bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous low‐frequency voltage oscillations in frog saccular hair cells
Authors: Catacuzzeno Luigi , Fioretti Bernard , Perin Paola , Franciolini Fabio
Published: October 2004

Spontaneous membrane voltage oscillations were found in 27 of 130 isolated frog saccular hair cells. Voltage oscillations had a mean peak‐to‐peak amplitude of 23 mV and a mean oscillatory frequency of 4.6 Hz. When compared with non‐oscillatory cells, oscillatory cells had significantly greater hyperpolarization‐activated and lower depolarization‐activated current densities. Two components, the hyperpolarization‐activated cation current, Ih, and the K+‐selective inward‐rectifier current, IK1, contributed to the hyperpolarization‐activated current, as assessed by the use of the IK1‐selective inhibitor Ba2+ and the Ih‐selective inhibitor ZD‐7288. Five depolarization‐activated currents were present in these cells (transient IBK, sustained IBK, IDRK, IA, and ICa), and all were found to have significantly lower densities in oscillatory cells than in non‐oscillatory cells (revealed by using TEA to block IBK, 4‐AP to block IDRK, and prepulses at different voltages to isolate IA). Bath application of either Ba2+ or ZD‐7288 suppressed spontaneous voltage oscillations, indicating that Ih and IK1 are required for generating this activity. On the contrary, TEA or Cd2+ did not inhibit this activity, suggesting that IBK and ICa do not contribute. A mathematical model has been developed to test the interpretation derived from the pharmacological and biophysical data. This model indicates that spontaneous voltage oscillations can be generated when the electrophysiological features of oscillatory cells are used. The oscillatory behaviour is principally driven by the activity of IK1 and Ih, with IA playing a modulatory role. In addition, the model indicates that the high densities of depolarization‐activated currents expressed by non‐oscillatory cells help to stabilize the resting membrane potential, thus preventing the spontaneous oscillations.
Persistent gamma oscillations in superficial layers of rat auditory neocortex: experiment and model
Authors: Traub Roger D. , Bibbig Andrea , LeBeau Fiona E. N. , Cunningham Mark O. , Whittington Miles A.
Published: October 2004

Persistent in vitro gamma oscillations, induced by bath application of carbachol and kainate (amongst other drugs), were discovered by Eberhard Buhl and collaborators in 1998. The oscillations are robust, in that they can continue for hours; but the oscillations are also intricate in their mechanisms: they depend upon phasic synaptic excitation and inhibition, upon electrical coupling between interneurones and between pyramidal neurones, and – at least in neocortex – they depend upon complex intrinsic properties of some of the neurones.
Plunger Slippage for Rod-Drawn Plunger Pumps
Authors: Chambliss R. Kyle , Cox James Christian , Lea James F.
Published: October 2004

A theoretical calculation is needed to predict pump slippage in a rod pumped well. Slippage lubricates the pump plunger and barrel and prevents galling of metals. Additionally, an estimate of plunger slippage is necessary to calculate pump efficiency. Historical plunger slippage equations have been proven incorrect by recent testing. A new method for calculating plunger pump slippage in rod pumped wells is introduced. This method involves calculating a velocity profile for an annulus with the inner wall moving parallel to the outer wall. An average velocity is determined for the annular fluid flow, which in turn is used to calculate the fluid slippage. The results are evaluated against the historical field data and compare favorably to recent testing for smaller plunger clearances. Work remains to be done at larger clearances.
Bias-temperature stress analysis of Cu∕ultrathin Ta∕SiO2∕Si interconnect structure
Authors: Lim Boon Kiat , Park Hun Sub , Chin Lian Kon , Woo Sun Woong , See Alex K. H. , Seet Chim-Seng , Lee Tae-Jong , Yakovlev Nikolai L.
Published: October 2004

Bias-temperature stress test was used to evaluate the efficiency of an ultrathin Ta diffusion barrier in Cu interconnects by assessing the failure mode of the Cu interconnect structure. Samples are stressed up to failure in order to study the actual failure mode of fabricated MOS capacitors. The time-to-failure (TTF) of samples is estimated to be at least 14 years under standard operating conditions, which is determined by extrapolating TTFs of current–time (I–t) curves measured at accelerated test conditions. The calculated activation energies of the capacitors is within range of normal time-dependent dielectric breakdown (TDDB) activation energies, suggesting TDDB-related failure. Tof-SIMS and I–t analyses strongly suggest a mixed mode failure mechanism in the capacitors, where Cu+ ion contamination is dominant at low field and high temperature stress conditions, while TDDB dominates at other conditions.
Growth characteristics of oxide during prolonged anodization of aluminum in preparing ordered nanopore arrays
Authors: Wu M. T. , Leu I. C. , Hon M. H.
Published: October 2004

In this study, one-step anodization was conducted on both mechanically polished and electropolished Al foils at different temperatures to examine their growth characteristics during prolonged anodization. Several unusual phenomena different from those reported previously were observed, especially for the preparation of ordered pore arrays on electropolished Al foils. First, under a constant voltage condition, a continuous increase of the oxidation current with fluctuation was observed in a prolonged period of anodization at high temperatures. Second, the ordered pore arrangement of the oxide initially obtained on the electropolished Al foil anodized at 25 °C was found to become disordered after being anodized for 72 h. Third, the total film thickness increased in the beginning and decreased in the prolonged period when the anodization was conducted at a high temperature. Thus, it is concluded that a highly ordered pore configuration with a large aspect ratio could only be obtained on the electropolished substrate by anodizing for a moderate period of time at low temperatures.
Integration of benzocyclobutene polymers and silicon micromachined structures using anisotropic wet etching
Authors: Ghalichechian Nima , Modafe Alireza , Ghodssi Reza , Lazzeri Paolo , Micheli Victor , Anderle Mariano
Published: October 2004

Integration of thick, low-k dielectric benzocyclobutene (BCB) film with deep etched structures in silicon allows the fabrication of microelectromechanical systems (MEMS) devices with low parasitic loss. A fabrication process is developed for integration of 1-μm-thick BCB low-k dielectric film and 200-μm-deep anisotropically etched grooves in silicon with potassium hydroxide (KOH). In order to protect the low-k film during the highly corrosive, long, high-temperature KOH etching process, gold (Au) is used as an etch mask. Chromium (Cr) is used to improve the adhesion of Au to the underlying BCB layer. Metal-BCB adhesion is the key parameter in this masking design. Partial cure of BCB at 210 °C for 40 min with appropriate surface treatment (adhesion promoter) prior to metallization and full cure at 250 °C for 1 h after metallization, together with Cr/Au sputtering at 200 °C, improves the adhesion dramatically. The adhesion strength of metal films to BCB was experimentally verified in a qualitative manner. V grooves were etched into silicon in 20 wt%, 80 °C KOH solution for 8 h in the presence of 1 μm BCB film. BCB was protected and kept intact with an Au mask layer during the etch process. In order to understand the mechanism of the adhesion improvement, the interface between BCB and the Cr/Au layer was studied using secondary ion mass spectroscopy and Auger electron spectroscopy. Adhesion improvement which is mainly due to cure management and use of adhesion promoter is associated with (1) the diffusion of silicon and carbon from the polymer structure into the Cr layer, and (2) the chemical interaction of BCB and Cr at the interface mainly in the form of the oxidation of Cr. The integration of BCB and the KOH etching process which was obtained by improving the adhesion of metal etch mask to the BCB film, together with the study of the interfaces, allow us to use thick low dielectric constant BCB film for fabrication of MEMS devices with very low parasitic loss.
Characteristics of polarity-controlled ZnO films fabricated using the homoepitaxy technique
Authors: Matsui Hiroaki , Saeki Hiromasa , Kawai Tomoji , Sasaki Atsushi , Yoshimoto Mamoru , Tsubaki Masato , Tabata Hitoshi
Published: October 2004

Hydrothermal ZnO(0001) substrates with high crystalline quality were employed in the fabrication of polarity-controlled ZnO films using laser molecular beam epitaxy. The repolished Zn- and O-polar surfaces of ZnO substrates displayed atomically flat surfaces and high crystalline quality even after annealing at high temperatures, as evidenced from high-resolution x-ray diffraction and atomic force microscopy analyses. The electrical and optical properties of Zn-polar ZnO films were significantly improved when annealed, as opposed to polished, substrates were used. This reduced the diffusion of impurities and suppressed the formation of a disordered degenerate layer that might have formed at the interface regions between the substrate and the film. On the other hand, the characteristics of O-polar ZnO films were almost independent of the ZnO substrate pretreatment. In particular, heat-treatment of the substrate for Zn-polar rather than O-polar growth played an important role in minimizing the surface damage generated during mechanical and mechano-chemical polishing. This study paid attention to the influence of heat-treatment on Zn-polar surfaces of high crystallinity ZnO substrates, providing information toward the fabrication of homoepitaxial growth in Zn-polarity.
Selectively deposited Ru top electrode on Pb(Zr0.3Ti0.7)O3 and Ru step coverage on TiN by digital chemical vapor deposition
Authors: Dey S. K. , Goswami J. , Bhaskar S. , Cao W. , Noh W. C.
Published: October 2004

A digital chemical vapor deposition (DCVD) process was used to selectively deposit ruthenium on hydroxyl-terminated Pb(Zr0.3Ti0.7)O3 (PZT) surface patterned with a photoresist; the PZT was on Ru/sapphire substrate. The DCVD of Ru was carried out at 280–320°C using an alternate delivery of Bis (2,2,6,6-tetramethyl-3,5-heptanedionato) (1,5-cyclooctadiene)Ru (dissolved in tetrahydrofuran) and oxygen. The ferroelectric hysteresis of Pb(Zr,Ti)O3 on Ru/sapphire with selectively deposited top Ru electrode by digital CVD was measured, which yielded a symmetric hysteresis loop with high remnant polarization of 40μC∕cm2. Additionally, Ru films, deposited by DCVD on high aspect ratio vias of TiN on Si, exhibited nearly 100% step coverage. This DCVD process shows promise for attaining three-dimensional metal/PZT/metal stacks for high density ferroelectric random access memories.
Enhancement of adhesion strength of Cu seed layer with different thickness in Cu∕low-k multilevel interconnects
Authors: Wang Grace , Jong Yoo Won , Balakumar S. , Seah C. H. , Hara T.
Published: October 2004

A systematic study was made on the properties of a copper (Cu) seed layer deposited with two different thicknesses and subsequent annealing to enhance the adhesion strength to avoid peeling and delamination in Cu∕low-dielectric constant (k) multilevel interconnects. Though the effects of annealing conditions have been much studied in the past, less is known about the relation between thermal stability of copper seeds at low and high annealing temperatures of 100 and 300°C, respectively, with seed thickness below 1000Å. Adhesion strength of copper seeds annealed at 100, 200, and 300°C in N2 ambient for 30min was carried out to study the impact on adhesion strength and the microstructure evolution of coupling effect of thin copper seed layers and low annealing temperatures. The lowest observed resistivity was 1.96μΩcm in the 1500Å Cu seed annealed at 300°C, which reduced from 2.10μΩcm in as-deposited condition. In the study, we found that minimal agglomeration of the Cu seed layer and stronger bonding at the Ta∕Cu interface indicates higher reliability for copper damascene structure. This further strengthens our claim that a lower annealing temperature is essential for enhancing adhesion strength and interfacial bonding between Cu∕dielectric.
Experimental aspects and modeling for quantitative measurements in scanning capacitance microscopy
Authors: Giannazzo F. , Goghero D. , Raineri V.
Published: October 2004

In this article we discuss the reliability of a quantification method for scanning capacitance microscopy (SCM) measurements based on the calculation of a calibration curve. We demonstrate that an accurate control of the conductive tip coating stability, low temperature oxidation and Si–SiO2 interface microroughness allows one to fabricate a nanometric metal-oxide-semiconductor device (nanoMOS), whose dC∕dV-V characteristics measured on a set of different concentration levels can be reproduced by simulation of an ideal nanoMOS with the realistic three-dimensional geometry. We also studied the impact of tip coating (metal and conductive diamond coated tips) and oxidation method (wet and UV∕ozone oxides) on the reproducibility of the measured SCM signal for different concentration levels both on p- and n-type Si staircase calibration samples, and we demonstrated that the UV∕ozone oxidation associated with the use of a diamond tip is the best solution. The experimental calibration curve obtained by this choice is well fitted by the calculated calibration curve. The maximum experimental errors affecting the measured SCM signal depending on doping concentrations have been determined and these errors have been used to estimate the maximum errors on the concentration values calculated by applying the theoretical calibration curve.
Growth and characterization of Sn-doped GaAsSb and GaAs epilayers on GaAs (001)
Authors: Uchitomi N. , Takei T. , Endoh M. , Jinbo Y.
Published: October 2004

We investigated the growth of GaAs1−xSbx(x⩽0.4) and GaAs epilayers with heavy Sn doping using molecular-beam epitaxy, and characterized the doping concentration as a function of Sn K-cell temperature. The carrier concentration was found to be expressed as a function of the reciprocal Sn effusion cell temperature with respect to GaAs1−xSbx(x=0.15) layers. At cell temperatures of 670–800°C, carrier concentrations ranging from 5×1016to8×1018cm−3 showed a simple exponential dependency. When the ratios of TO-mode to LO-mode intensities in GaAs1−xSbx(x=0.15) layers were measured as a function of Sn-cell temperature by micro-Raman scattering, the peak intensity ratio was linearly proportional to the Sn-cell temperature in the range of 700–900°C.
Fabrication of wide-IF 200–300GHz superconductor–insulator–superconductor mixers with suspended metal beam leads formed on silicon-on-insulator
Authors: Kaul Anupama B. , Bumble Bruce , Lee Karen A. , LeDuc Henry G. , Rice Frank , Zmuidzinas Jonas
Published: October 2004

We report on a fabrication process that uses SOI substrates and micromachining techniques to form wide-IF SIS mixer devices that have suspended metal beam leads for rf grounding. The mixers are formed on thin 25μm membranes of Si, and are designed to operate in the 200–300GHz band. Potential applications are in tropospheric chemistry, where increased sensitivity detectors and wide-IF bandwidth receivers are desired. They will also be useful in astrophysics to monitor absorption lines for CO at 230GHz to study distant, highly redshifted galaxies by reducing scan times. Aside from a description of the fabrication process, electrical measurements of these Nb∕Al–AlNx∕Nb trilayer devices will also be presented. Since device quality is sensitive to thermal excursions, the new beam lead process appears to be compatible with conventional SIS device fabrication technology.
Development of thin film getters suitable for field-emission display in high vacuum systems
Authors: Kim Kyung Chan , Ahn Han Jin , Yoon Young Joon , Baik Hong Koo , Lee Sung-Man , Lee Se-Jong
Published: October 2004

Recently, getters have been widely used in vacuum microelectronics requiring high vacuum. The conventional bulk getters require high-temperature activation processes to function properly as a getter, where outgassing of different gases, for example, H2, O2, H2O, CO, and CO2, contaminate the device. In addition, the conventional bulk getter itself is not suitable for microelectronic devices due to its size limitations. A thin-film getter is small enough for microelectronic applications that require no activation with excellent resonant gas absorption characteristics. Thus, it is fabricated and analyzed as a resolution to such problems. In this work, Zr film has been used as a getter material, and Ni and Pt films for catalysis and protection of the getter from oxidation. The introduction of Pt and Ni layers in thin-film getters exhibits the excellent absorption characteristics of impurity gases in high vacuum without high-temperature activation. Realization of thin-film getters overcomes the size limitations of bulk getters, enabling the getter to be used in microelectronic devices.
Al
Ga
N
∕
Ga
N
metal-oxide-semiconductor heterostructure field-effect transistors using barium strontium titanate
Authors: Hansen P. J. , Shen L. , Wu Y. , Stonas A. , Terao Y. , Heikman S. , Buttari D. , Taylor T. R. , DenBaars S. P. , Mishra U. K. , York R. A. , Speck J. S.
Published: October 2004

Use of high-k gate dielectrics in AlGaN∕GaN heterostructure field-effect transistors (HFETs) may reduce gate leakage and improve device reliability without adversely impacting transconductance and pinchoff voltage. To achieve this, AlGaN∕GaN metal-oxide-semiconductor heterostructure field-effect transistors have been formed by incorporating barium strontium titanate (BST) deposited by rf magnetron sputtering as the gate dielectric. The maximum current achieved was slightly lower than realized in standard devices without BST, while the gate leakage of the devices was reduced by ∼5 orders of magnitude compared to a conventional HFET for the as-deposited devices and 4 orders of magnitude for films annealed in N2. The transconductance and pinchoff voltage were found to vary with different dielectric constants of the BST films, being reduced by ∼25% for a 40nm film with a dielectric constant of 20, and by 14% upon annealing in N2 (dielectric constant ∼66) when compared to a baseline device with no oxide. It was found that the BST deposition temperature greatly affected mobility in the AlGaN∕GaN structure, with higher temperatures significantly reducing the HFET mobility.
Carbon-doped InP∕In0.53Ga0.47As single and double heterojunction bipolar transistors grown by solid-source molecular-beam epitaxy
Authors: Zhang R. , Yoon S. F. , Tan K. H. , Lew K. L. , Sun Z. Z.
Published: October 2004

Carbon-doped InP∕InGaAs single heterojunction bipolar transistors (SHBTs) and double heterojunction bipolar transistors (DHBTs) have been grown by solid-source molecular-beam epitaxy using CBr4 as p-type dopant precursor. DC characteristics of InP∕InGaAs composite collector DHBT have been compared with the SHBT. A current gain of 40 and breakdown voltage of 10V were obtained for the composite collector DHBT with no obvious knee-shaped characteristics or switching effect. The results show the composite collector design of DHBTs can effectively suppress the current blocking effect and improve the breakdown voltage. Furthermore, this study elucidates the complex breakdown mechanisms in the composite collector DHBTs.
Fabrication and characterization of 650nm resonant-cavity light-emitting diodes
Authors: Tsai Chia-Lung , Ho Chih-Wei , Huang Chun-Yuan , Lee Feng-Ming , Wu Meng-Chyi , Wang Hai-Lin , Ko Sum-Chien , Ho Wen-Jeng , Huang Jet , Deng J. R.
Published: October 2004

In this article, we report the fabrication and characterization of 650nm resonant-cavity light-emitting diodes (RCLEDs) with the GaInP∕AlGaInP multi-quantum-well active layer sandwiched between two AlGaAs∕AlAs distributed Bragg reflectors. We compare the performance of RCLEDs with different mesa diameters in the characteristics of forward voltage, light output power, external quantum efficiency, emission spectrum, and dynamic response. All the RCLEDs have a low forward voltage of 1.9–2.0V at 20mA. The RCLED with a window diameter of 120μm exhibits the maximum light output power of 0.79mW at 39mA, the best external quantum efficiency of 2.8% at 1.2mA, a peak wavelength of 647nm, and a full width at half-maximum of 14.5nm at 50mA. The RCLED with a 30μm diameter shows the maximum 3dB frequency bandwidth of 240MHz at a driving current of 40mA.
Oxidation-induced improvement in the sidewall morphology and cross-sectional profile of silicon wire waveguides
Authors: Takahashi Jun-ichi , Tsuchizawa Tai , Watanabe Toshifumi , Itabashi Sei-ichi
Published: October 2004

Progress in sidewall morphology smoothing of Si wire waveguides by thermal oxidization was observed using a focused-ion-beam (FIB) transmission-electron-microscopy technique. The roughness of Si∕SiO2 interface was drastically reduced with increasing oxidation time and temperature. Deformation of the cross-sectional profile of the waveguides was observed with secondary electron images of scanning FIB irradiation. The initial rectangular profile is transformed due to stress concentration at the rectangle corners at oxidation temperatures of 900 and 1000°C. In contrast, at 1100°C, the profile maintains the original rectangular profile due to the stress release by the viscous flowing of SiO2. These results indicate that the optimum oxidation condition for the Si wire waveguide has been found, which provides an extremely smooth sidewall without deformation of the cross-sectional profile.
VCAM-1 upregulation via PKCδ-p38 kinase-linked cascade mediates the TNF-α-induced leukocyte adhesion and emigration in the lung airway epithelium
Authors: Woo Chang-Hoon , Lim Jae-Hyang , Kim Jae-Hong
Published: October 2004

Vascular cell adhesion molecule (VCAM)-1 plays a central role in the recruitment of inflammatory cells, and its expression is rapidly induced by proinflammatory cytokines such as TNF-α. In the present study, we show that pretreatment with rottlerin, a specific inhibitor of protein kinase C (PKC)-δ, or transient transfection with antisense PKCδ oligonucleotides significantly inhibits TNF-α-induced expression of VCAM-1, but not of intercellular adhesion molecule (ICAM)-1 in human lung epithelium A549 cells. In addition, TNF-α was shown to induce the expression of VCAM-1 in a p38 kinase-dependent manner; also, TNF-α-induced p38 kinase activation was blocked by inhibition of PKCδ, suggesting that p38 kinase is apparently situated downstream of PKCδ in the TNF-α-signaling pathway to VCAM-1 expression. Notably, inhibition of the PKCδ-p38 kinase cascade also attenuated the TNF-α-induced adhesion of neutrophils to lung epithelium and the trafficking of leukocytes across the epithelium into the airway lumen in vivo. Together, these findings indicate that signaling via PKCδ-p38 kinase-linked cascade specifically induces expression of VCAM-1 in lung epithelium in response to TNF-α and that this effect is both functionally and clinically significant.
Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-κB in IL-1β-induced VCAM-1 expression in human tracheal smooth muscle cells
Authors: Wang Chien-Chun , Lin Wei-Ning , Lee Chiang-Wen , Lin Chih-Chung , Luo Shue-Fen , Wang Jong-Shyan , Yang Chuen-Mao
Published: October 2004

Interleukin-1β (IL-1β) has been shown to induce the expression of adhesion molecules on airway epithelial and smooth cells and contributes to inflammatory responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways for IL-1β-induced vascular cell adhesion molecule (VCAM)-1 expression were investigated in human tracheal smooth muscle cells (HTSMC). IL-1β induced expression of VCAM-1 protein and mRNA in a time-dependent manner, which was significantly inhibited by inhibitors of MEK1/2 (U0126 and PD-98059), p38 (SB-202190), and c-Jun NH2-terminal kinase (JNK; SP-600125). Consistently, IL-1β-stimulated phosphorylation of p42/p44 MAPK, p38, and JNK was attenuated by pretreatment with U0126, SB-202190, or SP-600125, respectively. IL-1β-induced VCAM-1 expression was significantly blocked by the specific NF-κB inhibitors helenalin and pyrrolidine dithiocarbamate. As expected, IL-1β-stimulated translocation of NF-κB into the nucleus and degradation of IκB-α were blocked by helenalin but not by U0126, SB-202190, or SP-600125. Moreover, the resultant enhancement of VCAM-1 expression increased the adhesion of polymorphonuclear cells to a monolayer of HTSMC, which was blocked by pretreatment with helenalin, U0126, SB-202190, or SP-600125 before IL-1β exposure or by anti-VCAM-1 antibody. Together, these results suggest that in HTSMC, activation of p42/p44 MAPK, p38, JNK, and NF-κB pathways is essential for IL-1β-induced VCAM-1 gene expression. These results provide new insight into the mechanisms of IL-1β action that cytokines may promote inflammatory responses in airway disease.
Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice
Authors: Wilson Michael R. , Choudhury Sharmila , Takata Masao
Published: October 2004

Although high-stretch mechanical ventilation has been demonstrated to induce lung inflammation, the roles of soluble mediators, in particular TNF, remain controversial. We have previously shown in mice that high-stretch ventilation, in the absence of preceding lung injury, induces expression of bioactive TNF in lung lavage fluid early in the course of injury, but the biological significance of this, if any, has yet to be determined. We therefore investigated the pulmonary inflammatory response to a transient period of high-stretch ventilation in anesthetized mice lacking TNF receptors and mice treated with anti-TNF antibodies. A standardized stretch-induced lung injury (assessed by lung mechanics, blood gases, and lavage protein content), followed by noninjurious low-stretch ventilation for 3 h, produced significant alveolar neutrophil infiltration in wild-type mice. However, neutrophil recruitment was substantially attenuated in TNF receptor double knockout mice and in wild-type mice treated with intratracheal anti-TNF antibody. This attenuation was not associated with decreased concentrations of neutrophil attractant CXC chemokines (macrophage inflammatory protein-2 and keratinocyte-derived chemokine) in lavage fluid. In contrast to intratracheal antibody, intravenous anti-TNF antibody did not reduce neutrophil infiltration, suggesting that the role of TNF signaling is localized within the alveolar space and does not require decompartmentalization of TNF into the circulation. These findings provide the first direct evidence that pulmonary inflammation induced by high-stretch ventilation without underlying lung injury possesses a significant TNF-dependent component. The results suggest a potential for regional anti-TNF treatment in attenuating stretch-induced pulmonary inflammation.
Differential localization of mammalian Lin-7 (MALS/Veli) PDZ proteins in the kidney
Authors: Olsen Olav , Wade James B. , Morin Nick , Bredt David S. , Welling Paul A.
Published: October 2004

Lin-7 PDZ proteins, also called MALS or Velis, have been shown to coordinate basolateral membrane expression of various target proteins in renal epithelial cell models. Three different Lin-7/MALS/Veli isoforms, encoded by separate genes, have been identified. Here, we show that each Lin-7/MALS/Veli isoform is expressed in the kidney. Using MALS isoform-specific antibodies in combination with cell-specific marker antibodies, we found the products of the three mammalian Lin-7/MALS/Veli genes are differentially expressed along the length of the nephron. MALS/Veli 1 is predominately expressed in the glomerulus, thick ascending limb of Henle’s loop (TAL), and the distal convoluted tubule (DCT). MALS/Veli 2 is exclusively expressed in the vasa recta. MALS/Veli 3 is largely located in the DCT and collecting duct. The subcellular localization of MALS/Veli proteins can vary, depending on the isoform and the cell type. In contrast to the predominate basolateral location of MALS/Veli 1 in the TAL and DCT and MALS/Veli 3 in the DCT, MALS/Veli 1 is found diffusely throughout the cytosol of intercalated cells. In the collecting duct, MALS/Veli 3 is chiefly located on the basal membrane. Collectively, these results suggest that different MALS/Veli isoforms may carry out cell type-specific functions. The TAL and distal segments appear to have the most significant capacity for a basolateral membrane-targeting mechanism involving different MALS/Veli isoforms.
Active cutaneous vasodilation in resting humans during mild heat stress
Authors: Kamijo Yoshi-Ichiro , Lee Kichang , Mack Gary W.
Published: October 2004

The role of skin temperature in reflex control of the active cutaneous vasodilator system was examined in six subjects during mild graded heat stress imposed by perfusing water at 34, 36, 38, and 40°C through a tube-lined garment. Skin sympathetic nerve activity (SSNA) was recorded from the peroneal nerve with microneurography. While monitoring esophageal, mean skin, and local skin temperatures, we recorded skin blood flow at bretylium-treated and untreated skin sites by using laser-Doppler velocimetry and local sweat rate by using capacitance hygrometry on the dorsal foot. Cutaneous vascular conductance (CVC) was calculated by dividing skin blood flow by mean arterial pressure. Mild heat stress increased mean skin temperature by 0.2 or 0.3°C every stage, but esophageal and local skin temperature did not change during the first three stages. CVC at the bretylium tosylate-treated site (CVCBT) and sweat expulsion number increased at 38 and 40°C compared with 34°C ( P < 0.05); however, CVC at the untreated site did not change. SSNA increased at 40°C ( P < 0.05, different from 34°C). However, SSNA burst amplitude increased ( P < 0.05), whereas SSNA burst duration decreased ( P < 0.05), at the same time as we observed the increase in CVCBTand sweat expulsion number. These data support the hypothesis that the active vasodilator system is activated by changes in mean skin temperature, even at normal core temperature, and illustrate the intricate competition between active vasodilator and the vasoconstrictor system for control of skin blood flow during mild heat stress.
Neck muscle fatigue and spatial orientation during stepping in place in humans
Authors: Schmid Micaela , Schieppati Marco
Published: October 2004

Neck proprioceptive input, as elicited by muscle vibration, can produce destabilizing effects on stance and locomotion. Neck muscle fatigue produces destabilizing effects on stance, too. Our aim was to assess whether neck muscle fatigue can also perturb the orientation in space during a walking task. Direction and amplitude of the path covered during stepping in place were measured in 10 blindfolded subjects, who performed five 30-s stepping trials before and after a 5-min period of isometric dorsal neck muscle contraction against a load. Neck muscle electromyogram amplitude and median frequency during the head extensor effort were used to compute a fatigue index. Head and body kinematics were recorded by an optoelectronic system, and stepping cadence was measured by sensorized insoles. Before the contraction period, subjects normally stepped on the spot or drifted forward. After contraction, some subjects reproduced the same behavior, whereas others reduced their forward progression or even stepped backward. The former subjects showed minimal signs of fatigue and the latter ones marked signs of fatigue, as quantified by the dorsal neck electromyogram index. Head position and cadence were unaffected in either group of subjects. We argue that the abnormal fatigue-induced afferent input originating in the receptors transducing the neck muscle metabolic state can modulate the egocentric spatial reference frame. Notably, the effects of neck muscle fatigue on orientation are opposite to those produced by neck proprioception. The neck represents a complex source of inputs capable of modifying our orientation in space during a locomotor task.
Muscle activation and blood flow do not explain the muscle length-dependent variation in quadriceps isometric endurance
Authors: Kooistra R. D. , de Ruiter C. J. , de Haan A.
Published: October 2004

We investigated the role of central activation in muscle length-dependent endurance. Central activation ratio (CAR) and rectified surface electromyogram (EMG) were studied during fatigue of isometric contractions of the knee extensors at 30 and 90° knee angles (full extension = 0°). Subjects ( n = 8) were tested on a custom-built ergometer. Maximal voluntary isometric knee extension with supramaximal superimposed burst stimulation (three 100-μs pulses; 300 Hz) was performed to assess CAR and maximal torque capacity (MTC). Surface EMG signals were obtained from vastus lateralis and rectus femoris muscles. At each angle, intermittent (15 s on 6 s off) isometric exercise at 50% MTC with superimposed stimulation was performed to exhaustion. During the fatigue task, a sphygmomanometer cuff around the upper thigh ensured full occlusion (400 mmHg) of the blood supply to the knee extensors. At least 2 days separated fatigue tests. MTC was not different between knee angles (30°: 229.6 ± 39.3 N·m vs. 90°: 215.7 ± 13.2 N·m). Endurance times, however, were significantly longer ( P < 0.05) at 30 vs. 90° (87.8 ± 18.7 vs. 54.9 ± 12.1 s, respectively) despite the CAR not differing between angles at torque failure (30°: 0.95 ± 0.05 vs. 90°: 0.96 ± 0.03) and full occlusion of blood supply to the knee extensors. Furthermore, rectified surface EMG values of the vastus lateralis (normalized to prefatigue maximum) were also similar at torque failure (30°: 56.5 ± 12.5% vs. 90°: 58.3 ± 15.2%), whereas rectus femoris EMG activity was lower at 30° (44.3 ± 12.4%) vs. 90° (69.5 ± 25.3%). We conclude that differences in endurance at different knee angles do not find their origin in differences in central activation and blood flow but may be a consequence of muscle length-related differences in metabolic cost.
Resuscitation with lactated Ringer solution limits the expression of molecular events associated with lung injury after hemorrhage
Authors: Kiang Juliann G. , Lu Xinyue , Tabaku Lindita S. , Bentley Timothy B. , Atkins James L. , Tsokos George C.
Published: October 2004

The aim of this study was to determine whether hemorrhage altered the caspase-3 activity and the ATP levels in rat lung and ileum tissues and determine whether resuscitation with lactated Ringer solution (LR) or whole blood (WB) reversed these changes. Male Sprague-Dawley rats were briefly anesthetized with isoflurane, and their mean arterial blood pressure was reduced from 110 to 40 mmHg by bleeding. The bled rat was then resuscitated with LR or autologous WB to bring mean arterial blood pressure back to 80 mmHg. Lung and ileum tissues were removed at the end of hemorrhage or at the end of the resuscitation period for specified bioassays. Hemorrhage increased cellular caspase-3 activity in the lung and the ileum. After the hemorrhaged rats received LR or WB, caspase-3 activity returned to the basal level in the lung and ileum, respectively. Likewise, hemorrhage decreased cellular ATP levels in lung and ileum. After LR or WB resuscitation, the cellular ATP level returned to the basal level only in the lung resuscitated with LR. The increased caspase-3 activity was associated with the increased expression of caspase-3 mRNA, which also returned to normal levels after either resuscitation. Similarly, hemorrhage increased the expression of inducible nitric oxide synthase and Kruppel-like factor 6 and decreased expression of Kruppel-like factor 4. Subsequent LR resuscitation normalized the expression of these genes in the lung tissue. Our results demonstrate that resuscitation with LR can reverse the expression of genes and their products that are thought to contribute to hemorrhage-induced lung injury.
On the sublinear operators factoring through Lq
Authors: Mezrag Lahcène , Tiaiba Abdelmoumene
Published: October 2004

Let 0 < p ≤ q ≤ +∞. Let T be a bounded sublinear
operator from a Banach space X into an Lp(Ω, μ)

and let ∇T
be the set of all linear operators ≤T.
In the present paper, we will show the following. Let C be a positive
constant. For all u in ∇T, Cpq(u) ≤ C (i.e., u
admits a factorization of the form
, where
is a bounded linear operator with , is the bounded
operator of multiplication by gu which is in (1/p = 1/q + 1/r),
and Cpq(u) is the constant
of q‐convexity of u) if and only if T admits the same
factorization; This is under the supposition that is latticially bounded. Without this condition
this equivalence is not true in general.
Nigerian Chimpanzees (Pan troglodytes vellerosus) at Gashaka: Two Years of Habituation Efforts
Authors: Sommer Volker , Adanu Jeremiah , Faucher Isabelle , Fowler Andrew
Published: October 2004

Cross-population comparisons of chimpanzees can shed light on the pathways of hominid evolution. So far, no eco-ethological data exist for the recently recognized subspecies Pan troglodytes vellerosus. We report on the first 2 years of a new long-term study from what is perhaps their last remaining stronghold: the Gashaka Gumti National Park, Nigeria. The mosaic habitat (woodland, lowland and gallery forest) receives 1,826 mm rain/year, with 4–5 months being completely dry. Primates at Gashaka are not hunted, and the chimpanzees are therefore relatively tolerant of human observers. We focused on the Gashaka-Kwano community, investing 3,000 h of patrols. A total of 95 sightings were achieved which lasted for an average of 27 min (range 1–190 min). Party size averaged 3.7 animals (range 1–17) but was, similarly to encounter length, susceptible to a wide range of methodological, social and ecological factors. The Kwano community comprises at least 35 members which occupy a home range of at least 26 km2, yielding a density of 1.3/km2. The area represents the West African equivalent of a chimpanzee site similar to the forest-woodland habitat in which early humans might have evolved.
Vitamin B6 Level Is Associated with Symptoms of Depression
Authors: Hvas Anne-Mette , Juul Svend , Bech Per , Nexø Ebba
Published: October 2004

Background: A low level of vitamin B6 might theoretically cause depression as vitamin B6 is a cofactor in the tryptophan-serotonin pathway. In the present study, we examined the association between depression and the phosphate derivative of vitamin B6 in plasma, pyridoxal phosphate (PLP). Methods: In 140 individuals, symptoms of depression were evaluated by the Major Depression Inventory, and biochemical markers of vitamin B deficiency were measured. Results: We found that 18 (13%) individuals were depressed. A low plasma level of PLP was significantly associated with the depression score (p = 0.002). No significant association was found between depression and plasma vitamin B12 (p = 0.13), plasma methylmalonic acid (p = 0.67), erythrocyte folate (p = 0.77), and plasma total homocysteine (p = 0.16). Conclusion: Our study suggests that a low level of plasma PLP is associated with symptoms of depression. Randomized trials are now justified and needed in order to examine whether treatment with vitamin B6 may improve symptoms of depression.
Hypercoagulability in Working Men and Women with High Levels of Panic-Like Anxiety
Authors: von Känel Roland , Kudielka Brigitte M. , Schulze Renate , Gander Marie-Louise , Fischer Joachim E.
Published: October 2004

Background: There is growing evidence that cardiovascular diseases are relatively more prevalent in subjects who feel anxious. An increased clotting diathesis might subject anxious individuals to an elevated arterial thrombotic risk. We investigated whether panic-like anxiety would relate to a hypercoagulable state. Methods: Study participants with a complete data set were 691 employees (mean age ± SD 40 ± 11 years, 83% men) recruited from two German companies. Subjects were asked to self-rate the onset of sudden feelings of panic in the previous week on a 4-point Likert scale: 0 = not at all (n = 416), 1 = not very often (n = 179), 2 = quite often (n = 55), and 3 = very often indeed (n = 41). Levels of fibrinogen, of the antifibrinolytic enzyme type 1 plasminogen activator inhibitor (PAI-1), and of the hypercoagulability marker fibrin D-dimer were measured in plasma. Results: While the level of D-dimer was significantly different across the 4 scores of panic feelings (F3, 687 = 6.49, p < 0.001), the levels of fibrinogen and PAI-1 were not. After having controlled for a range of confounders of hemostatic function, the 96 subjects reporting panic feelings either ‘quite often’ or ‘very often indeed’ had higher D-dimer levels (mean ± SEM 165 ± 12.0 vs. 145 ± 4.3 ng/ml, F20, 670 = 4.78, p = 0.030) and lower fibrinogen levels (259 ± 6.9 vs. 274 ± 2.5 mg/dl, F20, 670 = 4.71, p = 0.030) than the 595 subjects reporting panic feelings either ‘not at all’ or ‘not very often’. Conclusions: The findings suggest increased fibrin turnover with sudden feelings of panic. Prospective studies need to show whether such a procoagulant mechanism may contribute to the increased coronary risk with panic-like anxiety.
Personality Profile of HIV Outpatients: Preliminary Results and Remarks on Clinical Management
Authors: Fassino Secondo , Leombruni Paolo , Amianto Federico , Abbate-Daga Giovanni
Published: October 2004

Background: Currently, HIV is one of the most widely spread epidemics in the world. The specificity of the mode of transmission, the well-known severity of the prognosis, and the kind of therapies used are peculiarities of this illness. Personality traits of individuals with HIV may influence conditions for the infection itself. On the other hand, it is possible that personality traits may influence the course of the illness and the willingness of the patients to adhere to treatment. The present study assessed the personality traits of a heterogeneous group of seropositive subjects compared with healthy controls to determine specific temperament and character traits of this population. Methods: The Temperament and Character Inventory (TCI) was administered to 126 HIV-positive outpatients belonging to different risk categories for HIV infection and to a sample of healthy individuals matched for sex, age, and socioeconomic parameters. Results: Drug-dependent HIV-positive patients displayed higher scores in novelty seeking and harm avoidance and lower scores in self-directedness compared with healthy controls. Non-drug-dependent HIV-positive subjects scored significantly higher in self-transcendence. Conclusions: Temperament and character features significantly differentiate the HIV-positive subjects from controls and those belonging to the different risk categories for HIV infection. Drug-dependent subjects with HIV display more impulsiveness, which possibly predates the HIV infection. They are also more fearful and lack self-directedness. Non-drug-dependent subjects express higher self-transcendence resources, possibly to overcome their difficulties. Both the temperament and character features may influence compliance with treatment and require specific interventions considering these subgroups.
Diagnosing ICD-10 Depressive Episodes: Superior Criterion Validity of the Patient Health Questionnaire
Authors: Löwe Bernd , Gräfe Kerstin , Zipfel Stephan , Witte Steffen , Loerch Bernd , Herzog Wolfgang
Published: October 2004

Background: Diagnosing and monitoring depression in primary care remains an issue of significant public health concern. Clinicians and researchers need to know if any one screening instrument is superior to the others in diagnosing ICD-10 depressive episodes. This study aimed to examine the criterion validity for diagnosing ICD-10 depressive episodes of the Patient Health Questionnaire (PHQ) in comparison with 2 well-established instruments, the Hospital Anxiety and Depression Scale (HADS), and the WHO Well-Being Index 5 (WBI-5). Methods: Five hundred and one medical outpatients completed the questionnaires and had a clinical interview. The presence of a depressive episode was determined with the International Diagnostic Checklists (IDCL) for ICD-10 as the criterion standard. Coefficient kappa (ĸ), sensitivities and specificities were calculated and a statistical comparison of the areas under the receiver operating characteristic curves was performed. Results: Diagnostic agreement between the questionnaires and the IDCL was moderate (ĸ = 0.34–0.56), with the highest values for the PHQ. While all 3 questionnaires had reasonable sensitivity and specificity, the operating characteristics for the PHQ were significantly superior to both the HADS and the WBI-5 (p = 0.02). Conclusions: Any of the 3 screening instruments can be recommended for clinical use. However, this is the first comparative study to demonstrate the diagnostic advantage of a particular depression-screening instrument using the ICD-10 diagnostic criteria. The superior criterion validity of the PHQ is likely attributable to its closer representation of the current concept of depressive disorders.
Evolving Treatment Strategies for Anaemia in Cancer: Experience with Epoetin Beta
Authors: Aapro Matti , San Miguel Jésus
Published: October 2004

Epoetin represents the standard of care in the management of cancer therapy-related anaemia, increasing haemoglobin levels, reducing transfusion need and improving patient quality of life (QoL). Recent research aimed at improving convenience and ease of use has involved all epoetins. In particular, it has confirmed that epoetin beta 30,000 IU once weekly is equally effective as the conventional 10,000 IU three-times weekly regimen in alleviating cancer-related anaemia. Ongoing research aimed at improving still further the effectiveness of epoetins in anaemia treatment is examining the role of concomitant intravenous iron during epoetin beta therapy. With the recent debate over whether epoetin therapy has an effect on treatment outcome and survival, well-designed trials specifically powered to assess survival are required. The BReast cancer – Anaemia and the Value of Erythropoietin (BRAVE) trial is such a study, assessing the impact of epoetin beta on survival and QoL of patients with metastatic breast cancer scheduled to receive anthracycline- and/or taxane-based chemotherapy. The findings of such studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.
Epidemiology of Neuroendocrine Tumours
Authors: Taal B.G. , Visser O.
Published: October 2004

Neuroendocrine tumours account for only 0.5% of all malignancies. The incidence is approximately 2/100,000 with a female preponderance under the age of 50 years due to appendiceal location. The main primary sites are the gastrointestinal tract (62–67%) and the lung (22–27%). Presentation with metastatic disease accounts for 12–22%. In the last decades, the incidence has been rising. This might be due to more awareness, improved diagnostic tools or a change in definition. Most neuroendocrine tumours are mainly sporadic, but association with the multiple endocrine neoplasia type 1 syndrome and clustering within families is known. Also an increased risk of secondary cancers has been reported, but numbers are small. The 5-year survival is mainly associated with stage: 93% in local disease, 74% in regional disease and 19% in metastatic disease. In metastatic disease, survival increased since 1992, when treatment with octreotide became largely available in the Netherlands.