bluuebunny/crossref_metadata_2025 huggingface dataset:
P‐Stereogenic Phosphorus Compounds: Effect of Aryl Substituents on the Oxidation of Arylmethylphenylphosphanes under Asymmetric Appel Conditions
Authors: Rajendran Kamalraj V. , Kennedy Lorna , Gilheany Declan G.
Published: August 2010

The effects of aryl ring substitution on the dynamic resolution of aryl(methyl)phenylphosphanes under asymmetric Appel reaction conditions have been studied. As expected, substitution at the ortho position strongly affects the degree ofstereoselection that can be achieved. Unexpectedly, however, there was no variation of stereoselectivity with the electronic nature of the para substituents, which suggests that there are two selection processes in operation. An unusual halogen‐exchange process was observed in the arylphenylphosphinous chlorides on route to the required tertiary phosphane substrates.
A Facile Synthesis of Substituted Indenones and Piperidine‐2,6‐diones from the Baylis–Hillman Acetates
Authors: Basavaiah Deevi , Lenin Dandamudi V.
Published: August 2010

Baylis–Hillman acetates were conveniently transformed into substituted indenone and piperidine‐2,6‐dione frameworks by treatment with (di)phenylacetonitrile followed by Friedel–Crafts cyclization or imide formation.
Full Structural Characterization of an Extracellular Polysaccharide Produced by the Freshwater Cyanobacterium Oscillatoria planktothrix FP1
Authors: Silipo Alba , Molinaro Antonio , Molteni Monica , Rossetti Carlo , Parrilli Michelangelo , Lanzetta Rosa
Published: August 2010

Cyanobacteria, also known as blue‐green algae or Cyanophyta, represent one of the oldest forms of life on Earth. The organisms exhibit a high degree of biological adaptation and comprise a large group of aquatic and photosynthetic oxygenic prokaryotes that obtain their energy through photosynthesis. Cyanobacterial extracellular polysaccharides are high‐molecular‐mass hetero‐polysaccharides that are present on or released onto the cell surface and are characterized by high variability. In the present work we defined the structure of the extracellular polysaccharide produced by the freshwater cyanobacterium Oscillatoria planktothrix FP1. The structural determination, which was achieved by chemical, spectroscopic, and computational analyses, indicates a novel pentasaccharide repeating unit made up of glucose, mannose, and 2‐deoxy‐D‐ribo‐hexose, that has never previously been found in Nature. The elucidation of the structural and conformational features of the extracellular polysaccharide from Oscillatoria planktothrix is a first step toward understanding the biology of these important and interesting microorganisms.
Enantioselective One‐Pot Conjugate Addition of Grignard Reagents Followed by a Mannich Reaction
Authors: Šebesta Radovan , Bilčík Filip , Fodran Peter
Published: August 2010

Asymmetric addition of Grignard reagents to cyclohexenone, catalyzed by ferrocene diphosphanes, afforded chiral magnesium enolates. These enolates reacted in a one‐pot arrangement with N‐benzylidenetoluenesulfonamide to give β‐amino carbonyl compounds with three contiguous stereocenters. Two major diastereoisomers (dr = 60:40) of product with enantioselectivities up to 95 % ee were separated by flash chromatography.
Isolation and Synthesis of Chivotriene, a Chivosazole Shunt Product from Sorangium cellulosum
Authors: Brodmann Tobias , Janssen Dominic , Sasse Florenz , Irschik Herbert , Jansen Rolf , Müller Rolf , Kalesse Markus
Published: August 2010

A shunt product of chivosazole biosynthesis was isolated from the fermentation broth of Sorangium cellulosum, strain So ce 12. Its structure was elucidated by NMR spectroscopy and exhibits six chiral centers, a triene, and a labile β‐hydroxy ketone. The synthesis of chivotriene confirms the structure and in particular the proposed configuration at C22, which was originally deduced for chivosazole from the combination of its genetic and spectroscopic analyses. Remarkably, chivotriene exhibits biological activity usually not observed for segments of complex natural products. However, this activity is not connected to interference with the actin cytoskeleton, the intrinsic target of the chivosazoles.
Synthesis and Structural Analysis of Substituted Tripod‐Shaped Tri‐ and Tetra(p‐phenylene)s
Authors: Hierrezuelo Jesús , Guillén Elena , López‐Romero J. Manuel , Rico Rodrigo , López‐Ramírez M. Rosa , Otero J. Carlos , Cai Chengzhi
Published: August 2010

We report here the synthesis of several tripod‐shaped oligo(p‐phenylene)s with legs composed of three or four phenylene units. Each leg is end‐capped with an iodine atom or a TMS or carboxyl group, and an ethoxy group is present on the functional arm. The tripod containing methyl tri(ethylene glycol) side chains was designed for biological applications. The key step in the synthesis is the Pd‐catalyzed Suzuki cross‐coupling reaction of the silicon‐derived core molecule with the appropriately substituted p‐biphenyl moiety. This synthesis should be considered a new strategy for these compounds, as iterative coupling of the substituted p‐biphenyl building blocks with the first‐generation tripods will allow the homologation of the tripod legs to obtain giant tripod‐shaped oligo(p‐phenylene)s. Also, the iodine end‐capped leg with the ethoxy group on the functional arm permits modular design of the tripod for further functionalization, which will define the applications of the tripod‐nanostructured surfaces. The structure of some of the synthesized tripods was studied through both experimental (Raman spectra) and theoretical (DFT calculation) methods.
Verdazyl Radicals as Substrates for Organic Synthesis: Unique Access to Tetrahydropyrazolotriazinones, Pyrazolotriazinones and Dihydrotetrazinylacrylonitriles
Authors: Chen Eric K. Y. , Bancerz Matthew , Hamer Gordon K. , Georges Michael K.
Published: August 2010

1,5‐Dimethyl‐3‐phenyl‐6‐oxoverdazyl radical was recently shown to undergo a disproportionation reaction to form an azomethine imine, which reacted with a series of dipolarophiles, to form novel tetrahydropyrazolotetrazinone heterocyclic structures, demonstrating for the first time the use of verdazyl radicals as substrates for organic synthesis. Herein, we report on the chemistry of this verdazyl radical with captodative olefins and show that the reactions that occur, either an addition reaction or a hydrogen abstraction reaction followed by a cycloaddition reaction, are defined by the captodative olefin. Also highlighted is an intramolecular rearrangement of initially formed tetrahydropyrazolotetrazinone cycloadducts to either pyrazolotriazinone or tetrahydropyrazolotriazinone structures. While the rearrangement falls under the very general definition of the Dimroth rearrangement, the mechanism that is proposed is distinct and provides the opportunity to go from one particular structural motif to another under mild conditions, expanding the usefulness of this chemistry.
Rapid Assembly of Polyfunctional Structures Using a One‐Pot Five‐ and Six‐Component Sequential Groebke–Blackburn/Ugi/Passerini Process
Authors: Al‐Tel Taleb H. , Al‐Qawasmeh Raed A. , Voelter Wolfgang
Published: August 2010

Sequential addition of up to six components under well‐defined conditions results in the formation of novel structures with amino acid, peptide, and heterocyclic components. This process forms up to eight new bonds under very mild conditions and tolerates a broad spectrum of functional groups. An orthogonal union of the Groebke–Blackburn three‐component reaction with the Ugi four‐component or Passerini three component reaction was adopted to synthesize polyfunctionalized heterocycles. In terms of diversity oriented synthesis, 10 positions on the basic polycyclic structure can be varied. Straightforward batch splitting provides a simple and efficient method for preparing structurally complex analogs.
Evidence for a Non‐Concerted, Dissoziative Mechanism of the Palladium‐Catalyzed “Enolate Claisen Rearrangement” of Allylic Esters
Authors: Braun Manfred , Meletis Panos , Schrader Wolfgang
Published: August 2010

In an enolate Claisen rearrangement, deprotonated allyl phenylacetate undergoes a smooth conversion at –78 °C to 2‐phenyl‐4‐pentenoic acid under palladium(0) catalysis. By using labelled starting materials in crossover experiments, the reaction is shown to follow a dissoziative, non‐concerted, non‐[3,3]‐sigmatropic mechanism that involves palladium complexes and carboxylic‐acid dianions as intermediates.
Advances towards Highly Active and Stereoselective Simple and Cheap Proline‐Based Organocatalysts
Authors: Giacalone Francesco , Gruttadauria Michelangelo , Agrigento Paola , Lo Meo Paolo , Noto Renato
Published: August 2010

Ten 4‐acyloxy‐L‐prolines were screened as catalysts at loadings of 2–0.1 mol‐% for the direct asymmetric aldol reaction in water by using variable amounts of water. Among them, a new catalyst, the L‐proline carrying a trans‐4‐(2,2‐diphenylacetoxy) group, and a catalyst previously synthesized by us, the L‐proline carrying a trans‐4‐(4‐phenylbutanoyloxy) group, were found to be excellent catalysts for the aldol reaction between cyclohexanone or cyclopentanone and substituted benzaldehydes when employed in only 1 and 0.5 mol‐%,respectively, at room temperature without additives. For such catalysts, high turnover numbers were obtained, which are among the highest values obtained for enamine organocatalysis. Finally, these catalysts can be synthesized by direct O‐acylation from inexpensive molecules and successfully used in scaled‐up reactions.
Interactions do not only tell us when, but can also tell us how: Testing process hypotheses by interaction
Authors: Jacoby Johann , Sassenberg Kai
Published: August 2010

Hypotheses about psychological processes are often tested using traditional mediation analysis. This analysis relies on measurement of a transmitting variable. Conducting this analysis has become almost synonymous with examining process hypotheses. An alternative strategy to mediation analysis (the Testing‐a‐Process‐hypothesis‐by‐an‐Interaction Strategy, TPIS) is illustrated here. TPIS is based on a fully experimental design whereby a hypothesized process is tested by an interaction between the hypothesized cause of an effect and a contextual variable. In the interaction term, the contextual variable allows comparison of the causal effect observed when the process is uninterrupted to the effect observed when the process is interrupted. Thus, TPIS translates a theoretical process hypothesis into a statistical interaction hypothesis that uses a fully experimental design to directly examine the hypothesized process. Copyright © 2010 John Wiley & Sons, Ltd.
Determination of free bilirubin and its binding capacity by HSA using a microfluidic chip‐capillary electrophoresis device with a multi‐segment circular‐ferrofluid‐driven micromixing injection
Authors: Sun Hui , Nie Zhou , Fung Ying Sing
Published: August 2010

A PMMA microfluidic chip‐CE device with a multi‐segment circular‐ferrofluid‐driven micromixing injector has been developed for the determination of free bilirubin and its binding capacity by HSA at equilibrium. The design of the device and its fabrication by a low cost CO2laser are discussed for intended applications. Under optimized conditions, the total binding capacity of HSA for bilirubin was determined as 16.3±1.4 mg/l00 mL human serum (n=3) and residual binding capacity for bilirubin 9.8 mg/l00 mL (n=3) in normal infants. To assess risk of hyperbilirubinemia, free bilirubin and residual binding capacity by HSA provide a better indicator than total bilirubin, as neonates with impaired bilirubin binding capacity could be detected. In addition, residual binding capacity provides an advanced indicator to predict the onset of hyperbilirubinemia before the appearance of free bilirubin. HSA down to 94 nL is used in each titration and a full assay of four titrations takes up 376 nL HSA, sufficient for newborns with HSA in microliter range. The device has shown capable to provide adequate margin of protection to detect an early rising level of bilirubin and impaired binding capacity prior to the onset of jaundice condition.
Development of neurons on micropatterns reveals that growth cone responds to a sharp change of concentration of laminin
Authors: Xing Shige , Liu Wenwen , Huang Zhuo , Chen Long , Sun Kang , Han Dong , Zhang Wei , Jiang Xingyu
Published: August 2010

In this report we fabricated laminin (LN) stripes on a background of poly‐L‐lysine as substrates for the growth of rat hippocampal neurons, and found that a sharp change of the concentration of LN guides the growth of neurites by leading the growth cones in a time‐ and space‐dependent manner. The percentage of neurites that grow along the edge of LN stripes (where there is a sharp change of concentration) decreases as a function of the concentration of LN under a threshold value. The actin cytoskeleton plays an important role in the process of growth cone's response to the sharp change of concentration of LN on micropatterns. We believe that the findings here are useful for not only fundamental studies in neuroscience, but also helpful for the design of devices or chips for nervous prosthesis.
Differential methylation of CpG sites in two isoforms of myosin binding protein C, an important hypertrophic cardiomyopathy gene
Authors: Meurs Kathryn M. , Kuan Mani
Published: August 2010

Hypertrophic cardiomyopathy (HCM) is a common form of cardiac disease. Over 400 causative mutations have been identified in 20 sarcomere and myofilament related genes. The high density of mutations found in genes associated with HCM may suggest that mechanisms promoting increased mutability play a role in disease prevalence. The objective of this study was to evaluate the CpG methylation level of the exonic regions of the cardiac myosin binding protein C gene (MYBPC3), a common causal gene for HCM. To determine if the methylation level is gene specific and possibly involved with gene mutability, we also evaluated the methylation of the CpGs within the exonic regions of the skeletal muscle isoform of the myosin binding protein C gene (MYBPC2); there are no known mutations that lead to the development of familial human disease within this gene. We determined that although the mean number of CG sites was identical within the coding region of each gene, the mean methylation level of CpGs was significantly higher inMYBPC3thanMYBPC2(P< 0.0001). The results of this study suggest that there are unique aspects of this cardiac gene or its epigenetic environment which may result in increased genetic mutability. Evaluation of the methylation levels of additional causal cardiomyopathic genes is warranted. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Oncomutations as biomarkers of cancer risk
Authors: Parsons Barbara L. , Myers Meagan B. , Meng Fanxue , Wang Yiying , McKinzie Page B.
Published: August 2010

Cancer risk assessment impacts a range of societal needs, from the regulation of chemicals to achieving the best possible human health outcomes. Because oncogene and tumor suppressor gene mutations are necessary for the development of cancer, such mutations are ideal biomarkers to use in cancer risk assessment. Consequently, DNA‐based methods to quantify particular tumor‐associated hotspot point mutations (i.e., oncomutations) have been developed, including allele‐specific competitive blocker‐PCR (ACB‐PCR). Several studies using ACB‐PCR and model mutagens have demonstrated that significant induction of tumor‐associated oncomutations are measureable at earlier time points than are used to score tumors in a bioassay. In the particular case of benzo[a]pyrene induction of K‐Ras codon 12 TGT mutation in the A/J mouse lung, measurement of tumor‐associated oncomutation was shown to be an earlier and more sensitive endpoint than tumor response. The measurement of oncomutation by ACB‐PCR led to two unexpected findings. First, oncomutations are present in various tissues of control rodents and “normal” human colonic mucosa samples at relatively high frequencies. Approximately 60% of such samples (88/146) have mutant fractions (MFs) >10−5, and some have MFs as high as 10−3 or 10−4. Second, preliminary data indicate that oncomutations are present frequently as subpopulations in tumors. These findings are integrated into a hypothesis that the predominant preexisting mutations in particular tissues may be useful as generic reporters of carcinogenesis. Future research opportunities using oncomutation as an endpoint are described, including rodent to human extrapolation, dose‐response assessment, and personalized medicine. Environ. Mol. Mutagen., 2010. Published 2010 Wiley‐Liss, Inc.
Historical perspective on the development of the genetic toxicity test battery in the United States
Authors: Zeiger Errol
Published: August 2010

The currently used genetic toxicity testing battery (the Ames Salmonella test, the in vitro mammalian cell mouse lymphoma assay and/or the in vitro mammalian cell chromosome assay, and the rodent bone marrow chromosome aberration or micronucleus assay) had its origins in the early‐to‐mid 1970s. By the late 1970s, a large number of genetic tests had been proposed or recommended by the US‐EPA for identifying germ cell mutagens and carcinogens. After a number of modifications that were primarily directed toward minimizing the number of tests used, the test battery reached its current state in the mid‐1980s. This test battery, with some minor modifications in the timing or ordering of the tests is mandated by regulatory authorities worldwide. Although it would be intellectually satisfying to presume that this compendium of tests was developed and selected for regulatory screening based solely on scientific grounds, it was actually based on a combination of scientific data, theoretical considerations, chance, and advocacy, and not always in equal proportions. The evolution of the current genetic toxicity test battery, and some of the activities and considerations that directed this evolution are described. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Proposal of an in vivo comet assay using haemocytes of Drosophila melanogaster
Authors: Carmona Erico R. , Guecheva Temenouga N. , Creus Amadeu , Marcos Ricardo
Published: August 2010

This study presents the first application of an in vivo alkaline comet assay using haemocytes of Drosophila melanogaster larvae. These cells, which play a role similar to that of mammalian blood, can be easily obtained and represent an overall exposure of the treated larvae. To validate the assay, we evaluated the response of these cells to three well‐known mutagenic agents: ethyl methanesulfonate (EMS), potassium dichromate (PD), and gamma radiation (γ‐irradiation). Third‐instar Drosophila larvae were exposed to different concentrations of EMS (1, 2, and 4 mM) and PD (0.5, 1, and 2.5 mM) and to different doses of γ‐irradiation (2, 4, and 8 Gγ). Subsequently, haemolymph was extracted from the larvae, and haemocytes were isolated by centrifugation and used in the comet assay. Haemocytes exhibited a significant dose‐related increase in DNA damage, indicating that these cells are clearly sensitive to the treatments. These results suggest that the proposed in vivo comet test, using larvae haemocytes of D. melanogaster, may be a useful in vivo assay for genotoxicity assessment. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Expression of DNA repair and apoptosis genes in mitochondrial mutant and normal cells following exposure to ionizing radiation
Authors: Kulkarni Rohan , Thomas Robert A. , Tucker James D.
Published: August 2010

In double‐strand DNA damage repair, nonhomologous end joining (NHEJ) is more error‐prone than homologous recombination repair (HRR), indicating that the relative prevalence of NHEJ may lead to more incorrect repair and thus to increases in chromosome damage. If DNA damage is extensive and cells are unable to repair that damage they typically undergo apoptosis. The mechanism(s) by which cells decide to switch from DNA repair to apoptosis is unknown. Since DNA repair and apoptosis are both energy‐demanding processes, the answer may involve ATP utilization. We used human mitochondrial mutant cell lines obtained from people with phenotypic manifestations of compromised ATP generation. We hypothesized that these cells may not have adequate capacity for dealing with the additional demands for ATP required for repairing DNA damage after genotoxic exposure, perhaps making the cells more prone to undergo apoptosis instead of initiating repair. This study describes changes in the expression of genes involved in NHEJ or HRR, as well as genes involved in apoptosis, in one normal and two mitochondrial mutant human cell lines following ionizing radiation exposure. Compared to normal cells, both mutant cell lines showed reduced expression of genes involved in NHEJ and HRR. Analysis of expression changes in genes involved in apoptosis revealed marked increases in expression in the mutants compared to normal cells. These results indicate that following ionizing radiation exposure, mitochondrial mutant cells have decreased levels of mRNA expression of DNA repair genes and increased expression levels of genes involved in apoptosis compared to normal cells. This study provides information that might be useful in characterizing energy dependent processes following exposure to stress or genotoxic agents. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Genetics and women's health issues—The commitment of EMS to women scientists and gender‐associated disease topics
Authors: Witt Kristine L. , Moorman Patricia G. , Kovalchuk Olga , Holland Nina , Block Gladys , Andreassen Paul R.
Published: August 2010

This manuscript presents an overview of a symposium held at the 2009 annual meeting of the Environmental Mutagen Society (EMS) in St. Louis, MO. The symposium was sponsored by the Women in the Environmental Mutagen Society (WEMS) special interest group, and it covered current molecular genetics technologies and their impact on diagnosis and treatment of diseases that primarily or differentially affect women. Four speakers presented groundbreaking new information from such areas as cancer genetics, gene‐environment interactions, epigenetics, DNA repair, and molecular epidemiology. Although cancer was a primary focus of the symposium, other health issues such as obesity and cardiovascular disease were addressed. The rapid evolution in genomic technologies discussed in this symposium should provide new tools to explore some of the critical questions raised by the research projects described in this article. This symposium demonstrates that EMS provides a forum for the presentation, discussion, and extension of the data generated by the investigators featured in this article and other researchers engaged in the study of the molecular mechanisms and gene‐environment interactions that impact women's health. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Growing up with DNA repair and joining the EMS
Authors: Hanawalt Philip
Published: August 2010

I recount some personal history, as I rode the crest of the wave of discovery and excitement in the DNA repair field from the early 1960s and eventually came to appreciate that the Environmental Mutagen Society is the appropriate professional “home” for researchers in this field: it places them in the context of the broader genetic, societal, and regulatory issues raised from their studies. In return, the wisdom provided from basic research on cellular processing of damaged DNA is essential to mechanism‐based decisions in the domain of genetic toxicology. Environ. Mol. Mutagen., 2010. Published 2010 Wiley‐Liss, Inc.
Superoxide dismutase protects cells from DNA damage induced by trivalent methylated arsenicals
Authors: Tennant Alan H. , Kligerman Andrew D.
Published: August 2010

Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide. Heterozygous mice of strain B6;129S7‐Sod1tm1Leb/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod1tm1Leb), homozygous wild‐type (+/+), and homozygous knockout (Sod1tm1Leb/Sod1tm1Leb) for the Cu/Zn superoxide dismutase (Sod1) gene. Splenocytes from these mice were exposed to several concentrations of either sodium arsenite (As3 [0–200 μM]), monomethylarsonous acid (MMA3 [0–10 μM]), or dimethylarsinous acid (DMA3 [0–10 μM]) for 2 hr. Cells were then examined for DNA damage using the alkaline single cell gel electrophoresis assay. Methyl methanesulfonate (MMS) was used as a positive control. Splenocytes from each of the three genotypes for Sod1 were equally sensitive to MMS and As3. However, at equimolar concentrations, DMA3 and MMA3 produced significantly more DNA damage in the homozygous knockout mouse splenocytes than in the splenocytes from the wild‐type or heterozygous mice. These findings suggest that superoxide is involved either directly or indirectly in producing DNA damage in cells exposed to trivalent methylated arsenicals. These arsenicals may generate reactive oxygen species that damage DNA. This DNA damage may be a key factor in initiating cancer in vivo. Environ. Mol. Mutagen., 2011. Published 2010 Wiley‐Liss, Inc.
Antigenotoxic effects of p53 on spontaneous and ultraviolet light B–induced deletions in the epidermis of gpt delta transgenic mice
Authors: Masumura Kenichi , Sakamoto Yasuteru , Ikeda Megumi , Asami Yasuo , Tsukamoto Tetsuya , Ikehata Hironobu , Kuroiwa Yuichi , Umemura Takashi , Nishikawa Akiyoshi , Tatematsu Masae , Ono Tetsuya , Nohmi Takehiko
Published: August 2010

Tumor development in the skin may be a multistep process where multiple genetic alterations occur successively. The p53 gene is involved in genome stability and thus is referred to as “the guardian of the genome.” To better understand the antigenotoxic effects of p53 in ultraviolet light B (UVB)‐induced mutagenesis, mutations were measured in the epidermis of UVB‐irradiated p53+/+ and p53−/− gpt delta mice. In the mouse model, point mutations and deletions are separately identified by the gpt and Spi− assays, respectively. The mice were exposed to UVB at single doses of 0.5, 1.0, or 2.0 kJ/m2. The mutant frequencies (MFs) were determined 4 weeks after the irradiation. All doses of UVB irradiation enhanced gpt MFs by about 10 times than that of unirradiated mice. There were no significant differences in gpt MFs and the mutation spectra between p53+/+ and p53−/− mice. The predominant mutations induced by UVB irradiation were G:C to A:T transitions at dipyrimidines. In contrast, in unirradiated p53−/− mice, the frequencies of Spi− large deletions of more than 1 kb and complex‐type deletions with rearrangements were significantly higher than those of the Spi− large deletions in p53+/+ counterparts. The specific Spi− mutation frequency of more than 1 kb deletions and complex types increased in a dose‐dependent manner in the p53+/+ mice. However, no increase of such large deletions was observed in irradiated p53−/− mice. These results suggest that the antigenotoxic effects of p53 may be specific to deletions and complex‐type mutations induced by double‐strand breaks in DNA. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Germ cell mutagens: Risk assessment challenges in the 21st century
Authors: Singer Timothy M. , Yauk Carole L.
Published: August 2010

Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high‐throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations. Environ. Mol. Mutagen. 2010. © 2010 Government of Canada.
New and emerging technologies for genetic toxicity testing
Authors: Lynch Anthony M. , Sasaki Jennifer C. , Elespuru Rosalie , Jacobson‐Kram David , Thybaud Véronique , De Boeck Marlies , Aardema Marilyn J. , Aubrecht Jiri , Benz R. Daniel , Dertinger Stephen D. , Douglas George R. , White Paul A. , Escobar Patricia A. , Fornace Albert , Honma Masamitsu , Naven Russell T. , Rusling James F. , Schiestl Robert H. , Walmsley Richard M. , Yamamura Eiji , van Benthem Jan , Kim James H.
Published: August 2010

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow‐up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes
Authors: Hackenberg Stephan , Friehs Gudrun , Kessler Michael , Froelich Katrin , Ginzkey Christian , Koehler Christian , Scherzed Agmal , Burghartz Marc , Kleinsasser Norbert
Published: August 2010

Industrial application of titanium dioxide nanoparticles (TiO2‐NPs) as an additive in pharmaceutical and cosmetic products is increasing. However, the knowledge about the toxicity of this material is still incomplete and data concerning health and environmental safety and results of recent studies on TiO2 nanotoxicology are inconsistent. The in vitro geno‐ and cytotoxicity of TiO2‐NPs in the anatase crystal phase was evaluated in human peripheral blood lymphocytes from 10 male donors. Initially, transmission electron microscopy (TEM) was performed to describe particle morphology and size, the degree of particle aggregation, and the intracellular distribution. Cells were exposed to nanoparticles in increasing concentrations of 20, 50, 100, and 200 μg/ml for 24 hr. Cytotoxic effects were analyzed by trypan blue exclusion test and the single‐cell microgel electrophoresis (comet) assay was applied to detect DNA double‐strand breakage. TiO2‐NPs were sphere shaped with a diameter of 15–30 nm. Despite dispersive pretreatment, a strong tendency to form aggregates was observed. Particles were detected in the cytoplasm of lymphocytes, but also a transfer into the nucleus was seen. The trypan blue exclusion test did not show any decrease in lymphocyte viability, and there was no evidence of genotoxicity in the comet assay for any of the tested concentrations. In conclusion, TiO2‐NPs reached the cytoplasm as well as the nucleus and did not induce cyto‐ or genotoxic effects in human peripheral blood lymphocytes. Complement investigations on different human cell systems will be performed to estimate the biocompatibility of TiO2‐NPs. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.
Tall building vibration control using a TM‐MR damper assembly: Experimental results and implementation
Authors: Zemp Rene , de la Llera Juan C. , Roschke Paul
Published: August 2010

This paper summarizes the relevant results of the design, construction, testing, and implementation of a nominal 120 kN magnetorheological damper developed to control a free‐plan tall building in Santiago, Chile, equipped with two 160‐ton tuned masses. Cyclic as well as hybrid simulation tests were performed on the prototype damper. Global building responses using measured MR properties showed good correlation with analytical estimations. Also, a proposed physical controller for the MR damper was validated through hybrid and building pull‐back tests. Its performance is essentially equivalent to that of an LQR controller, but the information needed in its implementation is considerably less. Pull‐back tests of 10 cm amplitude were performed on one mass along the flexible edge of the building and its response controlled using the passive and controlled modes of the MR damper. The MR damper was capable of controlling the TM displacements very effectively, as well as the simulated building response for different ground motions and harmonic excitation. Copyright © 2010 John Wiley & Sons, Ltd.
Simulation of floor response spectra in shake table experiments
Authors: Maddaloni G. , Ryu K. P. , Reinhorn A. M.
Published: August 2010

Among several different experimental techniques, used to test the response of structures and to verify their seismic performance, the shake table testing allows to reproduce the conditions of true effects of earthquake ground motions in order to challenge complex model structures and systems. However, the reproduction of dynamic signals, due to the dynamics of the shake table and of the specimen, is usually imperfect even though closed‐loop control in a shake table system is used to reduce these errors and obtain the best fidelity reproduction. Furthermore, because of the dynamic amplifications in the specimen, the signal recorded at desired locations could be completely different from the expected effect of shake table motion. This paper focuses on the development of practical shake table simulations using additional ‘open loop’ feedforward compensation in form of inverse transfer functions (i.e. the ratio of the output structural response to an input base motion in the frequency domain) in order to obtain an acceptable reproduction of desired acceleration histories at specific locations in the specimen. As the first step, a well‐known global feedforward procedure is reformulated for the compensation of the table motion distortions due to the servo‐hydraulic system. Subsequently, the same concept is extended to the table‐structure system to adjust the shake table input in order to achieve a desired response spectrum at any floor of the specimen. Implementations show how such a method can be used in any experimental facility. Copyright © 2010 John Wiley & Sons, Ltd.
Shaking table test and analysis method on ultimate behavior of slender base‐isolated structure supported by laminated rubber bearings
Authors: Takaoka Eiji , Takenaka Yasuo , Nimura Arinori
Published: August 2010

This paper describes the results of shaking table tests to ascertain the ultimate behavior of slender base‐isolated buildings and proposes a time history response analysis method, which can predict the ultimate behavior of base‐isolated buildings caused by buckling fracture in laminated rubber bearings. In the tests, a base‐isolated structure model weighing 192 kN supported by four lead rubber bearings is used. The experimental parameters are the aspect ratio of height‐to‐distance between the bearings and the shape of and the axial stress on the bearings. The test results indicate that the motion types of the superstructure at large input levels can be classified into three types: the sinking type; the uplift type; and the mixed type. These behaviors depend on the relationship between the static ultimate lateral uplifting force on the superstructure and the lateral restoring characteristics of the base‐isolated story. In the analysis method, bearing characteristics are represented by a macroscopic mechanical model that is expanded by adding an axial spring to an existing model. Nonlinear spring characteristics are used for its rotational, shear, and axial spring. The central difference method is applied to solve the equation of motion. To verify the validity of the method, simulation analysis of the shaking table tests are carried out. The results of the analysis agree well with the test results. The proposed model can express the buckling behavior of bearings in the large deformation range. Copyright © 2010 John Wiley & Sons, Ltd.
An equivalent SDOF system model for estimating the response of R/C building structures with proportional hysteretic dampers subjected to earthquake motions
Authors: Oviedo A. Juan Andrés , Midorikawa Mitsumasa , Asari Tetsuhiro
Published: August 2010

For the purpose of estimating the earthquake response, particularly the story drift demand, of reinforced concrete (R/C) buildings with proportional hysteretic dampers, an equivalent single‐degree‐of‐freedom (SDOF) system model is proposed. Especially in the inelastic range, the hysteretic behavior of an R/C main frame strongly differs from that of hysteretic dampers due to strength and stiffness degradation in R/C members. Thus, the proposed model, unlike commonly used single‐spring SDOF system models, differentiates the restoring force characteristics of R/C main frame and hysteretic dampers to explicitly take into account the hysteretic behavior of dampers. To confirm the validity of the proposed model, earthquake responses of a series of frame models and their corresponding equivalent SDOF system models were compared. 5‐ and 10‐story frame models were studied as representative of low‐ and mid‐rise building structures, and different mechanical properties of dampers—yield strength and yield deformation—were included to observe their influence on the effectiveness of the proposed model. The results of the analyses demonstrated a good correspondence between estimated story drift demands using the proposed SDOF system model and those of frame models. Moreover, the proposed model: (i) led to better estimates than those given by a single‐spring SDOF system model, (ii) was capable of estimating the input energy demand and (iii) was capable of estimating the total hysteretic energy and the participation of dampers into the total hysteretic energy dissipation, in most cases. Results, therefore, suggest that the proposed model can be useful in structural design practice. Copyright © 2010 John Wiley & Sons, Ltd.
Performance‐based seismic assessment method for Taiwanese historic Dieh‐Dou timber structures
Authors: Tsai Pin‐Hui , D'Ayala Dina
Published: August 2010

Lateral force, response spectrum and step‐by‐step pushover analyses are performed and compared with the post‐earthquake survey of two Dieh‐Dou buildings seriously affected in the 1999 Chi‐Chi earthquake in Taiwan. The results show that the proposed FE model with finite translational and rotational stiffness can successfully be employed to assess the vulnerability of the frames. The fundamental period of Dieh‐Dou structures is about 1.0 s higher than that calculated by the simplified approach of the codes for regular frames; a modal analysis is, therefore, essential for this typology of structure. The elastic analysis, either lateral force or response spectrum, is shown to be reliable to assess Dieh‐Dou frames when quick results are desired. However, a non‐linear step‐by‐step pushover analysis has the advantage of greater accuracy, as it allows mapping the failure trend and indicating the critical elements. The lateral drifts are compared with the actual observed damage pattern and when the damage level is related to the peak ground acceleration on a vulnerability curve plot, it is shown that the joint failure combined with the lateral drift gives an indication of the global structural behaviour of this historic construction typology. Owing to the unique construction features of the Dieh‐Dou, the joint failure represents also a critical criterion in terms of maximum retention for conservation. Based on a damage level approach, an assessment methodology is suggested that would allow optimizing a strengthening strategy, for protection of these precious structures from future earthquakes while avoiding unnecessary interventions. Copyright © 2010 John Wiley & Sons, Ltd.
System identification and damage evaluation of degrading hysteresis of reinforced concrete frames
Authors: Loh Chin‐Hsiung , Mao Chien‐Hong , Huang Jhih‐Ren , Pan Tso‐Chien
Published: August 2010

In this study, signal processing approaches and nonlinear identification are used to measure seismic responses of reinforced concrete (RC) structures using the shaking table test. To analyze structural nonlinearity, an equivalent linear system with time‐varying model parameters, singular spectrum analysis to elucidate residual deformation, and wavelet packet transformation analysis to yield the energy distribution among components are adopted to detect the nonlinearity. Then, damage feature extraction is conducted using both the Holder exponent and the Level‐1 detail of the discrete wavelet component. Finally, the modified Bouc‐Wen hysteretic model and the system identification process are employed to the shaking table test data to evaluate the physical parameters, including the stiffness degradation, the strength deterioration and the pinching hysteresis. Finally, the identified stiffness and strength degradation functions from the test data of RC frames in relation to the degree of ground shaking, damage index and the identified nonlinear features are discussed. Based on the proposed method, both signal‐based and model‐based identifications, the relationship between the damage occurrence and severity of structural damage can be identified. Copyright © 2010 John Wiley & Sons, Ltd.
Evaluating the impact of soil redistribution on the in situ mineralization of soil organic carbon
Authors: Van Hemelryck Hendrik , Govers Gerard , Van Oost Kristof , Merckx Roel
Published: August 2010

Soil erosion, transport and deposition by water drastically affect the distribution of soil organic carbon (SOC) within a landscape. Moreover, soil redistribution may have a large impact on the exchange of carbon (C) between the pedosphere and the atmosphere. One of the large information gaps within this research domain, concerns the fate of SOC after erosion by water. According to different (mainly laboratory) studies, soil redistribution leads to aggregate breakdown, thereby exposing the contained SOC to mineralization.

Our study aims to quantify the extent to which such increased mineralization occurs in a real field situation. Carbon dioxide (CO2)‐efflux was measured in the field after an important erosion event for a continuous period of 112 days. The specific situation on the field ensured that almost none of eroded SOC was exported from the field. Measurements of CO2‐efflux were done in areas with sediment deposition, as well as in comparable areas without sedimentation. Comparison of these measurements allowed the net effect of soil deposition on CO2‐efflux to be assessed. Field data were complemented by measurements on incubated, undisturbed soil core samples, in order to disentangle the contribution of environmental factors (moisture, temperature) from any erosional effect on CO2‐efflux.

Results of these measurements on the field showed that CO2‐efflux was regulated by a complex interplay of different factors (mostly soil porosity, soil moisture and soil temperature).

In combination with the incubation measurements, it could be concluded that the processes of erosion and transport indeed led to an increased mineralization of SOC, as a result of aggregate breakdown and exposure of previously encapsulated SOC. This effect was, however, much smaller than observed in previous laboratory studies. Moreover, it was only important in the first weeks, immediately after the erosion event. The calculated net erosional effect on CO2‐efflux represented a mere 1·6% of total SOC, originally present in the soil. Copyright © 2010 John Wiley & Sons, Ltd.
A new method for simulating rigid body motion in incompressible two‐phase flow
Authors: Sanders Jessica , Dolbow John E. , Mucha Peter J. , Laursen Tod A.
Published: August 2010

Computational treatment of immersed rigid bodies, especially in the presence of free surfaces and/or breaking waves, poses several modeling challenges. A motivating example where these systems are of interest is found in offshore wave energy harvesting systems, where a floating structure converts mechanical oscillations to electrical energy. In this study, we take the first step in developing a robust computational strategy for treating rigid bodies with possible internal dynamics, such that they may be fully coupled to a fluid environment with free surfaces and arbitrarily large fluid motion.

Many schemes for fluid–solid interaction involve formulating and solving all of the equations of motion on a structured cartesian finite difference grid, but with overlaying Lagrangian representation of the solid that is used to track its position. Ultimately, most of these techniques, which include methods for deformable solids as well, solve the equations of motion completely on the Eulerian grid (see, for example, (J. Comput. Phys. 2005; 205:439–457) and (J. Comput. Phys. 2008; 227:3114–3140)). By contrast, we solve Lagrangian‐type rigid body equations coupled with the Eulerian formulation of the Navier Stokes equations for an immersed solid. This departure from the standard method facilitates the addition of the internal dynamics characteristic of power conversion systems. The study is based on a finite difference and level set description of a free surface between two immiscible fluids (for example water and air) for incompressible flow by Summan (J. Comput. Phys. 1994; 114:146–159). Copyright © 2010 John Wiley & Sons, Ltd.
Coupled fluid–solid interaction under shock wave loading
Authors: Tipton D. Gregory , Christon Mark A. , Ingber Marc S.
Published: August 2010

This paper considers the treatment of fluid–solid interaction problems under shock wave loading, where the solid experiences large bulk Lagrangian displacements. This work addresses the issues associated with using a level set as a generalized interface for fluid–solid coupling where the fluid–solid interface is embedded in an unstructured fluid grid. We outline the formulation used for the edge‐based unstructured‐grid Euler solver. The identification of the fluid–solid interface on the unstructured fluid mesh uses a super‐sampled ℒ︁2 projection technique, which in conjunction with a Lagrangian interface position, permits fast identification of the interface and the concomitant imposition of boundary conditions. The use of a narrow‐band approach for the identification of the wetted interface is presented with the details of the construction of interface conditions. A series of two and three‐dimensional shock‐body computations are presented to demonstrate the validity of the current approach on problems with static and dynamic interfaces, including projectile/shock interaction simulations. Copyright © 2010 John Wiley & Sons, Ltd.