bluuebunny/crossref_metadata_2025 huggingface dataset:
Beam plasma electromagnetic instabilities in a smooth density gradient: Application to the fast ignition scenario
Authors: Bret A. , Deutsch C.
Published: October 2005

The integrated growth rate of various relativistic beam∕plasma instabilities in a weakly varying plasma density gradient is calculated using a WKB-like approximation. It is proven that such an assumption can be made in fast ignition scenario conditions. The formalism is applied to the two-stream, the filamentation, and the two-stream∕filamentation instabilities, the latter instability being a mixture of the former two, and is the fastest growing one. The results are restricted to collisionless plasmas and nonrelativistic beam and plasma temperatures. Filamentation instability is reduced by the density gradient and eventually does not develop in the core, whereas two-stream and two-stream∕filamentation instabilities should saturate even before they feel the gradient. Various effects connected to the density gradient are discussed. It is found they should be negligible as long as these later instabilities remain in their respective linear regime.
Enhanced grain surface effect on the temperature-dependent behavior of spin-polarized tunneling magnetoresistance of nanometric manganites
Authors: Dey P. , Nath T. K.
Published: October 2005

We have investigated the effects of nanometric grain size on magnetoresistance (MR), especially on its temperature-dependent behaviors of single-phase nanocrystalline granular La0.7Sr0.3MnO3 and La0.7Ca0.3MnO3 samples with an average grain size in the nanometric regime (12 and 17 nm). Most interestingly, we observed that the magnitude of low-field MR, arising from spin-polarized tunneling of conduction electrons, as well as of high-field MR remains constant up to a sufficiently high temperature (∼200K), and then drops sharply with temperature. With the application of a magnetic field, strong freezing of surface spins occur at the defect sites (having strong pinning strength of spins) of disordered grains surface as a consequence of competitive interactions between grain-boundary pinning strength (k) and magnetic field. Thermal energy (kBT), up to a considerably high temperature, remains unable to flip them from their strained condition, resulting in such a temperature insensitive behavior of MR as well as of surface spin susceptibility (χb).
Three-dimensional observation system for pellet ablation traveling in the high-temperature plasmas
Authors: Sakamoto Ryuichi , Yamada Hiroshi
Published: October 2005

In order to investigate the ablation of a solid hydrogen pellet, which is injected into a high-temperature plasma with high speed (∼1km∕s) for the plasma refueling, a three-dimensional observation system using a fast camera has been developed. A stereo method has been employed to obtain the three-dimensional information of the pellet ablation. A pair of the stereo images, which have been taken from different locations, has been focused onto a single fast camera by using a bifurcated fiber scope to ensure the simultaneity of both images. The projection matrix, which is used for stereo reconstruction, is calibrated by taking images of a model plane of known coordinates from the actual camera positions. The measuring error of the stereo observation is within 2% in the depth direction.
Large-sized tubular graphite cones with nanotube tips
Authors: Shang N. G. , Jiang X.
Published: October 2005

Tubular graphite cones (TGCs) have been grown on planar steel substrates by microwave plasma-assisted chemical vapor deposition with a high concentration of methane and at a high substrate temperature. The largest TGCs can reach 110μm in length and 10μm in diameter at the root. Unique TGCs terminated in long extruding carbon nanotube tips are realized. Scanning micro-Raman spectroscopy of individual TGCs shows a high crystallinity of the tips and more disordered structure of the roots. A possible growth mechanism of TGCs is presented.
Growth of light-emitting silicate nanowires on individual Au particles in self-assembled hexagonal Au particle networks
Authors: Su P. Y. , Lu M. Y. , Hu J. C. , Cheng S. L. , Chen L. J. , Liang J. M.
Published: October 2005

Hierarchical growth of silicate nanowires on individual Au particles in self-organized hexagonal Au particle networks has been achieved by appropriate control of annealing conditions in N2 ambient. Cathodoluminescence data showed that the silicate nanowires emit light with a wavelength of 415nm. The scheme to form the regular Au particle network offers an effective and economical means to produce a universal template to grow functional structures without complex lithography.
Lens-shaped all-epitaxial quantum dot microcavity
Authors: Lu D. , Ahn J. , Freisem S. , Gazula D. , Deppe D. G.
Published: October 2005

Data are presented on a new type of microcavity that uses epitaxial overgrowth to localize self-organized quantum dots in a microcavity optical mode. The all-epitaxial design eliminates free surfaces from the active material, eliminates quantum dots from the mirror and passive cavity regions, and provides a mechanically robust design with high thermal conductivity. The epitaxial overgrowth leads to a new type of lens-shaped microcavity, while the mesa confinement leads to lithographically defined placement of the quantum dots near the center of the optical mode.
Effect of martensitic transformation on magnetoelectric properties of Ni2MnGa∕PbZr0.52Ti0.48O3 composite
Authors: Zhao K. , Chen K. , Dai Y. R. , Wan J. G. , Zhu J. S.
Published: October 2005

The magnetoelectric (ME) coefficient was measured as a function of temperature, from room temperature to 100°C, in a bilayer composite of Ni2MnGa∕PbZr0.52Ti0.48O3. A distinct peak of the ME coefficient was observed near the martensitic transformation temperature of the Ni2MnGa alloy. The effect of martensitic transition on the ME coefficient and the multiferroic properties were discussed.
Deducing nanopore structure and growth mechanisms in porogen-templated silsesquioxane thin films
Authors: Peng Hua-Gen , Vallery Richard S. , Liu Ming , Frieze William E. , Gidley David W. , Yim Jin-Heong , Jeong Hyun-Dam , Kim Jongmin
Published: October 2005

Adjusting the functional group of a porogen is found to have a tremendous effect on the pore structre of porous low dielectric constant films with silsesquioxane as the matrix precursor. The pore size and interconnection length measured by positronium annihilation lifetime spectroscopy can be used to deduce the pore shape and its evolution with porosity from templates of isolated porogen molecules through film percolation. Inert, self-linkable, and amphiphilic porogens are demonstrated to randomly aggregate three-dimensionally, linearly polymerize, and form micelles, respectively.
Photonic crystal band edge laser array with a holographically generated square-lattice pattern
Authors: Cho Chi-O , Jeong Jaewook , Lee Joonhee , Jeon Heonsu , Kim In , Jang Dong Hoon , Park Yoon Soo , Woo Jong Chun
Published: October 2005

We fabricated a photonic band edge laser array based on a two-dimensional square-lattice photonic crystal (PC) slab waveguide using a laser holography (LH) method, instead of the commonly used electron-beam lithography (EBL). The nature of the LH process enabled high-throughput large-area fabrication of band edge lasers. Moreover, the laser performance was comparable to that of reported EBL counterparts. Careful examination of the spectral positions of the observed modes with respect to the calculated photonic band structure identified three main band edge modes as the origins of lasing: M2, X2, and M1. Owing to the gradual change in the air-hole size of the PC, the lasing modes shifted monotonically along the laser array, resulting in an M1 mode span of ∼30nm (centered at 1550nm) over a distance of 5mm.
Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea
Authors: Tocchini-Valentini Giuseppe D. , Fruscoloni Paolo , Tocchini-Valentini Glauco P.
Published: October 2005

Members of the three kingdoms of life contain tRNA genes with introns. The introns in pre-tRNAs of Bacteria are self-splicing, whereas introns in archaeal and eukaryal pre-tRNAs are removed by splicing endonucleases. We have studied the structures of the endonucleases of Archaea and the architecture of the sites recognized in their pre-tRNA substrates. Three endonuclease structures are known in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaeota. The homotetramer cleaves only the canonical bulge–helix–bulge structure in its substrates. Variants of the substrate structure, termed bulge–helix–loops, appear in the pre-tRNAs of the Crenarcheota and Nanoarcheota. These variant structures can be cleaved only by the homodimer or heterotetramer forms of the endonucleases. Thus, the structures of the endonucleases and their substrates appear to have evolved together.
Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2/alternative splicing factor
Authors: Sanford Jeremy R. , Ellis Jonathan D. , Cazalla Demian , Cáceres Javier F.
Published: October 2005

The Ser/Arg-rich (SR) proteins constitute a family of highly conserved nuclear phosphoproteins that are involved in many steps of mRNA metabolism. Previously, we demonstrated that shuttling SR proteins can associate with translating ribosomes and enhance translation of reporter mRNAs both
in vivo
and
in vitro
. Here, we show that endogenous, cytoplasmic splicing factor 2/alternative splicing factor (SF2/ASF) associated with the translation machinery is hypophosphorylated, suggesting that the phosphorylation state of the Arg-Ser-rich (RS) domain may influence the role of SF2/ASF in cytoplasmic RNA processing. In agreement, we show that mutations mimicking a hypophosphorylated RS domain strongly increased SF2/ASF binding to cytoplasmic mRNA and its activity in translation. We also demonstrate that, whereas the RS domain is not required for the function of SF2/ASF in mRNA translation
in vivo
or
in vitro
, its second RNA recognition motif (RRM)2 plays a critical role in this process. Taken together, these data suggest that RS-domain phosphorylation may influence the association of SF2/ASF with mRNA, whereas RRM2 may play an important role in mediating protein–protein interactions during translation. These data are consistent with a model whereby reversible protein phosphorylation differentially regulates the subcellular localization and activity of shuttling SR proteins.
Functional food science and gastrointestinal physiology and function
Authors: Salminen S. , Bouley C. , Boutron M.-C. , Cummings J. H. , Franck A. , Gibson G. R. , Isolauri E. , Moreau M.-C. , Roberfroid M. , Rowland I.
Published: October 2005

The gut is an obvious target for the development of functional foods, acting as it does as the interface between diet and the metabolic events which sustain life. The key processes in digestive physiology which can be regulated by modifying diet are satiety, the rate and extent of macronutrient breakdown and absorption from the small bowel, sterol metabolism, the colonic microflora, fermentation, mucosal function and bowel habit, and the gut immune system. The intestinal microflora is the main focus of many current functional foods. Probiotics are foods which contain live bacteria which are beneficial to health whilst prebiotics, such as certain non-digestible oligosaccharides which selectively stimulate the growth of bifidobacteria in the colon, are already on the market. Their claimed benefits are to alleviate lactose maldigestion, increase resistance to invasion by pathogenic species of bacteria in the gut, stimulate the immune system and possibly protect against cancer. There are very few reports of well-designed human intervention studies with prebiotics as yet. Certain probiotic species have been shown to shorten the duration of rotavirus diarrhoea in children but much more work is needed on the mechanism of immunomodulation and of competitive exclusion and microflora modification. The develop-ment of functional foods for the gut is in its infancy and will be successful only if more fundamental research is done on digestive physiology, the gut microflora, immune system and mucosal function.
Functional food science and behaviour and psychological functions
Authors: Bellisle F. , Blundell J. E. , Dye L. , Fantino M. , Fern E. , Fletcher R. J. , Lambed J. , Roberfroid M. , Specter S. , Westenhöfer J. , Westerterp-Plantenga M. S.
Published: October 2005

The impact of ingesting various foods on psychological and behavioural functions is a topic of both interest and concern to the general public. In this article, the scientific literature concerning demonstrated cause-and-effect relationships is reviewed, beginning with methodological considerations specific to the quantification of particular behaviours and psychological events. The essential function of food is to satisfy hunger and the need for essential nutrients. The contributions of macronutrients to appetite and satiety are described, as well as their impact on metabolism and energy balance. Functional properties of macronutrient substitutes (high intensity sweeteners, fat replacers) and flavour enhancers are examined in relation to their contribution to hunger, satiety, and energy balance. The effects of foods and individual nutrients on the performance of diverse psychomotor tasks are studied with consideration given to the various validated quantitative tools used to assess behaviour. The effects of food components on activation, sedation, and affective states such as dysphoria are also reviewed, with special attention given to brain function and neuroactive substances such as serotonin and the endorphins. The case of hyperactivity in children is given special emphasis with reference to the potential influence of sugar and food additives. Safety issues related to food constituents and additives are discussed. Finally, a set of criteria is proposed for the evaluation and elaboration of studies in the behavioural and psychological fields, along with suggestions for future research.
Multicenter study of peroneal mononeuropathy: clinical, neurophysiologic, and quality of life assessment
Authors: Aprile Irene , Caliandro Pietro , La Torre Giuseppe , Tonali Pietro , Foschini Mariangela , Mondelli Mauro , Bertolini Carlo , Piazzini Diana B. , Padua Luca
Published: October 2005

Abstract  This is a multicenter study on peroneal mononeuropathy (PM), in which a multidimensional protocol was performed to evaluate (1) the predisposing factors and their occurrence; (2) the relationships between the etiological, clinical, and neurophysiologic findings; and (3) disability and quality of life (QoL) in a wide sample with PM. Clinical and neurophysiologic evaluation was performed in all patients; moreover, the group adopted validated disability and QoL measurements to obtain more comprehensive and reliable data on PM. From November 2002 to January 2004, 69 patients were enrolled consecutively in 11 Italian centers. Our data showed that PM involves men more frequently than women (male : female = 4.1:1). PM was idiopathic (16%) or due to prolonged posture (23.1%), surgery (20.3%), weight loss (14.5%), trauma (11.6%), bedridden condition (7.3%), external compression from cast (5.8%), and arthrogenic cyst at the fibula (1.4%). Unexpectedly, peroneal nerve lesions were not only due to surgical operation close to the peroneal region but were also associated with thoracic‐abdominal surgery. We observed conduction block in about 50–70% of postural and weight loss PM; in perioperative and idiopathic PM, conduction block or mixed damage was equally present; in PM due to trauma, we observed an exclusive axonal damage in about 60% of cases. Only in three cases (one postural PM, one idiopathic PM, and one weight loss PM), we observed a slowing of conduction velocity in the popliteal fossa‐fibular head segment without conduction block. The comparison between QoL in patients with PM and in healthy subjects showed a significant involvement of physical and mental aspects. With regard to disability, 68% of patients walked with difficulty. Our data show that (1) most of the cases of PM are due to an identifiable predisposing factor; (2) there is a good correlation between predisposing factors and clinical‐neurophysiologic findings; and (3) PM causes disability and deterioration of the physical and emotional aspects of QoL.
Synthesis of Vanadium Oxide Powders by Evaporative Decomposition of Solutions
Authors: Lawton Stanley A. , Theby Edward A.
Published: October 2005

Powders of the vanadium oxides V2O4, V6O13, and V2O5were produced by thermal decomposition of aqueous solutions of vanadyl sulfate hydrate in atmospheres of N2, H2mixed with N2, or air. The composition of the oxide powder was determined by the reactor temperature and gas composition. Residual sulfur concentrations in powders produced by decomposition at 740°C were less than 1 at.%, and these powders consisted of hollow, roughly spherical aggregates of particles less than 1 μm in diameter.
Modelling the human rhesus proteins: implications for structure and function
Authors: Conroy Matthew J. , Bullough Per A. , Merrick Mike , Avent Neil D.
Published: October 2005

The mammalian rhesus (Rh) proteins that carry the Rh blood group antigens of red blood cells are related to the ammonium channel (Amt) proteins found in both pro‐ and eukaryotes. However, despite their clinical importance the structure of the Rh antigens is presently unknown. We have constructed homology models of the human Rh proteins, RhD and RhAG using the structure of the Escherichia coli ammonia channel AmtB as a template, together with secondary structure predictions and the extensive available biochemical data for the Rh proteins. These models suggest that RhAG and the homologous non‐erythrocyte Rhesus glycoproteins, RhBG and RhCG, have a very similar channel architecture to AmtB. By comparison, RhD and RhCE have a different arrangement of residues, indicating that if they function as ammonia channels at all, they must do so by a different mechanism. The E. coli AmtB protein is a homotrimer and our models provoke a reassessment of the widely accepted tetrameric model of the organisation of the erythrocyte Rh complex. A critical analysis of previously published data, together with sequencing yield data, lead us to suggest that the erythrocyte Rh complex could indeed also be trimeric.
Interactive effects of elevated CO2, N deposition and climate change on extracellular enzyme activity and soil density fractionation in a California annual grassland
Authors: Henry Hugh A. L. , Juarez John D. , Field Christopher B. , Vitousek Peter M.
Published: October 2005

Elevated CO2, N deposition and climate change can alter ecosystem‐level nutrient cycling both directly and indirectly. We explored the interactive effects of these environmental changes on extracellular enzyme activity and organic matter fractionation in soils of a California annual grassland. The activities of hydrolases (polysaccharide‐degrading enzymes and phosphatase) increased significantly in response to nitrate addition, which coincided with an increase in soluble C concentrations under ambient CO2. Water addition and elevated CO2 had negative but nonadditive effects on the activities of these enzymes. In contrast, water addition resulted in an increase in the activities of lignin‐degrading enzymes (phenol oxidase and peroxidase), and a decrease in the free light fraction (FLF) of soil organic matter. Independent of treatment effects, lignin content in the FLF was negatively correlated with the quantity of FLF across all samples. Lignin concentrations were lower in the aggregate‐occluded light fraction (OLF) than the FLF, and there was no correlation between percent lignin and OLF quantity, which was consistent with the protection of soil organic matter in aggregates. Elevated CO2 decreased the quantity of OLF and increased the OLF lignin concentration, however, which is consistent with increased degradation resulting from increased turnover of soil aggregates. Overall, these results suggest that the effects of N addition on hydrolase activity are offset by the interactive effects of water addition and elevated CO2, whereas water and elevated CO2 may cause an increase in the breakdown of soil organic matter as a result of their effects on lignin‐degrading enzymes and soil aggregation, respectively.
Scenarios of freshwater fish extinctions from climate change and water withdrawal
Authors: Xenopoulos Marguerite A. , Lodge David M. , Alcamo Joseph , Märker Michael , Schulze Kerstin , Van Vuuren Detlef P.
Published: October 2005

Reductions in river discharge (water availability) like those from climate change or increased water withdrawal, reduce freshwater biodiversity. We combined two scenarios from the Intergovernmental Panel for Climate Change with a global hydrological model to build global scenarios of future losses in river discharge from climate change and increased water withdrawal. Applying these results to known relationships between fish species and discharge, we build scenarios of losses (at equilibrium) of riverine fish richness. In rivers with reduced discharge, up to 75% (quartile range 4–22%) of local fish biodiversity would be headed toward extinction by 2070 because of combined changes in climate and water consumption. Fish loss in the scenarios fell disproportionately on poor countries. Reductions in water consumption could prevent many of the extinctions in these scenarios.
Spatial analysis of growing season length control over net ecosystem exchange
Authors: Churkina Galina , Schimel David , Braswell Bobby H. , Xiao Xiangming
Published: October 2005

Using data from 28 flux measurement sites, we performed an analysis of the relationship between annual net ecosystem exchange (NEE) and the length of the carbon uptake period (CUP) (the number of days when the ecosystem is a net carbon sink). The observations suggest a linear correlation between the two quantities. The change in annual carbon exchange per day of the CUP differs significantly between deciduous and evergreen vegetation types. The sites containing vegetation with short‐lived foliage (less than 1 year) have higher carbon uptake and respiration rates than evergreen vegetation. The ratio between mean daily carbon exchange rates during carbon uptake and release periods is relatively invariant (2.73±1.08) across different vegetation types. This implies that a balance between carbon release and uptake periods exists despite different photosynthetic pathways, life forms, and leaf habits. The mean daily carbon sequestration rate for these ecosystems never exceeds the carbon emission rate by more than a factor of 3. Growing season lengths for the study sites were derived from the normalized difference vegetation index (NDVI) of advanced very‐high‐resolution radiometer and from the enhanced vegetation index (EVI) of VEGETATION SPOT‐4. NDVI and EVI were found to be closely related to the CUP, and consequently they also can be used to approximate annual carbon exchange of the ecosystems. This approach has potential for allowing extrapolation of NEE over large areas from remotely sensed data, given a certain amount of ancillary information. This method could complement the currently existing techniques for extrapolation, which rely upon modeling of the individual gross fluxes.
The conversion of the corn/soybean ecosystem to no‐till agriculture may result in a carbon sink
Authors: Bernacchi Carl J. , Hollinger Steven E. , Meyers Tilden
Published: October 2005

Mitigating or slowing an increase in atmospheric carbon dioxide concentration ([CO2]) has been the focus of international efforts, most apparent with the development of the Kyoto Protocol. Sequestration of carbon (C) in agricultural soils is being advocated as a method to assist in meeting the demands of an international C credit system. The conversion of conventionally tilled agricultural lands to no till is widely accepted as having a large‐scale sequestration potential. In this study, C flux measurements over a no‐till corn/soybean agricultural ecosystem over 6 years were coupled with estimates of C release associated with agricultural practices to assess the net biome productivity (NBP) of this no‐till ecosystem. Estimates of NBP were also calculated for the conventionally tilled corn/soybean ecosystem assuming net ecosystem exchange is C neutral. These measurements were scaled to the US as a whole to determine the sequestration potential of corn/soybean ecosystems, under current practices where 10% of agricultural land devoted to this ecosystem is no‐tilled and under a hypothetical scenario where 100% of the land is not tilled. The estimates of this analysis show that current corn/soybean agriculture in the US releases ∼7.2 Tg C annually, with no‐till sequestering ∼2.2 Tg and conventional‐till releasing ∼9.4 Tg. The complete conversion of land area to no till might result in 21.7 Tg C sequestered annually, representing a net C flux difference of ∼29 Tg C. These results demonstrate that large‐scale conversion to no‐till practices, at least for the corn/soybean ecosystem, could potentially offset ca. 2% of annual US carbon emissions.
Health economics of treating haemophilia A with inhibitors
Authors: KNIGHT C.
Published: October 2005

Summary.  Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life‐long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost‐effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.
Tailoring haemostatic treatment to patient requirements – an update on monitoring haemostatic response using thrombelastography
Authors: SØRENSEN B. , INGERSLEV J.
Published: October 2005

Summary.  Currently, there is no single haemostasis laboratory test that has the capacity to accurately illustrate the clinical effects of procoagulant or anticoagulant interventions. Although the time course of thrombin generation in plasma and the endogenous thrombin potential (ETP) may be useful coagulation parameters, clotting involves components other than thrombin (e.g. platelets, fibrinogen). The continuous coagulation profiles of thrombelastography may provide a more accurate reflection of in vivo biology, covering initiation, development and final clot strength during whole blood clot formation. This method has helped to clarify the mechanism of action of whole blood clot formation, demonstrating the differences from clotting in plasma, and the importance of platelets and tissue factor titrations. It has also been used to investigate hypocoagulation (in haemophilia A, rare coagulation disorders, anticoagulant therapy and dilutional coagulopathy), hypercoagulation and the ex vivo testing of haemostatic interventions. Thrombelastography has been shown to reflect the clinical efficacy of activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) in patients with haemophilia A with inhibitors and in patients with acquired haemophilia. Overall, tailoring laboratory assays to illustrate and correlate with clinical phenotypes is essential for effective coagulation monitoring. Applying an algorithm of preoperative, perioperative and postoperative tests, including thrombelastography, may enable physicians to achieve this.
Enhanced responsiveness to antigen contributes more to immunological memory in CD4 T cells than increases in the number of cells
Authors: Bates John T. , Pat Bucy R.
Published: October 2005

Although immunological memory is characterized by both an increase in the frequency of antigen‐specific T cells and a qualitative change in the pattern of their subsequent response, it is not clear which of these components is more significant in the overall enhanced response to secondary stimulation. To address this question for the CD4+ T‐cell response, T‐cell receptor (TCR) Tg T cells were adoptively transferred to normal syngeneic mice that were immunized with the relevant peptide. After the initial expansion of TCR Tg T cells, the size of the subsequent memory population of T cells was approximately the same as the size of the starting population, independent of the number of TCR Tg cells initially transferred. This result was not caused by redistribution of memory cells into non‐lymphoid tissues, although the relative frequency of antigen‐specific T cells in these sites was increased after immunization. The fraction of the antigen specific TCR Tg cells that responded by production of either interleukin‐2 or interferon‐γin vitro was substantially higher after immunization. Thus, the increased frequency of functionally responsive T cells was primarily caused by a higher fraction of responding T cells, rather than a substantial increase in the absolute number of antigen specific CD4+ TCR Tg T cells.
Construction and characterization of a humanized anti‐human CD3 monoclonal antibody 12F6 with effective immunoregulation functions
Authors: Li Bohua , Wang Hao , Dai Jianxin , Ji Junjie , Qian Weizhu , Zhang Dapeng , Hou Sheng , Guo Yajun
Published: October 2005

12F6 is a murine anti‐human CD3 monoclonal antibody, which competes with OKT3 for binding to human T cells and possesses more effective T‐cell suppression and activation properties compared to OKT3. It thus exhibits the potential to be developed as an immunoregulation agent for manipulating T‐cell functions and preventing acute allograft rejection. In an attempt to minimize the immunogenicity of murine 12F6 (m12F6) for potential clinical application, a humanized version of 12F6, denoted as hu12F6, was successfully constructed by complementary determining region (CDR) grafting and shown to maintain both T‐cell activation and suppression activities similar to m12F6. Furthermore, in order to reduce the first dose reaction syndrome caused by T‐cell activation following the first administration of anti‐CD3 antibodies, two amino acid mutations were introduced into the Fc region of hu12F6, resulting in the Fc‐mutated 12F6 humanized antibody (hu12F6mu). This Fc‐mutated version displayed a similar antigen‐binding affinity and specificity compared with hu12F6 and m12F6 but with much weaker FcR binding activity. hu12F6mu was shown to be much less potent in the induction of T‐cell proliferation, cytokine release (tumour necrosis factor‐α, interferon‐γ and interleukin‐10) and early activation marker expression on the cell surface (CD69 and CD25) than parental 12F6 and OKT3 did. In contrast, hu12F6mu was effective in modulating T‐cell receptor/CD3 and inhibiting mixed lymphocyte reaction with a similarity as compared to m12F6 and OKT3. In conclusion, the resultant hu12F6mu was much less mitogenic to T cells but retained potent immunosuppression, suggesting it might be an alternative to OKT3 as an immunosuppressive drug with less immunogenicity and toxicity for clinical application.
Resistance to chlamydial lung infection is dependent on major histocompatibility complex as well as non‐major histocompatibility complex determinants
Authors: Qiu Hongyu , Wang Shuhe , Yang Jie , Fan Yijun , George Joyee Antony , Han Xiaobing , Jiao Lei , Yang Xi
Published: October 2005

Our previous work has shown that C3H/HeN and C57BL/6 mice have differential susceptibility to Chlamydia trachomatis mouse pneumonitis (C. muridarum) lung infection. C3H/HeN (H‐2k) mice were found to be highly susceptible to C. muridarum infection with higher mortality and more severe morbidity compared to C57BL/6 (H‐2b) mice. To examine the role of major histocompatibility complex (MHC) genes on host resistance to chlamydial lung infection, we compared MHC congenic mice, B6.H2k [C57BL/6 background, C3H MHC (H‐2k)] and C3H.H2b [C3H/HeN background, C57BL/6 MHC (H‐2b)] and their corresponding wild type C57BL/6 mice and C3H/HeN mice, respectively, in susceptibility to C. muridarum infection. We found that B6.H2k, C3H.H2b and C3H/HeN mice are more susceptible to chlamydial lung infection compared to the wild type C57BL/6 mice by showing more serious body weight loss, higher in vivo chlamydial growth and more severe pathologic changes. Congenic B6.H2k mice showed significantly lower levels of IL‐12 and IFN‐γ production compared to C57BL/6 as well as C3H/HeN and C3H.H2b mice. One the other hand, although congenic C3H.H2b mice displayed similar cytokine response to C57BL/6 mice, they were highly susceptible to C. muridarum infection. Overall, the results suggest that protection against chlamydial lung infection is both MHC and non‐MHC gene dependent, and that the interaction between MHC and non‐MHC elements may contribute to host resistance to chlamydial infection.
Toll‐like receptor 3 agonist poly(I:C)‐induced antiviral response in human corneal epithelial cells
Authors: Kumar Ashok , Zhang Jing , Yu Fu‐Shin X.
Published: October 2005

The objective of this study was to examine the expression of Toll‐like receptor 3 (TLR3) by human corneal epithelial cells (HCECs) and to determine whether exposure to the TLR3 agonist polyinosinic‐polycytidylic acid [poly(I:C)]induces an antiviral response in these cells. Fluorescence‐activated cell sorter (FACS) analysis revealed TLR3 to be constitutively expressed and distributed intracellularly in HCECs. Stimulation of HCECs with the TLR3 agonist poly(I:C) induced the activation of nuclear factor (NF)‐κB and production of the proinflammatory cytokine interleukin (IL)‐6 and the chemokine IL‐8. Upon exposure to poly(I:C), HCECs initiated a potent antiviral response resulting in an increase of interferon (IFN)‐β mRNA expression (7‐fold). Poly(I:C) stimulation also up‐regulated mRNA expression of the antiviral chemokine IFN‐γ inducible protein 10 (IP10), myxovirus resistance gene A and 2′,5′‐oligoadenylate synthetase (5‐, 10‐ and 9‐fold, respectively), and secretion of IP10. These responses were also induced by exogenously added type 1 IFNs, but could not be blocked by pretreatment of the cells with anti‐TLR3 monoclonal antibody, suggesting that the receptor was not expressed on the cell surface. Furthermore, incubation of HCECs with an endosomal acidification inhibitor, chloroquine, markedly inhibited poly(I:C)‐mediated IFN‐β expression in HCECs. These results suggest that corneal epithelial cells are important sentinels of the corneal innate immune system against viral infection, and that stimulation of TLR3 can induce the expression of key proinflammatory cytokines and chemokines and antiviral genes that help in the defence of the cornea against viral infection.
Diagenetic signatures of stratal surfaces in the Upper Jurassic Fulmar Formation, Central North Sea, UKCS
Authors: BURNS FIONA E. , BURLEY STUART D. , GAWTHORPE ROB L. , POLLARD JOHN E.
Published: October 2005

Sedimentation rate and changes in relative sea level affect early diagenetic cementation along key stratal surfaces within the deeply buried Upper Jurassic Fulmar Formation, South Central Graben, UKCS. As a result of the bioturbated nature of the shallow marine strata, variations in ichnofabrics and cross‐cutting relationships between trace fossils are important in identifying and correlating stratal surfaces. Two transgressive and two regressive surfaces/sequence boundaries were studied, using petrographical, mineralogical and geochemical techniques. Cements, including early diagenetic pyrite framboids, grain‐rimming apatite, microcrystalline dolomite and ankerite, occur at, above and immediately below both transgressive and forced regressive surfaces/sequence boundaries. Breaks or subdued rates of sedimentation associated with both types of surfaces meant that the sediment package resided within early diagenetic zones for prolonged periods of time, enhancing diagenetic reactions at and below the surfaces. The distribution of ankerite, despite being a deep‐burial cement, was primarily controlled by concentrations of bioclasts that are particularly abundant at transgressive surfaces. The diagenetic character of the forced regressive surfaces/sequence boundaries is more complex than that of the transgressive surfaces, both in terms of mineralogy and paragenesis. This is attributed to the superimposition of diagenetic assemblages as a result of erosion, re‐sedimentation and sediment by‐passing. Although the diagenetic signature of the surfaces has been modified by dissolution/replacement reactions during deep burial, early diagenetic signatures can still be distinguished.
Genome‐wide expression profiling of the host response to root‐knot nematode infection in Arabidopsisa
Authors: Jammes Fabien , Lecomte Philippe , de Almeida‐Engler Janice , Bitton Frédérique , Martin‐Magniette Marie‐Laure , Renou Jean Pierre , Abad Pierre , Favery Bruno
Published: October 2005

During a compatible interaction, root‐knot nematodes (Meloidogyne spp.) induce the redifferentiation of root cells into multinucleate nematode feeding cells (giant cells). Hyperplasia and hypertrophy of the surrounding cells leads to the formation of a root gall. We investigated the plant response to root‐knot nematodes by carrying out a global analysis of gene expression during gall formation in Arabidopsis, using giant cell‐enriched root tissues. Among 22 089 genes monitored with the complete Arabidopsis transcriptome microarray gene‐specific tag, we identified 3373 genes that display significant differential expression between uninfected root tissues and galls at different developmental stages. Quantitative PCR analysis and the use of promoter GUS fusions confirmed the changes in mRNA levels observed in our microarray analysis. We showed that a comparable number of genes were found to be up‐ and downregulated, indicating that gene downregulation might be essential to allow proper gall formation. Moreover, many genes belonging to the same family are differently regulated in feeding cells. This genome‐wide overview of gene expression during plant–nematode interaction provides new insights into nematode feeding‐cell formation, and highlights that the suppression of plant defence is associated with nematode feeding‐site development.
Cell‐to‐cell movement of Potato Potexvirus X is dependent on suppression of RNA silencing
Authors: Bayne Elizabeth H. , Rakitina Daria V. , Morozov Sergey Y. , Baulcombe David C.
Published: October 2005

RNA silencing in transgenic and virus‐infected plants involves a mobile silencing signal that can move cell‐to‐cell and systemically through the plant. It is thought that this signal can influence long‐distance movement of viruses because protein suppressors of silencing encoded in viral genomes are required for long‐distance virus movement. However, until now, it was not known whether the mobile signal could also influence short‐range virus movement between cells. Here, through random mutation analysis of the Potato Potexvirus X (PVX) silencing suppressor P25, we provide evidence that it does. All mutants that were defective for silencing suppression were also non‐functional in viral cell‐to‐cell movement. However, we identified mutant P25 proteins that were functional as silencing suppressors but not as movement proteins and we conclude that suppression of silencing is not sufficient to allow virus movement between cells: there must be a second P25 function that is independent of silencing but also required for cell‐to‐cell movement. Consistent with this hypothesis, we identified two classes of suppressor‐inactive P25 mutants. One class of these mutants is proposed to be functional for the accessory function because their failure to support PVX movement could be complemented by heterologous suppressors of silencing. The second class of P25 mutants is considered defective for both the suppressor and second functions because the heterologous silencing suppressors did not restore virus movement. It is possible, based on analyses of short interfering RNA accumulation, that P25 suppresses silencing by interfering with either assembly or function of the effector complexes of RNA silencing.
Molecular mechanisms of constitutive activity: mutations at position 111 of the angiotensin AT1receptor
Authors: Nikiforovich G.V. , Mihalik B. , Catt K.J. , Marshall G.R.
Published: October 2005

Abstract: A possible molecular mechanism for the constitutive activity of mutants of the angiotensin type 1 receptor (AT1) at position 111 was suggested by molecular modeling. This involves a cascade of conformational changes in spatial positions of side chains along transmembrane helix (TM3) from L112 to Y113 to F117, which in turn, results in conformational changes in TM4 (residues I152 and M155) leading to the movement of TM4 as a whole. The mechanism is consistent with the available data of site‐directed mutagenesis, as well as with correct predictions of constitutive activity of mutants L112F and L112C. It was also predicted that the double mutant N111G/L112A might possess basal constitutive activity comparable with that of the N111G mutant, whereas the double mutants N111G/Y113A, N111G/F117A, and N111G/I152A would have lower levels of basal activity. Experimental studies of the above double mutants showed significant constitutive activity of N111G/L112A and N111G/F117A. The basal activity of N111G/I152A was higher than expected, and that of N111G/Y113A was not determined due to poor expression of the mutant. The proposed mechanism of constitutive activity of the AT1receptor reveals a novel nonsimplistic view on the general problem of constitutive activity, and clearly demonstrates the inherent complexity of the process of G protein‐coupled receptor (GPCR) activation.
Secondary structure analysis of synthetic peptides of the extracellular domain of the human follicle‐stimulating hormone receptor
Authors: Kene P.S. , Behere D.V. , Mahale S.D.
Published: October 2005

Abstract:  Follicle‐stimulating hormone receptor (FSHR) is a glycoprotein hormone receptor and possesses a large extracellular domain (ECD) instrumental in hormone binding. The ECD is characterized by the presence of leucine‐rich repeat (LRR) structures made up of α‐helices flanked by β‐strands. Our previous studies with the synthetic peptides corresponding to the potentially surface‐oriented regions of the ECD had led to the identification of some of these regions in either FSH‐binding or FSH‐induced cAMP production or both. This study was undertaken with an aim to correlate the findings made in vitro with the secondary structures of the respective peptides. Accordingly, all peptides were screened for their secondary structures in different biochemical environments. This study correlates the observed α‐helical signature with the previously demonstrated activity in signal generation for peptides 15–31 and 216–235 hFSHR, while FSH binding is correlated with the maintenance of β‐sheet structure in peptides 285–300 and 297–310 hFSHR as observed in vitro.
Tryptophan‐containing peptide helices: interactions involving the indole side chain*
Authors: Mahalakshmi R. , Sengupta A. , Raghothama S. , Shamala N. , Balaram P.
Published: October 2005

Abstract:  Two designed peptide sequences containing Trp residues at positions i and i + 5 (Boc‐Leu‐Trp‐Val‐Ala‐Aib‐Leu‐Trp‐Val‐OMe, 1) as well as i and i + 6 (Boc‐Leu‐Trp‐Val‐Aib‐Ala‐Aib‐Leu‐Trp‐Val‐OMe, 2) containing one and two centrally positioned Aib residues, respectively, for helix nucleation, have been shown to form stable helices in chloroform solutions. Structures derived from nuclear magnetic resonance (NMR) data reveal six and seven intramolecularly hydrogen‐bonded NH groups in peptides 1 and 2, respectively. The helical conformation of octapeptide 1 has also been established in the solid state by X‐ray diffraction. The crystal structure reveals an interesting packing motif in which helical columns are stabilized by side chain–backbone hydrogen bonding involving the indole Nɛ1H of Trp(2) as donor, and an acceptor C=O group from Leu(6) of a neighboring molecule. Helical columns also associate laterally, and strong interactions are observed between the Trp(2) and Trp(7) residues on neighboring molecules. The edge‐to‐face aromatic interactions between the indoles suggest a potential C‐H…π interaction involving the Cζ3H of Trp(2). Concentration dependence of NMR chemical shifts provides evidence for peptide association in solution involving the Trp(2) Nɛ1H protons, presumably in a manner similar to that observed in the crystal.
Development of highly potent and ective dynorphin A analogues as new medicines
Authors: Lung F.‐D.T. , Chen C.‐H. , Liu J.‐H.
Published: October 2005

Abstract:  Dynorphin A (Dyn A), a 17 amino acid peptide H‐Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐Arg‐Ile‐Arg‐Pro‐Lys‐Leu‐Lys‐Trp‐Asp‐Asn‐Gln‐OH, is a potent opioid peptide which interacts preferentially with κ‐opioid receptors. Research in the development of selective and potent opioid peptide ligands for the κ‐receptor is important in mediating analgesia. Several cyclic disulphide bridge‐containing peptide analogues of Dyn A, which were conformationally constrained in the putative message or address segment of the opioid ligand, were designed, synthesized and assayed. To further investigate the conformational and topographical requirements for the residues in positions 5 and 11 of these analogues, a systematic series of Dyn A1−11‐NH2 cyclic analogues incorporating the sulphydryl‐containing amino acids l‐ and d‐Cys and l‐ and d‐Pen in positions 5 and 11 were synthesized and assayed. Cyclic lactam peptide analogues were also synthesized and assayed. Several of these cyclic analogues, retained the same affinity and selectivity (vs. the μ‐ and δ‐receptors) as the parent Dyn A1−11‐NH2 peptide in the guinea‐pig brain (GPB), but exhibited a much lower activity in the guinea‐pig ileum (GPI), thus leading to centrally vs. peripherally selective peptides. Studies of the structure–activity relationship of Dyn A peptide provide new insights into the importance of each amino acid residue (and their configurations) in Dyn A analogues for high potency and good selectivity at κ‐opioid receptors. We report herein the progress towards the development of Dyn A peptide ligands, which can act as agonists or antagonists at cell surface receptors that modulate cell function and animal behaviour using various approaches to rational peptide ligand‐based drug design.