression Biomarker Thresholds to Identify Doses Associated With Tumorigenic Risks in Rats

2019 ◽  
Vol 171 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Chunhua Qin ◽  
Amy G Aslamkhan ◽  
Kara Pearson ◽  
Keith Q Tanis ◽  
Alexei Podtelezhnikov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Signature ◽  
Carcinogenic Risk ◽  
Drug Candidate ◽  
Short Term ◽  
Pharmaceutical Development ◽  
Aryl Hydrocarbon ◽  
Carcinogenic Potential ◽  
Liver Gene ◽  
Dose Levels

Abstract Aryl hydrocarbon receptor (AhR) activation is associated with carcinogenicity of non-genotoxic AhR-activating carcinogens such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD), and is often observed with drug candidate molecules in development and raises safety concerns. As downstream effectors of AhR signaling, the expression and activity of Cyp1a1 and Cyp1a2 genes are commonly monitored as evidence of AhR activation to inform carcinogenic risk of compounds in question. However, many marketed drugs and phytochemicals are reported to induce these Cyps modestly and are not associated with dioxin-like toxicity or carcinogenicity. We hypothesized that a threshold of AhR activation needs to be surpassed in a sustained manner in order for the dioxin-like toxicity to manifest, and a simple liver gene expression signature based on Cyp1a1 and Cyp1a2 from a short-term rat study could be used to assess AhR activation strength and differentiate tumorigenic dose levels from non-tumorigenic ones. To test this hypothesis, short-term studies were conducted in Wistar Han rats with 2 AhR-activating carcinogens (TCDD and PCB126) at minimally carcinogenic and noncarcinogenic dose levels, and 3 AhR-activating noncarcinogens (omeprazole, mexiletine, and canagliflozin) at the top doses used in their reported 2-year rat carcinogenicity studies. A threshold of AhR activation was identified in rat liver that separated a meaningful “tumorigenic-strength AhR signal” from a statistically significant AhR activation signal that was not associated with dioxin-like carcinogenicity. These studies also confirmed the importance of the sustainability of AhR activation for carcinogenic potential. A sustained activation of AhR above the threshold could thus be used in early pharmaceutical development to identify dose levels of drug candidates expected to exhibit dioxin-like carcinogenic potential.

scholarly journals Short –term Predication of Risk Management Integrating Artificial Neural Network (ANN)

2020 ◽  
Vol 9 (3) ◽  
pp. 2828-2833
Keyword(s):  
Neural Network ◽  
Risk Management ◽  
Software Development ◽  
Risk Mitigation ◽  
Risk Estimation ◽  
Risk Identification ◽  
Primary Study ◽  
Short Term ◽  
Software Projects ◽  
Artificial Neural Network Ann

The IT industry has boomed in the past few years with an ever increasing number of risk management applications being developed. There are inherent risks in software development projects and failure to deliver software projects within deadline or failure to develop software according to specifications can be costly. The software risks may occur during the project process. The management process of software risks consists the risk refinement, risk identification, risk monitoring, risk maintenance, risk estimation and risk mitigation. Neural Network has ability to stimulate hidden pattern recognition skill. The primary study of this paper is to focus on various risk management models and how risk tools may help in mitigating software risks during the project development. With the application of Neural Network, We propose short term risk management model which can predict the risk involvement with the upcoming project risks, analyzing from the previous projects causing serious loss in the IT project in terms of values on certain risk factors. Neural Network model can also ability to evaluate the assessment of risks in software development and acts as an effective instrument in analysis and minimizing risks that enable continuous improvement in software processes and products.

Methodological bases and practice of risk management of regional development (part 1)

2020 ◽  
Vol 18 (2) ◽  
pp. 114-126
Author(s):  
Valery V. Karpov ◽  
Anna G. Breusova ◽  
Anna A. Korableva
Keyword(s):  
Risk Management ◽  
Regional Development ◽  
Regional Economy ◽  
Full Range ◽  
Risk Identification ◽  
Territorial Development ◽  
Public Authorities ◽  
Strategic Risk ◽  
Risk Committee ◽  
State Programs

The article is devoted to the theoretical foundations and analysis of the experience of subjects of the Russian Federation in the field of regional development risk management. The article examines the concept of risk, its difference and relationship with the concepts of uncertainty, threat, danger, security and others. It is determined that dangers are constantly present in the regional economy. And risk, as a measurable uncertainty with multiple outcomes, for which the probability of occurrence of a risk event is calculated, is manifested as a result of the occurrence of a hazard. When comparing the concepts of risk and security, this means that the security of the regional economy is manifested in the ability to resist threats and manage risks, and not in the complete absence of dangers. It is revealed that ISO standards distinguish between the concepts of risk management and risk management. For further discussion, risk management is understood as a systematic approach to using the full range of mechanisms available to public authorities to reduce emerging risks and threats to the socio-economic development of the region. Further, the analysis of risk management in the practice of regional management on the example of the Omsk, Novosibirsk and Tyumen regions is carried out. The relevant tools in the activities of government bodies, such as territorial development strategies, state programs and projects, were identified, which allowed us to introduce a classification of risks with the allocation of strategic, tactical risks of territorial development and project management risks, among which there is a strategic level. The analysis of the implemented tools for compliance with the mandatory stages of risk management showed mainly the absence of risk identification, unified requirements for risk accounting and systematic risk management of regional development. Among the assessed regions, the Tyumen region has the best practices in terms of risk management. For a more detailed analysis authors highlighted the key institutional and instrumental elements of risk management such as risk committee, strategic risk map, risk register, action plan for risk management, and defined logical relationships between them.

CONCEPTUALISING RISK CULTURE ON ERM IMPLEMENTATION IN CONSTRUCTION COMPANIES

2020 ◽  
Vol 17 (1) ◽  
pp. 59
Author(s):  
Ching Ching Wong
Keyword(s):  
Risk Management ◽  
Risk Identification ◽  
The Body ◽  
Risk Indicators ◽  
Construction Companies ◽  
Risk Appetite ◽  
Risk Culture ◽  
Risk Treatment ◽  
Managing Risk ◽  
The Relationship

Enterprise Risk Management (ERM) is an effective technique in managing risk within an organization strategically and holistically. Risk culture relates to the general awareness, attitudes and behaviours towards risk management in an organisation. This paper presents a conceptual model that shows the relationship between risk culture and ERM implementation. The dependent variable is ERM implementation, which is measured by the four processes namely risk identification and risk assessment; risk treatment; monitor and consult; communicate and consult. The independent variables under risk culture are risk policy and risk appetite; key risk indicators; accountability; incentives; risk language and internal relationships. This study aims to empirically test the relationship between risk culture and ERM implementation among Malaysian construction public listed companies. Risk culture is expected to have direct effects and significantly influence ERM. This study contributes to enhance the body of knowledge in ERM especially in understanding significant of risk culture that influence its’ implementation from Malaysian perspective.

The Effects of Decision Aid Orientation on Risk Factor Identification and Audit Test Planning

2002 ◽  
Vol 21 (2) ◽  
pp. 39-56 ◽  
Author(s):  
Jean C. Bedard ◽  
Lynford E. Graham
Keyword(s):  
Risk Factors ◽  
Risk Management ◽  
Decision Aid ◽  
Decision Aids ◽  
Management Strategies ◽  
Risk Identification ◽  
Matched Pair ◽  
Audit Planning ◽  
Audit Firms ◽  
Risk Management Strategies

In auditing, risk management involves identifying client facts or issues that may affect engagement risk, and planning evidence-gathering strategies accordingly. The purpose of this paper is to examine whether auditors' identification of risk factors and planning of audit tests is affected by decision aid orientation, i.e., a “negative” focus wherein client risk and its consequences are emphasized, or a “positive” focus where such factors are not emphasized. Specifically, we expect that auditors will identify more risk factors using a negatively oriented risk identification decision aid, but only when engagement risk is relatively high. We address this issue in the context of auditors' knowledge of actual clients, manipulating decision aid orientation as negative or positive in a matched-pair design. Results show that auditors using the negative decision aid orientation identify more risk factors than do those using a positive orientation, for their higher-risk clients. We also find that decisions to apply substantive tests are more directly linked to specific risk factors identified than to direct risk assessments. Further, our results show that auditors with repeat engagement experience with the client identify more risk factors. The findings of this study imply that audit firms may improve their risk management strategies through simple changes in the design of decision aids used to support audit planning.

scholarly journals Effects of different returning method combined with decomposer on decomposition of organic components of straw and soil fertility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao Wang ◽  
Xuexin Wang ◽  
Peng Geng ◽  
Qian Yang ◽  
Kun Chen ◽  
...  
Keyword(s):  
Organic Carbon ◽  
Soil Fertility ◽  
Decomposition Rate ◽  
Microbial Biomass Carbon ◽  
No Tillage ◽  
Short Term ◽  
Straw Decomposition ◽  
Short Period ◽  
Straw Return ◽  
Forms Of Carbon

AbstractIn view of the problems of low straw decomposition rates and reduced soil fertility in southern Liaoning, China, we investigated the effects of no-tillage mode (NT), deep loosening + deep rotary tillage mode (PT), rotary tillage mode (RT) and the addition of decomposing agent (the next is called a decomposer) (NT + S, PT + S, RT + S) on the decomposition proportion of straw, respectively, by using the nylon net bag method in combination with 365-day field plot experiments. The decomposition rules of cellulose, hemicellulose and lignin as well as the dynamics of soil organic carbon (SOC), soil microbial biomass carbon (MBC) and soil dissolved organic carbon (DOC) in straw returned to the field for 15, 35, 55, 75, 95, 145 and 365 days were analyzed. The results showed that in the short term, the decomposition of straw was better in both the rotray tillage and deep loosening + deep rotary modes than in the no-tillage mode, and the addition of decomposer significantly promoted the decomposition of straw and the release of carbon from straw, among them, the RT + S treatment had the highest straw decomposition proportion and carbon release proportion in all sampling periods. After a one year experimental cycle, the RT + S treatment showed the highest proportion of cellulose, hemicellulose and lignin decomposition with 35.49%, 84.23% and 85.50%, respectively, and soil SOC, MBC and DOC contents were also higher than the other treatments with an increase of 2.30 g kg−1, 14.22 mg kg−1 and 25.10 mg kg−1, respectively, compared to the pre-experimental soil. Our results show that in the short term, to accelerate the decomposition rate of returned straw and increase the content of various forms of carbon in soil, rotary tillage can be used to return the straw to the field, while also spraying straw decomposer on its surface. This experiment used a new straw decomposer rich in a variety of microorganisms, combined with the comparison of a variety of straw return modes, and in-depth study of straw decomposition effects of cellulose, hemicellulose and lignin. Thus, a scheme that can effectively improve the decomposition rate of straw and the content of various forms of organic carbon in soil within a short period of time was explored to provide theoretical support for the southern Liaoning.

Short-term Load Forecasting by Using Improved GEP and Abnormal Load Recognition

2021 ◽  
Vol 21 (4) ◽  
pp. 1-28
Author(s):  
Song Deng ◽  
Fulin Chen ◽  
Xia Dong ◽  
Guangwei Gao ◽  
Xindong Wu
Keyword(s):  
Gene Expression ◽  
Probability Distribution ◽  
Detection Rate ◽  
Cross Validation ◽  
Normal Load ◽  
Gene Expression Programming ◽  
Load Forecasting ◽  
Short Term ◽  
Forecasting Models ◽  
Short Term Load Forecasting

Load forecasting in short term is very important to economic dispatch and safety assessment of power system. Although existing load forecasting in short-term algorithms have reached required forecast accuracy, most of the forecasting models are black boxes and cannot be constructed to display mathematical models. At the same time, because of the abnormal load caused by the failure of the load data collection device, time synchronization, and malicious tampering, the accuracy of the existing load forecasting models is greatly reduced. To address these problems, this article proposes a Short-Term Load Forecasting algorithm by using Improved Gene Expression Programming and Abnormal Load Recognition (STLF-IGEP_ALR). First, the Recognition algorithm of Abnormal Load based on Probability Distribution and Cross Validation is proposed. By analyzing the probability distribution of rows and columns in load data, and using the probability distribution of rows and columns for cross-validation, misjudgment of normal load in abnormal load data can be better solved. Second, by designing strategies for adaptive generation of population parameters, individual evolution of populations and dynamic adjustment of genetic operation probability, an Improved Gene Expression Programming based on Evolutionary Parameter Optimization is proposed. Finally, the experimental results on two real load datasets and one open load dataset show that compared with the existing abnormal data detection algorithms, the algorithm proposed in this article have higher advantages in missing detection rate, false detection rate and precision rate, and STLF-IGEP_ALR is superior to other short-term load forecasting algorithms in terms of the convergence speed, MAE, MAPE, RSME, and R 2 .

EXPRESS: Short-term upper limb immobilization impairs grasp representation

2020 ◽  
pp. 174702182098552
Author(s):  
Lucette Toussaint ◽  
Aurore Meugnot ◽  
Christel Bidet-Ildei
Keyword(s):  
Response Times ◽  
Motor Program ◽  
Control Group ◽  
Short Term ◽  
Small Sphere ◽  
Large Sphere ◽  
Short Period ◽  
Limb Immobilization ◽  
Laterality Task ◽  
Sensorimotor Processes

The present experiment aimed to gain more information on the effect of limb nonuse on the cognitive level of actions and, more specifically, on the content of the motor program used for grasping an object. For that purpose, we used a hand-grasping laterality task that is known to contain concrete information on manipulation activity. Two groups participated in the experiment: an immobilized group, including participants whose right hand and arm were fixed with a rigid splint and an immobilization vest for 24 hours, and a control group, including participants who did not undergo the immobilization procedure. The main results confirmed a slowdown of sensorimotor processes, which is highlighted in the literature, with slower response times when the participants identified the laterality of hand images that corresponded to the immobilized hand. Importantly, the grip-precision effect, highlighted by slower response times for hands grasping a small sphere versus a large sphere, is impaired by 24 hours of limb nonuse. Overall, this study provided additional evidence of the disengagement of sensorimotor processes due to a short period of limb immobilization.

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