bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of hyperglycaemia and its associated complications by finger millet (Eleusine coracanaL.) seed coat matter in streptozotocin-induced diabetic rats
Authors: Shobana Shanmugam , Harsha Mysore R. , Platel Kalpana , Srinivasan Krishnapura , Malleshi Nagappa G.
Published: October 2010

Finger millet (Eleusine coracana) is extensively cultivated and consumed in India and Africa. The millet seed coat is a rich source of dietary fibre and phenolic compounds. The effect of feeding a diet containing 20 % finger millet seed coat matter (SCM) was examined in streptozotocin-induced diabetic rats. Diabetic rats maintained on the millet SCM diet (diabetic experimental (DE) group) for 6 weeks exhibited a lesser degree of fasting hyperglycaemia and partial reversal of abnormalities in serum albumin, urea and creatinine compared with the diabetic control (DC) group. The DE group of rats excreted comparatively lesser amounts of glucose, protein, urea and creatinine and was accompanied by improved body weights compared with their corresponding controls. Hypercholesterolaemia and hypertriacylglycerolaemia associated with diabetes were also notably reversed in the DE group. Slit lamp examination of the eye lens revealed an immature subcapsular cataract with mild lenticular opacity in the DE group of rats compared to the mature cataract with significant lenticular opacity and corneal vascularisation in the DC group. Lower activity of lens aldose reductase, serum advanced glycation end products and blood glycosylated Hb levels were observed in the DE group. The millet SCM feeding showed pronounced ameliorating effects on kidney pathology as reflected by near normal glomerular and tubular structures and lower glomerular filtration rate compared with the shrunken glomerulus, tubular vacuolations in the DC group. Thus, the present animal study evidenced the hypoglycaemic, hypocholesterolaemic, nephroprotective and anti-cataractogenic properties of finger millet SCM, suggesting its utility as a functional ingredient in diets for diabetics.
The Lalonde–McDuff Conjecture and the fundamental group
Authors: Kędra Jarek
Published: October 2010

We give a simple proof of the Lalonde–McDuff Conjecture for aspherical manifolds.
Repunit Lehmer numbers
Authors: Cilleruelo Javier , Luca Florian
Published: October 2010

A Lehmer number is a composite positive integer n such that ϕ(n)|n − 1. In this paper, we show that given a positive integer g > 1 there are at most finitely many Lehmer numbers which are repunits in base g and they are all effectively computable. Our method is effective and we illustrate it by showing that there is no such Lehmer number when g ∈ [2, 1000].
Elementary operators and subhomogeneousC*-algebras
Authors: Gogić Ilja
Published: October 2010

LetAbe aC*-algebra and let ΘAbe the canonical contraction form the Haagerup tensor product ofM(A) with itself to the space of completely bounded maps onA. In this paper we consider the following conditions onA: (a)Ais a finitely generated module over the centre ofM(A); (b) the image of ΘAis equal to the set E(A) of all elementary operators onA; and (c) the lengths of elementary operators onAare uniformly bounded. We show thatAsatisfies (a) if and only if it is a finite direct sum of unital homogeneousC*-algebras. We also show that if a separableAsatisfies (b) or (c), thenAis necessarily subhomogeneous and theC*-bundles corresponding to the homogeneous subquotients ofAmust be of finite type.
The Future of Ontario French
Authors: GRIMM RICK , NADASDI TERRY
Published: October 2010

The present study is a Labovian sociolinguistic analysis of forms used to express the future tense in the spoken French of adolescents residing in Ontario, Canada. Two primary variants are examined: a) the periphrastic future (e.g.elle va partir); and b) the inflected future (e.g.elle partira). The general trend that emerges is that distribution rates of the periphrastic future are markedly higher than previous accounts of the variable and that many speakers are in fact categorical users of the periphrastic form in certain contexts. Note, too, that negation is not a strong predictor for all speakers with respect to the choice of the inflected future, a finding that is in strong contrast to previous analyses of the variable in Laurentian varieties of spoken French in Canada. After presenting the general results, we provide an in-depth analysis of the linguistic and social factors that condition variant use.
L'aspect de phase en français: le rôle des périphrases verbales
Authors: GOSSELIN LAURENT
Published: October 2010

Cet article porte sur les périphrases aspectuelles (commencer à, être en train de, etc.). On montre que si les grammaires divergent fortement à propos du statut lexical ou grammatical qu'il convient de leur accorder, il est néanmoins possible et pertinent de dissocier deux classes de périphrases, auxquelles on attribue un fonctionnement sémantique nettement différent. Les unes servent à construire un sous-procès, tandis que les autres indiquent un type de visée aspectuelle particulier. Cette analyse prend appui sur des études récentes (Kronning, François, Laca), qui montrent de façon indépendante, mais convergente, qu'il est nécessaire de dissocier deux classes de périphrases aspectuelles sur la base de leur comportement syntaxique.
Characteristics of Langmuir electric field waveforms and power spectra exhibiting nonlinear behavior in Earth's foreshock
Authors: Sigsbee K. , Kletzing C. A. , Pickett J. S. , Gurnett D. A. , Schwartz S. J. , Lefebvre B. , Lucek E. , Fazakerley A. N. , Kucharek H.
Published: October 2010

Langmuir wave characteristics in the Earth's foreshock were examined to identify possible nonlinear wave behavior for two case studies with data from the Cluster Wideband Data Plasma Wave Receiver. The occurrence rates of four types of power spectra near the foreshock edge were determined: (1) spectra with power at the local plasma frequency fpe only, (2) spectra with power at fpe and 2fpe, (3) spectra with double peaks near fpe, and (4) spectra with double peaks near fpe and peaks at low frequencies indicative of ion acoustic waves. For electric field waveform amplitudes between 0.1 and 22.0 mV/m, most power spectra fell into the fpe only and double‐peaked categories. The maximum Langmuir wave amplitudes and bump‐on‐tail reduced electron distribution functions from Cluster PEACE data were more consistent with saturation of wave growth by electrostatic decay than modulational instabilities. However, few spectra had the double peaks near fpe and ion acoustic waves indicative of electrostatic decay, suggesting other processes may also be at work. For amplitudes greater than 22.0 mV/m, most power spectra fell into the fpe and 2fpe category, but many of the harmonics were too weak to be clearly distinguished from harmonics caused by instrumental effects.
GRACE and AMSR‐E‐based estimates of winter season solid precipitation accumulation in the Arctic drainage region
Authors: Seo Ki‐Weon , Ryu Dongryeol , Kim Baek‐Min , Waliser Duane E. , Tian Baijun , Eom Jooyoung
Published: October 2010

Solid precipitation plays a major role in controlling the winter hydrological cycle and spring discharge in the Arctic region. However, it has not been well documented due to sharply decreasing numbers of precipitation gauges, gauge measurement biases, as well as limitations of conventional satellite methods in high latitudes. In this study, we document the winter season solid precipitation accumulation in the Arctic region using the latest new satellite measurements from the Gravity Recovery and Climate Experiment (GRACE) and the Advanced Microwave Scanning Radiometer‐Earth Observing System (AMSR‐E). GRACE measures the winter total water (mainly from snow water equivalent (SWE)) storage change through gravity changes while AMSR‐E measures the winter SWE through passive microwave measurements. The GRACE and AMSR‐E measurements are combined with in situ and numerical model estimates of discharge and evapotranspiration to estimate the winter season solid precipitation accumulation in the Arctic region using the water budget equation. These two satellite‐based estimates are then compared to the conventional estimates from two global precipitation products, such as the Global Precipitation Climatology Project (GPCP) and Climate Prediction Center's Merged Analysis of Precipitation (CMAP), and three reanalyses, the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis, the European Centre for Medium‐Range Weather Forecasts' ERA‐Interim, and the Japan Meteorological Agency's Climate Data Assimilation System (JCDAS) reanalysis. The GRACE‐based estimate is very close to the GPCP and ERA‐Interim estimates. The AMSR‐E‐based estimate is the most different from the other estimates. This GRACE‐based measurement of winter season solid precipitation accumulation can provide a new valuable benchmark to understand the hydrological cycle, to validate and evaluate the model simulation, and to improve data assimilation in the Arctic region.
Simple analytical solutions for oxygen transfer into anaerobic groundwater
Authors: Liu Sanheng , Liedl Rudolf , Grathwohl Peter
Published: October 2010

The oxygen flux from the atmosphere into aquifers plays a key role for the biodegradation of organic solutes in groundwater and changing the water chemistry in general. In this paper, simple analytical solutions for the reactive transport of oxygen into groundwater are derived and compared to numerical models. The oxygen transfer is described analogous to diffusion into a semi‐infinite domain with instantaneous reaction. We assume the capillary fringe does not exist and the concentration of oxygen is constant at the water table. Steady state analytical solutions are derived for the oxygen flux and for the concentration profiles of the reactants and products that could be volatile and nonvolatile. The simple approach is validated with numerical simulations. We can show that the analytical solutions agree very well with the numerical model. On the basis of this finding, simple analytical solutions can be used to calculate the depth of oxidation fronts in groundwater and the reactive transport of oxygen into groundwater.
Vadose zone transport in dry forests of central Argentina: Role of land use
Authors: Santoni C. S. , Jobbágy E. G. , Contreras S.
Published: October 2010

Most sedimentary plains occupied by semiarid woody ecosystems have low groundwater recharge rates and high vadose zone salt accumulation. Their cultivation has often led to drainage of water below root zone, displacement of solutes, and rising water tables, affecting, in most extreme cases, long‐term viability of agriculture. To explore this possibility in semiarid plains of South America, we characterized vadose flow using chloride data in dry forests of central Argentina, in an area that has been subject to intense deforestation and agricultural expansion during the last century. We selected five paired stands under natural dry forests and dryland agriculture (sites deforested ≥30 years ago) and sampled sediments (n = 3 boreholes) down to 6 m depth. Profiles were consistently dry and salty in forest stands with chloride inventories (0–6 m) of 150 g/m2to 9 × 103g/m2. Under cultivation 78% to 99% of the chloride stock was leached, and total water storage was ≥30% higher than in the dry forest, with soil water content close to field capacity. Estimates of groundwater recharge rates based on residual moisture flux approach (cumulative chloride versus cumulative water curves) suggested maximum values of 0.33 to 128.4 mm/yr for dry forest and agriculture, respectively. At agricultural stands recharge was also estimated using chloride front displacement, yielding minimum values ≥5.3 mm/yr. While the long‐term impact of cultivation on regional groundwater hydrology is still unclear in the region, our findings suggest that land salinization processes are possible and need careful monitoring in areas with high agricultural expansion.
Protons in the near‐lunar wake observed by the Sub‐keV Atom Reflection Analyzer on board Chandrayaan‐1
Authors: Futaana Y. , Barabash S. , Wieser M. , Holmström M. , Bhardwaj A. , Dhanya M. B. , Sridharan R. , Wurz P. , Schaufelberger A. , Asamura K.
Published: October 2010

Significant proton fluxes were detected in the near‐wake region of the Moon by an ion mass spectrometer on board Chandrayaan‐1. The energy of these nightside protons is slightly higher than the energy of the solar wind protons. The protons are detected close to the lunar equatorial plane at a 140° solar zenith angle, that is, ∼50° behind the terminator at a height of 100 km. The protons come from just above the local horizon and move along the magnetic field in the solar wind reference frame. We compare the observed proton flux with the predictions from analytical models of an electrostatic plasma expansion into a vacuum. The observed velocity is higher by a factor of 2 to 3 than the velocity predicted by analytical models. The simple analytical models cannot explain the observed ion dynamics along the magnetic field in the vicinity of the Moon.
On the reformation at quasi‐ and exactly perpendicular shocks: Full particle‐in‐cell simulations
Authors: Umeda Takayuki , Kidani Yoshitaka , Yamao Masahiro , Matsukiyo Shuichi , Yamazaki Ryo
Published: October 2010

A full particle‐in‐cell (PIC) simulation study is carried out on the reformation at quasi‐ and exactly perpendicular collisionless shocks with a relatively low Alfven Mach number (MA = 5). Previous self‐consistent one‐dimensional (1‐D) hybrid and full PIC simulations have demonstrated that ion kinetics are essential for the nonstationarity of perpendicular collisionless shocks. These results showed that reflection of ions at the shock front is responsible for the periodic collapse and redevelopment of a new shock front on a timescale of the ion cyclotron period, which is called the shock reformation. Recent 2‐D hybrid and full PIC simulations, however, suggested that the shock reformation does not take place at exactly perpendicular shocks with MA ∼ 5. By contrast, another 2‐D hybrid PIC simulation showed that the shock reformation persists at quasi‐perpendicular shocks with MA ∼ 5. Although these two works seem to be inconsistent with each other, the reason is not well understood because of several differences in numerical simulation conditions. Thus this paper gives a direct comparison between full PIC simulations of quasi‐ and exactly perpendicular shocks with almost the same condition. It is found that the time development of the shock magnetic field averaged over the shock‐tangential direction shows the transition from the reformation to no‐reformation phase. On the other hand, local shock magnetic field shows the evident appearance and disappearance of the shock front, and the period becomes longer in the no‐reformation phase than in the reformation phase.
Combined radial diffusion and adiabatic transport of radiation belt electrons with arbitrary pitch angles
Authors: Su Zhenpeng , Xiao Fuliang , Zheng Huinan , Wang Shui
Published: October 2010

Storm‐time radial diffusion of radiation belt electrons with arbitrary pitch angles in a time‐varying geomagnetic field is simulated based on our recently developed STEERB code. In particular, the fully adiabatic response of energetic electrons to the variation of geomagnetic field is self‐consistently incorporated. Simulation results show that the outward adiabatic transport (instead of outward radial diffusion) is primarily responsible for the main phase depletion of energetic electron fluxes at large pitch angles beyond 5Re (Re is the Earth's radius). However, combined radial diffusion and adiabatic transport contributes insignificantly to the main phase depletion of energetic electron fluxes within 5Re, or the recovery phase enhancement of energetic electron fluxes in the outer radiation belt. Moreover, the simulation with both radial diffusion and adiabatic transport shows that the pitch angle distribution of energetic outer zone electrons can evolve from a rounded 90°‐peaked distribution to a butterfly‐shaped distribution during the main phase, and back to a rounded 90°‐peaked distribution during the recovery phase. Such essential changes of pitch angle distribution may further affect the efficiency of other local loss and energization mechanisms.
Optical properties of aged Asian aerosols observed over the U.S. Pacific Northwest
Authors: Fischer E. V. , Jaffe D. A. , Marley N. A. , Gaffney J. S. , Marchany‐Rivera A.
Published: October 2010

A suite of gas‐phase and aerosol measurements were made during spring 2008 and spring 2009 at the Mount Bachelor Observatory (2763 masl), located in Oregon. Here we focus on multiwavelength observations of low RH submicron (μm) aerosol scattering (σsp) and absorption (σap), made with an integrating nephelometer and a particle soot absorption photometer. Using a combination of in situ observations, trajectory calculations and satellite observations, we identified seven plumes of Asian origin. These plumes included many of the highest σsp (34.8 Mm−1) and σap (5.7 Mm−1) hourly average values observed at MBO over the 2008 and 2009 campaigns. Of interest in this analysis is (1) whether the intensive optical properties differ between these seven plumes, (2) whether these differences can be linked to differences in composition, and (3) whether the intensive optical properties change during transpacific transport. Results show that the plumes clustered in terms of their optical properties; plumes hypothesized to contain a large fraction of mineral dust were the most distinct. We observed variability between plumes in the scattering Ångström (Ås) exponent. The average submicrometer Ås for all seven plumes was significantly larger than the same parameter observed closer to Asia. Therefore, we hypothesize that the aerosol size distribution shifts toward smaller particles during transpacific transport. The average submicrometer low‐RH aerosol single scatter albedo (ω) observed at MBO (0.88) was slightly larger than previous observations closer to the Asian coast, and the average backscatter fraction (b) was smaller, on the order of 20%.
Vertical cavity laser hygrometer for the National Science Foundation Gulfstream‐V aircraft
Authors: Zondlo Mark A. , Paige Mark E. , Massick Steven M. , Silver Joel A.
Published: October 2010

A vertical cavity diode laser hygrometer using two absorption lines near 1854 nm has been developed for the National Science Foundation Gulfstream‐V aircraft. This instrument operates from the surface to the lower stratosphere, measuring 6 orders of magnitude in water vapor concentration. The optical system consists of an open‐path multiple‐pass cell mounted on an aerodynamic pylon. The self‐operating hygrometer reports concentration in real time at 25 Hz and uses a novel approach for fitting the data with minimal correction terms for changes in ambient pressure and temperature. The instrument intercompares with existing research grade hygrometers in the 2%–10% range. A minimum detection limit of 3.6 × 1011 molecules/cm2 or 0.08 ppmv at 15 km altitude conditions is achieved. The design rationale, operation, and flight performance of the hygrometer are described in this work.
Bypassing the Duodenum Does Not Improve Insulin Resistance Associated With Diet‐Induced Obesity in Rodents
Authors: Kindel Tammy L. , Martins Paulo J.F. , Yoder Stephanie M. , Jandacek Ronald J. , Seeley Randy J. , D'Alessio David A. , Obici Silvana , Tso Patrick
Published: October 2010

Roux‐en‐y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized duodenal‐jejunal bypass (DJB) as a modification of gastric bypass to determine the effect of nutrient diversion from the foregut without gastric restriction on insulin resistance in obese rats. The effects of DJB or Sham surgery on glucose homeostasis were determined in both high‐fat‐fed Long‐Evans and Wistar rats. Body weight and food intake were measured weekly postoperatively, and body composition was monitored before and after surgery. Glucose tolerance was tested before and as early as 1 month postoperation; additionally, in Wistar rats, insulin sensitivity was determined by a hyperinsulinemic‐euglycemic clamp (HIEC). DJB did not affect body weight, body composition, glucose tolerance, or insulin concentrations over the period of the study. The average glucose infusion rate (GIR) during the HIEC was 6.2 ± 1.16 mg/kg/min for Sham rats compared to 7.2 ± 1.71 mg/kg/min for DJB rats (P = 0.62), and neither endogenous glucose production (EGP; P = 0.81) nor glucose utilization (glucose disappearance (Rd), P = 0.59) differed between DJB and Sham rats. DJB does not affect insulin resistance induced by a high‐fat diet in Long‐Evans and Wistar rats. These data suggest that duodenal bypass alone is an insufficient mechanism to alter insulin sensitivity independent of weight loss in obese, nondiabetic rodents.
Physical Activity Patterns Using Accelerometry in the National Weight Control Registry
Authors: Catenacci Victoria A. , Grunwald Gary K. , Ingebrigtsen Jan P. , Jakicic John M. , McDermott Michael D. , Phelan Suzanne , Wing Rena R. , Hill James O. , Wyatt Holly R.
Published: October 2010

The National Weight Control Registry (NWCR) was established in 1993 to examine characteristics of successful weight‐loss maintainers. This group consistently self‐reports high levels of physical activity. The aims of this study were to obtain objective assessments of physical activity in NWCR subjects and compare this to physical activity in both normal‐weight and overweight controls. Individuals from the NWCR (n = 26) were compared to a never obese normal‐weight control group matched to the NWCR group's current BMI (n = 30), and an overweight control group matched to the NWCR group's self‐reported pre‐weight‐loss BMI (n = 34). Objective assessment of physical activity was obtained for a 1‐week period using a triaxial accelerometer. Bouts of moderate‐to‐vigorous physical activity (MVPA) ≥10 min in duration, as well as nonbout MVPA (bouts of MVPA 1–9 min in duration) were summed and characterized. NWCR subjects spent significantly (P = 0.004) more time per day in sustained bouts of MVPA than overweight controls (41.5 ± 35.1 min/day vs. 19.2 ± 18.6 min/day) and marginally (P = 0.080) more than normal controls (25.8 ± 23.4). There were no significant differences between the three groups in the amount of nonbout MVPA. These results provide further evidence that physical activity is important for long‐term maintenance of weight loss and suggest that sustained volitional activity (i.e., ≥10 min in duration) may play an important role. Interventions targeting increases in structured exercise may be needed to improve long‐term weight‐loss maintenance.
Impact of Clock Gene Bmal1 Deficiency on Nutritionally Induced Obesity in Mice
Authors: Hemmeryckx Bianca , Himmelreich Uwe , Hoylaerts Marc F. , Lijnen Henri R.
Published: October 2010

To evaluate the hypothesis that the clock gene Bmal1 (brain and muscle arnt like protein‐1) plays a role in the development of obesity, 5‐week‐old male Bmal1‐deficient (Bmal1−/−) mice and wild‐type littermates (Bmal1+/+) were kept on a high‐fat diet (HFD) for 15 weeks. Despite an initial accelerated weight gain of Bmal1−/− mice, body weight and subcutaneous (SC) and gonadal (GON) adipose tissue mass were comparable to Bmal1+/+ mice at the end of the diet period. Noninvasive magnetic resonance imaging scanning revealed a modest increase in fat content in Bmal1−/− mice after 10 weeks of HFD, whereas at the start and the end of the HFD feeding no differences were observed between both genotypes. After 15 weeks of HFD, adipocyte and blood vessel size and density were similar for Bmal1+/+ and Bmal1−/− mice. However, the weight of major organs was significantly reduced in Bmal1−/− mice, confirming the premature ageing phenotype. Thus, we hypothesize that an initial accelerated increase in body weight and fat mass of Bmal1−/− mice on HFD may have been offset by the effect of premature ageing on organ weight, resulting in comparable weights after 15 weeks of HFD.
Flow-assisted Analysis
Authors: Roda Aldo , Mirasoli Mara , Roda Barbara , Reschiglian Pierluigi
Published: October 2010

The demand for direct, robust and quantitative determination of analytes even in complex matrices of different origin produced an increase interest in flow-assisted techniques for automatization of chemical analysis with high throughput and reproducibility. With this aim, thanks to simple instrumentation, high sensitivity and low background signal, chemiluminescence, bioluminescence and electrochemiluminescence represent suitable detection techniques to which flow-analysis can be coupled. In this Chapter the fundamental, instrumental setup and recent application are reviewed for flow-injection analysis and its variants, and for field-flow fractionation, a flow-assisted technique suitable to separate analytes with high molar mass, for the development of assays with reliability, rapidity and robustness. A discussion on the miniaturization of these approaches to add features such as low reagent consumption and reduced analysis time is also presented.
Analytical Applications of Chemiluminescence in Chromatography and Capillary Electrophoresis
Authors: García-Campaña Ana M. , Gámiz-Gracia Laura , Huertas-Pérez José F. , Lara Francisco J.
Published: October 2010

In this chapter the characteristics and applications of Chemiluminescence (CL) as detection system coupled with Gas Chromatography (GC), High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE) are presented. Considering the advantages of CL related to its high sensitivity and selectivity or the simplicity of the required instrumentation (no external light source is needed) and the potential of GC, HPLC or CE as the most useful separation techniques with great efficiency for multianalyte determinations, the combination of those methodologies has permitted the development of a wide variety of powerful analytical methods. Progress in the different systems developed, commercial and home-made configurations and analytical applications in different fields, such as clinical, pharmaceutical, environmental and food analysis, have been discussed here.
Chemiluminescence to Immunoassays
Authors: Seidel Michael , Niessner Reinhard
Published: October 2010

The extreme sensitivity of chemiluminescence analysis in combination of the high specificity of antibodies has resulted in many application of chemiluminescence immunoassays (CLIA) over the last three decades. Especially the reproducible analysis in complex matrices leads to the success of this method in clinical, food and environmental analysis. Principles of CLIAs will be addressed as well current improvements of CL labelling, CLIA processing and instrumentation. Many applications for CL-ELISA, CL-Microarrays, Flow-injection CLIA are given. Commercialised singleplex CLIA platforms as well new multiplexed CLIA platforms are presented and discussed in detail.
Biomolecular Interactions
Authors: Michelini Elisa , Cevenini Luca , Mezzanotte Laura , Coppa Andrea , Roda Aldo
Published: October 2010

This chapter discusses recent advances regarding biomolecular interaction detection strategies based on bioluminescence. The commonly used transcriptional approaches, such as yeast two hybrid assays and ubiquitin split, based on transcriptional activation of reporter genes following target protein interaction in the nucleus, have been replaced by more suitable strategies that allow to monitor interactions occurring in every cell compartment. Many bioanalytical tools for in vivo and in vitro applications have been proposed, mostly based on resonance energy transfer (RET) process, such as Fluorescence and Bioluminescence Resonance Energy Transfer (FRET and BRET). The applicability of BRET, thanks to its advantages with respect to the analogous FRET, to elucidate protein dynamics in living cells has been widely explored using different donors and acceptors, including quantum dots. In addition, the split luciferase complementation approach has been successfully employed for monitoring protein interactions in vivo and showed able to detect even weak interactions. Also combinations of these approaches, such as sequential BRET-FRET or split complementation-FRET, have been explored to detect more than two interacting proteins, but their analytical performance still need improvements and surely new ways of monitoring protein interactions will certainly emerge.
Ultrasensitive Bioanalytical Imaging
Authors: Mirasoli Mara , Venturoli Simona , Guardigli Massimo , Dolci Luisa Stella , Simoni Patrizia , Musiani Monica , Roda Aldo
Published: October 2010

Bio- and chemiluminescence imaging combines the high sensitivity of luminescence detection techniques with the possibility to localize and quantify signal emission down to the single-photon level, employing state-of-the art light imaging devices. These techniques have been employed for the development of sensitive analytical methods based on the evaluation of the spatial distribution of the photons emitted from the sample surface, both in macro- and microsamples.

The use of imaging detection offers the possibility to exploit the analytical features of bio- and chemiluminescence for the rapid and precise analyte quantification in membrane-based assays and for the development of high-throughput methods in high-density microtiter plate formats.

Furthermore, the high detectability of the bio- and chemiluminescent analytical signal also in small volumes makes it appropriate for miniaturized bioanalytical formats (e.g., microarrays, microfluidic devices) suitable for high-throughput screening assays and for point-of-care applications.

Finally, bio- and chemiluminescence detection have also been employed for the sensitive localization and quantification of target analytes (metabolites, enzymes, proteins, and nucleic acids) in tissue sections and single cells, also in multiplexed formats and for the monitoring of biomolecular interactions.
“In Vivo” Molecular Imaging
Authors: Kaijzel Eric L. , Snoeks Thomas J. A. , Que Ivo , Baiker Martin , Kok Peter , Lelieveldt Boudewijn P. , Löwik Clemens W. G. M.
Published: October 2010

Whole body optical imaging (OI) refers to in vivo bioluminescence and fluorescence imaging. This technology is one of the most rapidly emerging to non-invasively follow molecular and cellular processes in small laboratory animals. Optical imaging modalities are based on very sensitive devices capable of detecting and quantifying bioluminescent or fluorescent light that is transmitted through tissues from internal sources. This imaging of very weak visible light is rendered possible by the use of cooled charged coupled device (CCCD) cameras, peltier-cooled detectors, micro-plate channel intensifiers and liquid-nitrogen-cooled detectors aimed at enhancing the signal-to-noise ratio by decreasing the background or amplifying the signal. The role of molecular imaging in pre-clinical research is continuously evolving. Particularly in small animal models in biomedical research, optical imaging technologies are frequently used to visualize normal as well as aberrant cellular processes at a molecular-genetic or cellular level of function.

This chapter will focus on the application of whole body bioluminescence molecular imaging strategies -either alone or in combination with CT- in different fields (e.g. to study non-invasive and real-time imaging of gene expression, tumor progression and metastasis, and response to therapeutic intervention).
Biotechnological Improvements of Bioluminescent Systems
Authors: Hamorsky Krystal Teasley , Dikici Emre , Ensor C. Mark , Daunert Sylvia , Davis Audrey L. , Branchini Bruce R.
Published: October 2010

Genetic and biomolecular engineering are two of the leading disciplines in biotechnology that have lead to great advancements in protein engineering. Applications of analytical bioluminescence, such as genetic reporter assays, optical in vivo imaging, and cell viability assays can often be improved by enhancing wild-type bioluminescent systems. The ability to rationally or randomly modify proteins has expanded their employment in various bioanalytical applications. Specifically, a wide range of bioluminescent proteins and photoproteins have been engineered that can be utilized in many detection and diagnostic applications. Herein, we focus on the improvements of two of the most commonly studied photoproteins, aequorin and obelin, and their uses in a variety of bioanalytical applications. Techniques such as random mutagenesis, site-directed mutagenesis, bioluminescence resonance energy transfer, and the incorporation of coelenterazine analogues are discussed as ways that have expanded the palette of these designer proteins by altering their emission wavelengths and/or half-lifes. Strategic amino acid substitutions and insertions have been also used to improve luciferase stability in high temperature, extreme pH, and harsh chemical environments, and to customize their kinetic properties and bioluminescence colors. As researchers advance engineering techniques to expand the array of photoproteins, luciferases from fireflies, click beetles, marine organisms and bacteria, their use in bioanalytical applications will continue to grow and it is envisioned that photoproteins and bioluminescent proteins will become as diverse as their fluorescence counterparts.
Chemiluminescent and Bioluminescent Biosensors
Authors: Marquette Christophe A. , Blum Loïc J.
Published: October 2010

The present chapter gives an overview of the chemiluminescent and bioluminescent reactions' applications in the field of biosensors. Both light emitting reactions are, in a first part, thoroughly described together with biosensors and immunosensors basic concepts.

Then, analytical applications of these luminescent reactions are presented and commented. Particular attention is given to the experimental systems used (batch, flow, reaction triggering system) and the performances obtained (dynamic range, limit of detection). All over the chapter, electrochemiluminescence (as part of the chemiluminescent system) will be presented as a separated light emitting system since it has generated numbers of analytical applications and innovative experimental set ups.
Introduction to QSAR and Other In Silico Methods to Predict Toxicity
Authors: Madden J. C.
Published: October 2010

The philosophy of this book is to guide the reader through the different aspects of science involved in generating and using in silico techniques to make predictions for toxicity. The aim of this chapter is to provide an overview of how the different sections of the book link together to enable such predictions to be made. The chapter serves as an overall introduction to QSAR and in silico techniques, outlining how to go about generating and using the models. The text is supplemented by a flowchart providing guidance on the individual steps to be undertaken. This general overview is expanded upon in subsequent chapters of the book which provide a more detailed analysis of each individual step in the model building process. The chapter focuses on how to develop a QSAR for a toxicological endpoint. However, the methods described are equally applicable to developing QSARs for other endpoints, such as predicting drug activity or pharmacokinetic/toxicokinetic properties. The use of other in silico techniques, such as category formation and read across are also introduced in the chapter.
Calculation of Physico-Chemical and Environmental Fate Properties
Authors: Webb T. H. , Morlacci L. A.
Published: October 2010

The physico-chemical properties of a chemical substance influence its biological activity and its environmental fate and transport behaviour. Successful modeling of uptake, bioavailability, distribution, exposure potential and toxicity depends in part on the availability of reliable physicochemical descriptors for the chemicals of interest. Estimated properties can fill data gaps for chemicals that lack a complete set of reliable measured properties. Modern estimation methods can provide the desired data rapidly and cost-effectively. Property estimation is invaluable for the screening-level characterisation of chemicals when the measurement of properties is not possible or is impractical. The aim of this chapter is to illustrate how these properties can be successfully calculated and to provide practical advice for evaluating estimated data. Four readily available estimation suites of programs, each capable of calculating physico-chemical properties for diverse chemical substances from chemical structure alone are presented.
The Use of Frontier Molecular Orbital Calculations in Predictive Reactive Toxicology
Authors: Enoch S. J.
Published: October 2010

The aim of this chapter is to outline the use of quantum chemical descriptors in the modelling of chemical reactivity relevant to the prediction of toxicity. Chemical reactivity is an important component of a number of toxicological endpoints that involve the formation of a covalent bond between a biological macromolecule and a chemical. The chapter highlights how, within well defined mechanistic domains, simple and interpretable descriptors such as the energy of the lowest unoccupied molecular orbital can aid in the understanding of frontier orbital controlled chemical reactions. In addition, an outline of the importance of frontier molecular orbital theory is presented. The chapter illustrates the considerations that must be taken into account if the results of such calculations are going to be of practical use in regulatory environments.
Three-Dimensional Molecular Modelling of Receptor-Based Mechanisms in Toxicology
Authors: Madden J. C. , Cronin M. T. D.
Published: October 2010

Previous chapters have discussed the generation and use of relatively simple descriptors (such as log P, topological descriptors etc) in predicting toxicity; such descriptors alone can accurately predict certain endpoints. However, other endpoints require a more complex modelling process. Molecules exist as 3-dimensional entities and where toxicity is the result of specific spatially-related interactions between the toxicant and a biological macromolecule, for example receptor-mediated effects, models must be able to take into account this 3-dimensional interaction. This chapter will present a brief overview of the use of ligand-based and receptors-based 3-dimensional approaches in toxicity prediction. An introduction to relevant software and example case studies where the approaches have been successfully employed will be presented.
Characterisation, Evaluation and Possible Validation of In Silico Models for Toxicity: Determining if a Prediction is Valid
Authors: Cronin M. T. D.
Published: October 2010

This chapter describes the process whereby a (Q)SAR may be described, evaluated and, where possible, validated. The emphasis here is not to develop models, but to characterise them according to the guidance supplied by the Organisation for Economic Co-operation and Development (OECD) and the European Chemicals Agency (EChA). The backbone to this process are the OECD Principles for the Validation of (Q)SARs. Three case studies illustrating how to approach the OECD Principles are supplied.
Developing the Applicability Domain of In Silico Models: Relevance, Importance and Methods
Authors: Hewitt M. , Ellison C. M.
Published: October 2010

The past two decades has seen the rapid growth in the development and utilisation of computational technologies to predict the toxicity of chemicals. Most notably, widespread pressure to both reduce and replace current animal testing regimes has led to in silico modelling becoming a widely utilised tool in toxicological screening. Unfortunately, given that computational models are open to misuse, there has been, and still is, significant reluctance to accept them for regulatory use. In an effort to combat this, the validation of both model and predictions is now at the forefront of research, with the concept of applicability domain being central to the validation process.

In this chapter the applicability domain concept is defined and numerous methods for its characterisation are detailed and explored with the aid of a case study example. These approaches are shown to span from relatively simple descriptor-based methods to more complex approaches based upon structural similarity or mechanism of action. Given the wealth of differing approaches available and the different information each method yields about the model, a stepwise scheme which considers numerous methods is recommended. With appreciation of model architecture and subsequent utilisation, this chapter shows that a robust and multifaceted applicability domain can be generated. Once defined, the applicability domain serves as a critical screening stage ensuring that a model is fit-for-purpose and predictions are made with maximal confidence.
Adverse Outcome Pathways: A Way of Linking Chemical Structure to In Vivo Toxicological Hazards
Authors: Schultz T. W.
Published: October 2010

The concept of adverse outcome pathways is presented here as an organising principle to aid assessment and formation of toxicologically meaningful categories for hazard endpoints, especially chronic health effects where different molecular initiating events and different key biological events lead to the same in vivo outcome. A toxicologically meaningful category can be thought of as a group of chemicals whose human health and/or environmental toxicological properties are likely to be similar or follow a regular pattern for a particular hazard. An adverse outcome pathway is a description of plausible causal linkages, which illustrates how the molecular initiating event, leads to the key biochemical, cellular, physiological, behavioural etc. responses, which characterise the biological cascade across the different levels of biological organisation. The concept of the adverse outcome pathway is discussed in the context of the more stringent mechanism of action approach used in pharmacology. The value of this concept is demonstrated with five examples, each with a different type of molecular initiating event. The pathways concept is also discussed in context of elaborate hazards where the in vivo effects may be cumulative or life stage dependent.
An Introduction to Read-Across for the Prediction of the Effects of Chemicals
Authors: Dimitrov S. , Mekenyan O.
Published: October 2010

The process of the assessment of a property of one chemical based on the same property for one, or a few, different chemicals that are considered to be similar in some context is known as read across or the analogue approach. There is no practical limitation on the type of properties that could be the subject of read across including: physico-chemical properties; environmental fate; toxicological; and ecotoxicological effects. From a formal methodological point of view, read across is not usually recommended for predicting physicochemical properties that may be used as explanatory variables for predicting more complex environmental or (eco)toxicological effects. On the other hand, it should be noted, that grouping of chemicals to estimate the properties of untested chemicals has been routine practice in chemical engineering and physical chemistry for several decades.
Tools for Category Formation and Read-Across: Overview of the OECD (Q)SAR Application Toolbox
Authors: Diderichs R.
Published: October 2010

The Organisation for Economic Co-operation and Development (OECD) has an active role in promoting the use of (quantitiative) structure-activity relationships ((Q)SARs) for regulatory purposes, launching a new (Q)SAR project in 2003 with the aim of improving regulatory acceptance of QSARs. Part of this project consisted of the development of the (Q)SAR Application Toolbox, a first verison of whichhas been released for free download. The main feature of the Toolbox is to allow the user to group chemicals into toxicologically meaningful categories and to fill data gaps by read-across and trend analysis. The seminal features of the Toolbox are: (1) identification of relevant structural characteristics and potential mechanism or mode of action of a target chemical; (2) identification of other chemicals that have the same structural characteristics and/or mechanism or mode of action; (3) use of existing experimental data to fill the data gap(s). This chapter will discuss the use and application of the Toolbox.
Exposure Modelling for Risk Assessment
Authors: Marquart J.
Published: October 2010

This chapter describes a range of models that can be used to estimate exposures in a regulatory risk assessment process ranges from very simple (e.g. EMKG-Expo-tool) to complex (e.g. combination of ConsExpo and Advanced REACH Tool with Bayesian updates). For worker exposure assessment there is a greater choice of models, largely due to the fact that worker exposure has been studied more widely. The ECETOC TRA worker tool can be used as a first Tier model, although one has to take into account that the validity of its estimates is not very well known. For dermal exposure RISKOFDERM is the most logical choice for further Tier exposure assessment. It also is calibrated against measured data, but its scope is not as wide as that of the Advanced REACH Tool. In general, modelling of dermal exposure (for consumers as well as workers) is far less advanced than modelling of inhalation exposure. The models, their theoretical basis and advantages and disadvantages are discussed.
Toxicokinetic Considerations in Predicting Toxicity
Authors: Madden J. C.
Published: October 2010

The ability of a compound to elicit a toxic effect within an organism is dependent upon three factors (i) the external exposure of the organism to the toxicant in the environment or via the food chain (ii) the internal uptake of the compound into the organism and its transport to the site of action in sufficient concentration and (iii) the inherent toxicity of the compound. The in silico prediction of toxicity and the role of external exposure have been dealt with in other chapters of this book. This chapter focuses on the importance of ‘internal exposure’ i.e. the absorption, distribution, metabolism and elimination (ADME) properties of compounds which determine their toxicokinetic profile. An introduction to key concepts in toxicokinetics will be provided, along with examples of modelling approaches and software available to predict these properties. A brief introduction will also be given into the theory of physiologically-based toxicokinetic modelling.
Development of novel fuel ion ratio diagnostic techniques
Authors: Korsholm S. B. , Stejner M. , Conroy S. , Ericsson G. , Gorini G. , Tardocchi M. , von Hellermann M. , Jaspers R. J. E. , Lischtschenko O. , Delabie E. , Bindslev H. , Furtula V. , Leipold F. , Meo F. , Michelsen P. K. , Moseev D. , Nielsen S. K. , Salewski M.
Published: October 2010

To overcome the challenge of measuring the fuel ion ratio in the core (ρ<0.3) of ITER, a coordinated effort aiming at developing diagnostic techniques has been initiated. The investigated techniques are novel uses or further development of existing methods such as charge exchange recombination spectrometry, neutron spectrometry, and collective Thomson scattering. An overview of the work on the three diagnostic techniques is presented.