bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental Test of the Interaction of the Insurance and Information‐Signaling Hypotheses in Auditing*
Authors: O'Reilly Dennis M. , Leitch Robert A. , Tuttle Brad
Published: February 2007

Three incentives for hiring auditing services have been proposed in the literature: (1) to signal outsiders about the company's prospects, (2) to provide a potential source of loss recovery for investors (insurance), and (3) to reduce agency costs. The objective of this study is to examine the potential for the first two (signaling and insurance) to interact while controlling for agency costs. We conduct an experiment in which highly experienced financial analysts provide stock price estimates for a company that is under financial stress. We manipulate, between participants, the signal provided by the audit opinion (going‐concern modification, yes/no) and the ability of investors to recover losses from auditors. The key finding is that the effect of the going‐concern opinion on investor value judgements is moderated by the extent to which the auditor provides an insurance function. Specifically, the negative effect of a going‐concern opinion on the analysts' stock price estimates is reduced by the extent that the environment treats the auditor as an insurer.
The Impact of Cultural Values on Marketing Ethical Norms: A Study in India and the United States
Authors: Paul Pallab , Roy Abhijit , Mukhopadhyay Kausiki
Published: February 2007

This research investigates the relationship between the cultural values and the marketing ethics in two diverse countries: India and the United States. The results show that these countries are indeed culturally different, though the gaps have narrowed considerably since Hofstede's (1991) study. Furthermore, the results indicate significant differences in the interpretation of the marketing ethical norms between these two countries. The study concludes with an analysis of how different dimensions of culture influence the different facets of marketing ethical norms for both countries. Such a framework should provide valuable insights that international marketers can use to identify differences in the perception of ethical norms across nationalities and, thus, to design more effective and efficient international marketing and management strategies.
Making Business-to-Business International Internet Marketing Effective: A Study of Critical Factors Using a Case-Study Approach
Authors: Eid Riyad , Elbeltagi Ibrahim , Zairi Mohamed
Published: February 2007

The recent phenomenal growth in business activities dependent on the Internet has demonstrated that various potential advantages could be derived from using information and communication technology platforms. The Internet has enabled firms to reach out to global markets and has provided them with the opportunity to customize their strategies and offerings in an unprecedented way. These recent developments provide an exciting opportunity for research to study the dynamics involved in international Internet marketing (IIM) and, in particular, to examine closely the factors that could influence success in using this new technology for IIM activities. Using a business-to-business context and a multiple-case-study approach, this article focuses on two main areas of study: (1) the critical examination of the literature and identification of the most important factors that have a significant influence on business-to-business IIM and (2) the first-hand verification of how the identified factors are implemented in various organizational contexts.
Social Capital and its Influence on Changes in Internationalization Mode among Small and Medium-Sized Enterprises
Authors: Chetty Sylvie , Agndal Henrik
Published: February 2007

This article explores how social capital influences a firm to change its internationalization mode. The authors use an in-depth qualitative study to identify 36 internationalization mode changes in ten New Zealand and ten Swedish small and medium-sized enterprises. This article contributes to the internationalization mode literature by focusing on relationships and mode change. Using the network approach, the authors develop three categories of social capital and discuss their role in influencing mode change. The roles include the efficacy role, the serendipity role, and the liability role of social capital. These three roles incorporate both the positive and the negative aspects of social capital. The liability role is the most frequently observed form of social capital to influence mode change. The most frequent type of mode change is toward a high-control internationalization mode.
Strategic Variables that Influence Entry Mode Choice in Service Firms
Authors: Sanchez-Peinado Esther , Pla-Barber Jose , Hébert Louis
Published: February 2007

This work investigates how a firm's international strategy affects choice of entry mode in the service sector. The inherent complexity associated with studying a heterogeneous sector such as services requires researchers to investigate variables that go beyond those drawn from traditional empirical work on the manufacturing sector. The adoption of a broader theoretical perspective and the introduction of these new variables may well provide further evidence of the determinants of service firms’ entry mode choices. On the basis of 174 entry decisions of service firms, this study's results support the necessity of including additional strategic variables that specifically address this complex phenomenon, a decision that is not always associated just with efficiency and value-based considerations but with strategic issues as well. In addition, some variables that are routinely used in studies of the manufacturing sector were not significant or exhibited different results in different groups of service activities.
Vapor-phase diethyl oxalate pretreatment of wood chips: Part 1. Energy savings and improved pulps
Authors: Kenealy William , Horn Eric , Houtman Carl
Published: February 2007

Diethyl oxalate (DEO) was injected into a digester containing wood chips (pine, spruce, or aspen) preheated to 130–140°C and held for 30 min at the same temperature. When mechanical pulps were produced from these pretreated chips, savings in electrical refiner energy could be achieved. For southern yellow pine (Pinus taeda), the electrical refiner energy required to produce pulps with Canadian standard freeness (CSF) of 100 ml was 38– 55% less than for an untreated control. Energy savings were also observed for aspen (Populusspp.) and spruce (Piceaspp.). DEO-treated pine handsheets showed a 26% improvement in tear index compared with a control at 100 ml CSF. Under the pretreatment conditions de-scribed, DEO rapidly vaporizes, reacts with water already present in the chip, and forms an oxalic acid (OA) solution. Reported handsheet properties and energy savings for pine chips treated with a solution of OA are similar to DEO-treated handsheets. It can be concluded that the effect of DEO treatment is due to reactions catalyzed by OA.
Production of no-carrier-added123Iviaheavy-ion activation of natural antimony oxide
Authors: Maji Samir , Lahiri Susanta
Published: February 2007

Activation of natural Sb2O3with 48 MeV7Li3+beam results in the formation of no-carrier-added123I in the matrix along with the radionuclides123,125Xe and122Sb. The123I yield amounts to about 400 kBq/μAh and the radionuclidic impurity of124I to ∼1.2% of123I. Attempts to separate no-carrier-added iodine from bulk antimony target involved liquid-liquid extraction with TOA and HDEHP as well as precipitation of Sb2S3with thioacetamide. The precipitation technique was found to be the most effective for quantitative separation of123I from the bulk antimony oxide target.
Study of the solubility of amorphous and crystalline uranium dioxide by combined spectroscopic methods
Authors: Opel Karsten , Weiß S. , Hübener S. , Zänker H. , Bernhard Gert
Published: February 2007

Colloid formation and solubility of U(IV) in acidic HClO4/NaClO4solutions are investigated by coulometric titration. Quantification of traces of U(VI) by laser fluorescence spectroscopy proves that the tetravalent state of uranium had been maintained. Laser-induced breakdown detection (LIBD) is applied for the detection of traces of uranium colloids as the pH is increased. The pH values at the onset of colloid formation are used for thermodynamic calculations aimed at determining the solubility productsK°spof crystalline and amorphous uranium dioxides. The particle size of the colloids determined by means of LIBD is taken into account since it influences the solubility product. The results indicate the formation of crystalline UO2(cr) at low pH∼1 (logK°sp= -59.6±1.0) whereas the amorphous hydrous oxide UO2·xH2O(am) is formed at pH ∼ 3 (logK°sp= -54.1 ± 1.0). Measurements by EXAFS, XRD and REM confirm the occurrence of these different phases. The obtained solubility products fit well in the known series of solubility products of the other tetravalent actinides.
Comparative study on ion-isotopic exchange reaction kinetics by application of tracer technique
Authors: Lokhande R. S. , Singare P. U.
Published: February 2007

The radioactive isotopes 131I and 82Br were used to trace the ion-isotopic exchange reactions using industrial grade ion exchange resins Amberlite IRA-400. The experiments were performed to understand the effect of temperature and concentration of ionic solution on kinetics of exchange reactions. Both the exchange reactions were greatly influenced by rise in temperature, which result in higher percentage of ions exchanged. For bromide ion-isotopic exchange reactions, the calculated values of specific reaction rate/min-1, and amount of ions exchanged/mmol were obtained higher than that for iodide ion-isotopic exchange reactions under identical experimental conditions. The observed variation in the results for two ion-isotopic exchange reactions was due to the difference in the ionic size of bromide and iodide ions.
Separation of 137mBa from its parent 137Cs from an equilibrium mixture using amide incorporated Amberlite IRC-50
Authors: Maji Samir , Basu Sukalyan
Published: February 2007

A chelating resin was synthesized by incorporating amide group into Amberlite IRC-50, a weakly acidic polymer. The new resin was employed in the separation of 137mBa from its parent 137Cs from an equilibrium mixture. The adsorbed daughter was recovered using 0.01 M EDTA at pH 10.
Direct space methods of structure determination from powder diffraction: principles, guidelines and perspectives
Authors: Černý Radovan , Favre-Nicolin Vincent
Published: February 2007

In the last twenty five years structure determination from powder diffraction has evolved from a complex, time-consuming method to one easily usable. While the use of direct methods is restricted to samples well crystallized (sharp peaks, high resolution diffraction), structure solution using global optimization in direct space have become extremely popular, using either publicly or commercially available software. In this article we present a short history of direct space methods of structure determination from powder diffraction, and a list of available software. We then give an overview of frequent issues when solving structures in direct space, as well as how algorithms are currently evolving to solve more complex structures.
The use of lattice-parameter changes to trace the kinetics of phase transformations powder-diffraction analysis of disorder-order transformations in Ni1+δSn
Authors: Leineweber Andreas , Mittemeijer Eric J.
Published: February 2007

The measurement of lattice-parameter changes by X-ray powder diffraction as a function of the progress of a phase transformation (e.g. as a function of the annealing time at a given annealing temperature) is a powerful means to study the kinetics of phase transformations in crystalline solids. Generally applicable diffraction methods have been developed and applied in a study of the kinetics of different types of disorder → order-related phase transformations in Ni1 + δSn alloys (δ = 0.50, 0.35). It has been demonstrated, in particular, how the activation energies of occurring processes can be determined from annealing-time-dependent data recorded at different annealing temperatures. Two approaches have been presented and applied:(i) a general approach constrained by identity of the start states and the end states of the transformation for all investigated annealing temperatures(ii) an explicit model-based approach adopting a specific time and temperature dependence of the meas ured lattice parameters.
Diffraction stress analysis of elastic grain interaction in polycrystalline materials
Authors: Welzel Udo , Mittemeijer Eric J.
Published: February 2007

Recent insight on the elastic grain interaction in polycrystalline solids has been summarized. A breakthrough in this classical field of mechanical behaviour of solid bodies is due to highly accurate (X-ray) diffraction stress analysis. The occurrence of so-called direction-dependent grain interaction, i.e. different grain-interaction constraints prevail along different directions in a specimen, can be proven. Important practical examples of direction-dependent grain interaction are the occurrence of surface anisotropy in thin films (and, possibly, surface regions of bulk polycrystals) and the occurrence of a grain-shape (morphological) texture. Recent experimental investigations by X-ray (synchrotron) diffraction analysis and recent theoretical analysis have been reviewed.
Surface Chemistry of Semiconductor Nanocrystals
Authors: Mews Alf
Published: February 2007

The fluorescence properties of CdSe semiconductor nanocrystals are investigated after surface modification with different kinds of molecular ligands. We show that the fluorescence is decreasing after removal of the excess ligands because the ligands are usually not strongly bound to the surface. The ligand exchange by multi-functional dye labelled polymer ligands allows to investigate the nanocrystal–ligand interaction by fluorescence resonance energy transfer (FRET-) experiments. Individual nanocrystal-dye complexes are investigated by single particle fluorescence microscopy and spectroscopy to show large inhomogeneities among the prepared structures.
Photoactivity of Sol–Gel Derived Nitridated Zn
x
Ti
y
O
z
-Films
Authors: Starukh G. , Toscani S. , Boursicot S. , Spanhel Lubomir
Published: February 2007

Zn
x
Ti
y
O
z
layers were prepared by sol–gel method and nitridated yielding photoactivity in the visible wavelength region. The condensation process of these nanostructures and their subsequent sintering was followed by using XRD-, UV/Vis-, micro-Raman-, FTIR- and thermal analysis measurements. The oxynitride formation during the nitridation process was confirmed by XPS and UV-Vis spectroscopy. The photocatalytical studies of methylene blue (MB) degradation revealed the activity of coloured oxynitride layers under the visible light irradiation. Furthermore, a metachromasy of MB infiltrated within the nanostructured films was observed for the first time. This blue shift in the optical absorption spectrum of MB became even more pronounced during the photodegradation process of this dye.
Photothermal Properties of Gold Nanoparticles
Authors: Petrova Hristina , Hu Min , Hartland Gregory V.
Published: February 2007

This paper describes our recent time-resolved spectroscopy studies of the properties of gold particles at high laser excitation levels. In these experiments, an intense pump laser pulse rapidly heats the particle, creating very high lattice temperatures — up to the melting point of bulk gold. These high temperatures can have dramatic effects on the particle and the surroundings. The lattice temperature created is determined by observing the coherently excited the vibrational modes of the particles. The periods of these modes depend on temperature, thus, they act as an internal thermometer. We have used these experiments to provide values for the threshold temperatures for explosive boiling of the solvent surrounding the particles, and laser induced structural transformations in non-spherical particles. The results of these experiments are relevant to the use of metal nanoparticles in photothermal therapy, where laser induced heating is used to selectively kill cells.
Influence of the Choice of Indium Precursor and Ligand on the Synthesis of InP Nanocrystals
Authors: Zerzouf O. , Haase M.
Published: February 2007

Well-crystallized InP nanocrystals with particle diameters ranging from 2 to 5.5nm were prepared via the reaction between tris(trimethylsilyl)phosphine and different indium precursors. The classic TOP/TOPO reaction medium was replaced by the weakly coordinating solvent diphenylether, which contained a strongly coordinating ligand at low concentrations. Different phosphine oxides, phosphines, phosphates, phosphites and phosphonates were used as ligands and their influence on the growth of InP nanocrystals was studied. The synthesis procedure allows to prepare crystalline InP quantum dots (QDs) at temperatures as low as 150°C and within short reaction times. The final size of the InP QDs is remarkably independent of the choice of ligand and indium precursor.
On the discriminant of the power of an algebraic number
Authors: Dubickas Artūras
Published: February 2007

Let
α
be an algebraic number which is not a root of a rational number. We show that the discriminant of
αn
tends to infinity with
n
tending to infinity and give a lower bound for this discriminant in terms of the degree of
α
, its Mahler’s measure and
n
.
Marcinkiewicz-Fejér Means of double VIlenkin-Fourier series
Authors: Goginava Ushangi
Published: February 2007

The boundedness of the Marcinkiewicz maximal operator for double Vilenkin-Fourier series from the martingale Hardy-Lorentz spaceHp,qinto the Lorentz spaceLp,qis studied.
Representations of (2, n )-semigroups by multiplace functions
Authors: Dudek Wiesław , Trokhimenko Valentin
Published: February 2007

We describe the representations of (2,
n
)-semigroups, i.e., sets with
n
binary associative operations, by partial
n
-place functions and prove that any such representation is a union of some family of representations induced by Schein’s determining pairs.
Direct estimate on pointwise simultaneous approximation by combinations of Baskakov operators
Authors: Xie Linsen , Zhang Xiaoping
Published: February 2007

In this paper we obtain a direct estimate on the pointwise simultanous approximation by the combinations of Baskakov operators.
The b -chromatic number of the cartesian product of two graphs
Authors: Kouider Mekkia , Mahéo Maryvonne
Published: February 2007

In this paper we study the
b
-chromatic number of the cartesian product of two graphs. The
b
-chromatic number of a graph
G
is defined as the maximum number
k
of colors that can be used to color the vertices of
G
, such that we obtain a proper coloring and each color
i
has at least one representative
χi
adjacent to a vertex of every color
j
, 1 ≦
j
≠
i
≦
k
. In this paper we get ρ(
G□H
) ≦ ρ(
G
)(
nH
+ 1) + Δ(
H
) + 1, when the girth of
G
is assumed to be greater than or equal to 7.
q -Laguerre type linear positive operators
Authors: Özarslan Mehmet
Published: February 2007

The main object of this paper is to define theq-Laguerre type positive linear operators and investigate the approximation properties of these operators. The rate of convegence of these operators are studied by using the modulus of continuity, Peetre’sK-functional and Lipschitz class functional. The estimation to the difference |Mn+1,q(ƒ;χ)−Mn,q(ƒ;χ)| is also obtained for the Meyer-König and Zeller operators based on theq-integers [2]. Finally, ther-th order generalization of theq-Laguerre type operators are defined and their approximation properties and the rate of convergence of thisr-th order generalization are also examined.
Differential shrinkage effects in the core-drilling method
Authors: McGinnis M. J. , Pessiki S.
Published: February 2007

The core-drilling method is a technique that is used to determine stresses in concrete. In the method, a small hole is drilled into the concrete, and the resulting displacements are related to stresses present in the structure via elasticity theory. One source of complication when applying the method is the presence of differential shrinkage stresses. The exterior of a concrete specimen dries and shrinks faster than the interior, thus causing tension stresses on the exposed faces, and compressive stresses on the interior. These stresses tend to dissipate with time as the moisture profile becomes more uniform. However, for relatively young concrete specimens these stresses can be significant. In the current work, the moisture distribution and corresponding differential shrinkage stresses are analytically predicted in concrete plate specimens by solving a non-linear diffusion equation with appropriate boundary conditions. These differential shrinkage stresses are then evaluated numerically in the core-drilling method. It is shown that these differential shrinkage stresses can result in large discrepancies in applied versus measured stresses, especially for concrete specimens that are particularly young (less than 3 years of age), particularly thick (greater than 150 mm thick), or cast/stored in a very dry environment. Application of the procedure detailed herein to the results of a previous hole drilling study in concrete plates improved measured accuracy from 47% relative error to 34% error if it is assumed that the previous plates were stored in a 50% relative humidity environment.
Impact resistance of high-strength fibre-reinforced concrete
Authors: Zhang M. H. , Sharif M. S. H. , Lu G.
Published: February 2007

The current paper presents results from a laboratory experimental study on the resistance of concrete to simulated impact loading of fragments. The impact of fragments was simulated by the impact of ogive-nosed projectiles with a diameter of 12·6 mm and a mass of 15 g travelling at velocities from ∼610 to 710 m/s. The concrete tested had 28 day compressive strengths from 45 to 170 MPa. Effects of the content, type and length of fibres in concrete and the compressive and flexural tensile strength of the concrete on the impact resistance are evaluated and discussed. The results indicate that the incorporation of a small amount of fibres can reduce the crater diameter effectively as the fibres are able to bridge cracks and to hold concrete together. However, in order to reduce the penetration depth, reduced water-to-cement ratio and increased strength of the concrete matrix are required. A strong aggregate with bigger sizes seem to be beneficial to improve the impact resistance so long as the workability is satisfactory and the aggregate sizes meet requirements based on the size of structural members and the spacing between reinforcing bars and spacing between reinforcing bar and formwork.
Repair of heat-damaged reinforced concrete T-beams using FRC jackets
Authors: Haddad R. H. , Shannag M. J. , Hamad R. J.
Published: February 2007

A series of 16 under-reinforced concrete (RC) T-beams were cast, heated at 600°C for 2·5 h, repaired and then tested under four-point loading to study the effectiveness of using externally applied high-strength fibre reinforced concrete (FRC) jackets as a method of increasing the flexural capacity of beams. The overall response of the beams loaded up to failure, the onset of cracking and cracking pattern, serviceability, stiffness and ductility were described. Four types of fibre were used: glass, high-performance polypropylene (HPP), hooked end steel and brass-coated steel (BCS) with fibre content ranging from 1 to 2%. The beams repaired with steel-FRC jackets applied at the sides of the beams' web and the bottom of the flange, exhibited a substantial improvement in their flexural behaviour compared with control (undamaged) ones. They regained a large proportion of the control beams' ultimate load capacity, and showed a typical flexural failure with an increase in the first cracking load. The beams repaired with HPP and glass fibres exhibited a marginal improvement in their flexural behaviour compared with control ones with a typical flexural failure and a decrease in the first cracking load. Based on the findings of the present study, high-strength steel-FRC jackets may be considered as a promising material for maintenance and rehabilitation of concrete structures.
Signatures of rapid climatic changes in organic matter records in the western Mediterranean Sea during the last glacial period
Authors: Baudin François , Combourieu-Nebout Nathalie , Zahn Rainer
Published: February 2007

Records of calcium carbonate, organic matter (organic carbon content, palynology) and planktonic foraminiferal oxygen isotopes from ODP Site 976, Alboran Sea, are used to reconstruct the evolution of continental climates and oceanic productivity in the westernmost Mediterranean over the past 50,000 years. The records mimic the Greenland ice core records in that they display the Heinrich events and the rapid Dansgaard/Oeschger-type stadial-interstadial oscillations. Warm interstadials correlate with an expansion of deciduous forests on the adjacent continents and enhanced river runoff and organic matter flux from terrestrial sources. In contrast, cold stadials are characterized by an expansion of semi-desert vegetation, reduced river runoff and limited terrestrial organic matter flux. The organic carbon record displays a longer-term cyclicity that correlates with the North Atlantic ’Bond’ cooling cycles. The records enable the documentation of rapid changes of continental climates in the western Mediterranean borderlands that caused changes in river runoff and in oceanic productivity that were driven by rapid fluctuations of the Atlantic inflow into the Mediterranean Sea. The combined terrestrial-marine patterns demonstrate the close linking of western Mediterranean climate with the climatic evolution in the North Atlantic region.
Health Professionals' Attitude toward Euthanasia: A Cross-Sectional Study from Turkey
Authors: Turla Ahmet , Özkara Erdem , Özkanli Çağlar , Alkan Nevzat
Published: February 2007

There is an ongoing debate on the definition of euthanasia and attempts to change laws about euthanasia and its practice in many countries. It is the medical doctors and the other health professionals who will elucidate the issue. Therefore, we performed this study to reveal attitude of Turkish health professionals toward euthanasia. This is an observational and cross-sectional study and data were collected with a questionnaire. The questionnaire was distributed to 545 health professionals in Samsun, a city in the Black Sea Region in Turkey. Data were analyzed with SPSS package programs. Of all health professionals included in the study, 43.5% were medical doctors and 45.5% auxiliary health professionals. Of all participants, 33.6% did not object to euthanasia and 7.9% were asked to perform euthanasia. Eighty point seven percent of the participants noted that euthanasia could be abused even if a euthanasia law were passed. It can be concluded that the health professionals should have a chance to discuss euthanasia and that their attitude toward and their expectations and worries about euthanasia should be taken into account when a euthanasia law is drafted.
A Review of Employment Conditions as Social Determinants of Health Part II: The Workplace
Authors: Moure-Eraso Rafael , Flum Marian , Lahiri Supriya , Tilly Chris , Massawe Ephraim
Published: February 2007

This is the second part of an article on employment conditions as social determinants of health and health inequalities. In part I of this article, we explored structural (external) employment conditions that affect health inequalities and health gradients. In this article, we try to examine the internal aspects of employment conditions that affect the same variables. It is not our intention to “box” employment conditions in a rigid framework within an internal domain of person-hazard interaction. The objective of examining this variable is to scrutinize internal aspects of employment conditions at a comprehensive policy level in conjunction with external contextual variables. Major occupational health concerns are examined in relationship to globalization, child labor, and work in the formal and informal sectors. Interventions that can eliminate or greatly reduce these exposures as well as those that have been unsuccessful are reviewed. Innovative interventions including work organization change, cleaner production, control banding, national and international coalitions, participatory training, and participatory approaches to improving the work environment are reviewed.
Dioxin Cancer Risk — Example of Hormesis?
Authors: Tuomisto Jouko , Pekkanen Juha , Kiviranta Hannu , Tukiainen Erkki , Vartiainen Terttu , Viluksela Matti , Tuomisto Jouni T.
Published: February 2007

A recent case-control study implied an inverse correlation between the measured body burden of dioxins (polychlorinated dibenzo- p-dioxins and polychlorinated dibenzofurans, PCDD/F) and the risk of soft tissue sarcoma in normal population exposed to dioxins mainly via food. The surprising result could not be explained by biases or confounding. There is no a priori confounding by occupational chemicals in a random sample from general population, but exposures to other lipid soluble chemicals with similar sources might be expected to associate with that of dioxins. One such group is polychlorinated biphenyls (PCB). Therefore three most relevant dioxin-like PCB compounds PCB 77, PCB 126, and PCB 169 were now analyzed from the same patients. Cases were 110 soft-tissue sarcoma patients undergoing surgery for their disease, and referents were 227 patients operated for appendicitis. Dioxin and PCB concentrations were analyzed from subcutaneous fat samples by high-resolution gas chromatography—mass spectrometry and TCDD equivalent concentrations (WHO-TEq) were calculated by using toxicity equivalency factors of WHO. The highest risk of sarcoma was found in the septile with the lowest body burden of sum WHO-TEq, and the differences of septiles 2 and 6 from septile 1 were statistically significant. If soft sarcoma risk is true at high occupational levels of dioxins, the provocative result suggests that a possibility of a J-shaped dose-response curve should be taken into consideration and studied further. This is also supported by the similar J-shaped dose responses in animal studies.
Structural Changes Revealed by Fourier Transform Infrared and Circular Dichroism Spectroscopic Analyses Underlie tNOX Periodic Oscillations
Authors: Kim Chinpal , Layman Sara , Morré Dorothy M. , Morré D. James
Published: February 2007

A recurring pattern of spectral changes indicative of periodic changes in the proportion of β-structure and a-helix of a recombinant ECTO-NOX fusion protein of tNOX, with a cellulose binding domain peptide, was demonstrated by Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopic analyses. The pattern of structural changes correlated with oscillatory patterns of enzymatic activities exhibited by the protein previously interpreted as indicative of a clock function. The pattern consisted of a repeating pattern of oscillations with a period length of 21 min with five maxima (two separated by 5 min and 3 separated by 4 to 4.5 min) within each 21 min repeat. Oscillatory patterns were not obvious in comparable FTIR or CD spectra of albumin, ribonuclease or concanavalin A. The period length was constant at 5, 15, 25, 35 and 45° C (temperature compensated) and oscillations occurred independently of substrate presence. Spectra obtained in deuterium oxide yielded a longer period length of 26 min both for oscillations in enzymatic activity and absorbance ratios determined by FTIR. Taken together the findings suggest that the regular patterns of oscillations exhibited by the ECTO-NOX proteins are accompanied by recurrent global changes in the conformation of the protein backbone that directly modulate enzymatic activity.
The Temporal Hormesis of Drug Therapies
Authors: Dudekula Noor , Arora Vikas , Callaerts-Vegh Zsuzsanna , Bond Richard A.
Published: February 2007

Recent publications in the field of asthma therapeutics and studies performed over the last decade in the treatment of chronic heart failure suggest a phenomenon called ‘temporal hormesis’. This phenomenon can be defined as the beneficial action of drug after chronic administration as opposed to its detrimental acute effects. Temporal hormesis may be related to the classification of the drug molecule as an agonist, antagonist or an inverse agonist. This phenomenon may be a more general principal applicable in the treatment of other diseases apart from asthma and chronic heart failure.
Hormesis: Implications for Cancer Risk Assessment
Authors: Borak Jonathan , Sirianni Greg
Published: February 2007

Current guidelines for cancer risk assessment emphasize a toxicant's “mode of action”, rather than its empirically derived dose-response relationship, for determining whether linear low-dose extrapolation is appropriate. Thus, for reasons of policy, demonstration of hormesis is generally insufficient to justify a non-linear approach, although it may provide important insights into the actions of toxicants. We evaluated dose-response characteristics of four carcinogens reported to have hormetic dose-response curves: cadmium chloride; ionizing radiation; PAHs; and, 2,3,7,8-TCDD. For each, the study that documented hormesis in one organ also provided evidence of non-hormetic dose-responses in other organs or non-hormetic responses for seemingly similar carcinogens in the same species and organs. Such inconsistency suggests toxicologic reasons that the finding of hormesis alone is not sufficient to justify use of non-linear low-dose extrapolations. Moreover, available data in those examples are not sufficient to know whether hormesis is a property of the toxicants, the target organ, or the exposed species. From the perspectives of cancer risk assessment, the greatest informational value of hormesis may be that it provokes mechanistic studies intended to explain why hormesis occurs.
The Effect of Random Error in Exposure Measurement upon the Shape of the Exposure Response
Authors: Crump Kenny S.
Published: February 2007

Although statistical analyses of epidemiological data usually treat the exposure variable as being known without error, estimated exposures in epidemiological studies often involve considerable uncertainty. This paper investigates the theoretical effect of random errors in exposure measurement upon the observed shape of the exposure response. The model utilized assumes that true exposures are log-normally distributed, and multiplicative measurement errors are also log-normally distributed and independent of the true exposures. Under these conditions it is shown that whenever the true exposure response is proportional to exposure to a power r, the observed exposure response is proportional to exposure to a power K, where K < r. This implies that the observed exposure response exaggerates risk, and by arbitrarily large amounts, at sufficiently small exposures. It also follows that a truly linear exposure response will appear to be supra-linear—i.e., a linear function of exposure raised to the K-th power, where K is less than 1.0. These conclusions hold generally under the stated log-normal assumptions whenever there is any amount of measurement error, including, in particular, when the measurement error is unbiased either in the natural or log scales. Equations are provided that express the observed exposure response in terms of the parameters of the underlying log-normal distribution. A limited investigation suggests that these conclusions do not depend upon the log-normal assumptions, but hold more widely. Because of this problem, in addition to other problems in exposure measurement, shapes of exposure responses derived empirically from epidemiological data should be treated very cautiously. In particular, one should be cautious in concluding that the true exposure response is supra-linear on the basis of an observed supra-linear form.
A Graphical Method to Evaluate Exposure-Response Relationships in Epidemiologic Studies Using Standardized Mortality or Morbidity Ratios
Authors: van Wijngaarden Edwin
Published: February 2007

In occupational epidemiology, exposure-response analyses play an important role in the evaluation of the etiologic relevance of chemical and physical exposures. The standardized mortality or morbidity ratio (SMR) has been commonly used in occupational cohort studies. Statistical approaches to evaluate exposure-response patterns using SMRs have mostly been limited to analyses in which the exposure under investigation is categorized. Here, a graphical method for evaluating exposure-response patterns is presented based on SMR estimates across moving exposure windows. This method is demonstrated using the results of two hypothetical cohort studies. The proposed approach may be useful for graphical exploration of exposure-response trends in situations where the number of observed cases is small.
Modeling Nonlinear Dose-Response Relationships in Epidemiologic Studies: Statistical Approaches and Practical Challenges
Authors: May Susanne , Bigelow Carol
Published: February 2007

Non-linear dose response relationships pose statistical challenges for their discovery. Even when an initial linear approximation is followed by other approaches, the results may be misleading and, possibly, preclude altogether the discovery of the nonlinear relationship under investigation. We review a variety of straightforward statistical approaches for detecting nonlinear relationships and discuss several factors that hinder their detection. Our specific context is that of epidemiologic studies of exposure-outcome associations and we focus on threshold and J-effect dose response relationships. The examples presented reveal that no single approach is universally appropriate; rather, these (and possibly other) nonlinearities require for their discovery a variety of both graphical and numeric techniques.
Radiation Risk Prediction and Genetics: The Influence of the TP53 Gene in vivo
Authors: Mitchel R. E. J.
Published: February 2007

Risk prediction and dose limits for human radiation exposure are based on the assumption that risk is proportional to total dose. However, there is concern about the appropriateness of those limits for people who may be genetically cancer prone. The TP53 gene product functions in regulatory pathways for DNA repair, cell cycle checkpoints and apoptosis, processes critical in determining ionizing radiation risk for both carcinogenesis and teratogenesis. Mice that are deficient in TP53 function are cancer prone. This review examines the influence of variations in TP53 gene activity on cancer and teratogenic risk in mice exposed to radiation in vivo, and compares those observations to the assumptions and predictions of radiation risk inherent in the existing system of radiation protection. Current assumptions concerning a linear response with dose, dose additivity, lack of thresholds and dose rate reduction factors all appear incorrect at low doses. TP53 functional variations can further modify radiation risk from either high or low doses, or risk from radiation exposures combined with other stresses, and those modifications can result in both quantitative and qualitative changes in risk.
Stochastic Thresholds: A Novel Explanation of Nonlinear Dose-Response Relationships for Stochastic Radiobiological Effects
Authors: Scott Bobby R.
Published: February 2007

New research data for low-dose, low- linear energy transfer (LET) radiation-induced, stochastic effects (mutations and neoplastic transformations) are modeled using the recently published NEOTRANS3 model. The model incorporates a protective, stochastic threshold (StoThresh) at low doses for activating cooperative protective processes considered to include presumptive p53-dependent, high-fidelity repair of nuclear DNA damage in competition with presumptive p53-dependent apoptosis and a novel presumptive p53-independent protective apoptosis mediated (PAM) process which selectively removes genomically compromised cells (mutants, neoplastic transformants, micronucleated cells, etc.). The protective StoThresh are considered to fall in a relatively narrow low-dose zone (Transition Zone A). Below Transition Zone A is the ultra-low-dose region where it is assumed that only low-fidelity DNA repair is activated along with presumably apoptosis. For this zone there is evidence for an increase in mutations with increases in dose. Just above Transition Zone A, a Zone of Maximal Protection (suppression of stochastic effects) arises and is attributed to maximal cooperation of high-fidelity, DNA repair/apoptosis and the PAM process. The width of the Zone of Maximal Protection depends on low-LET radiation dose rate and appears to depend on photon radiation energy. Just above the Zone of Maximal Protection is Transition Zone B, where deleterious StoThresh for preventing the PAM process fall. Just above Transition Zone B is a zone of moderate doses where complete inhibition of the PAM process appears to occur. However, for both Transition Zone B and the zone of complete inhibition of the PAM process, high-fidelity DNA repair/apoptosis are presumed to still operate. The indicated protective and deleterious StoThresh lead to nonlinear, hormetic-type dose-response relationships for low-LET radiation-induced mutations, neoplastic transformation and, presumably, also for cancer.
Effects of Specific Dosages of Magnesium and Zinc on the Teratogenicity of Cadmium, Nickel, and Cobalt in Xenopus Embryos, as Assessed by the Fetax Test
Authors: Boga Ayper , Sertdemir Yasar
Published: February 2007

The objective of this study was to determine if exposure to divalent cations, Cd2+, Ni2+, and Co2+ would lead to malformations in Xenopus laevis embryos, and whether addition of Mg2+ and Zn2+; separately and in combination, would reduce their toxicity and teratogenicity on the embryos of Xenopus laevis as assessed by 96-h FETAX tests. Results indicate that exposure to Cd2+, Ni2+ or Co2+ lead to an increase in toxicity and teratogenicity in embryos, whereas Mg2+, Zn2+, or a combination of them reduced the toxic and teratogenic effects of these divalent cations. Modulation of Cd2+, Ni2+ or Co2+ toxicity and teratogenicity by Mg2+ and Zn2+, varied with the metal. Zn2+ was observed to be a better suppressor of Co2+ toxicity and teratogenicity than Mg2+. In contrast, Ni2+, and Cd2+ teratogenicity was reduced more prominently by Mg2+. On the other hand, combination of Mg2+ and Zn2+ showed potentialization effect on all divalent cation toxicity and teratogenicity. We concluded that Mg2+ and Zn2+ reduced the toxicity and teratogenicity of Cd2+, Ni2+, Co2+.
Low-Dose Radiation-Induced Protective Process and Implications for Risk Assessment, Cancer Prevention, and Cancer Therapy
Authors: Scott B. R.
Published: February 2007

A low-dose protective apoptosis-mediated (PAM) process is discussed that appears to be turned on by low-dose gamma and X rays but not by low-dose alpha radiation. PAM is a bystander effect that involves cross-talk between genomically compromised [ e.g., mutants, neoplastically transformed, micronucleated] cells and nongenomically compromised cells. A novel neoplastic cell transformation model, NEOTRANS3, is discussed that includes PAM. With NEOTRANS3, PAM is activated by low doses and inhibited by moderate or high doses and is, therefore, a hormetic process. A low-dose region of suppression of the transformation frequency below the spontaneous frequency relates to the hormetic zone over which PAM is presumed to operate. The magnitude of suppression relates to what is called the hormetic intensity. Both the hormetic intensity and width of the hormetic zone are expected to depend on dose rate, being more pronounced after low dose rates. It is expected that PAM likely had a significant role in the following observations after chronic irradiation: (1) what appears to be a tremendous reduction in the cancer incidence below the spontaneous level for Taiwanese citizens residing for years in cobalt-60 contaminated apartments; and (2) the published reductions in the lung cancer incidence below the spontaneous level in humans after protracted X irradiation and after chronic gamma plus alpha irradiation. Implications of PAM for cancer prevention and low-dose cancer therapy are briefly discussed.
The Occurrence of Hormesis in Plants and Algae
Authors: Cedergreen Nina , Streibig Jens C. , Kudsk Per , Mathiassen Solvejg K. , Duke Stephen O.
Published: February 2007

This paper evaluated the frequency, magnitude and dose/concentration range of hormesis in four species: The aquatic plant Lemna minor, the micro-alga Pseudokirchneriella subcapitata and the two terrestrial plants Tripleurospermum inodorum and Stellaria media exposed to nine herbicides and one fungicide and binary mixtures thereof. In total 687 dose-response curves were included in the database. The study showed that both the frequency and the magnitude of the hormetic response depended on the endpoint being measured. Dry weight at harvest showed a higher frequency and a larger hormetic response compared to relative growth rates. Evaluating hormesis for relative growth rates for all species showed that 25% to 76% of the curves for each species had treatments above 105% of the control. Fitting the data with a dose-response model including a parameter for hormesis showed that the average growth increase ranged from 9±1% to 16±16% of the control growth rate, while if measured on a dry weight basis the response increase was 38±13% and 43±23% for the two terrestrial species. Hormesis was found in >70% of the curves with the herbicides glyphosate and metsulfuron-methyl, and in >50% of the curves for acifluorfen and terbuthylazine. The concentration ranges of the hormetic part of the dose-response curves corresponded well with literature values.
Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer
Authors: Pollycove Myron
Published: February 2007

Antimutagenic DNA damage-control is the central component of the homeostatic control essential for survival. Over eons of time, this complex DNA damage-control system evolved to control the vast number of DNA alterations produced by reactive oxygen species (ROS), generated principally by leakage of free radicals from mitochondrial metabolism of oxygen. Aging, mortality and cancer mortality are generally accepted to be associated with stem cell accumulation of permanent alterations of DNA, i.e., the accumulation of mutations. In a young adult, living in a low LET background of 0.1 cGy/y, the antimutagenic system of prevention, repair and removal of DNA alterations reduces about one million DNA alterations/cell/d to about one mutation/cell/d. DNA alterations from background radiation produce about one additional mutation per 10 million cells/d. As mutations accumulate and gradually degrade the antimutagenic system, aging progresses at an increasing rate, mortality increases correspondingly, and cancer increases at about the fourth power of age. During the past three decades, genomic, cellular, animal and human data have shown that low-dose ionizing radiation, including acute doses up to 30 cGy, stimulates each component of the homeostatic antimutagenic control system of antioxidant prevention, enzymatic repair, and immunologic and apoptotic removal of DNA alterations. On the other hand, high-dose ionizing radiation suppresses each of these antimutagenic protective components. Populations living in high background radiation areas and nuclear workers with increased radiation exposure show lower mortality and decreased cancer mortality than the corresponding populations living in low background radiation areas and nuclear workers without increased radiation exposure. Both studies of cancer in animals and clinical trials of patients with cancer also show, with high statistical confidence, the beneficial effects of low-dose radiation.