bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospects in NSAID-derived chemoprevention of colorectal cancer
Authors: Chell S. , Patsos H.A. , Qualtrough D. , H-Zadeh A.M. , Hicks D.J. , Kaidi A. , Witherden I.R. , Williams A.C. , Paraskeva C.
Published: August 2005

There is strong evidence for an important role for increased COX (cyclo-oxygenase)-2 expression and PG (prostaglandin) E2 production in colorectal tumorigenesis. PGE2 acts through four E-prostanoid receptors (EP1–4). COX-2 has therefore become a target for the potential chemoprevention and therapy of colorectal cancer. However, any therapeutic/preventive strategy has the potential to have an impact on physiological processes and hence result in side effects. General COX (COX-1 and -2) inhibition by traditional NSAIDs (non-steidal anti-inflammatory drugs), such as aspirin, although chemopreventive, has some side effects, as do some conventional COX-2-selective NSAIDs. As PGE2 is thought to be the major PG species responsible for promoting colorectal tumorigenesis, research is being directed to a number of protein targets downstream of COX-2 that might allow the selective inhibition of the tumour-promoting activities of PGE2, while minimizing the associated adverse events. The PGE synthases and E-prostanoid receptors (EP1–4) have therefore recently attracted considerable interest as potential novel targets for the prevention/therapy of colorectal cancer. Selective (and possibly combinatorial) inhibition of the synthesis and signalling of those PGs most highly associated with colorectal tumorigenesis may have some advantages over COX-2-selective inhibitors.
The role of the Wnt signalling pathway in colorectal tumorigenesis
Authors: Behrens J.
Published: August 2005

Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. Mutations in the tumour suppressor APC (adenomatous polyposis coli) genes occur early in the development of CRC and lead to the stabilization of the Wnt pathway component β-catenin and to the constitutive activation of Wnt signalling. Stabilizing mutations of β-catenin can also lead to its accumulation, qualifying β-catenin as a proto-oncogene. Here I will summarize the biochemical interactions occurring in Wnt signalling and describe how alterations in Wnt pathway components lead to CRC.
Relationship between the role of the adenomatous polyposis coli protein in colon cancer and its contribution to cytoskeletal regulation
Authors: Näthke I.
Published: August 2005

A unique feature of colon cancer is that truncation mutations in the APC (adenomatous polyposis coli) gene are common to most tumours. The high penetrance of APC mutations, especially in gut epithelium, supports the idea that APC may be involved in a number of the processes that govern the normal maintenance of this tissue: differentiation, migration, proliferation and apoptosis. Indeed, APC is involved in the regulation of β-catenin and it also is an important regulator of the cytoskeleton. Thus mutations in APC lead to the accumulation of β-catenin, which causes changes in differentiation, and they also produce changes in cytoskeletal organization, which results in altered cell migration and disrupted mitotic spindles. The function of APC in cytoskeletal organization is related to its effect on microtubules and F-actin. Depleting APC from cultured cells leads to changes in cytoskeletal organization. In addition, N-terminal fragments of APC, like those commonly found in tumours, compromise cell migration in Dictyostelium and in early developing chicken embryos. Consistent with the idea that such dominant effects are normally balanced by interactions within the full-length molecule, protein interactions of N-terminal fragments expressed in tumour cells can be altered by binding to C-terminal regions of APC commonly lost in tumours. This review summarizes effects of APC on the cytoskeleton and discusses how these functions of APC may contribute to its role in cancer.
A study of the horseradish peroxidase catalytic site by FTIR spectroscopy
Authors: Ingledew W.J. , Rich P.R.
Published: August 2005

Vibrational changes in the catalytic site of horseradish peroxidase were investigated by FTIR (Fourier-transform infrared) spectroscopy in the 1000–2500 cm−1 range. Difference spectra were generated by photolysis of the haemII-CO compound at different pH/pD values. The spectra report on the fine structure around the catalytic site and show vibrational changes of protein backbone, amino acid residues and cofactors. Assignments of the FTIR vibrations can be made based upon known crystal structures, comparisons with absorption frequencies and extinction coefficients of model amino acids and cofactors, effects of H2O/2H2O exchange and changes of pH/pD. Concomitant with the photolysis of the CO ligand are changes due to haem and protein vibrations, predominant among which are arginine and histidine residue vibrations.
Experimental and modeling study of the ion-molecule association reaction H3O++H2O(+M)→H5O2+(+M)
Authors: Hamon S. , Speck T. , Mitchell J. B. A. , Rowe B. , Troe J.
Published: August 2005

Experimental results for the rate of the association reaction H3O++H2O(+M)→H5O2+(+M) obtained with the Cinétique de Réactions en Ecoulement Supersonique Uniforme flow technique are reported. The reaction was studied in the bath gases M=He and N2, over the temperature range of 23–170K, and at pressures between 0.16 and 3.1mbar. At the highest temperatures, the reaction was found to be close to the limiting low-pressure termolecular range, whereas the limiting high-pressure bimolecular range was approached at the lowest temperatures. Whereas the low-pressure rate coefficients can satisfactorily be reproduced by standard unimolecular rate theory, the derived high-pressure rate coefficients in the bath gas He at the lowest temperatures are found to be markedly smaller than given by simple ion-dipole capture theory. This result differs from previous observations on the related reaction NH4++NH3(+M)→N2H7+(+M). This observation is tentatively attributed to more pronounced contributions of the valence part of the potential-energy surface to the reaction in H5O2+ than in N2H7+. Falloff curves of the reaction H3O++H2O(+M)→H5O2+(+M) are constructed over wide ranges of conditions and represented in compact analytical form.
Response functions for dimers and square-symmetric molecules in four-wave-mixing experiments with polarized light
Authors: Smith Eric Ryan , Farrow Darcie A. , Jonas David M.
Published: July 2005

Four-wave-mixing nonlinear-response functions are given for intermolecular and intramolecular vibrations of a perpendicular dimer and intramolecular vibrations of a square-symmetric molecule containing a doubly degenerate state. A two-dimensional particle-in-a-box model is used to approximate the electronic wave functions and obtain harmonic potentials for nuclear motion. Vibronic interactions due to symmetry-lowering distortions along Jahn-Teller active normal modes are discussed. Electronic dephasing due to nuclear motion along both symmetric and asymmetric normal modes is included in these response functions, but population transfer between states is not. As an illustration, these response functions are used to predict the pump-probe polarization anisotropy in the limit of impulsive excitation.
Nucleation of pores in brittle solids under load
Authors: Kukushkin Sergey A.
Published: August 2005

The microscopic mechanism of appearance and evolution of pores and cracks is proposed to investigate the process of micropore nucleation in solids under impact and fixed loadings. The size distribution function and the critical size of pores are defined. The dependencies between the rate of pore nucleation and the rate of pore accumulation in solids under loading are specified. The temperature influence on the pore appearance process is examined.
Observation of OD− by microwave spectroscopy
Authors: Cazzoli Gabriele , Puzzarini Cristina
Published: July 2005

For the first time the rotational spectrum of the molecular anion OD− has been observed by microwave spectroscopy. OD− has been produced both by a positive and negative glow discharge; by investigating the Doppler shift in both cases, the unshifted frequency of the J=1←0 rotational transition has been derived. This allowed us to improve the value of the ground-state rotational constant: B0=299264.940(90)MHz. In order to assess that a negative ion has really been observed, the cation N2H+ has been produced and investigated in the same experimental conditions.
Chromatic dispersion compensators via highly dispersive photonic crystals
Authors: Yang S. Y. , Chang C. T.
Published: July 2005

We calculated the phase index np, group index ng, and chromatic dispersion D from photonic band structures in two-dimensional (2D) photonic crystals consisting of triangular-arrayed cylindrical rods. We found that both the np and ng increase rapidly as the frequency of a propagating electromagnetic wave approaches the gap-band edges due to Bragg reflection, thus causing D to be large. The chromatic dispersion D is evaluated to be four to five orders of magnitude greater than the conventional single-mode fiber dispersion and should be useful as dispersion compensation for fiber-optic communications. In addition, the np, ng, and D of the 2D photonic crystals for E- and H-polarized waves are also examined.
Theoretical and experimental investigation of strongly localized plasmons on triangular metal wedges for subwavelength waveguiding
Authors: Pile D. F. P. , Ogawa T. , Gramotnev D. K. , Okamoto T. , Haraguchi M. , Fukui M. , Matsuo S.
Published: August 2005

We report numerical analysis and experimental observation of strongly localized plasmons guided by a triangular metal wedge. Dispersion and dissipation of such wedge plasmons are analyzed using the finite-difference time-domain algorithm. Experimental observation is conducted by the end-fire excitation and near-field detection of the predicted plasmons on a 40° silver nanowedge. Good agreement with the theoretically predicted propagation distances is demonstrated. Differences between the theoretical and experimental field distribution are explained by insufficient resolution of the near-field optical probe.
Liquid-liquid phase transitions in supercooled water studied by computer simulations of various water models
Authors: Brovchenko Ivan , Geiger Alfons , Oleinikova Alla
Published: August 2005

Liquid-liquid and liquid-vapor coexistence regions of various water models were determined by Monte Carlo (MC) simulations of isotherms of density fluctuation-restricted systems and by Gibbs ensemble MC simulations. All studied water models show multiple liquid-liquid phase transitions in the supercooled region: we observe two transitions of the TIP4P, TIP5P, and SPCE models and three transitions of the ST2 model. The location of these phase transitions with respect to the liquid-vapor coexistence curve and the glass temperature is highly sensitive to the water model and its implementation. We suggest that the apparent thermodynamic singularity of real liquid water in the supercooled region at about 228 K is caused by an approach to the spinodal of the first (lowest density) liquid-liquid phase transition. The well-known density maximum of liquid water at 277 K is related to the second liquid-liquid phase transition, which is located at positive pressures with a critical point close to the maximum. A possible order parameter and the universality class of liquid-liquid phase transitions in one-component fluids are discussed.
A molecular dynamics study of nitric oxide in water: Diffusion and structure
Authors: Zhou Zhongwu , Todd B. D. , Travis Karl P. , Sadus Richard J.
Published: August 2005

We present molecular dynamics simulations of the diffusion coefficients and structure of water-nitric oxide mixtures at ambient (298 K) and in vivo (310 K) conditions. A two-site rigid-body molecular model with partial charges and a Lennard-Jones potential on both sites is proposed for nitric oxide and used in conjunction with the extended simple point-charge model for liquid water in our simulations. The diffusion coefficients obtained from the simulations are in good agreement with experimental data. The results from intermolecular partial pair functions show that under these thermodynamic conditions, the existence of nitric oxide in liquid water has little impact on the structure of water and the tendency to form H bonds between water molecules. We also find that it is unlikely that H bonds form between the hydrogen atoms in water and either the nitrogen or the oxygen atom on the nitric oxide at the temperatures and densities examined in this study. This study suggests that in low concentrations nitric oxide molecules exist as free molecules in liquid water rather than forming complexes with water molecules.
Microwave diagnostics of small plasma objects
Authors: Shneider M. N. , Miles R. B.
Published: August 2005

We suggest an approach for using microwave radiation in collisional, weakly ionized plasma diagnostics when plasma dimensions are relatively small compared with the microwave wavelength. We show that in this case the microwave diagnostics can be based on the measurement of the radiation scattered by an oscillating plasma dipole, similar to the Rayleigh scattering of an atom in light. Examples considered show possibilities of obtaining the decaying plasma parameters (time dependence of charge density and information about loss rates, for instance) from the measured scattered signal.
Characterization of in-grown stacking faults in 4H–SiC (0001) epitaxial layers and its impacts on high-voltage Schottky barrier diodes
Authors: Fujiwara H. , Kimoto T. , Tojo T. , Matsunami H.
Published: July 2005

The density, shape and structure of in-grown stacking faults in 4H–SiC (0001) epitaxial layers have been characterized by cathodeluminescence, photoluminescence and high-resolution transmission electron microscopy. These analyses indicate that in-grown stacking faults are of 8H structure, and are generated mostly near the epilayer/substrate interface during chemical vapor deposition. The impact of the stacking faults on the performance of 4H–SiC (0001) Schottky barrier diodes has been investigated. It is revealed that the stacking faults cause the lowering of Schottky barrier height as well as the decrease of breakdown voltage.
The lower boundary of the hydrogen concentration required for enhancing oxygen diffusion and thermal donor formation in Czochralski silicon
Authors: Huang Y. L. , Ma Y. , Job R. , Fahrner W. R. , Simoen E. , Claeys C.
Published: August 2005

Hydrogen-enhanced thermal donor formation is achieved in p-type Czochralski silicon after exposure to hydrogen plasma and posthydrogenation annealing. Hydrogen diffusivities for the temperatures between 350 and 450 °C are determined based on spreading resistance probe measurement. The hydrogen diffusion is found to be trap limited. Two relationships (for different temperature ranges) are established to describe the lower boundary of the hydrogen concentration required for enhancing oxygen diffusion and thermal donor formation in silicon. The result reveals that hydrogen atoms both in free and in trapped states can enhance the oxygen diffusion.
Yoke-free magnetic system for low field studies in magnetically affected reaction yield spectroscopy
Authors: Kalneus Evgeny V. , Stass Dmitri V. , Grishin Yuri A.
Published: July 2005

The article reports the development of a specialized magnetic system for application in low field studies of chemical reactions involving paramagnetic intermediates. We have designed and built a yoke-free magnetic system optimized for creating rather low static homogeneous magnetic fields that can be cleanly swept through zero value. The actually built system creates magnetic field in the range from “−500” to “+500” G in a cylindrical working region with a length of 8 cm and a diameter of 1 cm with a relative field homogeneity of about 10−4 without using ferromagnetic elements or employing a field-sensing feedback loop. At a distance of greater than or equal to 15 cm from the center of the system along the sweeping axis, the magnetic field does not exceed 100 G due to active shielding, which allows putting magnetic field-sensitive elements of the installation that close to the sample. We have tried to provide a detailed account of the design choices we faced and the compromises we had reached for each key aspect of the system, being rather specific about the reasoning behind each decision. The system actually built was thoroughly tested to verify the assumptions made at the design and the calculation stages and to check their practical realizability. The system will serve as the basis of a magnetically affected reaction yield spectrometer that is currently being developed in our laboratory, but hopefully can also be used in a wider array of applications centered around studies in low magnetic fields.
Surface preparation of hard ionic crystals by ultrahigh vacuum cleavage
Authors: Barth Clemens , Claeys Christian , Henry Claude R.
Published: July 2005

A complete procedure for the preparation of clean surfaces of especially hard ionic crystals by ultrahigh vacuum (UHV) cleavage is given and exemplified by the preparation of the (001) surface of single MgO crystals. All important tools that are needed for the preparation are explained in detail. We present a device that allows precise cleavages in UHV and show how it can be easily integrated into an existing UHV system equipped with a linear manipulator. Cleaving ionic crystals produces charges on and below the fresh surface, which strongly hamper experiments like dynamic scanning force microscopy. In the case of MgO imaging is mostly impossible right after cleavage. We show that it is sufficient to anneal MgO crystals at temperatures higher than 350°C in order to reduce a large part of the charges. For the annealing, an UHV oven is used that can be annealed up to 550°C without leaving the upper 10−10mbar pressure region. Our techniques can be used in principle also for softer ionic crystals such as KBr, KCl, NaCl, and for other hard materials such as semiconducting ZnO.
Tunable pulse-width, electro-optically cavity-dumped, rf-excited Z-fold waveguide CO2 laser
Authors: Tian Zhaoshuo , Sun Zhenghe , Qu Shiliang
Published: July 2005

In this paper, an electro-optically cavity-dumped, rf-excited, Z-folded waveguide CO2 laser is presented. Theoretical studies on the laser output wave form and method to control laser pulse width and output power are made. In the experiment, a pulse width of a cavity-dumped laser can be changed from 12 to 32 ns. However, the corresponding peak powers reduce from 7000to2800W at a pulse repetition rate of 10kHz. The experimental results are consistent with the theoretical analyses.
High-Reynolds-number simulation of turbulent mixing
Authors: Yeung P. K. , Donzis D. A. , Sreenivasan K. R.
Published: August 2005

A brief report is given of a new 20483 direct numerical simulation of the mixing of passive scalars with uniform mean gradients in forced, stationary isotropic turbulence. The Taylor-scale Reynolds number is close to 700 and Schmidt numbers of 1 and 1∕8 are considered. The data provide the most convincing evidence to date for the inertial-convective scaling. Significant departures from small-scale isotropy are sustained in conventional measures. Subject to some stringent resolution requirements, the data suggest that commonly observed differences between the intermittency of energy and scalar dissipation rates may in part be a finite-Reynolds-number effect.
Bonding of nitrogen in dilute InAsN and high In-content GaInAsN
Authors: Wagner J. , Köhler K. , Ganser P. , Maier M.
Published: July 2005

Dilute InAs1−yNy and high In-content Ga1−xInxAs1−yNy layers with y⩽0.012 and x⩾0.92 were grown by rf-nitrogen plasma source molecular-beam epitaxy on InP substrates using a metamorphic GaInAs buffer layer. The bonding of nitrogen in these alloys was analyzed by Raman spectroscopy, showing that nitrogen is incorporated in dilute InAsN as isolated NAs for a nitrogen content of y=0.005; two additional nitrogen-related modes were found to appear at higher nitrogen contents (y=0.012), possibly due to the formation of higher-order di-nitrogen In–N complexes. The addition of a small amount of Ga to the InAsN ([Ga]⩽8%) was found to lead to an almost complete change from pure In–N bonding to a preferential bonding of the substitutional nitrogen to at least one Ga neighbor. Further, the effect of nitrogen incorporation on the higher-lying E1 and E1+Δ1 interband transitions of InAsN has been studied by spectroscopic ellipsometry, revealing a high-energy shift of both interband transitions with increasing nitrogen content at a rate similar to that reported for dilute GaAsN [J. Wagner et al., Appl. Phys. Lett. 77, 3592 (2000)].
Self-assembled supported Co nanocrystals: The adhesion energy of face-centered-cubic Co on SrTiO3(001)-(2×2)
Authors: Silly Fabien , Castell Martin R.
Published: July 2005

We have investigated the structure and morphology of self-assembled cobalt nanocrystals supported on a SrTiO3(001)-(2×2) substrate using scanning tunneling microscopy. Nanocrystals with a truncated pyramid shape were imaged, allowing crystallographic identification of the cluster facets. These nanocrystals result from the epitaxial growth of fcc Co on SrTiO3(001). The dimension of the nanocrystal facets at equilibrium and an energy minimization calculation result in γadh=(3.96±0.37)J∕m2 for the adhesion energy of face-centered-cubic Co∕SrTiO3(001)-(2×2).
X-ray phase contrast tomography with a bending magnet source
Authors: Peele A. G. , De Carlo F. , McMahon P. J. , Dhal B. B. , Nugent K. A.
Published: August 2005

X-ray radiography and x-ray tomography are important tools for noninvasive characterization of materials. Historically, the contrast mechanism used with these techniques has been absorption. However, for any given sample there are x-ray energies for which absorption contrast is poor. Alternatively, when good contrast can be obtained, radiation damage from an excessive dose may become an issue. Consequently, phase-contrast methods have in recent years been implemented at both synchrotron and laboratory facilities. A range of radiographic and tomographic demonstrations have now been made, typically utilizing the coherent flux from an insertion device at a synchrotron or a microfocus laboratory source. In this paper we demonstrate that useful results may be obtained using a bending magnet source at a synchrotron. In particular we show that the same beamline can be used to make and characterize a sample made by x-ray lithographic methods.
Study for a portable IR sensor to detect the blood temperature during coronary bypass implantation
Authors: Giovannetti Giulio , Hartwig Valentina , Francesconi Raffaello , Landini Luigi , Benassi Antonio
Published: August 2005

The objective of this research was to investigate the possibility of using an infrared prototype device for the detection of the blood temperature during a surgical operation for coronary bypass implantation. The correlation between the fluid temperature time behavior and the fluid flow rate was demonstrated. Each blood vessel acts like a thermal wave emitter, so the amount of heat is proportional to the blood flow detected by the IR sensor. The idea was to design a low cost portable device with the advantage that it can be placed near the region of interest. We chose a pyroelectric sensor for its high-quality cost ratio. Because this kind of sensor detects only a variable infrared source, we used an electromechanical chopper for modulating the radiation. It consists of an electronic shutter whose opening speed is controlled by an astable multivibrator. The output signal was analyzed using a dedicated electronic circuit including a bandpass filter and an amplifier; then an acquisition board was employed for capturing and displaying the signal using a PC. Prototype assessment was made with laboratory equipment and in vivo measurements were made during surgical operation on a small pig.
The Role of Target Salience in Crowding
Authors: Felisberti Fatima M , Solomon Joshua A , Morgan Michael J
Published: July 2005

We studied ‘crowding’ in the parafovea using orientation identification of a Gabor target as the task, and flanking Gabors on an isoeccentric circle as distractors. Orientation-discrimination thresholds were raised by nearby flanking distractors. This crowding effect was increased by the number of distractors and decreased by the spatial separation between target and distractors. Crowding was greatest when the target was in the centre of the distractor array and smallest when the target was on the edge of the array. A cue indicating the position of the target improved performance when the position was otherwise unknown and the spatial separation between target and distractors was large, but the cue had no significant effect when separation was small. Increasing the contrast of the target relative to the distractors reduced crowding, but targets of smaller contrast than that of the distractors are even harder to identify than those of the same contrast. Putting the target and distractors in different depth planes decreased crowding for some observers, but there were qualitative individual differences. A large (say, 45°) difference in orientation between target and distractors caused the target to ‘pop out’ in a presence/absence task, despite the evidence from other studies that crowding is still found in these conditions. We conclude that salience has, at best, modest effects on crowding.
Chemical composition and feeding value of urea-treated corncobs ensiled with additives for sheep
Authors: Sarwar M. , Khan M. Ajmal , Nisa M.
Published: July 2005

This study examined the effects of various additives on ammonia nitrogen (N) capture in urea-treated corncobs (UTC), and measured the effect of UTC ensiled with or without enzose on nutrient intake, digestibility, N balance, and growth performance in sheep. In Expt 1, 5% UTC were ensiled in laboratory silos using enzose, cane molasses, acidified cane molasses, and acidified water (having a pH of 4.4, similar to enzose), each at 0, 4, 5, and 6% of corncobs dry matter (DM). Total N, ammonia N, and neutral detergent insoluble N (NDIN) contents in UTC ensiled with additives were significantly higher than in those ensiled without additives. Total N and NDIN contents of UTC were affected both by additive type and level. Total N and NDIN contents of UTC ensiled with enzose were significantly higher than of those ensiled with other additives. Neutral detergent fibre (NDF) and hemicellulose contents of UTC ensiled with additives were significantly higher than of those ensiled without additives. The NDF and hemicellulose were higher in UTC ensiled with enzose compared with all other additives. In Expt 2, 32 Lohi breed sheep, 4 months of age and of similar weights, were randomly assigned to 4 dietary groups. The control ration contained 30% DM from UTC ensiled without enzose, and the other 3 rations contained 30, 35, and 40% DM from UTC ensiled with enzose. Dry matter, OM, and NDF intakes were significantly increased in sheep fed increasing levels of UTC ensiled with enzose. Dry matter and NDF digestibilities were significantly higher in sheep fed UTC ensiled with enzose than in those fed UTC ensiled without enzose. The DM and NDF digestibilities were similar in sheep fed diets containing varying levels of UTC ensiled with enzose. Nitrogen balance was positive and was significantly higher in sheep fed rations containing UTC ensiled with enzose than in those fed UTC ensiled without enzose. Daily weight gain was higher in sheep fed rations containing UTC ensiled with enzose than in those fed UTC ensiled without enzose. These results indicated that ensiling UTC with enzose improved ammonia N capture. Inclusion of 5% UTC ensiled with 5% enzose up to 40% DM resulted in better nutrient intake, digestibility, N balance, and growth in Lohi sheep.
Plasma and tissue α-tocopherol concentrations and meat colour stability in sheep grazing saltbush (Atriplex spp.)
Authors: Pearce K. L. , Masters D. G. , Smith G. M. , Jacob R. H. , Pethick D. W.
Published: July 2005

Dry senesced pastures available during the summer and autumn period in Western Australia and other areas with a Mediterranean climate are low in vitamin E. The use of expensive and labour-intensive supplements to prevent nutritional myopathy induced by vitamin E deficiency in weaner sheep is common. Low vitamin E concentrations in the muscle preslaughter can also reduce the shelf life of meat. There is growing interest in incorporating saltbush into farming systems in Western Australia. The potential for saltbush to boost the vitamin E status of sheep and improve the shelf life of meat was investigated. Fifty (2 × 25) 18-month-old Merino hogget wethers (average liveweight 48 kg) were grazed on either a saltbush-dominant saline pasture or on a ‘control’ dry pasture, stubble plot for 14 weeks. At the start of the experiment, all animals were orally supplemented with 2500 IU of dl-α-tocopherol acetate in 6.25 mL solution. The α-tocopherol content in saltbush was 139 and 116 mg/kg dry matter for old man and river saltbush, respectively. Concentrations of α-tocopherol were measured in plasma at Weeks 0, 4, 8, and 12 and in muscle and liver samples taken at slaughter. Grazing on saltbush significantly elevated α-tocopherol concentrations in the liver and muscle compared with grazing on dry pasture, well above the threshold for vitamin E inadequacy (P < 0.001). Plasma α-tocopherol concentrations in sheep fed saltbush increased up to Week 8 and then decreased until the end of the experiment as availability of saltbush declined (P < 0.05). Plasma α-tocopherol in sheep fed dry pasture increased in the first 4 weeks due to the initial vitamin E treatment but declined thereafter, indicating that the pasture was low in vitamin E. The high muscle concentrations of α-tocopherol in sheep fed saltbush also improved colour stability and may have had an influence on drip and cooking loss. The meat from the saltbush-grazed sheep was moister but drip and cooking loss was the same as from the drier meat of the control sheep. In conclusion, this study demonstrates that saltbush is a potential vitamin E source for sheep.
Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation
Authors: Matsuzaki Hitomi , Daitoku Hiroaki , Hatta Mitsutoki , Aoyama Hisanori , Yoshimochi Kenji , Fukamizu Akiyoshi
Published: August 2005

The FOXO family of forkhead transcription factors plays a key role in a variety of biological processes, including metabolism, cell proliferation, and oxidative stress response. We previously reported that Foxo1, a member of the FOXO family, is regulated through reversible acetylation catalyzed by histone acetyltransferase cAMP-response element-binding protein (CREB)-binding protein (CBP) and NAD-dependent histone deacetylase silent information regulator 2, and that the acetylation at Lys-242, Lys-245, and Lys-262 of Foxo1 attenuates its transcriptional activity. However, the molecular mechanism by which acetylation modulates Foxo1 activity remains unknown. Here, we show that the positive charge of these lysines in Foxo1 contributes to its DNA-binding, and acetylation at these residues by CBP attenuates its ability to bind cognate DNA sequence. Remarkably, we also show that acetylation of Foxo1 increases the levels of its phosphorylation at Ser-253 through the phosphatidylinositol 3-kinase–protein kinase B signaling pathway, and this effect was overridden on the acetylation-deficient Foxo1 mutant. Furthermore, in
in vitro
kinase reactions, the association of wild-type Foxo1 and its target DNA sequence inhibits the protein kinase B-dependent phosphorylation of Foxo1, whereas mutated Foxo1 proteins, which mimic constitutively acetylated states, are efficiently phosphorylated even in the presence of the DNA. These results suggest that acetylation regulates the function of Foxo1 through altering the affinity with the target DNA and the sensitivity for phosphorylation.
Laccase 2
is the phenoloxidase gene required for beetle cuticle tanning
Authors: Arakane Yasuyuki , Muthukrishnan Subbaratnam , Beeman Richard W. , Kanost Michael R. , Kramer Karl J.
Published: August 2005

Cuticle tanning (or sclerotization and pigmentation) in invertebrates involves the oxidative conjugation of proteins, which renders them insoluble and hardens and darkens the color of the exoskeleton. Two kinds of phenoloxidases, laccase and tyrosinase, have been proposed to participate in tanning, but proof of the true identity of the enzyme(s) responsible for this process has been elusive. We report the cloning of cDNAs for laccases and tyrosinases from the red flour beetle,
Tribolium castaneum
, as well as their developmental patterns of expression. To test for the involvement of these types of enzymes in cuticle tanning, we performed RNA interference experiments to decrease the levels of individual phenoloxidases. Normal phenotypes were obtained after dsRNA-mediated transcript depletion for all phenoloxidases tested, with the exception of laccase 2. Insects injected with dsRNA for the
laccase 2
gene failed to tan, were soft-bodied and deformed, and subsequently died in a dsRNA dose-dependent fashion. The results presented here support the hypothesis that two isoforms of laccase 2 generated by alternative splicing catalyze larval, pupal, and adult cuticle tanning in
Tribolium
.
Spatial location and requirements for the assembly of the
Agrobacterium tumefaciens
type IV secretion apparatus
Authors: Judd Paul K. , Kumar Renu B. , Das Anath
Published: August 2005

Type IV secretion is used by pathogenic microorganisms to transfer effector macromolecules to eukaryotic target cells. The VirB/D4 apparatus of
Agrobacterium tumefaciens
transfers DNA and proteins to plant cells. We postulated that the cell pole is the site of assembly of the
A. tumefaciens
type IV apparatus. Using immunofluorescence microscopy, we now demonstrate that 10 of the VirB proteins localized primarily to one cell pole and a macromolecular VirB complex is assembled at the pole. Neither the assembly of the complex nor polar localization of a VirB protein requires ATP utilization by the VirB ATPases. The requirement of other VirB proteins for the polar localization of at least six VirB proteins indicates an essential role of protein–protein interaction in polar targeting. Four proteins (VirB3, VirB4, VirB8, and VirB11) could target themselves to a cell pole independent of a VirB protein. We provide evidence that VirB6–VirB10 are the structural components of the type IV apparatus. Using strains that express defined subsets of the
virB
genes, we demonstrate that VirB7–VirB10 are the minimum components sufficient for the assembly of a polar VirB complex. VirB6 associates with this complex to form the type IV secretion apparatus. VirB8 functions as the assembly factor and targets the apparatus to the cell pole.
S -Ketamine Anesthesia Increases Cerebral Blood Flow in Excess of the Metabolic Needs in Humans
Authors: Långsjö Jaakko W. , Maksimow Anu , Salmi Elina , Kaisti Kaike , Aalto Sargo , Oikonen Vesa , Hinkka Susanna , Aantaa Riku , Sipilä Hannu , Viljanen Tapio , Parkkola Riitta , Scheinin Harry
Published: July 2005

Background

Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.

Methods

Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia. Whole brain estimates for cerebral blood volume were obtained using kinetic modeling.

Results

The mean +/- SD serum S-ketamine concentration was 159 +/- 21 ng/ml at the subanesthetic and 1,959 +/- 442 ng/ml at the anesthetic levels. The total S-ketamine dose was 10.4 mg/kg. S-ketamine increased heart rate (maximally by 43.5%) and mean blood pressure (maximally by 27.0%) in a concentration-dependent manner (P = 0.001 for both). Subanesthetic S-ketamine increased whole brain CBF by 13.7% (P = 0.035). The greatest regional CBF increase was detected in the anterior cingulate (31.6%; P = 0.010). No changes were detected in CMRO2. Anesthetic S-ketamine increased whole brain CBF by 36.4% (P = 0.006) but had no effect on whole brain CMRO2 or GMR. Regionally, CBF was increased in nearly all brain structures studied (greatest increase in the insula 86.5%; P < 0.001), whereas CMRO2 increased only in the frontal cortex (by 15.7%; P = 0.007) and GMR increased only in the thalamus (by 11.7%; P = 0.010). Cerebral blood volume was increased by 51.9% (P = 0.011) during anesthesia.

Conclusions

S-ketamine-induced CBF increases exceeded the minor changes in CMRO2 and GMR during anesthesia.
Role of Adenosine Receptors in Volatile Anesthetic Preconditioning against Neutrophil-induced Contractile Dysfunction in Isolated Rat Hearts
Authors: Hu Guochang , Salem M Ramez , Crystal George J.
Published: July 2005

Background

The authors tested the hypothesis that adenosine receptors in polymorphonuclear neutrophils and the heart mediate the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction.

Methods

Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as index of contractility. Neutrophils and platelet-activating factor were added to perfusate for 10 min followed by 30 min of recovery. The effect of selective pretreatment of the neutrophils and the hearts with 1.0 minimum alveolar concentration isoflurane or sevoflurane on the neutrophil-induced contractile dysfunction was assessed. Studies were performed in the absence and presence of the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 microM). Neutrophil retention was determined from difference between those administered and collected in coronary effluent and from myeloperoxidase concentration in myocardial samples. Superoxide production of neutrophils was measured by spectrophotometry.

Results

Under control conditions (no anesthetic pretreatment), activated neutrophils caused marked and persistent reductions in left ventricular developed pressure, associated with increases in neutrophil retention and myeloperoxidase activity. Pretreatment of the neutrophils or the heart with either isoflurane or sevoflurane abolished these effects. Pretreatment of the neutrophils also reduced the platelet-activating factor-induced increase in superoxide production by 29 and 33%, respectively. 8-Phenyltheophylline blunted the effects of anesthetic pretreatment of the neutrophils, whereas it did not alter the effects of anesthetic pretreatment of the heart.

Conclusion

An activation of adenosine receptors in neutrophils, but not in the heart, plays a role in the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction.
Propofol Inhibits Long-term Potentiation but Not Long-term Depression in Rat Hippocampal Slices
Authors: Nagashima Kimimoto , Zorumski Charles F. , Izumi Yukitoshi
Published: July 2005

Background

Although propofol is known to produce amnesia when used for anesthesia, mechanisms underlying its effects on memory are poorly understood. The current study was designed to examine the effects of propofol on forms of synaptic plasticity thought to contribute to memory processing.

Methods

Extracellular excitatory postsynaptic potentials were recorded from the CA1 region of rat hippocampal slices. Long-term potentiation (LTP) was induced using theta-burst stimulation (10 bursts of 4 pulses at 100 Hz, applied at 5 Hz) of the Schaffer-collateral pathway, while low-frequency stimulation (1 Hz x 900 pulses) was delivered to induce long-term depression. The authors also used higher-frequency stimulation (10 bursts of 4 pulses at 200 Hz, applied at 5 Hz) in the presence of MK-801 to examine the effects of propofol on an N-methyl-D-aspartate receptor-independent form of LTP.

Results

At 30 microM, propofol inhibited LTP induction produced by theta-burst stimulation but had less effect on LTP maintenance. Similarly, when LTP was induced by 200-Hz stimulation in the presence of MK-801, propofol also blocked LTP induction. Propofol did not block LTP induction in the presence of picrotoxin, a specific antagonist of gamma-aminobutyric acid type A receptors, suggesting that modulation of gamma-aminobutyric acid type A receptors participates in propofol-mediated LTP inhibition. Propofol did not inhibit long-term depression.

Conclusions

Propofol inhibits LTP induction through modulation of gamma-aminobutyric acid type A receptors but not via inhibition of N-methyl-D-aspartate receptors. However, other factors also possibly contribute to propofol-mediated LTP inhibition.
Overlapping Induction of Anesthesia
Authors: Hanss Robert , Buttgereit Björn , Tonner Peter H. , Bein Berthold , Schleppers Andreas , Steinfath Markus , Scholz Jens , Bauer Martin
Published: July 2005

Background

Overlapping induction (OI), i.e., induction of anesthesia with an additional team while the previous patient is still in the operating room (OR), was investigated.

Methods

The study period was 60 days in two followed by three ORs during surgical Block Time (7:30 am until 3:00 pm). Patients were admitted the day before surgery and were thus available and did not have surgery that day unless there was a time reduction. Facilities were already constructed. Number of cases, Nonsurgical Time (Skin Suture Finish until next Procedure Start Time), Turnover Time, and Anesthesia Control Time plus Turnover Time were studied. In addition, economic benefit was calculated.

Results

Three hundred thirty-five cases were studied. Using OI, the time of care of regularly scheduled cases was shortened, and the number of cases performed within OR Block Time increased (151 to 184 cases; P < 0.05). Nonsurgical Time (in h:min) decreased (1:08 +/- 0:26 to 0:57 +/- 0:18; P < 0.001), Turnover Time decreased (0:38 +/- 0:24 to 0:25 +/- 0:15; P < 0.05), and Anesthesia Control Time plus Turnover Time decreased (0:43 +/- 0:23 to 0:28 +/- 0:18; P < 0.001). Subgroup analysis showed a significant benefit of OI only in three ORs. In three ORs, economic benefit can be gained at a case mix index greater than 0.3 besides additional costs.

Conclusions

Overlapping induction increased productivity and profit despite the expense of additional staff. Subgroup analysis emphasizes the importance of the number of ORs involved in OI.
Changes in Arterial Pressure during Mechanical Ventilation
Authors: Michard Frédéric
Published: July 2005

Mechanical ventilation induces cyclic changes in vena cava blood flow, pulmonary artery blood flow, and aortic blood flow. At the bedside, respiratory changes in aortic blood flow are reflected by "swings" in blood pressure whose magnitude is highly dependent on volume status. During the past few years, many studies have demonstrated that arterial pressure variation is neither an indicator of blood volume nor a marker of cardiac preload but a predictor of fluid responsiveness. That is, these studies have demonstrated the value of this physical sign in answering one of the most common clinical questions, Can we use fluid to improve hemodynamics?, while static indicators of cardiac preload (cardiac filling pressures but also cardiac dimensions) are frequently unable to correctly answer this crucial question. The reliable analysis of respiratory changes in arterial pressure is possible in most patients undergoing surgery and in critically ill patients who are sedated and mechanically ventilated with conventional tidal volumes.
Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study
Authors: Virtanen Jyrki K. , Voutilainen Sari , Happonen Pertti , Alfthan Georg , Kaikkonen Jari , Mursu Jaakko , Rissanen Tiina H. , Kaplan George A. , Korhonen Maarit J. , Sivenius Juhani , Salonen Jukka T.
Published: August 2005

Background Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial.

Design and methods The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46–64 years and free of prior stroke, examined in 1991–1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Results At baseline the mean serum tHcy concentration was 10.9 μmol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23–6.24] for any stroke and 2.61 (95% CI: 1.02–6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (> 11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14–0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15–1.09), compared with men in the lowest third.

Conclusion Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.
Exercise training in chronic heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle
Authors: Gielen Stephan , Adams Volker , Linke Axel , Erbs Sandra , Möbius-Winkler Sven , Schubert Andreas , Schuler Gerhard , Hambrecht Rainer
Published: August 2005

Background Chronic heart failure (CHF) is accompanied by an inflammatory activation which occurs both systemically and in the skeletal muscle. Exercise training has been shown to reduce the local expression of cytokines and inducible nitric oxide synthase (iNOS) in muscle biopsies of CHF patients. INOS-derived NO can inhibit oxidative phosphorylation and contribute to skeletal muscle dysfunction in CHF.

Design To investigate the correlation between changes in local iNOS expression associated with regular exercise and changes in aerobic enzyme activities in the skeletal muscle of patients with CHF. Twenty male CHF patients [ejection fraction 25% (SE 2), age 54 (SE 2) years] were randomized to a training ( n = 10) or a control group (C, n = 10).

Methods At baseline and after 6 months skeletal muscle iNOS expression was measured by real-time polymerase chain reaction. INOS protein and protein nitrosylation were assessed by immunohistochemistry. Cytochrome c oxidase (COX) activity was quantified electrochemically using the Clark oxygen electrode.

Results Exercise training led to a 27% increase in cytochrome c oxidase activity [from 21.8 (SE 3.2) to 27.7 (SE 3.5) nmol O2/mg per min, P=0.02 versus baseline]. Changes in iNOS expression and iNOS protein content were inversely correlated with changes in COX-activity ( r= −0.60, P=0.01; r= −0.71, P<0.001).

Conclusions The inverse correlation between iNOS expression/iNOS protein content and COX-activity indicates that local anti-inflammatory effects may contribute to improved muscular oxidative metabolism.