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Search Results: 1 - 10 of 27418 matches for " Robert Barouki "
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Developmental origins of non-communicable disease: Implications for research and public health
Robert Barouki, Peter D Gluckman, Philippe Grandjean, Mark Hanson, Jerrold J Heindel
Environmental Health , 2012, DOI: 10.1186/1476-069x-11-42
Abstract: For many years biologists considered the developmental period to be controlled by a strict, hard-wired genetic program, and thus it was uncertain how it could be influenced by the environment. It is now clear that development is plastic, and that it allows the organism to respond to the surrounding environment, especially during early development when cells are differentiating and tissues are developing. This capacity is based on molecular pathways that lead to control of gene expression and induction of specific phenotypes in the absence of DNA sequence modification [1]. These pathways, as currently understood, include DNA methylation, histone covalent modification, and noncoding RNA expression. Such epigenetic modifications can be passed from one cell generation to the next and, in some cases, when germ cells are targeted, can be transgenerationally transmitted [2]. Furthermore, these changes can be cell, tissue, and sex specific, and time dependent. In many cases they may not be apparent during a latent period which may last from months to years or decades. Thus, each individual has one genome, but will hold multiple epigenomes.The ability to respond to environmental conditions can be evolutionarily advantageous by allowing fine-tuning of gene expression, likely through epigenetic mechanisms [3]. Thus, developmentally plastic processes allow the organism to adapt to changing environments in order to maintain or improve reproductive capability in part by sustaining health through the reproductive period. However, interference with these developmentally-adaptive processes may also have adverse consequences on some functions and disease risks later in life. Furthermore, these mechanisms are also sensitive to environmental stimuli other than the nutrients and physiological factors that are normative, in evolutionary terms, to the human environment. Indeed, drugs, industrial chemicals, tobacco smoke, and other environmental exposures can affect these same mechanisms l
Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse
Aline Chevallier, Antoine Mialot, Jean-Maurice Petit, Pedro Fernandez-Salguero, Robert Barouki, Xavier Coumoul, Mathieu Beraneck
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053520
Abstract: The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR?/?) leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR), were investigated. The OKR is less effective in the AhR?/? mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressedin the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR?/? mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR?/? mice might give insights into the developmental mechanisms which lead to congenital eye disorders.
A Head and Neck Cancer Tumor Response-Specific Gene Signature for Cisplatin, 5-Fluorouracil Induction Chemotherapy Fails with Added Taxanes
Céline Tomkiewicz, Stéphane Hans, Marie Hélène Mucchielli, Nicolas Agier, Hervé Delacroix, Laetitia Marisa, Daniel Brasnu, Lawrence P. Aggerbeck, Cécile Badoual, Robert Barouki, Martine Aggerbeck
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047170
Abstract: Background It is a major clinical challenge to predict which patients, with advanced stage head and neck squamous cell carcinoma, will not exhibit a reduction in tumor size following induction chemotherapy in order to avoid toxic effects of ineffective chemotherapy and delays for instituting other therapeutic options. Further, it is of interest to know to what extent a gene signature, which identifies patients with tumors that will not respond to a particular induction chemotherapy, is applicable when additional chemotherapeutic agents are added to the regimen. Methodology/Principal Findings To identify genes that predict tumor resistance to induction with cisplatin/5-fluorouracil (PF) or PF and a taxane, we analyzed patient tumor biopsies with whole genome microarrays and quantitative reverse transcriptase-PCR (TLDA) cards. A leave one out cross-validation procedure allowed evaluation of the prediction tool. A ten-gene microarray signature correctly classified 12/13 responders and 7/10 non-responders to PF (92% specificity, 82.6% accuracy). TLDA analysis (using the same classifier) of the patients correctly classified 12/12 responders and 8/10 non-responders (100% specificity, 90.9% accuracy). Further, TLDA analysis correctly predicted the response of 5 new patients and, overall, 12/12 responders and 13/15 non-responders (100% specificity, 92.6% accuracy). The protein products of the genes constituting the signature physically associate with 27 other proteins, involved in regulating gene expression, constituting an interaction network. In contrast, TLDA-based prediction (with the same gene signature) of responses to induction with PF and either of two taxanes was poor (0% specificity, 25% accuracy and 33.3% specificity, 25% accuracy). Conclusions/Significance Successful transfer of the microarray-based gene signature to an independent, PCR-based technology suggests that TLDA-based signatures could be a useful hospital-based technology for determining therapeutic options. Although highly specific for tumor responses to PF induction, the gene signature is unsuccessful when taxanes are added. The results illustrate the subtlety in developing “personalized medicine”.
Expression of Calcineurin Activity after Lung Transplantation: A 2-Year Follow-Up
Sylvia Sanquer, Catherine Amrein, Dominique Grenet, Romain Guillemain, Bruno Philippe, Veronique Boussaud, Laurence Herry, Celine Lena, Alphonsine Diouf, Michelle Paunet, Eliane M. Billaud, Fran?oise Loriaux, Jean-Philippe Jais, Robert Barouki, Marc Stern
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059634
Abstract: The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineurin during the first 2 years after lung transplantation. From March 2004 to October 2008, 107 patients were prospectively enrolled and their follow-up was performed until 2009. Calcineurin activity was measured in peripheral blood mononuclear cells. We report that calcineurin activity was linked to both acute and chronic rejection. An optimal activity for calcineurin with two thresholds was defined, and we found that the risk of rejection was higher when the enzyme activity was above the upper threshold of 102 pmol/mg/min or below the lower threshold of 12 pmol/mg/min. In addition, we report that the occurrence of malignancies and viral infections was significantly higher in patients displaying very low levels of calcineurin activity. Taken together, these findings suggest that the measurement of calcineurin activity may provide useful information for the management of the prevention therapy of patients receiving lung transplantation.
Introduction to a Requirements Engineering Framework for Aeronautics  [PDF]
Robert Abo
Journal of Software Engineering and Applications (JSEA) , 2010, DOI: 10.4236/jsea.2010.39105
Abstract: This paper introduces a framework to produce and to manage quality requirements of embedded aeronautical systems, called the ‘Requirements Engineering Framework’ (REF). It aims at making the management of the requirement lifecycle easier, from the specification of the purchaser’s needs, to their implementation in the final products, and also their verification, while controlling costs. REF is based on the main standards of aeronautics, in particular RTCA DO-254, and RTCA DO-178B standards. An implementation of REF, using the IBM Rational DOORS and IBM Rational Change tools, is also presented in this paper.
Pricing Options in Jump Diffusion Models Using Mellin Transforms  [PDF]
Robert Frontczak
Journal of Mathematical Finance (JMF) , 2013, DOI: 10.4236/jmf.2013.33037
Abstract:

This paper is concerned with the valuation of options in jump diffusion models. The partial integro-differential equation (PIDE) inherent in the pricing problem is solved by using the Mellin integral transform. The solution is a single integral expression independent of the distribution of the jump size. We also derive analytical expressions for the Greeks. The results are implemented and compared to other approaches.

Australia’s Out-Dated Concern over Fishing Threatens Wise Marine Conservation and Ecologically Sustainable Seafood Supply  [PDF]
Robert Kearney
Open Journal of Marine Science (OJMS) , 2013, DOI: 10.4236/ojms.2013.32006
Abstract:

Seafood plays an important role in human nutrition and its increased consumption is actively recommended for sustenance and health benefits in both developing and developed countries. In parallel to this, the public receives confusing advice as to what seafood is sustainably produced and is frequently misled about the environmental impacts of fishing, especially in locations such as Australia where contemporary fishery management has a conservation and sustainability focus. It is recognised globally that Australia’s traditional fishery management driven by strict sustainability and biodiversity regulations, has achieved impressive results in managing both fish stocks and the effects of fishing on marine environments. Despite this, continued pressure from non-government organisations (NGOs) and a perpetuation of the misuse of management terms such as overfished is used to promote the misguided need for ever increasing fishing restrictions, most obviously in protected areas. This paper questions the motives of some NGOs and governments in Australia in pursuing additional restrictions on fishing which are mostly unnecessary and disproportionate to the sustainability requirements of other sources of food. This is done within the context of the global need for sustainable seafood supply and the need for effective marine conservation that addresses all threats to marine ecosystems in proportion to the magnitude of each threat.

Wearable and wireless accelerometer systems for monitoring Parkinson’s disease patients—A perspective review  [PDF]
Robert LeMoyne
Advances in Parkinson's Disease (APD) , 2013, DOI: 10.4236/apd.2013.24021
Abstract: Parkinson’s disease is a growing medical concern as societies, such as the United States of America, become progressively aged. Therapy strategies exist for the amelioration of Parkinson’s disease symptoms, and the quantification of attributes, such as hand tremor, can provide valuable feedback. Wearable and wireless accelerometer systems for monitoring Parkinson’s disease patients have been progressively advanced over the course of the past half-decade. In particular, wireless accelerometer nodes and smartphones, such as the iPhone, hold promise for optimizing therapy strategy by providing convenient quantified feedback. This perspective review addresses the current advances in wearable and wireless accelerometer systems for monitoring Parkinson’s disease patients and forecasts for the near future.
A Study of Lateralized Cognitive Processes in Upper-Division Electrical Engineering Students’: Correlating Written Language Functions with Analytical Reasoning in Microelectronics  [PDF]
Robert Melendy
World Journal of Engineering and Technology (WJET) , 2014, DOI: 10.4236/wjet.2014.22008
Abstract: The human brain is asymmetrical in function, with each of its two hemispheres being somewhat responsible for distinct cognitive and motor tasks, to include writing. It stands to reason that engineering students who have established entrance into their upper-division programs will have demonstrated cognitive proficiency in math and logical operations, abstract and analytical reasoning and language usage, to include writing. In this study the question was asked: is there a correlation between an upper-division electrical engineering students’ analytical reasoning ability and their descriptive writing ability? Descriptive writing is taken here to mean a students’ ability to identify key physical aspects of a mathematical model and to express—in words—a concise and well-balanced description that demonstrates a deep conceptual understanding of the model. This includes more than a description of the variables or the particular application to an engineering problem; it includes a demonstrated recognition of the basic physics that govern the model, certain limitations (idealizations) inherent in the model, and an understanding of how to make practical experimental measurements to verify the governing physics in the model. A student at this level may demonstrate proficiency in their analytical reasoning skills and hence be capable of correctly solving a given problem. However, this does not guarantee that the same student is skilled in associating equations with their physical meaning on a deep conceptual level or in understanding physical limitations of the equation. Consequently, such a student may demonstrate difficulty in mapping their comprehension of the model into written language that demonstrates a sound conceptual understanding of the governing physics. The findings represent a sample of two independent class sections of Electrical and Computer Engineering junior’s first course in Microe-lectronic Devices and Circuits during fall semesters 2012 and 2013 at a private mid-size university in NW Oregon. A total of three exams were administered to each of the 2012/2013 groups. Correlations between exam scores that students achieved on their descriptive writing of microelectronics phenomena and their analytical problem-solving abilities were examined and found to be quite significant.
Foilized pouches can prevent the transmission of HIV from mother to child using multi-drug therapies  [PDF]
Robert Malkin
Journal of Biomedical Science and Engineering (JBiSE) , 2014, DOI: 10.4236/jbise.2014.71007
Abstract: Children can become HIV positive (HIV+) from their mother during home birth. If the infant ingests antiretroviral (ARV), medications immediately after birth, the risk of transmission can be dramatically reduced. We have previously proposed the use of foilized, polyethylene-lined pouches to store ARV’s. Using the pouch, the mother receives the medication at an antenatal care visit, months before delivery, and if she delivers at home, tears open the pouch and drips the medication into her child’s mouth. In this work, we extend the use of the pouch to store a modern ARV, Lamivudine (3TC), often used in multi-drug regimens. Under laboratory conditions, pouches were filled with 3TC and stored at 25?C/60% relative humidity (RH) for twelve months. We found that the 3TC was stable throughout the year (maximum 5.6% of labeled concentration change). The preservatives were somewhat degraded by the act of repackaging the medicine, but sufficient preservatives remained to maintain the medication. The same impurities were identified in the 3TC stored in the pouches and the samples removed from the bottles indicating that the pouches do not introduce new impurities (impurities that are not already introduced by the bottle). We conclude that the pouch can preserve this modern ARV for up to twelve months.
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