bluuebunny/crossref_metadata_2025 huggingface dataset:
Collisional radiative model of an argon atmospheric capillary surface-wave discharge
Authors: Yanguas-Gil A. , Cotrino J. , González-Elipe A. R.
Published: November 2004

The characteristics of a microwave surface-wave sustained plasma operated at atmospheric pressure in an open-ended dielectric tube are investigated theoretically as a first step in the development of a self-consistent model for these discharges. The plasma column is sustained in flowing argon. A surface-wave discharge that fills the whole radial cross section of the discharge tube is considered. With experimental electron temperature profiles [García et al., Spectrochim. Acta, Part B 55, 1733 (2000)] the numerical model is used to test the validity of the different approximations and to study the influence of the different kinetic processes and power loss mechanisms on the discharge.
Stiffness characterization of corner-filleted flexure hinges
Authors: Lobontiu Nicolae , Garcia Ephrahim , Hardau Mihail , Bal Nicolae
Published: November 2004

The paper formulates the closed-form stiffness equations that can be used to characterize the static, modal, and dynamic behavior of single-axis corner-filleted flexure hinges, which are incorporated into macro/microscale monolithic mechanisms. The derivation is based on Castiliagno’s first theorem and the resulting stiffness equations reflect sensitivity to direct- and cross-bending, axial loading, and torsion. Compared to previous analytical work, which assessed the stiffness of flexures by means of compliances, this paper directly gives the stiffness factors that completely define the elastic response of corner-filleted flexure hinges. The method is cost-effective as it requires considerably less calculation steps, compared to either finite element simulation or experimental characterization. Limit calculations demonstrate that the known engineering equations for a constant cross-section flexure are retrieved from those of a corner-filleted flexure hinge when the fillet radius becomes zero. The analytical model results are compared to experimental and finite element data and the errors are less than 8%. Further numerical simulation based on the analytical model highlights the influence of the geometric parameters on the stiffness properties of a corner-filleted flexure hinge.
Shape precompensation in two-photon laser nanowriting of photonic lattices
Authors: Sun Hong-Bo , Suwa Tooru , Takada Kenji , Zaccaria Remo Proietti , Kim Moon-Soo , Lee Kwang-Sup , Kawata Satoshi
Published: November 2004

We first analyze why most of the photonic crystals produced by two-photon photopolymerization technique exhibit no photonic band gap effect. And then subdiffraction-limited resolution-enabled finely quantified pixel writing, a scheme that has been used in micromachine fabrication, is adopted as the solution. As a result, higher accuracy in depicting and better reproducibility in both fabrication and photonic band gap effect observation are obtained. More important, the method allows for precise precompensation of the structure shrinkage induced by photochemical reactions of polymerization, which may pave the way to high-fidelity fabrication of polymer photonic and optoelectronic devices that require strictly the structural parameters.
Detection of chemical species using ultraviolet microdisk lasers
Authors: Fang W. , Buchholz D. B. , Bailey R. C. , Hupp J. T. , Chang R. P. H. , Cao H.
Published: November 2004

We have utilized hybrid zinc oxide∕silica microdisk lasers to sense volatile organic compounds, such as toluene and nitrobenzene. Nonspecific adsorption of these organic molecules onto the microdisk surface causes an increase in the disk refractive index, ultimately resulting in a redshift of the observed lasing wavelengths. The monitoring of these shifts provides the sensing modality. Microdisk lasers were found to respond rapidly and reversibly to the investigated chemicals demonstrating, in principal, the chemical and biological sensing capabilities of such devices.
Precise magnetoresistance and Hall resistivity measurements in the diamond anvil cell
Authors: Boye Shawn A. , Rosén Daniel , Lazor Peter , Katardjiev Ilia
Published: November 2004

An experimental system in combination with a technique for creating samples has been developed for conducting magnetotransport measurements of 3d ferromagnets as a function of temperature and pressure. Polycrystalline Ni0.985O0.015 thin film samples have been manufactured for experiments at zero pressure and in the diamond anvil cell (DAC) such that the contacts are of a predetermined size. This ensures that the placement of the leads in the pressure chamber of the DAC does not affect the quality of the measurement. Magnetoresistance and Hall resistivity measurements are preformed using the van der Pauw technique and the constant current method. The performance of the experimental apparatus is demonstrated by magnetotransport measurements of Ni0.985O0.015 thin films between 285 and 455 K in applied magnetic fields up to 10 T. The change in magnetic resistivity measured in the transverse configuration at zero pressure in the DAC, −0.0162(2) μΩ  cm T−1 at 297 K, is observed to be negative and linear up to the maximum applied field. The extraordinary Hall coefficient measured at zero pressure and 297 K is found to be RE=−30.4(1)×10−10 m3 C−1.
Magnetization of a nonferromagnetic metal spacer sandwiched between two magnetically ordered layers
Authors: Gorobets V. Yu.
Published: November 2004

The exchange coupling of magnetically ordered layers (MOLs) through a nonmagnetic metallic spacer is calculated. The induced magnetization in the spacer, taking into account the influence of an external magnetic field, is calculated, too. This calculation shows that the energy of coupling of the MOLs through the nonmagnetic metallic spacer is a long-periodic function of the spacer thickness and magnetic field, i.e., the exchange coupling between the layers varies from ferromagnetic to antiferromagnetic and vice versa depending on the spacer thickness and magnetic field. Also this calculation shows that in nonferromagnetic spacer the induced magnetization can undergo many complete rotations, depending on distance to the boundaries with the MOLs. Moreover, absolute value of the induced magnetization decays nonmonotonically with distance from the interfaces inside the spacer. It is shown that the character of the decay of the absolute value of the magnetization from the interfaces into the interior of the spacer is influenced by magnetic field.
Effect of Al∕N ratio during nucleation layer growth on Hall mobility and buffer leakage of molecular-beam epitaxy grown AlGaN∕GaN heterostructures
Authors: Storm D. F. , Katzer D. S. , Binari S. C. , Shanabrook B. V. , Zhou Lin , Smith David J.
Published: November 2004

Al Ga N ∕ Ga N high electron mobility transistor structures have been grown by plasma-assisted molecular beam epitaxy on semi-insulating 4H-SiC utilizing an AlN nucleation layer. The electron Hall mobility of these structures increases from 1050cm2∕Vs to greater than 1450cm2∕Vs when the Al∕N flux ratio during the growth of the nucleation layer is increased from 0.90 to 1.07. Buffer leakage currents increase abruptly by nearly three orders of magnitude when the Al∕N ratio increases from below to above unity. Transmission electron microscopy indicates that high buffer leakage is correlated with the presence of stacking faults in the nucleation layer and cubic phase GaN in the buffer, while low mobilities are correlated with high dislocation densities.
Evaluation of the effectiveness of back-side damage gettering in silicon introduced by a cavitating jet
Authors: Kumano H. , Sasaki T. , Soyama H.
Published: November 2004

Photocapacitance measurements have been performed to evaluate the electrical effectiveness of gettering by back-side damage, introduced by a cavitating jet into silicon wafers. The silicon wafers, which had their back sides damaged previously in localized areas, were intentionally contaminated and subsequently thermally treated to diffuse the contamination through the wafer. The density of deep levels varied between the areas with back-side damage and those without. The results obtained on back-side damaged areas were closer to those on the original starting material. These results confirm that the back-side damage introduced by a cavitating jet can function as gettering sites.
Stability of two-layer Newtonian plane Couette flow past a deformable solid layer
Authors: Shankar V. , Kumar Lalit
Published: November 2004

The linear stability of two-layer plane Couette flow of Newtonian fluids (designated by labels A and B) of thicknesses (1−β)R and βR, and viscosities μa and μb past a soft, deformable linear viscoelastic solid of thickness HR, shear modulus G, and viscosity ηw is determined using a combination of low wavenumber asymptotic analysis and a numerical method. There are two qualitatively different interfacial modes in this system, viz., the two-fluid interfacial mode due to viscosity stratification [“mode 1;” C. S. Yih “Instability due to viscosity stratification,” J. Fluid Mech. 27, 337 (1967)], and the fluid–solid interfacial mode [“mode 2;” Kumaran, Fredrickson, and Pincus, “Flow induced instability of the interface between a fluid and a gel at low Reynolds number,” J. Phys II 4, 893 (1994)]. The respective effects of solid layer deformability and fluid viscosity stratification on mode 1 and mode 2 are analyzed in detail using both asymptotic and numerical methods. Results of our low wavenumber asymptotic analysis show that the deformability of the solid layer has a dramatic effect on the interfacial instability (mode 1) between the two Newtonian fluids: When the more viscous fluid is of smaller thickness (an unstable configuration for the two-fluid mode 1 instability), the solid layer could completely stabilize the two-fluid interfacial instability, when the nondimensional elasticity parameter Γ=Vμb/(GR) increases beyond a critical value. Here V is the dimensional velocity of the top moving plate. When the more viscous fluid is of larger thickness compared to the less viscous fluid (a stable configuration in rigid channels), it is shown that the solid layer could destabilize or stabilize the two-fluid interfacial mode, depending on the solid layer thickness H. Numerical results at finite values of wavenumber k reveal that the stabilization of the two-fluid interfacial mode predicted by the low wavenumber analysis extends to moderate values of k. For high values of k, the perturbations are localized near the two-fluid interface. Increase in Γ therefore does not have any effect on the high k unstable modes, which are stabilized by the presence of nonzero interfacial tension in the two-fluid interface. When Γ is further increased, the interfacial mode between fluid B and the solid layer becomes unstable. It is demonstrated here that the parameters Γ (representing the shear modulus of the solid), solid layer thickness H, and the solid layer viscosity ηw can be chosen such that both the interfacial modes are stabilized at all wavenumbers, for a fixed top plate velocity.
Direct synthesis of single crystalline In2O3 nanopyramids and nanocolumns and their photoluminescence properties
Authors: Guha P. , Kar S. , Chaudhuri S.
Published: November 2004

Single crystalline indium oxide pyramid and column structures were synthesized by a simple physical evaporation technique. The pyramid structure was obtained without any catalytic action while the column structure was produced using gold as the catalyst. The nanostructures were characterized by x-ray diffraction, scanning electron microscopy and transmission electron microscopy. A blue-green photoluminescence band in the visible region was observed in the In2O3 structures which could be ascribed to the existence of a large amount of singly ionized oxygen vacancies, confirmed by electron paramagnetic resonance.
Semiconductor microwave mirror for a measurement of the dynamical Casimir effect
Authors: Braggio C. , Bressi G. , Carugno G. , Lombardi A. , Palmieri A. , Ruoso G. , Zanello D.
Published: November 2004

According to QED a metallic mirror set in motion in quantum vacuum gives rise to “dissipated” energy in the form of real photons. This phenomenon, called dynamical Casimir effect, has never been observed due to unsolved technical difficulties: in order to obtain an experimentally measurable number of photons from vacuum fluctuations a reflecting surface has in fact to vibrate at very high frequencies (≃109 Hz). As these frequencies are too high to be achieved with a purely mechanical oscillation, our idea is to switch an effective microwave mirror on and off at very short intervals of time changing the reflectivity of a semiconductor layer by shining a pulsed laser beam on its surface. The first step to study the feasibility of this technique is to show that a semiconductor slab when illuminated by a laser behaves indeed as a metal. This article presents the measurements that confirm this demand, obtained by uniformly illuminating large (several square centimeters) surfaces of silicon and GaAs.
Soft x-ray pulse height analyzer in the HT-7 tokamak
Authors: Shi Yuejiang , Chen Zhongyong , Wan Baonian , Lv Bo , Hu Liqun , Lin Shiyao , Hu Qinsheng , Qian Jinping , Liu Haiqing , Liu Shengxia , Xu Yucun , Shan Jiafang , Li Jiangang
Published: November 2004

A new soft x-ray pulse height analyzer (PHA), based on a Silicon Drift Detector (SDD) linear array consisting of 15 SDD detectors, has been installed in the HT-7 tokamak. The energy resolution of 150–180 eV at photon energy of 6 keV is achieved for the SDD with Peltier cooling. The effective time response of the SDD PHA is 50 ms. The profiles of electron temperature and the intensity of metallic impurities can be obtained with a spatial resolution of 3 cm. The performance and first experimental results from the new PHA system are presented.
Dependence of ferromagnetic properties on carrier transfer at GaMnN∕GaN:Mg interface
Authors: Arkun F. E. , Reed M. J. , Berkman E. A. , El-Masry N. A. , Zavada J. M. , Reed M. L. , Bedair S. M.
Published: November 2004

We report on the dependence of ferromagnetic properties of metalorganic chemical vapor deposition grown GaMnN films on carrier transfer across adjacent layers. We found that the magnetic properties of GaMnN, as a part of GaMnN∕GaN:Mg heterostructures, depend on the thickness of both the GaMnN film and the adjacent GaN:Mg layer and on the presence of a wide band gap barrier at this interface. These results are explained based on the occupancy of the Mn energy band and how the occupancy can be altered due to carrier transfer at the GaMnN∕GaN:Mg interfaces.
Effect of stacking fault energy on plastic deformation of nanocrystalline face-centered cubic metals
Authors: Ebrahimi F. , Ahmed Z. , Li H.
Published: November 2004

The effect of stacking fault energy (SFE) on the tensile stress–strain behavior of nanocrystalline face-centered cubic (fcc) metals was investigated. The stacking fault energy of nickel was decreased by alloying with copper or iron. It was found that, as predicted by a recent simulation study, decreasing the SFE increases the strain hardening rate of the nanocrystalline fcc metals. The effect was more pronounced in the nickel–copper alloy, which had a smaller average grain size.
Multilayer three-dimensional photolithography with traditional planar method
Authors: Yao Peng , Schneider Garrett J. , Miao Binglin , Murakowski Janusz , Prather Dennis W. , Wetzel Eric D. , O’Brien Daniel J.
Published: November 2004

We describe and demonstrate a method for the realization of three-dimensional lithography through the use of repeated planar photolithography processes. This process is based on the use of a commercially available resist system and consists of tailoring the resist response by controlling the exposure, development, and baking aspects of the process. In particular, postexposure bake is studied in detail as a primary working mechanism which, when combined with a small UV exposure and strong absorption, vertically confined photoacid is produced. As a result, the possibility of re-exposure in lower layers during top layer exposure is eliminated. In the course of this letter, we discuss issues related to this process and how they were overcome. Last, as a demonstration of the proposed method, we present three- and four-layer, three-dimensional “woodpile” photonic crystal structures.
Quantum confinement in ZnO nanorods
Authors: Gu Y. , Kuskovsky Igor L. , Yin M. , O’Brien S. , Neumark G. F.
Published: November 2004

The colloidal-synthesized ZnO nanorods with radius of 1.1±0.1nm (less than the bulk exciton Bohr radius, aB∼2.34nm) have been studied by optical methods combined with simple model calculations. The quantum confinement has been observed in these nanorods. The exciton binding energy is shown to be significantly enhanced due to one-dimensional confinement. Additionally, it is suggested that the green luminescence in ZnO involves free holes.
Laser manipulation of iron for nanofabrication
Authors: Myszkiewicz G. , Hohlfeld J. , Toonen A. J. , Van Etteger A. F. , Shklyarevskii O. I. , Meerts W. L. , Rasing Th. , Jurdik E.
Published: November 2004

We fabricate iron nanolines by depositing an atomic beam of iron through a far-off resonant laser standing wave (SW) onto a glass-ceramic substrate. The laser SW is tuned 200MHz above the D45→F5o5Fe56 transition at a vacuum wavelength of 372.099nm. The resulting nanolines exhibit a period of 186nm, a height above the background of 8nm and a full width at half maximum of 95nm. These nanostructures cover a surface area of ≃1.6×0.4mm2, corresponding to ≃8600 iron lines with a length of ≃400μm.
Spin polarization and barrier-oxidation effects at the Co∕alumina interface in magnetic tunnel junctions
Authors: Telling N. D. , van der Laan G. , Ladak S. , Hicken R. J.
Published: November 2004

The electronic structure and polarization in magnetic tunnel junctions prepared with varying degrees of barrier-layer oxidation have been studied using x-ray absorption spectroscopy across the Co L2,3 absorption edges. It was found that the Co electronic structure near the Co∕alumina interface tended to that of cobalt oxide as the barrier oxidation time was increased. However, the net Co 3d spin polarization, determined from x-ray magnetic circular dichroism, increased for moderate oxidation times compared to that obtained for an under-oxidized Co∕Al interface. It is proposed that the expected dilution of the measured polarization due to the formation of (room temperature) paramagnetic cobalt oxide, is offset by an increase in the Co 3d spin-polarization of the interface layer as the interface bonding changes from Co–Al to Co–O with increasing oxidation times.
Essential Roles of CD8+CD122+ Regulatory T Cells in the Maintenance of T Cell Homeostasis
Authors: Rifa'i Muhaimin , Kawamoto Yoshiyuki , Nakashima Izumi , Suzuki Haruhiko
Published: November 2004

Regulation of immune system is of paramount importance to prevent immune attacks against self-components. Mice deficient in the interleukin (IL)-2/IL-15 receptor β chain, CD122, are model animals of such immune attacks and characteristically have a high number of abnormally activated T cells. Here, we show that the transfer of CD8+CD122+ cells into CD122-deficient neonates totally prevented the development of abnormal T cells. Furthermore, recombination activating gene–2−/− mice that received wild-type mice–derived CD8+CD122− cells died within 10 wk after cell transfer, indicating that normal CD8+CD122− cells become dangerously activated T cells in the absence of CD8+CD122+ T cells. CD8+CD122+ cells could control activated CD8+ or CD4+ T cells both in vivo and in vitro. Our results indicate that the CD8+CD122+ population includes naturally occurring CD8+ regulatory T cells that control potentially dangerous T cells.
ATM Is Required for Efficient Recombination between Immunoglobulin Switch Regions
Authors: Reina-San-Martin Bernardo , Chen Hua Tang , Nussenzweig André , Nussenzweig Michel C.
Published: November 2004

Ataxia telangiectasia mutated (ATM) kinase is critical for initiating the signaling pathways that lead to cell cycle checkpoints and DNA double strand break repair. In the absence of ATM, humans and mice show a primary immunodeficiency that includes low serum antibody titers, but the role of ATM in antigen-driven immunoglobulin gene diversification has not been defined. Here, we show that although ATM is dispensable for somatic hypermutation, it is required for efficient class switch recombination (CSR). The defect in CSR is not due to alterations in switch region transcription, accessibility, DNA damage checkpoint protein recruitment, or short-range intra-switch region recombination. Only long-range inter-switch recombination is defective, indicating an unexpected role for ATM in switch region synapsis during CSR.
A simple combinatorial proof of a generalization of a result of Polo
Authors: Caselli Fabrizio
Published: November 2004

We provide a simple combinatorial proof of, and generalize, a theorem of Polo which asserts that for any polynomial

P
∈

N

[
q
]

P\in \mathbb N[q]

such that

P
(
0
)
=
1

P(0)=1

there exist two permutations

u
u

and

v
v

in a suitable symmetric group such that

P
P

is equal to the Kazhdan-Lusztig polynomial

P

u

v

P^{v}_{u}

.
Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viability
Authors: Arispe Nelson , Doh Michael , Simakova Olga , Kurganov Boris , Maio Antonio De
Published: November 2004

Heat shock proteins (hsps) are involved in multiple cellular processes during normal and stress conditions, particularly in the folding of polypeptides. A newly recognized property of the members of the Hsp70 family is their ability to interact with lipids, opening ion conductance pathways in artificial membranes, and integrating into natural membranes. The formation of Hsp70 channels in biological membranes and their function is still elusive. In this study, we showed that Hsp70 and Hsc70 display a highly selective interaction with phosphatidylserine moieties on membranes, followed by rapid incorporation into the lipid bilayer. Addition of Hsp70 or Hsc70 into the extracellular medium resulted in a viability decrease of cells beading PS on the exterior surface, such as PC12 cells. This toxic effect is modulated by the presence of ATP or ADP and can be blocked by screening PS moieties with annexin 5. These observations suggest that the presence of Hsp70 in the extracellular medium may be an accelerator of apoptosis since the presence of PS on the surface is an early indicator of this process. These findings may also explain the toxicity observed in cells overexpressing Hsp70s and provide a rational for the tight regulation of Hsp70 expression.—Arispe, N., Doh, M., Simakova, O., Kurganov, B., De Maio, A. Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viabifity.FASEBJ. 18, 1636–1645 (2004)
Weight loss regulates inflammation‐related genes in white adipose tissue of obese subjects
Authors: ClÉment Karine , Viguerie Nathalie , Poitou Christine , Carette Claire , Pelloux VÉronique , Curat Cyrile A. , Sicard Audrey , Rome Sophie , Benis Arriel , Zucker Jean‐Daniel , Vidal Hubert , Laville Martine , Barsh Gregory S. , Basdevant Arnaud , Stich Vladimir , Cancello Raffaella , Langin Dominique
Published: November 2004

Adipose tissue produces inflammation and immunity molecules suspected to be involved in obesity‐related complications. The pattern of expression and the nutritional regulation of these molecules in humans are poorly understood. We analyzed the gene expression profiles of subcutaneous white adipose tissue from 29 obese subjects during very low calorie diet (VLCD) using cDNA microarray and reverse transcription quantitative PCR. The patterns of expression were compared with that of 17 non‐obese subjects. We determined whether the regulated genes were expressed in adipocytes or stromavascular fraction cells. Gene expression profiling identified 100 inflammation‐related transcripts that are regulated in obese individuals when eating a 28 day VLCD but not a 2 day VLCD. Cluster analysis showed that the pattern of gene expression in obese subjects after 28 day VLCD was closer to the profile of lean subjects than to the pattern of obese subjects before VLCD. Weight loss improves the inflammatory profile of obese subjects through a decrease of proinflammatory factors and an increase of anti‐inflammatory molecules. The genes are expressed mostly in the stromavascular fraction of adipose tissue, which is shown to contain numerous macrophages. The beneficial effect of weight loss on obesity‐related complications may be associated with the modification of the inflammatory profile in adipose tissue.— Clément, K., Viguerie, N., Poitou, C., Carette, C., Pelloux, V., Curat, C. A., Sicard, A., Rome, S., Benis, A., Zucker, J.‐D., Vidal, H., Laville, M., Barsh, G. S., Basdevant, A., Stich, V., Cancello R., Langin, D. Weight loss regulates inflammation‐related genes in white adipose tissue of obese subjects. FASEB J. 18, 1657–1669 (2004)
Human C-Reactive Protein Increases Cerebral Infarct Size after Middle Cerebral Artery Occlusion in Adult Rats
Authors: Gill Ramanjit , Kemp John A. , Sabin Caroline , Pepys Mark B.
Published: November 2004

Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.
Protein Ubiquitination in Postsynaptic Densities after Transient Cerebral Ischemia
Authors: Liu Chen Li , Martone Maryann E. , Hu Bingren R.
Published: November 2004

The mechanisms underlying neurologic deficits and delayed neuronal death after ischemia are not fully understood. In the present study, we report that transient cerebral ischemia induces accumulation of ubiquitinated proteins (ubi-proteins) in postsynaptic densities (PSDs). By immunoelectron microscopy, we demonstrated that ubi-proteins were highly accumulated in PSD structures after ischemia. On Western blots, ubi-proteins were markedly increased in purified PSDs at 30 minutes of reperfusion, and the increase persisted until cell death in the CA1 region after ischemia. In the resistant DG area, however, the changes were transient and significantly less pronounced. Deposition of ubi-proteins in PSDs after ischemia correlates well with PSD structural damage in the CA1 region as viewed by electron microscopy. These results suggest that the ubiquitin-proteasome system fails to repair and remove damaged proteins in PSDs. The changes may demolish synaptic neurotransmission, contribute to neurologic deficits, and eventually lead to delayed neuronal death after transient cerebral ischemia.
Valproate is Neuroprotective against Malonate Toxicity in Rat Striatum: An Association with Augmentation of High-Affinity Glutamate Uptake
Authors: Morland Cecilie , Boldingh Karen Astrid , Iversen Evy Grini , Hassel Bjørnar
Published: November 2004

The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 μmol (1 M) of the succinate dehydrogenase inhibitor malonate. VPA-treated animals developed smaller lesions than control animals: 10 ± 2 mm3 versus 26 ± 8 mm3 (means ± SD; P = 10−4). Injection of NaCl that was equiosmolar with 1 M malonate caused lesions of only 1.2 ± 0.4 mm3 in control animals, whereas physiologic saline produced no lesion. VPA pretreatment reduced the malonate-induced extracellular accumulation of glutamate. This effect paralleled an increase in the striatal level of the glutamate transporter GLT, which augmented high-affinity glutamate uptake by 25%, as determined from the uptake of [3H] glutamate into striatal proteoliposomes. Malonate caused a 76% reduction in striatal adenosine triphosphate (ATP) content, but the glial, ATP-dependent formation of glutamine from radiolabeled glucose or glutamate was intact, indicating that glial ATP production supported uptake of glutamate. Striatal levels of HSP-70 and fos were reduced, and the levels of bcl-2 and phosphorylated extracellular signal-regulated kinase remained unaffected, but histone acetylation was increased by VPA treatment. The results suggest that augmentation of glutamate uptake may contribute importantly to VPA-mediated neuroprotection in striatum.
Cerebral Hemodynamic Reserve and Early Neurologic Deterioration in Acute Ischemic Stroke
Authors: Álvarez Francisco José , Segura Tomás , Castellanos Mar , Leira Rogelio , Blanco Miguel , Castillo Jose , Dávalos Antonio , Serena Joaquín
Published: November 2004

Early neurological deterioration (END) is associated with increased mortality and morbidity. Although several predictive factors have been reported, there are little data about the hemodynamic factors. Our aim was to determine the capacity of cerebral hemodynamic reserve (CHR) to predict END. We studied 100 hospitalized patients with a first ever ischemic stroke of the middle cerebral artery (MCA) within the first 24 hours of symptoms onset. END was defined as a drop of at least one point in the Canadian Stroke Scale between admission and 72 hours. The mean flow velocity (mV) in the MCA and the CHR were measured by means of transcranial Doppler within the first 24 hours of admission. The CHR was expressed as the percentage increase in the MCA mV divided by the absolute increase in the end-tidal CO2 pressure in mm Hg after carbogen inhalation. END was observed in 23 patients. Reduced values of the mV in the symptomatic MCA ( P = 0.043) and of the CHR in the symptomatic hemisphere ( P < 0.001) were significantly associated with END. A CHR of less than 2%/1 mm Hg was independently associated with END (OR 8.45, 95% CI 1.82–39.2) after adjusting for potential confounders. CHR impairment within the first 24 hours of acute ischemic stroke is associated with a higher risk of END. This technique may be useful in selecting patients requiring a more intensive management.
Does the Acute Diffusion-Weighted Imaging Lesion Represent Penumbra as Well as Core? A Combined Quantitative PET/MRI Voxel-Based Study
Authors: Guadagno Joseph V. , Warburton Elizabeth A. , Aigbirhio Franklin I. , Smielewski Piotr , Fryer Tim D. , Harding Sally , Price Christopher J. , Gillard Jonathan H. , Carpenter T. Adrian , Baron Jean-Claude
Published: November 2004

In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is widely held to represent the core of irreversible damage and is therefore crucial in selecting patients for thrombolysis. However, recent research suggests it may also represent penumbra. An illustrative patient was imaged 7 hours after stroke onset with back-to-back 3T diffusion tensor imaging and quantitative positron emission tomography, which showed a DWI lesion and misery perfusion, respectively. Using previously validated voxel-based probabilistic CBF, CMRO2, and Oxygen Extraction Fraction (OEF) thresholds, the authors show that the DWI lesion contained not only core but also substantial proportions of penumbra. Also, severe apparent diffusion coefficient reductions were present within the potentially salvageable penumbra as well as in the core. These findings have potential implications regarding treatment decisions.
Inhibition of Toll-like Receptor and Cytokine Signaling—A Unifying Theme in Ischemic Tolerance
Authors: Karikó Katalin , Weissman Drew , Welsh Frank A.
Published: November 2004

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1β and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.
Discrimination between ricin and sulphur mustard toxicityin vitrousing Raman spectroscopy
Authors: Notingher Ioan , Green Chris , Dyer Chris , Perkins Elaine , Hopkins Neil , Lindsay Chris , Hench Larry L.
Published: November 2004

A Raman spectroscopy cell-based biosensor has been proposed for rapid detection of toxic agents, identification of the type of toxin and prediction of the concentration used. This technology allows the monitoring of the biochemical properties of living cells over long periods of time by measuring the Raman spectra of the cells non-invasively, rapidly and without use of labels (Notingheret al.2004 doi:10.1016/j.bios.2004.04.008). Here we show that this technology can be used to distinguish between changes induced in A549 lung cells by the toxin ricin and the chemical warfare agent sulphur mustard. A multivariate model based on principal component analysis (PCA) and linear discriminant analysis (LDA) was used for the analysis of the Raman spectra of the cells. The leave-one-out cross-validation of the PCA-LDA model showed that the damaged cells can be detected with high sensitivity (98.9%) and high specificity (87.7%). High accuracy in identifying the toxic agent was also found: 88.6% for sulphur mustard and 71.4% for ricin. The prediction errors were observed mostly for the ricin treated cells and the cells exposed to the lower concentration of sulphur mustard, as they induced similar biochemical changes, as indicated by cytotoxicity assays. The concentrations of sulphur mustard used were also identified with high accuracy: 93% for 200 μM and 500 μM, and 100% for 1000 μM. Thus, biological Raman microspectroscopy and PCA-LDA analysis not only distinguishes between viable and damaged cells, but can also discriminate between toxic challenges based on the cellular biochemical and structural changes induced by these agents and the eventual mode of cell death.
At the interface between signaling and executing anaphase—Cdc14 and the FEAR network
Authors: D'Amours Damien , Amon Angelika
Published: November 2004

Anaphase is the stage of the cell cycle when the duplicated genome is separated to opposite poles of the cell. The irreversible nature of this event confers a unique burden on the cell and it is therefore not surprising that the regulation of this cell cycle stage is complex. In budding yeast, a signaling network known as the Cdc fourteen early anaphase release (FEAR) network and its effector, the protein phosphatase Cdc14, play a key role in the coordination of the multiple events that occur during anaphase, such as partitioning of the DNA, regulation of spindle stability, activation of microtubule forces, and initiation of mitotic exit. These functions of the FEAR network contribute to genomic stability by coordinating the completion of anaphase and the execution of mitotic exit.
A novel, high-performance random array platform for quantitative gene expression profiling
Authors: Kuhn Kenneth , Baker Shawn C. , Chudin Eugene , Lieu Minh-Ha , Oeser Steffen , Bennett Holly , Rigault Philippe , Barker David , McDaniel Timothy K. , Chee Mark S.
Published: November 2004

We have developed a new microarray technology for quantitative gene-expression profiling on the basis of randomly assembled arrays of beads. Each bead carries a gene-specific probe sequence. There are multiple copies of each sequence-specific bead in an array, which contributes to measurement precision and reliability. We optimized the system for specific and sensitive analysis of mammalian RNA, and using RNA controls of defined concentration, obtained the following estimates of system performance: specificity of 1:250,000 in mammalian poly(A+) mRNA; limit of detection 0.13 pM; dynamic range 3.2 logs; and sufficient precision to detect 1.3-fold differences with 95% confidence within the dynamic range. Measurements of expression differences between human brain and liver were validated by concordance with quantitative real-time PCR (R2= 0.98 for log-transformed ratios, and slope of the best-fit line = 1.04, for 20 genes). Quantitative performance was further verified using a mouse B- and T-cell model system. We found published reports of B- or T-cell-specific expression for 42 of 59 genes that showed the greatest differential expression between B- and T-cells in our system. All of the literature observations were concordant with our results. Our experiments were carried out on a 96-array matrix system that requires only 100 ng of input RNA and uses standard microtiter plates to process samples in parallel. Our technology has advantages for analyzing multiple samples, is scalable to all known genes in a genome, and is flexible, allowing the use of standard or custom probes in an array.
Plant Proteins That Interact with VirB2, theAgrobacterium tumefaciensPilin Protein, Mediate Plant Transformationw⃞
Authors: Hwang Hau-Hsuan , Gelvin Stanton B.
Published: November 2004

Agrobacterium tumefaciens uses a type IV secretion system (T4SS) to transfer T-DNA and virulence proteins to plants. The T4SS is composed of two major structural components: the T-pilus and a membrane-associated complex that is responsible for translocating substrates across both bacterial membranes. VirB2 protein is the major component of the T-pilus. We used the C-terminal–processed portion of VirB2 protein as a bait to screen an Arabidopsis thaliana cDNA library for proteins that interact with VirB2 in yeast. We identified three related plant proteins, VirB2-interacting protein (BTI) 1 (BTI1), BTI2, and BTI3 with unknown functions, and a membrane-associated GTPase, AtRAB8. The three BTI proteins also interacted with VirB2 in vitro. Preincubation of Agrobacterium with GST-BTI1 protein decreased the transformation efficiency of Arabidopsis suspension cells by Agrobacterium. Transgenic BTI and AtRAB8 antisense and RNA interference Arabidopsis plants are less susceptible to transformation by Agrobacterium than are wild-type plants. The level of BTI1 protein is transiently increased immediately after Agrobacterium infection. In addition, overexpression of BTI1 protein in transgenic Arabidopsis results in plants that are hypersusceptible to Agrobacterium-mediated transformation. Confocal microscopic data indicate that GFP-BTI proteins preferentially localize to the periphery of root cells in transgenic Arabidopsis plants, suggesting that BTI proteins may contact the Agrobacterium T-pilus. We propose that the three BTI proteins and AtRAB8 are involved in the initial interaction of Agrobacterium with plant cells.
Red‐winged blackbirds Agelaius phoeniceus use carotenoid and melanin pigments to color their epaulets
Authors: McGraw Kevin J. , Wakamatsu Kazumasa , Clark Anne B. , Yasukawa Ken
Published: November 2004

Over the past three decades, the red‐winged blackbird Agelaius phoeniceus has served as a model species for studies of sexual selection and the evolution of ornamental traits. Particular attention has been paid to the role of the colorful red‐and‐yellow epaulets that are striking in males but reduced in females and juveniles. It has been assumed that carotenoid pigments bestow the brilliant red and yellow colors on epaulet feathers, but this has never been tested biochemically. Here, we use high‐performance liquid chromatography (HPLC) to describe the pigments present in these colorful feathers. Two red ketocarotenoids (astaxanthin and canthaxanthin) are responsible for the bright red hue of epaulets. Two yellow dietary precursors pigments (lutein and zeaxanthin) are also present in moderately high concentrations in red feathers. After extracting carotenoids, however, red feathers remained deep brown in color. HPLC tests show that melanin pigments (primarily eumelanin) are also found in the red‐pigmented barbules of epaulet feathers, at an approximately equal concentration to carotenoids. This appears to be an uncommon feature of carotenoid‐based ornamental plumage in birds, as was shown by comparable analyses of melanin in the yellow feathers of male American goldfinches Carduelis tristis and the red feathers of northern cardinals Cardinalis cardinalis, in which we detected virtually no melanins. Furthermore, the yellow bordering feathers of male epaulets are devoid of carotenoids (except when tinged with a carotenoid‐derived pink coloration on occasion) and instead are comprised of a high concentration of primarily phaeomelanin pigments. The dual pigment composition of red epaulet feathers and the melanin‐only basis for yellow coloration may have important implications for the honesty‐reinforcing mechanisms underlying ornamental epaulets in red‐winged blackbirds, and shed light on the difficulties researchers have had to date in characterizing the signaling function of this trait. As in several other birds, the melanic nature of feathers may explain why epaulets are used largely to settle aggressive contests rather than to attract mates.
The management of side‐effects during therapy for hepatitis C
Authors: Aspinall R. J. , Pockros P. J.
Published: November 2004

The results of interferon and ribavirin combination therapy for chronic hepatitis C infection have substantially improved in recent years, such that the majority of patients in randomized‐controlled trials now achieve a sustained virological response. However, adverse effects are commonplace, often disabling and may lead to interruption or cessation of therapy with subsequent loss of efficacy. Constitutional, neuropsychiatric and haematological reactions have proved particularly troublesome. In this review, we discuss these adverse effects in more detail and highlight recent advances in their management.
Sleep dysfunction in patients with gastro‐oesophageal reflux disease: prevalence and response to GERD therapy, a pilot study
Authors: Chand N. , Johnson D. A. , Tabangin M. , Ware J. C.
Published: November 2004

Background : There is little information on the prevalence of pathological sleep disorders in patients with gastro‐oesophageal reflux disease and whether pharmacological treatment of patients with gastro‐oesophageal reflux disease will lead to improvement in sleep.

Aims:  This pilot study determined the prevalence of sleep disorder in patients with erosive gastro‐oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy – a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep.

Methods : Eighteen patients with erosive gastro‐oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy.

Results : Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro‐oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P ≤ 0.0001). Median global Pittsburgh Sleep Quality Index score decreased from 8.50 at baseline to 4.50 at week 4 (P = 0.002) and to 7.00 at week 8 (P = 0.043). There were no significant changes in actigraphy measurements.

Conclusions : Sleep disturbance is common in patients with gastro‐oesophageal reflux disease with erosive oesophagitis. This study which is the first to evaluate sleep abnormalities and gastro‐oesophageal reflux disease using a validated questionnaire, demonstrates that in patients with gastro‐oesophageal reflux disease, sleep improvement, may be effected by gastro‐oesophageal reflux disease therapy. Actigraphy may be inappropriate for measurement of sleep disturbance in gastro‐oesophageal reflux disease patients.
Tolerability of spironolactone in patients with chronic heart failure – a cautionary message
Authors: Witham Miles D. , Gillespie Neil D. , Struthers Allan D
Published: November 2004

Aim

To assess how well heart failure patients tolerate spironolactone in routine clinical practice.

Design

Retrospective analysis of 226 patients attending a specialist heart failure clinic.

Results

One hundred and thirty of 226 (57.5%) patients tried spironolactone at least once. Forty‐four of 130 (33.8%) discontinued spironolactone due to side‐effects after a mean of 11.1 months; 59/141 (41.8%) trials of spironolactone resulted in at least one side‐effect; therapy was stopped in 30/141 (21.3%) trials due to raised potassium or creatinine. Significant risk factors for raised potassium/creatinine were age and baseline potassium level.

Conclusions

Potentially serious side‐effects are common despite appropriate use of spironolactone.