bluuebunny/crossref_metadata_2025 huggingface dataset:
Brominated and chlorinated dioxins, PCBs and brominated flame retardants in Scottish shellfish: Methodology, occurrence and human dietary exposure
Authors: Fernandes Alwyn , Dicks Pamela , Mortimer David , Gem Martin , Smith Frankie , Driffield Malcolm , White Shaun , Rose Martin
Published: January 2008

The most commonly consumed shellfish species produced in Scotland – mussels, oysters and scallops – were investigated for the occurrence of a range of brominated and chlorinated contaminants in order to establish current levels and estimate human dietary exposure. Flesh from individual sub‐samples was representatively pooled and 35 composites were analysed for brominated and chlorinated dioxins (PBDD/Fs, PCDD/Fs), brominated and chlorinated biphenyls (PBBs, PCBs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDs) and tetrabromobisphenol A (TBBPA). The analytical methodology used 13C12 labelled surrogates of the target compounds, with GC coupled to (usually) high resolution MS, and LC‐MS/MS for HBCD and TBBPA analysis. Positive identifications were made in the majority of samples for most analytes with the exception of TBBPA and most PBDD congeners measured. None of the levels detected for PCDD/F and PCB were above the maximum permitted levels specified in European Union regulations. The levels of brominated furans predominated over brominated dioxins, reflecting the environmental distribution and source emission profiles of these contaminants, and relatively high levels of the tri‐brominated congeners were observed. Levels of the flame retardant chemicals reflected current and legacy use, with appreciable concentrations of PBDEs and HBCDs (predominantly alpha‐HBCD) but far lower levels of PBBs. TBBPA was not detected in any of the species. In general, mussels and oysters displayed relatively higher levels of contamination than scallops, although the gonad tissue of the latter showed significant levels of brominated dioxins. The estimated adult dietary intakes of PCDD/Fs and PCBs arising from the consumption of a typical portion of these foods in combination with an otherwise average UK diet were in the range 0.5–0.6 pg World Health Organisation (WHO)‐toxic equivalent (TEQ)(2005)/kg bodyweight per day. These estimated dietary intakes are well within the Tolerable Daily Intake for dioxins and dioxin‐like PCBs of 2 pg WHO‐TEQ(2005)/kg bodyweight/day endorsed by the independent expert Committee on Toxicology of Chemicals in Food, Consumer Products and the Environment. The corresponding intakes for sumPBDEs and sumHBCDs were 5.6–6.1 and 5.9–7.9 ng/kg bodyweight/day respectively.
Dynamic policies for uncertain time‐critical tasking problems
Authors: Glazebrook Kevin D. , Punton Emma L.
Published: January 2008

A recent paper by Gaver et al. 6 argued the importance of studying service control problems in which the usual assumptions (i) that tasks will wait indefinitely for service and (ii) that successful service completions can be observed instantaneously are relaxed. Military and other applications were cited. They proposed a model in which arriving tasks are available for service for a period whose duration is unknown to the system's controller. The allocation of a large amount of processing to a task may make more likely its own successful completion but may also result in the loss of many unserved tasks from the system. Gaver et al. 6 called for the design of dynamic policies for the allocation of service which maximizes the rate of successful task completions achieved, or which come close to doing so. This is the theme of the paper. We utilize dynamic programming policy improvement approaches to design heuristic dynamic policies for service allocation which may be easily computed. In all cases studied, these policies achieve throughputs close to optimal. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Hydrophilic and hydrophobic copolymers of a polyaspartylhydrazide bearing positive charges as vector for gene therapy
Authors: Cavallaro Gennara , Licciardi Mariano , Mandracchia Delia , Pitarresi Giovanna , Giammona Gaetano
Published: January 2008

BACKGROUND: The design of polymeric vectors for gene delivery provided with specific properties is one of the most critical aspects for a successful gene therapy. These polymers should be biocompatible as well as able to carry efficiently DNA to target tissues and to transfect it into cells.

RESULTS: The formation of complexes of poly[(α,β‐asparthylhydrazide)–poly(ethylene glycol)] and poly[(α,β‐asparthylhydrazide)–hexadecylamine] copolymers functionalised with glycidyltrimethylammonium chloride (PAHy–PEG‐GTA and PAHy–C16‐GTA, respectively) with DNA was studied. The effects of the introduction of hydrophilic (PEG) or hydrophobic (C16) moieties on the chains of PAHy–GTA copolymers, such as the stabilising effect on the DNA structure, were evaluated. In particular, we observed a high DNA protection by PAHy–PEG‐GTA copolymers. Degradation studies led us to suppose a particular aqueous conformation of the polyionic complex of PAHy–PEG2000‐GTA in which DNA should be internalised into an inner core surrounded by a PEG hydrophilic shell; while no significant protection was detected with PAHy–C16‐GTA in which DNA should be disposed on the surface of the complex, freely exposed to DNase II action.

CONCLUSION: The insertion of PEG or C16 chains into the polymeric structure of PAHy–GTA copolymers changes significantly the DNA complexing and protecting ability of the PAHy–GTA copolymers, showing that hydrophilic and hydrophobic side chains can play a crucial role in supramolecular arrangements of interpolyelectrolyte complexes between DNA and PAHy copolymers. Copyright © 2008 Society of Chemical Industry
Proteome analysis of apoptosis signaling by S‐trityl‐L‐cysteine, a potent reversible inhibitor of human mitotic kinesin Eg5
Authors: Kozielski Frank , Skoufias Dimitrios A. , Indorato Rose‐Laure , Saoudi Yasmina , Jungblut Peter R. , Hustoft Hanne K. , Strozynski Margarita , Thiede Bernd
Published: January 2008

Mitotic kinesins represent potential drug targets for anticancer chemotherapy. Inhibitors of different chemical classes have been identified that target human Eg5, a kinesin responsible for the establishment of the bipolar spindle. One potent Eg5 inhibitor is S‐trityl‐L‐cysteine (STLC), which arrests cells in mitosis and exhibits tumor growth inhibition activity. However, the underlying mechanism of STLC action on the molecular level is unknown. Here, cells treated with STLC were blocked in mitosis through activation of the spindle assembly checkpoint as shown by the phosphorylated state of BubR1 and the accumulation of mitosis specific phosphorylation on histone H3 and aurora A kinase. Using live cell imaging, we observed prolonged mitotic arrest and subsequent cell death after incubation of GFP‐α‐tubulin HeLa cells with STLC. Activated caspase‐9 occurred before cleavage of caspase‐8 leading to the accumulation of the activated executioner caspase‐3 suggesting that STLC induces apoptosis through the intrinsic apoptotic pathway. Proteome analysis following STLC treatment revealed 33 differentially regulated proteins of various cellular processes, 31 of which can be linked to apoptotic cell death. Interestingly, four identified proteins, chromobox protein homolog, RNA‐binding Src associated in mitosis 68 kDa protein, stathmin, and translationally controlled tumor protein can be linked to mitotic and apoptotic processes.
Proteomic identification of specific glycosyltransferases functionally implicated for the biosynthesis of a targeted glyco‐epitope
Authors: Lin Chi‐Hung , Lin Chia‐Wei , Khoo Kay‐Hooi
Published: January 2008

Functional glycomic and glycoproteomic analyses often entail correlating the mapped glycosylation pattern of a cell against the activities of specific glycosyltransferases it expresses. While the mRNA transcripts can be readily mapped, the expression of a functional glycosyltransferase at protein level has defied most current proteomic approaches. To enable identification of these low abundant Golgi residing membrane bound proteins, we have developed a novel semigel‐based shotgun proteomic workflow incorporating subcellular fractionation and one‐step affinity enrichment of the detergent solubilized Golgi preparation on resins derivatized with nucleotide diphosphates. Applying the strategy to a colonic adenocarcinoma, Colo205, which is known to aberrantly synthesize abundant fucosylated extended type 1 chain, we first validated that β3‐galactosyltransferase 5 (β3GalT5) is indeed the overexpressed β3GalT. This and β4GalT1 are the two galactosyltrasferases which were positively identified by proteomic analysis of the eluted fractions from uridine diphosphate (UDP)‐affinity column. Substituting UDP with a guanidine diphosphate (GDP)‐affinity column and monitoring the eluted fractions for enriched α3/4‐fucosyltransferase (FucT) activities, we then identified FucT3 and FucT6 as the two major α3/4FucTs expressed in Colo205 at the protein level. Our proteomic analysis demonstrated that not all GDP‐utilizing glycosyltransferases bind and are retained similarly by the GDP‐affinity column and that specific activity assay along with optimization of binding and elution conditions is critical for successful identification of a particular subset of the targeted glycosyltransferases. Only OFUT1, a protein O‐FucT, was additionally identified to coelute with the α3/4FucT activity, and not other GDP‐fucose utilizing FucTs.
Synthesis and thermolysis of Diels–Alder adducts of 2,9‐dialkylpentacenes with diethyl azodicarboxylate
Authors: Okamoto Kazuo , Shiodera Kouta , Kawamura Takumi , Ogino Kenji
Published: January 2008

A series of Diels–Alder adducts of 2,9‐dialkylpentacenes with diethyl azodicarboxylate were synthesized, and their thermolysis behaviors or retro‐Diels–Alder reactions to regenerate dialkylpentacene were investigated via thermogravimetric analysis, IR and UV–Vis spectroscopy. Synthesized Diels–Alder adducts or precursors formed stable molecular glass. The transparent films on glass slide or silicon wafer were easily fabricated by cast or spin‐coating process. The precursors were smoothly converted to corresponding dialkylpentacenes by heating at 300°C. The domain size of regenerated dialkylpentacenes was in the range of 50–200 µm. Copyright © 2008 John Wiley & Sons, Ltd.
Electron ionisation and electrospray ionisation mass spectrometric study of a series of isomeric methyl‐, dimethyl‐ and trimethylalloxazines
Authors: Prukała Dorota , Prukała Wiesław , Koczorowski Ryszard , Khmelinskii Igor V. , Sikorska Ewa , Sikorski Marek
Published: January 2008

Electron ionisation (EI) mass spectra and electrospray ionisation (ESI) mass spectra at different cone voltages of a series of isomeric methyl‐ and dimethylalloxazines are discussed, and compared with those of lumichrome, and 1‐ and 3‐methyllumichrome. Examination of ESI mass spectra taken at a higher cone voltage and the use of isotope‐labelled methanol allow us to discuss the fragmentation pathways of [M+H]+ and [M–H]− ions. The fragmentation pathways of all of the compounds and the characteristic fragment ions formed in EI‐MS are compared with published data. The influence of methyl and dimethyl substituents in the benzene ring on the fragmentation pathways leading to the loss of 43 and 45 Da upon both electron and electrospray ionisation is described. Copyright © 2008 John Wiley & Sons, Ltd.
Optimal boundary control of cardiac alternans
Authors: Dubljevic Stevan
Published: January 2008

Alternation of normal electrical activity in the myocardium is believed to be linked to the onset of life‐threatening ventricular arrhythmias and sudden cardiac death. In this paper, a spatially uniform unstable steady state of small amplitude of alternans described by parabolic partial differential equations (PDEs) is stabilized by boundary optimal control methods. A finite dimensional linear quadratic regulator (LQR) is utilized in both a full‐state‐feedback control structure and in a compensator design with the Luenberger observer, and it achieves global stabilization in a finite size tissue cable length. The ability to realize such control algorithm is analyzed based on the structure of the amplitude of alternans equation and the control methodology applied. Copyright © 2008 John Wiley & Sons, Ltd.
Control of 5‐FOA and 5‐FU resistance by Saccharomyces cerevisiae YJL055W
Authors: Ko Nolan , Nishihama Ryuichi , Pringle John R.
Published: January 2008

In a URA3/5‐FOA‐based dosage‐suppressor screen, we isolated a plasmid containing the little‐characterized ORF YJL055W. Further analysis showed that this gene did not suppress the mutation of interest. Instead, overexpression of Yjl055Wp directly suppressed the non‐viability of URA3+ cells in the presence of 5‐FOA. Overexpression of Yjl055Wp also suppressed the lethality induced by 5‐FU, but deletion of YJL055W had no detectable effect on resistance to either 5‐FOA or 5‐FU. Based on these observations and a previous report that a yjl055wΔ mutant has increased sensitivity to purine‐analogue mutagens, we suggest that Yjl055Wp may function in one of several pathways for the detoxification of base analogues. However, its precise mechanism of action remains unknown. Copyright © 2008 John Wiley & Sons, Ltd.
Gas chromatographic analysis for long chain sultones in olefin sulfonates
Authors: Callahan J. , Gildenberg L. , Omelczenko N.
Published: January 2008

Abstract and Summary

A gas Chromatographic method is described for the analysis of tetradecane‐l,4‐sultone (C14 delta sultone) and the combination of 2‐chlorotetradecane‐1,3‐sultone (C14 2‐chloro gamma sultone), and 1‐tetradecene‐l,3‐sultone (C14 unsaturated gamma sultone) in neutral oils isolated from olefin sulfonate. Samples of the neutral oil are diluted in hexane and injected directly into the gas Chromatograph. Quantitative data are obtained by comparison to known amounts of the respective sultones. Through the use of silica gel column chromatography followed by gas chromatography of collected fractions, separation and individual quantitation of the 2‐chlorotetradecane‐1,3 sultone and l‐tetradecene‐l,3‐sultone can be obtained. Routine use for control purposes has shown the method to be reliable and interlaboratory agreement of data has been good.
Identification of sulfur compounds in rapeseed oil
Authors: Daun J. K. , Hougen F. W.
Published: January 2008

Abstract and Summary

Seven sulfur compounds were found in industrially extracted rapeseed oils. Four of these were identified as 3‐butenyl‐, 4‐pentenyl‐, and phenethyl isothiocyanate, and 5‐vinyl‐2‐oxazolidinethione. These compounds are hydrolysis products from glucosinolates present in the seed.
Recovery of short, medium, and long chain fatty acid methyl esters using wet halogenated hydrocarbons
Authors: MacGee Joseph , Allen Kenneth G.
Published: January 2008

Abstract and Summary

Fatty acid methyl esters are prepared and analyzed by gas liquid chromatography using a simple procedure that does not involve evaporation steps or drying of the final extract. The esters of fatty acids down to caproate (C6) are recovered quantitatively. The long chain fatty acid esters, including the polyunsaturated esters, are also recovered quantitatively and are at least as stable as esters isolated by conventional procedures. Preparation of the esters in methanolic reagents is followed by partition of the mixture between a small volume of ethylene chloride and a large volume of water. The lower halogenated hydrocarbon phase contains the methyl esters ready for analysis, and the aqueous phase contains the methanol, catalysts, and other water‐soluble materials.
The Impact of Surgical and Percutaneous Coronary Revascularization on the Cardiac Myocyte
Authors: Khabbaz Kamal R. , Levitsky Sidney
Published: January 2008

Re‐establishing coronary blood flow to a segment of myocardium suffering from cessation or diminution of flow, either with surgical or percutaneous approaches, may be complicated by injury to the myocardium. During surgical revascularization with coronary artery bypass grafting (CABG), aortic cross‐clamping and subsequent reduction in oxygen transport to the myocardium may result in cardiac myocyte injury and myonecrosis. This injury can be compounded if protection of the myocardium using myocardial protective strategies is not adequate. Ischemia/reperfusion cellular alterations may contribute to this injury as well. Percutaneous coronary interventions (PCI) are also associated with myonecrosis resulting from side branch compromise, distal embolization of debris, and plugging of the microcirculation, as well as ischemia/reperfusion injury. Intracoronary filtering devices have not been shown to improve outcomes associated with such complications. Which revascularization strategy is associated with superior outcomes and less cardiac myocyte necrosis is an area of continuing controversy.
Analysis of Human Oral Mucosa Ex Vivo for Fatty Acid Compositions Using Fourier‐transform Infrared Spectroscopy
Authors: Yoshida Satoshi , Okazaki Yuhki , Yamashita Takumi , Ueda Hiroshi , Ghadimi Reza , Hosono Akihiro , Tanaka Tsutomu , Kuriki Kiyonori , Suzuki Sadao , Tokudome Shinkan
Published: January 2008

The purpose of this research was to develop an infrared spectroscopic technique (Fourier transform infrared spectroscopy with attenuated total reflectance system; FTIR‐ATR) for non‐invasive measurement of saturated and unsaturated fatty acid compositions in human oral mucosa obtained from three nationalities; Iranian, Vietnamese, and Indonesian. The histogram patterns of fatty acid compositions for three nationalities suggest that the pattern of unsaturated fatty acids were quite different, although the distribution profiles of fatty acid to lipid ratios in FTIR‐ATR has a similar normal pattern with small difference in skewness and mode. The second derivative infrared spectra of the mucosal tissues in the wavenumber regions from 1,600 to 1,760 cm−1 and 2,800 to 3,050 cm−1 were analyzed with partial least squares (PLS) multivariate regression analysis method. With this analysis method we compared predicted values with the measured values of ten categorized fatty acid compositions, i.e., a(saturated C17 or lower), b(C16:1 + C17:1), c(C18:0), d(C18:1), e(C18:2), f(saturated C20 or longer), g(C20:3 + C20:4), h(C22:1 + C24:1), i(C22:6), j(γC18:3). Almost all fatty acid compositions of oral mucosa were well predicted with differences between predicted and measured values within ±5% of total, however, errors were relatively larger in minor components such as C22:6 than major components.
Physical and Chemical Characterizations of Normal and High‐Oleic Oils from Nine Commercial Cultivars of Peanut
Authors: Davis J. P. , Dean L. O. , Faircloth W. H. , Sanders T. H.
Published: January 2008

Density and viscosity data as a function of temperature (5–100 °C) were collected for oils (normal and high‐oleic) from nine cultivars of peanut. Density decreased linearly (R2 ≥ 0.99) with increasing temperature for all oils, whereas viscosity (dynamic or kinematic) decreased exponentially with increasing temperature. At any particular temperature, dynamic viscosity increased linearly (R2 ≥ 0.95) with decreasing oil density among the various oils. Slopes of the linear fits (with units of kinematic viscosity) for dynamic viscosity versus density plots decreased in an exponential fashion as the measurement temperature decreased. High‐oleic oils had both the lowest densities and highest viscosities, with viscosity differences being most apparent at cooler temperatures. Increasing contents of oleic acid, decreasing contents of linoleic acid, and decreasing contents of palmitic acid were each associated with decreased density and increased viscosity among the oils. Two of the three high‐oleic oils had the significantly (p < 0.05) highest content of total tocopherols, while the other high‐oleic oil was statistically grouped with the oils having the 2nd highest total tocopherol content. This suggests a link between increased total tocopherols and high‐oleic peanut oils; however, no obvious linear correlations were observed in tocopherol content and oil physical properties (density or viscosity).
Determination of Melting Points, Specific Heat Capacity and Enthalpy of Catfish Visceral Oil During the Purification Process
Authors: Sathivel Subramaniam , Prinyawiwatkul Witoon , Negulescu Ioan I. , King Joan M.
Published: January 2008

Changes in melting points, enthalpy, and specific heat capacity of catfish visceral oil at each step of the purification process were studied. Melting points of −46.2 to 21.2 °C for crude oil, −45.9 to 11.5 °C for degummed oil, −44.3 to 11.4 °C for neutralized oil, −47.1 to 9.9 °C for bleached oil and −52.3 to 8.0 °C for deodorized oil were observed. Enthalpy (kJ/kg) was 74.1 for crude oil, 74.7 for degummed oil, 75.1 for neutralized oil, 79.3 for bleached oil, and 84.3 for deodorized oil. The specific heat capacities at 20 °C for crude, degummed, neutralized, bleached, and deodorized oils were 1.69, 1.96, 1.97, 1.91, and 1.83 kJ/kg °C, respectively.
POINCARÉ DUALITY FORK-THEORY OF EQUIVARIANT COMPLEX PROJECTIVE SPACES
Authors: GREENLEES J. P. C. , WILLIAMS G. R.
Published: January 2008

We make explicitPoincaré dualityfor the equivariantK-theory of equivariant complex projective spaces. The case of the trivial group provides a new approach to theK-theory orientation [3].
OSCILLATION CRITERIA FOR CERTAIN DAMPED PDE'S WITH p-LAPLACIAN
Authors: XU ZHITING
Published: January 2008

Some oscillation criteria are obtained for the damped PDE with p-Laplacian

The results established here are extensions of some classical oscillation theorems due to Fite-Wintner and Kamenev for second order ordinary differential equations, and improve and complement recent results of Mařík and Usami.
ON THE DIOPHANTINE EQUATION x2 + 5a 13b = yn
Authors: ABU MURIEFAH FADWA S. , LUCA FLORIAN , TOGBÉ ALAIN
Published: January 2008

In this note, we find all the solutions of the Diophantine equation x2 + 5a 13b = yn in positive integers x, y, a, b, n≥ 3 with x and y coprime.
THE UNIT SUM NUMBER OF SOME PROJECTIVE MODULES
Authors: ASHRAFI NAHID
Published: January 2008

The unit sum number u(R) of a ring R is the least k such that every element is the sum of k units; if there is no such k then u(R) is ω or ∞ depending whether the units generate R additively or not. If RM is a left R-module, then the unit sum number of M is defined to be the unit sum number of the endomorphism ring of M. Here we show that if R is a ring such that R/J(R) is semisimple and $\Z_{2}$ is not a factor of R/J(R) and if P is a projective R-module such that JP ≪ P, (JP small in P), then u(P)= 2. As a result we can see that if P is a projective module over a perfect ring then u(P)=2.
Reconstructing the ‘Sacred Canopy’: Mother Serafima and Novodevichy Monastery
Authors: DANIEL WALLACE L.
Published: January 2008

Since the collapse of the Soviet Union in 1991, the Orthodox Church and the Russian government have sought to restore monasteries, viewing them as key institutions in the regeneration of religion. Novodevichy Monastery in Moscow has historically been one of Russia's most important religious centres and its most famous monastery for women. Returned to the Church in 1994, Novodevichy was administered by Mother Serafima, a remarkable woman whose life covered most of the twentieth century. In reconstructing monastic life, she placed charity at the centre of her endeavours. In her struggles and her efforts to rebuild the ‘sacred canopy’ at Novodevichy is depicted, in microcosmic form, Russia's own quest to recover its heritage and redefine its identity.
Hedging rule for reservoir operations: 1. A theoretical analysis
Authors: You Jiing‐Yun , Cai Ximing
Published: January 2008

Hedging rule policies for reservoir operations accept small deficits in current supply to reduce the probability of a severe water shortage later. This paper expands a theoretical analysis and develops a conceptual two‐period model for reservoir operation with hedging that includes uncertain future reservoir inflow explicitly. Extended analysis of the model properties and influencing factors is presented with a general utility function, addressing (1) the starting and ending water availability for hedging, (2) the range of hedging that is related to water demand levels, (3) inflow uncertainty, and (4) evaporation loss. Some intuitive knowledge on reservoir operation is proved or reconfirmed analytically; and new knowledge is derived. This theoretical analysis provides an updated basis for further theoretical study, and the theoretical findings can be used to improve numerical modeling for reservoir operation.
Solar flux variability of Mars' exosphere densities and temperatures
Authors: Forbes Jeffrey M. , Lemoine Frank G. , Bruinsma Sean L. , Smith Michael D. , Zhang Xiaoli
Published: January 2008

Using densities derived from precise orbit determination of the Mars Global Surveyor (MGS) spacecraft from 1999 to mid‐2005, the response of Mars' exosphere to long‐term solar change is established and compared to that of Earth and Venus. At Mars, exosphere temperatures (weighted towards high‐latitude Southern Hemisphere daytime conditions) change only 36–50% as much as those at Earth as solar activity increases from solar minimum to solar maximum, whereas the response at Venus is one‐fifth that at Mars. General circulation models suggest that this difference may be strongly influenced by adiabatic cooling associated with the thermosphere general circulation. However, other processes such as differences in CO2 cooling rates may also be playing a role.
Constitutive relationships and physical basis of fault strength due to flash heating
Authors: Beeler N. M. , Tullis T. E. , Goldsby D. L.
Published: January 2008

We develop a model of fault strength loss resulting from phase change at asperity contacts due to flash heating that considers a distribution of contact sizes and nonsteady state evolution of fault strength with displacement. Laboratory faulting experiments conducted at high sliding velocities, which show dramatic strength reduction below the threshold for bulk melting, are well fit by the model. The predicted slip speed for the onset of weakening is in the range of 0.05 to 2 m/s, qualitatively consistent with the limited published observations. For this model, earthquake stress drops and effective shear fracture energy should be linearly pressure‐dependent, whereas the onset speed may be pressure‐independent or weakly pressure‐dependent. On the basis of the theory, flash weakening is expected to produce large dynamic stress drops, small effective shear fracture energy, and undershoot. Estimates of the threshold slip speed, stress drop, and fracture energy are uncertain due to poor knowledge of the average contact dimension, shear zone thickness and gouge particle size at seismogenic depths.
An ecosystem model for tropical forest disturbance and selective logging
Authors: Huang Maoyi , Asner Gregory P. , Keller Michael , Berry Joseph A.
Published: January 2008

A new three‐dimensional version of the Carnegie‐Ames‐Stanford Approach (CASA) ecosystem model (CASA‐3D) was developed to simulate regional carbon cycling in tropical forest ecosystems after disturbances such as logging. CASA‐3D has the following new features: (1) an alternative approach for calculating absorbed photosynthetically active radiation (APAR) using new high‐resolution satellite images of forest canopy gap fraction; (2) a pulse disturbance module to modify aboveground carbon pools following forest disturbance; (3) a regrowth module that simulates changes in community composition by considering gap phase regeneration; and (4) a radiative transfer module to simulate the dynamic three‐dimensional light environment above the canopy and within gaps after forest disturbance. The model was calibrated with and tested against field observations from experimental logging plots in the Large‐scale Biosphere Atmosphere Experiment in Amazonia (LBA) project. The sensitivity of key model parameters was evaluated using Monte Carlo simulations, and the uncertainties in simulated NPP and respiration associated with model parameters and meteorological variables were assessed. We found that selective logging causes changes in forest architecture and composition that result in a cascading set of impacts on the carbon cycling of rainforest ecosystems. Our model sensitivity and uncertainty analyses also highlight the paramount importance of measuring changes in canopy gap fraction from satellite data, as well as canopy light‐use efficiency from ecophysiological measurements, to understand the role of forest disturbance on landscape and regional carbon cycling in tropical forests. In sum, our study suggests that CASA‐3D may be suitable for regional‐scale applications to assess the large‐scale effects of selective logging, to provide guidance for forest management, and to understand the role of forest disturbance in regional and global climate studies.
A risk‐driven approach for subsurface site characterization
Authors: de Barros F. P. J. , Rubin Y.
Published: January 2008

We present a probabilistic framework to addressing adverse human health effects due to groundwater contamination. One of the main challenges in health risk assessment is in relating it to subsurface data acquisition and to improvement in our understanding of human physiological responses to contamination. In this paper we propose to investigate this problem through an approach that integrates flow, transport and human health risk models with hydrogeological characterization. A human health risk cumulative distribution function is analytically developed to account for both uncertainty and variability in hydrogeological as well as human physiological parameters. With our proposed approach, we investigate under which conditions the reduction of uncertainties from flow physics, human physiology and exposure related parameters might contribute to a better understanding of human health risk assessment. Results indicate that the human health risk cumulative distribution function becomes less sensitive to uncertainty in physiological parameters at lower risk values associated with longer traveltimes. We also present a graphical tool that allows to investigate the relative impact of hydrogeological and physiological parameters in human health risk. A metric α that relates hydrogeological uncertainty to physiological uncertainty was developed to help decision makers set priorities in data acquisition. Other results show that the worth of hydrogeological characterization in human health risk depends on the time the contaminant plume takes to cross the control plane and on the exposure duration of the population to certain chemicals.
Cerebral Blood Volume Quantification in a C6 Tumor Model Using Gadolinium per (3,6-Anhydro) α-Cyclodextrin as a New Magnetic Resonance Imaging Preclinical Contrast Agent
Authors: Lahrech Hana , Perles-Barbacaru Adriana-Teodora , Aous Soâd , Le Bas Jean-François , Debouzy Jean-Claude , Gadelle Andrée , Fries Pascal H
Published: January 2008

In magnetic resonance imaging (MRI), cerebral blood volume (CBV) quantification is dependent on the MRI sequence and on the properties of the contrast agents (CAs). By using the rapid steady-state T1 method, we show the potential of gadolinium per (3,6-anhydro) α-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd3+ with per (3,6-anhydro)-α-cyclodextrin), for the CBV quantification in the presence of blood—brain barrier lesions. After biocompatibility and relaxivity experiments, in vivo experiments on rats were performed on a C6 tumor model with 0.05 mmol Gd-ACX/kg (<1/10 of the median lethal dose) injected at a 25mmol/L concentration, inducing neither nephrotoxicity nor hemolysis. On T1-weighted images, a signal enhancement of 170% appeared in vessels after injection, but not in the tumor (during the 1 h of observation), in contrast to the 90% signal enhancement obtained with Gd-DOTA (a clinical MRI CA) injected at a T1 isoefficient dose. This result shows the absence of Gd-ACX extravasation into the tumor tissue and its confinement to the vascular space. Fractional CBV values were found similar to Gd-ACX and Gd-DOTA in healthy brain tissue and in the contralateral hemisphere of tumor-bearing rats, whereas only Gd-ACX was appropriate for CBV quantification in tumor regions.
Toll-Like Receptor 9: A New Target of Ischemic Preconditioning in the Brain
Authors: Stevens Susan L , Ciesielski Thomas MP , Marsh Brenda J , Yang Tao , Homen Delfina S , Boule Jo-Lynn , Lessov Nikola S , Simon Roger P , Stenzel-Poore Mary P
Published: January 2008

Preconditioning with lipopolysaccharide (LPS), a toll-like receptor 4 (TLR4) ligand, provides neuroprotection against subsequent cerebral ischemic brain injury, through a tumor necrosis factor (TNF)α-dependent process. Here, we report the first evidence that another TLR, TLR9, can induce neuroprotection. We show that the TLR9 ligand CpG oligodeoxynucleotide (ODN) can serve as a potent preconditioning stimulus and provide protection against ischemic brain injury. Our studies show that systemic administration of CpG ODN 1826 in advance of brain ischemia (middle cerebral artery occlusion (MCAO)) reduces ischemic damage up to 60% in a dose- and time-dependent manner. We also offer evidence that CpG ODN preconditioning can provide direct protection to cells of the central nervous system, as we have found marked neuroprotection in modeled ischemia in vitro. Finally, we show that CpG preconditioning significantly increases serum TNFα levels before MCAO and that TNFα is required for subsequent reduction in damage, as mice lacking TNFα are not protected against ischemic injury by CpG preconditioning. Our studies show that preconditioning with a TLR9 ligand induces neuroprotection against ischemic injury through a mechanism that shares common elements with LPS preconditioning via TLR4.
The epigenetic signature of CFTR expression is co-ordinated via chromatin acetylation through a complex intronic element
Authors: Paul Thankam , Li SiDe , Khurana Sanjeev , Leleiko Neal S. , Walsh Martin J.
Published: January 2008

The CFTR (cystic fibrosis transmembrane conductance regulator) gene is a tightly regulated and differentially expressed transcript in many mucosal epithelial cell types. It appears that DNA sequence variations alone do not explain CFTR-related gastrointestinal disease patterns and that epigenetic modifiers influence CFTR expression. Our aim was to characterize the native chromatin environment in cultured cells for intestinal CFTR expression by determining the relationship between histone acetylation and occupation of CFTR by multiple transcription factors, through a common regulatory element. We used HDAC (histone deacetylase) inhibition and ChIP (chromatin immunoprecipitation) analyses to define regions associated with acute acetylation of histone at the CFTR locus. We identified a region within the first intron associated with acute acetylation of histone H4 as an epigenetic signature corresponding to an intestine-specific enhancer element for CFTR. DHS (DNase I-hypersensitivity) assays and ChIP were used to specify control elements and occupation by regulatory factors. Quantitative ChIP procedures indicate that HNF1α (hepatic nuclear factor 1α) and Cdx2 (caudal homeobox protein 2) occupy and regulate through a novel intronic enhancer element of CFTR and that Tcf4 (T-cell factor 4) overlaps the same DNA element. RNAi (RNA interference) of Tcf4 and HNF1α decreased intestinal cell CFTR expression, identifying these as positive regulatory factors and CFTR as a target for Wnt signalling. We have linked the acetylation signature of nucleosomal histones to active intestinal CFTR expression and occupation by transcription factors HNF1α, Cdx2 and Tcf4 which converge to modify chromatin architecture. These studies suggest the therapeutic potential of histone modification strategies, such as inhibition of HDAC activity, to treat CFTR-associated disease by selectively enhancing CFTR expression.
The C-terminus of connexin43 adopts different conformations in the Golgi and gap junction as detected with structure-specific antibodies
Authors: Sosinsky Gina E. , Solan Joell L. , Gaietta Guido M. , Ngan Lucy , Lee Grace J. , Mackey Mason R. , Lampe Paul D.
Published: January 2008

The C-terminus of the most abundant and best-studied gap-junction protein, connexin43, contains multiple phosphorylation sites and protein-binding domains that are involved in regulation of connexin trafficking and channel gating. It is well-documented that SDS/PAGE of NRK (normal rat kidney) cell lysates reveals at least three connexin43-specific bands (P0, P1 and P2). P1 and P2 are phosphorylated on multiple, unidentified serine residues and are found primarily in gap-junction plaques. In the present study we prepared monoclonal antibodies against a peptide representing the last 23 residues at the C-terminus of connexin43. Immunofluorescence studies showed that one antibody (designated CT1) bound primarily to connexin43 present in the Golgi apparatus, whereas the other antibody (designated IF1) labelled predominately connexin43 present in gap junctions. CT1 immunoprecipitates predominantly the P0 form whereas IF1 recognized all three bands. Peptide mapping, mutational analysis and protein–protein interaction experiments revealed that unphosphorylated Ser364 and/or Ser365 are critical for CT1 binding. The IF1 paratope binds to residues Pro375–Asp379 and requires Pro375 and Pro377. These proline residues are also necessary for ZO-1 interaction. These studies indicate that the conformation of Ser364/Ser365 is important for intracellular localization, whereas the tertiary structure of Pro375–Asp379 is essential in targeting and regulation of gap junctional connexin43.
Molecular cloning and biochemical characterization of sialidases from zebrafish (Danio rerio)
Authors: Manzoni Marta , Colombi Paolo , Papini Nadia , Rubaga Luana , Tiso Natascia , Preti Augusto , Venerando Bruno , Tettamanti Guido , Bresciani Roberto , Argenton Francesco , Borsani Giuseppe , Monti Eugenio
Published: January 2008

Sialidases remove sialic acid residues from various sialo-derivatives. To gain further insights into the biological roles of sialidases in vertebrates, we exploited zebrafish (Danio rerio) as an animal model. A zebrafish transcriptome- and genome-wide search using the sequences of the human NEU polypeptides as templates revealed the presence of seven different genes related to human sialidases. neu1 and neu4 are the putative orthologues of the mammalian sialidases NEU1 and NEU4 respectively. Interestingly, the remaining genes are organized in clusters located on chromosome 21 and are all more closely related to mammalian sialidase NEU3. They were thus named neu3.1, neu3.2, neu3.3, neu3.4 and neu3.5. Using RT–PCR (reverse transcription–PCR) we detected transcripts for all genes, apart from neu3.4, and whole-mount in situ hybridization experiments show a localized expression pattern in gut and lens for neu3.1 and neu4 respectively. Transfection experiments in COS7 (monkey kidney) cells demonstrate that Neu3.1, Neu3.2, Neu3.3 and Neu4 zebrafish proteins are sialidase enzymes. Neu3.1, Neu3.3 and Neu4 are membrane-associated and show a very acidic pH optimum below 3.0, whereas Neu3.2 is a soluble sialidase with a pH optimum of 5.6. These results were further confirmed by subcellular localization studies carried out using immunofluorescence. Moreover, expression in COS7 cells of these novel zebrafish sialidases (with the exception of Neu3.2) induces a significant modification of the ganglioside pattern, consistent with the results obtained with membrane-associated mammalian sialidases. Overall, the redundancy of sialidases together with their expression profile and their activity exerted on gangliosides of living cells indicate the biological relevance of this class of enzymes in zebrafish.
Structure-based design of small peptide inhibitors of protein kinase CK2 subunit interaction
Authors: Laudet Béatrice , Barette Caroline , Dulery Vincent , Renaudet Olivier , Dumy Pascal , Metz Alexandra , Prudent Renaud , Deshiere Alexandre , Dideberg Otto , Filhol Odile , Cochet Claude
Published: January 2008

X-ray crystallography studies, as well as live-cell fluorescent imaging, have recently challenged the traditional view of protein kinase CK2. Unbalanced expression of catalytic and regulatory CK2 subunits has been observed in a variety of tissues and tumours. Thus the potential intersubunit flexibility suggested by these studies raises the likely prospect that the CK2 holoenzyme complex is subject to disassembly and reassembly. In the present paper, we show evidence for the reversible multimeric organization of the CK2 holoenzyme complex in vitro. We used a combination of site-directed mutagenesis, binding experiments and functional assays to show that, both in vitro and in vivo, only a small set of primary hydrophobic residues of CK2β which contacts at the centre of the CK2α/CK2β interface dominates affinity. The results indicate that a double mutation in CK2β of amino acids Tyr188 and Phe190, which are complementary and fill up a hydrophobic pocket of CK2α, is the most disruptive to CK2α binding both in vitro and in living cells. Further characterization of hotspots in a cluster of hydrophobic amino acids centred around Tyr188–Phe190 led us to the structure-based design of small-peptide inhibitors. One conformationally constrained 11-mer peptide (Pc) represents a unique CK2β-based small molecule that was particularly efficient (i) to antagonize the interaction between the CK2 subunits, (ii) to inhibit the assembly of the CK2 holoenzyme complex, and (iii) to strongly affect its substrate preference.
The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein
Authors: Hsieh Yi-Ching , Tu Pei-Jung , Lee Ying-Yuan , Kuo Chun-Chen , Lin Yi-Chien , Wu Chi-Fang , Lin Jing-Jer
Published: January 2008

Imp4p is a component of U3 snoRNP (small nucleolar ribonucleoprotein) involved in the maturation of 18S rRNA. We have shown that Imp4p interacts with Cdc13p, a single-stranded telomere-binding protein involved in telomere maintenance. To understand the role of Imp4p in telomeres, we purified recombinant Imp4p protein and tested its binding activity towards telomeric DNA using electrophoretic mobility-shift assays. Our results showed that Imp4p bound specifically to single-stranded telomeric DNA in vitro. The interaction of Imp4p to telomeres in vivo was also demonstrated by chromatin immunoprecipitation experiments. Significantly, the binding of Imp4p to telomeres was not limited to yeast proteins, since the hImp4 (human Imp4) also bound to vertebrate single-stranded telomeric DNA. Thus we conclude that Imp4p is a novel telomeric DNA-binding protein that, in addition to its role in rRNA processing, might participate in telomere function.
The role of Schizosaccharomyces pombe SUMO ligases in genome stability
Authors: Watts F.Z. , Skilton A. , Ho J.C.-Y. , Boyd L.K. , Trickey M.A.M. , Gardner L. , Ogi F.-X. , Outwin E.A.
Published: January 2008

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins.
Genetic polymorphisms within the human Toll-like receptor 2 subfamily
Authors: Tapping R.I. , Omueti K.O. , Johnson C.M.
Published: January 2008

Infectious disease is a formidable selective force in Nature as is evident from the complexity of immune systems across multicellular species. TLRs (Toll-like receptors) constitute central pattern-recognition molecules of the innate immune system that sense bacterial, viral, fungal, protozoan and helminth organisms and activate responses that provide immediate as well as long-term protection for the host. The present article reviews the function and evolution of vertebrate TLRs with an emphasis on the subfamily of receptors comprising human TLR1, 2, 6 and 10. The idea that TLRs undergo strong purifying selection provides the framework for the discussion of single nucleotide polymorphisms, many of which are associated with the incidence of infectious disease.
HPV: from infection to cancer
Authors: Stanley M.A. , Pett M.R. , Coleman N.
Published: January 2008

Infection with HPV (human papillomavirus) 16 is the cause of 50% or more of cervical cancers in women. HPV16 infection, however, is very common in young sexually active women, but the majority mount an effective immune response and clear infection. Approx. 10% of individuals develop a persistent infection, and it is this cohort who are at risk of cancer progression, with the development of high-grade precursor lesions and eventually invasive carcinoma. Effective evasion of innate immune recognition seems to be the hallmark of HPV infections, since the infectious cycle is one in which viral replication and release is not associated with inflammation. Furthermore, HPV infections disrupt cytokine expression and signalling with the E6 and E7 oncoproteins particularly targeting the type I IFN (interferon) pathway. High doses of IFN can overcome the HPV-mediated abrogation of signalling, and this may be the basis for the therapeutic effects on HPV infections of immune-response modulators such as the imidazoquinolones that induce high levels of type I IFNs by activation of TLR (Toll-like receptor) 7. Using the unique W12 model of cervical carcinogenesis, some of these IFN-related interactions and their relevance in the selection of cells with integrated viral DNA in cancer progression have been investigated. Our data show that episome loss associated with induction of antiviral response genes is a key event in the spontaneous selection of cervical keratinocytes containing integrated HPV16. Exogenous IFN-β treatment of W12 keratinocytes in which the majority of the population contain episomes results only in the rapid emergence of IFN-resistant cells, loss of episome-containing cells and a selection of cells containing integrated HPV16 in which the expression of the transcriptional repressor E2 is down-regulated, but in which E6 and E7 are up-regulated.
Synthetic agonists of Toll-like receptors 7, 8 and 9
Authors: Agrawal S. , Kandimalla E.R.
Published: January 2008

TLRs (Toll-like receptors) are a family of innate immune receptors that induce protective immune responses against infections. Single-stranded viral RNA and bacterial DNA containing unmethylated CpG motifs are the ligands for TLR7 and TLR8 and 9 respectively. We have carried out extensive structure–activity relationship studies of DNA- and RNA-based compounds to elucidate the impact of nucleotide motifs and structures on these TLR-mediated immune responses. These studies have led us to design novel DNA- and RNA-based compounds, which act as potent agonists of TLR9 and TLR7 and 8 respectively. These novel synthetic agonists produce different immune response profiles depending on the structures and nucleotide motifs present in them. The ability to modulate TLR-mediated immune responses with these novel DNA- and RNA-based agonists in a desired fashion may allow targeting a broad range of diseases, including cancers, asthma, allergies and infections, alone or in combination with other therapeutic agents, and their use as adjuvants with vaccines. IMO-2055, our first lead candidate, is a TLR9 agonist that is currently in clinical evaluation in oncology patients. A second candidate, IMO-2125, is also a TLR9 agonist that has been shown to induce high and sustained levels of IFN (interferon) in non-human primates and is being evaluated in HepC-infected human subjects.