bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory of dynamic barriers, activated hopping, and the glass transition in polymer melts
Authors: Schweizer Kenneth S. , Saltzman Erica J.
Published: July 2004

A statistical mechanical theory of collective dynamic barriers, slow segmental relaxation, and the glass transition of polymer melts is developed by combining, and in some aspects extending, methods of mode coupling, density functional, and activated hopping transport theories. A coarse-grained description of polymer chains is adopted and the melt is treated as a liquid of segments. The theory is built on the idea that collective density fluctuations on length scales considerably longer than the local cage scale are of primary importance in the deeply supercooled regime. The barrier hopping or segmental relaxation time is predicted to be a function primarily of a single parameter that is chemical structure, temperature, and pressure dependent. This parameter depends on the material-specific dimensionless amplitude of thermal density fluctuations (compressibility) and a reduced segmental density determined by the packing length and backbone characteristic ratio. Analytic results are derived for a crossover temperature Tc, collective barrier, and glass transition temperature Tg. The relation of these quantities to structural and thermodynamic properties of the polymer melt is established. A universal power-law scaling behavior of the relaxation time below Tc is predicted based on identification of a reduced temperature variable that quantifies the breadth of the supercooled regime. Connections between the ratio Tc/Tg, two measures of dynamic fragility, and the magnitude of the local relaxation time at Tg logically follow. Excellent agreement with experiment is found for these generic aspects, and the crucial importance of the experimentally observed near universality of the dynamic crossover time is established. Extensions of the theory to treat the full chain dynamics, heterogeneity, barrier fluctuations, and nonpolymeric thermal glass forming liquids are briefly discussed.
Theoretical calculations of infrared absorption, vibrational circular dichroism, and two-dimensional vibrational spectra of acetylproline in liquids water and chloroform
Authors: Hahn Seungsoo , Lee Hochan , Cho Minhaeng
Published: July 2004

Infrared absorption, vibrational circular dichroism, and two-dimensional infrared pump-probe and photon echo spectra of acetylproline solutions are theoretically calculated and directly compared with experiments. In order to quantitatively determine interpeptide interaction-induced amide I mode frequency shifts, high-level quantum chemistry calculations were performed. The solvatochromic amide I mode frequency shift and fluctuation were taken into account by carrying out molecular dynamics simulations of acetylproline dissolved in liquids water and chloroform and by using the extrapolation method developed recently. We first studied correlation time scales of the two amide I vibrational frequency fluctuations, cross correlation between the two fluctuating local mode frequencies, ensemble averaged conformations of the acetylproline molecule in liquids water and chloroform. The corresponding conformations of the acetylproline in liquids water and chloroform are close to the ideal 310 helix and the C7 structure, respectively. A few methods proposed to determine the angle between the two transition dipoles associated with the amide I vibrations were tested and their limitations are discussed.
Electric-field driven director oscillations in a nematic liquid crystal: A NMR investigation
Authors: Luckhurst G. R. , Miyamoto T. , Sugimura A. , Timimi B. A. , Zimmermann H.
Published: July 2004

We have investigated the oscillatory behavior of the nematic director for 4-pentyl-4′-cyanobiphenyl (5CB) when it is subjected to a static magnetic field and a sinusoidal electric field. In these experiments the two fields were inclined at about 50° and the frequency of the electric field was varied from several hertz to ≈1000 Hz. The director orientation was measured using time-resolved deuterium NMR spectroscopy since this has the advantage of being able to determine the state of director alignment in the sample. In fact, for all of the frequencies studied the director is found to remain uniformly aligned. Since the diamagnetic and dielectric anisotropies are both positive the director oscillates in the plane formed by the two fields. These oscillations were observed to continue for many cycles, indicating that the coherence in the director orientation was not lost during this motion. The maximum and minimum angles made by the director with the magnetic field were determined, as a function of frequency, from the NMR spectrum averaged over many thousand cycles of the oscillations. At low frequencies (several hertz) these limiting angles are essentially independent of frequency but as the frequency increases the two angles approach each other and become equal at high frequencies, typically 1000 Hz. Our results are well explained by a hydrodynamic theory in which the sinusoidal time dependence of the electric field is included in the torque-balance equation. This analysis also shows that, for a range of frequencies between the high and low limits, these NMR experiments can give dynamic as well as static information concerning the nematic phase.
Effect of solvent quality on the conformations of a model comb polymer
Authors: Sheng Yu-Jane , Cheng Kuang-Ling , Ho Chun-Chih
Published: July 2004

The effect of solvent quality on the equilibrium structure of a densely branched comb polymer is investigated based on the structure factor analyses by off-lattice Monte Carlo simulations. First, theta temperature (θ∞) must be determined to identify the solvent condition. We locate the characteristic temperature θA(N) at which the second virial coefficient vanishes and the transition temperature θR(N) at which radius of gyration Rg of the chain varies most rapidly with temperature, i.e., d2Rg/dT2|θR=0. N represents the total number of monomers of a comb. As N→∞, θA and θR coincide to a point that is identified as the true theta temperature (θ∞). The structure factors of the main chain, the side chain, and the whole polymer are calculated, respectively. It is found that at T=θ∞, the structural factors S(qRg) for the overall comb polymers match quite well with those of their Gaussian counterparts. When T<θ∞, the overall comb polymer assumes collapsed conformations, similar to a homogeneous sphere. However, the structure factor of the side chain indicates that it always remains in an expanded state regardless of the solvent condition. It is attributed to the strong interactions between side chains. The same effect leads to enhanced rigidity of the main chain in comparison to the linear chain, as clearly observed from the rescaled Kratky plot.
A computer simulation study of water drying at the interface of protein chains
Authors: Huang Qiang , Ding Shangwu , Hua Chih-Yu , Yang Hsiao-Ching , Chen Cheng-Lung
Published: July 2004

This study investigated the water drying (cavitation) in the interfacial region of two chains of a dimeric protein by nanosecond molecular dynamics simulations using explicit water representation. Separation-induced cavity of water was directly observed in the region. We evaluated the separation length scale of two chains on which the drying transition occurs, and the average number of water molecules that are expelled from the interfacial region during the transition. The obtained values can be rationalized by Kelvin equation for finite lateral size of confinement [K. Lum and A. Luzar, Phys. Rev. E 56, R6283 (1997)]. Also, we found that the drying transition is accompanied by an exponential reduction in the average hydrogen-bond number per interfacial water molecule. The results of this study may deepen the understanding of how hydrophobic interaction drives the assembly of protein chains.
Electronic structure of crystalline copper phthalocyanine
Authors: Lozzi L. , Santucci S. , La Rosa S. , Delley B. , Picozzi S.
Published: July 2004

The electronic structure of copper-phthalocyanine (CuPc) has been studied both experimentally and theoretically. Experiments have been performed on α and β crystalline phases, using photoemission spectroscopy to probe core levels and valence band spectra. Different photon energies have been used, in order to probe different sample depths. Only minor differences have been observed in the experimental data on the two different phases, except for a small charge effect on the β phase crystal. First-principles calculations have been performed using the density functional for molecular and three-dimensional periodic solids (Dmol3) code on both the single CuPc molecule and the β phase, allowing the identification of the different atomic and angular contributions to the experimental density of states. In particular, the highest occupied molecular level is mainly due to Cu and N states. The comparison between theoretical data obtained for the CuPc in the β phase and in the single molecule shows that the interchain interaction between the molecules is negligible, whereas slightly stronger intrachain interactions occur.
Magnetic fields and uniformity of radio frequency power deposition in low-frequency inductively coupled plasmas with crossed internal oscillating currents
Authors: Tsakadze E. L. , Ostrikov K. , Tsakadze Z. L. , Vladimirov S. V. , Xu S.
Published: July 2004

Radial and axial distributions of magnetic fields in a low-frequency (∼460 kHz) inductively coupled plasma source with two internal crossed planar rf current sheets are reported. The internal antenna configuration comprises two orthogonal sets of eight alternately reconnected parallel and equidistant copper litz wires in quartz enclosures and generates three magnetic (Hz, Hr, and Hφ) and two electric (Eφ and Er) field components at the fundamental frequency. The measurements have been performed in rarefied and dense plasmas generated in the electrostatic (E) and electromagnetic (H) discharge modes using two miniature magnetic probes. It is shown that the radial uniformity and depth of the rf power deposition can be improved as compared with conventional sources of inductively coupled plasmas with external flat spiral (“pancake”) antennas. Relatively deeper rf power deposition in the plasma source results in more uniform profiles of the optical emission intensity, which indicates on the improvement of the plasma uniformity over large chamber volumes. The results of the numerical modeling of the radial magnetic field profiles are found in a reasonable agreement with the experimental data.
Room temperature operation of InAs∕AlSb quantum cascade lasers
Authors: Teissier R. , Barate D. , Vicet A. , Alibert C. , Baranov A. N. , Marcadet X. , Renard C. , Garcia M. , Sirtori C. , Revin D. , Cockburn J.
Published: July 2004

The room temperature operation of InAs∕AlSb quantum cascade lasers is reported. The structure, grown by molecular beam epitaxy on an InAs substrate, is based on a vertical transition design and a low loss n+-InAs plasmon enhanced waveguide. The lasers emitting near 4.5μm operate in pulse regime up to 300K. The threshold current density of 3.18-mm-long lasers is 1.5kA∕cm2 at 83K and 9kA∕cm2 at 300K.
Generation and detection of ultrabroadband terahertz radiation using photoconductive emitters and receivers
Authors: Shen Y. C. , Upadhya P. C. , Beere H. E. , Linfield E. H. , Davies A. G. , Gregory I. S. , Baker C. , Tribe W. R. , Evans M. J.
Published: July 2004

We report the coherent generation and detection of ultrabroadband terahertz (THz) radiation using low-temperature-grown GaAs photoconductive antennas as both emitters and receivers. THz radiation with frequency components over 15THz was obtained, the highest reported for a THz time-domain system based on photoconductive antennas. Such a system has a smooth spectral distribution between 0.3 and 7.5THz, ideal for spectroscopic applications. In addition, sharp spectral features at 8.0 and 8.8THz were observed, and explained in terms of optical phonon resonances in the photoconductive antennas.
Real-time evolution of the indium tin oxide film properties and structure during annealing in vacuum
Authors: Rogozin A. , Shevchenko N. , Vinnichenko M. , Prokert F. , Cantelli V. , Kolitsch A. , Möller W.
Published: July 2004

Indium tin oxide films produced by reactive middle frequency magnetron sputtering were annealed in a vacuum. The electrical and optical properties of the film have been studied in situ along with direct characterization of the crystalline structure. Even in the amorphous state, the film resistivity significantly decreases with increasing temperature due to a free-electron density enhancement, likely by the generation of oxygen vacancies. A rapid crystallization within the temperature range of 250–280°C leads to a further decrease of the resistivity due to Sn donor activation. The resistivity and the optical properties depend nonlinearly on the crystalline fraction.
Concentration quenching of Eu-related luminescence in Eu-doped GaN
Authors: Bang Hyungjin , Morishima Shinichi , Sawahata Junji , Seo Jongwon , Takiguchi Mikio , Tsunemi Masato , Akimoto Katsuhiro , Nomura Masaharu
Published: July 2004

The dependence of Europium (Eu)-related luminescence intensity on the Eu concentration in Eu-doped GaN was studied. This luminescence is observed at 622nm and originates from the intra-4f transition of the Eu3+ ion. The intensity of the luminescence increased with increasing Eu concentration, up to about 2at.%, and then abruptly decreased. It was found that polycrystalline growth began to be induced at Eu concentrations of more than 2at.%. In addition, clear evidence for the formation of EuN compounds was obtained by x-ray diffraction and extended x-ray absorption fine structure analysis. The cause of the concentration quenching is likely to be related to the polycrystalline growth as well as EuN formation.
Near-infrared laser emission from luminescent plastic waveguides
Authors: Kobayashi Takeyuki , Savatier Jean-Baptiste , Jordan Grace , Blau Werner J. , Suzuki Yasuhiro , Kaino Toshikuni
Published: July 2004

We have demonstrated optical gain and laser emission in multimoded plastic waveguides containing a near-infrared-emitting compound, 2-(6-(4-dimethylaminophenyl)-2,4-neopentylene-1,3,5-hexatrienyl)-3-methyl-benzothiazolium perchlorat. The poly(1-vinyl-2-pyrrolidone)-base planar waveguides, 1cm in length and 50μm in thickness, doped with 0.5wt% of the compound have exhibited lasing at 820nm under transverse nanosecond photoexcitation at 532nm. Optical feedback is provided by the 4% reflective facets of the cleaved waveguide edges. The threshold for lasing is found to be 128±30μJ∕cm2 (25.5±5.9kW∕cm2). Gain spectroscopy has shown a moderate net modal gain of 2.6±0.3cm−1 (11.3±1.3dB∕cm) at 820nm for the pump fluence of 115μJ∕cm2 (23.1kW∕cm2). Our results will open the door to the study and development of compact plastic waveguide lasers and amplifiers operating in the near-infrared region.
Molecular oxygen adsorption on partially hydrogenated diamond (100) surfaces
Authors: Bobrov K. , Comtet G. , Hellner L. , Dujardin G. , Hoffman A.
Published: July 2004

Molecular oxygen has been found to be easily adsorbed on the partially hydrogenated diamond C(100)-(2×1):H surfaces, whereas the clean and fully hydrogenated C(100) surfaces are completely inert to molecular oxygen. The partially hydrogenated diamond C(100)-(2×1) surfaces have been prepared by (i) in situ hydrogen photodesorption from the fully hydrogenated surface and (ii) in situ hydrogen adsorption on the clean surface. The surface reactivity has been monitored through the changes of the valence band photoemission spectra upon molecular oxygen exposure. These results suggest that oxygen adsorption occurs on the isolated carbon dangling bonds produced, on partially hydrogenated surfaces, from the breaking of the π-bonding of paired dangling bonds.
Particle size scaling of the giant electrorheological effect
Authors: Wen Weijia , Huang Xianxiang , Sheng Ping
Published: July 2004

This letter shows that by decreasing the size of the barium titanyl oxalate nanoparticles coated with urea, achieved through Rb doping, the giant electrorheological (GER) effect can attain a yield stress of >250kPa. The shear thinning effect observed in parallel-plate sandwich configuration is also reported, and attributed to the centrifugal sedimentation effect of the inhomogeneous structures induced by applied electric field. In addition, it is found from experiments that the ER effect is very sensitive to the solid particles volume fraction.
Targeted Disruption of the Protein Kinase SGK3/CISK Impairs Postnatal Hair Follicle Development
Authors: McCormick James A. , Feng Yuxi , Dawson Kevin , Behne Martin J. , Yu Benjamin , Wang Jian , Wyatt Amanda W. , Henke Guido , Grahammer Florian , Mauro Theodora M. , Lang Florian , Pearce David
Published: July 2004

Members of the serum- and glucocorticoid-regulated kinase (SGK) family are important mediators of growth factor and hormone signaling that, like their close relatives in the Akt family, are regulated by lipid products of phosphatidylinositol-3-kinase. SGK3 has been implicated in the control of cell survival and regulation of ion channel activity in cultured cells. To begin to dissect the in vivo functions of SGK3, we generated and characterized Sgk3 null mice. These mice are viable and fertile, and in contrast to mice lacking SGK1 or Akt2, respectively, display normal sodium handling and glucose tolerance. However, although normal at birth, by postpartum day 4 they have begun to display an unexpected defect in hair follicle morphogenesis. The abnormality in hair follicle development is preceded by a defect in proliferation and nuclear accumulation of β-catenin in hair bulb keratinocytes. Furthermore, in cultured keratinocytes, heterologous expression of SGK3 potently modulates activation of β-catenin/Lef-1–mediated gene transcription. These data establish a role for SGK3 in normal postnatal hair follicle development, possibly involving effects on β-catenin/Lef-1–mediated gene transcription.
The Royal Society and the Tartar lamb
Authors: Appleby John H.
Published: July 2004

The Tartar, Scythian or vegetable lamb— zoophyte, or creature on the borderline
between an animal and a plant— was a subject of interest to the Royal Society for many years. For convenience, the material connected with it has been arranged under three main headings on a broadly chronological basis.
The patent literature of Nobel Laureate Dennis Gabor (1900-1979)
Authors: Tanner P.G. , Allibone T.E.
Published: July 2004

In the Royal Society's biographical memoir of Dennis Gabor, F.R.S., only a brief reference was made to Gabor's numerous patents, as when it was written there had been insufficient time to study all of them in the Patent Office. However, an opportunity to collect all the patents and review them was presented when three US students from Worcester Polytechnic Institute, Worcester, Massachusetts, visited City University in 1988 to undertake their ‘Interactive Qualifying Project’ as part of their degrees and were given by one of the authors the task of studying Gabor's patents. They listed 16 German, 31 Canadian, 62 British and 63 US patents. It was not possible in the time available to get the German patents translated, copies of the Canadian patents were not readily available in London, and 60 per cent of the US patents mostly duplicated the British ones. However, the full titles and filing dates of all 172 patents were recorded, and abstracts of the British and US patents were written. The whole was woven into a brief life of Gabor. A copy of the students' report is lodged with the Gabor Archive at Imperial College, London. This review of Gabor's patents makes full use of the students' work; the list of patents, filing dates, etc., are copied with only small changes, and use has been made of some of the abstracts.
Environmental and social influences on emerging infectious diseases: past, present and future
Authors: McMichael A. J.
Published: July 2004

During the processes of human population dispersal around the world over the past 50 000–100 000 years, along with associated cultural evolution and inter–population contact and conflict, there have been several major transitions in the relationships ofHomo sapienswith the natural world, animate and inanimate. Each of these transitions has resulted in the emergence of new or unfamiliar infectious diseases.

The three great historical transitions since the initial advent of agriculture and livestock herding, fromca. 10 000 years ago, occurred when: (i) early agrarian–based settlements enabled sylvatic enzootic microbes to make contact withHomo sapiens; (ii) early Eurasian civilizations (such as the Greek and Roman empires, China and south Asia) came into military and commercial contact,ca. 3000–2000 years ago, swapping their dominant infections; and (iii) European expansionism, over the past five centuries, caused the transoceanic spread of often lethal infectious diseases. This latter transition is best known in relation to the conquest of the Americas by Spanishconquistadores, when the inadvertent spread of measles, smallpox and influenza devastated the Amerindian populations.

Today, we are living through the fourth of these great transitional periods. The contemporary spread and increased lability of various infectious diseases, new and old, reflect the combined and increasingly widespread impacts of demographic, environmental, behavioural, technological and other rapid changes in human ecology. Modern clinical medicine has, via blood transfusion, organ transplantation, and the use of hypodermic syringes, created new opportunities for microbes. These have contributed to the rising iatrogenic problems of hepatitis C, HIV/AIDS and several other viral infections. Meanwhile, the injudicious use of antibiotics has been a rare instance of human action actually increasing ‘biodiversity’.

Another aspect of this fourth transition is that modern hyper–hygienic living restricts microbial exposure in early life. This, in the 1950s, may have contributed to an epidemic of more serious, disabling, poliomyelitis, affecting older children than those affected in earlier, more endemic decades.

As with previous human–microbe transitions, a new equilibrial state may lie ahead. However, it certainly will not entail a world free of infectious diseases. Any mature, sustainable, human ecology must come to terms with both the need for, and the needs of, the microbial species that help to make up the interdependent system of life on Earth. Humans and microbes are not ‘at war’; rather, both parties are engaged in amoral, self–interested, coevolutionary struggle. We need to understand better, and therefore anticipate, the dynamics of that process.
What have we learnt from SARS?
Authors: Weiss Robin A. , McLean Angela R.
Published: July 2004

With outbreaks of infectious disease emerging from animal sources, we have learnt to expect the unexpected. We were, and are, expecting a new influenza A pandemic, but no one predicted the emergence of an unknown coronavirus (CoV) as a deadly human pathogen. Thanks to the preparedness of the international network of influenza researchers and laboratories, the cause of severe acute respiratory syndrome (SARS) was rapidly identified, but there is no complacency over the global or local management of the epidemic in terms of public health logistics. The human population was lucky that only a small proportion of infected persons proved to be highly infectious to others, and that they did not become so before they felt ill. These were the features that helped to make the outbreak containable. The next outbreak of another kind of transmissible disease may well be quite different.
The aetiology of SARS: Koch's postulates fulfilled
Authors: Osterhaus A. D. M. E. , Fouchier R. A. M. , Kuiken T.
Published: July 2004

Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS–CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (
Macaca fascicularis
). SARS–CoV–infected macaques developed a disease comparable to SARS in humans; the virus was re–isolated from these animals and they developed SARS–CoV–specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS–CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS–CoV were also developed. These animal models allow comparative pathogenesis studies for SARS–CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon–α, a drug approved for human use, limits SARS–CoV replication and lung damage in experimentally infected macaques.

Finally, we argue that, given the worldwide nature of the socio–economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.
Animal origins of SARS coronavirus: possible links with the international trade in small carnivores
Authors: Bell Diana , Roberton Scott , Hunter Paul R.
Published: July 2004

The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long–term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.
Dispersion of flightless adults of the Asian lady beetle, Harmonia axyridis, in greenhouses containing cucumbers infested with the aphid Aphis gossypii: effect of the presence of conspecific larvae
Authors: Gil Lionel , Ferran André , Gambier Jacques , Pichat Sandrine , Boll Roger , Salles Michelle
Published: July 2004

Most females of the Asian lady beetle, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), stop laying eggs if conspecific larvae are present. We studied the effect of this inhibition on the dispersion of this insect in a greenhouse containing cucumbers uniformly infested with the aphid Aphis gossypii Glover (Homoptera: Aphididae). In the absence of conspecific larvae, the adults moved around at random, sinuously, and independently. They spent most of their time walking on the ground and only a little time on the aphid‐infested plants. When the cucumber plants in one half of the greenhouse had conspecific larvae on them, the whole adult population migrated to the larva‐free half of the greenhouse. Consequently, most eggs were laid in that part of the greenhouse which was devoid of larvae. The consequences of this spatio‐temporal interaction between larvae and adults for the biological control of aphids is discussed.
Male‐killing Wolbachia in the butterfly Hypolimnas bolina
Authors: Mitsuhashi Wataru , Fukuda Haruo , Nicho Kazunari , Murakami Ritsuko
Published: July 2004

Some lines of the butterfly Hypolimnas bolina L. (Lepidoptera: Nymphalidae) are characterized by their female‐biased sex ratio. In these lines, most males die before reaching the middle larval stage. However, the cause of the bias remains unclear. We detected the proteobacterium Wolbachia in all individuals in the female‐biased butterfly lines and in some of the lines with a normal sex ratio. Tetracycline treatment of adult females of a female‐biased line led to a significant increase in both the hatch rate of their eggs (F1) and the male‐to‐female ratio of F1 pupae. In addition, certain assays of tetracycline treatment on mother butterflies significantly increased the male to female ratio of F1 adults. Known bacterial sex ratio distorters other than Wolbachia were not detected by diagnostic PCR assay, nor by the sequencing of 16S rDNA amplified using general prokaryotic 16S rDNA primers. These results strongly suggest that the distortion of the sex ratio is due to the killing of males by the inherited Wolbachia. Sequences of the 16S rDNA amplified using Wolbachia‐specific primers, the cell division protein gene (ftsZ), the molecular chaperone groE genes (groE operon), and the Wolbachia surface protein gene (wsp) from Wolbachia in lines belonging to three subspecies of the butterfly (bolina, jacintha, and philippensis) revealed no variation among lines nor between female‐biased lines and a normal one.
Combining genetic engineering and traditional breeding to provide elevated resistance in potatoes to Colorado potato beetle
Authors: Cooper Susannah G. , Douches David S. , Grafius Edward J.
Published: July 2004

The sustainable deployment of resistant crop varieties is a critical issue for the implementation of biotechnology in crop pest management. Feeding, biomass accumulation, and mortality were evaluated for susceptible, insecticide‐resistant, andBacillus thuringiensis(Bt) Cry 3A‐selected Colorado potato beetle (Leptinotarsa decemlineataSay) (Coleoptera, Chrysomelidae) larvae fed on: cultivated potato, aSolanum chacoenseline expressing leptine glycoalkaloids, a transformed line expressing Bt toxin, or the leptine line transformed to express Bt toxin. Larvae selected for resistance to Bt‐Cry3A performed better on Bt foliage, but not as well on the leptine foliage, compared to susceptible or insecticide‐resistant larvae. Neither leptine nor Bt toxin completely inhibited the feeding and growth of 3rd and 4th instars of all three strains of Colorado potato beetle. However, for all three strains of Colorado potato beetle on leptine + Bt foliage, feeding was almost zero, growth was zero or negative, and mortality was near 100%.
Determinants of Sovereign Eurobonds Yield Spread
Authors: Amira Khaled
Published: July 2004

We examine the determinants of sovereign Eurobond spread at issuance covering 1991–2000. The results of the regression models showed that yield spread increases with maturity, issue size and gross fees and decreases with credit rating and the number of managers. Higher‐grade issuers also pay a relatively higher spread to borrow long‐term funds and for smaller issues. The findings are consistent with the notion of a term structure ‘liquidity premium.’ Low‐grade issuers pay a higher spread than better‐rated countries. However, low‐grade countries pay high spread for larger funds. Credit rating is found to provide additional information in explaining the spread on sovereign Eurobonds beyond that provided by macroeconomic variables.
Labour Supply and the Risk of Divorce: An Analysis of Australian Data
Authors: Austen Siobhan
Published: July 2004

This article examines the possible consequences of rising divorce risks for the pattern of married women's labour supply in the Australian labour market. An extension of Becker's (1965) model of time allocation is used to inform an empirical analysis of this issue based on the 1997 Negotiating the Life Course Survey data. The empirical analysis in the article features a model that controls for the possibility of an endogenous relationship between women's involvement in paid work and the risk of divorce. Results show a significant positive relationship between the risk of divorce and the probability that a woman will be involved in full‐time work.
CGRP Receptors
Authors: Cutrer F. Michael
Published: July 2004

Neuronal Expression and Regulation of CGRP Promoter Activity Following Viral Gene Transfer into Cultured Trigeminal Ganglia Neurons

We examined the regulation of calcitonin gene‐related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta‐galactosidase reporter gene (AdCGRP‐lacZ) yielded expression in about 50% of the CGRP‐expressing neurons. The CGRP‐lacZ reporter gene was preferentially expressed in neurons, with 91% co‐expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV‐lacZ reporter was predominantly expressed in non‐neuronal cells, with only 29% co‐expression with CGRP. We then asked whether the CGRP promoter in the viral vector could be regulated by serotonin receptor type 1 (5‐HT(1)) agonists. Promoter activity was decreased two‐ to threefold by treatment with five 5‐HT(1B/D) agonists, including the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for migraine treatment. As controls, CMV promoter activity was not affected, and 5‐HT(1B/D) receptor antagonists blocked the repression caused by sumatriptan and eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis.
Nitric Oxide
Authors: Cutrer F. Michael
Published: July 2004

Nuclear Factor‐kappaB as a Molecular Target for Migraine Therapy

Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in immune and inflammatory responses in many tissues. The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, a NO donor as well, also increases iNOS expression. Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. We show that intravenous GTN increases NO production within macrophages. L‐N(6)‐(1‐iminoethyl)lysine, a selective iNOS inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic activity to delayed NO production. iNOS expression is preceded by significant nuclear factor kappa B (NF‐kappaB) activity, as reflected by a reduction in the inhibitory protein‐kappa‐B‐alpha (IkappaBalpha) and activation of NF‐kappaB after GTN infusion. I‐kappa‐B‐alpha degradation, NF‐kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti‐inflammatory drug used for migraine treatment. These findings suggest that GTN promotes NF‐kappaB activity and inflammation with a time course consistent with migraine attacks in susceptible individuals. We conclude, based on results with this animal model, that blockade of NF‐kappaB activity provides a novel transcriptional target for the development of anti‐migraine drugs.

Effects of the Nitric Oxide Donor, DEA/NO on Cortical Spreading Depression

Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nomega‐nitro‐L‐arginine methyl ester (L‐NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2‐(N,N‐diethylamino)‐diazenolate‐2‐oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid‐base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 microM) had little effect on CSD by itself, but it reversed in a concentration‐dependent manner the effects of NOS inhibition by 1 mM L‐NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for the subsequent, rapid recovery of cellular ionic homeostasis. In this case, the molecular targets for NO may be located either on brain cells to suppress mechanisms directly involved in CSD genesis, or on local blood vessels to couple flow to the increased energy demand associated with CSD.
5‐HT1F
Authors: Cutrer F. Michael
Published: July 2004

Possible Antimigraine Mechanisms of Action of the 5HT1F Receptor Agonist LY334370

This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(−5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg‐1, i.v.) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg‐1, i.v.) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg per kg, i.v.), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second‐order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetized rats at 3 mg per kg, i.v. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.

Novel Potent 5‐HT(1F) Receptor Agonists: Structure‐Activity Studies of a Series of Substituted N‐[3‐(1‐methyl‐4‐piperidinyl)‐1H‐pyrrolo[3,2‐b]pyridin‐5‐yl]amides

Compound 1a (LY334370), a selective 5‐HT(1F) receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clinical efficacy for the acute treatment of migraine. Although 1a was greater than 100‐fold selective over both the 5‐HT(1B) and 5‐HT(1D) receptors, it exhibited appreciable 5‐HT(1A) receptor affinity. Described here is the synthesis and evaluation of a series of pyrrolo[2,3‐c]pyridine and pyrrolo[3,2‐b]pyridine (2a and 3a) as well as pyrrolo[3,2‐d]pyrimidine (4a) analogues of 1a, compounds prepared in an effort to identify SSOFRAs with improved selectivity over other 5‐HT(1) receptor subtypes. The pyrrolo[3,2‐b]pyridine analogue 3a showed high 5‐HT(1F) receptor affinity but offered no improvement in selectivity compared to 1a. However, the C‐5 acetamide derivative, 3b, was greater than 100‐fold selective over the 5‐HT(1A), 5‐HT(1B), and 5‐HT(1D) receptors. SAR studies of this series determined that alkylamides in particular exhibited high selectivity for the 5‐HT(1F) receptor. Replacement at C‐5 with other substituents decreased affinity or selectivity. These SAR studies identified SSOFRAs that demonstrated oral activity in the neurogenic plasma protein extravasation model, a model indicative of antimigraine activity.
CGRP Receptor Antagonists
Authors: Bigal Marcelo E.
Published: July 2004

Calcitonin Gene‐Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine

BACKGROUND: Calcitonin gene‐related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP‐receptor antagonist might be effective in the treatment of migraine attacks.

METHODS: In an international, multicenter, double‐blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP‐receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group‐sequential adaptive treatment‐assignment design was used to minimize the number of patients exposed.

RESULTS: The 2.5‐mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P = 0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain‐free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5‐mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events.

CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.
5‐HTIF Receptor Agonist
Authors: Bigal Marcelo E.
Published: July 2004

Selective Seratonin 1F (5‐HT(1F)) Receptor Agonist LY334370 for Acute Migraine: A Randomised Controlled Trial

BACKGROUND: Triptans (5‐HT(1B/1D) receptor agonists) are effective drugs for acute migraine, but the side‐effect of coronary vasoconstriction restricts their use in patients who are at risk of coronary artery disease. We have studied the efficacy of LY334370, a selective serotonin 1F (5‐HT(1F)) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine relief.

METHODS: We gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients with moderate or severe migraine headaches in a double blind, parallel group study. We measured efficacy by sustained response, response at 2 h, pain free at 2 h, and sustained pain free.

RESULTS: The proportions of patients with defined endpoints for placebo and LY334370 20, 60, and 200 mg, respectively, were: sustained response, two of 26 (8%), three of 22 (14%), 11 of 30 (37%), and 11 of 21 (52%) (dose response p < 0.001); response, five of 26 (19%), four of 22 (18%), 15 of 30 (50%), and 15 of 21 (71%) (p < 0.001); pain free, one of 26 (4%), none of 22, eight of 30 (27%), and eight of 21 (38%) (p = 0.001); sustained pain free, one of 26 (4%), none of 22, seven of 30 (23%), and seven of 21 (33%) (p = 0.002); recurrence rates, one of five (20%), none of four, four of 15 (27%), and three of 15 (20%). More patients given LY334370 than placebo reported asthenia, somnolence, and dizziness.

CONCLUSION: Our findings show that LY334370 is effective in treatment of acute migraine through selective trigeminovascular neuronal inhibition.
NOS Inhibition
Authors: Bigal Marcelo E.
Published: July 2004

A Dose‐Response Study of Nitric Oxide Synthase Inhibition in Different Vascular Beds in Man

BACKGROUND: Nitric oxide (NO) is an almost ubiquitous messenger molecule and is implicated in several disorders. NG monomethyl L‐arginine (L‐NMMA:546C88) is an inhibitor of all three NO synthases (NOS), the enzymes that catalyse the production of NO. The present study was performed to evaluate the dose‐response relation of L‐NMMA to improve the design and interpretation of studies in migraine sufferers and other diseases.

METHODS: In a double‐blind, placebo‐controlled, cross‐over design, six healthy volunteers were randomised to receive three different doses of L‐NMMA (0.3 mg/kg, 1 mg/kg, 3 mg/kg) or placebo (5% dextrose) intravenously (iv) over 5 min on four different days. On a fifth study day, in an open design, the same subjects received L‐NMMA in the dose 6 mg/kg iv over 15 min. The effect of L‐NMMA on the maximal mean blood velocity (Vmean) in the middle cerebral artery (MCA) (transcranial Doppler), the luminal diameter of the radial artery (high‐frequency ultrasound), mean arterial blood pressure (MAP), heart rate and electrocardiogram were repeatedly followed every 5 min until 60 min after start of the infusion, then every 15 min during the following hour, and at 3 h and 4 h.

RESULTS: Inhibition of NOS had no effect on Vmean in MCA or on the diameter of the radial artery, but MAP increased and heart rate decreased dose dependently. With a dose of 6‐mg/kg L‐NMMA infused over a 15‐min period, the maximum MAP increase was 20% 20 min after the start of L‐NMMA infusion. The maximum decrease of heart rate was 24% 15 min after start of the L‐NMMA infusion.

CONCLUSION: L‐NMMA in a dose that caused marked changes in systemic blood pressure and heart rate had no effect on cerebral and radial arteries in man.
GABAA Receptors
Authors: Bigal Marcelo E.
Published: July 2004

GABA Receptors Modulate Trigeminovascular Nociceptive Neurotransmission in the Trigeminocervical Complex

METHODS: GABA (gamma‐aminobutyric acid) receptors involved in craniovascular nociceptive pathways were characterised by in vivo microiontophoresis of GABA receptor agonists and antagonists onto neurones in the trigeminocervical complex of the cat. Extracellular recordings were made from neurons in the trigeminocervical complex activated by supramaximal electrical stimulation of superior sagittal sinus, which were subsequently stimulated with L‐glutamate.

RESULTS: Cell firing evoked by microiontophoretic application of L‐glutamate (n = 30) was reversibly inhibited by GABA in every cell tested (n = 19), the GABA(A) agonist muscimol (n = 10) in all cells tested, or both where tested, but not by iontophoresis of either sodium or chloride ions at comparable ejection currents. Inhibited cells received wide dynamic range (WDR) or nociceptive specific input from cutaneous receptive fields on the face or forepaws. The inhibition of trigeminal neurons by GABA or muscimol could be antagonized by the GABA(A) antagonist N‐methylbicuculline, 1(S), 9(R) in all but two cells tested (n = 16), but not by the GABA(B) antagonist 2‐hydroxysaclofen (n = 11). 5. R(‐)‐baclofen, a GABA(B) agonist, inhibited the firing of three out of seven cells activated by L‐glutamate. Where tested, this inhibition could be antagonized by 2‐hydroxysaclofen. These baclofen‐inhibited cells were characterized as having low threshold mechanoreceptor/WDR input.

CONCLUSION: GABA thus appears to modulate nociceptive input to the trigeminocervical complex mainly through GABA(A) receptors. GABA(A) receptors may therefore provide a target for the development of new therapeutic agents for primary headache disorders.
Basic Science: Prejunctional and Presynaptic Trigeminovascular Targets: What Preclinical Evidence Is There?
Authors: Goadsby Peter J.
Published: July 2004

Inhibition of trigeminovascular nociceptive traffic by a prejunctional/presynaptic mechanism is an attractive approach for the treatment of migraine. It has been shown that blocking the presumed postsynaptic actions of calcitonin gene‐related peptide (CGRP) is an effective acute antimigraine strategy, so that blockade of CGRP release by presynaptic inhibition also seems promising. A number of targets are reviewed including serotonin 5‐HT1F and 5‐HT1D receptor agonists, adenosine A1 receptor agonists, nociceptin, and vanilloid VR1 receptors. For each, the preclinical rationale for their involvement in prejunctional/presynaptic mechanisms is reviewed. Development of one or more such compounds offers the exciting prospect of new nonvasoconstrictor treatments for migraine and cluster headache.