bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastable zone determination of lipid systems: Ultrasound velocity versus optical back‐reflectance measurements
Authors: Chaleepa Kesarin , Szepes Anikó , Ulrich Joachim
Published: March 2010

The metastable zone width (MZW) of a multi‐component system as influenced by the process parameters cooling rate, agitation speed, and additive concentration was determined via ultrasound velocity measurements. The results were compared with those obtained by optical back‐reflectance measurements (ORM) using coconut oil as a model substance. Increasing the cooling rate led to the shift of the nucleation point to lower temperatures. This tendency was better visualized by the ultrasonic curves while a significant disturbance of the ORM signal could be observed. Agitation led to an increase of the nucleation temperature and hence a narrower metastable zone. The influence of an additive on the MZW was found to strongly depend on its concentration. The MZW detected by the ultrasound technique was narrower compared to that obtained by the ORM method, indicating the faster response to the phase transition of the ultrasound technique. Another advantage of the ultrasound technique was the in situ evaluation of the experimental data, while ORM needed a linear fitting to estimate the saturation temperature. Furthermore, ultrasound velocity measurements are based on density determination of the medium whereas the ORM sensor is able to detect only particles that are located within the measuring zone and possess a well‐defined size.

Practical applications: MZW is one of the most important parameters that determine the characteristics of crystalline products. However, a proper technique that can be used in MZW detection in fat systems has rarely been reported, due to the difficulties in dealing with natural fats. The findings of this study can greatly help those who are involved in the field of fat crystallization from both the academic and the practical point of view. This is due to the fact that new and promising techniques for the online and in situ determination of the MZW of fats, with high accuracy, and reproducibility, under most process conditions, were clarified in this work. The readers can easily follow the procedure developed in this paper. Also information about the influence of process parameters and additives on the MZW is included.
Synthesis and Photophysical Properties of 3,5‐Bis(oxopyridinyl)‐ and 3,5‐Bis(pyridinyloxy)‐Substituted Boron‐Dipyrromethenes
Authors: Khan Tamanna K. , Rao M. Rajeswara , Ravikanth M.
Published: March 2010

Nucleophilic substitution reactions of 2‐, 3‐ and 4‐hydroxypyridines with 3,5‐dibromo meso‐aryl and meso‐furyl boron‐dipyrromethenes (BODIPYs) resulted in the formation of the corresponding 3,5‐bis(oxopyridinyl)‐BODIPYs and 3,5‐bis(pyridinyloxy)‐BODIPYs in decent yields. The effect of a pyridone versus an oxypyridine at the 3‐ and 5‐positions on the spectral, electrochemical and photophysical properties were studied as a function of solvent. The 3,5‐bis(oxopyridinyl)‐BODIPYs exhibit broad, red‐shifted absorption and emission bands, decreased quantum yields and lifetimes, displayed large Stokes shifts and easier reductions than did the 3,5‐bis(pyridinyloxy)‐BODIPYs. The differences in the properties of these two classes of BODIPY dyes are attributed to the extension of π‐delocalization associated with the electron‐deficient nature of the pyridone groups.
Simple, coupled algorithms for solving creeping flows and their application to electro‐osmotic flows
Authors: Suh Yong Kweon , Kang Sangmo
Published: March 2010

In this study we developed simple, coupled algorithms for solving low‐Reynolds‐number flows applicable to micro‐scale flows such as electro‐osmotic flows. The most popular scheme, i.e. the projection method, is not suitable for such flows because of its undesirable slip effect on boundaries at low‐Reynolds‐numbers. In our method, the velocity and pressure are strongly coupled, and the momentum and pressure equations are solved iteratively by using the successive over relaxation (SOR) method while exchanging the unknown variables as soon as they have been updated. The developed methods are applied to a model flow for evaluating their performance. It was found that the coupled schemes are indeed superior to a projection method, i.e. the fractional‐step method, in both numerical accuracy and CPU time. The code is then applied to a dc electro‐osmotic flow within a cavity driven by electrical force acting on the ions spread in the fluid. In this application, the system of equations for the fluid flow and that for the ion transport are solved in a decoupled way, but each system is solved by using fully implicit schemes. From the simulations and by introducing the concept of vorticity source, we can identify two roles of the body force, one contributing to build‐up of the osmotic pressure and the other to the fluid flow. The interesting reverse flow occurring after the external potentials applied on the electrodes have been shut off is also investigated in terms of the vorticity source. Copyright © 2010 John Wiley & Sons, Ltd.
Prescribing options for leukaemia in the spotlight at ASH 2009
Authors: Pinn Stephen
Published: March 2010

UK doctors figured prominently during the clinical sessions at the 51st annual meeting of the American Society of Hematology (ASH) held in New Orleans, December 4‐8, 2009, which attracted a worldwide audience of more than 25 000 blood disorder and oncology specialists. Copyright © 2010 John Wiley & Sons, Ltd.
Performance Tests and Pressure Drop Measurements in the Anode Flowfield of a μDMFC
Authors: Hsieh S.‐S. , Chen W.‐C.
Published: March 2010

Cell performance tests and measurements of the pressure drops in the anode flow channels of a custom‐made microdirect methanol fuel cell (μDMFC) are conducted and studied for different methanol concentrations (0.5–2 M), flow rates (10–20 sccm) and operating temperatures (40–80 °C). The anode flowfields consist of three channel/four pass flow channels with widths of 500–2000 μm and a total length of 300–400 mm. Moreover, flow characteristics of the CO2 gas bubbles and methanol solution in the anode flow channels are identified and analysed for CO2 fraction through visualisation. Finally, an optimal channel size for the present μDMFC is obtained.
Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells
Authors: Tirnitz-Parker Janina E. E. , Viebahn Cornelia S. , Jakubowski Aniela , Klopcic Borut R. S. , Olynyk John K. , Yeoh George C. T. , Knight Belinda
Published: March 2010

Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis.

In vivo

studies have suggested that a tumor necrosis factor family member, tumor necrosis factor–like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin–positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFκB subunit by RNA interference.

Conclusion:

TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFκB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (Hepatology 2010)
Bid Agonist Regulates Murine Hepatocyte Proliferation by Controlling Endoplasmic Reticulum Calcium Homeostasis
Authors: Ni Hong-Min , Baty Catherine J. , Li Na , Ding Wen-Xing , Gao Wentao , Li Min , Chen Xiaoyun , Ma Jianjie , Michalopoulos George K. , Yin Xiao-Ming
Published: March 2010

BH3-interacting domain death agonist (Bid), a BH3-only B cell lymphoma 2 family molecule, is generally known for its importance in activating the mitochondrial apoptosis pathway after death receptor engagement, particularly in hepatocytes. However, Bid also promotes hepatocyte proliferation during liver regeneration and carcinogenesis. This study was designed to examine the hypothesis that Bid regulates endoplasmic reticulum calcium concentration ([Ca2+]ER) homeostasis to affect hepatocyte proliferation. We found that serum-stimulated hepatocyte proliferation was dependent on calcium, and the depletion of calcium with thapsigargin or ethylene glycol tetraacetic acid (EGTA) inhibited the proliferation. Subcellular fractionation showed that a portion of Bid was inserted into the endoplasmic reticulum (ER)–enriched membranes, and single-cell calcium imaging indicated that Bid was important for maintaining the [Ca2+]ER level. Bid-deficient hepatocytes manifested delayed and reduced serum-stimulated proliferation, which was corrected by ionomycin or reconstitution of Bid, particularly an ER-targeted Bid. Finally, B cell lymphoma 2–associated X protein (Bax) could also be found in the ER-enriched membranes, and Bax deficiency caused the same proliferation defect. However, Bid/Bax double deletion in hepatocytes did not further augment the defect, which suggested that Bid and Bax worked by the same regulatory mechanism in [Ca2+]ER control.

Conclusion:

Bid regulates hepatocyte proliferation by positively affecting [Ca2+]ER homeostasis, and this could be important for liver regeneration and carcinogenesis. (Hepatology 2010)
Hippocampal epigenetic modification at the brain‐derived neurotrophic factor gene induced by an enriched environment
Authors: Kuzumaki Naoko , Ikegami Daigo , Tamura Rie , Hareyama Nana , Imai Satoshi , Narita Michiko , Torigoe Kazuhiro , Niikura Keiichi , Takeshima Hideyuki , Ando Takayuki , Igarashi Katsuhide , Kanno Jun , Ushijima Toshikazu , Suzuki Tsutomu , Narita Minoru
Published: March 2010

Environmental enrichment is an experimental paradigm that increases brain‐derived neurotrophic factor (BDNF) gene expression accompanied by neurogenesis in the hippocampus of rodents. In the present study, we investigated whether an enriched environment could cause epigenetic modification at the BDNF gene in the hippocampus of mice. Exposure to an enriched environment for 3–4 weeks caused a dramatic increase in the mRNA expression of BDNF, but not platelet‐derived growth factor A (PDGF‐A), PDGF‐B, vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), or glial fibrillary acidic protein (GFAP), in the hippocampus of mice. Under these conditions, exposure to an enriched environment induced a significant increase in histone H3 lysine 4 (H3K4) trimethylation at the BDNF P3 and P6 promoters, in contrast to significant decreases in histone H3 lysine 9 (H3K9) trimethylation at the BDNF P4 promoter and histone H3 lysine 27 (H3K27) trimethylation at the BDNF P3 and P4 promoters without any changes in the expression of their associated histone methylases and demethylases in the hippocampus. The expression levels of several microRNAs in the hippocampus were not changed by an enriched environment. These results suggest that an enriched environment increases BDNF mRNA expression via sustained epigenetic modification in the mouse hippocampus. © 2010 Wiley‐Liss, Inc..
Emotional consequences of wheel running in mice: Which is the appropriate control?
Authors: Dubreucq Sarah , Marsicano Giovanni , Chaouloff Francis
Published: March 2010

An overview of the literature on the emotional impacts of wheel running reveals contradictory findings. Among the hypotheses underlying such a discrepancy, that related to the different housing conditions of the controls, i.e., standard housing without any object or housing with blocked running wheels, merits attention. We addressed this point in C57Bl/6N mice by examining the consequences of chronic wheel running on anxiety, context fear recall, and behavioral despair compared either to standard control housing or to housing with blocked wheels. Compared to standard housing, wheel running proved anxiolytic while facilitating fear memory. On the other hand, wheel running increased behavioral despair but influenced neither anxiety nor fear memory when compared to housing with blocked wheels. This study suggests that investigations aimed at measuring the emotional consequences of wheel running should take into consideration the housing conditions of the controls to which are compared the runners. © 2010 Wiley‐Liss, Inc.
Recollection‐related hippocampal activity during continuous recognition: A high‐resolution fMRI study
Authors: Suzuki Maki , Johnson Jeffrey D. , Rugg Michael D.
Published: March 2010

We used high‐resolution functional magnetic resonance imaging to investigate whether successful recollection during continuous recognition is associated with relative enhancement of hippocampal activity, consistent with prior findings from experiments employing separate study and test phases. While being scanned, subjects discriminated between new and repeated pictures. Each picture, which was repeated once after an interval of between 10 and 30 items, was surrounded by a frame that was colored gray, blue, or orange. When an item repeated, its frame color determined the correct response. Repeated items surrounded by a gray frame always required an “old” judgment. A repeated item surrounded by a blue or an orange frame required a different response depending whether it was represented in the same (Target) or a different (Nontarget) color from the first presentation. Consistent with the results from previous continuous recognition experiments, robust new > old effects were found in bilateral hippocampus. In addition, an across‐subjects correlational analysis identified a cluster of voxels in right hippocampus where recollection‐related activity (operationalized by the contrast between correctly vs. incorrectly judged Nontargets) was positively correlated with recollection performance. Thus, successful recollection during continuous recognition is associated with a relative enhancement of hippocampal activity. © 2010 Wiley‐Liss, Inc.
Survey of methodologies for developing media screening values for ecological risk assessment
Authors: Barron Mace G. , Wharton Steven R.
Published: March 2010

This review evaluates the methodologies of 13 screening value (SV) compilations that have been commonly used in ecological risk assessment (ERA), including compilations from state and U.S. federal agencies, the Oak Ridge National Laboratory (ORNL), Canada, The Netherlands, and Australia. The majority of surfacewater SVs were primarily derived for the protection of aquatic organisms using 2 approaches: (1) a statistical assessment of toxicity values by species groupings, such as “ambient water quality criteria,” or (2) extrapolation of a lowest observed adverse effect level determined from limited toxicity data using an uncertainty factor. Sediment SVs were primarily derived for the protection of benthic invertebrates using 2 approaches: (1) statistical interpretations of databases on the incidence of biological effects and chemical concentrations in sediment, or (2) values derived from equilibrium partitioning based on a surfacewater SV. Soil SVs were derived using a diversity of approaches and were usually based on the lowest value determined from soil toxicity to terrestrial plants or invertebrates and, less frequently, from modeled, incidental soil ingestion or chemical accumulation in terrestrial organisms. The various SV compilations and methodologies had varying levels of conservatism and were not consistent in the pathways and receptors considered in the SV derivation. Many SVs were derived from other compilations and were based on outdated values, or they relied on only older toxicity data. Risk assessors involved in ERA should carefully evaluate the technical basis of SVs and consider the uncertainty in any value used to determine the presence or absence of risk and the need for further assessment.
Actinides in deer tissues at the rocky flats environmental technology site
Authors: Todd Andrew S. , Sattelberg R. Mark
Published: March 2010

Limited hunting of deer at the future Rocky Flats National Wildlife Refuge has been proposed in U.S. Fish and Wildlife planning documents as a compatible wildlife-dependent public use. Historically, Rocky Flats site activities resulted in the contamination of surface environmental media with actinides, including isotopes of americium, plutonium, and uranium. In this study, measurements of actinides [Americium-241 (241Am); Plutonium-238 (238Pu); Plutonium-239,240 (239,240Pu); uranium-233,244 (233,234U); uranium-235,236 (235,236U); and uranium-238 (238U)] were completed on select liver, muscle, lung, bone, and kidney tissue samples harvested from resident Rocky Flats deer (N = 26) and control deer (N = 1). In total, only 17 of the more than 450 individual isotopic analyses conducted on Rocky Flats deer tissue samples measured actinide concentrations above method detection limits. Of these 17 detects, only 2 analyses, with analytical uncertainty values added, exceeded threshold values calculated around a 1 × 10−6 risk level (isotopic americium, 0.01 pCi/g; isotopic plutonium, 0.02 pCi/g; isotopic uranium, 0.2 pCi/g). Subsequent, conservative risk calculations suggest minimal human risk associated with ingestion of these edible deer tissues. The maximum calculated risk level in this study (4.73 × 10−6) is at the low end of the U.S. Environmental Protection Agency's acceptable risk range.
Risk assessment for children exposed to decabromodiphenyl (oxide) ether (deca) in the United States
Authors: Hays Sean M , Pyatt David W
Published: March 2010

Decabromodiphenyl (oxide) ether (Deca) is a widely used brominated flame retardant in the United States predominantly in the hard-plastic housings of consumer electronics and in flame-retarded backing on textiles used in furniture. A child-specific exposure assessment of Deca was performed for the US Environmental Protection Agency's Voluntary Children's Chemical Evaluation Program (VCCEP). The VCCEP guidance for a tier 1 exposure assessment requires that a screening-level assessment be conducted using currently available data and conservative assumptions. For Deca, relevant exposure pathways considered were general environmental exposures (e.g., exposures to contaminated soil, dust, air, and food), breast milk exposures, inhalation of Deca-containing particulates in air, and mouthing Deca-containing consumer products. For each of these scenarios, a mid-range and upper estimate of age-appropriate intakes were calculated. The calculated intakes indicate that, despite the uncertainties, children appear to be exposed to Deca at levels at least 1 order of magnitude, with most being several orders of magnitude, below the National Academy of Sciences reference dose for Deca of 4 mg/kg/d. This analysis indicates that, using the available data, current levels of Deca in the United States are unlikely to represent an adverse health risk for children.
Assessment of persistency and bioaccumulation in pesticide registration frameworks within the organization for economic cooperation and development
Authors: Montforts Mark HMM
Published: March 2010

This article describes the results of a survey conducted in 2003 on methods used by different member countries within the Organization for Economic Cooperation and Development (OECD) to evaluate persistent and bioaccumulative pesticides. The objectives were to establish the differences in taking persistence (P) and bioaccumulation (B) into account in the decision-making process and to establish the influence of the assessors' subjectivity to data interpretation and data selection. Fifteen countries participated in the survey, which generated a vast amount of information on decision making, risk assessment, risk classification, and data treatment. Survey results indicated clear differences in approaches to the use of P, B, and toxicity (T) information in scientific risk assessment. Using the same data for 2 different pesticides, several OECD member countries responded differently in classifying both substances as P, B, and T. Differences in regulatory decision-making were also apparent because, based on identical classifications, several OECD member countries adopted different decisions on pesticide registration; recommendations were based, with respect to technical guidance, on data handling, training of assessors, and handling of uncertainty in risk assessment.
Risk-based decision making to manage contaminated sediments
Authors: Bridges Todd S , Apitz Sabine E , Evison Leah , Keckler Kymberlee , Logan Mary , Nadeau Steve , Wenning Richard J
Published: March 2010

This paper summarizes discussion among the 7 authors who served on an expert panel at the Third Battelle International Conference on Remediation of Contaminated Sediments held in New Orleans, Louisiana, USA, in January 2005. In this article, the authors review how sediment management decisions are currently made and address the question of how management decisions should be made in the future. It is arguably the case that sediment remediation presents greater challenges and more complexity than traditional land-based clean-ups. Although understanding of these challenges and complexities has grown over the last 25 y, there has been, until recently, relatively little innovation in the approaches used to manage the environmental risks posed by contaminated sediments. New methods that facilitate a more rigorous analysis of the multiple criteria considered in decision making have been developed. These methods, collectively known as multicriteria decision analysis (MCDA), coupled with the use of comparative-risk assessment and cost/benefit analysis, are proposed as an effective, efficient, and credible foundation for evaluating remedy alternatives at contaminated sediment sites.
The role of monitored natural recovery in sediment remediation
Authors: Magar Victor S , Wenning Richard J
Published: March 2010

The long-term goal of monitored natural recovery (MNR) is to achieve ecological recovery of biological endpoints in order to protect human and ecological health. Insofar as ecological recovery is affected by surface-sediment-contaminant concentrations, the primary recovery processes for MNR are natural sediment burial and contaminant transformation and weathering to less toxic forms. This paper discusses the overall approach for effective implementation of MNR for contaminated sediment sites. Several lines of evidence that may be used to demonstrate natural recovery processes are summarized, including documentation of source control; evidence of contaminant burial; measurement of surface sediment mixing depths and the active sediment benthic layer; measurement of sediment stability; contaminant transformation and weathering; modeling sediment transport, contaminant transport, and ecological recovery; measuring ecological recovery and long-term risk reduction; knowledge of future plans for use and development of the site; and watershed and institutional controls. In general, some form of natural recovery is expected and should be included as part of a remedy at virtually all contaminated sediment sites. Further, MNR investigations and an understanding of natural recovery processes provide cost-effective information and support the evaluation of more aggressive remedies such as capping, dredging, and the use of novel amendments. The risk of dredging or capping may be greater than the risk of leaving sediments in place at sites where capping or dredging offer little long-term environmental gain but pose significant short-term risks for workers, local communities, and the environment.
Cost-benefit analysis and the water framework directive in Scotland
Authors: Hanley Nick , Black Andrew R
Published: March 2010

The Water Framework Directive seeks to achieve the enhancement of aquatic ecosystem quality for all waters across Europe. However, it recognizes the need to accommodate social and economic considerations, so Heavily Modified Water Bodies may be designated where achievement of the Directive's objectives may result in disproportionate costs. This necessitates the use of cost and benefit data, which may be hard to acquire. Benefits and costs of implementing the Directive also can be tested at the national level. This paper considers the evaluation of costs and benefits at 2 scales in Scotland: microlevel analysis, for case studies on the rivers Tummel and Dee and the Forth Estuary, and macrolevel analysis. In the microlevel analysis, costs of hydroelectric power generation are compared with the marginal benefits of increased fisheries revenues and are argued to be disproportionate. In the estuary environment, the benefits of returning an area to ecologically productive salt marsh and mudflats are compared with the costs of lost agricultural revenue. In the macrolevel analysis, we compare the costs to impacted industries with the estimated national benefits from implementing the Directive. We find that for Scotland as a whole, implementation is predicted to result in positive net social benefits.
Costs and benefits of communicating product safety information to the public via the internet
Authors: Saouter Erwan , Andreasent Ina
Published: March 2010

Procter&Gamble (P&G) developed Science-in-the-Box (SIB; www.scienceinthebox.com) after discussions with their stakeholders as to how the consumer products company could better communicate key environmental performance and safety information to the public. A series of workshops enabled P&G to understand that consumers and other key business decision makers wanted meaningful information about the science behind P&G products. In addition, it was clear that making such information available would produce business benefits by encouraging long-term relationships with decision makers ranging from consumers and retailers to policy makers and nongovernmental organizations. These benefits were not necessarily quantifiable in the short term, but they still had to be balanced by the costs in terms of resource commitment and potential intellectual property issues. Since its inception in September 2002, SIB has successfully reached key target audiences and built improved credibility and confidence in P&G products and approaches. The website is now available in English, French, Spanish, German, and Italian and is used by consumers, journalists, teachers, scientists, and policy makers. Several user surveys carried out during the initial developmental period, together with unsolicited e-mail feedback, have demonstrated that SIB has successfully created a platform for continuous dialogue with consumers and other interested parties.
Characterizing the risks to aquatic ecosystems: A tentative approach in the context of freshwater dredged material disposal
Authors: Babut Marc P. , Delmas Hélène , Bray Marc , Durrieu Claude , Perrodin Yves , Garne Jeanne
Published: March 2010

The development of relevant frameworks for assessing ecological risks posed by dredged material management does not only involve an appropriate selection of assessment and measurement endpoints but also requires a sound approach to both risk characterization and the associated uncertainty. A formal methodology addressing both aspects has been developed in France for freshwater sediment deposits in water. Both exposure and effects measurements are 1 st transformed into scores or classes. As far as possible, class boundaries are based on existing knowledge or expertise. Benthic organism exposure is based on a ratio of the deposit area to the burrow pit area, whereas pelagic species exposure is based on the ratio of porewater volume to water column volume. The combination of exposure and effect scores yields risk scores, or classes, which are linked to management decisions. Uncertainty is assessed with respect to a set of 4 predetermined criteria for exposure (the strength of association with the assessment endpoint, spatial and temporal representativeness, and the use of standard methods) and 4 criteria for effects (strength of association, the distinction between effect and no effect, sensitivity, and the use of standard methods). This approach was applied to 8 sediments from French canals contaminated to varying degrees.
Assessment of aquatic ecological risk and site-specific criteria of copper in San Francisco Bay, California, USA
Authors: Arnold W. Ray , Warren-Hicks William J.
Published: March 2010

A new regression-based copper toxicity model was applied in a case study of San Francisco Bay, California, USA, to demonstrate its utility in estimating risk and site-specific water quality criteria. This was accomplished using probabilistic techniques and a simple model relating dissolved organic carbon (DOC) concentrations with the toxicity of dissolved copper to embryos of the most copper sensitive taxon (Mytilus) in the US Environmental Protection Agency's (USEPA) water quality criteria database. Similar probabilistic techniques were applied to data developed for San Francisco Bay using the USEPA's water-effect ratio (WER) methods for comparison with the DOC-based method. Based on 595 site- and date-specific DOC model observations at 26 sites in San Francisco Bay, none suggested risk of chronic toxicity. Safety factors (1/risk quotient) on average across all sites ranged from 2.4 to 9.1. Comparisons were made between 1) estimates of site-specific criteria made using the DOC method, 2) estimates of site-specific criteria made using the WER method, 3) USEPA national and California Toxics Rule criteria, and 4) region-specific criteria recommended for regulatory implementation by the Clean Estuary Partnership. The DOC- and WER-based methods indicated that copper criteria for San Francisco Bay could be increased above USEPA and California Toxics Rule criteria and will retain the level of protection (≥97%) embodied in the USEPA copper saltwater water quality criteria. The DOC method overall was more conservative (i.e., implies the need for lower criteria in the Bay) than the WER method. The DOC method suggests that the region-specific criteria being recommended for regulatory implementation would be underprotective in some areas and yet could be increased and remain protective in other areas of San Francisco Bay.
Comparison of tropical and temperate freshwater animal species' acute sensitivities to chemicals: Implications for deriving safe extrapolation factors
Authors: Kwok Kevin WH , Leung Kenneth MY , Lui Gilbert SG , Chu Vincent KH , Lam Paul KS , Morritt David , Maltby Lorraine , Brock Theo CM , Van den Brink Paul J , Warne Michael St J , Crane Mark
Published: March 2010

Toxicity data for tropical species are often lacking for ecological risk assessment. Consequently, tropical and subtropical countries use water quality criteria (WQC) derived from temperate species (e.g., United States, Canada, or Europe) to assess ecological risks in their aquatic systems, leaving an unknown margin of uncertainty. To address this issue, we use species sensitivity distributions of freshwater animal species to determine whether temperate datasets are adequately protective of tropical species assemblages for 18 chemical substances. The results indicate that the relative sensitivities of tropical and temperate species are noticeably different for some of these chemicals. For most metals, temperate species tend to be more sensitive than their tropical counterparts. However, for un-ionized ammonia, phenol, and some pesticides (e.g., chlorpyrifos), tropical species are probably more sensitive. On the basis of the results from objective comparisons of the ratio between temperate and tropical hazardous concentration values for 10% of species, or the 90% protection level, we recommend that an extrapolation factor of 10 should be applied when such surrogate temperate WQCs are used for tropical or subtropical regions and a priori knowledge on the sensitivity of tropical species is very limited or not available.
Addressing public health risks for cyanobacteria in recreational freshwaters: The oregon and vermont framework
Authors: Stone David , Bress William
Published: March 2010

Toxigenic cyanobacteria, commonly known as blue green algae, are an emerging public health issue. The toxins produced by cyanobacteria have been detected across the United States in marine, freshwater and estuarine systems and associated with adverse health outcomes. The intent of this paper is to focus on how to address risk in a recreational freshwater scenario when toxigenic cyanobacteria are present. Several challenges exist for monitoring, assessing and posting water bodies and advising the public when toxigenic cyanobacteria are present. These include addressing different recreational activities that are associated with varying levels of risk, the dynamic temporal and spatial aspects of blooms, data gaps in toxicological information and the lack of training and resources for adequate surveillance. Without uniform federal guidance, numerous states have taken public health action for cyanobacteria with different criteria. Vermont and Oregon independently developed a tiered decision-making framework to reduce risk to recreational users when toxigenic cyanobacteria are present. This framework is based on a combination of qualitative and quantitative information.
Field studies in pesticide registration: Questioning the answers
Authors: Montforts Mark HMM , de Jong Frank MW
Published: March 2010

The principal conclusion of a workshop in October 2005 at RIVM (Bilthoven, The Netherlands) on the assessment of field studies with pesticides for authorization is that the lack of a definition of acceptability of effects is recognized as a problem by all stakeholders: Industry, risk assessors, and regulators. Because of this lack of definition in the legislation, it is unclear what critical effect values should be assessed in field studies. Despite the extensive documentation on field study performance, the decision making is not based on justifiable scientific opinions or publicly shared values but on technical limitations of the test design instead. In the workshop, research was identified that should result in a scientific basis for value judgments applied in decision making.
Insight into the variation in calculated human exposure to soil contaminants using seven different european models
Authors: Swartjes Frank A
Published: March 2010

In order to get insight into the variation in calculated human exposure, the outputs of 7 European exposure models have been compared. Twenty scenarios, differing with respect to land use, soil type, and contaminant, formed the basis for calculating human exposure to soil contaminants. All calculations were performed twice: Once with a standardized set of parameters for all models and once with the own default parameters. This led to the conclusion that the variation in calculated total exposure (combining all exposure pathways) is large (the majority of the outputs is in between a factor of 100 higher and a factor of 100 lower than the scenario medians). In addition, variation for exposure due to indoor air inhalation is also large. The variation for exposure due to crop consumption is substantial (the majority of the outputs is in between a factor of 10 higher and a factor of 10 lower than the scenario medians) and limited for exposure due to soil ingestion (limited = the majority of the outputs is within a factor of 5 higher and a factor of 5 lower than the scenario medians). The variation in calculated exposure increases when a contaminant is more mobile and, particularly, more volatile. The variation due to selection of input parameters does only yield an additional variation over the variation due to model algorithms for exposure due to soil ingestion and, to a lesser extent, for exposure due to crop consumption. The variation in calculated exposure is not dependent on the soil type and hardly dependent (only for exposure due to soil ingestion) on land use. The choice of model is a very significant factor for the absolute value of calculated exposure. For the promotion of uniformity it was recommended to construct a toolbox for the calculation of human exposure, for general use, including standardized tools and flexible tools, the latter to account for region-specific or country-specific (geographical, ethnological, and cultural) elements and national policy decisions.
Improving uncertainty analysis in european union risk assessment of chemicals
Authors: Verdonck Frederik AM , Souren Astrid , van Asselt Marjolein BA , van Sprang Patrick A , Vanrolleghem Peter A
Published: March 2010

Handling uncertainty in the current European Union (EU) risk assessment of new and existing substances is problematic for several reasons. The known or quantifiable sources of uncertainty are mainly considered. Uncertainty is insufficiently, explicitly communicated to risk managers and decision makers but hidden and concealed in risk quotient numbers that appear to be certain and, therefore, create a false sense of certainty and protectiveness. The new EU chemical policy legislation, REACH, is an opportunity to learn from interdisciplinary thinking in order to evolve to smart risk assessment: an assessment in which awareness and openness to uncertainty is used to produce better characterizations and evaluations of risks. In a smart risk assessment context, quantifying uncertainty is not an aim but just a productive means to refine the assessment or to find alternative solutions for the problem at stake. Guidance and examples are given on how to differentiate, assess, and use uncertainty.
How well can we predict the toxicity of pesticide mixtures to aquatic life?
Authors: Belden Jason B , Gilliom Robert J , Lydy Michael J
Published: March 2010

Results of published pesticide mixture toxicity experiments conducted with aquatic organisms were compiled and evaluated to assess the accuracy of predictive mixture models. Three types of models were evaluated: Concentration addition (CA), independent action (IA), and simple interaction (SI). The CA model was the most often tested (207 experiments), followed by SI (59) and IA (37). The reviewed experiments are listed in the Supplemental material to provide a resource for future investigators. The predictive accuracy of each model was quantified for each experiment by the model deviation ratio (MDR), which was calculated by dividing the predicted toxicity by the observed toxicity. Eighty-eight percent of all experiments that evaluated the CA model had observed effective concentrations within a factor of 2 of predicted values (MDR values from 0.5–2.0). The median MDR was 1, about 5% of MDRs were less than 0.5, and about 5% were greater than 2, indicating unbiased estimates overall. The predictive accuracy of CA and IA models was influenced, however, by the different modes of action (MOA) of the pesticides. For experiments with pesticides with the same MOA, CA more accurately predicted effective concentrations for more experiments compared to IA, which tended to underpredict toxicity. The IA model was somewhat more accurate than the CA model for most mixtures with different MOAs, but in most cases there were relatively small differences between the models. Additionally, 80% of SI experiments had an MDR value below 2.0 despite a bias towards experiments that are likely to have an interaction. Thus, results indicate that the CA model may be used as a slightly conservative, but broadly applicable model with a relatively small likelihood of underestimating effects due to interactions.
Genetic variations of DNA repair genes and their prognostic significance in patients with acute myeloid leukemia
Authors: Shi Jing‐Yi , Ren Zhi‐Hong , Jiao Bo , Xiao Run , Yun Hai‐Yang , Chen Bing , Zhao Wei‐Li , Zhu Qi , Chen Zhu , Chen Sai‐Juan
Published: March 2010

Common genetic variations in genes involved in DNA repair or response to genotoxic stress may influence both cancer susceptibility and treatment response individually or interactively. However, in acute myeloid leukemia (AML), the relevance of these genetic variations remains to be fully established. In this study, we analyzed 42 genetic variations among 15 candidate genes in 307 AML patients and 560 age‐sex matched controls. Their associations with chemotherapy response were further evaluated in combination with other well‐established prognostic factors. An increased risk of AML was found in individuals heterozygous for XPD 2251A>C (rs13181) with an odds ratio (OR) of 1.637 (95% confidence interval [CI]: 1.118–2.395), and the increased risk could be attributed to C allele (OR = 1.505, 95% CI: 1.061–2.134). Postchemotherapy response analysis revealed that AML patients heterozygous for ATM 4138C>T (rs3092856) or GG homozygous for TP53 215C>G (rs1042522) were independently linked to inferior treatment outcomes. These results uncover novel prognostic factors for AML patients treated with chemotherapy and may also indicate an etiological role of XPD in this disease.
Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: Systematic review and meta‐analysis
Authors: Cho Lisa Y. , Yang Jae Jeong , Ko Kwang‐Pil , Park Boyoung , Shin Aesun , Lim Min Kyung , Oh Jin‐Kyoung , Park Sohee , Kim Yoon Jun , Shin Hai‐Rim , Yoo Keun‐Young , Park Sue K.
Published: March 2010

A subadditive effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is possible because superinfection of one virus tends to inhibit infection of the other virus. However, studies have reported inconsistent findings, and two meta‐analyses of studies from various countries (1998) and China (2005) reported a supraadditive effect for hepatocellular carcinoma (HCC) risk. Thus, we reevaluate HBV/HCV monoinfection and coinfection. Of 411 reports, we included 59 studies that assessed the association between HBV/HCV monoinfection and coinfection for HCC risk. HCC risk because of high/detectable HBV DNA and HBeAg infection was higher than HBsAg infection, whereas anti‐HCV vs anti‐HCV/HCV RNA was not different. Geographically, HCC risk was significantly higher in nonendemic than in HBV or HCV endemic areas. Subadditive effect for HCC risk was presented in recently published studies, cohort studies and studies conducted in HBV/HCV nonendemic areas; an additive effect was presented in studies conducted in HBV endemic areas; a supraadditive effect was presented in previously published studies, case‐control studies and studies conducted in HCV endemic areas. Our results suggest HBV/HCV coinfection for HCC risk is not significantly greater than HBV/HCV monoinfection, and HCC risk due to HBV or HCV is higher in nonendemic than endemic areas. The p‐heterogeneity was significant for most analyses, except HBV(+)/HCV(+) and HBV biomarker analyses. Prevention strategies targeted toward HBV or HCV monoinfected patients are needed. In addition, tailored prevention to reduce infectivity such as HBV markers (HBeAg, HBV DNA) is needed.
Unimpeded skin carcinogenesis in K14‐HPV16 transgenic mice deficient for plasminogen activator inhibitor
Authors: Masset Anne , Maillard Catherine , Sounni Nor Eddine , Jacobs Nathalie , Bruyére Françoise , Delvenne Philippe , Tacke Marlene , Reinheckel Thomas , Foidart Jean‐Michel , Coussens Lisa M. , Noël Agnès
Published: March 2010

Angiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the plasminogen activator inhibitor‐1 (PAI‐1). Considering the recognized importance of PAI‐1 in the regulation of tumor angiogenesis and invasion in murine models of skin tumor transplantation, we explored the functional significance of PAI‐1 during early stages of neoplastic progression in the transgenic mouse model of multistage epithelial carcinogenesis (K14‐HPV16 mice). We have studied the effect of genetic deletion of PAI‐1 on inflammation, angiogenesis, lymphangiogenesis and tumor progression. In this model, PAI‐1 deficiency neither impaired keratinocyte hyperproliferation or tumor development nor affected the infiltration of inflammatory cells and development of angiogenic or lymphangiogenic vasculature. We are reporting evidence for concomitant lymphangiogenic and angiogenic switches independent to PAI‐1 status. Taken together, these data indicate that PAI‐1 is not rate limiting for neoplastic progression and vascularization during premalignant progression, or that there is a functional redundancy between PAI‐1 and other tumor regulators, masking the effect of PAI‐1 deficiency in this long‐term model of multistage epithelial carcinogenesis.
C‐Myc is a Nrf2‐interacting protein that negatively regulates phase II genes through their electrophile responsive elements
Authors: Levy Smadar , Forman Henry Jay
Published: March 2010

c‐Myc is a transcription factor that is implicated in many cellular processes including proliferation, apoptosis and cancers. Recently, c‐Myc was shown to be involved in regulation of glutamate cysteine ligase through E‐box sequences. This investigation examined whether c‐Myc also regulates phase II genes through interaction with the electrophile response element (EpRE). Experiments were conducted in human bronchial epithelial cells using si‐RNA to knock down c‐Myc. RT‐PCR and reporter assays were used to measure transcription and promoter activity. c‐Myc downregulated transcription and promoter activity of phase II genes. Chromatin immunoprecipitation verified binding of c‐Myc to EpRE while coimmunoprecipitation demonstrated interaction of c‐Myc with Nrf2. c‐Myc also forms a ternary complex with Nrf2 and p‐c‐Jun. Finally, c‐Myc decreased Nrf2 stability. Thus, our results suggest regulation of the EpRE/Nrf2 signaling pathway by c‐Myc through both interaction with the EpRE binding complex and increased degradation of Nrf2. © 2010 IUBMB IUBMB Life, 62(3): 237–246, 2010
Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity
Authors: Kim Ju‐Young , Hwang Ji‐Hwan , Cha Mi‐Ran , Yoon Mi‐Young , Son Eun‐Soon , Tomida Akihiro , Ko Bosung , Song Si‐Whan , Shin‐ya Kazuo , Hwang Yong‐il , Park Hae‐Ryong
Published: March 2010

Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor‐specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose‐deprived conditions. Here we identify arctigenin (ARC‐G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC‐G blocked expression of UPR target genes such as phosphorylated‐PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2α during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase‐9 and ‐3. Furthermore, ARC‐G suppressed tumor growth of colon cancer HT‐29 xenografts. Our results demonstrate that ARC‐G can be served as a novel type of antitumor agent targeting the UPR in glucose‐deprived solid tumors. J. Cell. Physiol. 224:33–40, 2010 © 2010 Wiley‐Liss, Inc.