bluuebunny/crossref_metadata_2025 huggingface dataset:
An “Omics” view of drug development
Authors: Altman Russ B. , Rubin Daniel L. , Klein Teri E.
Published: November 2004

The pharmaceutical industry cannot be blamed for having a love/hate relationship with the fields of pharmacogenetics and pharmacogenomics. At the same time that pharmacogenetics and pharmacogenomics promise to save pipeline drugs by identifying subsets of the population for which they work best, they also threaten to increase the complexity of new drug applications, fragment markets, and create uncertainty for prescribers who simply do not understand or have time to master “personalized medicine.” Most importantly, the logical case for genetics‐specific drug selection and dosing is much more mature than the practical list of drugs for which outcomes are demonstrably improved. Understandably, pharmaceutical developers and regulators have been careful in creating strategies for using genetics in drug development, and only recently has the FDA begun to establish preliminary rules for pharmacogenetic testing. A growing public academic effort in pharmacogenetics and pharmacogenomics is helping flesh out the basic science underpinnings of the field, and this should combine with extensive efforts of industry to create a solid foundation for future use of genetics in drug development. Two grand challenges to accelerate our capabilities include the characterization of all human genes involved in the basic pharmacokinetics of drugs, and the detailed study of the genes and pathways associated with G‐protein‐coupled receptors and how they are affected by genetic variation. Drug Dev. Res. 62:81–85, 2004. © 2004 Wiley‐Liss, Inc.
Application of expression genomics in drug development and genomic medicine
Authors: Chin Khew‐Voon , Selvanayagam Zachariah E. , Vittal Ragini , Kita Tsunekazu , Kudoh Kazuya , Yang Chung S. , Wong Yick Fu , Cheung Tak Hong , Yeo Winnie , Chung Tony Kwok Hung , Lin Yong , Liao Jason , Shih Joe Weichung , Yap Sook Fan , Lin Albert W.
Published: November 2004

Expressed sequence tags and genome sequencing have virtually uncovered all the genes and transcripts in the human genome. Functional genomic analysis of these genes will undoubtedly reveal their physiological roles in cells in the near future. Coupled with the advent of DNA microarray, cellular response to perturbation can now be examined at genome‐wide levels in a single analysis, yielding clues to the network of pathways and interacting pathways that underlie a comprehensive systems response to exposure to small molecule perturbants. This post‐genomic information will be the foundation for knowledge‐based in silico systems biology. It is envisioned that querying such relational databases will generate testable hypotheses as well as revealing information on networks of regulatory genes and pathways that could further fuel and shape molecular and drug target discovery, and ushering in a new era in genomic medicine. In this review, we will first discuss examples of laboratory results generated from high‐throughput microarray analyses that illuminated previously unrecognized networks of regulatory genes and pathways that point to the mechanisms of action for the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate, and the green tea polyphenol, epi‐gallocatechin gallate. We will then focus on the application of gene expression profiles in genomic medicine for predicting treatment response in cancer, using clinical specimens obtained from patients. These studies and others point to an increasing trend in modern biology in which high‐throughput genome scale comprehensive biological information is incorporated into databases for constructing and reconstructing pathways and networks of interacting pathways that constitute a physiological response to environmental perturbation at the organism or systems levels. Drug Dev. Res. 62:124–133, 2004. © 2004 Wiley‐Liss, Inc.
Adrenocortical response to stress in fasted and unfasted artificially reared 12‐day‐old rat pups
Authors: Ward Glenn , Xing Hua Cheng , Carnide Nancy , Slivchak Jane , Wainwright Patricia
Published: November 2004

Recent studies have compared artificially reared (AR) rats with dam‐reared rats on behavioral outcomes but, despite the fact that they are deprived of their mothers during the stress hyporesponsive period (SHRP), little is known about the effects of AR on the development of the stress response. In this study, the corticosterone (CORT) response to a stressor (saline injection ip) on postnatal Day 12 was assessed in rat pups that had been either dam‐reared (DR) or artificially reared since Day 5. In the preceding 24 hr, half the pups in the DR group were maternally deprived (DEP). To control for the food deprivation consequent to maternal deprivation in these groups, half the pups in the AR groups also underwent 24‐hr food deprivation (DEP). In the nondeprived condition AR pups did not differ from DR pups on untreated CORT levels or on levels at 1‐hr poststress (i.e., all rats demonstrated low levels of CORT characteristic of the SHRP). In contrast, both maternally deprived DR pups and food‐deprived AR pups exhibited increased untreated CORT levels as well as a significant increase at 30‐min poststress, but CORT elevations were lower in the AR groups than in the DR groups. Thus, long‐term maternal deprivation through artificial rearing in rats does not affect the reduced CORT levels and reduced CORT responsiveness associated with the SHRP; however, if animals are food deprived, then all show increased basal CORT levels and a greater CORT response to stress, although this response is lower in AR groups than in DR groups. These results suggest that rat pups artificially reared with adequate nutrition will still exhibit the SHRP. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 245–250, 2004.
Intraocular injection of tamoxifen‐loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis
Authors: de Kozak Yvonne , Andrieux Karine , Villarroya Henri , Klein Christophe , Thillaye‐Goldenberg Brigitte , Naud Marie‐Christine , Garcia Elisabeth , Couvreur Patrick
Published: November 2004

In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non‐steroidal estrogen receptor modulator, in retinal soluble antigen (S‐Ag)‐induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)‐coated nanoparticles (NP‐PEG‐TAM). The localization of the nanoparticles within the eye was investigated using fluorescent‐labeled PEG‐coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP‐PEG‐TAM performed 1–2 days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP‐PEG‐TAM injection significantly reduced EAU compared to injection of NP‐PEG‐TAM with 17β‐estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class II+ inflammatory cells and low expression of TNF‐α, IL‐1β, and RANTES mRNA were noted in eyes of NP‐PEG‐TAM‐treated rats. Intravitreal injection of NP‐PEG‐TAM decreased S‐Ag lymphocyte proliferation, IFN‐γ production by inguinal lymph node cells, and specific delayed‐type hypersensitivity indicative of a reduced Th1‐type response. It increased the anti‐S‐Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP‐PEG‐TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen‐loaded nanoparticles may represent a new option for the treatment of experimental uveitis.
Inhibition of mast cells by interleukin‐10 gene transfer contributes to protection against acute myocarditis in rats
Authors: Palaniyandi Suresh S. , Watanabe Kenichi , Ma Meilei , Tachikawa Hitoshi , Kodama Makoto , Aizawa Yoshifusa
Published: November 2004

Progression of acute myocarditis involves a variety of inflammatory events. Mast cells have been implicated as the source of various cytokines, chemokines and histamine in acute inflammation and fibrosis. Interleukin (IL)‐10 has well‐known immunomodulatory actions that are exerted during the recovery phase of myocarditis. In this study, 9‐week‐old male Lewis rats were immunized with cardiac myosin. A plasmid vector expressing mouse IL‐10 cDNA (800 μg per rat) was then transferred three times (7, 12 and 17 days after immunization) into the tibialis anterior muscles of the rats by electroporation. Microscopic examination of mast cells was carried out on toluidine blue‐stained transverse sections of the mid ventricles. Mouse IL‐10 gene transfer significantly reduced mast cell density, cardiac histamine concentration and mast cell growth, and prevented mast cell degranulation. Furthermore, improvement in both myocardial function and the overall condition of the rats was evident from the reduction in the heart weight‐to‐body weight ratio and inflammatory infiltration as well as improvement in hemodynamic and echocardiographic parameters. These findings suggest that IL‐10 gene transfer by electroporation protected against myocarditis via mast cell inhibition.
Distal regulatory elements play an important role in regulation of the human IL‐5 gene
Authors: Urwin Debra L. , Schwenger Gretchen T. F. , Groth David M. , Sanderson Colin J.
Published: November 2004

Eosinophil infiltration of the lung is a feature of both allergic and nonallergic asthma, and IL‐5 is the key cytokine regulating the production and activation of these cells. Despite many studies focusing on the IL‐5 promoter in both humans and mice there is as yet no clear picture of how the IL‐5 gene is regulated. The aim of this study was to determine if distal regulatory elements contribute to appropriate regulation of the human IL‐5 (hIL‐5) gene. Activity of the –507/+44 hIL‐5 promoter was compared to expression of the endogenous IL‐5 gene in PER‐117 T cells. The IL‐5 promoter was not sufficient to reproduce a physiological pattern of IL‐5 expression. Further, functional analysis of the 5′ and 3′ intergenic regions revealed a number of novel regulatory elements. We have identified a conserved enhancer located approximately 6.2 kb upstream of the hIL‐5 gene. This region contains two potential GATA‐3‐binding sites and increases expression from the hIL‐5 promoter by up to ninefold.
Interleukin 1 plays a major role in the development of Th2‐mediated immunity
Authors: Helmby Helena , Grencis Richard K.
Published: November 2004

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th)2‐type response, involving interleukin (IL)‐4, IL‐9 and IL‐13. Here, we show that Th2 response‐associated resistance is dependent on the presence of IL‐1α and IL‐1β. When lymph node cells from naive IL‐1α‐ or IL‐1β‐deficient mice were subjected to Th2 polarization in vitro, they failed to polarize in the presence of IL‐4 alone, but required the addition of exogenous IL‐1α or IL‐1β. Furthermore, we demonstrate that both IL‐1α‐ and IL‐1β‐deficient mice are susceptible to chronic T. muris infection and that the inability to expel the worms is associated with a defect in the development of a Th2 response in the mesenteric lymph nodes. These results provide the first demonstration of the critical role of IL‐1 in regulating Th2 responses during gastrointestinal nematode infection.
Down‐regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation
Authors: Kobayashi Naoki , Takata Hiroshi , Yokota Shumpei , Takiguchi Masafumi
Published: November 2004

Multi‐color flow cytometric analysis on human CD8+ T cell subsets revealed that CXCR4 is predominantly expressed on CD8+ T cells with the naive CD27+CD28+CD45RA+ phenotype, and is down‐regulated during differentiation into those with an effector phenotype. The down‐regulation of CXCR4 expression during peripheral differentiation was supported by the fact that the expression of CXCR4 on CD8+ T cells was negatively correlated with that of perforin. The analysis of CCR5, CCR7, and CXCR4 co‐expression further showed that CD8+ T cells expressing a high level of CXCR4 are CCR7+CCR5− naive or central memory subsets, and those expressing a low level of CXCR4 were included in the CCR7−CCR5+/− memory/effector and effector subsets. Epstein Barr virus‐specific CD8+ T cells, which mostly express the memory phenotype, expressed CXCR4, while human cytomegalovirus‐specific CD8+ T cells, which mostly express the effector phenotype, partially expressed this receptor, showing that the expression of CXCR4 is also down‐regulated during differentiation of viral antigen‐specific CD8+ T cells. The classification of human CD8+ T cells based on the expression of these chemokine receptors should prove useful for studies that clarify the differentiation of human CD8+ T cells.
Leader visioning and adaptability: Bridging the gap between research and practice on developing the ability to manage change
Authors: Zaccaro Stephen J. , Banks Deanna
Published: November 2004

The construction of organizational vision and the ability to manage the change engendered by visions represent core organizational competencies that foster competitive advantage for organizations. However, while a significant body of conceptual and empirical research studies supports these as core competencies, high numbers of HR professionals are either not aware of this research or still dispute the utility of these skills. In this article, we discuss three gaps between leadership research and practice. The first refers to the value of organizational visions. The second reflects beliefs about the importance of change management skills for HR managers. The final gap concerns the utility of training and development programs that target visioning and change management skills. We discuss some reasons for these gaps between leadership research and HR practices. We also describe some components of visioning, adaptability and managing change, and provide some supportive conceptual and empirical research. We suggest the use of developmental work assignments as a leader development strategy that we believe is most appropriate for growing these core competencies. © 2004 Wiley Periodicals, Inc.
The importance of pay in employee motivation: Discrepancies between what people say and what they do
Authors: Rynes Sara L. , Gerhart Barry , Minette Kathleen A.
Published: November 2004

A majority of human resources professionals appear to believe that employees are likely to overreport the importance of pay in employee surveys. However, research suggests the opposite is actually true. We review evidence showing the discrepancies between what people say and do with respect to pay. We then discuss why pay is likely to be such an important general motivator, as well as a variety of reasons why managers might underestimate its importance. We note that pay is not equally important in all situations or to all individuals, and identify circumstances under which pay is likely to be more (or less) important to employees. We close with recommendations for implementing research findings with respect to pay and suggestions for evaluating pay systems. © 2004 Wiley Periodicals, Inc.
An initial assessment of the use of gradient elution in microemulsion and micellar liquid chromatography
Authors: Bryant Simon M. , Altria Kevin D.
Published: November 2004

Novel microemulsion and micellar HPLC separations have been achieved using gradient elution and columns packed with reverse phase material. Initial attempts at gradient microemulsion liquid chromatography proved impossible on use of a microemulsion successfully used in capillary electrophoresis. Optimisation of the microemulsion composition allowed the generation of stable microemulsions to achieve separations in HPLC. The novel use of organic‐solvent micellar chromatography in gradient elution mode was shown to give efficient separations. A range of efficient separations of pharmaceuticals and related impurities were obtained. Acidic, basic, and neutral solutes were resolved covering a wide range of water solubilities and polarities. Elution times were in the order of 4–15 minutes. Separations were briefly compared to those accomplished with a micellar HPLC system. It is proposed that gradient elution in both microemulsion and micellar HPLC can be regarded as a highly successful means of achieving resolution of complex mixtures and should be considered for routine analysis and further investigation.
SAGE profiling of UV‐induced mouse skin squamous cell carcinomas, comparison with acute UV irradiation effects
Authors: Rundhaug Joyce E. , Hawkins Kathleen A. , Pavone Amy , Gaddis Sally , Kil Hyunsuk , Klein Russell D. , Berton Thomas R. , McCauley Elisabeth , Johnson David G. , Lubet Ronald A. , Fischer Susan M. , Aldaz C. Marcelo
Published: November 2004

Ultraviolet (UV) irradiation is the primary environmental insult responsible for the development of most common skin cancers. To better understand the multiple molecular events that contribute to the development of UV‐induced skin cancer, in a first study, serial analysis of gene expression (SAGE) was used to compare the global gene expression profiles of normal SKH‐1 mice epidermis with that of UV‐induced squamous cell carcinomas (SCCs) from SKH‐1 mice. More than 200 genes were found to be differentially expressed in SCCs compared to normal skin (P < 0.0005 level of significance). As expected, genes related to epidermal proliferation and differentiation were deregulated in SCCs relative to normal skin. However, various novel genes, not previously associated with skin carcinogenesis, were also identified as deregulated in SCCs. Northern blot analyses on various selected genes validated the SAGE findings: caspase‐14 (reduced 8.5‐fold in SCCs); cathepsins D and S (reduced 3‐fold and increased 11.3‐fold, respectively, in SCCs); decorin, glutathione S‐transferase omega‐1, hypoxia‐inducible factor 1α, insulin‐like growth factor binding protein‐7, and matrix metalloproteinase‐13 (increased 18‐, 12‐, 12‐, 18.3‐, and 11‐folds, respectively, in SCCs). Chemokine (C‐C motif), ligand 27 (CCL27), which was found downregulated 12.7‐fold in SCCs by SAGE, was also observed to be strongly downregulated 6–24 h after a single and multiple UV treatments. In a second independent study we compared the expression profile of UV‐irradiated versus sham‐treated SKH‐1 epidermis. Interestingly, numerous genes determined to be deregulated 8 h after a single UV dose were also deregulated in SCCs. For instance, genes whose expression was upregulated both after acute UV‐treated skin and SCCs included keratins 6 and 16, small proline‐rich proteins, and S100 calcium binding protein A9. Studies like those described here do not only provide insights into genes and pathways involved in skin carcinogenesis but also allow us to identify early UV irradiation deregulated surrogate biomarkers of potential use in chemoprevention studies. © 2004 Wiley‐Liss, Inc.
A sinh transformation for evaluating nearly singular boundary element integrals
Authors: Johnston Peter R. , Elliott David
Published: November 2004

An implementation of the boundary element method requires the accurate evaluation of many integrals. When the source point is far from the boundary element under consideration, a straightforward application of Gaussian quadrature suffices to evaluate such integrals. When the source point is on the element, the integrand becomes singular and accurate evaluation can be obtained using the same Gaussian points transformed under a polynomial transformation which has zero Jacobian at the singular point.

A class of integrals which lies between these two extremes is that of ‘nearly singular’ integrals. Here, the source point is close to, but not on, the element and the integrand remains finite at all points. However, instead of remaining flat, the integrand develops a sharp peak as the source point moves closer to the element, thus rendering accurate evaluation of the integral difficult.

This paper presents a transformation, based on the sinh function, which automatically takes into account the position of the projection of the source point onto the element, which we call the ‘nearly singular point’, and the distance from the source point to the element. The transformation again clusters the points towards the nearly singular point, but does not have a zero Jacobian. Implementation of the transformation is straightforward and could easily be included in existing boundary element method software.

It is shown that, for the two‐dimensional boundary element method, several orders of magnitude improvement in relative error can be obtained using this transformation compared to a conventional implementation of Gaussian quadrature. Asymptotic estimates for the truncation errors are also quoted. Copyright © 2004 John Wiley & Sons, Ltd.
Uncommon histiocytic disorders: The non‐Langerhans cell histiocytoses
Authors: Weitzman Sheila , Jaffe Ronald
Published: November 2004

Background

Histiocytic disorders are currently identified by their component cells. The non‐Langerhans Cell Histiocytoses (non‐LCH) are a group of disorders defined by the accumulation of histiocytes that do not meet the phenotypic criteria for the diagnosis of Langerhans cells (LCs). The non‐LCH consist of a long list of diverse disorders which have been difficult to categorize. A conceptual way to think of these disorders that make them less confusing and easier to remember is proposed based on immunophenotyping and clinical presentation.

Results

Clinically the non‐LCH can be divided into 3 groups, those that predominantly affect skin, those that affect skin but have a major systemic component, and those that primarily involve extracutaneous sites, although skin may be involved. Immunohistochernically many of the non‐LCH appear to arise from the same precursor cell namely the dermal dendrocyte. Juvenile Xanthogranuloma (JXG) is the model of the dermal dendrocyte‐derived non‐LCH. Other non‐LCH with differing clinical presentation and occurring at different ages but with an identical immunophenotype appear to form a spectrum of the same disorder, deriving from the same precursor cell at different stages of maturation. They should be considered as members of a JXG family. Non‐JXG family members include Sinus histiocytosis with massive lymphadenopathy (Rosai‐Dorfman disease).

Conclusion

The non‐LCH can be classified as JXG family and non‐JXG family and subdivided according to fairly clear‐cut clinical criteria. Utilization of this type of approach will allow better categorization, easier review of the literature and more accurate therapy decision‐making. © 2004 Wiley‐Liss, Inc.
Identifying citrus limonoid aglycones by HPLC‐EI/MS and HPLC‐APCI/MS techniques
Authors: Manners Gary D. , Breksa Andrew P.
Published: November 2004

HPLC coupled with normal phase electron ionisation (EI) and atmospheric pressure chemical ionisation (APCI)/mass spectrometry methods has been applied to identify 17 known neutral limonoid aglycones from Citrus sources. The HPLC‐MS data from the known limonoids provided chromatographic characteristics, APCI‐derived molecular weight data and EI fragmentation data for each limonoid. EI fragmentation patterns for the limonoids were correlated with structural characteristics. The EI fragmentation patterns coupled with APCI‐derived molecular weights were utilised as a potential method by which to discern the structural character of unknown citrus limonoids. Copyright © 2004 John Wiley & Sons, Ltd.
Alloy and phonon scattering limited mobility in strain‐free ternary Si1–x–yGexCy
Authors: Mukhopadhyay Bratati , Basu P. K.
Published: November 2004

Estimates are made of the mobility limited by alloy disorder and phonon scattering mechanisms in strain free Ge‐rich ternary layer Si1–x–yGexCy grown on Si substrate. The expression for alloy scattering potential in ternary was derived for the first time using virtual crystal approximation and it differs from the expressions for ternary and quaternary alloys of III–V compounds. The phonon scattering processes are taken to be identical with those in pure Ge. Conservative estimates of mobility made by using reasonable values of alloy scattering potential indicate that mobility is predominantly limited by alloy scattering for 0.85 < x < 1 and the effect of C mole fraction (y) is not much significant for y < 0.1. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quasi‐localized low‐frequency vibrational modes of disordered solids I. Study by photon echo
Authors: Vainer Yu. G. , Naumov A. V. , Kol'chenko M. A. , Personov R. I.
Published: November 2004

According to the modern conception, the dynamics of amorphous solids in the intermediate interval of low temperatures (from a few up to dozens of Kelvins) is determined mainly by quasi‐localized low‐frequency vibrational modes (LFMs). Up to now, it is known very little about a nature and properties of these excitations in disordered solids. High‐selective laser spectroscopy of impurity centres, embedded to transparent disordered matrix as a probe, is a very powerful method for deriving information about LFMs. In the two presented papers the results of our photon echo (PE) and single molecule spectroscopy (SMS) studies of LFMs in organic amorphous solids are discussed. In the first part we review the recent results of our PE‐studies. Two cases are analyzed: (a) a coupling of chromophores with a continuous broad spectrum of LFMs, which shape was taken from light scattering experiments, and (b) a coupling of chromophores with continuous LFMs spectra, calculated on the base of the soft potentials model. In the second part we consider the results of our studies of LFMs in a glassy polymer on microscopic level using SMS. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ultrafast spectroscopy of localised vibrational modes in amorphous silicon using a free electron laser
Authors: Wells J.‐P. R. , van Hattum E. D. , Schropp R. E. I. , Phillips P. J. , Carder D. A. , Habraken F. H. P. M. , Dijkhuis J. I.
Published: November 2004

Ultrafast vibrational relaxation of localised modes associated with hydrogen, deuterium and oxygen in amorphous silicon based alloys are discussed. The availability of internal defect vibrations to act as accepting modes is discovered to be a crucial factor in the population decay dynamics. Phase relaxation is shown to have both a temperature dependent component due to elastic phonon scattering as well as an excitation dependence contributed by non‐equilibrium phonons. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Energy levels of two interacting particles in an anharmonic potential
Authors: Saha B. , Sil A. N. , Das A. K. , Mukherjee P. K.
Published: November 2004

Energy levels of two interacting mass points in an anharmonic model potential (Morse type) have been studied. Analytic expression for the energy levels has been worked out. The model potential is shown to support bound states under certain conditions. The number of such states has been found to depend on the parameters of the potential. The potential is expected to be more realistic, particularly in presence of environments for diatomic molecules and artificial atoms. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
The derivation of the characteristic function and the spectral density distribution of a Hamiltonian of N‐coupled morse oscillators: The large N‐limit
Authors: Bancewicz Małgorzata
Published: November 2004

This paper reports a derivation of the characteristic function and the frequency function of spectral density distribution of a Hamiltonian representing a system of N‐coupled Morse oscillators. The procedure utilized previously evaluated large‐N expressions for spectral density distribution moments. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Ab initio and DFT investigation of the structures and properties of chloromethyl and chlorofluoromethyl peroxyl radicals
Authors: El‐Taher S.
Published: November 2004

Ab initio and Density Functional Theory (DFT) calculations were performed to determine the equilibrium geometries, charge distributions, spin density distributions, dipole moments, electron affinities (EAs), and C–O bond dissociation energies (BDEs) of CH2ClO2• CHCl2O2•, CCl3O2•, CF2ClO2•, CFCl2O2•, and CHFClO2• peroxyl radicals. The C–H BDEs of the parent methanes were calculated using the same levels of theories. Both MP2(full) and B3LYP methods, using the 6‐31G(d,p) basis set, were found to be capable of accurately predicting the geometries of peroxyl radicals. The B3LYP/6‐31G(d,p) method was found to be comparable to high ab initio levels in predicting C–O BDEs of studied peroxyl radicals and C–H BDEs of the parent alkanes. The progressive chlorine substitution of hydrogen atoms in methyl peroxyl radicals results in an increase (decrease) of the spin density on the terminal (inner) oxygen, a decrease in dipole moments, and an increase in electron affinities. The substitution of fluorine by chlorine in the series CF3O2• – CCl3O2• was found to lengthen (destabilize) the C–O bonds. Both C–O BDEs and EAs of peroxyl radicals (RO2•) were found to correlate well with Taft σ* substituent constants for the R groups. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Does internal water influence electron tunneling in proteins? Example of cytochrome c oxidase
Authors: Zheng Xuehe , Medvedev Dmitry M. , Stuchebrukhov Alexei A.
Published: November 2004

In a recent study, the internal electron transfer in bovine heart cytochrome c oxidase (CcO) was examined using the tunneling currents method at the extended Hückel level of electronic structure. No internal water was present in the published structure of the enzyme, and none was taken into account in the calculations. Through computer simulation, we recently found an intriguing water hydrogen bond network in the vicinity of CcO catalytic site and in the region of electron tunneling. In this work, we reexamine the problem, with the focus on the possibility of the influence of water on electron transfer process. The calculations are carried out with the tunneling currents method implemented using more accurate ZINDO/S quantum chemical model. Results for the electron transfer from heme a to heme a3, a key step in the function of the enzyme, are presented. With molecular dynamics simulations, we identify configurations in which the water molecules interfere with the tunneling pathway. The tunneling matrix element is evaluated by the flux theorem of the tunneling currents method, and is found to be 0.34 cm−1 in the “dry” system and 1.38 cm−1 in the “wet” system. The analysis of the tunneling flux indicates that the impact of water is localized on Phe377 and spread to the methyl group and to His376, both on the heme a3 side of the ET pathway. The increase of the tunneling coupling by a factor of 4 in this case demonstrates that internal water in proteins can influence ET rate in proteins by as much as an order of magnitude. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Tip studies using CFD and comparison with tip loss models
Authors: Hansen Martin O. L. , Johansen Jeppe
Published: November 2004

The flow past a 95 kW Tellus rotor equipped with LM8·2 blades is computed using computational fluid dynamics for a standard tip and a swept tip. The difference in the near‐tip flow for the two tips for various tip speed ratios is examined and 3D airfoil data are extracted. The radial distribution of the averaged axial induction factor and the normal and tangential loads are compared with those of a standard blade element momentum code using 2D calibrated airfoil data for a wind speed of 9 m s−1, where the agreement in computed power is good. Further, a comparison with a new tip loss model proposed by Shen et al. has been performed for the same wind speed. Copyright © 2004 John Wiley & Sons, Ltd.
Aeroelastic stability of wind turbines: the problem, the methods and the issues
Authors: Riziotis V. A. , Voutsinas S. G. , Politis E. S. , Chaviaropoulos P. K
Published: November 2004

Aeroelastic stability is a key issue in the design process of wind turbines towards both enchanced stability and increased fatigue life. The theory and models behind the state‐of‐the‐art aeroelastic stability tools developed for the analysis of the complete wind turbine at the Centre for Renewable Energy Sources and the National Technical University of Athens are presented in this article. Application examples of stability calculations for a pitch, variable speed and a stall‐regulated wind turbine are also presented. Copyright © 2004 John Wiley & Sons, Ltd.
The effect of roughness at high Reynolds numbers on the performance of aerofoil DU 97‐W‐300Mod
Authors: Timmer W. A. , Schaffarczyk A. P.
Published: November 2004

This article discusses the results of wind tunnel measurements performed on a modified DU 97‐W‐300 aerofoil at Reynolds numbers between 1 × 106 and 10 × 106 in the cryogenic wind tunnel of DNW in Köln, Germany. The aerofoil was modified by reducing the trailing edge thickness from 1·74% to 0·49% of the chord. Although the measurements showed large scatter when flow separation occurred on the model, it was possible to establish the variation with Reynolds number of the maximum lift coefficient, the maximum lift/drag ratio and the design lift coefficient for a Mach number of 0·2. Furthermore, the effect of wrap‐around Carborundum 60 roughness and zigzag tape of 0·4 mm thickness on the upper and lower surfaces was studied. The experimental results were compared with RFOIL calculations. The measurements indicate that there was no significant variation in the maximum lift coefficient with Reynolds number for the clean aerofoil. In contrast to the RFOIL calculations, the experimental maximum lift/drag ratio decreased with increasing Reynolds number from an average of 95 at R = 3 × 106 to about 85 at R = 10 × 106. The Carborundum 60 roughness had a larger negative effect on the aerofoil performance than the zigzag tape, but in both cases the aerofoil performance improved drastically with increasing Reynolds number. Copyright © 2004 John Wiley & Sons, Ltd.
Paulo Freire, Eduardo Frei, Literacy Training and the Politics of Consciousness Raising in Chile, 1964 to 1970
Authors: KIRKENDALL ANDREW J.
Published: November 2004

This article examines the politics of literacy during the administration of Chilean President Eduardo Frei. Literacy training was an essential part of Christian Democratic efforts to promote agrarian reform and rural unionisation and incorporate the peasantry into the Chilean political system. Paulo Freire, working for the ministries of agriculture and education, was able to employ his innovative ‘consciousness raising’ techniques throughout Chile. In practice, the campaign often blurred the line between creating a critical consciousness and creating a Christian Democratic consciousness, while Freire himself became caught up in political struggles within the administration over the extent and pace of reform.
Latin America, Chile and East Asia: Policy-Networks and Successful Diversification
Authors: FAUST JÖRG
Published: November 2004

Latin American countries have a long tradition of attempting to diversify their external relations. In this context, since the end of the Cold War East Asia has gained increasing importance. However, despite the rising interest in improved political and economic links, these attempts at diversification showed only modest results, Chile being a noteworthy exception within this overall trend. The following analysis presents an empirical overview of the development of relations between Latin America and East Asia with special emphasis on Chile, demonstrating how domestic transformation has affected the Asia-Pacific policies of Latin American countries. The main conclusion is that while in most countries domestic conflicts over the future course of political and economic development have hampered the creation of a consistent Asia-Pacific policy, the elite settlement in Chile has enabled strategic actors to create a policy network which provides the institutional basis for successfully diversifying external relations to East Asia.
A technique for collection of nematodes from the alimentary tract of sheep
Authors: Hamilton FJ
Published: November 2004

An apparatus and technique are described for the separation, collection, and cleansing of nematodes from the alimentary tract of sheep. Large quantities of worms have been collected in satisfactory condition, and relatively quickly, to provide material for biochemical and immunological studies, and for worm counts.
Differential effects of certain phenoxyacetic acid compounds and phenylcarbamates on plant species. II. Effects of foliage applications with special reference to yields of wheat
Authors: Moore RM
Published: November 2004

The effects of foliage sprays of various phenoxyacetic acid derivatives and of isopropyl n-phenylcarbamate on a dicotyledon, Phaseolus vulgaris, were compared. The carbamate was without effect and although all phenoxyacetic acid compounds were markedly toxic, they differed in the rapidity of their action. Wheat (Triticum vulgare) exhibited differential responses to phenoxyacetic acid compounds and to isopropyl phenylcarbaniate at different growth stages. Applications of four phenoxyacetic acid compounds to wheat at different stages of development, from late seedling to flowering, showed that grain yields were reduced most markedly by applications in the seedling stage; the butyl ester and amine salt of 2,4-dichlorophenoxyacetic acid were more toxic than the sodium salt.
0.1 per cent. foliage sprays of isopropyl phenylcarbamate had no effect on wheat in the late seedling or tillering stages, but severely depressed the yield of grain when applied at flowering. Barley (Hordeum vulgare) responded similarly. Higher concentrations applied to wheat at pre-shooting also reduced grain yields.
Flax (Linum sitatissimum), although susceptible to pre-emergence treatment, was not affected by foliage sprays of isopropyl phenylcarbamate at any growth-stage. 0.1 per cent. applications of 2,4-dichlorophenoxyacetic acid as the sodium salt reduced flax yields only when applied at the seedling stage.
Insectary tests with insecticides to protect sheep against body strike
Authors: Waterhouse DF , Scott MT
Published: November 2004

Areas on the backs of sheep were sprayed with several insecticides and a comparison was made of the degree and length of protection thus provided against oviposition, and in one experiment against strike, by Lucilia cuprina when the sheep were exposed to a dense population of flies in an insectary. Indole plugs were tied into the fleece to provide conditions suitable for oviposition. Under these conditions, DDT gave better protection than other insecticides. In 2 per cent. concentration it gave excellent protection for 6-8 weeks; in 1 per cent. concentration the protective period was shorter, although valuable protection was still given. A noticeable feature of the DDT treatments was their long partial protection after some oviposition was permitted, an effect which was not as marked with other insecticides. Crude BHC preparations gave valuable protection when applied at 0.3 per cent. gamma isomer. Intermittent artificial rain, amounting to 17 inches, did not affect the protection afforded by 1.0 per cent. DDT or 0.5 per cent. BHC over a 64-day period. Chlordane gave some protection, but it was less effective than DDT, and chlorinated camphene did not give useful protection. In vitro tests indicated that none of the insecticides was ovicidal. However, in larvicidal tests BHC was extremely toxic, the vapour killing larvae rapidly even when contact with the solid material was prevented. None of the other insecticides had a fumigating action, although in high concentrations they were often lethal on contact.
Studies on the nutrition of pasture plants in the south-west of Western Australia. 2. Visual symptoms of mineral deficiencies on the Dwalganup strain of Trifolium subterraneum L
Authors: Rossiter RC
Published: November 2004

The visual symptoms of several mineral deficiencies on the Dwalganup strain of subterranean clover are outlined. Phosphorus, nitrogen, and molybdenum deficiencies particularly reduce the rate of leaf production and leaf size. They may be distinguished by leaf colour-dark green in phosphorus deficiency and greenish yellow to pale yellow in nitrogen and molybdenum deficiency. Sulphur deficiency reduces the rate of leaf production after the onset of symptoms. Leaf size was not greatly affected by the degree of sulphur deficiency studied. The older leaves were uniformly lemon yellow in colour. Both potassium and zinc deficiency result in very pronounced reduction in leaf size. Potassium deficiency, in addition, shows marginal necrosis of older leaves, while with zinc deficiency leaf shape is profoundly affected. Copper deficiency particularly reduces seed production. The leaves are lighter green in colour than normal. With calcium (and manganese) deficiency, no prominent symptoms were recorded on the soils used. The advantages and limitations of diagnosis by visual symptoms are discussed.
Growth of orange shoots
Authors: Sauer MR
Published: November 2004

Growth of orange shoots in the Mildura area occurs in three flushes, initiated in July, December, and February. Most important is the July (spring) flush, which produces many more shoots than the later flushes combined and also sets the orange crop. Spring shoot growth is concluded about the end of September but leaf growth and flower development continue until the end of October. Spring leaves are smaller than those of later flushes. Leaves on flower shoots are smaller than those on vegetative growth. Spring shoots may be divided into five morphological classes, ranging from flowers with no leaves to vegetative shoots (Fig. 1). Leafy inflorescences set more fruit than leafless inflorescences and produce more new shoots. The stalks of leafless inflorescences generally do not persist for more than a few months. Most new shoots arise in near-terminal leaf axils on vegetative growth of the preceding spring or summer. Vegetative shoots tend to produce more flowering shoots than inflorescences do. Proportionately fewer flowering shoots are produced by fruiting shoots than by inflorescences which do not set fruit. The tendency of a shoot to produce new floral or vegetative shoots is apparently modified by the nature of the current shoot population. The ability of a particular shoot to produce a fruitful inflorescence is not affected by the nature of the shoot on which it arises.
Physical analysis of the fleece of sheep for biological purposes. I. Actual and apparent cross-sectional areas of a staple of fleece wool under lateral compression
Authors: Wilson LT
Published: November 2004

An investigation has been made of errors associated with calculations of the sum of the cross-sectional areas of fibres in a staple of wool from the apparent cross-sectional area of the staple when compressed in a slot. The general mechanism of the compression process has been elaborated, and the errors associated with various conditions suggested. The staple size mainly considered was about that coming from one square inch of skin. The range of mean fibre diameter was from 16 to 32 microns.
The seasonal variation in the ruminal microorganisms of grazing sheep
Authors: Moir RJ
Published: November 2004

Samples of rumen liquor were taken by stomach tube, at approximately monthly intervals for a period of 19 months, from three mature Merino wethers grazing annual pastures in a Mediterranean-type climate in Western Australia. Counts were made, on the rumen liquor samples, of the total numbers of 'free' microorganisms, of protozoa, and of the organism Oscillospira guilliermondi. Qualitative variations in the organisms present were examined by means of wet iodine preparations and the Gram stain. Marked seasonal fluctuations in the numbers of total organisms were found. Two definite levels were evident, a high level associated with the green grazing in winter, with a peak in the spring, and a low level associated with the dry grazing. The lowest mean count obtained was 32 million per cu. mm. in April 1949, and the highest was 88 million per cu. mm. in November 1948. The numbers of protozoa and of Oscillospira were found to follow a similar seasonal cycle, the former showing an extremely high spring peak. Except for minor additions during the period of green grazing, all morphological types were found to be constantly present, but the balance of the many constituent organisms changed at different times of the year. The relation of these various changes in the numbers and balance of the ruminal microorganisms to changes in the chemical composition of the grazing, particularly the protein content, is briefly discussed and the need for further investigation of the influence of dietary changes on these organisms is stressed.
The effect of the ingestion of urea on the rate of wool production by Merino sheep
Authors: Peirce AW
Published: November 2004

Urea did not increase the wool production of mature sheep when added at the rate of 15 g. daily, equivalent to 7 g. nitrogen, to a low protein ration containing a high proportion of 'fibre'. An equivalent amount of nitrogen in the form of wheat gluten, when added to a similar basal diet, however, led to increases of 35 per cent. in total wool production and 11 per cent. in fibre diameter.
The addition of 15 g. urea to a low protein ration which contained a high proportion of a readily available carbohydrate (potato starch) brought about increases of 32 per cent. in total wool production and 9 per cent. in fibre diameter. An equivalent amount of nitrogen in the form of wheat gluten, when added to a similar basal diet, led to increases of 64 per cent. in total wool production and 17 per cent. in fibre diameter.
Definition of potato virus Y strains by some solangceous species
Authors: Hutton EM , Peak JW
Published: November 2004

By their differing reactions, Lycium halimifolium, L. rhombifolium, Physalis floridana, and Capsicum annuum distinguished between four strains of potato virus Y, P. floriduna giving the best differentiation. The avirulent strain produced no symptoms in L. rhombifolium and P. floridana, and virus development was restricted in P. floridana. The two varieties of C. annuum were immune to virus Y except for the tolerant reaction of one to a virulent strain. Nicotiana glutinosa indicated virulence of a Y strain when inoculated concurrently with virulent X strain.
Lime and molybdenum in clover development on acid soils
Authors: Anderson AJ , Moye DV
Published: November 2004

In a study of the factors concerned in the effect of lime on subterranean clover (Trifolium subterraneum L.) on an acid soil where nodulation is defective, it has been found that responses equal to those obtained with heavy dressings of lime can be obtained by the application of molybdenum together with only 2 cwt. of lime per acre at seeding. Marked response to molybdenum was obtained only where low levels of lime were used. Where heavier dressings of lime were applied the clover grew normally and did not then require treatment with molybdenum. Where no lime was used nodulation was defective and, during the first two )ears, response to molybdenum did not occur or was very small. Nodulation subsequently improved on the unlimed soil and response to molybdenum progressively increased over the five-year period of the experiments. In the year of sowing best results were obtained where the inoculated seed was drilled with the lime. The evidence suggests that defective nodulation of subterranean clover may be expected on new land where the soil reactions are less than pH 5.0, and that soils of higher pH but with minimum values less than pH 5.5 are also suspect. The importance of treatment with adequate superphosphate in addition to lime and molybdenum in the development of subterranean clover on this acid soil is stressed. The interpretation and significance of the positive and negative lime-molybdenum interactions obtained are discussed.